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Title:
PROCESS FOR THE SYNTHESIS OF BETA-AMINOCARBONYLS
Document Type and Number:
WIPO Patent Application WO/2013/067646
Kind Code:
A1
Abstract:
The present application provides processes and intermediates useful in the production of β- aminocarbonyl- or β-aminothiocarbonyl-containing compounds. Provided herein is a process for synthesizing β-aminocarbonyl- or β-aminothiocarbonyl-containing compounds from an alkene and a hydrazone. Also provided herein is a process for synthesizing β-aminocarbonyl- or β-aminothiocarbonyl-containing compounds from an alkene and a hydrazine. The present application further provides intermediate aminoisocyanate and iminoisocyanate compounds, and methods for synthesizing the starting hydrazone and hydrazine compounds.

Inventors:
BEAUCHEMIN ANDRE MARTIN (CA)
CLAVETTE CHRISTIAN (CA)
GAN WEI (CA)
MARKIEWICZ THOMAS (CA)
TODERIAN AMY BEVERLY (CA)
Application Number:
CA2012/050798
Publication Date:
May 16, 2013
Filing Date:
November 09, 2012
Export Citation:
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Assignee:
UNIVERSITY OF OTTAWA (Room 3042, 800 King Edward AvenueOttawa, Ontario K1N 6N5, CA)
International Classes:
C07C251/72; C07C21/00; C07C263/00; C07C265/00; C07C327/38; C07C331/16; C07D231/00
Other References:
JONES, D. W.: "Generation of an N-isocyanatoimine and its cycloadditions leading to sterically stabilised zwitterions", J. CHEM. SOC., CHEM. COMMUN., 1982, pages 766 - 768, XP055067043
CLAVETTE, C. ET AL.: "A tunable route for the synthesis of azomethine imines and beta-aminocarbonyl compounds from alkenes", J. AM. CHEM. SOC., vol. 134, 11 September 2012 (2012-09-11), pages 16111 - 16114, XP055067044
Attorney, Agent or Firm:
OSLER, HOSKIN & HARCOURT LLP et al. (Suite 1900, 340 Albert StreetOttawa, Ontario K1R 7Y6, CA)
Download PDF:
Claims:
THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for synthesizing of a β-aminocarbonyl- or a β-aminothiocarbonyl- containing compound of Formula I:

Formula I

the process comprising:

reacting an alkene of Formula II or an alkyne of Formula III

R1 - CH=CH - R5 R1 - C≡C - R5

Formula II Formula III where:

R1 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl, or OR6, where R6 is a substituted or unsubstituted linear, branched or cyclic alkyl;

R5 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl; or

R1 and R5, together with the carbon atoms to which they are bound, join to form a substituted or unsubstitued cycloalkyl, cycloalkenyl or aryl, or a heterocycle; with an imino compound of Formula IV: H

R" where:

7 8 9 9 7

LG is a leaving group, such as NR R , OR", or SR where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R8 and R9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

2. The process of claim 1, wherein the reaction between the alkene of Formula II or the alkyne of Formula III and the imino compound of Formula IV is an intermolecular reaction.

3. The process of claim 1, wherein the reaction between the alkene of Formula II or the alkyne of Formula III and the imino compound of Formula IV is an intramolecular reaction in which the alkene of Formula II or the alkyne of Formula III forms part of R' or R" of the imino compound of Formula IV.

4. The process of any one of claims 1 - 3, which comprises the step of forming an intermediate iminoisocyanate of Formula V:

Formula V

from the imino compound of Formula IV, optionally with the addition of heat.

5. The process of any one of claims 1 - 4, wherein the alkene of Formula II is a hexene, a heptene, an octene, n-butyl vinyl ether, 1 ,4-butanediol divinyl ether,

cyclohexylvinyl ether, 3,4-dihydro-2H-pyran, 1 -vinyl-2-pyrrolidinone, norbornene, 2,3- dihydrofuran, styrene, 4-methoxysytrene, 4-fluorostyrene, a cycloalkene, such as cyclohexene, a cyclodiene, such as a cyclohexadiene or a cyclooctadiene, norbornadiene, 1- ((but-3-enyloxy)methyl)benezene, lH-indene, dihyronaphthalene, vinylferrocene, N- vinyloxypyrrolidin-2-one, vinyl-«-butylether, and vinyloxycyclohexane, each of which is optionally substituted.

6. The process of any one of claims 1 - 5, wherein R' and R" are each independently Η; a substituted or unsubstituted, linear or branched C1-C12 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, alkenyl, cyclohexyl; or a substituted or unsubstituted C6-Ci5 aryl, such as phenyl, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 4- EtOC6H4, 2-ClC6H , 2-BrCeH , naphthyl, pyridyl, 2-styrenyl or indolyl; or a heterocycle, such as furanyl, thiophenyl or pyrrolyl.

7. The process of any one of claims 1 - 5, wherein R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, such as cyclopropyl, cyclopentyl, adamantyl, or l,7,7-trimethylbicyclo[2.2.1]heptan-2-yl;

cycloalkenyl, such as cyclohexenyl; or aryl, which is optionally a 6-5-6 or 6-6-6 ring system, such as a fluorenyl ring system; or a heterocycle, such as indolyl.

8. The process of any one of claims 1 - 7, wherein LG is OTdu, OPh, NHTdu, NHPh, N/Pr2, OCH2CF3, OEt, SEt, SPh, CH3CH2OH, or CF3CH2OH.

9. The process of any one of claims 1 - 8, wherein the reaction reaction between the alkene of Formula II or the alkyne of Formula III and the imino compound of Formula IV is performed in the presence of a catalyst.

10. The process of claim 9, wherein the catalyst is a base catalyst.

11. The process of any one of claims 1 - 10, which further includes the step of cleaving the N - N bond of an azomethine imine product of the reaction between the alkene of Formula II or the alkyne of Formula III and the imino compound of Formula IV.

12. A process for synthesizing of a compound of Formula I or Formula VI:

Formula I Formula VI

the process comprising:

reacting an alkene of Formula II or an alkyne of Formula III

Formula II Formula III where:

R1 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl or OR6, where R6 is a substituted or unsubstituted linear, branched or cyclic alkyl;

R5 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle,; or

R1 and R5, together with the carbon atoms to which they are bound, join to form a substituted or unsubstitued cycloalkyl or cycloalkenyl, or a heterocycle;

with an iminoisocyanate of Formula V:

R"

Formula V

where: R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

13. The process of claim 12, wherein the reaction between the alkene of Formula II or the alkyne of Formula III and the iminoisocyanate of Formula V is an intermolecular reaction.

14. The process of claim 12, wherein the reaction between the alkene of Formula II or the alkyne of Formula III and the iminoisocyanate of Formula V is an intramolecular reaction in which the alkene of Formula II or the alkyne of Formula III forms part of R' or R" of the iminoisocyanate of Formula V.

15. The process of any one of claims 12 - 14, which is for synthesizing of a compound of Formula VI.

16. The process of claim 15, wherein the process additionally comprises the step of treating the compound of Formula VI with NaBH4 to form a compound of Formula Via:

Formula Via.

17. The process of any one of claims 12 - 16, wherein the alkene of Formula II is an alkene, such as hexene, n-butyl vinyl ether, 1,4-butanediol divinyl ether, cyclohexylvinyl ether, 3,4-dihydro-2H-pyran, l-vinyl-2-pyrrolidinone, norbornene, 2,3-dihydrofuran, styrene, 4-methoxysytrene, 4-fluorostyrene, a cycloalkene, such as cyclohexene, a cyclodiene, such as a cyclohexadiene or a cyclooctadiene, norbornadiene, l-((but-3-enyloxy)methyl)benezene, lH-indene, dihyronaphthalene, vinylferrocene, N-vinyloxypyrrolidin-2-one, vinyl-w- butylether, and vinyloxycyclohexane, each of which is optionally substituted.

18. The process of any one of claims 12 - 17, wherein R' and R" are each independently Η; a substituted or unsubstituted, linear or branched C1-C12 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, alkenyl, cyclohexyl; or a substituted or unsubstituted C6-Ci5 aryl, such as phenyl, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 4- EtOC6H4, 2-ClC6H , 2-BrCeH , naphthyl, pyridyl, 2-styrenyl or indolyl; or a heterocycle, such as furanyl, thiophenyl or pyrrolyl.

19. The process of any one of claims 12 - 17, wherein R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, such as cyclopropyl, cyclopentyl, adamantyl, or l,7,7-trimethylbicyclo[2.2.1]heptan-2-yl;

cycloalkenyl, such as cyclohexenyl; or aryl, which is optionally a 6-5-6 or 6-6-6 ring system, such as a fluorenyl ring system; or a heterocycle, such as indolyl.

20. A process for synthesizing of an iminoisocyanate compound of Formula V:

Formula V

the process comprising:

heating a compound of Formula IV:

R'

Formula IV where:

7 8 9 9 7

LG is a leaving group, such as NR R , OR", or SR where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R8 and R9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

21. The process of claim 20, wherein R' and R" are each independently H; a substituted or unsubstituted, linear or branched C1-C12 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, alkenyl, cyclohexyl; or a substituted or unsubstituted C6-Ci5 aryl, such as phenyl, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 4-EtOC6H4, 2-ClC6H4, 2-BrC6H4, naphthyl, pyridyl, 2-styrenyl or indolyl; or a heterocycle, such as furanyl, thiophenyl or pyrrolyl.

22. The process of claim 20, wherein R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, such as cyclopropyl, cyclopentyl, adamantyl, or l,7,7-trimethylbicyclo[2.2.1]heptan-2-yl; cycloalkenyl, such as cyclohexenyl; or aryl, which is optionally a 6-5-6 or 6-6-6 ring system, such as a fluorenyl ring system; or a heterocycle, such as indolyl.

23. The process of any one of claims 20 - 22, wherein LG is OTdu, OPh, NHTdu,

NHPh, N/Pr2, OCH2CF3, OEt, SEt, SPh, CH3CH2OH, or CF3CH2OH.

24. A compound of the Formula IV:

Formula IV where:

7 8 9 9 7

LG is a leaving group, such as NR R , OR", or SR where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R8 and R9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

25. The compound of claim 24, wherein R' and R" are each independently H; a substituted or unsubstituted, linear or branched C1-C12 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, alkenyl, cyclohexyl; or a substituted or unsubstituted C6-C15 aryl, such as phenyl, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 4-EtOC6H4, 2-ClC6H4, 2-BrC6H4, naphthyl, pyridyl, 2-styrenyl or indolyl; or a heterocycle, such as furanyl, thiophenyl or pyrrolyl.

26. The process of claim 24, wherein R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, such as cyclopropyl, cyclopentyl, adamantyl, or l,7,7-trimethylbicyclo[2.2.1]heptan-2-yl; cycloalkenyl, such as cyclohexenyl; or aryl, which is optionally a 6-5-6 or 6-6-6 ring system, such as a fluorenyl ring system; or a heterocycle, such as indolyl.

27. The process of any one of claims 24 - 26, wherein LG is OTdu, OPh, NHTdu,

NHPh, N/Pr2, OCH2CF3, OEt, SEt, SPh, CH3CH2OH, or CF3CH2OH.

28. A compound of Formula V:

R"

Formula V where:

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S,

with the proviso that when R' is 2,4,6-trimethylphenyl, R" cannot be:

29. The compound of claim 28, wherein R' and R" are each independently H; a substituted or unsubstituted, linear or branched Ci-Ci2 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, alkenyl, cyclohexyl; or a substituted or unsubstituted C6-C15 aryl, such as phenyl, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 4-EtOC6H4, 2-ClC6H4, 2-BrC6H4, naphthyl, pyridyl, 2-styrenyl or indolyl; or a heterocycle, such as furanyl, thiophenyl or pyrrolyl.

30. The process of claim 28, wherein R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, such as cyclopropyl, cyclopentyl, adamantyl, or l,7,7-trimethylbicyclo[2.2.1]heptan-2-yl; cycloalkenyl, such as cyclohexenyl; or aryl, which is optionally a 6-5-6 or 6-6-6 ring system, such as a fluorenyl ring system; or a heterocycle, such as indolyl.

31. A process for synthesizing a β-aminocarbonyl or β-aminothiocarbonyl compound of the Formula VIII:

Formula VIII

comprising the steps of: reacting an alkene of Formula II or an alkyne of Formula III

R1 - CH=CH - R5 R1 - C≡C - R5

Formula II Formula III where:

R1 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl, or OR6, where R6 is a substituted or unsubstituted linear, branched or cyclic alkyl;

R5 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle; or

R1 and R5, together with the carbon atoms to which they are bound, join to form a substituted or unsubstitued cycloalkyl or cycloalkenyl, or a heterocycle;

with an amino compound of Formula IX:

Formula IX where:

7 8 9 9 7

LG is a leaving group, such as NR R , OR", or SR where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R8 and R9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S, wherein the reaction between the alkene of Formula II or the alkyne of Formula III and the amino compound of Formula IX is an intermolecular reaction.

32. The process of claim 31, wherein R' and R" are each independently H; a substituted or unsubstituted, linear or branched C1-C12 alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, alkenyl, cyclohexyl; or a substituted or unsubstituted C6-C15 aryl, such as phenyl, 2-MeOC6H4, 3-MeOC6H4, 4-MeOC6H4, 4-EtOC6H4, 2-ClC6H4, 2-BrC6H4, naphthyl, pyridyl, 2-styrenyl or indolyl; or a heterocycle, such as furanyl, thiophenyl or pyrrolyl.

33. The process of claim 31, wherein R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, such as cyclopropyl, cyclopentyl, adamantyl, or l,7,7-trimethylbicyclo[2.2.1]heptan-2-yl; cycloalkenyl, such as cyclohexenyl; or aryl, which is optionally a 6-5-6 or 6-6-6 ring system, such as a fluorenyl ring system; or a heterocycle, such as indolyl.

34. The process of any one of claims 31 - 33, which comprises the step of forming an intermediate aminoisocyanate of Formula Va:

N

R"^ R"

Formula Va

from the amino compound of Formula IX, optionally with the addition of heat.

35. The process of any one of claims 31 - 34, wherein the alkene of Formula II is an alkene, such as hexene, n-butyl vinyl ether, 1,4-butanediol divinyl ether, cyclohexylvinyl ether, 3,4-dihydro-2H-pyran, l-vinyl-2-pyrrolidinone, norbornene, 2,3-dihydrofuran, styrene, 4-methoxysytrene, 4-fluorostyrene, a cycloalkene, such as cyclohexene, a cyclodiene, such as a cyclohexadiene or a cyclooctadiene, norbornadiene, l-((but-3-enyloxy)methyl)benezene, lH-indene, dihyronaphthalene, vinylferrocene, N-vinyloxypyrrolidin-2-one, vinyl-w- butylether, and vinyloxycyclohexane.

36. The process of any one of claims 31 - 35, wherein LG is OTdu, OPh, Nt Bu, NHPh, N/Pr2, OCH2CF3, OEt, SEt, SPh, CH3CH2OH, CF3CH2OH,.

37. The process of any one of claims 31 - 36, wherein the reaction reaction between the alkene of Formula II or the alkyne of Formula III and the amino compound of Formula IX is performed in the presence of a catalyst.

38. The process of any one of claims 31 - 37, which further includes the step of cleaving the N - N bond of a 3-pyrazolidinone product of the reaction between the alkene of Formula II or the alkyne of Formula III and the amino compound of Formula IX.

Description:
PROCESS FOR THE SYNTHESIS OF BETA-AMINOCARBONYLS

FIELD

[0001] The present invention pertains to the field of synthetic chemistry. In particular, the present invention relates to a process for the synthesis of β-aminocarbonyl- or β-aminothiocarbonyl-containing compounds, and to compounds useful in the synthesis of such β-aminocarbonyl- or β-aminothiocarbonyl-containing compounds.

BACKGROUND

[0002] β-Aminocarbonyl motifs comprise the general formula o

R 1 N

i ■

[0003] β-Aminocarbonyls are present in a variety of biologically active compounds and are commonly used in the synthesis of pharmaceuticals. Compounds comprising a β- aminocarbonyl motif include ritalin (a psychostimulant), taxol (antineoplastic), penicillin G (antimicrobial), in oligomers such as β-17 (antimicrobial) and natural products. Beta-lactams are a family of antibiotics that possess the β-aminocarbonyl motif. Another important application area is for beta-peptides; these promising therapeutic macromolecules are more resistant to protease degradation than conventional peptides - a major limitation of alpha- peptide based therapies.

[0004] Several approaches have been developed to access these motifs reliably, yet important limitations still need to be addressed (e.g., practicality, cost or accessibility of reagents, inefficient multi-step procedures, etc.). A complementary approach -alkene aminocarbonylation - is only now emerging as an alternative route, which offers a strategic advantage in pharmaceutical research and manufacturing either by providing access to new molecules (biopharmaceutical research), by allowing for late-stage derivatization (drug discovery) and by providing a rapid access to complex structures from very inexpensive starting materials (manufacturing). Indeed, direct approaches to such motifs from alkene and alkyne (inexpensive, broadly available and structurally diverse starting materials) are severely underdeveloped; metal-catalyzed approaches are rare and very limited in scope.

[0005] The most direct technology available to convert alkenes into beta- aminocarbonyl motifs is indirect and involves the very hazardous reagent

chlorosulfonylisocyanate (CSI) and provides access to beta-lactams via ionic intermediates. This reagent is also very reactive and therefore often incompatible with the sensitive molecules used in drug discovery. Formation of beta-aminocarbonyl motifs is typically performed using the Michael reaction (i.e., reaction of the β carbon-N bond; "C-N") or the Mannich reaction (i.e., reaction of the β carbon-α carbon bond; "C-C"). In the

aminocarbonylation of alkenes, both the C-C and C-N bonds are simultaneous formed. This is particularly advantageous compared to previous methods, since it can be performed using more inexpensive starting materials.

[0006] Hydrazine-based compounds, such as hydrazides, can be used as starting materials in aminocarbonylation formation (Roveda et al, J. Am. Chem. Soc, 2009, 131 :8740). For example, hydrazides comprising a leaving group X and an alkene group can react intramolecularly to form an aminocarbonylation compound with varying yields depending on the leaving group and the substituents on the alkene:

[0007] Only limited examples of intermolecular reactivity of hydrazides are known.

For example, Jones in 1982 disclosed a dipolar cycloaddition product shown below.

(where Mes = 2,4,6-trimethylphenyl)

Jones postulated that this compound forms a reactive N-isocyanatoimine and did not show the chemical reactivity of related 1,3-dipoles because of the extreme steric protection of the iminium carbon. No other dipolar hydrazones were disclosed or suggested in Jones.

[0008] Thermal degradation of hydrazides has been previously shown to produce aminoisocyanates as intermediates.

[0009] Intramolecular reaction of hydrazones with alkenes has shown that ketohydrazones have increased reactivity and stability, and permit isolation of the azomethine imine product. In the intramolecular aminocarbonylation reaction of hydrazides, an aminoisocyanate is formed as an intermediate:

[0010] Despite being thermodynamically favourable, this reaction involves a difficult intramolecular proton transfer step. Further, Lockley and Lwowski (Tetrahedron Letters, 1974; 48: 4263-66) has shown that aminoisocyanates can dimerize and only limited reactions with alkynes have been reported. Thus, there remains a need for a simple

aminocarbonylation process.

[0011] This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.

SUMMARY

[0012] An object of the present application is to provide a process for synthesizing β- aminocarbonyls.

[0013] In accordance with one aspect, there is provided a process for synthesizing of a β-aminocarbonyl- or β-aminothiocarbonyl-containing compound of Formula I:

Formula I process comprising:

reacting an alkene of Formula II or an alkyne of Formula III

R 1 - CH=CH - R 5 R 1 - C≡C - R 5

Formula II Formula III where:

R 1 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl, or OR* where R 6 is a substituted or unsubstituted linear, branched or cyclic alkyl;

R 5 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle; or

R 1 and R 5 , together with the carbon atoms to which they are bound, join to form a substituted or unsubstitued cycloalkyl, cycloalkenyl, aryl, or a heterocycle; with a hydrazone compound of Formula IV:

Formula IV

where:

7 8 9 9 7

LG is a leaving group, such as NR R , OR", or SR where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R 8 and R 9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

[0014] In certain embodiments, this process proceeds via an intermediate iminoisocyanate of Formula V:

R"

Formula V

where R', R" and Z are as defined above.

[0015] In one embodiment, the process proceeds via an intramolecular reaction in which the alkene of Formula II or the alkyne of Formula III forms part of R' or R" of the hydrazone of Formula IV. In a specific example of this embodiment, the hydrazone of Formula IV comprises an alkyne of Formula III in one of the R' or R" substituents.

[0016] In accordance with another aspect, there is provided a process for synthesizing of a compound of Formula I or Formula VI:

Formula I Formula VI

the process comprising:

reacting an alkene of Formula II or an alkyne of Formula III

R 1 - CH=CH - R 5 R 1 - C≡ C - R 5

Formula II Formula III where:

R 1 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl or OR 6 , where R 6 is a substituted or unsubstituted linear, branched or cyclic alkyl;

R 5 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle,; or

R 1 and R 5 , together with the carbon atoms to which they are bound, join to form a substituted or unsubstitued cycloalkyl or cycloalkenyl, or a heterocycle;

with an iminoisocyanate of Formula V:

Formula V

where:

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

[0017] In one embodiment, the above process proceeds via an intramolecular reaction in which the alkene of Formula II or the alkyne of Formula III forms part of R' and R" of the iminoisocyanate of Formula V. In a specific example of this embodiment, the

iminoisocyanate of Formula V comprises an alkyne of Formula III in one of the R' and R" substituents.

[0018] In accordance with another aspect, there is provided a process for synthesizing of a compound of Formula VI:

Formula VI

the process comprising: reacting an alkene of Formula II or an alkyne of Formula III

Formula II Formula III where:

R 1 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl, or OR 6 , where R 6 is a substituted or unsubstituted linear, branched or cyclic alkyl;

R 5 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle; or

R 1 and R 5 , together with the carbon atoms to which they are bound, join to form a substituted or unsubstitued cycloalkyl or cycloalkenyl, or a heterocycle;

with a hydrazone compo

Formula IV

where:

LG is a leaving group, such as NR R , OR , or SR , where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R 8 and R 9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S. [0019] Optionally, the process additionally comprises the step of treating the compound of Formula VI with NaBH 4 to form a compound of Formula Via:

Formula Via.

[0020] In accordance with another embodiment, the process further includes the step of cleaving the N - N bond of the compound of Formula VI or the compound of Formula Via to produce a compound of Formula I.

[0021] In one embodiment, the above process proceeds via an intramolecular reaction in which the alkene of Formula II or the alkyne of Formula III forms part of R' and R" of the hydrazone of Formula IV. In a specific example of this embodiment, the hydrazone of Formula IV comprises an alkyne of Formula III in one of the R' and R" substituents.

[0022] In accordance with another aspect, there is provided a process for synthesizing of an iminoisocyanate compound of Formula V:

Formula V the process comprising: heating a compound of Formula IV:

Formula IV

where:

LG is a leaving group, such as NR R , OR , or SR , where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R 8 and R 9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

[0023] In accordance with another aspect of the invention, there is provided a hydrazone compound of the Formula IV:

Formula IV where LG, Z, R' and R" are as defined above.

[0024] In accordance with another aspect of the invention, there is provided an iminoisocyanate compound of Formula V:

Formula V where Z, R' and R" are as defined above, with the proviso that when R' is 2,4,6- trimethylphenyl, R" cannot be:

[0025] In accordance with another aspect of the present invention, there is provided a process for synthesizing a β-aminocarbonyl or β-aminothiocarbonyl compound of the Formula VIII:

comprising the steps of: reacting an alkene of Formula II or an alkyne of Formula III

- CH=CH - R 5 R 1 - C≡C - R

Formula II Formula III where:

R 1 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted heterocycle, or a substituted or unsubstituted aryl, or OR 6 , where R 6 is a substituted or unsubstituted linear, branched or cyclic alkyl;

R 5 is H, a substituted or unsubstituted, linear, branched or cyclic alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle; or

R 1 and R 5 , together with the carbon atoms to which they are bound, join to form a substituted or unsubstitued cycloalkyl or cycloalkenyl, or a heterocycle;

with an amino compound of Formula IX:

Formula IX where:

7 8 9 9 7

LG is a leaving group, such as NR R , OR", or SR where R' is H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl; and R 8 and R 9 a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl;

R' and R" are each independently H, a substituted or unsubstituted, linear or branched alkyl or a substituted or unsubstituted aryl, or a substituted or unsubstituted heterocycle, or R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, cycloalkenyl or aryl, or a heterocycle, with the proviso that R' and R" are not both H; and

Z is O or S.

[0026] In one embodiment, the above process proceeds via an intramolecular reaction in which the alkene of Formula II or the alkyne of Formula III forms part of R' and R" of the hydrazine of Formula IX. In a specific example of this embodiment, the hydrazine of Formula IX comprises an alkyne of Formula III in one of the R' and R" substituents.

[0027] In certain embodiments, R' and R" together form an aryl which is a 6-5-6 or 6-

6-6 ring system. In one particular embodiment, the aryl is derived from fluorenone. In other embodiments, R' and R", together with the carbon atom to which they are bound, form a substituted or unsubstituted cycloalkyl, such as cyclopropyl, cyclopentyl, adamantyl, or 1,7,7- trimethylbicyclo[2.2.1]heptan-2-yl; cycloalkenyl, such as cyclohexenyl; or a heterocycle, such as indolyl.

[0028] Advantageously, the β-aminocarbonylation or β-aminothiocarbonylation products can be synthesized with common and inexpensive alkenes and alkynes. Further, commercially available ketones and hydrazine derivatives can also be used. Several of these reagents and products are crystalline, rendering them practical to use and easily purified.

[0029] The process described herein also provides the generation upon heating of an aminoisocyanate or iminoisocyanate intermediate, which then reacts to give the desired products. The process, thus, demonstrates the utility of aminoisocyanates and

iminoisocyanates as starting materials or intermediates in aminocarbonylation or

aminothiocarbonylation, for example, aminocarbonylation or aminothiocarbonylation using relatively inexpensive, commonly-available reagents using milder conditions than were previously possible.

BRIEF DESCRIPTION OF THE FIGURES

[0030] For a better understanding of the present invention, as well as other aspects and further features thereof, reference is made to the following description which is to be used in conjunction with the accompanying drawings, where: [0031] Figure 1 depicts the Oak Ridge Thermal Ellipsoid Plot (ORTEP) of the crystal structure of (±)-cis-\ -diphenylmethylene-3-oxo-tetrahydro-lH-furo[2,3-c]pyrazolidi ne-l - ium-2-ide (5n);

[0032] Figure 2 depicts the ORTEP of the crystal structure of (±)-exo-2-(2,4- dimethylpentan-3-ylidene)-4-thione-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (5p);

[0033] Figure 3 depicts the ORTEP of the crystal structure of (±)-exo-2-(l-methyl-l-

(2-furanyl)-methylene)-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (8); and

[0034] Figure 4 depicts the ORTEP of the crystal structure of (±)-exo-2-(2,4- dimethylpentan-3-ylidene)-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (3a).

[0035] Figure 5 depicts the transition state structures for the intermolecular aminocarbonylation of ethylene (A) and norbomene (B) using dimethyliminoisocyanate.

[0036] Figure 6 depicts the crystal structure of (±)-exo-2-[N-(9H-fluoren-9-ylidene)]-

4-oxo-2,3-diazatricyclo-[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (3z).

DETAILED DESCRIPTION

[0037] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0038] As used in the specification and claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise.

[0039] The term "comprising" as used herein will be understood to mean that the list following is non-exhaustive and may or may not include any other additional suitable items, for example one or more further feature(s), component(s) and/or ingredient(s) as appropriate.

[0040] As used herein, "alkyl" refers to a linear, branched or cyclic, saturated or unsaturated hydrocarbon group which can be unsubstituted or is optionally substituted with one or more substituent. Examples of saturated straight or branched chain alkyl groups include, but are not limited to, methyl, ethyl, 1 -propyl, 2-propyl, 1 -butyl, 2-butyl, 2-methyl-l - propyl, 2-methyl-2-propyl, 1-pentyl, 2-pentyl, 3-pentyl, 2-methyl-l -butyl, 3-methyl-l -butyl, 2-methyl-3 -butyl, 2,2-dimethyl-l -propyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-l-pentyl, 3- methyl-l-pentyl, 4-methyl-l-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2- pentyl, 2,2-dimethyl-l -butyl, 3,3-dimethyl-l-butyl and 2-ethyl-l -butyl, 1-heptyl and 1-octyl. As used herein the term "alkyl" encompasses cyclic alkyls, or cycloalkyl groups. The term "cycloalkyl" as used herein refers to a non-aromatic, saturated monocyclic, bicyclic or tricyclic hydrocarbon ring system containing at least 3 carbon atoms. Examples of C 3 -Ci 2 cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbomyl, adamantyl, bicyclo[2.2.2]oct-2-enyl, and bicyclo[2.2.2]octyl. The term "cycloalkyl" is used herein to specifically refer to a cyclic alkyl group.

[0041] As used herein, the term "alkene" refers to a straight, branched or cyclic hydrocarbon group containing at least one double bond which can be unsubstituted or optionally substituted with one or more substituents. As used herein, the term "alkenyl" refers to a functional group based on an alkene, which contains at least one double bond. The term "cycloalkenyl" is used herein to specifically refer to a cyclic alkenyl group.

[0042] As used herein, "alkyne" refers to an unsaturated, straight or branched chain hydrocarbon group containing at least one triple bond which can be unsubstituted or optionally substituted with one or more substituents. As used herein, the term "alkynyl" refers to a functional group based on an alkyne, which contains at least one double bond. The term "cycloalkynyl" is used herein to specifically refer to a cyclic alkynyl group.

[0043] As used herein, "aryl" refers to hydrocarbons derived from benzene or a benzene derivative that are unsaturated aromatic carbocyclic groups of from 6 to 100 carbon atoms, or from which may or may not be a fused ring system; in some embodiments 6 to 50, in other embodiments 6 to 25, and in still other embodiments 6 to 15. The aryls may have a single or multiple rings. The term "aryl" as used herein also includes substituted aryls and heteroaryls. Examples include, but are not limited to phenyl, naphthyl, xylene, phenylethane, substituted phenyl, substituted naphthyl, substituted xylene, substituted phenylethane, pyridyl, substituted pyridyl, and the like.

[0044] As used herein, "heterocycle" or "heterocyclic compound" refers to a cyclic compound that has at least one heteroatom as a member of its ring(s). As used herein, heterocycle includes "heteroaryl", which refers to an aryl that includes from 1 to 10, in other embodiments 1 to 4, heteroatoms, which can be substituted or unsubstituted.

[0045] As used herein, a "heteroatom" refers to an atom that is not carbon or hydrogen, such as nitrogen, oxygen, sulfur, phosphorus, chlorine, bromine, and iodine

[0046] As used herein, a "leaving group" refers to a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common leaving groups are halides such as CI " , Br " , and Γ, sulfonate esters, such as para-toluenesulfonate ("tosylate", TsO " ), water (H 2 0), ammonia (NH 3 ), alcohols (ROH), thiols (RSH), thiolates (RS-), alkoxides (RO-), amines (HNR 2 ), silyl esters, acid halides such as acid chlorides, carboxylic acids (RC0 2 H), carboxylates (RC0 2 -), phosphate esters

[(RO) 2 (P=0)OH] and their anions [(RO) 2 (P=0)0-], and heterocyclic compounds such as imidazole.

[0047] As used herein, "substituted" means having one or more substituent moieties whose presence does not interfere with the desired function or reactivity. Examples of substituents include alkyl, alkenyl, alkynyl, cycloalkyl (non-aromatic ring), Si(alkyl) 3 , Si(alkoxy)3, alkoxyl, amino, alkylamino, alkenylamino, amide, amidine, guanidine, hydroxyl, thioether, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyloxy, carbonate, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphate ester, phosphonato, phosphinato, cyano, halo, acylamino, imino, sulfhydryl, alkylthio, thiocarboxylate, dithiocarboxylate, sulfate, sulfato, sulfonate, sulfamoyl, sulfonamide, nitro, nitrile, azido, heterocyclyl, ether, ester, silicon-containing moieties, thioester, or a combination thereof. The substituents may themselves be substituted. For instance, an amino substituent may itself be mono or independently disubstituted by further substituents defined above, such as alkyl, alkenyl, alkynyl, and cycloalkyl (non-aromatic ring).

[0048] As used herein, the term "unsubstituted" refers to any open valence of an atom being occupied by hydrogen. Also, if an occupant of an open valence position on an atom is not specified then it is hydrogen.

[0049] The present application provides processes and intermediates useful in the production of β-aminocarbonyl or β- aminothiocarbonyl-containing compounds. In one aspect, there is a provided a process for synthesizing β-aminocarbonyl-containing compounds, or azomethine imine compounds, according to the following scheme using an alkene.

Hydrazone Iminoisocyanate Azomethine imine where only one R can be H.

[0050] In some embodiments, it has been found that the carbonyl-containing hydrazone starting reagent can be formed in situ on addition of COX 2 (where X is a halogen) to the hydrazone.

[0051] Exemplary COX 2 compounds include phosgene (COCl 2 ), Ι,Γ-carbonyldimidazole and phenyl chloroformate.

[0052] The dipole product of the above reaction can be treated to cleave the N-N bond and thereby produce a β-aminocarbonyl-containing compound.

[0053] The use of alkenes and hydrazones as reagents for the synthesis of β-aminocarbonyl or β-aminothiocarbonyl motifs has been found to provide, for example, reactivity at various temperatures (dependant on identity of X) and the ability to use a variety of solvents, or no solvent at all. By changing the substituents on the hydrazone starting material (R 1 , R" and X can be varied), it is possible to tune the reaction and to tailor the reagent depending on the target product. Similarly the reaction is sufficiently robust to permit the use of various alkenes, including vinyl ethers (O substituted) and non-activated alkenes (such as 1-hexene), thereby allowing tuning of the reaction and tailoring of the reagents based on the target product.

[0054] Both the hydrazone reagents and dipole products are typically crystalline, which simplifies the reaction process in comparison to processes that make use of non-crystalline starting materials and intermediates.

[0055] In accordance with one aspect of this application, there is provided a method of synthesizing an iminoisocyanate by heating the hydrazone starting material.

[0056] In another aspect, there is a provided a process for synthesizing β-aminocarbonyl- containing compounds, or 3-pyrazolidinones, from a hydrazine starting material according to the following scheme, using an alkene.

Hydrazine Aminoisocyanate 3-pyrazolidinone

[0057] The transition state structures for the intermolecular aminocarbonylation of (A) ethylene and (B) norbomene, are shown in Figure 5. Relevant bond distances in angstroms are shown. Arrows indicate the atomic movements which correspond to the imaginary normal mode.

[0058] The 3-pyrazolidinone product of the above reaction can be treated to cleave the N-N bond and thereby produce a β-aminocarbonyl-containing compound.

[0059] The use of alkenes and hydrazines as reagents for the synthesis of β-aminocarbonyl or β-aminothiocarbonyl compounds also provides a highly tunable synthetic route. For example, reactivity at various temperatures (dependant on X), ability to use a variety of solvents and to change the substituents on the hydrazine and the alkene allows the reaction to be tailored specifically for the target product. [0060] In certain embodiments of this process, the hydrazone can be reacted with other alkenes or alkynes, such as, but not limited to, silyl enol ethers, vinyl acetates, TMS acetylenes or vinyl silanes, for example.

[0061] In certain embodiments of this process, the analogous thiocarbonyl derivatives can be used as the starting hydrazone material.

[0062] Although not necessary, in certain embodiments, the reaction can be performed in the presence of a catalyst. In one non-limiting example, the catalyst is a base catalyst, which can significantly improve the efficiency of the reaction and/or permit the use of a lower temperature (e.g., a 70°C reaction temperature instead of 100°C reaction temperature).

[0063] Chiral reagents (e.g., alkenes and/or hydrazones and/or hydrazines) can be used to control formation of chiral centres in the target product.

[0064] Enantiopure beta-aminocarbonyls can be obtained, using the process of the present application, using three approaches, as follows: i) Asymmetric catalysis of the reaction.

In this approach, either a stoichiometric or sub-stoichiometric amount of a chiral additive is added to the reaction mixture to obtain a product mixture favouring one of the two enantiomers. From the moment a mixture favouring one of the two enantiomers is obtained, an enantiopure compound may be available via a recrystallization. ii) Kinetic resolution of the racemic product obtained from the reaction (racemic is a 1 : 1 mixture of enantiomers).

In this approach, the reaction is performed in the presence of an enantiopure chiral reagent or catalyst (for example, as referenced above). A reaction is formed in which one of the two enantiomers reacts faster than the other. Therefore, either the enantiomer that has reacted or the enantiomer that has not reacted can be separated and obtained as two different products. Each can be present as a mixture favouring one of the two enantiomers. Kinetic resolution has been used to obtain enantiopure beta-amino acids and derivatives both chemically and enzymatically, such as on the fluorenone dipole itself. iii) Chiral Resolution (separation), for example, either by crystallization or by chiral chromatography.

This can be achieved by selective crystallisation of one enantiomer in the form of an enantioenriched solid (typically by using either an enantiopure chiral amine base or an enantiopure chiral acid, via formation of diastereomic salts) or by using chiral chromatography.

[0065] In certain embodiments of this process, the analogous thiocarbonyl derivatives can be used as the starting hydrazone or hydrazine material.

[0066] There are various methods that can be used to synthesize the starting hydrazone and hydrazine starting materials. Details of some methods are provided in the Examples below. Also provided in the Examples are details of reaction conditions used in certain exemplary aminocarbonylation/aminothiocarbonylation and aminocarbonylation/aminothiocarbonylation reactions.

[0067] To gain a better understanding of the invention described herein, the following examples are set forth. It should be understood that these examples are for illustrative purposes only. Therefore, they should not limit the scope of this invention in any way.

EXAMPLES

[0068] General Experimental Information.

[0069] Infrared spectra were recorded on a Bomem Michelson 100 Fourier transform infrared (IR) spectrometer as neat thin films on NaCl plates and are reported in cm "1 . *H NMR and 13 C NMR spectra were recorded in deuterated solvents using Bruker AC-400, AC- 300 spectrometers at ambient temperature, unless otherwise indicated. The data are reported as follows: chemical shift in ppm using solvent as the reference (CDCI 3 at 7.26 ppm, CeD 6 at 7.15 ppm or DMSO-d 6 at 2.50 ppm for ¾ NMR and CDC1 3 at 77.0 ppm or DMSO-d 6 at 39.43 for 13 C NMR), multiplicity (b = broad, s = singlet, d = doublet, t = triplet, q = quartet, sept = septuplet, m = multiplet), coupling constants (Hz) and integration. High resolution mass spectra (HRMS) were acquired on a Kratos Concept-11 A mass spectrometer with an electron beam of 70ev at the Ottawa-Carl eton Mass Spectrometry Centre. [0070] Materials.

[0071] Unless otherwise noted, all commercially available materials were purchased from commercial sources and used without further purification.

[0072] Example 1 : Intermolecular Aminocarbonylation

[0073] In this example, intermolecular aminocarbonylation reactions were performed to demonstrate the successful use of imino compounds of Formula IV, having different leaving groups or different imino groups, in β-aminocarbonylation reactions at different temperatures.

[0074] In certain examples, R 1 and R 2 together form the fluorenyl ring system (a 6-5-

6 ring system). Other ring systems such as 6-6-6 can be used, and these rings can be substituted or unsubstituted. Without wishing to be bound by theory, these planar ring systems (particularly the central ring) may favour the reaction in the formation of the isocyante intermediate.

[0075] An exemplary general reaction scheme is as follows (with Ot-Bu as the leaving group):

[0076] Another exemplary reaction scheme is illustrated as follows:

alkene aminocarbonylation [0077] A summary of reactions tested is provided in Tables 1, 2 and 2a below, where yield was determined based on quantification of the dipole by NMR:

Table 1: β-aminocarbonylation Using Imino Compounds Having Different Leaving Groups

Entry LG 150 °C 120 °C 100 °C 80 °C

1 NH'Bu 12% 2%

2 NHPh 20% 4%

3 NiPr 2 90% 69% 46% 13%

4 OCH 2 CF 3 82% 55% 30% 9%

5 OEt 100% 8% 0

6 O'Bu 98% 69% 23% 7%

7 OPh 92% 85% 84% 38% b

8 SEt 98% 64% 46% 11 %

9 SP 90% 69% 60% 31 % a. The yields are NMR yields

b. This yield is at 70 °C

Table 2: β-aminocarbonylation Using Imino Compounds Having Different Imino Groups

X^Bu or OPh 3a -g, w-z

SM Product SM Product

rxn Table 2a. Alkene Aminocarbonylation Using Aldehyde-Derived Hydrazones

Entry Product Equiv of Time (h) yield (%)

alkene

1 R = 2-furyl, 12a 2 1.5 53 2 R = 2-thiophenyl, 12b 1.2 1.5 46 3 R = C 6 H 5 , 12c 5 3 53 c 4 R = 2-MeOC 6 H 4 , 12d 2 3 34 5 R = 3-MeOC 6 H 4 , 12e 2 3 36 6 R = 2-ClC 6 H 4 , 12f 5 1

7 R = 2-BrC 6 H 4 , 12g 5 1 43 d,f R = 1-naphthyl, 12h 5 3 44

12 Ar = 2-MeOC 6 H 4 , 121 1.5 70' Entry Product 6 Equiv of Time (h) yield (%)

alkene

13 Ar = 3-MeOC 6 H 4 , 12m 2 1.5 6(

14 Ar = 4-MeOC 6 H 4 , 12n 2 1.5 60

15 Ar = 1-naphthyl, 12o 2 1 31 d

Conditions: hydrazone (1 equiv), alkene (1.2-10 equiv, see above) in PhCF 3 (0.05 M) heated in a sealed vial (microwave reactor, 130 °C, 3 h). The identity of the major stereoisomer was secured by NOE experiments on 2a. Stereochemistry of other dipoles was assigned by analogy. c 120 °C. d NMR yield. e 150 °C. f 140 °C.

[0078] Ketohydrazones demonstrated increased reactivity and stability as compared to aldhydrazones, and as such, ketohydrazones can be used for the isolation of azomethine imine product. However, aldydrazones have been shown to produce azomethine imines under different reaction conditions (see Example 7, below).

[0079] A second cycloaddition resulting in an undesirable azomethine imine cycloaddition may occur in the presence of large amounts of excess alkene. Without wishing to be bound by theory, one possible pathway for this second cycloaddition is as follows:

[0080] Synthesis of Starting Materials for Table 1

[0081] The starting materials shown in Table 1 were synthesized according to the scheme shown below (Scheme 1). Entries 1-5 correspond to starting compounds la-e and entries 7-9 correspond to starting compounds lg-i. These starting compounds were made from ferf-butyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarboxylate (Table 1, entry 6, If).

Scheme 1

[0082] General procedure A: To a 2-5 mL microwave ("μ\ν") tube were added If (460 mg, 2.0 mmol), trifluorotoluene (4 mL), and the nucleophile (10 mmol, 5 equiv). The tube was then sealed with a microwave cap and heated for 3 minute at 150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and purified by silica gel chromatography to give the corresponding products. The reaction proceeds, for example, as set out below:

NH Ph 63% NH'BU 90%

[0083] General procedure B: To a 2-5 mL μw tube were added If (460 mg, 2.0 mmol), the nucleophile (2 mL). The tube was then sealed with a microwave cap and heated for 3 minutes at 150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and purified by silica gel chromatography to give the corresponding products. The reaction proceeds, for example, as set out below:

C H3CH2OH 68% C F3CH 2OH 57%

[0084] General procedure C (Berger, R.; Duff, K.; Leighton, J. L. J. Am. Chem. Soc. 2004, 126, 5686): To a round bottom flask were added the corresponding carbazate, ketone (2 equiv), methanol and a catalytic amount of AcOH (5-15 mol%). The reaction solution was refluxed overnight (10-14 h), then cooled to ambient temperature, concentrated under reduced pressure and purified by silica gel chromatography or direct recrystallization to give the corresponding products. The reaction proceeds, for example, as set out below:

[0085] V-teri-Butyl-2-(2,4-dimethylpentan-3-ylidene)hydrazinecarbox amide (Table 1, entry 1, la).

[0086] Synthesized according to general procedure A using f-butylamine (730 mg, 1.1 mL, 10 mmol, 5 equiv) as nucleophile. The reaction mixture was concentrated under reduced pressure and isolated by silica gel chromatography (20% EtOAc in hexane). The title compound was obtained as a white solid (410 mg, 90% yield). TLC Rf 0.61 in 20% EtOAc in hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.40 (bs, 1H), 6.16 (s, 1H), 2.97-2.86 (m, 1H), 2.55 (sept, J = 6.73 Hz, 1H), 1.07 (d, J = 6.97 Hz, 6H), 1.04 (d, J = 6.75 Hz, 6H); 13 C NMR (100 MHz, CDCls) δ ppm 159.4 (C), 156.2 (C), 49.8 (C), 30.3 (CHi), 29.3 (3CH 3 ), 27.9 (CHi), 22.0 (2CH 3 ), 18.9 (2CH 3 ); IR 3391, 2963, 2930, 2870, 1675, 1530, 1457, 1390, 1362, 1306, 1139, 913, 764 cm "1 ; HRMS(EI):Exact mass calcd for C 12 H 25 N 3 O [M] + : 227.1993. Found: 227.1983.

[0087] 2-(2,4-Dimethylpentan-3-ylidene)- V-phenylhydrazinecarboxamide (Table 1, entry 2, lb)

[0088] Synthesized according to general procedure A using aniline (930 mg, 0.90 mL, 10 mmol, 5 equiv) as nucleophile. The reaction mixture was concentrated under reduced pressure and isolated by silica gel flash chromatography (30% EtOAc in hexane). The title compound was obtained as a white solid (310 mg, 63% yield). TLC Rf 0.63 in 30% EtOAc in hexanes. Ti NMR (400 MHz, CDC1 3 ) δ ppm 9.15 (bs, 1H), 8.34 (s, 1H), 7.52 (d, J = 7 ' .93 Hz, 2H), 7.30 (t, J = 7.90 Hz, 2H), 7.03 (t, J = 7.38 Hz, 1H), 3.14-3.01 (m, 1H), 2.66 (sept, J = 6.73 Hz, 1H), 1.15 (d, J = 6.88 Hz, 12H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 161.9 (C), 154.5 (C), 138.5 (C), 128.9 (2CHi), 122.9 (CHi), 119.2 (2CH), 30.2 (CHi), 28.4 (CHi), 22.1 (2CHi), 19.0 (2CHi); IR 3376, 3196, 3103, 2963, 2935, 2871, 1678, 1593, 1538, 1501, 1448, 1295, 1216, 1136, 1070, 1034, 755, 692 cm "1 ; HRMS(EI): Exact mass calcd for Ci 4 H 2 iN 3 0 [M] + :247.1679. Found: 247.1667.

[0089] 2-(2,4-Dimethylpentan-3-ylidene)-AyV-diisopropylhydrazinecar boxamide (Table 1, entry 3, lc)

[0090] Synthesized according to general procedure B using diisopropyl amine (2 mL) as nucleophile and solvent. The reaction mixture was concentrated under reduced pressure and isolated by silica gel flash chromatography (20% EtOAc in hexane). The title compound was obtained as a white solid (270 mg, 52% yield). TLC Rf 0.49 in 20% EtOAc in hexanes. l NMR (400 MHz, CDC1 3 ) δ ppm 7.12 (s, 1H), 3.88 (sept, J = 6.66 Hz, 2H), 2.73 (sept, J = 6.19 Hz, 1H), 2.57 (sept, J = 6.78 Hz, 1H), 1.25 (d, J = 6.83 Hz, 12H), 1.10 (d, J = 7.06 Hz, 6H), 1.06 (d, J = 6.85 Hz, 6H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 161.6 (C), 156.3 (C), 46.4 (2CHi), 31.1 (CHi), 27.7(CHi), 21.7 (2CH 3 ), 21.4 (4CH 3 ), 18.9 (2CH 3 ). IR 3228, 2968, 2871, 1702, 1634, 1447, 1342, 1135, 1072, 1019, 741 cm "1 ; HRMS(EI): Exact mass calcd for C14H2 9 N 3 O [M] + : 255.2305. Found: 255.2312.

[0091 ] 2,2,2-Trifluoroethyl 2-(2,4-dimethylpentan-3-ylidene)hydrazineccarboxylate (Table 1, entry 4, Id)

[0092] Synthesized according to general procedure B using 2,2,2-trifluoroethanol (2 mL) as nucleophile and solvent. The reaction mixture was concentrated under reduced pressure and isolated by silica gel flash chromatography (15% EtOAc in hexane). The title compound was obtained as a white solid (370 mg, 72% yield). TLC Rf 0.34 in 15% EtOAc in hexanes. l NMR (300 MHz, CDC1 3 ) δ ppm 7.96 (s, 1H), 4.52 (q, J = 8.33 Hz, 2H), 2.78 (sept, J = 7.02 Hz, 1H), 2.62 (sept, J = 6.78 Hz, 1H), 1.16-1.08 (m, 12H); 13 C NMR (75 MHz, CDCI 3 ) δ ppm 162.7 (C), 147.5 (C), 118.7 (q, J = 277.37 Hz, C), 56.8 (q, J = 36.86 Hz, CH 2 ), 27.1 (CH), 23.6 (CH), 17.2 (CH 3 ), 14.6 (CH 3 ); IR (film) 3229, 2972, 2932, 1724, 1532, 1223, 1171, 998cm "1 ; HRMS(EI): Exact mass calcd for CioHnFsNzOz [M] + :254.1237. Found: 254.1250. [0093] Ethyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarboxylate (Table 1, entry 5, le) E t

[0094] Synthesized according to general procedure B using ethanol (2 mL) as nucleophile and solvent. The reaction mixture was concentrated under reduced pressure and isolated by silica gel flash chromatography (30% EtOAc in hexane). The title compound was obtained as a white solid (270 mg, 68% yield). TLC Rf 0.42 in 30% EtOAc in hexanes. ¾ NMR (400 MHz, CDCls) δ ppm 7.71 (s, 1H), 4.21 (q, J = 7.09 Hz, 2H), 2.74 (sept, J = 7.08 Hz, 1H), 2.61 (sept, J = 6.78 Hz, 1H), 1.28 (t, J = 7.09 Hz, 3H), 1.13 (d, J = 7.07 Hz, 6H), 1.10 (d, J = 6.82 Hz, 6H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 164.2 (C), 154.0 (C), 61.6 (CH 2 ), 31.8 (CHi), 27.7 (CHi), 21.4 (CH 3 ), 18.9 (2CH 3 ), 14.6 (2CH 3 ). IR 3199, 3038, 2954, 2866, 1733, 1701, 1542, 1364, 1312, 1252, 1230, 1097, 1040, 1007, 700 cm "1 ; HRMS(EI): Exact mass calcd for Ci 0 H 20 N 2 O 2 [M] + :200.1520. Found: 200.1523.

[0095] iS-Ethyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarbothioate (Table 1, entry 8, lh)

[0096] Synthesized according to general procedure A using ethanethiol (621 mg, 0.70 mL, 10 mmol, 5 equiv) as nucleophile. The reaction mixture was concentrated under reduced pressure and isolated by silica gel flash chromatography (15% EtOAc in hexane). The title compound was obtained as a white solid (390 mg, 90% yield). TLC Rf 0.43 in 15% EtOAc in hexanes. Ti NMR (400 MHz, CDC1 3 ) δ ppm 9.26 (bs, 1H), 2.91-2.76 (m, 3H), 2.60 (sept, J = 6.70 Hz, 1H), 1.28 (t, J =7.40 Hz, 3H), 1.11 (d, J = 6.91 Hz, 12H); 13 C NMR (100 MHz, CDCI 3 ) δ ppm 173.0 (C), 163.8 (C), 30.8 (CHi), 28.3 (CHi), 23.1 (CH 2 ), 21.9 (CH 3 ), 19.0 (CH 3 ), 15.2 (CH 3 ). IR 3190, 2968, 2930, 2874, 1646, 1466, 1312, 1264, 1220, 1068, 732, 688 cm "1 ; HRMS(EI): Exact mass calcd for Ci 0 H 20 N 2 OS [M] + : 216.1291. Found: 126.1301. [0097] ^-Phenyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarbothioate (Table 1, entry 9, li)

[0098] Synthesized according to general procedure A using benzenethiol (1.1 g, 1.1 ml, 10 mmol, 5 equiv) as nucleophile. The reaction mixture was concentrated under reduced pressure and isolated by silica gel flash chromatography (15% EtOAc in hexane). The title compound was obtained as a white solid (290 mg, 55% yield). TLC Rf 0.32 in 15% EtOAc in hexanes. Ti NMR (400 MHz, CDC1 3 ) δ ppm 9.90 (s, 1H), 7.56-7.47 (m, 2H), 7.39-7.32 (m, 3H), 2.72 (sept, J = 6.86 Hz, 1H), 2.60 (sept, J = 6.74 Hz, 1H), 1.14 (d, J = 6.75 Hz, 6H), 0.92 (d, J = 6.92 Hz, 6H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 172.0 (C), 164.9 (C), 135.8 (CH), 129.5 (C), 128.8 (CH), 128.6 (CH), 30.5 (CH), 28.3 (CH), 22.0 (CH 3 ), 18.8 (CH 3 ). IR 2971, 2931, 2868, 1654, 1406, 1303, 1266, 1217, 1064 cm "1 ; HRMS(EI): Exact mass calcd for Ci 4 H 2 oN 2 OS [M] + : 264.1291. Found: 264.1295.

[0099] feri-Butyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarboxylate (Table 1, entry 6, If)

[00100] Synthesized according to general procedure C using ferf-butyl carbazate (10 g, 76 mmol), 2,4-dimethylpentan-3-one (22 mL, 152 mmol, 2 equiv), acetic acid (0.50 mL, 8.7 mmol) and methanol (250 mL). The target compound was directly recrystalized from hexanes as a white solid (15 g, 87%). ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.60 (bs, 1H), 2.73 (sept, J = 7.04 Hz, 1H), 2.59 (sept, J = 6.81 Hz, 1H), 1.47 (s, 9H), 1.12 (d, J = 7.03 Hz, 6H), 1.10 (d, J = 6.08 Hz, 6H). 13 C NMR (CDC1 3 , 100 MHz) ) δ ppm 163.4 (C), 153.0 (C), 80.7 (C), 31.6 (CH), 28.4 (CH 3 ), 27.8 (CH), 21.5 (CH 3 ), 19.0 (CH 3 ). IR (film) 3208, 2973, 2934, 1736, 1703, 1528, 1369, 1251, 1179, 1047 cm "1 . HRMS (EI): Exact mass calcd for Ci 2 H 24 N 2 0 2 [M] + : 228.1838; found: 228.1747. [00101] Phenyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarboxylate (Table 1, entry

7, lg)

[00102] To a 10-20 mL μ-w tube was added phenyl carbazate (synthesized according to known procedure: Lu, X.; Reid, D. L.; Warkentin, J. Can. J. Chem. 2001, 79, 319-327; 1.3 g, 9.0 mmol), 2,4-dimethylpentan-3-one (2.5 mL, 18 mmol), acetic acid (90 drops) and methanol (17 mL). The tube was then sealed with a microwave cap and heated for 1.5 h at 65 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and purified by silica gel chromatography. Recrystalization from 20% EtOAc in hexanes to give target compound (1.1 g, 50% yield) as a white solid, mp: 90-91 °C. *H NMR (400 MHz, CDCls) δ ppm 8.08 (s, 1H), 7.38-7.31 (m, 2H), 7.22-7.15 (m, 3H), 2.82 (sept, J = 7.02 Hz, 1H), 2.65 (sept, J = 6.75 Hz, 1H), 1.19-1.12 (m, 9H). 13 C NMR (75 MHz, CDC1 3 ) δ ppm 166.2 (C), 156.3 (C), 150.8 (C), 129.3 (CH), 125.5 (CH), 121.5 (CH), 31.6 (CH), 27.9 (CH), 21.5 (CH 3 ), 18.9 (CH 3 ); IR 3214, 3028, 2963, 2930, 2872, 1723, 1529, 1492, 1246, 1038, 1000, 737, 704, 683 cm "1 ; HRMS(EI): Exact mass calcd for C14H2 0 N2O2 [M] + :

248.1519. Found: 248.1495.

[00103] Synthesis of Starting Materials for Table 2

[00104] feri-Butyl 2-cyclopentylidenehydrazinecarboxylate (Table 2, entry 2, 2b)

[00105] Synthesized according to general procedure C using ferf-butyl carbazate, cyclopentanone and acetic acid in methanol. The title compound was obtained as a white solid. The spectral data matched that of a previous literature report (Ghali, N. I.; Venton, D. L.; Hung, S. C; Le Breton, G. C. Journal of Organic Chemistry 1981, 46, 5413). l NMR (300 MHz, CDCI 3 ) δ ppm 7.17 (bs, 1H), 2.45 (t, J = 7.2, 2H), 2.16 (t, J = 7.1, 2H), 1.84 (quin, J= 7.1, 2H), 1.73 (quin, J = 7.0, 2H), 1.50 (s, 9H).

[00106] tert-Butyi 2-(diphenylmethylene)hydrazinecarboxylate (Table 2, 2d)

[00107] Synthesized according to general procedure C using ferf-butyl carbazate (500 mg, 3.8 mmol), benzophenone (1.4 g, 7.6 mmol, 2 equiv) and acetic acid (0.2 mL) in methanol (30 mL). The title compound was obtained as a white solid (550 mg, 49% yield). TLC R f 0.53 20% EtOAc in hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.66 (s, 1H), 7.60-7.47 (m, 5H), 7.31-7.22 (m, 5H), 1.48 (s, 9H); 13 C NMR (100 MHz, CDC1 3 ) ) δ ppm 137.2, 129.8, 129.7, 129.3, 128.5, 128.1, 127.4, 28.3.

[00108] feri-Butyl 2-(propan-2-ylidene)hydrazinecarboxylate (Table 2, 2e) fBu

[00109] Synthesized according to general procedure C using tot-butyl carbazate (0.50 g, 3.8 mmol), acetone (15 mL, as regent and solvent) and acetic acid (0.20 mL). The reaction mixture was concentrated under reduced pressure and isolated by silica gel flash

chromatography (30% EtOAc in hexane). The title compound was obtained as a white solid (0.52 g, 79% yield). TLC Rf 0.29 in 30% EtOAc in hexanes. ¾i NMR (CDC1 3 , 300 MHz) δ 7.76 (s, 1H), 2.54 (dsextet, J = 13.3, 6.6, 1H), 1.46 (s, 9H), 1.05 (d, J = 6.9, 6H); 13 C NMR (CDCI 3 , 100 MHz) d ppm 169.9 (CH), 152.3 (CH), 80.9 (C), 31.4 (CH), 28.4 (CH 3 ), 20.0 (CH) IR (film); 3207, 2967, 2329, 1755, 1680 cm "1 ; HRMS (EI): Exact mass calcd for C 9 Hi 8 N 2 0 2 [M] + : 186.1368; found: 186.1325. (E)-tert-butyl 2-(3,3-dimethylbutan-2-ylidene)hydrazinecarboxylate (Table 2,

[00111] Synthesized according to general procedure C using ferf-butyl carbazate, 3,3- dimethylbutan-2-one and acetic acid in methanol. The title compound was obtained as a white solid. l NMR (CDC1 3 , 300 MHz) ) δ 7.37 (s, 1H), 1.74 (s, 3H), 1.48 (s, 9H), 1.12 (s, 9H); 13 C NMR (CDC1 3 , 100 MHz) d ppm 158.0 (C), 153.0 (C), 80.7 (C), 38.7 (C), 28.4 (CH 3 ), 27.6 (CH 3 ), 11.1 (CH 3 ); IR (film); 3210, 2953, 1748, 1734, 1684 cm "1 ; HRMS (EI): Exact mass calcd for C11H22N2O2 [M] + : 214.1681; found: 214.1619.

[00112] tert-Butyi 2-Adamantanylidenehydrazinecarboxylate (Table 2, 2g) o

O f Bu

[00113] Synthesized according to general procedure C using ferf-butyl carbazate, 2- admantanone and acetic acid in methanol. The title compound was obtained as a white solid. Ti NMR (CDC1 3 , 300 MHz) ) δ 7.54 (d, J= 0.2 Hz, 1H), 2.90 (s, 1H), 2.69 (s, 1H), 1.97-1.74 (m, 14H), 1.47 (s, 10H); 13 C NMR (CDC1 3 , 100 MHz) δ ppm 162.7 (C), 153.4 (C), 80.7 (C), 39.4 (CH), 37.6 (CH 2 ), 36.4 (CH 2 ), 30.7 (CH), 28.4 (CH 3 ), 27.8 (CH); IR (film); 3210, 2979, 2914, 2853, 1728, 1702, 1534 cm "1 ; HRMS (EI): Exact mass calcd for C15H24N2O2 [M] + : 264.1838. Found Fragments: 57.0710 (100%), 41.0392 (33%), 79.0554 (17.3%), 81.0698 (16.3%), 39.0238 (16.2%). [00114] fert-Butyl 2-(l,7,7-trimethylbicyclo[2.2.1]heptan-2- ylidene)hydrazinecarboxylate (Table 2, 2i)

[00115] Synthesized according to general procedure C using ferf-butyl carbazate, camphor and acetic acid in methanol. ¾ NMR (CDC1 3 , 300 MHz) δ 7.17 (bs, 1H), 2.28 (dt, J = 16.4, 3.7 Hz, 1H), 1.95 (t, J = 4.4 Hz, 1H), 1.89-1.60 (m, 3H), 1.46 (s, 9H), 1.46-1.37 (m, 1H), 1.20-1.08 (m, 1H), 1.04 (s, 3H), 0.89 (s, 3H), 0.71 (s, 3H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 165.3 (C), 152.8 (C), 80.6 (C), 52.6 (C), 48.0 (C), 44.0 (CH 3 ), 33.3 (CH 2 ), 32.5 (CH 2 ), 28.4 (3CH 3 ), 27.4 (CH 2 ), 19.6 (CH 3 ), 18.7 (CHi), 11.2 (CH 3 ).

[00116] Phenyl 2-benzylidenehydrazinecarboxylate (Table 2, 2y).

9

[00117] Synthesized according to general procedure C using phenyl carbazate (1.5 g, 10 mmol), benzaldehyde (1.1 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solide (2.1 g, 88% yield). TLC R f = 0.33 in 20% EtOAc/hexanes. ¾ NMR (300 MHz, CDC1 3 ) ppm δ 8.30-8.25 (m, 2H), 7.47-7.41 (m, 3H), 7.16 (s, 1H), 4.44 (d, J = 6.67 Hz, 1H), 2.81-2.72 (m, 2H), 2.67 (d, J = 2.78 Hz, 1H), 1.76-1.55 (m, 2H), 1.45-1.19 (m, 4H). 13 C NMR (75 MHz, CDC1 3 ) ppm δ 150.6 (C), 146.2 (C), 133.4 (C), 130.3 (CH), 129.4 (CH), 128.7 (CH), 127.5 (CH), 125.8 (CH), 121.5 (CH). IR (film); 3225, 3061, 1729. 1543, 1488, 1219, 772 cm "1 ; HRMS(EI): Exact mass calcd for Ci 4 Hi 2 N 2 0 2 [M] + : 240.0893. Found: 240.0880. Phenyl 2-(9H-fluoren-9-ylidene)hydrazinecarboxylate (Table 2, 2z).

[00119] Synthesized according to general procedure C using phenyl carbazate (1.5 g, 10 mmol), fluoren-9-one (1.8 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as yellow solide (2.1 g, 67% yield). TLC R f = 0.31 in 20% EtOAc/hexanes. l NMR (400 MHz, CDCl 3 ) ppm <i 9.18 (s, 1H), 7.91 (d, J = 7.48 Hz, 1H), 7.82 (d, J = 7.63 Hz, 1H), 7.66 (d, J = 7.51 Hz, 1H), 7.56 (d, J = 7.43 Hz, 1H), 7.47-7.21 (m, 9H). 13 C NMR (100 MHz, CDCls) ppm c 150.6 (C), 142.6 (C), 139.5 (C), 136.8 (C), 131.4 (CH), 130.3 (CH), 129.7 (C), 129.6 (CH), 128.4 (CH), 128.1 (CH), 126.0 (CH), 125.6 (CH), 122.6 (CH), 121.5 (CH), 121.0 (CH), 119.7 (CH). ). IR (film) 1716, 1735, 1490, 1471, 1219, 1171, 772 cm "1 ; HRMS(EI): Exact mass calcd for C2 0 H14N2O2 [M] + : 314.1050. Found: 314.1056.

[00120] Intermolecular Aminocarbonylation Reactions for Table 1 and Table 2

[00121] General procedure A: An oven or flame dried 2-5 mL μw tube with a stir bar was capped with a septum and purged with argon for 5 minutes. The acyl hydrazone (0.2 mmol), trifloroutoluene (4 mL), corresponding alkene (2 mmol, 10 equiv) were added to the sealed tube. The septum was removed and the tube was then quickly sealed with a microwave cap and heated for 2-6 hours at 80-150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by H NMR using 1,4- dimethoxybenzene or 1,3,5-trimethoxybenzene as an internal standard. The corresponding product was purified using a pipe silica gel column (using EtOAc to wash out byproducts first, then using 10-20% methanol in EtOAc to wash out the target compound).

[00122] General procedure B (neat reaction): To a 0.2-0.5 mL μw tube were added the acyl hydrazone (0.2 mmol) and corresponding alkene (2 mmol, 10 equiv). Then it was sealed with a microwave cap and heated for 2-5 hours at 80-150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by H NMR using 1,4-dimethoxybenzene or 1,3,5-trimethoxybenzene as an internal standard. The corresponding product was purified using a pipe silica gel column (using ethyl acetate (EtOAc) to wash out by products first, then using 10-20% methanol in EtOAc to wash out the target compound).

[00123] General procedure C (gram-scale reaction): To a dry round-bottom flask, acyl hydrazone and alkene were disolved in trifluorotonluene, equipped with a reflux condenser and stirred under argon. The mixture was heated to 100 °C in an oil bath for 6 h. The mixture was then cooled to room temperature, the stir bar removed, and TFT evaporated to give a dark residue. The crude mixture was purified by passing through a silica plug, eluting first with 1/4 : EtOAc/DCM to remove excess alkene and a purple byproduct, then then 9/1 : EtOAc/MeOH to elute the product. Solvent removed by evaporation to give the product (819 mg, 82%) as a yellow solid.

[00124] (±)-exo-2-(2,4-dimethylpentan-3-ylidene)-4- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (3a)

[00125] Synthesized according to general procedure A using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (50 mg, 0.20 mmol) and norbornene (190 mg, 2.0 mmol). The title compound (at 100 °C, 45 mg, 91% isolated yield, 84% NMR yield; at 150 °C, 92 NMR yield; at 120 C, 85% NMR yield, at 70 C, 38% NMR yield) was obtained as yellow oil. TLC Rf 0.54 in 15% methanol in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 4.18 (d, J = 7.17 Hz, 1H), 3.00 (sept, J = 6.50 Hz, 1H), 2.85-2.71 (m, 2H), 2.63 (d, J = 7.10 Hz, 1H), 2.39 (s, 1H), 1.66-1.53 (m, 2H), 1.39 (d, J = 10.79 Hz, 1H), 1.33 (t, J = 6.95, 6.95 Hz, 6H), 1.31-1.23 (m, 2H), 1.21 (d, J = 6.72 Hz, 3H), 1.18-1.12 (m, 4H); 13 C NMR (100 MHz, CDCls) δ ppm 183.3, 161.2, 72.6 (CHi), 51.0 (CHi), 43.1 (CHi), 39.1 (CHi), 32.7 (CH , 32.2 (CH 2 ), 29.9 (<¾), 27.1 (CH 2 ), 25.4 (CH 2 ), 19.0 (CH 3 ), 18.9 (CH 3 ), 16.9 (CH 3 ), 16.5 (CH 3 ). IR (film); 2959, 2879, 1652, 1582, 1362, 1020 cm "1 ; HRMS (EI): Exact mass calcd for Ci 5 H 24 N 2 0i [M] + : 248.1883; found: 248.1905. [00126] The ORTEP of the crystal structure for compound 3a is shown in Figure 4, and the X-ray data is provided in Tables 27 - 33.

[00127] (±)-exo-2-Cyclopentanylidene-4-oxo-2,3-diazatricyclo [4,3,1 6 ' 9 ,0] decane-2-ium 3-ide (3b)

[00128] Synthesized according to general procedure A using ferf-butyl 2- cyclopentanylidenehydrazinecarboxylate 2b (40 mg, 0.20 mmol) and norbornene (190 mg, 2.0 mmol). The reaction was under 150 °C. The title compound (31 mg, 70%) was obtained as yellow oil. ¾ NMR (CDC1 3 , 300 MHz) ) δ 4.15 (d, J = 6.9, 1H), 2.66 (m, 7H), 1.93 (m, 4H), 1.60-1.43 (m, 3H), 1.25-1.18 (m, 3H); 13 C NMR (CDC1 3 , 100 MHz) d ppm , 183.4 (C), 160.4 (C), 72.4 (CH), 52.6 (CH), 40.7 (CH), 39.1 (CH), 33.9 (CH 2 ), 32.4 (CH 2 ), 31.9 (CH 2 ), 27.0 (CH 2 ), 25.9 (CH 2 ), 25.2 (CH 2 ), 24.4 (CH 2 ); IR (film); 2971, 2918, 2850, 1664, 1569, 1405 cm "1 ; HRMS (EI): Exact mass calcd for Ci 3 Hi 8 N 2 0i [M] + : 218.1414; found: 218.1726.

[00129] (±)-exo-2-Diphenylmethylene-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2- ium-3-ide (3d)

[00130] Synthesized according to general procedure A using ferf-butyl 2- diphenylmethylenehydrazinecarboxylate 2d (60 mg, 0.20 mmol) and norbornene (190 mg, 2.0 mmol). The reaction was under 150 °C. The title compound (31 mg, 70%) was obtained as yellow oil. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.88 (dd, J = 8.21, 1.62 Hz, 2H), 7.53-7.49 (m, 3H), 7.41-7.27 (m, 5H), 4.61 (d, J = 1.12 Hz, 1H), 2.76 (d, J = 3.72 Hz, 1H), 2.68 (d, J = 7.11 Hz, 1H), 2.20 (d, J = 4.54 Hz, 1H), 1.60-1.45 (m, 2H), 1.35-1.08 (m, 3H), 0.75-0.66 (m, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 185.3, 144.6, 134.7, 133.9, 131.9 (CHi), 131.0 (CHi), 130.3 (CHi), 129.9 (CHi), 129.2 (CHi), 127.9 (CHi), 75.4 (CHi), 50.7 (CHi), 42.0 (CHi), 39.8 (CHi), 32.2 (CH 2 ), 27.1 (CH 2 ), 25.4 (CH 2 ). HRMS(EI): Exact mass calcd for C 2 iH 20 N 2 O [M] + : 316.1571. Found: 316.1540.

[00131] (±)-exo-2-(Propan-2-ylidene)-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2- ium-3-ide (3e)

[00132] Synthesized according to general procedure A using ferf-butyl 2-(propan-2- ylidene)hydrazinecarboxylate 2e (34 mg, 0.20 mmol) and norbomene (190 mg, 2.0 mmol). The reaction was under 150 °C. The title compound (29 mg, 70%) was obtained as yellow oil. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 4.17 (d, J = 7.13 Hz, 1H), 2.75 (d, J = 7.09 Hz, 1H), 2.70 (s, 1H), 2.52 (s, 1H), 2.28 (s, 3H), 2.24 (s, 3H), 1.65-1.52 (m, 2H), 1.45-1.38 (m, 1H), 1.29-1.11 (m, 3H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 183.3, 147.6, 71.5 (CHi), 52.7 (CHi), 41.8 (CHi), 39.0 (CHi), 32.3 (CH 2 ), 27.0 (CH 2 ), 25.3 (CH 2 ), 22.8 (CH 3 ), 21.4 (CH 3 ).

HRMS (EI): Exact mass calcd for CnHi 6 N 2 0 [M] + : 192.1258. Found: 192.1239.

[00133] (±)-exo-2-(3,3-dimethylbutan-2-ylidene)-4-oxo-2,3- diazatricyclo [4,3,1 6 ' 9 ,0] decane-2-ium-3-ide (3f)

[00134] Synthesized according to general procedure A using ferf-butyl 2-(3,3- dimethylbutan-2-ylidene)hydrazinecarboxylate 2f (45 mg, 0.20 mmol) and norbomene (190 mg, 2.0 mmol). The reaction was under 150 °C. The title compound (40 mg, 70%) was obtained as yellow oil. ¾i NMR (CDC1 3 , 400 MHz) δ 4.26 (d, J = 7.0, 1H), 2.67 (s, 1H), 2.61 (d, J = 7.0, 1H), 2.46 (s, 1H), 2.19 (s, 3H), 1.55 (m, 2H), 1.30 (s, 9H), 1.16 (m, 4H); 13 C NMR (CDCI 3 , 100 MHz) d ppm 183.0 (C), 157.5 (C), 74.1 (CH), 50.9 (CH), 42.0 (CH), 39.4 (CH 3 ), 38.9 (C), 32.0 (CH 2 ), 27.0 (CH 2 ), 26.2 (CH 3 ), 25.1 (CH 3 ), 19.0 (CH 3 ); HRMS (EI): Exact mass calcd for Ci 4 H 22 N 2 0i [M] + : 234.1732; found: 234.1718. [00135] (±)-exo-2-(2-Admantanylidene)-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane- 2-ium-3-ide (3g)

[00136] Synthesized according to general procedure A using ferf-butyl 2-(admantan-2- ylidene)hydrazinecarboxylate 2g (53 mg, 0.20 mmol) and norbomene (190 mg, 2.0 mmol). The reaction was under 150 °C. The title compound (49 mg, 86%) was obtained as yellow oil. l NMR (CDCls, 300 MHz) ) δ 4.12 (d, J = 7.2, 1H), 3.85 (s, 1H), 2.93 (s, 1H), 2.67 (d, J = 8.5, 2H), 2.32 (s, 1H), 2.09-1.80 (m, 12H), 1.52-1.40 (m, 3H), 1.13-1.08 (m, 3H); 13 C NMR (CDCI 3 , 100 MHz) δ ppm 182.6 (C), 161.4 (C), 70.3 (CH), 51.7 (CH), 42.5 (CH), 38.6 (CH), 38.6 (CH 2 ), 38.5 (CH 2 ), 37.5 (CH 2 ), 37.4 (CH 2 ), 35.3 (CH), 34.8 (CH), 34.4 (CH 2 ), 32.0 (CH 2 ), 26.7 (CH), 26.6 (CH 2 ), 26.6 (CH), 24.9 (CH 2 ); IR (film); 2964, 2924, 2855, 1656, 1596, 1342, 1320, 1279 cm "1 ; HRMS (EI): Exact mass calcd for Ci 8 H 24 N 2 0i [M] + : 284.1883; found: 284.1877.

[00137] (±)-exo-2-(l,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)-4 -oxo-2,3- diazatricyclo [4,3,1 6 ' 9 ,0] decane-2-ium-3-ide (3i)

[00138] ¾ NMR (CDCI 3 , 300 MHz) δ 3.95 (d, J = 6.9, 1H), 2.77-2.57 (m, 4H), 2.27

(s, 1H), 2.05 (s, 1H), 1.62-1.53 (m, 4H), 1.47 (s, 3H), 1.28-1.14 (m, 6H), 0.93-0.80 (m, 7H); 13 C NMR (CDCI 3 , 100 MHz) d ppm 183.3 (C), 161.3(C), 72.9 (CH), 57.1 (C), 51.4 (CH), 49.4 (C), 43.8 (CH), 41.5 (CH 2 ), 38.8 (CH), 37.3 (CH 2 ), 32.2 (CH 2 ), 29.7 (CH), 27.1 (CH 2 ), 26.7 (CH 2 ), 25.7 (CH 2 ), 20.3 (CH 3 ), 18.6 (CH 3 ), 13.9 (CH 3 ). [00139] (±)-exo-2-Benzylidene-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3- ide (Table 2, 3y):

[00140] Synthesized according to general procedure A using phenyl 2- benzylidinehydrazinecarboxylate (48 mg, 0.20 mmol) and norbornene (188 mg, 2.0 mmol). The reaction temperature is 120 °C and the reaction time is 3 h. The title compound (51% isolated yield) was obtained as yellow solid. TLC R f = 0.47 in 20% MeOH in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 8.31-8.25 (m, 2H), 7.46-7.38 (m, 3H), 7.13 (s, 1H), 4.42 (d, J = 7.02 Hz, 1H), 2.75 (s, 1H), 2.70-2.65 (m, 2H), 1.73-1.56 (m, 2H), 1.40 (d, J = 10.97 Hz, 1H), 1.35-1.25 (m, 2H), 1.21 (d, J = 11.83 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) ppm δ 186.2 (C), 132.2 (CH), 131.8 (CH), 131.6 (2CH), 129.5 (C), 128.8 (2CH), 76.9 (CH), 50.0 (CH), 44.3 (CH), 39.2 (CH), 32.4 (CH 2 ), 27.5 (CH 2 ), 24.9 (CH 2 ). IR (film) 3051, 2961, 2874, 2233, 1659, 1588, 1568, 1451, 1290, 1001, 908, 690 cm "1 . HRMS(EI): Exact mass calcd for Ci 5 Hi 6 N 2 0 [M] + : 240.1257. Found: 240.1256.

[00141] (±)-exo-2- [N-(9H-fluoren-9-ylidene)] -4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 2, 3z)

[00142] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and norbomene (38 mg, 0.4 mmol). The reaction temperature is 100 °C and the reaction time is 2 h. The title compound (94% NMR yield, 93% isolated yield) was obtained as yellow solid. TLC Rf 0.16 in 100% EtOAc. l NMR (400 MHz, CDC1 3 ) ppm δ 8.87 (d, J = 7.73 Hz, 1H), 7.58 (d, J = 7.43 Hz, 1H), 7.50 (d, J = 7.37 Hz, 1H), 7.45 (d, J = 7.87 Hz, 1H), 7.34 (t, J = 7.46 Hz, 2H), 7.28-7.22 (m, 2H), 4.80 (d, J = 6.77 Hz, 1H), 2.86 (d, J = 6.72 Hz, 1H), 2.81 (s, 2H), 1.77-1.63 (m, 2H), 1.50 (d, J = 11.89 Hz, 1H), 1.46-1.36 (m, 2H), 1.18 (d, J = 11.03 Hz, 1H). U C NMR (100 MHz, CDCls) ppm δ 185.8 (C), 141.6 (C), 139.5 (C), 139.1 (C), 131.7 (CH), 131.6 (C), 131.0 (CH), 130.7 (CH), 129.9 (C), 129.0 (CH), 128.1 (CH), 125.2 (CH), 120.9 (CH), 119.6 (CH), 74.7 (CH), 50.8 (CH), 42.2 (CH), 40.0 (CH), 32.1 (CH 2 ), 27.2 (CH 2 ), 25.3 (CH 2 ). ). IR (film); 2973, 2876, 1669, 1606, 1549, 1450, 1281, 1130, 1087, 727 cm "1 . HRMS(EI): Exact mass calcd for C 2 iHi 8 N 2 0 [M] + : 314.1414. Found: 314.1414.

[00143] Experimental conditions for synthesis of compounds in Table 2a

[00144] General Information: Purification of reaction products was carried out by flash column chromatography using Silicycle silica gel (40-63 μηι), unless otherwise noted. Analytical thin layer chromatography (TLC) was performed on aluminum, cut to size. Visualization was accomplished with UV light followed by staining with a potassium permanganate solution and heating.

[00145] ¾ NMR and 13 C NMR spectra were recorded on Bruker AVANCE 300 MHz and 400 MHz spectrometers at ambient temperature, unless otherwise indicated. Spectral data were reported in ppm using solvent as the reference (CDCb at 7.26 ppm, CeDe at 7.15 ppm or DMSO-c e at 2.50 ppm for ¾ NMR and CDCb at 77.0 ppm or DMSO-c e at 39.43 for 13 C NMR). H NMR data was reported as: multiplicity (ap = apparent, br = broad, s = singlet, d = doublet, t = triplet, q = quartet, quint. = quintet, sext. = sextuplet, sept = septuplet, m = multiplet), integration and coupling constant(s) in Hz. Infrared (IR) spectra were obtained with neat thin films on a sodium chloride disk and were recorded on a Bomem Michelson 100 Fourier transform infrared spectrometer (FTIR). High-resolution mass spectroscopy (HRMS) was performed on a Kratos Concept-11 A mass spectrometer with an electron beam of 70ev at the Ottawa-Carl eton Mass Spectrometry Centre.

[00146] Materials

[00147] Unless otherwise noted, all commercially available materials were purchased from commercial sources and used without further purification.

[00148] Preparation of Hvdrazones (Tables 2a and 3a)

[00149] The starting materials in were made from the condensation of acyl hydrazines with aldehydes (Table 2a, entries 1-16) or ketone (Table 3a, entries 1-16). [00150] General procedure A: Procedure taken from Leighton and coworkers (Berger, R.; Duff, K.; Leighton, J. L. J. Am. Chem. Soc. 2004, 126, 5686-5687.) To a round bottom flask were added the corresponding carbazate, ketone (1-2 equiv), methanol and a catalytic amount of AcOH (5-15 mol%). The reaction solution was refluxed overnight (10-14 h), then cooled to ambient temperature, concentrated under reduced pressure and purified by silica gel chromatography or direct recrystallization to give the corresponding hydrazones.

[00151] Phenyl 2-(furan-2-ylmethylene)hydrazinecarboxylate (Table 2a, entry 1).

[00152] Synthesized according to general procedure A using furan-2-carbaldehyde (290 mg, 3.0 mmol), phenyl hydrazinecarboxylate (460 mg, 3.0 mmol), and methanol (3.0 mL). The title compound was obtained as a very light brown solid (550 mg, 79% yield). TLC R f 0.72 in 60% EtOAc in hexanes. ¾ NMR (400 MHz; DMSO-c 6 ) δ 11.69 (s, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.45-7.41 (m, 2H), 7.29-7.25 (m, 1H), 7.23-7.20 (m, 2H), 6.89 (dd, J = 3.4 and 0.4 Hz, 1H), 6.62 (dd, J = 3.4 and 1.8 Hz, 1H). 13 C NMR (101 MHz; DMSO-c 6 ) δ 152.0, 150.9, 149.6, 145.4, 136.00, 129.9, 126.0, 122.3, 113.7, 112.6 IR (film) 1729, 1540, 1496, 1219, 769, 686, 672 cm "1 . HRMS(EI): Exact mass calcd for C12H1 0 N2O 3 [M] + : 230.0691. Found: 230.0694.

[00153] Phenyl 2-(thiophen-2-ylmethylene)hydrazinecarboxylate (Table 2a, entry 2).

[00154] Synthesized according to general procedure A using thiophene-2-carbaldehyde (900 mg, 8.0 mmol), phenyl hydrazinecarboxylate (610 mg, 4.0 mmol), methanol (10 mL) and AcOH (10 drops). The title compound was obtained as a brown solid (750 mg, 76% yield). TLC R f 0.70 in 60% EtOAc in hexanes. ¾ NMR (300 MHz, CDC1 3 ) δ 8.39 (s, 1H), 8.29 (s, 1H), 7.39 (dd, J = 9.1 and 6.4 Hz, 3H), 7.27 (s, 1H), 7.24-7.19 (m, 3H), 7.05 (dd, J = 5.0 and 3.7 Hz, 1H). 13 C NMR (101 MHz; DMSO-c 6 ) δ 151.4, 150.5, 140.8, 138.8, 130.5, 129.5, 128.6, 127.8, 125.5, 121.8 IR (film) 1710, 1571, 1489, 1267, 1211, 1034, 933, 804, 772, 711, 689 cm "1 . HRMS(EI): Exact mass calcd for C12H1 0 N2O2S [M] + : 246.0463. Found: 246.0468.

[00155] Phenyl 2-benzylidenehydrazinecarboxylate (Table 2a, entry 3).

[00156] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), benzaldehyde (1.1 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from the unpurified mixture, filtered and dried in vacuo. The title compound was obtained as colorless solid (2.1 g, 88% yield), mp: 170-172 °C (methanol). TLC R f = 0.33 in 20% EtOAc/hexanes. ¾ NMR (300 MHz, CDC1 3 ) δ 8.30-8.25 (m, 2H), 7.47-7.41 (m, 3H), 7.16 (s, 1H), 4.44 (d, J = 6.7 Hz, 1H), 2.81-2.72 (m, 2H), 2.67 (d, J = 2.8 Hz, 1H), 1.76-1.55 (m, 2H), 1.45-1.19 (m, 4H). 13 C NMR (75 MHz, CDC1 3 ) δ 150.6 (C), 146.2 (C), 133.4 (C), 130.3 (CH), 129.4 (CH), 128.7 (CH), 127.5 (CH), 125.8 (CH), 121.5 (CH). IR (film); 3225, 3061, 1729. 1543, 1488, 1219, 772 cm "1 ; HRMS(EI): Exact mass calcd for C14H12N2O2 [M] + : 240.0893. Found: 240.0880.

[00157] Phenyl 2-(2-methoxybenzylidene)hydrazinecarboxylate (Table 2a, entry 4).

[00158] Synthesized according to general procedure A using 2-methoxybenzaldehyde (4.8 mmol, 654 mg), phenyl hydrazinecarboxylate (4.8 mmol, 730 mg), methanol (10 mL). The title compound was obtained as a white solid (1.08 g, 83% yield). TLC R f 0.79 in 60%

EtOAc in hexanes. ¾ NMR (300 MHz, CDC1 3 ) δ 8.42 (s, 2H), 8.04-8.02 (m, 1H), 7.38 (q, J

= 7.9 Hz, 3H), 7.26-7.23 (m, 4H), 7.01-6.89 (m, 2H), 3.87 (s, 3H). 13 C NMR (101 MHz; DMSO-c e) δ 157.5, 151.6, 150.5, 141.1, 131.4, 129.4, 125.47, 125.40, 122.1, 121.8, 120.7, 111.8, 55.7. IR (film) 1727, 1544, 1489, 1219, 1034, 771, 685, 675 cm "1 . HRMS(EI): Exact mass calcd for C15H14N2O 3 [M] + : 270.1004. Found: 270.1031.

[00159] Phenyl 2-(3-methoxybenzylidene)hydrazinecarboxylate (Table 2a, entry 5).

[00160] Synthesized according to general procedure A using 3-methoxybenzaldehyde (8 mmol, 1.09 g), phenyl hydrazinecarboxylate (4 mmol, 609 mg), methanol (10 mL) and AcOH (10 drops). The title compound was obtained as a white solid (443 mg, 41% yield). TLC R f 0.49 in 40% EtOAc in hexanes. Ti NMR (400 MHz; DMSO-c 6 ): δ 11.75 (s, 1H), 8.13 (t, J = 0.2 Hz, 1H), 7.43 (dd, J = 8.4 and 7.5 Hz, 2H), 7.34 (d, J = 7.9 Hz, 1H), 7.28-7.21 (m, 5H), 6.99 (ddd, J = 8.2, 2.6 and 0.9 Hz, 1H), 3.79 (s, 3H). 13 C NMR (101 MHz; DMSO-c 6 ): δ 159.5, 145.5, 135.5, 129.9, 129.5, 125.5, 121.8, 119.6, 118.8, 116.1, 115.2, 111.1, 55.2 IR (film) 1736, 1544, 1490, 1366, 1218, 1035, 771, 683 cm "1 . HRMS(EI): Exact mass calcd for C15H14N2O 3 [M] + : 270.1004. Found: 270.1061.

[00161] Phenyl 2-(2-chlorobenzylidene)hydrazinecarboxylate (Table 2a, entry 6).

[00162] Synthesized according to general procedure A using 2-chlorobenzaldehyde (8 mmol, 1.12 g), phenyl hydrazinecarboxylate (4 mmol, 609 mg), methanol (10 mL) and AcOH (10 drops). The title compound was obtained as a white solid (815 mg, 74% yield). TLC R f 0.50 in 30% EtOAc in hexanes. ¾ NMR (400 MHz; CDC1 3 ): δ 8.62 (s, 1H), 8.44 (s, 1H), 8.12 (dd, J = 7.4 and 1.8 Hz, 1H), 7.42-7.36 (m, 3H), 7.31 (qd, J = 7.2 and 2.1 Hz, 2H), 7.26- 7.21 (m, 3H). U C NMR (101 MHz; DMSO-c 6 ): δ 152.1, 150.9, 142.1, 133.3, 131.83, 131.81, 130.4, 130.0, 128.1, 127.3, 126.1, 122.3IR (film) 1730, 1545, 1492, 1362, 1219, 1037, 772 cm^.HRMS EI): Exact mass calcd for C 14 H 11 CIN 2 O 2 [M] + : 274.0509. Found: 274.0497.

[00163] Phenyl 2-(2-bromobenzylidene)hydrazinecarboxylate (Table 2a, entry 7).

[00164] Synthesized according to general procedure A using 2-bromobenzaldehyde (8 mmol, 1.48 g), phenyl hydrazinecarboxylate (4 mmol, 609 mg), methanol (10 mL) and AcOH (10 drops). The title compound was obtained as a white solid (490 mg, 38% Yield). TLC R f 0.61 in 30% EtOAc in hexanes. Ti NMR (400 MHz; CDC1 3 ): δ 8.65 (s, 1H), 8.41 (s, 1H), 8.11-8.09 (m, 1H), 7.56 (dd, J = 8.0 and 1.1 Hz, 1H), 7.40 (t, J = 7.9 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.25-7.20 (m, 4H). 13 C NMR (101 MHz; DMSO-c 6 ): δ 151.6, 150.4, 144.0, 133.1, 132.9, 131.6, 129.5, 128.1, 127.2, 125.6, 123.2, 121.8 IR (film) 1729, 1546, 1492, 1467, 1219, 1021, 773, 668, 672 cm "1 . HRMS(EI): Exact mass calcd for Ci 4 HiiBrN 2 0 2 [M] + : 318.0004. Found: 317.9988.

[00165] Phenyl 2-(naphthalen-l-ylmethylene)hydrazinecarboxylate (Table 2a, entry

8).

[00166] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), 1-naphthaldehyde (1.6 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (2.7 g, 93% yield). TLC R f = 0.47 in 30% EtOAc/hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.75-8.42 (m, 3H), 7.93-7.69 (m, 3H), 7.57-7.36 (m, 3H), 7.32 (t, J = 7.6 Hz, 2H), 7.21-7.12 (m, 3H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 133.8 (C), 130.9 (CH), 130.7 (C), 129.4 (CH), 129.0 (C), 128.8 (CH), 127.9 (CH), 127.3 (CH), 126.2 (CH), 125.8 (CH), 125.2 (CH), 124.0 (CH), 121.5 (CH). IR (film) 3226, 3038, 1731, 1539, 1490, 1216, 910, 770 cm "1 . HRMS(EI): Exact mass calcd for Ci 8 Hi 4 N 2 0 2 [M] + : 290.1050. Found: 290.1070.

[00167] Phenyl 2-((l-methyl-lH-pyrrol-2-yl)methylene)hydrazinecarboxylate (Table 2a, entry 11).

[00168] Synthesized according to general procedure A using 1 -methyl- lH-pyrrole-2- carbaldehyde (3 mmol, 327 mg), phenyl hydrazinecarboxylate (3 mmol, 457 mg), and methanol (3 ml). The title compound was obtained as a light pink solid (374 mg, 51% yield). TLC Rf 0.84 in 60% EtOAc in hexanes. ¾ NMR (300 MHz, CDC1 3 ) ppm δ 7.83 (s, 1H), 7.63 (dd, J = 7.6 Hz and 2.0 Hz, 2H), 7.56 (s, 1H), 7.38-7.30 (m, 3H), 3.94 (7, J = 6.8 Hz, 2H), 1.47 (d, J = 6.5, 1H), 1.33 (d, J = 6.8, 11H). 13 C NMR (101 MHz; CD 3 OD): δ 141.0, 130.4, 130.3, 129.0, 128.4, 126.6, 126.4, 122.7, 116.3, 109.4, 36.7 IR (film) 3237, 1732, 1549, 1494, 1350, 1221, 1030, 773 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 Hi 3 N 3 0 2 [M] + : 243.1008. Found: 243.1014.

[00169] Phenyl 2-(4-methoxybenzylidene)hydrazinecarboxylate (Table 2a, entry 14).

[00170] Synthesized according to general procedure A using phenyl carbazate (1.0 g, 6.6 mmol), 4-methoxybenzaldehyde (0.90 g, 6.6 mmol) in MeOH (20 mL) and AcOH (7 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (1.1 g, 62% yield). TLC R f = 0.47 in 40% EtOAc/hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.52 (s, 1H), 7.92 (s, 1H), 7.61 (d, J = 8.7 Hz, 2H), 7.42-7.29 (m, 2H), 7.24-7.11 (m, 3H), 6.87 (d, J = 8.4 Hz, 2H), 3.80 (s, 3H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 161.3 (C), 129.4 (CH), 129.0 (CH), 126.2 (C), 125.7 (CH), 121.4 (CH), 114.1 (CH), 55.3 (CH 3 ). IR (film) 3223, 1731, 1605, 1510, 1219, 1031, 911, 767 cm "1 . HRMS(EI): Exact mass calcd for C15H14N2O 3 [M] + : 270.0999. Found: 270.1033.

[00171] Procedure for Aminocarbonylation of Alkenes (Tables 2a and 3 a)

[00172] General procedure B: An oven or flam dried 2-5 mL μ-w tube with a stir bar was capped with a septum and purged with argon for 5 minutes. The acyl hydrazone (0.2 mmol), trifloroutoluene (2-4 mL) and the corresponding alkene were added to the sealed tube. The septum was removed and the tube was then quickly sealed with a microwave cap and heated for 1-3 hours at 80-150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by X H NMR using 1 ,4-dimethoxybenzene or 1,3,5-trimethoxybenzene as an internal standard. The corresponding product was purified using a small column or a pipette silica gel column (using dichloromethane then EtOAc to wash out by-products first, then using 10-20% methanol in EtOAc or dichloromethane to wash out the target compound) unless noted otherwise.

[00173] (±)-exo-( )-2-(Furan-2-ylmethanene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 2a, entry 1, 12a) (The E composition was determined by a NOESY experiment.)

[00174] Synthesized according to general procedure B using using phenyl 2-(furan-2- ylmethylene)hydrazinecarboxylate (46 mg, 0.20 mmol), norbornene (38 mg, 0.4 mmol). The reaction time was 1.5 hours. The title compound (53% isolated yield, 48% NMR yield) was obtained as yellow oil. TLC R f 0.30 in 10% methanol in EtOAc. *H NMR (300 MHz, CDC1 3 ) ppm <5 7.89 (d, J = 3.6 Hz, 1H), 7.58 (d, J = 1.3 Hz, 1H), 7.20 (d, J = 0.3 Hz, 1H), 6.63-6.61 (m, 1H), 4.39 (d, J = 7.0 Hz, 1H), 2.74 (d, J = 7.6, 2H), 2.63 (d, J = 1.5 Hz, 1H), 1.66 (d, J = 10.0, 2H), 1.41-1.21 (m, 4H)13C NMR (101 MHz; CDC13): δ 185.8, 146.15, 146.08, 121.2, 120.7, 113.7, 75.3, 50.9, 44.1, 39.2, 32.4, 27.5, 24.8. IR (film) 1653, 1594, 1558, 1472, 1330, 1292, 1219, 1004, 777, 689 cm "1 . HRMS(EI): Exact mass calcd for C1 3 H14N2O2 [M] + : 230.1061. Found: 230.1054. [00175] (±)-exo-( )-2-(Thiophen-2-ylmethylene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 2a, entry 2, 12b).

[00176] Synthesized according to general procedure B using using phenyl 2-(thiophen-2- ylmethylene)hydrazinecarboxylate (49 mg, 0.20 mmol), norbornene (23 mg, 0.24 mmol). The reaction time was 1.5 hours. The title compound (46% isolated yield, 45% NMR yield) was obtained as yellow oil. TLC R f 0.23 in 10% methanol in EtOAc. ¾ NMR (300 MHz, CDC1 3 ) ppm δ 7.73 (d, J = 4.9 Hz, 1H), 7.56-7.53 (m, 2H), 7.16 (t, J = 4.4 Hz, 1H), 4.41 (d, J = 6.8 Hz, 1H), 2.77 (d, J = 5.9 Hz, 2H), 2.66 (s, 1H), 1.66 (d, J = 9.7 Hz, 2H), 1.31 (m, 4H). 13 C NMR (101 MHz; CDC13): δ 184.4, 135.7, 133.6, 132.6, 127.6, 126.9, 74.4, 51.4, 44.0, 39.2, 32.5, 27.5, 24.8 IR (film) 1650, 1589, 1353, 1221, 912, 770, 744 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 Hi 4 N 2 OS [M] + : 246.0827. Found: 246.0808.

[00177] (±)-exo-( )-2-Benzylidene-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3- ide (Table 2a, entry 3, 12c).

[00178] Synthesized according to general procedure B using phenyl 2- benzylidinehydrazinecarboxylate (48 mg, 0.20 mmol) and norbomene (188 mg, 2.0 mmol). The reaction temperature is 120 °C and the reaction time is 3 h. The title compound (51% isolated yield) was obtained as yellow solid. TLC R f = 0.47 in 20% MeOH in EtOAc. *H NMR (400 MHz, CDC1 3 ) δ 8.31-8.25 (m, 2H), 7.46-7.38 (m, 3H), 7.13 (s, 1H), 4.42 (d, J = 7.0 Hz, 1H), 2.75 (s, 1H), 2.70-2.65 (m, 2H), 1.73-1.56 (m, 2H), 1.40 (d, J = 11.0 Hz, 1H), 1.35-1.25 (m, 2H), 1.21 (d, J = 11.8 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ 186.2 (C), 132.2 (CH), 131.8 (CH), 131.6 (2CH), 129.5 (C), 128.8 (2CH), 76.9 (CH), 50.0 (CH), 44.3 (CH), 39.2 (CH), 32.4 (CH2), 27.5 (CH2), 24.9 (CH2). IR (film) 3051, 2961, 2874, 2233, 1659, 1588, 1568, 1451, 1290, 1001, 908, 690 cm-1. HRMS(EI): Exact mass calcd for C15H16N20 [M] + : 240.1257. Found: 240.1256.

[00179] (±)-exo-( )-2-(2-Methoxybenzylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 2a, entry 4, 12d).

[00180] Synthesized according to general procedure B using using phenyl 2-(2- methoxybenzylidene)hydrazinecarboxylate (54 mg, 0.20 mmol), norbornene (23 mg, 0.24 mmol). The reaction time was 3 hours. The title compound (34% isolated yield, 32% NMR yield) was obtained as a white solid. TLC Rf 0.37 in 10% methanol in EtOAc. l NMR (300 MHz, CDCls) δ 9.22 (dd, J = 8.0 and 1.7 Hz, 1H), 7.65 (s, 1H), 7.42 (ddd, J = 8.4, 7.4 and 1.7 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 6.90 (dd, J = 8.4, 0.8, 1H), 4.42 (dd, J = 7.1 and 1.0 Hz, 1H), 3.90 (s, 3H), 2.79 (s, 1H), 2.70 (t, J = 5.7 Hz, 2H), 1.68 (d, J = 10.1 Hz, 2H), 1.47-1.42 (m, 1H), 1.36-1.31 (m, 2H), 1.27-1.25 (m, 1H) 13 C NMR (101 MHz; CDC1 3 ) δ 186.1, 158.1, 133.3, 132.7, 127.2, 121.1, 118.4, 110.1, 77.0, 55.7, 50.1, 44.5, 39.2, 32.5, 27.6, 24.9 IR (film) 1656, 1588, 1568, 1482, 1440, 1306, 1283, 1218, 1024, 1002, 686, 672 cm "1 . HRMS(EI): Exact mass calcd for Ci 6 Hi 8 N 2 0 2 [M] + : 270.1368. Found: 270.1356.

[00181] (±)-ex0-( )-2-(3-Methoxybenzylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 2a, entry 5, 12e).

[00182] Synthesized according to general procedure B using phenyl 2-(3- methoxybenzylidene)hydrazinecarboxylate (54 mg, 0.20 mmol), norbornene (23 mg, 0.24 mmol). The reaction time was 3 hours. The title compound (36% isolated yield, 32% NMR yield) was obtained as a white solid. TLC ¾ 0.21 in 10% methanol in EtOAc. l NMR (400 MHz, CDCI 3 ) ppm δ 8.09 (t, J = 2.0, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.10 (s, 1H), 7.02 (ddd, J = 8.3, 2.6 and 0.8 Hz, 1H), 4.44 (d, J = 7.0 Hz, 1H), 3.85 (s, 3H), 2.79 (dt, J = 0.7 and 0.4 Hz, 1H), 2.72 (d, J = 7.0 Hz, 1H), 2.69 (d, J = 3.4 Hz, 1H), 1.68 (ddd, J = 9.8, 6.6 and 3.1 Hz, 2H), 1.46-1.43 (m, 1H), 1.37-1.30 (m, 2H), 1.27-1.24 (m, 1H) 13 C NMR (101 MHz; CDC1 3 ): δ 186.1, 159.8, 131.9, 130.7, 129.7, 124.3, 118.6, 115.4, 77.0, 55.6, 50.0, 44.3, 39.3, 32.5, 27.6, 24.9 IR (film) 2964, 1660,1583, 1434, 1288, 1105, 1087, 1043, 1003, 773, 682 cm "1 . HRMS(EI): Exact mass calcd for Ci 6 Hi 8 N 2 0 2 [M] + : 270.1368. Found: 270.1368.

[00183] (±)-exo-( )-2-( aphth-l-ylmethylene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 2a, entry 8, 12h).

[00184] Synthesized according to general procedure B using phenyl 2-(naphthalen-l- ylmethylene)hydrazinecarboxylate (58 mg, 0.20 mmol), norbornene (188 mg, 2.0 mmol). The reaction time was 1 hours. The title compound (36% isolated yield, 44% NMR yield) was obtained as a white solid. TLC R f 0.36 in 10% methanol in dichlomethane. *H NMR (400 MHz, CDCI 3 ) δ ppm 9.48 (d, J = 7.6 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.94 (s, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.63-7.48 (m, 3H), 4.57 (d, J = 6.5 Hz, 1H), 2.88- 2.69 (m, 3H), 1.84-1.60 (m, 2H), 1.47 (d, J = 10.8 Hz, 1H), 1.41-1.32 (m, 2H), 1.26 (d, J = 10.80 Hz, 1H). 13 C NMR (125 MHz, CDC1 3 ) δ ppm 186.5 (C), 133.4 (C), 132.4 (CH), 131.5 (CH), 131.1 (C), 129.6 (CH), 127.6 (CH), 126.2 (CH), 125.8 (CH), 124.4 (C), 121.3 (CH), 77.5 (CH), 50.0 (CH), 44.7 (CH), 39.2 (CH), 32.5 (CH 2 ), 27.6 (CH 2 ), 25.0 (CH 2 ). IR (film) 2971, 2878, 1658, 1576, 1513, 1326, 1285, 1217, 1108, 1001, 772 cm "1 . HRMS(EI): Exact mass calcd for Ci 9 Hi 8 N 2 0 [M] + : 290.1414. Found: 290.1379. [00185] (±)-cis-( )-l-(Furan-2-ylmethylene)-3-oxotetrahydro-lH-furo[2,3- c]pyrazolidine-l-ium-2-ide (Table 2a, entry 9, 12i).

[00186] Synthesized according to general procedure B using using phenyl 2-(furan-2- ylmethylene)hydrazinecarboxylate (46 mg, 0.20 mmol), 2,3-dihydrofuran (28 mg, 0.40 mmol). The reaction time was 1 hours. The title compound (82% isolated yield, 81% NMR yield) was obtained as yellow oil. TLC R f 0.26 in 10% methanol in EtOAc. ¾ NMR (300 MHz, CDCls) ppm 5 7.93 (d, J = 3.7 Hz, 1H), 7.63 (dd, J = 1.7 and 0.6 Hz, 1H), 7.41 (d, J = 0.6 Hz, 1H), 6.65 (ddd, J = 3.7, 1.7 and 0.7 Hz, 1H), 6.08 (d, J = 6.1 Hz, 1H), 4.18-4.12 (m, 1H), 3.63 (ddd, J = 12.3, 9.0 and 5.4 Hz, 1H), 3.42-3.37 (m, 1H), 2.48-2.42 (m, 1H), 2.27- 2.12 (m, 1H) 13 C NMR (75 MHz; CDC1 3 ): δ 183.2, 147.1, 145.8, 122.4, 122.0, 113.9, 100.6, 68.5, 46.4, 29.9. IR (film) 1657, 1600, 1469, 1219, 1064, 774, 686, 671 cm "1 . HRMS(EI): Exact mass calcd for C 10 H 10 N 2 O 3 [M] + : 206.0691. Found: 206.0705.

[00187] (±)-cis-( )-l-(Thiophen-2-ylmethylene)-3-oxotetrahydro-lH-furo[2,3- c]pyrazolidine-l-ium-2-ide (Table 2a, entry 10, 12j).

[00188] Synthesized according to general procedure B using using phenyl 2-(thiophen-2- ylmethylene)hydrazinecarboxylate (49 mg, 0.20 mmol), 2,3-dihydrofuran (28 mg, 0.40 mmol). The reaction time was 1.5 hours. The title compound (90% isolated yield, 87% NMR yield) was obtained as yellow oil. TLC R f 0.19 in 10% methanol in EtOAc. δ ¾ NMR (300 MHz; CDCI 3 ): δ 7.79 (d, J = 5.0 Hz, 1H), 7.71 (d, J = 0.5 Hz, 1H), 7.63 (dd, J = 3.9 and 0.7 Hz, 1H), 7.17 (dd, J = 5.0 and 3.9 Hz, 1H), 6.12 (d, J = 6.2 Hz, 1H), 4.13 (t, J = 8.2 Hz, 1H), 3.62 (ddd, J = 12.3, 9.0 and 5.4 Hz, 1H), 3.42 (dd, J = 8.8 and 6.2 Hz, 1H), 2.48-2.42 (m, 1H), 2.20-2.14 (m, 1H) 13 C NMR (101 MHz; CDC1 3 ): δ 182.0, 136.6, 134.8, 132.1 , 127.9, 127.8, 99.8, 68.5, 47.0, 29.9. IR (film) 1654, 1594, 1418, 1352, 1322, 1219, 1063, 773 cm "1 . HRMS(EI): Exact mass calcd for C1 0 H1 0 N2O2S [M] + : 222.0463. Found: 222.0452.

[00189] (±)-cis-( )-l-(2-Methoxybenzyldiene)-3-oxotetrahydro-lH-furo[2,3- c]pyrazolidine-l-ium-2-ide (Table 2a, entry 12, 121).

[00190] Synthesized according to general procedure B using phenyl 2-(2- methoxybenzylidene)hydrazinecarboxylate (54 mg, 0.20 mmol), dihydrofuran (28 mg, 0.40 mmol), and PhCF 3 (2 ml). The reaction time was 1 hour. The title compound was obtained as a white solid (32 mg, 65% yield). TLC R f 0.25 in 10% methanol in EtOAc. ¾ NMR (300 MHz; CDCI 3 ): δ 9.19 (dd, J = 8.0 and 1.3 Hz, 1H), 7.90 (s, 1H), 7.48-7.43 (m, 1H), 7.06 (t, J = 7.7 Hz, 1H), 6.92 (d, J = 8.3 Hz, 1H), 6.09-6.07 (m, 1H), 4.17 (t, J = 8.4 Hz, 1H), 3.88 (d, J = 0.4 Hz, 3H), 3.72-3.63 (m, 1H), 3.40-3.35 (m, 1H), 2.50 (dd, J = 12.7 and 5.2 Hz, 1H), 2.30-2.18 (m, 1H). 13 C NMR (75 MHz; CDC1 3 ): δ 183.4, 158.9, 134.2, 133.0, 129.2, 121.1, 118.0, 110.2, 102.1, 68.4, 55.7, 45.6, 29.9 IR (film) 2983, 1663, 1591, 1574, 1480, 1349, 1287, 1249, 1221, 1066, 772 cm "1 . HRMS(EI): Exact mass calcd for C1 3 H14N2O 3 [M] + : 246.1004. Found: 246.0976.

[00191] (±)-cis-( )-l-(4-Methoxybenzyldiene)-3-oxotetrahydro-lH-furo[2,3- c]pyrazolidine-l-ium-2-ide (Table 2a, entry 14, 12n).

[00192] Synthesized according to general procedure B using using phenyl 2-(4- methoxybenzylidene)hydrazinecarboxylate (54 mg, 0.20 mmol), 2,3-dihydrofuran (28 mg, 0.40 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (30 mg, 61%). This product is very labile, and an analytically pure sample could not be obtained for NMR analysis. TLC R f 0.55 in 10% methanol in dichlomethane. *H NMR (400 MHz, CDCls) δ ppm 8.27 (d, J = 9.0 Hz, 2H), 7.27 (s, 1H), 6.91 (d, J = 9.1 Hz, 2H), 6.05 (d, J = 6.2 Hz, 1H), 4.10 (t, J = 8.4 Hz, 1H), 3.82 (s, 3H), 3.66-3.58 (m, 1H), 3.32 (dd, J = 9.2 and 6.3 Hz, 1H), 2.43 (dd, J = 12.5 and 5.2 Hz, 1H), 2.22-2.10 (m, 1H). 13 C NMR (100 MHz, CDCI 3 ) δ ppm 183.2 (C), 163.0 (C), 134.5 (CH), 134.3 (CH), 114.4 (CH), 101.5 (CH), 68.4 (CH 2 ), 55.6 (CH 3 ), 45.8 (CH), 29.9 (CH 2 ). IR (film) 1674, 1544, 1367, 776 cm _1 .HRMS(EI): Exact mass calcd for Ci 3 Hi 4 N 2 0 3 [M] + : 246.0999. Found: 246.0978.

[00193] X-ray Crystallographic Proof of Structure 1,9-Diaza[7, 6, l 4 ' 7 , 0 3 8 ,0 10 14 ,0]tetrdecan-2-one

Table 2b. Crystal data and structure refinement for 1.9-diaza[7. 6. I 4 ' 7 . 0 3 ' 8 .0 10 ' 14 .0]tetrdecan- 2-one.

Identification code ab002

Empirical formula C14 H20 N2 O

Formula weight 232.32

Temperature 200(2) K

Wavelength 0.71073 A

Crystal system, space group Triclinic, P-l

Unit cell dimensions a = 6.4840(13) A alpha = 85.839(13) deg.

b = 9.9421(19) A beta = 72.127(12) deg.

c = 9.963(2) A gamma = 80.358(12) deg.

Volume 602.5(2) A 3

Z, Calculated density 2, 1.281 Mg/m 3

Absorption coefficient 0.081 mm "1

F(000) 252

Crystal size 0.25 χ 0.23 χ 0.08 mm

Theta range for data collection 2.08 to 28.45 deg.

Limiting indices -8 < h < 8, -13 < k < 3, -9 < 1 < 13

Reflections collected / unique 6280 / 2652 [R(int) = 0.0355]

Completeness to theta = 28.45 86.9 %

Absorption correction Semi-empirical from equivalents Max. and min. Transmission 0.9935 and 0.9799

Refinement method Full-matrix least-squares

Data / restraints / parameters 2652 / 0 / 155

Goodness-of-fit on F 2 1.064

Final R indices [I>2sigma(I)] Rl = 0.0515, wR2 = 0.1604

R indices (all data) Rl = 0.1089, wR2 = 0.2150

Extinction coefficient 0.036(16)

Largest diff. peak and hole 0.333 and -0.322 e.A "3

Table 2c. Atomic coordinates ( χ 10 4 ) and equivalent isotropic

displacement parameters (A 2 χ 10 3 ) for l,9-diaza[7, 6, l 4 ' 7 , 0 3 ' 8 ,0 10 ' 14 ,0]tetrdecan-2-one

U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

x y z U(eq)

N(l) 1441(2) 3875(2) 2230(2) 34(1)

N(2) 3100(2) 4136(1) 2825(2) 30(1)

0(1) 1152(2) 2791(2) 371(2) 54(1)

C(l) 2187(3) 2987(2) 1155(2) 36(1)

C(2) 4428(3) 2261(2) 1171(2) 33(1)

C(3) 4421(3) 784(2) 1739(2) 36(1)

C(4) 6808(3) 173(2) 1630(2) 45(1)

C(5) 7249(3) 900(2) 2817(2) 43(1)

C(6) 5073(3) 1861(2) 3433(2) 37(1)

C(7) 4947(2) 2996(2) 2327(2) 31(1)

C(8) 3402(3) 976(2) 3328(2) 40(1)

C(9) -68(3) 5141(2) 2288(2) 40(1)

C(10) 1428(3) 6245(2) 1972(2) 36(1)

C(l l) 641(3) 7440(2) 2984(3) 47(1)

C(12) 1760(3) 7037(2) 4119(2) 45(1)

C(13) 4034(3) 6345(2) 3292(2) 40(1)

C(14) 3595(2) 5501(2) 2218(2) 32(1)

Table 2d. Bond lengths [A] and angles [deg] for l,9-diaza[7, 6, l 4 ' 7 , 0 3 ' 8 ,0 10 ' 14 ,0]tetrdecan-2- one

N(l)-C(l) 1.355(2)

N(l)-N(2) 1.4433(16)

N(l)-C(9) 1.452(2)

N(2)-C(7) 1.4926(17)

N(2)-C(14) 1.490(2)

0(1)-C(1) 1.220(2) c i)-c(2) 1.514(2) c 3)-C(3) 1.536(3) c 3)-C(7) 1.554(2) c 3)-C(8) 1.530(3) c 3)-C(4) 1.539(2) c [4)-C(5) 1.550(2) c )-C(6) 1.543(2) c )-C(8) 1.537(3) c [6)-C(7) 1.530(3) c 9)-C(10) 1.538(3) c io)-c(] 1) 1.531(2) c io)-c(] 4) 1.5552(18) c i i)-c(] 2) 1.518(3) c i2)-c(] 3) 1.524(2) c i3)-c(] 4) 1.525(2) c i)-N(i) -N(2) 114.31(12) c i)-N(i) -C(9) 126.53(15)

N (2)-N(i; )-C(9) 106.95(12)

N (1)-N(2; )-C(7) 104.62(11)

N (1)-N(2; )-C(14) 103.56(12) c C7)-N(2) -C(14) 114.25(13)

0 (i)-c(i) -N(l) 124.56(15)

0 (i)-c(i) -C(2) 127.47(16)

N (i)-c(i) -C(2) 107.90(13) c i)-c(2) -C(3) 113.50(15) c i)-C(2) -C(7) 104.06(12) c 3)-C(2) -C(7) 103.13(14) c ^8)-C(3) -C(2) 102.37(14) c $)-C(3) -C(4) 102.03(14) c 3)-C(3) -C(4) 107.19(16) c 3)-C(4) -C(5) 102.80(13) c ^6)-C(5) -C(4) 103.15(11) c ^8)-C(6) -C(7) 103.55(13) c ^8)-C(6) -C(5) 101.02(13) c )-C(6) -C(5) 106.53(17)

N (2)-C(7) -C(6) 114.05(15)

N (2)-C(7) -C(2) 106.60(11) c [6)-C(7) -C(2) 102.78(14) c 3)-C(8) -C(6) 93.98(16)

N (1)-C(9) -C(10) 103.63(12) c i i)-c(] 0)-C(9) 114.96(17) c i i)-c(] 0)-C(14) 105.64(13) c 9)-C(10)-C(14) 104.21(14) c i2)-C(] 1)-C(10) 104.66(13) c i i)-c(] 2)-C(13) 103.17(16) c i4)-c(] 3)-C(12) 103.82(12)

N (2)-C(14)-C(13) 111.01(15)

N (2)-C(14)-C(10) 105.03(13) c i3)-C(14)-C(10) 105.77(12) Symmetry transformations used to generate equivalent atoms:

Table 2e. Anisotropic displacement parameters (A 2 χ 10 3 ) for 1.9-diazar7. 6.

0 3 ' 8 .0 10 ' 14 .01tetrdecan-2-one .

The anisotropic displacement factor exponent takes the form:

-2 pi 2 [ h 2 a* 2 Ul l + ... + 2 h k a* b* U12 ]

Ul l U22 U33 U23 U13 U12

N(l) 25(1) 34(1) 49(1) -4(1) -20(1) -1(1)

N(2) 24(1) 29(1) 40(1) -4(1) -16(1) 1(1)

0(1) 62(1) 52(1) 64(1) -4(1) -46(1) -2(1)

C(l) 36(1) 36(1) 42(1) 2(1) -22(1) -4(1)

C(2) 31(1) 36(1) 33(1) -5(1) -13(1) 0(1)

C(3) 39(1) 32(1) 40(1) -6(1) -18(1) -2(1)

C(4) 44(1) 39(1) 53(1) -15(1) -22(1) 11(1)

C(5) 40(1) 37(1) 56(1) -10(1) -26(1) 10(1)

C(6) 41(1) 35(1) 38(1) -9(1) -22(1) 7(1)

C(7) 25(1) 27(1) 43(1) -6(1) -15(1) 1(1)

C(8) 41(1) 39(1) 39(1) 1(1) -14(1) -2(1)

C(9) 26(1) 38(1) 57(1) -1(1) -20(1) 3(1)

C(10) 32(1) 35(1) 44(1) 1(1) -19(1) 1(1)

C(l l) 36(1) 36(1) 71(2) -10(1) -24(1) 9(1)

C(12) 39(1) 45(1) 51(1) -16(1) -15(1) 4(1)

C(13) 31(1) 34(1) 59(1) -12(1) -22(1) 3(1)

C(14) 24(1) 31(1) 41(1) -5(1) -12(1) 1(1)

Table 2f. Hydrogen coordinates ( χ 10 4 ) and isotropic displacement parameters (A 2 χ 10 3 ) for l,9-diaza[7, 6, l 4 ' 7 , 0 3 ' 8 ,0 10 ' 14 ,0]tetrdecan-2-one.

x y z U(eq)

H(2A) 5553 2322 231 39

H(3A) 3656 222 1308 43

H(4A) 7817 378 695 54

H(4B) 6965 -828 1796 54

H(5A) 7580 236 3540 52

H(5B) 8484 1422 2431 52

H(6A) 4846 2186 4402 44

H(7A) 6377 3348 1942 37 H(8A) 3469 108 3878 48

H(8B) 1882 1470 3583 48

H(9A) -1160 5257 3233 48

H(9B) -847 5168 1571 48

H(10A) 1699 6584 973 43

H(11A) 1077 8295 2491 57

H(11B) -974 7569 3396 57

H(12A) 972 6400 4824 54

H(12B) 1849 7849 4606 54

H(13A) 4983 7029 2816 48

H(13B) 4744 5754 3919 48

H(14A) 4835 5422 1321 38

Table 2g. Torsion angles [deg] for l,9-diaza[7, 6, l 4 ' 7 , 0 3 ' 8 ,0 10 ' 14 ,0]tetrdecan-2-one.

C( ;i)-N(l)-N(2)-C(7) -17.0(2)

C( ;9)-N(l)-N(2)-C(7) -162.15(16)

C( ;i)-N(l)-N(2)-C(14) 102.94(17)

C( ;9)-N(l)-N(2)-C(14) -42.19(18)

N (2)-N(l)-C(l)-0(l) -168.0(2)

C( ;9)-N(l)-C(l)-0(l) -30.9(3)

N (2)-N(l)-C(l)-C(2) 14.8(2)

C( ;9)-N(l)-C(l)-C(2) 151.90(18)

0 (1)-C(1)-C(2)-C(3) -71.8(3)

N (1)-C(1)-C(2)-C(3) 105.28(18)

O (1)-C(1)-C(2)-C(7) 176.9(2)

N (1)-C(1)-C(2)-C(7) -6.1(2)

C( ;i)-C(2)-C(3)-C(8) -75.35(17)

C( ;7)-C(2)-C(3)-C(8) 36.58(15)

C( ;i)-C(2)-C(3)-C(4) 177.73(14)

C( ;7)-C(2)-C(3)-C(4) -70.34(16)

C( ;8)-C(3)-C(4)-C(5) -34.7(2)

C( ;2)-C(3)-C(4)-C(5) 72.4(2)

C( ;3)-C(4)-C(5)-C(6) -1.3(2)

C( ;4)-C(5)-C(6)-C(8) 36.5(2)

C( ;4)-C(5)-C(6)-C(7) -71.34(19)

N (1)-N(2)-C(7)-C(6) -101.02(16)

C( ;i4)-N(2)-C(7)-C(6) 146.46(13)

N (1)-N(2)-C(7)-C(2) 11.68(19)

C( ;i4)-N(2)-C(7)-C(2) -100.84(16)

C( ;8)-C(6)-C(7)-N(2) 82.34(16)

C( ;5)-C(6)-C(7)-N(2) -171.60(11)

C( ;8)-C(6)-C(7)-C(2) -32.63(16)

C( ;5)-C(6)-C(7)-C(2) 73.43(15)

C( ;i)-C(2)-C(7)-N(2) -3.8(2)

C( ;3)-C(2)-C(7)-N(2) -122.56(14)

C( ;i)-C(2)-C(7)-C(6) 116.40(16)

C( ;3)-C(2)-C(7)-C(6) -2.32(15) C(2)-C(3)-C(8)-C(6) -54.75(14)

C(4)-C(3)-C(8)-C(6) 56.11(16)

C(7)-C(6)-C(8)-C(3) 53.69(15)

C(5)-C(6)-C(8)-C(3) -56.50(16)

C(l)-N(l)-C(9)-C(10) -102.6(2)

N(2)-N(l)-C(9)-C(10) 37.0(2)

N(l)-C(9)-C(10)-C(l l) -132.18(16)

N(l)-C(9)-C(10)-C(14) -17.06(19)

C(9)-C(10)-C(l l)-C(12) 92.61(18)

C(14)-C(10)-C(l l)-C(12) -21.7(2)

C(10)-C(l l)-C(12)-C(13) 38.6(2)

C(l l)-C(12)-C(13)-C(14) -40.5(2)

N(l)-N(2)-C(14)-C(13) 143.10(12)

C(7)-N(2)-C(14)-C(13) -103.74(14)

N(l)-N(2)-C(14)-C(10) 29.23(16)

C(7)-N(2)-C(14)-C(10) 142.39(13)

C(12)-C(13)-C(14)-N(2) -86.53(17)

C(12)-C(13)-C(14)-C(10) 26.9(2)

C(l l)-C(10)-C(14)-N(2) 114.20(17)

C(9)-C(10)-C(14)-N(2) -7.33(18)

C(l l)-C(10)-C(14)-C(13) -3.3(2)

C(9)-C(10)-C(14)-C(13) -124.82(17)

Symmetry transformations used to generate equivalent atoms: Table 2h. Hydrogen bonds for l,9-diaza[7, 6, l 4 ' 7 , 0 3 ' 8 ,0 10 ' 14 ,0]tetrdecan-2-one [A and deg.].

D-H...A d(D-H) d(H . A) d(D . A) <(DHA)

[00194] Example 2: Intermolecular Aminocarbonylation of Various Alkenes

[00195] In this example, intermolecular aminocarbonylation reactions were performed to demonstrate the successful use of imino compounds of Formula IV in β-aminocarbonylation of various alkenes. A summary of the reactions is provided in Table 3 below. Table 3: β-aminocarbonylation/β-aminothiocarbonylation of Various Alkenes

5p

68% isolated yield

77% NMR yield

100TC

Table 3a: Alkene Aminocarbonvlation using ketone-derived hvdrazones

entry product 16 yield (%) isomer ratio 6

1 R = Ph, 16a 68 2:1

2 R = 4-EtC 6 H 4 , 16b 64 2:1

3 R = 2-furyl, 16c 92 δ 3:1

4 R = 2-thiophenyl, 16d 82 >20:1

5 R = 2-pyridinyl, 16e 58 2:1

6 R = (£)-2-styrenyl, 16f 51 2:1

7 R =cyclopropyl, 16g 66 2:1

8 R = ί-Bu, 16h 82 >20:1

9 R = 2-indolyl, 16i 70 2:1 6

14 R = Ph, X = S, 16n 46 >20: 1

15 c R = ferrocenyl, X = S, 16o 53 >20: 1

16 R = n-Bu, X = O, 16p 36 3: 1 a Conditions: hydrazone (1 equiv), alkene (10 equiv) in PhCF 3 (0.05 M) heated in a sealed vial (microwave reactor, 130 °C, 3 h). b The identity of the major stereoisomer was secured by NOE experiments on 6c, 6f, 61 and 6k, and by X-ray crystallographic analysis of 6c. Stereochemistry of other dipoles was assigned by analogy. c 5 equiv of norbomene were used. d Of-Bu subst. hydrazone was used at 150 °C. [00196] Preparation of Starting Materials for Table 3

[00197] Phenyl 2-(diphenylmethylene)hydrazinecarboxylate (4n)

Ph

[00198] Synthesized according to general procedure C, as set out in Example 1, using phenyl carbazate (150 mg, 1 mmol), 2,4-dimethylpentan-3-one (364 mg, 2 mmol), acetic acid (5 drops) and methanol (10 mL). The title compound was isolated using flash

chromatography (20% EtOAc in hexne) as a white solid (220 mg, 70% yield). TLC Rf 0.33 in 20% EtOAc in hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.28-7.86 (m, 1H), 7.65-7.52 (m, 5H), 7.45-7.07 (m, 10H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 136.8, 131.7, 130.1 (CHi), 130.0 (CHi), 129.8 (CHi), 129.5 (CHi), 128.4 (CHi), 128.3 (CHi), 127.7 (CHi), 125.8 (CHi), 121.4 (CHi). IR 4453, 4198, 3351, 3055, 2987, 2306, 1768, 1730, 1476, 1422, 1266, 1198, 896, 742 cm "1 . HRMS(EI): Exact mass calcd for C2 0 H1 6 N2O2 [M] + : 316.1206. Found:

316.1234.

Phenyl 2-(2-admantan-2-ylidene)hydrazinecarboxylate (4o)

O

Λ OPh

[00200] Synthesized according to general procedure C, as set out in Example 1, using phenyl carbazate (1.0 g, 6.6 mmol), 2-admantanone (1.2 g, 7.9 mmol, 1.2 equiv), acetic acid (20 drops) and methanol (20 mL). The title compound was isolated using flash

chromatography (20% EtOAc in hexane) as a white solid (1.5 g, 93% yield). TLC Rf 0.34 in 20% EtOAc in hexanes. mp: 144-145 °C. *H NMR (400 MHz, CDC1 3 ) δ ppm 8.02 (bs, 1H), 7.34 (t, J = 7.85 Hz, 2H), 7.22-7.14 (m, 3H), 2.98 (bs, 1H), 2.77 (bs, 1H), 2.06-1.75 (m, 12H); 13 C NMR (75 MHz, CDC1 3 ) δ ppm 166.0 (C), 150.8 (C), 129.3 (2CHi), 125.5 (CHi), 121.5 (2CHi), 47.0 (CHi), 39.4 (CHi), 38.9 (2CH 2 ), 37.6 (2CH 2 ), 36.2 (CH 2 ), 30.9 (CHi), 27.7 (CHi). IR 3055, 2989, 2929, 2859, 1764, 1480, 1261, 1197, 896, 734 cm "1 . HRMS(EI): Exact mass calcd for C14H2 9 N 3 O [M] : 284.1520. Found: 191.1 (100%), 162.0 (12%), 134.1 (11%), 94.0 (51%), 93.1 (14%).

[00201] Methyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarbodithioate (4ρ')

[00202] Synthesized according to general procedure C, as set out in Example 1, using methyl hydrazinecarbodithioate (14 g, 110 mmol), 2,4-dimethylpentan-3-one (20 g, 25 mL, 172 mmol, 1.5 equiv), acetic acid (1 mL) and methanol (300 mL). The title compound was isolated using flash chromatography (20% EtOAc in hexane) as a crystalline (10 g, 40% yield). TLC Rf 0.67 in 20% EtOAc in hexanes. mp: 46-47 °C. 1H NMR (400 MHz, CDC1 3 ) δ ppm 9.98 (s, 1H), 2.88 (sept, J = 6.94 Hz, 1H), 2.64 (sept, J = 6.73 Hz, 1H), 2.56 (s, 3H), 1.14 (d, J = 7.09 Hz, 6H), 1.13 (d, 6.86 Hz, 6H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 201.4 (C), 166.5 (C), 31.1(CHi), 28.5 (CHi), 21.9 (2 CH 3 ), 19.1 (CH 3 ), 17.7 (CH 3 ). IR (film) 3207, 2969, 2927, 2877, 1625, 1456, 1295, 1061, 1018, 957 cm "1 . HRMS(EI): Exact mass calcd for C9Hi 8 N 2 S 2 [M] + : 218.0906. Found: 175.0 (86.6%), 171.1(11.5), 128.0 (11%), 113.0 (0.4%), 43.1 (100%).

2-(2,4-Dimethylpentan-3-ylidene)- V, V-diisopropylhydrazinecarbothioamide

[00204] This compound was made according to a known procedure: Hu, W.; Zhou, W.; Xia, C; Wen, X. Bioorg. & Med. Chem. Lett. 2006, 16, 2213-2218.

[00205] To a solution of methyl 2-(2,4-dimethylpentan-3-ylidene)hydrazinecarbodithioate (2.2 mg, 10 mmol) in 50 mL ethanol was added diisopropylamine (2.0 g, 2.8 mL, 1.5 equiv). The mixture was refluxed for 16 h and the TLC tests showed the reaction is complete. The mixture was cooled down to room temperature and concentrated under reduced pressure. The residue was purified using flash chromatography (10% EtOAc in hexane) to give the product (1.9 g, 70% yield) as a yellow oil. TLC Rf 0.51 in 10% EtOAc in hexanes. ¾ NMR (400 MHz, CDCls) δ ppm 14.02 (s, 1H), 5.67 (bs, 1H), 3.63 (bs, 1H), 3.26 (sept., J = 7.07 Hz, 1H), 2.77 (sept, J = 6.85 Hz, 1H), 1.36-1.12 (m, 24H); 13 C NMR (75 MHz, CDC1 3 ) δ ppm 181.8 (C), 161.3 (C), 51.6 (b, <¾), 47.2 (b, <¾), 31.5 ((¾), 30.8 ((¾), 20.9 (CH 3 ), 20.8 (b, 2CH 3 ), 18.1 (CH 3 ). IR (film) 2983, 2880, 2724, 2206, 1600, 1461, 1301, 1136, 913, 730 cm "1 . Exact mass calcd for C14H2 9 N 3 S1 [M] + : 271.2077. Found: 271.2085.

[00206] Intermolecular Aminocarbonylation Reations for Table 3

[00207] (±)-cis-l-(2,4-Dimethylpentan-3-ylidene)-tetrahydro-lH-furo [2,3- c]pyrazolidine-l-ium-2-ide (5a)

[00208] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (50 mg, 0.20 mmol) and 2-3- dihydrofuran (0.16 mL, 2.0 mmol). The reaction was under 80 °C. The title compound was obtained as a yellow oil (45 mg, 99% isolated yield and 99% NMR yield). TLC Rf 0.14 in 10% methanol in EtOAc. ¾ NMR (300 MHz, CDC1 3 ) δ ppm 5.04 (d, J = 6.33 Hz, 1H), 2.99 (t, J = 8.34 Hz, 1H), 2.56-2.45 (m, 1H), 2.27-2.10 (m, 2H), 1.79 (sept, J = 6.96 Hz, 1H), 1.38 (dd, J = 12.60, 5.16 Hz, 1H), 1.13-0.90 (m, 1H), 0.26 (d, J = 6.94 Hz, 6H), 0.10 (t, J = 6.18 Hz, 6H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 180.9 (C), 165.1 (C), 97.6 (CHi), 68.3 (CH 2 ), 46.1 (CHi), 32.8 (CHi), 30.2 (CH 2 ), 30.1 (CHi), 19.2 (CH 3 ), 18.7 (CH 3 ), 16.7 (CH 3 ), 16.6 (CH 3 ). IR 3424, 2965, 2876, 1651, 1574, 1451, 1394, 1236, 1125, 1067, 1017, 925, 799 cm "1 . HRMS(EI): Exact mass calcd for Ci 2 H 20 N 2 O 2 [M] + : 224.1520. Found: 224.1511. [00209] 5-«-Butyloxy- l-(2,4-dimethylpentan-3-ylidene)-3-oxopyrazolidine- l-ium-2- ide (5b)

[00210] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (50 mg, 0.20 mmol) and w-butyl vinyl ether (0.26 mL, 2.0 mmol). The reaction was under 80 °C. The title compound was obtained as a yellow oil (41 mg, 81% isolated yield and 79% NMR yield). TLC Rf 0.17 in 10% methanol in EtOAc. ¾ NMR (300 MHz, CDC1 3 ) δ ppm 5.92 (dd, J = 7.52, 1.47 Hz, 1H), 3.51-3.40 (m, 1H), 3.24-3.08 (m, 2H), 2.87 (sept, J = 6.97 Hz, 1H), 2.77 (dd, J = 17.44, 7.68 Hz, 1H), 2.59 (d, J = 17.38 Hz, 1H), 1.58-1.41 (m, 2H), 1.40-1.21 (m, 8H), 1.16 (t, J = 6.55 Hz, 6H), 0.84 (t, J = 7.29 Hz, 3H); 13 C NMR (75 MHz, CDC1 3 ) δ ppm 179.4 (C), 164.9 (C), 92.4 (CHi), 63.7 (CH 2 ), 34.0 (CH 2 ), 32.0 (CHi), 31.3 (CH 2 ), 30.2 (CHi), 19.1 (CH 2 ), 19.0 (CH 3 ), 18.9 (CH 3 ), 16.6 (CH 3 ), 16.5 (CH 3 ), 13.7 (CH 3 ). IR 3411, 2961, 2874, 1651, 1581, 1467, 1392, 1259, 1106, 1019, 722 cm "1 . HRMS(EI): Exact mass calcd for Ci 9 H 28 N 2 0 2 [M] + : 254.1989. Found: 254.1967.

[00211 ] l-(2,4-Dimethylpentan-3-ylidene)-3-oxo-5-(4-vinyloxy-«- butyloxy)pyrazolidine- l-ium-2-ide (5c)

[00212] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (50 mg, 0.2 mmol) and 1 ,4-butanediol divinyl ether(0.32 mL, 2.0 mmol). The reaction was under 80 °C. The title compound was obtained as a yellow oil (46 mg, 78% isolated yield and 76% NMR yield). TLC Rf 0.18 in 10% methanol in EtOAc. ¾ NMR (300 MHz, CDC1 3 ) δ ppm 6.38 (dd, J = 14.36, 6.81 Hz, 1H), 5.94 (dd, J = 7.63, 1.72 Hz, 1H), 4.10 (dd, J = 14.34, 1.82 Hz, 1H), 3.93 (dd, J = 6.79, 1.78 Hz, 1H), 3.68-3.57 (m, 2H), 3.56-3.45 (m, 1H), 3.29-3.08 (m, 2H), 2.96-2.84 (m, 1H),

2.79 (dd, J = 17.49, 7.67 Hz, 1H), 2.60 (dd, J = 17.48, 1.33 Hz, 1H), 1.72-1.55 (m, 4H), 1.37 (d, J = 7.04 Hz, 3H), 1.34 (d, J = 6.99 Hz, 3H), 1.17 (t, J = 6.31Hz, 6H); 13 C NMR (75 MHz, CDC1 3 ) δ ppm 179.4 (C), 165.2 (C), 151.6 (CHi), 92.3 (CHi), 86.5 (CH 2 ), 67.2 (CH 2 ), 63.6 (CH 2 ), 34.0 (CH 2 ), 32.1 (<¾), 30.2 (<¾), 26.1 (CH 2 ), 25.5 (CH 2 ), 19.0 (CH 3 ), 18.9 (CH 3 ), 16.6 (CH 3 ), 16.5 (CH 3 ). IR 3378, 2945, 2875, 1647, 1576, 1470, 1392, 1195, 1107, 699 cm "1 . HRMS(EI): Exact mass calcd for Ci 6 H 28 N 2 0 3 [M] + : 296.2094. Found: 296.2088.

[00213] 5-Cyclohexyloxy-l-(2,4-dimethylpentan-3-ylidene)-3-oxopyrazo lidine-l-ium- 2-ide (5d)

[00214] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (50 mg, 0.2 mmol) and cyclohexyl vinyl ether(0.28 mL, 2.0 mmol). The reaction was under 80 °C. The title compound was obtained as a yellow oil (49 mg, 89% isolated yield and 88% NMR yield). TLC Rf 0.21 in 10% methanol in EtOAc. ¾ NMR (300 MHz, CDC1 3 ) δ ppm 5.82 (dd, J = 7.39, 1.87 Hz, 1H), 3.57-3.48 (m, 1H), 3.08 (sept, J = 6.70 Hz, 1H), 2.89-2.74 (m, 2H), 2.59 (dd, J = 17.17, 1.90 Hz, 1H), 1.87-1.78 (m, 1H), 1.77-1.60 (m, 3H), 1.52-1.44 (m, 1H), 1.34 (d, J = 6.94 Hz, 3H), 1.31 (d, J = 6.96 Hz, 3H), 1.28-1.08 (m, 11H). 13 C NMR (100 MHz, CDCl 3 ) ½pm 179.8 (C), 164.8 (C), 91.6 (CHi), 76.0 (CHi), 36.1 (CH 2 ), 33.5 (CH 2 ), 32.6 (CH 2 ), 32.2 (CHi), 30.2 (CHi), 25.2 (CH 2 ), 24.0 (2CH 2 ), 19.0 (CH 3 ), 18.8 (CH 3 ), 16.6 (CH 3 ), 16.4 (CH 3 ). ); IR (film) 3419, 2932, 2859, 1667, 1533, 1447, 1271, 1069 cm "1 . Exact mass calcd for Ci 6 H 28 N 2 0 2 [M] + : 280.2145. Found: 280.2130. [00215] 5-teri-Butyloxy-l-(2,4-dimethylpentan-3-ylidene)-3-oxopyrazo lidine-l-ium-2- ide (5e)

[00216] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (50 mg, 0.2 mmol) and ferf-butyl vinyl ether (0.19 mL, 2.0 mmol). The reaction was under 80 °C. The title compound was obtained as a yellow oil (38 mg, 75% isolated yield and 84% NMR yield). TLC Rf 0.17 in 10% methanol in EtOAc. ¾ NMR (300 MHz, CDC1 3 ) δ ppm 5.81 (dd, J = 6.87, 2.34 Hz, 1H), 3.06 (sept, J = 6.73 Hz, 1H), 2.88-2.76 (m, 2H), 2.63 (d, J = 17.78 Hz, 1H), 1.36 (d, J = 6.74 Hz, 3H), 1.32 (d, J = 6.89 Hz, 3H), 1.28 (s, 9H), 1.18 (d, J = 6.70 Hz, 3H), 1.14 (d, J = 6.83 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) ½pm 179.7 (C), 164.8 (C), 89.1 (CHi), 77.4 (C), 39.3, 32.0 (CHi), 30.4 (CHi), 28.8 (3CH 3 ), 19.0 (CH 3 ), 18.7 (CH 3 ), 16.6 (CH 3 ), 16.5 (CH 3 ). ); IR (film) 3058, 2985, 2301, 1661, 1605, 1266, 1140, 745 cm "1 . HRMS(EI): Exact mass calcd for C14H2 6 N2O2 [M] + : 254.1989. Found: 254.2009.

[00217] (±)-cis- l-(2,4-Dimethylpentan-3-ylidene)-3-oxo-tetrahydro-2H-pyro [2,3- c]pyrazolidine-l-ium-2-ide (5f)

[00218] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (90.2 mg, 0.363 mmol) and 3,4-dihydro- 2H-pyran (0.331 mL, 3.63 mmol) heated at 80°C for 3 hours. The title compound was obtained as a white solid (60.8 mg, 0.255 mmol, 70% isolated yield and 70% NMR yield). TLC R f = 0.3 in 5% MeOH/CH 2 Cl 2 . *H NMR (CDC1 3 , 300 MHz) δ 5.93 (d, J = 7.7, 1H), 3.63-3.44 (m, 2H), 3.14 (7, j = 6.7, 1H), 2.83 (7, j = 6.9, 1H), 2.67 (t, J = 3.7, 1H), 2.19 (d, J = 10.9, 1H), 1.72-1.58 (m, 3H), 1.28 (dd, J = 13.8, 7.0, 6H), 1.09 (d, J = 6.7, 6H); 13 C NMR (CDCI 3 , 100 MHz) δ ppm 181.4 (C), 165.3 (C), 91.1 (CH), 61.1 (CH 2 ), 37.9 (CH), 32.3 (CH), 30.0 (CH), 19.2 (CH 2 ), 19.1 (CH 3 ), 18.8 (CH 3 ), 16.6 (CH 3 ), 16.5 (CH 3 ), 16.3 (CH 2 ); IR (film); 2971, 2876, 1649, 1577, 1135, 1063, 1048, 1016 cm "1 ; HRMS (EI): Exact mass calcd for Ci 3 H 22 N 2 0 2 [M] + : 238.1681 ; found: 238.2 (2.5%), 195.1 (23.2%), 155.1 (17.2%), 124.1 (17.5%), 111.0 (36.9%), 97.0 (45.6%), 84.1 (100.0%), 83.1 (21.6%), 83.1 (17.1%), 70.1 (19.4%), 56.1 (20.9%), 55.1 (73.0%), 43.1 (63.3%).

[00219] l-(2,4-Dimethylpentan-3-ylidene)-3-oxo-5-(2-oxopyrrolidin-l- yl)pyrazolidin- l-ium-2-ide (5g)

[00220] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (65.4 mg, 0.263 mmol) and l-vinyl-2- pyrrolidinone (0.353 mg, 3.18 mmol) heated at 80°C for 3 hours. The title compound was obtained as a white solid (53.6 mg, 0.202 mmol, 77% isolated yield and 82% NMR yield). *H NMR (CDC1 3 , 300 MHz) δ 6.58 (dd, J = 9.0, 1.7, 1H), 3.40 (ddd, J = 9.9, 8.4, 6.4, 1H), 3.07- 2.80 (m, 4H), 2.50-2.27 (m, 3H), 2.16-1.89 (m, 2H), 1.35 (dd, J = 8.1, 7.0, 6H), 1.15 (d, J = 6.6, 3H), 0.98 (d, J = 6.6, 3H); 13 C NMR (CDC1 3 , 100 MHz) δ ppm 179.2 (C), 173.6 (C), 165.1 (C), 71.2 (CH), 41.3 (CH 2 ), 33.9 (CH 2 ), 31.9 (CH), 30.4 (CH 2 ), 30.4 (CH), 18.9 (CH 2 ), 18.7 (CH 3 ), 17.8 (CH 3 ), 16.7 (CH 3 ), 16.4 (CH 3 ); IR (film); 2972, 2930, 1691, 1645, 1579, 1417, 1265, 1014 cm "1 ; HRMS (EI): Exact mass calcd for Ci 4 H 23 N 3 0 2 [M] + : 265.1785;

found: 265.1765.

[00221 ] l-(2,4-Dimethylpentan-3-ylidene)- 5-(4-methoxyphenyl)-3-oxopyrazolidine- 1- ium-2-ide (5h)

[00222] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate lg (63.4 mg, 0.255 mmol) and 4- methoxystyrene (0.34 mL, 2.55 mmol) heated at 120°C for 3 hours. The title compound was obtained as a white solid (31.2 mg, 43% isolated yield and 54% NMR yield). TLC R f = 0.26 in 5% MeOH/CH 2 Cl 2 . 1H NMR (CDC1 3 , 300 MHz) δ 7.13 (d, J = 8.8, 2H), 6.87 (d, J = 8.8, 2H), 5.53 (dd, J = 9.9, 2.8, 1H), 3.78 (s, 3H), 3.18 (dd, J = 16.4, 9.9, 1H), 2.89 (dt, J = 13.4, 6.7, 1H), 2.78 (dt, J = 13.9, 6.9, 1H), 2.49 (dd, J = 16.4, 2.8, 1H), 1.41 (d, J = 6.9, 6H), 1.13 (d, J = 6.8, 3H), 0.51 (d, J = 6.6, 3H); 13 C NMR (CDC1 3 , 100 MHz) d ppm 181.1 (C), 162.6 (C), 159.8 (C), 132.3 (C), 126.5 (CH), 115.0 (CH), 69.7 (CH), 55.5 (CH), 40.4 (CH 2 ), 32.9 (CH), 30.3 (CH), 19.0 (CH 3 ), 17.7 (CH 3 ), 16.9 (CH 3 ), 16.4 (CH 3 ), ; IR (film); 2964, 2918, 2846, 2010, 1675, 1577, 1513, 1251, 1014 cm "1 ; HRMS (EI): Exact mass calcd for

CnH 24 N 2 0 2 [M] + : 288.1838; found: 288.1823.

[00223] (±)-cis-(Z)-l-(2,4-Dimethylpentan-3-ylidene)-3-oxo-l,3,3a,4 ,5,8,9,9a- octahydrocycloocta[c]pyrazol-l-ium-2-ide (5i)

[00224] ¾-NMR (400 MHz; CDC1 3 ): δ ppm 5.81-5.74 (m, 1H), 5.59 (ddt, J= 8.6, 8.4, 3.1 Hz, 1H), 4.90-4.82 (m, 1H), 2.87 (sept, J = 6.8 Hz, 1H), 2.85 (sept, J = 6.8 Hz, 1H), 2.81- 2.65 (m, 2H), 2.56 (d, J = 16.5 Hz, 1H), 2.45-2.37 (m, 1H), 2.31-2.02 (m, 4H), 1.89-1.77 (m, 1H), 1.39 (d, J= 7.0 Hz, 3H), 1.35 (d, J= 7.0 Hz, 3H), 1.25 (d, J= 6.7 Hz, 3H), 1.21 (d, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CDC1 3 ) ^Dppm 183.0 (C), 161.4 (C), 133.3 (CHi), 125.7 (CHi), 68.6 (CHi), 47.4 (CHi), 32.7 (CHi), 30.2 (CHi), 29.0 (CH 2 ), 28.7 (CH 2 ), 25.4 (CH 2 ), 22.6 (CH 2 ), 19.5 (CH 3 ), 19.3 (CH 3 ), 17.2 (CH 3 ), 17.0 (CH 3 ); HRMS(EI): Exact mass calcd for Ci 6 H 26 N 2 Oi [M] + : 262.2040. Found: 262.2029. [00225] (±)-cis-l-(2,4-Dimethylpentan-3-ylidene)-3-oxo-l,3,3a,4,5,7 a- hexahydroindazol-l-ium-2-ide (5j)

[00226] ¾-NMR (300 MHz; CDC1 3 ) δ ppm 6.23-6.14 (m, IH), 5.52 (dt, J= 10.0, 3.2 Hz, IH), 5.19-5.11 (m, IH), 3.07 (sept, J = 6.8 Hz, IH), 3.07-2.99 (m, IH), 2.86 (d, J= 7.0 Hz, IH), 2.38 (dt, J = 13.4, 2.6 Hz, IH), 2.28-2.07 (m, IH), 1.96 (dt, J= 18.1, 5.7 Hz, IH), 1.74- 1.60 (m, IH), 1.37 (d, J= 7.0 Hz, 3H), 1.35 (d, J= 6.9 Hz, 3H), 1.26 (d, J= 6.7 Hz, 3H), 1.22 (d, J= 6.7 Hz, 3H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 182.8 (C), 161.6 (C), 137.6 (CHi), 120.1 (CHi), 64.6 (CHi), 39.7 (CHi), 32.7 (CHi), 30.1 (CHi), 20.9 (CH 2 ), 20.0 (CH 2 ), 19.3 (CH 3 ), 19.2 (CH 3 ), 17.1 (CH 3 ), 16.9 (CH 3 ); HRMS(EI): Exact mass calcd for Ci 4 H 22 N 2 0i [M] + : 234.1727. Found: 191.1 (0.1%), 136.1 (3.6%), 43.1 (91.6%).

[00227] (±)-cis-l-(2,4-Dimethylpentan-3-ylidene)-3-oxo-l,3,3a,4,5,7 a- hexahydroindazol-l-ium-2-ide (Table 3, 5j)

A

[00228] Synthesized according to general procedure B using phenyl 2-(2,4- dimethylpentan-3-ylidene)hydrazinecarboxylate Id (50 mg, 0.20 mmol) and 1,3- cyclohexadiene (4e, 0.19 mL, 2.0 mmol) heated at 120 °C for 3 hours. The title compound and its regioisomer (28 mg, 60%) were obtained as an inseparable 7: 1 mixture (yellow oil). TLC R f =0.33 in 5% MeOH/CH 2 Cl 2 . ¾-NMR (300 MHz; CDC1 3 ) *denotes presence of regioisomer as a minor product δ ppm 6.23-6.14 (m, IH), *6.11-6.02 (m, IH), *5.92-5.81 (m, IH), 5.52 (dt, J = 10.0, 3.2 Hz, IH), 5.19-5.11 (m, IH), *4.73 (ddt, J= 12.8, 5.5, 2.8 Hz, IH), *3.36-3.26 (m, IH), 3.04 (sept, J= 6.8 Hz, IH), 3.07-2.99 (m, IH), 2.86 (d, J= 7.0 Hz, IH), 2.38 (dt, J= 13.4, 2.6 Hz, 1H), 2.28-2.07 (m, 1H), 1.96 (dt, J= 18.1, 5.7 Hz, 1H), 1.74-1.60 (m, 1H), 1.37 (d, J = 7.0 Hz, 3H), 1.35 (d, J= 6.9 Hz, 3H), 1.26 (d, J= 6.7 Hz, 3H), 1.22 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDC1 3 ) SU ppm 182.8 (C), *181.4 (C), 161.6 (C), 137.6 (CH), *126.7 (CHi), *123.2 (CH),120.1 (CH), 64.6 (CH), *64.5 (CH), *42.5 (CH), 39.7 (CH), 32.7 (CH), 30.1 (CH), *30.1 (CH), *26.7 (CH 2 ), *22.5 (CH 2 ), 20.9 (CH 2 ), 20.0 (CH 2 ), 19.3 (CH 3 ), 19.2 (CH 3 ), 17.1 (CH 3 ), 16.9 (CH 3 ). IR (film); 2927, 2851, 1706, 1695, 1595, 1095, 915, 738 cm "1 ; MS mlz (relative intensity): 43.1 (91.6%), 136.1 (3.6%), 191.1 (0.1%).

[00229] (±)-exo-2-(2,3-Dimethylpentan-3-ylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (5k)

[00230] ¾ NMR (300 MHz, CDC1 3 ) δ ppm 6.43 (dd, J = 5.67, 3.00 Hz, 1H), 6.08 (dd, J = 5.64, 3.11 Hz, 1H), 4.44 (d, J = 7.08 Hz, 1H), 3.31 (s, 1H), 3.11 (sept, J = 6.73 Hz, 1H), 3.03 (s, 1H), 2.92 (d, J = 6.96 Hz, 1H), 2.83 (sept., J = 6.96 Hz, 1H), 1.72-1.56 (m, 2H), 1.37 (t, J = 6.80 Hz, 6H), 1.29-1.17 (m, 6H); 13 C NMR (75 MHz, CDC1 3 ) δ ppm 181.8 (C), 162.0 (C), 142.5 (CHi), 133.5 (CHi), 74.1 (CHi), 51.0 (CHi), 49.0 (CHi), 44.7 (CHi), 43.2 (CH 2 ), 32.7 (CH , 30.0 (CH , 19.1 (CH 3 ), 19.0 (CH 3 ), 16.9 (CH 3 ), 16.8 (CH 3 ). HRMS(EI): Exact mass calcd for Ci 5 H 22 N 2 0i [M] + : 246.1732. Found: 246.1712.

[00231 ] l-(2,4-Dimethylpentan-3-ylidene)-3-oxo-5-trimethylsilylpyraz olidine- l-ium-2- ide (51)

[00232] ¾-NMR (400 MHz; CDC1 3 ): δ ppm 4.57 (ddt, J= 12.5, 8.8, 1.8 Hz, 1H), 2.92- 2.76 (m, 3H), 2.27 (dd, J= 15.8, 1.8 Hz, 1H), 1.37 (d, J= 7.0 Hz, 3H), 1.35 (d, J = 6.9 Hz, 3H), 1.24 (d, J = 6.8 Hz, 3H), 1.23 (s, 2H), 1.19 (d, J = 6.8 Hz, 3H), 0.92 (dd, J= 14.3, 1.6 Hz, 1H), 0.10 (s, 9H); U C NMR (100 MHz, CDC1 3 ) δ ppm 181.2 (C), 160.4 (C), 64.3 (CHi), 38.4 (CH 2 ), 32.3 (CHi), 30.1 (CHi), 26.0 (CH 2 ), 19.2 (CH 3 ), 18.9 (CH 3 ), 17.1 (CH 3 ), 16.8 (CH 3 ), -1.0 (3CH 3 ); HRMS(EI): Exact mass calcd for Ci 4 H 28 N 2 0iSii [M] + : 268.1971. Found: 268.1954. l-(2,4-Dimethylpentan-3-ylidene)- 5-«-pentanyl -3-oxopyrazolidine-l

[00234] Synthesized according to general procedure B using ferf-butyl 2-(2,4- dimethylpentan-2-ylidene)hydrazinecarboxylate lg (46 mg, 0.20 mmol) and l-hexene(4 mL). The reaction was under 150 °C. The title compound (31 mg, 66%) was obtained as yellow oil. ¾ NMR (CDC1 3 , 300 MHz) δ 4.59 (t, J = 9.0, 1H), 2.99-2.75 (m, 3H), 2.37 (dd, J = 16.1, 1.8, 1H), 1.78-1.55 (m, 2H), 1.38-1.18 (m, 16H), 0.88 (t, J = 7.0, 3H); 13 C NMR (CDC1 3 , 100 MHz) d ppm 181.4 (C), 161.8 (C), 66.1 (CH), 36.1 (CH 2 ), 35.0 (CH 2 ), 32.3 (CH), 30.2 (CH), 26.6 (CH 2 ), 22.4 (CH 2 ), 19.3 (CH 3 ), 19.1 (CH 3 ), 17.0 (CH 3 ), 16.9 (CH 3 ), 13.9 (CH 3 ).

[00235] (±)-cis- l-(Admantan-2-ylidene)-tetrahydro- LH-furo [2,3-c] pyrazolidine- 1- ium-2-ide (5o)

[00236] Synthesized according to general procedure B using phenyl 2-(admantan-2- ylidene)hydrazinecarboxylate (57 mg, 0.20 mmol) and 2-3-dihydrofuran (0.16 mL, 2.0 mmol). The reaction was under 80 °C. The title compound was obtained as a yellow oil (34 mg, 65% isolated yield and 70% NMR yield). TLC Rf 0.13 in 20% methanol in EtOAc. ¾ NMR (300 MHz, CDC1 3 ) δ ppm 6.09 (d, J = 6.36 Hz, 1H), 4.09 (t, J = 8.27 Hz, 1H), 3.88 (bs, 1H), 3.67 (ddd, J = 12.27, 8.82, 5.27 Hz, 1H), 3.41 (dd, J = 9.25, 6.43 Hz, 1H), 3.24 (bs, 1H), 2.49 (dd, J = 12.67, 5.22 Hz, 1H), 2.20-1.86 (m, 1H); 13 C NMR (75 MHz, CDC1 3 ) δ ppm 180.8 (C), 165.9 (C), 95.8 (CHi), 68.4 (CH 2 ), 47.4 (CHi), 39.7 (CH 2 ), 38.5 (CH 2 ), 38.4 (CH 2 ), 37.8 (CH 2 ), 35.8 (CH 2 ), 35.4 (CHi), 35.0 (CHi), 30.1 (CH 2 ), 27.1 (CHi), 26.9 (CHi). IR 2931, 2862, 2253, 1702, 1659, 1602, 1453, 1387, 913, 740, 650 cm "1 .

[00237] (±)-cis-l-Diphenylmethylene-3-oxo-tetrahydro-lH-furo[2,3-c] pyrazolidine-l- ium-2-ide (5n)

[00238] Synthesized according to general procedure B using phenyl 2- (diphenylmethylene)hydrazinecarboxylate (64 mg, 0.20 mmol) and 2,3-dihydrofuran (0.16 mL, 2.0 mmol). The title compound was obtained as a yellow oil (43 mg, 74% isolated yield and 76% NMR yield at 100 °C; 64% NMR yield at 120 °C). TLC Rf 0.14 in 10% methanol in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.99-7.95 (m, 2H), 7.55-7.42 (m, 5H), 7.42-7.31 (m, 3H), 5.87 (d, J = 5.73 Hz, 1H), 3.80 (ddd, J = 12.52, 8.80, 5.01 Hz, 1H), 3.39 (dd, J = 8.32, 5.77 Hz, 1H), 2.56 (dd, J = 12.51, 4.92 Hz, 1H), 2.11-1.98 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) ^ ppm 182.91, 147.9, 133.5, 133.3, 132.5 (CHi), 131.7 (CHi), 130.5 (2CHi), 128.6 (CHi), 128.1 (CHi), 99.7 (CHi), 68.7 (CH 2 ), 47.0 (CHi), 29.7 (CH 2 ). IR (film) 3066, 2959, 2881, 1666, 1545, 1208, 1067, 698 cm "1 ; HRMS(EI):Exact mass calcd for Ci 8 Hi 6 N 2 0 2 [M] + : 292.1206. Found: 292.1176.

[00239] The ORTEP of the crystal structure for compound 5n is shown in Figure 1, and the X-ray data is provided in Tables 6 - 12.

[00240] (±)-exo-2-(2,4-Dimethylpentan-3-ylidene)-4-thione-2,3- diazatricyclo [4,3,1 6 ' 9 ,0] decane-2-ium-3-ide (5p)

[00241] Synthesized according to general procedure B using 2-(2,4-dimethylpentan-3- ylidene)-N,N-diisopropylhydrazinecarbothioamide (54 mg, 0.20 mmol) and norbomene (190 mg, 2.0 mmol, 10 equiv). The title compound was obtained as a yellow oil (36 mg, 68% isolated yield, 77% NMR yield) as a yellow oil. TLC Rf 0.35 in EtOAc. ¾ NMR (400 MHz, CDCI 3 ) δ ppm 4.19 (d, J = 6.95 Hz, 1H), 3.11 (d, J = 6.96 Hz, 1H), 3.00 (sept, J = 6.74 Hz, 1H), 2.93-2.84 (m, 2H), 2.40-2.37 (m, 1H), 1.66-1.52 (m, 2H), 1.39 (d, J = 6.97 Hz, 3H), 1.36 (d, J = 6.95 Hz, 3H), 1.27 (d, J = 6.69 Hz, 3H), 1.21 (d, J = 6.76 Hz, 3H). 13 C NMR (100 MHz, CDCI 3 ) δ ppm 202.6 (C), 168.7 (C), 72.3 (CHi), 62.7 (CHi), 43.5 (CHi), 41.8 (CHi), 34.3 (CHi), 32.0 (CH 2 ), 30.9 (CHi), 26.7 (CH 2 ), 25.5 (CH 2 ), 18.9 (CH 3 ), 18.9 (CH 3 ), 18.2 (CH 3 ), 17.7 (CH 3 ). IR (film) 3420, 2966, 2929, 2877, 1592, 1423, 1267, 1146, 1116, 1002, 732 cm "1 . HRMS(EI): Exact mass calcd for Ci 5 H 24 N 2 Si [M] + : 264.1655. Found:

264.1661.

[00242] The ORTEP of the crystal structure for compound 5p is shown in Figure 2, and the X-ray data is provided in Tables 13 - 19.

[00243] 3-butyl-2-(9H-fluoren-9-ylidene)-5-oxopyrazolidin-2-ium-l-id e (Table 3, 5aa)

[00244] Synthesized according to general procedure A (uW, 3h, 150C) using hydrazone 4b (0.25 mmol, 78.6 mg) and 1-hexene (2.5 mmol, 0.31 mL), heating to 150 °C for 3 h. The title compound (55.6 mg, 73%) was obtained as a yellow solid. ¾ NMR (400MHz ,CDC1 3 ) δ 9.03 - 8.96 (m, 1 H), 7.73 - 7.66 (m, 1 H), 7.63 - 7.58 (m, 1 H), 7.48 (m, 1 H), 7.46 - 7.39 (m, 2 H), 7.38 - 7.29 (m, 2 H), 5.30 - 5.19 (m, 1 H), 3.10 (dd, J= 8.4, 16.5 Hz, 1 H), 2.69 (dd, J = 1.7, 16.5 Hz, 1 H), 2.16 - 2.04 (m, 1 H), 1.96 - 1.82 (m, 1 H), 1.56 - 1.30 (m, 4 H), 0.94 - 0.85 (m, 3 H). 13 C NMR (400 MHz, CDC1 3 ) δ 183.4, 142.0, 139.7, 139.5, 131.9, 131.7, 131.4, 131.0, 129.7, 129.2, 128.2, 125.0, 121.1, 119.6, 68.5, 35.9, 34.5, 27.4, 22.4, 13.8. IR (film); 2957, 2867, 1663, 1606, 1450, 1355, 1278, 1200, 1128, 1093, 1087, 976, 779, 731, 701, 671, 654 cm "1 . HRMS (EI): Exact mass calcd for C 20 H 20 N 2 O [M]+: 304.1576. Found: 304.1581. [00245] 2-(9H-fluoren-9-ylidene)-5-oxo-3-[(trimethylsilyl)methyl]pyr azolidin-2-ium- 1-ide (Table 3, 5bb)

[00246] Synthesized according to general procedure (uW, 3h, lOOC) using hydrazone

(0.25 mmol, 79.2 mg) and allyl trimethylsilane (2.5 mmol, 0.40 mL). The title compound (68 mg, 81%) was obtained as a yellow solid. TLC R f = 0.35 in EtOAc. ¾ NMR (400MHz , CDCls) δ 8.99 (d, J = 7.4 Hz, 1 H), 7.70 (d, J = 7.3 Hz, 1 H), 7.61 (d, J = 7.1 Hz, 1 H), 7.51 (d, J = 8.1 Hz, 1 H), 7.46 - 7.38 (m, 2 H), 7.38 - 7.32 (dappt, J= 1.2, 7.7 Hz, 1 H), 7.32 - 7.27 (dappt, J = 1.1, 7.8 Hz, 1 H), 5.41 - 5.31 (m, 1 H), 3.13 (dd, J = 8.4, 16.2 Hz, 1 H), 2.59 (dd, J = 1.6, 16.3 Hz, 1 H), 1.57 (dd, J = 1.9, 14.4 Hz, 1 H), 1.37 (dd, J = 12.8, 14.4 Hz, 1 H), 0.27 - 0.04 (s, 9 H). 13 C NMR (400 MHz, CDC1 3 ) δ 183.2, 141.8, 139.6, 138.7, 131.8, 131.7, 131.2, 130.8, 129.6, 129.1, 127.8, 125.3, 121.1, 119.6, 67.2, 37.8, 24.9, -0.7 (3C). IR (film); 3055, 2956, 1668, 1603, 1546, 1447, 1349, 1273, 1254, 1200, 1120, 1094, 1079, 972, 843, 771, 729 cm "1 . HRMS (EI): Exact mass calcd for C2 0 H22N2OS1 [M]+: 334.1501. Found: 334.1476.

[00247] Gram Scale Reaction: Hydrazone 4b (3.0 mmol, 943 mg), allyl trimethylsilane

(15 mmol, 5 equiv., 2.4 mL), and TFT (60 mL) combined in a 100 mL round-bottom flask, equipped with a reflux condenser. The mixture was heated to 100 °C in an oil bath and stirred for 6 h. The mixture changed from clear and yellow to dark purple with some precipitate. After 6 h the mixture was cooled to room temperature, the stir bar removed, and TFT evaporated to give a dark residue. This was purified by passing through a silica plug, eluting first with 1/4 : EtOAc/DCM to remove excess alkene and a purple byproduct, then then 9/1 : EtOAc/MeOH to elute the product. Solvent removed by evaporation to give the product (819 mg, 82%) as a yellow solid. [00248] 3-(2-(benzyloxy)ethyl)-2-(9H-fluoren-9-ylidene)-5-oxopyrazol idin-2-ium- 1-ide (Table 3, 5cc)

[00249] Synthesized according to general procedure (oil, 6h, lOOC) using hydrazone 4b (0.25 mmol, 77.6 mg) and l-((but-3-enyloxy)methyl)benzene (2.5 mmol, 0.372 g). The title compound (49 mg, 52%) was obtained as a yellow solid. TLC R f = 0.22 in EtOAc. ¾ NMR (400MHz ,CDC1 3 ) 5 8.95 (d, J= 7.7 Hz, 1 H), 8.00 (d, J= 8.0 Hz, 1 H), 7.59 (d, J = 7.3 Hz, 1 H), 7.54 (d, J = 7.3 Hz, 1 H), 7.42 - 7.24 (m, 9 H), 7.09 - 7.02 (m, 1 H), 5.50 (m, 1 H), 4.57 (s, 2 H), 3.77 (apptd, J= 4.0, 9.4 Hz, 1 H), 3.66 - 3.57 (m, 1 H), 3.03 (dd, J = 8.1, 16.4 Hz, 1 H), 2.63 (dd, J = 1.3, 16.5 Hz, 1 H), 2.60 - 2.50 (m, 1 H), 1.95 - 1.84 (m, 1 H). 13 C NMR (400 MHz, CDCls) δ 183.2, 141.7, 140.0, 138.2, 137.8, 131.9, 131.6, 131.4, 131.0, 129.5, 129.0, 128.6 (2C), 128.4, 128.1, 127.7 (2C), 126.7, 120.8, 119.6, 73.6, 66.2, 66.0, 35.6, 35.1. IR (film); 3059, 2854, 1671, 1667, 1603, 1546, 1455, 1360, 1280, 1128, 1090, 1004, 770, 737 cm "1 . HRMS (EI): Exact mass calcd for C25H22N2O2 [M]+: 382.1681. Found: 382.1679.

[00250] (±)-cis-l-(9H-fluoren-9-ylidene)-3-oxooctahydroindazol-l-iu m-2-ide (Table 3, 5dd):

O

[00251] Synthesized according to general procedure (uW, 3h. 150°C) using hydrazone (0.25 mmol, 79.1 mg) and excess cyclohexene (49 mmol, 5 mL) as the solvent. The title compound (37.3, 49%) was obtained as a yellow solid. TLC R f = 0.26 in EtOAc. l NMR (400MHz ,CDC1 3 ) 5 8.97 (d, J= 7.7 Hz, 1 H), 7.64 (d, J= 7.5 Hz, 1 H), 7.57 (d, J = 7.5 Hz, 2 H), 7.38 (appt, J = 7.4 Hz, 2 H), 7.30 (dappt, J = 2.8, 7.5 Hz, 2 H), 5.34 (td, J = 7.2, 9.9 Hz, 1 H), 3.09 (appt, J = 6.4 Hz, 1 H), 2.55 - 2.42 (m, 2 H), 1.82 - 1.64 (m, 3 H), 1.62 - 1.49 (m, 1 H), 1.46 - 1.27 (m, 2 H). U C NMR (400 MHz, CDC1 3 ) δ 185.0, 141.9, 139.8, 139.4, 131.8, 131.6, 131.3, 130.8, 129.7, 129.1, 128.3, 125.0, 121.1, 119.6, 67.8, 40.7, 29.0, 21.8, 21.6 (2C). IR (film); 3059, 2938, 2857, 1676, 1607, 1555, 1450, 1372, 1312, 1278, 1249, 1200, 1133, 1119, 1082, 1062, 962, 918, 776, 728, 675, 663 cm "1 . HRMS (EI): Exact mass calcd for C 2 oHi 8 N 2 0 [M]+: 302.1419. Found: 302.1435.

[00252] (±)-cis-l-(9H-fluoren-9-ylidene)-3-oxo-l,3,3a,4,5,7a-hexahy droindazol-l-ium- 2-ide (Table 3, 5ee):

[00253] Synthesized according to general procedure A (3h, 100°C) using hydrazone 4b (0.24 mmol, 76.2 mg) and 1,3-cyclohexadiene (2.5 mmol, 0.24 mL). The title compound (0.0386 mg, 52%, 14: 1 mixture of regioisomers) was obtained as a yellow solid. TLC R f = 0.21 in EtOAc. ¾ NMR (400MHz , CDC1 3 ) δ 8.99 (d, J= 7.7 Hz, 1H), 7.65 - 7.73 (m, 2H), 7.62 (d, J= 7.4 Hz, 1H), 7.39 - 7.47 (m, 2H), 7.30 - 7.38 (m, 2H), 6.21 - 6.30 (m, 1H), 5.86 - 6.00 (m, 2H), 3.29 - 3.40 (m, 1H), 2.45 - 2.54 (m, 1H), 2.21 - 2.34 (m, 1H), 2.04 - 2.15 (m, 1H), 1.82 - 1.94 (m, 1H). 13 C NMR (400 MHz, CDC1 3 ) δ 184.9, 142.0, 139.8, 139.8, 137.7, 131.9, 131.6, 131.3, 130.9, 129.9, 129.1, 128.3, 125.2, 121.1, 119.6, 119.4, 66.3, 39.7, 20.9, 19.5. IR (film); 3043, 2924, 2852, 1660, 1603, 1549, 1450, 1359, 1302, 1274, 1121, 1073, 963, 777, 725 cm "1 . HRMS (EI): Exact mass calcd for C 20 Hi 6 N 2 O [M]+: 300.1263. Found: 300.1269.

[00254] (±)-exo-2-[N'-(9H-fluoren-9-ylidene)]-4-oxo-2,3-diazatricyc lo[4,3,l 6 9 ,0]dec-7- ene-2-ium-3-ide (Table 3, 5ff):

[00255] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and norbornadiene (184 mg, 2 mmol). The reaction temperature is 120 °C and the reaction time is 1 h. The title compound (87% NMR yield, 88% isolated yield) was obtained as yellow solid. TLC Rf 0.46 in 10% MeOH in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 8.83 (d, J = 7 ' .72 Hz, 1H), 7.57 (d, J = 7.15 Hz, 1H), 7.53-7.44 (m, 2H), 7.40-7.18 (m, 4H), 6.50 (dd, J = 5.43, 2.81 Hz, 1H), 6.26 (dd, J = 5.30, 2.93 Hz, 1H), 5.01 (d, J = 6.31 Hz, 1H), 3.41 (s, 1H), 3.36 (s, 1H), 3.13 (d, J = 6.68 Hz, 1H), 1.76 (d, J = 9.82 Hz, 1H), 1.63 (d, J = 9.97 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) ppm (5184.1 (C), 142.5 (CH), 141.8 (C), 139.7 (C), 139.4 (C), 133.5 (CH), 131.8 (CH), 131.5 (C), 131.3 (CH), 130.9 (CH), 129.9 (C), 129.0 (CH), 128.2 (CH), 125.4 (CH), 121.0 (CH), 119.6 (CH), 76.4 (CH), 51.0 (CH), 48.1 (CH), 45.3 (CH), 42.9 (CH 2 ). IR (film) 7990, 1653, 1606, 1550, 1290, 1133, 775, 727 cm "1 . HRMS(EI): Exact mass calcd for C 2 iHi 6 N 2 0 [M] + :

314.1257. Found: 312.1269.

[00256] 2-(9H-fluoren-9-ylidene)-5-oxo-3-phenylpyrazolidin-2-ium-l-i de (Table 3,

5gg)

[00257] Synthesized according to general procedure (uW and oil, 6h, 100°C) using hydrazone (0.25 mmol, 78.2 mg) and styrene (2.5 mmol, 0.30 mL). The title compound (51.9 mg, 64%) was obtained as a yellow solid. TLC R f = 0.27 in EtOAc. ¾ NMR (400 MHz, CDCI 3 ) δ 9.13 (d, J= 7.5 Hz, 1 H), 7.59 (dd, J= 3.9, 7.2 Hz, 2 H), 7.49 - 7.43 (m, 1 H), 7.43 - 7.25 (m, 8 H), 7.05 (m, 1 H), 6.37 (m, 1 H), 3.56 (dd, J = 9.6, 16.4 Hz, 1 H), 2.89 - 2.78 (dd, J = 1.64, 16.3 Hz, 1 H). 13 C NMR (400 MHz, CDC1 3 ) δ 182.4, 141.8, 141.3, 140.3, 137.9, 132.3, 131.7(2), 131.6(8), 131.1, 129.8, 129.3, 129.2, 128.7, 128.0 (2C), 125.9, 124.7 (2C), 120.8, 119.7, 72.2, 40.7 IR (film); 3067, 3021, 2922, 1668, 1603, 1447, 1345, 1276, 1242, 1124, 1090, 980, 778, 725, 713 cm "1 . HRMS (EI): Exact mass calcd for C 22 Hi 6 N 2 0 [M]+: 324.1263. Found: 324.1272. [00258] 2-(9H-fluoren-9-ylidene)-3-(4-fluorophenyl)-5-oxopyrazolidin -2- (Table 3, entry 10, 5hh).

[00259] Synthesized according to general procedure C using hydrazone (0.2618 g, 0.8335 mmol), 4-fluorostyrene (1.0180 g, 8.335 mmol) in trifluorotoluene (1.7 mL) and heated in a sealed tube. The title compound was obtained as yellow crystals (0.1540 g, 54 % yield). TLC R f = 0.63 in 10% MeOH/CH 2 Cl 2 . 1H NMR (CDC1 3 , 300 MHz) δ ppm 9.05 (d, J = 7.6, 1H), 7.53 (d, J = 7.5, 2H), 7.40-7.21 (m, 6H), 7.01 (t, J = 8.3, 3H), 6.33 (d, J = 8.9, 1H), 3.47 (dd, J = 16.3, 9.2, 1H), 2.67 (d, J = 16.1 , 1H); 13 C NMR (CDC1 3 , 100 MHz) δ ppm 182.3, (C), 164.2 (C), 160.9 (C), 141.9 (C), 141.3 (C), 140.3 (C), 133.9 (C), 133.9 (C), 132.5 (CH), 131.7 (CH), 131.6 (CH), 131.3 (CH), 129.3 (CH), 129.2 (CH), 128.1 (CH), 126.8 (CH), 126.7 (CH), 125.9 (CH), 121.0 (CH), 120.0 (CH), 1 17.1 (CH), 1 16.8 (CH), 71.6 (CH), 40.9 (CH 2 ); IR (film); 3268, 2918, 2854, 2325, 1968, 1656, 1565, 1421 , 1269, 733 cm "1 . HRMS (EI): Exact mass calcd for C 22 H 18 N 2 0i[M] + : 342.1 168; found: 342.1185.

[00260] 2-(9H-fluoren-9-ylidene)-3-(4-methoxyphenyl)-5-oxopyrazolidi n-2-ium-l-ide (Table 3, entry 11, 5ii)

[00261] Synthesized according to general procedure (uW, 3h, 100 °C) using hydrazone

(0.25 mmol, 79.8 mg) and 4-methoxystyrene (2.5 mmol, 0.33 mL). The title compound (67 mg, 74%) was obtained as a yellow solid. TLC R f = 0.23 in 100% EtOAc. ¾ NMR (400 MHz ,CDC1 3 ) δ 9.12 (d, J = 7.5 Hz, 1 H), 7.58 (dd, J = 3.0, 7.2 Hz, 2 H), 7.47 - 7.33 (m, 3 H), 7.29 (m, 1 H), 7.21 - 7.14 (m, 2 H), 7.11 - 7.02 (m, 1 H), 6.88 - 6.81 (m, 2 H), 6.30 (m, 1 H), 3.73 (s, 3 H), 3.46 (dd, J = 9.2, 16.3 Hz, 1 H), 2.72 (dd, J = 1.8, 16.3 Hz, 1 H). U C NMR (101 MHz, CDCls) δ 182.6, 159.7, 141.8, 141.4, 140.3, 132.3, 131.7 (2C), 131.1, 129.9, 129.4, 129.2, 128.0, 126.1, 126.0 (2C), 120.8, 119.7, 115.1 (2C), 71.9, 55.3, 40.9. IR (film); 3063, 2945, 2835, 1664, 1607, 1546, 1508, 1447, 1341, 1299, 1273, 1250, 1177, 1117, 1094, 1078, 1025, 984, 911, 828, 779, 725 cm "1 . HRMS (EI): Exact mass calcd for C 23 Hi 8 N 2 0 2 [M]+: 354.1368. Found: 354.1374.

[00262] Gram Scale: Hydrazone (3.0 mmol, 943 mg), 4-methoxystyrene (15 mmol, 5 equiv., 2.0 mL), and TFT (60 mL) combined in a 100 mL RBF, equipped with a reflux condenser. The mixture was heated to 100 °C in an oil bath and stirred for 6 h. The mixture changed from clear and yellow to dark brown with some precipitate. After 6 h the mixture was cooled to room temperature, the stir bar removed, and TFT evaporated to give a dark oil. This was purified by passing through a silica plug, eluting first with 1/4 : EtOAc/DCM to remove excess alkene and a purple byproduct, then then 9/1 : EtOAc/MeOH to elute the product. Solvent removed by evaporation to give the product (749 mg, 71%) as a yellow solid.

[00263] l-(9H-Fluoren-9-ylidine)-3,3a,4,8b-tetrahydro-2H-indeno[2,l- c]- pyrazolidine-l-ium-2-ide (Table 3, 5jj):

A a

[00264] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and lH-indene (232 mg, 2.0 mmol). The reaction temperature is 120 °C and the reaction time is 2 h. The title compound (51% isolated yield) was obtained as yellow solid and was obtained as a 6: 1 regioisomeric mixture favouring A. TLC Rf 0.26 in 100% EtOAc. ¾ NMR (300 MHz, CDC1 3 ) ppm ^8.94 (d, J = 7.80 Hz, 1H), 7.99 (d, J = 7.95 Hz, 1H), 7.74 (d, J = 7.41 Hz, 1H), 7.64 (d, J = 7.48 Hz, 1H), 7.52-7.26 (m, 7H), 7.13-7.05 (m, 1H), 6.78 (d, J = 7.20 Hz, 1H), 3.74 (t, J = 7.53 Hz, 1H), 3.67 (d, J = 16.75 Hz, 1H), 3.34 (dd, J = 16.64, 8.44 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) ppm δ 185.8 (C), 143.4 (C), 142.3 (C), 140.1 (C), 137.1 (C), 132.2 (CH), 131.7 (C), 131.6 (CH), 131.4 (CH); 130.6 (C), 130.3 (CH), 129.2 (CH), 128.4 (CH), 127.5 (CH), 126.1 (CH), 125.5 (CH), 125.3 (CH), 121.3 (CH), 119.8 (CH), 76.0 (CH), 45.9 (CH), 33.3 (CH 2 ). ). IR (film) 2981, 1670, 1606, 1546, 1282, 1120, 775, 728 cm! . HRMS(EI): Exact mass calcd for C 23 Hi 6 N 2 0 [M] + : 336.1257. Found: 336.1233.

[00265] l-(9H-Fluoren-9-ylidine)-3-(l,2,3,4-tetrahydro-naphtalene)-p yrazolidine-l- ium-2-ide (Table 3, 5kk).

B

[00266] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (0.2349g, 0.7478 mmol), dihydronaphthalene (0.9134 g, 7.478 mmol) in trifluorotoluene (1.5 mL) and heated at 120 °C for three hours. Volatiles were removed and the crude product was isolated by column chromatography with 100% CH 2 C1 2 , then 50% EtOAc/w-hexanes and gradually increased to 100% EtOAc. Product was obtained as a mixture of regioisomer A (32% NMR yield) and B (20% NMR yield). Regioisomer A was obtained as yellow crystals (0.0684 g, 0.195 mmol, 26% yield). TLC R f = 0.30 in 100% EtOAc. ¾ NMR (CDCls, 300 MHz) δ ppm 9.10 (d, J = 7.4, 1H), 7.72 (dd, J = 14.7, 7.3, 2H), 7.44 (dq, J = 19.8, 9.9, 4H), 7.27 (d, J = 6.5, 2H), 7.20 (d, J = 7.7, 2H), 7.08 (t, J = 8.1, 1H), 6.26 (s, 1H), 3.69 (s, 1H), 2.98 (d, J = 13.6, 1H), 2.75 (t, J = 12.1, 1H), 2.42 (s, 1H), 2.02 (s, 1H); 13 C NMR (CDC1 3 , 100 MHz) δ ppm 185.4 (C), 142.4 (C), 142.3 (C), 140.3 (C), 139.9 (C), 132.5 (C), 132.0 (CH), 131.7 (CH), 131.5 (CH), 130.5 (C), 129.5 (CH), 129.3 (CH), 129.0 (C), 128.8 (CH), 128.5 (CH), 126.9 (CH), 126.0 (CH), 125.5 (CH), 121.2 (CH), 119.9 (CH), 69.8, 42.6, 28.5, 21.4; IR (film) 3059, 2914, 2850, 1672, 1603, 1550, 1451, 1257, 1132, 729; cm "1 ; HRMS (EI): Exact mass calcd for C 24 Hi 8 N 2 0i[M] + : 350.1419; found:

350.1438. [00267] 2-(9H-fluoren-9-ylidene)-3-(penta(ferrocenyl)cyclopentadieny l)-5- oxopyrazolidin-2-ium-l-ide (Table 3, 5mm).

[00268] Synthesized according to general procedure C using hydrazone (0.0800 g, 0.255 mmol), vinyl-ferrocene (0.0541 g, 0.255 mmol) in trifiuorotoluene (1.28 mL) and heated at 80 °C for three hours. Volatiles were removed and the crude product was isolated by column chromatography with 100% CH 2 CI 2 , then 50% EtOAc/w-hexanes and gradually increased to 100% EtOAc. The title compound was obtained as dark red crystals (0.1024 g, 0.237 mmol, 93 % isolated yield). TLC R f = 0.22 in 100 % EtOAc. ¾ NMR (CDC1 3 , 300 MHz) δ ppm 8.90 (d, J = 7.6, 1H), 7.97 (dd, J = 7.1, 4.0, 2H), 7.62-7.48 (m, 4H), 7.30 (t, J = 7.5, 1H), 6.35-6.33 (m, 1H), 4.36 (d, J = 20.6, 2H), 4.15 (d, J = 0.3, 1H), 3.84 (s, 1H), 3.34-3.33 (m, 12H), 3.14 (d, J = 15.7, 1H); 13 C NMR (CDC1 3 , 100 MHz) δ ppm 184.3, 140.7, 139.9, 138.3, 132.2 (CH), 131.1 (CH), 130.3 (CH), 129.8 (C), 129.3 (CH), 128.6 (CH), 127.0 (CH), 121.5 (CH), 120.9 (CH), 89.2 (C), 69.5 (CH), 69.3 (CH), 67.8 (CH), 67.5 (CH), 67.4 (CH), 66.6 (CH), 40.4 (CH 2 ); IR (film); 3086, 2975, 1664, 1546, 1273, 1120, 733 cm "1 ; HRMS (EI): Exact mass calcd for C2 8 H 26 FeiN 2 0i[M] + : 432.0925; found: 432.0951.

[00269] l-[N'-(9H-fluoren-9-ylidene)]-3-oxo-5-(2-oxopyrrolidine-l-yl )pyrazolidine-l- ium-2-ide (Table 3, 5nn):

[00270] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and N-vinyloxypyrrolidin-2-one (127 mg, 1.0 mmol). The reaction temperature is 100 °C and the reaction time is 2 h. The title compound (30% NMR yield, 40% isolated yield) was obtained as yellow solid. TLC Rf 0.21 in 100% EtOAc. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 9.00 (d, J = 7.82 Hz, 1H), 7.79 (d, J = 8.06 Hz, 1H), 7.61 (d, J = 7.51 Hz, 1H), 7.58 (d, J = 7.42 Hz, 1H), 7.44 (t, J = 7.48 Hz, 1H), 7.39 (t, J = 7.52 Hz, 1H), 7.33 (t, J = Ί .61 Hz, 1H), 7.28-7.23 (m, 1H), 7.15 (d, J = 8.00 Hz, 1H), 3.39 (dd, J = 17.13, 8.00 Hz, 1H), 3.28 (dd, J = 17.18, 8.38 Hz, 1H), 3.09 (td, J = 9.33, 3.75 Hz, 1H), 2.56 (dd, J = 17.19, 1.09 Hz, 1H), 2.43-2.35 (m, 2H), 2.12-1.97 (m, 1H), 1.94- 1.79 (m, 1H). 13 C NMR (100 MHz, CDC1 3 ) ppm δ 181.3 (C), 175.1 (C), 141.9 (C), 141.7 (C), 140.6 (C), 132.9 (CH), 132.2 (CH), 131.9 (CH), 131.5 (C), 129.3 (CH), 129.2 (C), 128.9 (CH), 125.7 (CH), 120.9 (CH), 119.9 (CH), 74.9 (CH), 42.2 (CH 2 ), 35.6 (CH 2 ), 30.9 (CH 2 ), 17.8 (CH 2 ). ). IR (film) 2989, 1673, 1602, 1545, 1453, 1411, 1270, 1217, 772 cm "1 .

HRMS(EI): Exact mass calcd for C 20 Hi 7 N 3 O 2 [M] + : 331.1315. Found: 331.1351.

[00271] 5-«~Butyloxy-l-[N'-(9H-fluoren-9-ylidene)]-3-oxopyrazolidin e-l-ium-2-ide (Table 3, 5pp)

[00272] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and vinyl-ft-butylether (40 mg, 0.4 mmol). The reaction temperature is 100 °C and the reaction time is 2 h. The title compound (73% NMR yield, 78% isolated yield) was obtained as yellow solid. TLC Rf 0.23 in 100% EtOAc. Ti NMR (400 MHz, CDC1 3 ) ppm δ 8.88 (d, J = 7.76 Hz, 1H), 7.81 (d, J = 7 ' .92 Hz, 1H), 7.56 (d, J = 7.48 Hz, 1H), 7.51 (d, J = 7.40 Hz, 1H), 7.40-7.33 (m, 2H), Ί .29-1.22 (m, 2H), 6.51 (d, J = 6.63 Hz, 1H), 3.60 (dt, J = 8.64, 6.29 Hz, 1H), 3.29-3.22 (m, 1H), 3.01 (dd, J = 17.70, 7.76 Hz, 1H), 2.83 (dd, J = 17.68, 1.68 Hz, 1H), 1.48-1.37 (m, 2H), 1.24-1.09 (m, 2H), 0.71 (t, J = 7.38 Hz, 3H). 13 C NMR (100 MHz, CDC1 3 ) ppm 5181.7 (C), 141.7 (C), 141.4 (C), 140.5 (C), 132.4 (CH), 131.5 (CH), 131.4 (1CH, 1C), 129.7 (C), 129.0 (CH), 128.4 (CH), 126.8 (CH), 120.7 (CH), 119.8 (CH), 93.9 (CH), 63.0 (CH 2 ), 33.4 (CH 2 ), 31.1 (CH 2 ), 19.0 (CH 2 ), 13.6 (CH 3 ). IR (film) 2962, 2930, 2872, 1669, 1608, 1544, 1446, 1272, 1197, 1128, 911,726 cm "1 . HRMS(EI): Exact mass calcd for C 20 H 20 N 2 O 2 [M] + : 320.1519. Found: 320.1529. [00273] 5-Cyclohexyloxy-l~[N'-(9H-fluoren-9-ylidene)]-3-oxopyrazolid ine-l-ium-2- ide (Table 3, 5qq)

[00274] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and vinyloxycyclohexane (50 mg, 0.4 mmol). The reaction temperature is 100 °C and the reaction time is 2 h. The title compound (76% NMR yield, 69% isolated yield) was obtained as yellow solid. TLC R f = 0.32 in 100% EtOAc. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 8.93 (d, J = 7.69 Hz, 1H), 7.96 (d, J = 8.05 Hz, 1H), 7.60 (d, J = 7.50 Hz, 1H), 7.56 (d, J = 7.31 Hz, 1H), 7.44-7.35 (m, 2H), 7.33-7.25 (m, 2H), 6.56 (d, J = 7.73 Hz, 1H), 3.84-3.74 (m, 1H), 3.04 (dd, J = 17.76, 7.91 Hz, 1H), 2.85 (dd, J = 17.78, 1.60 Hz, 1H), 1.86-1.61 (m, 2H), 1.49-1.19 (m, 5H), 1.16-1.00 (m, 3H). 13 C NMR (100 MHz, CDC1 3 ) ppm ^182.0 (C), 141.7 (C), 141.6 (C), 140.5 (C), 132.4 (CH), 131.6 (CH), 131.5 (C), 131.4 (CH), 129.8 (C), 129.0 (CH), 128.4 (CH), 127.2 (CH), 120.7 (CH), 119.7 (CH), 93.5 (CH), 73.9 (CH), 34.3 (CH 2 ), 34.2 (CH 2 ), 33.1 (CH 2 ), 25.1 (CH 2 ), 23.8 (2CH 2 ). IR (film) 2938, 2853, 1670, 1604, 1550, 1448, 1272, 752 cm "1 . HRMS(EI): Exact mass calcd for C 22 H 22 N 2 0 2 [M] + : 346.1676. Found: 346.1695.

[00275] (±)-cis-l-[N'-(9H-fluoren-9-ylidene)]-3-oxotetrahydro-lH-fu ro[2,3- c]pyrazolidine-l-ium-2-ide (Table 3, 5rr):

[00276] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and 2,3-dihydrofuran (28 mg, 0.4 mmol). The reaction temperature is 100 °C and the reaction time is 2 h. The title compound (65% NMR yield, 57% isolated yield) was obtained as yellow solid. TLC Rf 0.28 in 10% MeOH in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 8.92 (d, J = 7.75 Hz, 1H), 7.97 (d, J = 8.06 Hz, 1H), 7.64 (d, J = 7.53 Hz, 1H), 7.60 (d, J = 7.45 Hz, 1H), 7.47-7.26 (m, 4H), 6.67 (d, J = 6.05 Hz, 1H), 4.24 (t, J = 8.48 Hz, 1H), 3.82 (ddd, J = 12.65, 9.06, 5.08 Hz, 1H), 3.55 (dd, J = 9.16, 6.21 Hz, 1H), 2.64 (dd, J = 12.67, 5.04 Hz, 1H), 2.32 (tdd, J = 12.58, 9.10, 8.15 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) ppm δ 183.3 (C), 141.8 (C), 140.6 (C), 132.6 (CH), 131.6 (CH), 131.5 (C), 131.5 (CH), 130.0 (C), 129.1 (CH), 129.0 (C), 128.4 (CH), 126.2 (CH), 120.8 (CH), 119.8 (CH), 98.7 (CH), 68.9 (CH 2 ), 46.3 (CH), 30.4 (CH 2 ). IR (film) 1670, 1607, 1549, 1450, 1347, 1278, 913, 743 cm "1 . HRMS(EI): Exact mass calcd for Ci 8 Hi 4 N 2 0 2 [M] + : 290.1050. Found: 290.1030.

[00277] (±)-cis-l-[N'-(9H-fluoren-9-ylidene)]-3-oxotetrahydropyrno[ 2,3- c]pyrazolidine-l-ium-2-ide (Table 3, entry 24, 5ss)

[00278] Synthesized according to general procedure A using phenyl 2-[N-(9H-fluoren-9- ylidene)]hydrazinecarboxylate (63 mg, 0.20 mmol) and 3,4-dihydro-2H-pyran (34 mg, 0.4 mmol). The reaction temperature is 100 °C and the reaction time is 2 h. The title compound (78% NMR yield, 77% isolated yield) was obtained as yellow solid. TLC Rf 0.22 in 100% EtOAc. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 8.91 (d, J = 7.74 Hz, 1H), 7.77 (d, J = 7 ' .92 Hz, 1H), 7.56 (d, J = 7.48 Hz, 1H), 7.52 (d, J = 7 A3 Hz, 1H), 7.41-7.32 (m, 2H), 7.30-7.22 (m, 2H), 6.49 (d, J = 7.56 Hz, 1H), 3.84-3.75 (m, 1H), 3.73-3.66 (m, 1H), 3.01-2.95 (m, 1H), 2.46-2.38 (m, 1H), 1.93-1.71 (m, 3H). 13 C NMR (100 MHz, CDC1 3 ) ppm ^183.9 (C), 141.7 (C), 141.6 (C), 140.5 (C), 132.3 (CH), 131.5 (C), 131.4 (CH), 131.3 (CH), 129.9 (C), 129.0 (CH), 128.4 (CH), 126.6 (CH), 120.7 (CH), 119.8 (CH), 93.0 (CH), 61.3 (CH 2 ), 37.8 (CH), 19.2 (CH 2 ), 16.2 (CH 2 ). IR (film) 1661, 1606, 1553, 1276, 1262, 912, 765, 749 cm "1 .

HRMS(EI): Exact mass calcd for Ci 9 Hi 6 N 2 0 2 [M] + : 304.1206. Found: 304.1195. [00279] Similar aminocarbonylation reactions were performed using general procedure B, as described above, to generate the following products:

[00280] Preparation of starting materials for Table 3a

[00281] (E and )-Phenyl 2-(l-phenylethylidene)hydrazinecarboxylate (Table 3a, entry 1).

[00282] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), acetophenone (1.2 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (1.6 g, 62% yield) and a mixture of E and Z isomers (E/Z ratio = 5: 1) TLC Rf = 0.34 in 20% EtOAc/hexanes. For E isomer. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.23 (s, 1H), 7.81-7.76 (m, 2H), 7.40-7.32 (m, 5H), 7.25-7.19 (m, 3H), 2.23 (s, 3H). 13 C NMR (100 MHz, CDC1 3 )150.7 (C), 137.7 (C), 129.8 (CH), 129.5 (CH), 129.4 (CH), 128.4 (CH), 126.4 (CH), 125.7 (CH), 121.5 (CH), 13.0 (CH 3 ). IR (film) 3195, 3050, 1745, 1720, 1539, 1236, 1197, 752, 687 cm "1 . HRMS(EI): Exact mass calcd for C15H14N2O2 [M] + : 254.1050. Found: 254.1023. [00283] (E and Z)-Phenyl 2-(l-(4-ethylphenyl)ethylidene)hydrazinecarboxylate (Table 3a, entry 2).

[00284] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), l-(4-ethylphenyl)ethanone (1.5 g, 10 mmol) in MeOH (30 niL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (2.3 g, 82% yield) and a mixture of E and Z isomers (E/Z ratio = 6: 1) TLC Rf = 0.35 in 20% EtOAc/hexanes. For E isomer: ¾ NMR (400 MHz, CDCls) δ ppm 8.20 (s, 1H), 7.71 (d, J = 8.2 Hz, 2H), 7.41-7.34 (m, 2H), 7.24-7.15 (m, 5H), 2.65 (q, J = 7.6 Hz, 2H), 2.21 (s, 3H), 1.22 (t, J = 7.6 Hz, 3H); 13 C NMR (100 MHz, CDCI 3 ) δ ppm 145.9 (C), 135.2 (C), 129.4 (CH), 127.9 (CH), 126.4 (CH), 125.7 (CH), 121.6 (CH), 28.6 (CH 2 ), 15.4 (CH 3 ), 13.0 (CH 3 ). IR (film) 3232, 1750, 1727, 1406, 1222, 1193, 920, 770 cm "1 . HRMS(EI): Exact mass calcd for Ci 7 Hi 8 N 2 0 2 [M] + : 282.1363. Found: 282.1397.

[00285] (E fl«rf )-Phenyl 2-(l-(furan-2-yl)ethylidene)hydrazinecarboxylate (Table 3a, entry 3).

[00286] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), l-(furan-2-yl)ethanone (1.1 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (1.7 g, 70% yield) and a mixture of E and Z isomers (E/Z ratio = 1.5: 1) TLC Rf = 0.31 in 40% EtOAc/hexanes. For E isomer: Ti NMR (400 MHz, CDCI 3 ) δ ppm 8.16 (s, 1H), 7.63 (s, 1H), 7.41-7.29 (m, 2H), 7.23-7.15 (m, 3H), 6.72 (d, J = 3.5 Hz, 1H), 6.57-6.53 (m, 1H), 2.31 (s, 3H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 151.3 (C), 143.9 (CH), 129.4 (CH), 125.7 (CH), 121.4 (CH), 114.6 (CH), 111.6 (CH), 21.1 (CH) 3 . IR (film) 1737, 1528, 1494, 1207, 1020, 770 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 Hi 2 N 2 0 3 [M] + : 244.0842. Found: 244.0834.

[00287] (E and )-Phenyl 2-(l-(thiophen-2-yl)ethylidene)hydrazinecarboxylate (Table 3a, entry 4).

[00288] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), l-(thiophen-2-yl)ethanone (1.3 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). The title compound was obtained by column chromatography as colorless solid (2.2 g, 85% yield) and a mixture of E and Z isomers (E/Z ratio = 17: 1) TLC Rf = 0.19 in 30% EtOAc/hexanes. For E isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 10.37 (s, 1H), 7.37 (t, J = 7.8 Hz, 2H), 7.31 (dd, J = 5.1 and 0.9 Hz, 1H), 7.29 (d, J = 3.7 Hz, 1H), 7.24-7.16 (m, 3H), 7.00 (dd, J = 5.1 and 3.8 Hz, 1H), 2.25 (s, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 150.7 (C), 142.9 (C), 129.4 (CH), 128.2 (CH), 127.1 (CH), 126.7 (CH), 125.7 (CH), 121.5 (CH), 13.5 (CH 3 ). IR (film) 3202, 1722, 1540, 1490, 1203, 770 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 Hi 2 N 2 0 [M] + : 260.0614. Found: 260.0609.

[00289] ( s)-Phenyl 2-(l-(pyridin-2-yl)ethylidene)hydrazinecarboxylate (Table 3a, entry 5).

[00290] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), l-(pyridine-2-yl)ethanone (1.2 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). The title compound was obtained by column chromatography as light brown solid (2.1 g, 88% yield). TLC Rf = 0.35 in 40% EtOAc/hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.56 (d, J = 4.8 Hz, 1H), 8.35 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.67 (ddd, J = 8.1, 7.8 and 1.7 Hz, 1H), 7.38 (t, J = 7.9 Hz, 2H), 7.27-7.18 (m, 4H), 2.39 (s, 3H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 154.8 (C), 148.4 (CH), 136.4 (CH), 129.4 (CH), 125.8 (CH), 123.9 (CH), 121.4 (CH), 121.0 (CH), 10.9 (CH 3 ). ). IR (film) 3288, 1740, 1525, 1495, 1431, 1209, 770 cm "1 . LRMS (EI): 162.1(41%), 105.1 (29%), 94.0 (70%), 78.0 (100%). (HRMS could not be obtained for compounds 15e, 15i and 16i).

[00291] ( s)-Phenyl 2-(l-(4-styrylphenyl)ethylidene)hydrazinecarboxylate (Table 3a, entry 6).

[00292] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), (E)-l-(4-styrylphenyl)ethanone (1.5 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (2.5 g, 90% yield) and a mixture of E and Z isomers (E/Z ratio > 20: 1) TLC Rf = 0.36 in 20% EtOAc/hexanes. For E isomer: ¾ NMR (500 MHz, CDCI 3 ) δ ppm 8.23 (s, 1H), 7.46 (d, J = 7.3 Hz, 2H), 7.42-7.16 (m, 8H), 7.07 (d, J = 16.4 Hz, 1H), 6.89 (d, J = 16.5 Hz, 1H), 2.06 (s, 3H). 13 C NMR (125 MHz, CDC1 3 ) δ ppm. 150.6 (C), 136.0 (C), 133.8 (CH), 129.3 (CH), 128.7 (CH), 128.6 (CH), 128.5 (CH), 126.9 (CH), 125.7 (CH), 121.3 (CH), 10.7 (CH 3 ). IR (film) 3233, 3030, 1743, 1524, 1489, 1212, 774 cm "1 . HRMS(EI): Exact mass calcd for Ci 7 Hi 6 N 2 0 2 [M] + : 280.1206. Found: 280.1204.

[00293] Phenyl 2-(l-cyclopropylethylidene)hydrazinecarboxylate (Table 3a, entry 7).

[00294] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), 1-cyclopropylethanone (0.84 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (1.6 g, 73% yield) and a mixture of diastereomers. TLC Rf = 0.20 in 30% EtOAc/hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.77-7.66 (m, 1H), 7.41-7.28 (m, 2H), 7.22-7.06 (m, 3H), 2.48-1.34 (m, 4H), 1.16-0.60 (m, 4H). 13 C NMR (100 MHz, CDCls) δ ppm 150.7 (C), 129.4 (CH), 129.3 (CH), 125.6 (CH), 121.5 (CH), 30.1 (CH 3 ), 21.2 (CH), 20.2 (CH 3 ), 18.1 (CH), 11.9 (CH 3 ), 10.7 (CH 2 ), 10.2 (CH), 5.5 (CH 2 ), 5.1 (CH 2 ). IR (film) 3253, 3012, 1736, 1528, 1488, 1212, 1020, 767 cm "1 . HRMS(EI): Exact mass calcd for Ci 2 H 14 N 2 0 2 [M] + : 218.1050. Found: 218.1033.

[00295] ( s)-Phenyl 2-(3,3-dimethylbutan-2-ylidene)hydrazinecarboxylate (Table 3a, entry 8).

[00296] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), 3,3-dimthylbutan-2-one (1.0 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture, filtered and dried in vacuo. The title compound was obtained as colorless solid (1.4 g, 60% yield). TLC Rf = 0.37 in 30% EtOAc/hexanes. ¾i NMR (400 MHz, CDC1 3 ) δ ppm 7.82 (s, 1H), 7.35 (t, J = 7.9 Hz, 1H), 7.22-7.14 (m, 1H), 1.15 (s, 9H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 160.8 (C), 150.7 (C), 129.3 (CH), 125.5 (CH), 121.5 (CH), 38.8 (C), 27.5 (CH 3 ), 11.2 (CH 3 ). IR (film) 3262, 2967, 1736, 1532, 1488, 1215, 1024, 766 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 Hi 8 N 2 0 2 [M] + : 234.1363. Found: 234.1352.

[00297] (£ Phenyl 2-(l-(lH-indol-2-yl)ethylidene)hydrazinecarboxylate (Table 3a entry 9).

[00298] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), l-(lH-indol-2-yl)ethanone (1.6 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). The title compound was obtained by column chromatography as light brown solid (2.2 g, 75% yield). TLC Rf = 0.32 in 40% EtOAc/hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.56 (ddd, J = 4.85, 1.69, 0.90 Hz, 1H), 8.35 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.67 (td, J = 8.0 and 1.8 Hz, 1H), 7.38 (t, J = 7.9 Hz, 2H), 7.27-7.18 (m, 4H), 2.38 (s, 3H). 13 C NMR (100 MHz, CDCls) δ ppm 154.8 (C), 150.6 (C), 148.4 (CH), 136.3 (CH), 129.4 (CH), 125.8 (CH), 123.9 (CH), 121.4 (CH), 121.0 (CH), 10.9 (CH 3 ). IR (film) 3249, 3012, 1742, 1530, 1492, 1467, 1205, 1148, 1018, 769 cm "1 . LRMS(EI): 162.1 (100%), 150.0 (0.3%), 116.1 (0.4%), 94.0 (51%).

[00299] ( s)-Phenyl 2-(2,3-dihydro-inden-l-ylidene)hydrazinecarboxylate (Table 3a, entries 10-11).

[00300] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), 2,3-dihydroinden-l-one (1.3 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture, filtered and dried in vacuo. The title compound was obtained as colorless solid (2.5 g, 94% yield). TLC Rf = 0.39 in 30% EtOAc/hexanes. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.99 (s, 1H), 7.88 (d, J = 7.5 Hz, 1H), 7.42-7.15 (m, 7H), 3.17-3.08 (m, 2H), 2.77-2.68 (m, 2H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 160.1 (C), 151.7 (C), 150.8 (C), 148.0 (C), 137.2 (C), 130.8 (CH), 129.4 (CH), 127.2 (CH), 125.7 (CH), 125.3 (CH), 122.4 (CH), 121.5 (CH), 28.4 (CH 2 ), 26.1 (CH 2 ). IR (film) 3228, 1733, 1532, 1492, 1215, 709 cm "1 . HRMS(EI): Exact mass calcd for Ci 6 Hi 4 N 2 0 2 [M] + : 266.1050. Found: 266.1075.

(is,Z)-Phenyl 2-(cyclohex-2-enylidene)hydrazinecarboxylate (Table 3a, entry

[00302] Synthesized according to general procedure A using phenyl carbazate (1.5 g, 10 mmol), cyclohex-2-enone (1.0 g, 10 mmol) in MeOH (30 mL) and AcOH (10 drops). Product was directly recrystallized from crude mixture and dried in vacuo. The title compound was obtained as colorless solid (1.8 g, 80% yield) and a mixture of E and Z isomers (E/Z ratio > 11 : 1). TLC Rf = 0.37 in 30% EtOAc/hexanes. For E isomer: *H NMR (400 MHz, CDC1 3 ) δ ppm 8.20 (s, 1H), 7.34 (t, J = 7.9 Hz, 2H), 7.23-7.10 (m, 4H), 6.29 (s, 2H), 2.32 (t, J = 6.6 Hz, 2H), 2.17 (td, J = 6.1 and 1.7 Hz, 2H), 1.83-1.75 (m, 2H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 152.0 (C), 150.7 (C), 137.1(CH), 129.3 (CH), 127.5 (CH), 125.7 (CH), 121.5 (CH), 24.6 (CH 2 ), 23.6 (CH 2 ), 20.9 (CH 2 ). IR (film) 3218, 2934, 1743, 1523, 1488, 1201, 1023, 775 cm " HRMS(EI): Exact mass calcd for Ci 3 Hi 4 N 2 0 2 [M] + : 230.1050. Found: 230.1021.

[00303] feri-Butyl 2-(l,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazine- carboxylate (Table 3a, entry 13).

[00304] Synthesized according to general procedure A using ferf-butyl carbazate (0.87 g, 5.7 mmol), (i?)-camphor (0.83 g, 6.3 mmol) and acetic acid (2.0 mL) in ethanol (30 mL). The reaction mixture was concentrated in-vacuo and purified by silica gel column flash chromatography (40% EtOAc/hexanes). The title compound was obtained as a white solid (0.87 g, 3.27 mmol, 57% yield).TLC R f = 0.45 in 20% EtOAc/hexanes. ¾ NMR (CDC1 3 , 300 MHz) δ 7.17 (s, br, 1H), 2.28 (dt, J = 16.4 and 3.7 Hz, 1H), 1.95 (t, J = 4.4 Hz, 1H), 1.89-1.60 (m, 3H), 1.46 (s, 9H), 1.46-1.37 (m, 1H), 1.20-1.08 (m, 1H), 1.04 (s, 3H), 0.89 (s, 3H), 0.71 (s, 3H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 165.3 (C), 152.8 (C), 80.6 (C), 52.6 (C), 48.0 (C), 44.0 (CH 3 ), 33.3 (CH 2 ), 32.5 (CH 2 ), 28.4 (3CH 3 ), 27.4 (CH 2 ), 19.6 (CH 3 ), 18.7 (CH), 11.2 (CH 3 ). IR (film); 3051, 2968, 2873, 2075, 1721, 1542, 1269, 1178 cm "1 ; MS m/z (relative intensity): 57.0710 (100%), 41.0392 (33%), 79.0554 (17.3%), 81.0698 (16.3%), 39.0238 (16.2%). [00305] Preparation of products from Table 3a

[00306] (±)-exo-(£,Z)-2-(l-Phenylethylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium- -ide (Table 3a, entry 1, 16a).

[00307] Synthesized according to general procedure B using using phenyl 2-(l- phenylethylidene)hydrazinecarboxylate (51 mg, 0.20 mmol), norbornene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (35 mg, 61%) and a mixture of E/Z isomers (ratio = 2: 1 E/Z). TLC R f 0.50 in 10% methanol in dichlomethane. For Z isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.44 (d, J = 6.3 Hz, 2H), 7.37-7.30 (m, 3H), 4.54 (d, J = 7.1 Hz, 1H), 2.67 (d, J = 7.8 Hz, 1H), 2.64 (s, 1H), 2.56 (s, 3H), 1.92 (s, 1H), 1.46-1.36 (m, 1H), 1.33 (d, J = 11.0 Hz, 1H), 1.22-1.15 (m, 1H), 1.15-1.05 (m, 1H), 0.98 (d, J = 10.9 Hz, 1H), 0.77-0.68 (m, 1H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 183.9 (C), 147.4 (C), 134.9 (C), 130.2 (CH), 129.4 (CH), 127.1 (CH), 72.7 (CH), 52.0 (CH), 41.3 (CH), 39.5 (CH), 32.0 (CH 2 ), 27.0 (CH 2 ), 25.0 (CH 2 ), 24.2 (CH 3 ). IR (film) 2956, 2834, 1726, 1681, 1601, 1478, 1209, 1146, 1066, 818 cm "1 . HRMS(EI): Exact mass calcd for Ci 6 Hi 8 N 2 0 [M] + : 254.1414. Found: 254.1379.

[00308] (±)-exo-(£,Z)-2-[l-(4-Ethylphenyl)ethylidene]-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 2, 16b).

[00309] Synthesized according to general procedure B using using phenyl 2-[l-(4- ethylphenyl)ethylidene]hydrazinecarboxylate (56 mg, 0.20 mmol), norbornene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (36 mg, 64%) and a mixture of E/Z isomers (ratio = 2: 1 E/Z). TLC R f 0.30 in 10% methanol in dichlomethane. For Z isomer: *H NMR (400 MHz, CDC1 3 ) δ ppm 7.31-7.23 (m, 4H), 4.57 (d, J = 7.3 Hz, 1H), 2.73-2.65 (m, 4H), 2.56 (s, 3H), 1.96 (d, J = 4.6 Hz, 1H), 1.45 (tt, J = 12.1 and 4.4 Hz, 1H), 1.39-1.27 (m, 2H), 1.23 (t, J = 7.6 Hz, 3H), 1.15-1.07 (m, 1H), 1.00 (d, J = 10.9 Hz, 1H), 0.81-0.72 (m, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 183.8 (C), 147.7 (C), 146.7 (C), 132.2 (C), 128.8 (CH), 127.1 (CH), 72.6 (CH), 52.0 (CH), 41.3 (CH), 39.6 (CH), 32.0 (CH 2 ), 28.7 (CH 2 ), 27.0 (CH 2 ), 25.1 (CH 2 ), 24.3 (CH 3 ), 15.1 (CH 3 ). IR (film) 3228, 1733, 1532, 1492, 1215, 773 cm "1 . HRMS(EI): Exact mass calcd for Ci 8 H 22 N 2 0i [M] + : 282.1727. Found: 282.1696.

[00310] (±)-exo-( )-2-[(l-Furan-2-yl)ethylidene]-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide and (±)-ex0-(is)-2-[(l-Furan-2-yl)ethylidene]- 4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 3, 16c).

[00311] Synthesized according to general procedure B using using phenyl 2-(l-(furan-

2-yl)ethylidene)hydrazinecarboxylate (49 mg, 0.20 mmol), norbomene (190 mg, 2.0 mmol). The reaction time was 1 hour. The Z isomer was obtained as yellow solid (31 mg, 69%). T he structure of the isomer was determined by NOESY NMR experiments. TLC R f 0.22 in 10% methanol in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.20 (d, J = 3.6 Hz, 1H), 7.55 (s, 1H), 6.58 (dd, J = 3.6 and 1.7 Hz, 1H), 4.33 (d, J = 7.0 Hz, 1H), 2.79-2.74 (m, 2H), 2.64 (s, 1H), 2.56 (s, 3H), 1.72-1.54 (m, 2H), 1.44 (d, J = 11.0 Hz, 1H), 1.37-1.24 (m, 2H), 1.17 (d, J = 11.0 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 184.5 (C), 147.2 (C), 145.4 (CH), 132.1 (C), 122.8 (CH), 113.5 (CH), 72.7 (CH), 51.3 (CH), 42.1 (CH), 39.2 (CH), 32.2 (CH 2 ), 27.0 (CH 2 ), 25.4 (CH 2 ), 15.8 (CH 3 ). IR (film) 2963, 2874, 1644, 1568, 1475, 1353, 1310, 1217, 1134, 771 cm "1 . HRMS(EI): Exact mass calcd for Ci 4 H 16 N 2 0 2 [M] + : 244.1206. Found: 244.1193. The E isomer was obtained as yellow solid (11 mg, 23%). TLC ¾ 0.10 in 10% methanol in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.64 (d, J = 1.3 Hz, 1H), 6.90 (d, J = 3.6 Hz, 1H), 6.60 (dd, J = 3.6 and 1.7 Hz, 1H), 4.85 (d, J = 7.1 Hz, 1H), 2.79 (d, J = 7.1 Hz, 1H), 2.72 (s, 1H), 2.56 (s, 1H), 2.43 (s, 3H), 1.67-1.53 (m, 2H), 1.43 (d, J = 10.8 Hz, 1H), 1.36-1.26 (m, 2H), 1.10 (d, J = 11.0 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 183.6 (C), 146.4 (C), 145.8 (CH), 133.6 (C), 117.9 (CH), 113.0 (CH), 73.8 (CH), 52.2 (CH), 42.7 (CH), 39.4 (CH), 32.0 (CH 2 ), 27.0 (CH 2 ), 25.2 (CH 2 ), 19.5 (CH 3 ).

[00312] (±)-exo-( )-2-[(l-Thiophen-2-yl)ethylidene]-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 4, 16d).

[00313] Synthesized according to general procedure B using using phenyl 2-[l-(thiophen- 2-yl)ethylidene]hydrazinecarboxylate (52 mg, 0.20 mmol), norbomene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (43 mg, 82%). TLC R f 0.51 in 10% methanol in dichlomethane. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.67 (dd, J = 5.1 and 0.6 Hz, 1H), 7.61 (dd, J = 4.0 and 0.9 Hz, 1H), 7.11 (dd, J = 5.1 and 4.1 Hz, 1H), 4.36 (d, J = 7.1 Hz, 1H), 2.78-2.72 (m, 2H), 2.64 (s, 3H), 2.62 (s, 1H), 1.68-1.53 (m, 2H), 1.39 (d, J = 11.0 Hz, 1H), 1.32-1.24 (m, 2H), 1.14 (d, J = 11.0 Hz, 1H). 13 C NMR (100 MHz, CDCls) δ ppm 183.0 (C), 135.8 (CH), 134.7 (C), 131.3 (CH), 126.7 (CH), 72.4 (CH), 52.0 (CH), 42.4 (CH), 39.3(CH), 32.3 (CH 2 ), 27.1 (CH 2 ), 25.3 (CH 2 ), 17.8 (CH 3 ) . IR (film) 2965, 2878, 1635, 1570, 1349, 1316, 1215, 770, 740 cm "1 . HRMS(EI): Exact mass calcd for Ci 4 Hi 6 N 2 0 [M] + : 260.0978. Found: 260.0984.

[00314] (±)-exo-(£,Z)-2-[l-(Pyridin-2-yl)ethylidene] -4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 5, 16e).

[00315] Synthesized according to general procedure B using using phenyl 2-[l-(pyridin-2- yl)ethylidene]hydrazinecarboxylate (51 mg, 0.20 mmol), norbornene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (30 mg, 58%) and a mixture of E/Z isomers (ratio = 2: 1 E/Z). TLC R f 0.54 in 10% methanol in dichlomethane. For Z isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.67 (dd, J = 5.1 and 0.6 Hz, 1H), 7.61 (dd, J = 4.0 and 0.9 Hz, 1H), 7.11 (dd, J = 5.1 and 4.1 Hz, 1H), 4.36 (d, J = 7.1 Hz, 1H), 2.78-2.72 (m, 2H), 2.64 (s, 3H), 2.62 (s, 1H), 1.68-1.53 (m, 2H), 1.39 (d, J = 11.0 Hz, 1H), 1.32-1.24 (m, 2H), 1.14 (d, J = 11.0 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 183.0 (C), 135.8 (CH), 134.7 (C), 131.3 (CH), 126.7 (CH), 72.4 (CH), 52.0 (CH), 42.4 (CH), 39.3 (CH), 32.3 (CH 2 ), 27.1 (CH 2 ), 25.3 (CH 2 ), 17.8 (CH 3 ) . IR (film) 2965, 2878, 1635, 1570, 1349, 1316, 1215, 770, 740 cm "1 . HRMS(EI): Exact mass calcd for Ci 4 Hi 6 N 2 0 [M] + : 260.0978. Found: 260.0984.

[00316] (±)-exo-(£,^)-2-[(£)-4-Phenylbut-3-en-2-ylidene] -4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 6, 16f).

[00317] Synthesized according to general procedure B using using phenyl 2-(l-(4- styrylphenyl)ethylidene)hydrazinecarboxylate (51 mg, 0.20 mmol), norbornene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (29 mg, 51%) and a mixture of E/Z isomers (ratio = 2: 1 E/Z). TLC R f 0.51 in 10% methanol in dichlomethane. For Z isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.46 (dd, J = 7.9 and 1.4 Hz, 2H), 7.43-7.36 (m, 3H), 7.10 (d, J = 15.8 Hz, 1H), 6.98 (d, J = 15.8 Hz, 1H), 4.44 (d, J = 7.1 Hz, 1H), 2.80 (d, J = 7.1 Hz, 1H), 2.74 (s, 1H), 2.64 (s, 1H), 2.48 (s, 3H), 1.70-1.57 (m, 2H), 1.43 (d, J = 11.0 Hz, 1H), 1.28 (d, J = 10.0 Hz, 1H), 1.23-1.15 (m, 2H). 13 C NMR (100 MHz, CDCI 3 ) δ ppm 183.6 (C), 143.0 (C), 138.8 (CH), 135.2 (C), 130.1 (CH), 129.2 (CH), 127.4 (CH), 118.5 (CH), 71.3 (CH), 52.0 (CH), 43.1 (CH), 38.9 (CH), 32.6 (CH 2 ), 27.2 (CH 2 ), 25.2 (CH 2 ), 16.4 (CH 3 ). IR (film) 2969, 2877, 1641, 1543, 1365, 1293, 754 cm "1 . HRMS(EI): Exact mass calcd for Ci 8 H 20 N 2 O [M] + : 280.1570. Found: 280.1580. [00318] (±)-exo-(£, )-2-(l-Cyclopropylethylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 7, 16g).

[00319] Synthesized according to general procedure B using using phenyl 2-(l- cyclopropylethylidene)hydrazinecarboxylate (44 mg, 0.20 mmol), norbomene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (29 mg, 66%) and a mixture of E/Z isomers (ratio = 2: 1 E/Z). TLC R f 0.22 in 10% methanol in dichlomethane. For Z isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 4.30 (d, J = 7.1 Hz, 1H), 2.75 (d, J = 6.9 Hz, 1H), 2.71 (s, 1H), 2.68 (s, 1H), 1.87-1-81 (m, 4H), 1.67-1.50 (m, 2H), 1.45 (d, J = 11.0 Hz, 1H), 1.32-0.82 (m, 7H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 182.4 (C), 151.6 (C), 70.7 (CH), 52.2 (CH), 41.9 (CH), 38.8 (CH), 32.3 (CH 2 ), 26.9 (CH 2 ), 25.1 (CH 2 ), 14.8 (CH), 14.4 (CH 3 ), 7.8 (CH 2 ), 7.6 (CH 2 ). IR (film) 3422, 3226, 2966, 2877, 1641, 1583, 1361, 1296, 1074, 748 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 Hi 8 N 2 0 [M] + : 218.1414. Found: 218.1430.

[00320] (±)-exo-( )-2-(3,3-Dimethylbutan-2-ylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 8, 16h).

[00321] Synthesized according to general procedure B using using phenyl 2-(3,3- dimethylbutan-2-ylidene)hydrazinecarboxylate (44 mg, 0.20 mmol), norbomene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (38 mg, 82%). TLC R f 0.13 in 5% methanol in dichlomethane. ¾i NMR (400 MHz, CDC1 3 ) δ ppm 4.24 (d, J = 1.1 Hz, 1H), 2.77 (s, 3H), 2.66 (d, J = 7.0 Hz, 1H), 2.50 (s, 1H), 2.22 (s, 3H), 1.67-1.56 (m, 2H), 1.37 (s, 9H), 1.32-1.10 (m, 4H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 183.1 (C), 156.2 (C), 74.2 (CH), 50.9 (CH), 42.1 (CH), 39.4 (CH), 32.0 (CH 2 ), 27.1 (CH 2 ), 26.2 (CH 3 ), 25.2 (CH 2 ), 18.8 (CH 3 ). IR (film) 3422, 2961, 2878, 1638, 1568, 1352, 1220, 772 cm "1 . HRMS(EI): Exact mass calcd for C14H22N2O [M] + : 234.1727. Found: 234.1733.

[00322] (±)-exo-(^,^)-2-[l-(lH-Indol-2-yl)ethylidene] -4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 9, 16i).

[00323] Synthesized according to general procedure B using using phenyl 2-(l-(indol-2- yl)ethylidene)hydrazinecarboxylate (59 mg, 0.20 mmol), norbornene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (41 mg, 70%) and a mixture of E/Z isomers (ratio = 3: 1 E/Z). TLC R f 0.42 in 10% methanol in dichlomethane. For Z isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.66 (d, J = 4.8 Hz, 1H), 7.84 (tdt, J = 7.9 and 1.8 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.34 (ddd, J = 7.7, 4.8 and 0.9 Hz, 1H), 5.52 (d, J = 7.2 Hz, 1H), 2.71-2.64 (m, 5H), 1.79 (d, J = 4.6 Hz, 1H), 1.55-1.48 (m, 1H), 1.36-1.30 (m, 2H), 1.25-1.19 (m, 1H), 1.03-0.94 (m, 2H). 13 C NMR (100 MHz, CDC1 3 ) ^ ppm 184.6 (C), 152.4 (C), 150.5 (C), 149.3 (CH), 142.3 (C), 137.3 (CH), 124.4 (CH), 124.3 (CH), 73.0 (CH), 51.4 (CH), 41.9 (CH), 39.7 (CH), 32.0 (CH 2 ), 27.1 (CH 2 ), 24.9 (CH 2 ), 22.1 (CH 3 ). IR (film) 3423, 3230, 2964, 2877, 1652, 1588, 1322, 1131, 750 cm "1 . HRMS(EI): Exact mass calcd for Ci 8 Hi 9 N 3 0i [M] + : 293.1523. Found: 293.1253.

[00324] (±)-exo-(£,Z)-2-(2,3-Dihydroinden-l-ylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 10, 16j).

[00325] Synthesized according to general procedure B using using phenyl 2-(2,3- dihydroinden-l-ylidene)hydrazinecarboxylate (53 mg, 0.20 mmol), norbornene (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow solid (42 mg, 80%) and a mixture of E/Z isomers (ratio = 2: 1 E/Z). TLC R f 0.44 in 10% methanol in dichlomethane. For Z isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.96 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.3 Hz, 1H), 7.36-7.29 (m, 2H), 4.18 (d, J = 6.9 Hz, 1H), 3.27-2.99 (m, 4H), 2.78 (s, 1H), 2.76-2.70 (m, 2H), 1.71-1.57 (m, 2H), 1.54 (d, J = 10.9 Hz, 1H), 1.33-1.21 (m, 2H), 1.17 (d, J = 10.9 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 184.1 (C), 150.2 (C), 149.9 (C), 133.5 (C), 132.7 (CH), 130.5 (CH), 127.5 (CH), 124.8 (CH), 73.4 (CH), 51.4 (CH), 40.7 (CH), 39.1 (CH), 32.2 (CH 2 ), 29.6 (CH 2 ), 28.9 (CH 2 ), 26.9 (CH 2 ), 25.4 (CH 2 ). IR (film) 2965, 1655, 1603, 1582, 1330, 1220, 771 cm "1 . HRMS(EI): Exact mass calcd for C n Hi 8 N 2 0 [M] + : 266.1414. Found: 266.1422.

[00326] (±)-cis-(£, )-l-(2,3-Dihydroinden-l-ylidene)-3-oxotetrahydro-lH-furo[2,3 - c]pyrazolidine-l-ium-2-ide (Table 3a, entry 11, 16k).

[00327] Synthesized according to general procedure B using using phenyl 2-(2,3- dihydroinden-l-ylidene)hydrazinecarboxylate (53 mg, 0.20 mmol), dihydrofuran (70 mg, 1.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow solid (24 mg, 80%) and a mixture of E/Z isomers (ratio = 6: 1 E/Z). TLC R f 0.50 in 10% methanol in dichlomethane. For Z isomer: ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.94 (d, J = 8.5 Hz, 1H), 7.49 (t, J = 1.5 Hz, 1H), 7.40-7.34 (m, 2H), 6.08 (d, J = 6.2 Hz, 1H), 4.11 (t, J = 8.4 Hz, 1H), 3.70 (ddd, J = 12.4, 8.9 and 5.2 Hz, 1H), 3.47-3.41 (m, 2H), 3.28-3.22 (m, 2H), 3.14-3.04 (m, 1H), 2.54 (dd, J = 12.7 and 5.2 Hz, 1H), 2.19 (tdd, J = 12.5, 9.4 and 8.0 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) <5 ppm 181.9 (C), 151.4 (C), 133.6 (CH), 133.2(C), 131.1 (C), 130.8 (CH), 127.7 (CH), 125.1 (CH), 98.4 (CH), 68.3 (CH 2 ), 46.7 (CH), 30.2 (CH 2 ), 29.1 (CH 2 ), 29.0 (CH 2 ). [00328] (±)-exo-(£,Z)-2-(Cyclohex-2-enylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (Table 3a, entry 12, 161).

[00329] Synthesized according to general procedure B using using phenyl 2-(cyclohex-2- ylidene)hydrazinecarboxylate (46 mg, 0.20 mmol), norborne (190 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (37 mg, 81%) and a mixture of E/Z isomers (ratio = 3: 1 E/Z). TLC R f 0.45 in 10% methanol in dichlomethane. For E isomer: Ti NMR (500 MHz, CDC1 3 ) δ ppm 7.59-7-54 (m, 1H), 7.36 (dt, J = 10.2 and 1.8 Hz, 1H), 5.21 (d, J = 7.1 Hz, 1H), 3.88 (dt, J = 18.4 and 6.3 Hz, 1H), 3.79 (dt, J = 14.0 and 6.6 Hz, 1H), 3.70 (d, J = 7.2 Hz, 1H), 3.67 (s, 1H), 3.53 (s, 1H), 3.28-3.21 (m, 2H), 2.82- 2-75 (m, 2H), 2.58-2.52 (m, 2H), 2.37 (d, J = 10.9 Hz, 1H), 2.27-2.19 (m, 2H), 2.12 (d, J = 10.9 Hz, 1H). 13 C NMR (125 MHz, CDC1 3 ) δ ppm 183.5 (C), 143.9 (C), 143.7 (CH), 119.2 (CH), 70.6 (CH), 51.8 (CH), 42.7 (CH), 38.9 (CH), 32.5 (CH 2 ), 27.7 (CH 2 ), 27.1 (CH 2 ), 25.2 (CH 2 ), 20.5 (CH 2 ). IR (film) 3436, 2961, 2879, 1636, 1557, 1347, 1285, 1220, 773 cm "1 . HRMS(EI): Exact mass calcd for Ci 4 Hi 8 N 2 0 [M] + : 230.1414. Found: 230.1415.

[00330] (±)-exo-2-(l,7,7-Trimethylbicyclo[2.2.1]heptan-2-ylidene)-4 -oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]-decane-2-ium-3-ide (Table 3a, entry 13, 16m).

[00331] Synthesized according to general procedure A using ierf-butyl 2-(l,7,7- trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazinecarboxylate 5m (69 mg, 0.26 mmol) and norbomene (245 mg, 2.6 mmol) in α,α,α-trifluorotoluene (5.0 mL). The reaction was heated at 150 °C for three hours. The title compound was obtained a mixture of diastereoisomers and isolated by column chromatography using 5% MeOH/CH 2 Cl 2 (99% NMR yield, 24:9:34:33 dr, 60 mg, 0.21 mmol, 80% isolated yield). TLC R f = 0.49 in 10% MeOH/CH 2 Cl 2 . ¾ NMR (CDCI 3 , 300 MHz) *mixture of four diastereoisomers δ 4.39-3.98 (m, 1H), 2.92-2.69 (m, 3H), 2.56-2.14 (m, 2H), 2.05-1.12 (m, 14H), 0.92-0.78 (m, 6H); 13 C NMR (CDC1 3 , 100 MHz) *mixture of four diastereoisomers δ ppm 183.4 (C), 183.4 (C), 182.3 (C), 181.9 (C), 165.1 (C), 164.1 (C), 162.8 (C), 162.6 (C), 73.7 (CH), 72.9 (CH), 70.6 (CH), 70.1 (CH), 57.3, 56.8, 55.3, 54.6, 53.5, 52.8, 52.2, 51.5, 51.4, 51.4, 51.3, 50.7, 49.5, 46.4, 44.1, 43.8, 43.7, 43.3, 42.7, 41.5, 41.1, 40.6, 39.2, 39.2, 39.0, 38.8, 38.2, 37.5, 34.1, 33.0, 32.8, 32.4, 32.3, 32.3, 32.1, 31.3, 29.7 (CH 2 ), 27.1 (CH 2 ), 27.0 (CH 2 ), 27.0 (CH 2 ), 26.9 (CH 2 ), 26.8 (CH 2 ), 26.8 (CH 2 ), 26.7 (CH 2 ), 26.5 (CH 2 ), 25.8 (CH 2 ), 25.7 (CH 2 ), 25.3 (CH 2 ), 25.0 (CH 2 ), 20.4 (CH 2 ), 20.4 (CH 2 ), 20.2 (CH 2 ), 20.1 (CH 2 ), 19.1 (CH 2 ), 18.8 (CH 2 ), 18.6 (CH 2 ), 18.5 (CH 2 ), 14.5 (CH 3 ), 13.9 (CH 3 ), 13.4 (CH 3 ), 12.9 (CH 3 ); IR (film); 2964, 2922, 2880, 1744, 1672, 1592, 1375, 1303, 790 cm "1 ; HRMS (EI): Exact mass calcd for Ci 8 H 26 N 2 0 [M] + : 286.2045; found: 286.2045. One of the four diastereoisomers was isolated by silica gel column chromatography using 40% /-PrOH/toluene. ¾ NMR (CDC1 3 , 300 MHz) δ 3.95 (d, J = 6.9, 1H), 2.77-2.57 (m, 4H), 2.27 (s, 1H), 2.05 (s, 1H), 1.62-1.53 (m, 4H), 1.47 (s, 3H), 1.28-1.14 (m, 6H), 0.93-0.80 (m, 7H); 13 C NMR (CDC1 3 , 100 MHz) d ppm 183.3 (C), 161.3(C), 72.9 (CH), 57.1 (C), 51.4 (CH), 49.4 (C), 43.8 (CH), 41.5 (CH 2 ), 38.8 (CH), 37.3 (CH 2 ), 32.2 (CH 2 ), 29.7 (CH), 27.1 (CH 2 ), 26.7 (CH 2 ), 25.7 (CH 2 ), 20.3 (CH 3 ), 18.6 (CH 3 ), 13.9 (CH 3 ); HRMS (EI): Exact mass calcd for Ci 8 H 26 N 2 0i [M] + : 286.2045; found: 286.2049.

[00332] ( )-3-Oxo-5-phenyl-l-(thiophen-2-yl)ethylidenepyrazolidine-l-i um-2-ide (Table 3a, entry 14, 16n).

[00333] Synthesized according to general procedure B using using phenyl 2-[l-(thiophen-

2-yl)ethylidene]hydrazinecarboxylate (52 mg, 0.20 mmol), styrene (200 mg, 2.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (25 mg, 46%). TLC

R f 0.25 in 6% methanol in dichlomethane. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.77 (dd, J =

5.1 and 1.0 Hz, 1H), 7.62 (dd, J = 4.1 and 1.1 Hz, 1H), 7.38-7.27 (m, 3H), 7.23-7.19 (m, 2H),

7.14 (dd, J = 5.1 and 4.1 Hz, 1H), 5.73 (dd, J = 9.8 and 2.8 Hz, 1H), 3.38 (dd, J = 16.5 and

9.9 Hz, 1H), 2.66 (dd, J = 16.5 and 2.9 Hz, 1H), 2.37 (s, 3H). 13 C NMR (125 MHz, CDC1 3 ) δ ppm 180.4 (C), 138.9 (C), 137.2 (C), 136.6 (CH), 134.7 (C), 131.8 (CH), 129.7 (CH), 128.8 (CH), 126.8 (CH), 125.2 (CH), 69.8 (CH), 41.3 (CH 2 ), 17.6 (CH 3 ). IR (film) 3076, 2982, 1644, 1567, 1306, 1217, 773 cm "1 . HRMS(EI): Exact mass calcd for C15H14OS [M] + : 270.0821. Found: 270.0842.

[00334] ( )-5-Ferrocenyl-3-oxo- l-(thiophen-2-yl)ethylidenepyrazolidine- l-ium-2-ide (Table 3a, entry 15, 16o).

[00335] Synthesized according to general procedure B using using phenyl 2-[l-(thiophen- 2-yl)ethylidene]hydrazinecarboxylate (52 mg, 0.20 mmol), vinyl ferrocene (210 mg, 1.0 mmol). The reaction time was 1 hour. The title compound was obtained as yellow oil (40 mg, 46%). TLC R f 0.31 in 6% methanol in dichlomethane. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 7.71 (d, J = 5.0 Hz, 1H), 7.58 (d, J = 3.8 Hz, 1H), 7.10 (t, J = 4.5 Hz, 1H), 5.52 (d, J = 8.0 Hz, 1H), 4.31-4.13 (m, 9 H), 3.41 (dd, J = 16.1 and 8.6 Hz, 1H), 3.31 (d, J = 16.1 Hz, 1H), 2.58 (s, 3H). 13 C NMR (125 MHz, CDC1 3 ) δ ppm 181.1 (C), 136.9 (C), 136.5 (CH), 134.7 (C), 131.6 (CH), 126.6 (CH), 86.6 (C), 69.4 (CH), 69.3 (CH), 68.8 (CH), 68.0 (CH), 66.4 (CH), 65.9 (CH), 41.6 (CH 2 ), 17.9 (CH 3 ). IR (film) 1645, 1563, 1413, 1349, 1302, 1217, 773 cm "1 . HRMS(EI): Exact mass calcd for Ci 9 Hi 8 N 2 OSFe [M] + : 378.0484. Found: 378.0434.

[00336] (^^-[l-iFuran-l-ylJethylideneJJ-S-oxo-S-pentylpyrazolidine-l -ium-l-ide (Table 3a, entry 16, 16p).

[00337] Synthesized according to general procedure B using using phenyl 2-[l-(furan-

2-yl)ethylidene]hydrazinecarboxylate (49 mg, 0.20 mmol), 1-hexene (4 mL) as solvent. The reaction time was 1 hour. The title compound was obtained as yellow oil (18 mg, 36%) and a mixture of E/Z isomers (ratio = 3: 1 E/Z). For Z isomer: TLC R f 0.39 in 10% methanol in dichlomethane. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 8.22 (d, J = 3.6 Hz, 1H), 7.57 (d, J = 1.1 Hz, 1H), 6.62 (dd, J = 3.6 and 1.7 Hz, 1H), 4.71-4.62 (m, 1H), 2.96 (dd, J = 16.2 and 8.7 Hz, 1H), 2.56 (s, 3H), 2.51 (dd, J = 16.2 and 1.9 Hz, 1H), 1.86-1.74 (m, 2H), 1.42-1.25 (m, 4H), 0.89 (t, J = 7.0 Hz, 1H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 182.4 (C), 147.1 (C), 145.6 (CH), 123.2 (CH), 113.7 (CH), 66.4 (CH), 36.5 (CH 2 ), 34.2 (CH 2 ), 27.1 (CH 2 ), 22.3 (CH 2 ), 15.2 (CH 3 ), 13.8 (CH 3 ). IR (film) 2962, 2867, 1645, 1571, 1359, 1303, 903, 775 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 H 18 N 2 0 2 [M] + : 234.1363. Found: 234.1379.

[00338] Example 3: Reaction of Hvdrazones with Various Nucleophiles

Table 4: Reaction of hydrazones with various nucleophiles

Entry Hydrazine Nucleophile (Nu) Product Solvent Yield (%1 b

in the microwave for 20 minutes at 120 o°Cr.. b D Isolated yields

[00339] General procedure (microwave): A flame dried 5-mL microwave tube was charged with a stir bar, capped with a septum and purged with argon. The corresponding hydrazine (1.00 equiv) and the nucleophile were added to the sealed tube, while keeping it under argon. PhCF 3 was also added to reagents mix, bringing the concentration to 0.2 M. The septum was removed and the tube was then quickly sealed with a microwave cap, which was placed in the microwave under the conditions described for each substrate combination. The solution was then analysed by H NMR using para-dimethoxybenzene as an internal standard and was purified by silica gel chromatography to afford the corresponding products.

[00340] Preparation of hydrazones

[00341] General procedure for the formation of the hydrazones of Table 4: To a flamed dried round bottom (250-mL) charged with a magnetic stir bar, acetic acid (1 equiv, 0,04 mol), hexanes (50.0 mL), ferf-butylcarbazate (1 equiv, 0.04 mol) and 2,4-dimethylpentan-3- one (1 equiv, 0.04 mol) were added at room temperature. The reaction was performed in an oil bath over night at 70 °C. The reaction was followed by TLC and when the ketone was all consumed, the crude was concentrated under reduce pressure and re-crystalized in hexanes. Then, the obtained compound was purified by flash chromatography (10% ethyl acetate in pet ether) and the resulting white solid was analysed by H NMR.

[00342] 2-(2,4-dimethylpentan-3-ylidene)-N-hexylhydrazinecarboxamide (Table 4, entry 2a)

[00343] This compound was synthesized according to general procedure (120 °C, 20 minutes) in trifluorotoluene from the hydrazone of Table 4 (0.2283 g, 0.001 mol) and the corresponding nucleophile (2 equiv). The reaction mixture was concentrated under reduced pressure and isolated using flash chromatography (10 % ethyl acetate in dichloromethane). The compound obtained was a bright yellow oil (0.2017 g, 79 % yield). TLC was performed at Rf 0.59 in 3% methanol in dichloromethane. H NMR (CDC1 3 , 300 Hz) δ ppm 8.35 (s, 1H), 6,14 (s, 1H), 3,21 (q, J = 7.00 Hz, 2H), 2.84 (spt, J = 7.00 Hz, 1H), 2.52 (spt, J = 6.70 Hz, 1H), 1.47 (quint, J =7.02, 6.78, 7.17, 7.35, 2H), 1.24 (m, 6H), 1.03 (dd, J =7.6, 7.0 12H), 0.81 (t, J = 6.57, 6.69, 3H); 13 C NMR (CDC1 3 , 75 Hz) δ ppm 160.2 (C), 157.0 (C), 39.5 (CH2), 31.5 (CH2), 30.1 (CH2), 30.1 (CH), 27.9 (CH), 26.5 (CH2), 22.5 (CH2), 21.9 (2CH3), 18.8 (2CH3), 13.9 (CH3); IR (film); 3420, 3207, 2960, 2929, 2857, 1679, 1538, 1066 cm-1; HRMS (EI): Exact mass calcd for C14H29N30 [M]+: 255,3996; found :

255,2319.

[00344] 2-(2,4-dimethylpentan-3-ylidene)-N-phenylhydrazinecarboxamid e (Table 4, entry 2b)

[00345] This compound was synthesized according to general procedure (120 °C, 20 minutes) from the hydrazone of Table 4 (0.2283 g, 0.001 mol) and the corresponding nucleophile (2 equiv). The reaction mixture was concentrated under reduced pressure and isolated using flash chromatography (12 % ethyl acetate in hexanes). The compound obtained was yellow crystals (0.1927 g, 78% yield). TLC was performed at Rf 0,65 in 30 % ethyl acetate in hexanes. ¾ NMR (CDC1 3 , 300 Hz) δ ppm 8.73 (s, 1H), 8.30 (s, 1H), 7.52 (d, J= 1.2, 1H), 7.49 (d, J= 0.9, 1H), 7.29 (m, 2H), 7.03 (m, 1H), 2.99 (spt, J= 6.9, 1H), 2.65 (spt, J= 6.7, 1H) 1.14 (dd, J=6.9, 1.6, 12H); 13 C NMR (CDC1 3 , 75 Hz) δ ppm 161.1 (C), 154.3 (C), 138.4 (C), 128.2 (2CH), 122.9 (CH), 119.2 (CH), 30.3 (CH), 28.3 (CH), 22.0 (2CH3), 18.9 (2CH3); IR (film); 2967, 2933, 2872, 1683, 1590,1538,1443, 1033 cm-1; HRMS (EI): Exact mass calcd for C14H21N30 [M]+: 247,1685; found : 247.1679.

[00346] N-(tert-butyl)-2-(2,4-dimethylpentan-3-ylidene)hdyrazinecarb oxamide (Table 4, entry 2c)

[00347] This compound was synthesized according to general procedure (120 °C, 20 minutes) from the hydrazone of Table 4 (0.2283 g, 0.001 mol) and the corresponding nucleophile (2 equiv). The reaction mixture was concentrated under reduced pressure and isolated using flash chromatography (1 % methanol in dichloromethane). The compound obtained was a white powder (0.1902 g, 83% yield). TLC was performed at Rf 0.57 in 3 % methanol in dichloromethane. ¾ NMR (CDC1 3 , 300 Hz) δ ppm 8.88 (s, 1H), 6.16 (s, 1H), 3.00 (spt, J= 6.9, 1H), 2.53 (spt, J= 6.7, 1H), 1.33 (s, 9H), 1.04 (t, J= 6.9, 9H); 13 C NMR (CDCI 3 , 75 Hz) δ ppm 159.3 (C), 155.8 (C), 49.8 (C), 30.4 (CH), 29.3 (3CH3), 27,9 (CH), 21.8 (2CH3), 18.8 (2CH3); IR (film); 3397, 2963, 1679, 1531, 1143 cm-1; LRMS m/z (relative intensity): 85.0769 (100%), 100.0990 (62.4%), 184.1438 (61.8%),128.1308 (42.7%), 128.0819 (24.4%), 113.1097 (23.5 %)

N'-(2,4-dimethylpentan-3-ylidene)morpholine-4-carbohydraz ide (Table 4,

[00349] This compound was synthesized according to general procedure (120 °C, 20 minutes) from the hydrazone of Table 4 (0.2283 g, 0.001 mol) and the corresponding nucleophile (2 equiv). The reaction mixture was concentrated under reduced pressure and isolated using flash chromatography (2 % methanol in dichloromethane). The compound obtained was a white solid (0.2184 g, 91 % yield). TLC was performed at Rf 41 in 3 % methanol in dichloromethane. H NMR (400 MHz), CDC1 3 ) δ ppm 7.66 (s, 1H), 3.61 (t, J=4.32, 5.03, 4H), 3.51 (t, J=5.00, 4.28, 4H), 2.80 (spt, J=13.8, 6.9, 1H), 2.51 (spt, 13.4, 6.7, 1H), 1.02 (d, J=7, 6H), 0.97 (d, J=6.8, 6H); 13 C NMR (CDC1 3 , 75 Hz) δ ppm 162.2 (C), 158.3 (C), 68.8 (CH2), 46.1 (CH2), 30.5 (CH), 27.3 (CH), 21.9 (2CH3), 18.7 (2CH3).

[00350] Example 4: Intramolecular Aminocarbonylation of Various Alkenes

[00351] In this example, intramolecular aminocarbonylation reactions were performed to demonstrate the successful use of imino compounds of Formula IV in intramolecular β- aminocarbonylation of various alkenes. [00352] Preparation of Starting Materials

[00353] (E)-tert-Butyl 2-(hept-6-en-2-ylidene)hydrazinecarboxylate (6a)

[00354] Synthesized according to general procedure C. The title compound was obtained as a white solid. *H NMR (CDCI 3 , 300 MHz) *denotes minor isomers δ ppm 7.38 (d, J = 38.9, 1H), 5.78 (ddt, J = 17.0, 10.3, 6.7, 1H), 5.10-4.93 (m, 2H), 2.32-2.27 (m, 2H), 2.07 (d, J = 6.9, 2H), 1.78 (s, 3H), 1.62 (quintet, J = 7.7, 2H), 1.50 (s, 9H); 13 C NMR (CDC1 3 , 100 MHz) *denotes minor isomers d ppm 152.9 (C), 138.2 (CH), *137.5 (CH), * 116.1 (CH 2 ), 115.0 (CH 2 ), 80.9 (C), 38.5 (CH 2 ), 33.4 (CH 2 ), *28.9 (CH 3 ), 28.3 (CH 3 ), 25.9 (CH 2 ), *24.3 (CH 2 ), *23.4 (CH 2 ), 14.7 (CH 2 ); HRMS (EI): Exact mass calcd for Ci 2 H 22 N 2 0 2 [M] + :

226.1681 ; found: 170.1 (20.9%), 153.1 (10.9%), 116.1 (42.5%), 98.0 (11.1%), 72.1 (38.9%), 57.1 (100.0%), 41.0 (35.1%), 39.0 (11.2%).

[00355] (E)-tert-Butyi 2-((Z)-oct-6-en-2-ylidene)hydrazinecarboxylate (6b)

[00356] Synthesized according to general procedure C using ferf-butyl carbazate (220 mg, 1.6 mmol, 2 equiv), (Z)-oct-6-en-2-one (171 mg, 1.4 mmol), acetic acid (10 drops) and methanol (3 mL). The title compound was isolated using flash chromatography (20% EtOAc in hexane) as a white solid with a ratio of 7:2 of E/Z isomers. (311 mg, 96% yield). H NMR (400 MHz, CDCI 3 ) δ ppm 7.42 (bs, 1H), 5.55-5.27 (m, 2H), 2.30-2.08 (m, 2H), 2.07-1.98 (m, 2H), 1.75 (s, 3H), 1.60-1.51 (m, 5H), 1.46 (bs, 9H); 13 C NMR (100 MHz, CDCl 3 ) ½pm 174.4 (C), 153.0 (C), 129.8 (CH), 124.4 (CH), 80.9 (C), 38.6 (CH 2 ), 28.3 (3CH 3 ), 26.5 (2CH 2 ), 14.6 (CH 3 ), 12.8 (CH 3 ). IR 3226, 3013, 2979, 2931, 2802, 1724, 1701, 1504, 1449, 1391, 1367, 1307, 1275, 1247, 1169, 1051, 1026, 878, 780 cm "1 . HRMS(EI): Exact mass calcd for Ci 3 H 24 N 2 0 2 [M] + : 240.1832. Found: 167.1 (6.8%), 139.1 (1.5%), 124.1, (0.8%), 116.1 (65%), 57.1 (100%).

[00357] Intramolecular Aminocarbonylation Reations

[00358] General procedure A: An oven or flame dried 2-5 mL μ-w tube with a stir bar was capped with a septum and purged with argon for 5 minutes. The acyl hydrazone (0.2 mmol), trifluorotoluene (4 mL were added to the sealed tube, while keeping it under an argon atmosphere. The septum was removed and the tube was then quickly sealed with a microwave cap and heated for 2-5 hours at 80-150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by *H NMR using 1,4-dimethoxybenzene or 1,3,5-trimethoxybenzene as an internal standard. The

corresponding product was purified using a pipe silica gel column (using EtOAc to wash out by products first, then using 10-25% methanol in EtOAc to wash out the target compound).

[00359] 7-Methyl-2-oxo-2,3,3a,4,5,6-hexahydropyrazolo[l,5-a]pyridin- 8-ium-l-ide (7a)

[00360] Synthesized according to general procedure A. The reaction was under 150 °C.

^ NMR CDCls, 300 MHz) δ 4.19 (q, J = 8.6, 1H), 2.79 (dd, J = 15.6, 8.4, 1H), 2.70-2.52 (m, 3H), 2.34 (s, 1H), 2.28 (t, J = 0.9, 3H), 1.99 (t, J = 10.6, 1H), 1.84-1.66 (m, 2H); 13 C NMR (CDCls, 100 MHz) d ppm , 180.5 (C), 149.9 (C), 64.6 (CH), 37.6 (CH 2 ), 30.2 (CH 2 ), 27.3 (CH 2 ), 20.9 (CH 3 ), 18.3 (CH 2 ); IR (film); 2916.9, 2849.9, 1679.4, 1582.1, 1380.9, 1340.6, 1085.7 cm "1 ; HRMS (EI): Exact mass calcd for C 8 Hi 2 N 2 0i [M] + : 152.0944; found: 152.0955. [00361] 3,7-Dimethyl-2-oxo-2,3,3a,4,5,6-hexahydropyrazolo[l,5-a]pyri din-8-ium- 1-ide (7b)

[00362] Synthesized according to general procedure A using (E)-ter f-butyl 2-((Z)-oct-

6-en-2-ylidene)hydrazinecarboxylate (48 mg, 0.20 mmol). The reaction was under 150 °C. The title compound was obtained as a yellow oil (13 mg, 39% isolated yield and 46% NMR yield). The stereochemistry was assigned according to NOE NMR. TLC Rf 0.06 in 25% methanol in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) δ ppm 4.25-4.14 (m, 1H), 2.80 ( p, J = 7.53 Hz, 1H), 2.67 (dd, J = 20.52, 5.67 Hz, 1H), 2.60-2.48 (m, 1H), 2.26 (s, 3H), 2.11-2.01 (m, 2H), 1.81-1.67 (m, 2H), 1.14 (d, J = 7.48 Hz, 3H); 13 C NMR (100 MHz, CDC1 3 ) δ ppm 184.9 (C), 149.1 (C), 67.1 (CH), 40.8 (CH), 30.3 (CH 2 ), 22.8 (CH 2 ), 20.7 (CH 3 ), 18.3 (CH 2 ), 13.0 (CH 3 ). IR 3398, 2947, 1679, 1584, 1450, 1377, 1341, 1148, 1101 cm "1 ; HRMS(EI): Exact mass calcd for C 9 Hi 4 N 2 0 [M] + : 166.1101. Found: 166.1103.

[00363] The results of additional intramolecular reactions are provided below:

2.3 equiv aniline, C.5 h. S7¾

-.1 equi HNiFn C5 h.2e¾

5 *qurvH Fr-C.5h.41¾

5 *quivHWFr; 1.5 h.5C¾

5 equrv H Efc.2 h. Sf¼

D.f M

□ Fh 3%

ΞΕ

3Fh 7¾

Ketohydrazone

[00364] Hydrazones derived from aliphatic aldehydes can be effective when the azomethine imine can perform a subsequent [3+2] cycloaddition (see below). The preference for an intermolecular over an intramolecular aminocarbonylation event is noteworthy. In

- Ill - contrast to 13a, methylketone 13b performed an intramolecular aminocarbonylation in the absence of norbomene.

13a

84% NMR yield

48 % isolated yield

[00365] Heating in the absence of C Hi 0 did not afford the desired dipole, but a 35% unoptimized yield of a dimer in which the dipole reacted in a [3+2] with an equivalent of the imino-isocyanate.

[00366] Preparation of reagents

[00367] tert-Butyl 2-(hex-5-enylidene)hydrazinecarboxylate (13a). o

f-Bu X N H

[00368] 5-Hexen-l-ol was oxidized to to hex-5-enal according to previously reported procedure by the Mukai group Mukai, C; Nomura, I.; Katagaki, S. J. Org. Chem. 2003, 68, 1376. The title compound was then formed according to general procedure A using ferf-butyl carbazate (1.015 g, 7.68 mmol) and crude mixture of hex-5-enal (9.98 mmol). Observed a mixture of E and Z isomers in 3.6: 1 ratio, respectively. The crude mixture was purified by column chromatography (30% EtOAc/ft-hexanes) and isolated as a white solid (1.38 g, 65% yield). TLC R f = 0.36 (30% EtOAc/hexanes); ¾ NMR (400 MHz, CDCL 3 ) *denotes minor isomer δ ppm 7.69 (s, 1H), 7.14 (t, J= 5.2 Hz, 1H), *6.61 (t, J= 5.2 Hz, 1H), 5.77 (tdd, J = 6.8 Hz, 13.2 Hz, 12.1 Hz, 1H), 5.04-4.92 (m, 2H), 2.29 (tdd, J = , 2H), 2.09-2.03 (m, 2H), * 1.66 (m, J = 7.2 Hz, 2H), 1.59 (m, J= 8.0 Hz, 2H), * 1.51 (s, 9H), 1.48 (s, 9H); 13 C NMR (400 MHz, CDCls) δ ppm 152.9 (C), 147.0 (C), *146.0 (C), 137.9 (CH), *137.3 (CH), * 115.9 (CH 2 ), 115.1 (CH 2 ), 81.0 (CH), 33.2 (CH 2 ), *33.0 (CH 2 ), 31.6 (CH 2 ), 28.2 (CH 3 ), 25.9 (CH 2 ), *25.5 (CH 2 ), *25.0 (CH 2 ); IR (film) 3241, 3078, 2983, 2934, 2865, 1710, 1641, 1539, 1360, 1254, 1166, 1048, 1017, 904, 866, 763 cm "1 ; LRMS m/z (relative intensity) 57.0715 (100%), 41.0384 (23.9%), 29.0399 (17.7%), 58.0534 (12.7%), 39.0233 (9.2%).

[00369] tert-Ru yX 2-(hept-6-en-2-ylidene)hydrazinecarboxylate (13b).

[00370] To a round bottom flask, ferf-butyl-acetoacetate (4.44 g, 28.1 mmol) was dissolved in dry THF (141 mL) stirred under argon and cooled to 0 °C. Potassium tert- butoxide (3.15 g, 28.1 mmol) is then added in small portions and then stirred for 1 hour after which sodium iodide is added (2.11 g, 14.1 mmol). 4-Bromobutene (3.80 g, 28.1 mmol) is then added dropwise over fifteen minutes. Solution is then allowed to warm up to room temperature followed by reflux for twenty hours. Reaction is allowed to cool and then quenched with a saturated ammonium chloride solution and water. Organic layer is extracted three times with ether, dried with sodium sulphate and volatiles are removed. Crude mixture is then dissolved in a 1 : 1 : 1 mixture of concentrated HC1, water and methanol (30 mL) which is then refluxed for 1 hour. Reaction is quenched with 10% aq. NaOH and extracted three times with ether. Following this, the ferf-butyl carbazate (4.08 g, 30.9 mmol) is condensed on the crude mixture of hept-6-en-2-one following general procedure A in methanol (34.3 mL). Product was purified by column chromatography with 4% Et 2 0/CH 2 C1 2 and obtained as a white solid (1.82 g, 8.06 mmol) in a 29% isolated yield over three steps. TLC Rf = 0.33 in 40% EtOAc/«-hexanes. ^-NMR (300 MHz; CDC1 3 ): *denotes minor traces of regioisomer δ 7.38 (d, J = 39.1 Hz, 1H), 5.78 (ddt, J= 17.0, 10.3, 6.7 Hz, 1H), 5.09-4.92 (m, 2H), 2.30 (dd, J = 8.9, 6.9 Hz, 2H), 2.08 (m, 2H), 1.78 (s, 3H), 1.64 (m, 2H), 1.50 (s, 9H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm * 152.9 (C), 152.9 (C), * 152.7 (C), 152.7 (C), 138.3 (CH), * 116.1 (CH 2 ), 115.0 (CH 2 ), 80.9 (C), 38.5 (CH 2 ), 33.4 (CH 3 ), *33.3 (CH 3 ), *28.9 (CH 3 ), 28.3 (CH 3 ), 25.9 (CH 2 ), *24.3 (CH 2 ), *23.4 (CH), 14.7 (CH 2 ). LRMS (EI): 57.07 (100%), 116.06 (43%), 72.07 (39%), 41.04 (35%), 170.11 (21%).

[00371] Preparation of products

[00372] 7-Methyl-2-oxo-2,3,3a,4,5,6-hexahydropyrazolo [ 1,5- a] pyridin-8-ium- 1-ide (product).

[00373] Synthesized according to general procedure B: An oven or flam dried 2-5 mL μ-w tube with a stir bar was capped with a septum and purged with argon for 5 minutes. The acyl hydrazone (0.2 mmol), trifloroutoluene (2-4 mL) and the corresponding alkene were added to the sealed tube. The septum was removed and the tube was then quickly sealed with a microwave cap and heated for 1-3 hours at 80-150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by *H NMR using 1,4-dimethoxybenzene or 1,3,5-trimethoxybenzene as an internal standard. The

corresponding product was purified using a small column or a pipette silica gel column (using dichloromethane then EtOAc to wash out by-products first, then using 10-20% methanol in EtOAc or dichloromethane to wash out the target compound) unless noted otherwise. In this example, ferf-butyl 2-(hept-6-en-2 ylidene)hydrazine-carboxylate (0.277 g, 1.22 mmol) was used. The title compound was purified by column chromatography (10% MeOH/CH 2 Cl 2 ) and obtained as a yellow oil (0.0879 g, 0.578 mmol, 82% NMR yield, 47% isolated yield). TLC R f = 0.18 in 10% methanol in dichlomethane. X H-NMR (300 MHz; CDC13): δ 4.17 (dd, J = 1.1, 1.0 Hz, 1H), 2.85-2.52 (m, 4H), 2.37-2.30 (m, 4H), 2.02 (s, 1H), 1.76 (d, J = 10.6 Hz, 2H). 13 C NMR (100 MHz, CDC1 3 ) δ ppm 180.5 (C), 149.9 (C), 64.6 (CH 3 ), 37.6 (CH 2 ), 30.3 (CH 2 ), 27.3 (CH 2 ), 18.3 (CH 2 ). IR (film) 2917, 2850, 1679, 1582, 1380, 1341, 1085 cm "1 . HRMS(EI): Exact mass calcd for C 8 Hi 2 N 2 0i[M] + : 152.0950. Found: 152.0955.

[00374] General Procedure C: To a 10-20 mL microwave vial were added the hydrazone (1 equiv), the corresponding alkene (10 equiv), the corresponding dipolarophile and α,α,α-trifluorotoluene (0.05 M). The vial was then quickly sealed with a microwave cap and heated in a microwave reactor for 6 hours at 120 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard. The corresponding product was then purified using silica gel chromatography.

[00375] 1,9-Diaza[7, 6, l 47 , 0 3 8 ,0 10 14 ,0]tetrdecan-2-one (product).

[00376] Synthesized from general procedure C using ferf-Butyl 2-(hex-5- enylidene)hydrazinecarboxylate (0.053 g, 0.25 mmol) and norbornene (235 g, 25 mmol). The reaction time was three hours. The title compound was obtained as a white solid and a single diastereoisomer (0.036 g, 0.16 mmol, 62% yield). TLC R f = 0.30 in 100% EtOAc. *H NMR (300 MHz; CDC1 3 ): δ ppm 4.08 (dd, J= 11.6, 9.3 Hz, 1H), 3.03 (d, J = 7.9 Hz, 2H), 2.79 (td, J= 8.3, 4.6 Hz, 1H), 2.72 (d, J = 7.9 Hz, 1H), 2.63 (dd, J = 11.6, 5.8 Hz, 1H), 2.56 (d, J= 2.1 Hz, 1H), 2.31 (d, J= 3.6 Hz, 1H), 1.81-1.43 (m, 9H), 1.22-1.07 (m, 3H). 13 C NMR (100 MHz, CDCI 3 ) δ ppm 171.1 (C), 73.8 (CH), 68.7 (CH), 53.8 (CH 2 ), 46.9 (CH 2 ), 44.2 (CH), 43.9(CH), 39.4 (CH 2 ), 33.7 (CH 2 ), 32.1 (CH 2 ), 31.1 (CH 2 ), 28.3 (CH 2 ), 25.2 (CH 2 ), 24.6 (CH 2 ). IR (film) 3428, 1656, 1097 cm "1 ; HRMS(EI): Exact mass calcd for Ci 4 H 20 N 2 Oi [M] + : 232.1576. Found: 232.1565.

[00377] Example 5: Intermolecular Aminocarbonylation of Various Alkenes

[00378] In this example two imino compounds of Formula IV, containing an t-butoxy leaving group or a O-phenyl leaving group, were reacted with various alkenes according to the reaction shown in the scheme below:

Table 5: % Isolated Yield of dipole product of Aminocarbonylation

Ph Ph-F H 43% NMR 3 yield

Ph O-Bu H 79% (81% 3

NMR

yield)

Ph O-Bu-0- H 76% (78% 3

CH=CH 2 NMR

yield)

Ph O-cyclohexyl H 88% (89% 3

NMR

yield)

Ph O-t-Bu H 75 (84% 3

NMR

yield)

Ph R + R 5 = 70 (70% 3 hetercyclic NMR

(CsO) yield)

Ph R + R 5 = 99 (99% 3 heterocyclic NMR

(C 4 0) yield)

Ph R + R 5 = 19 (21% 3 hetercyclic NMR

(CsO) -0- yield)

Bn(3)

Ph = phenyl; i-Pr 2 = di-isopropyl; Et = ethyl; Bu = buty ; Me = methy

Note 1 = reacted in e 2 = reacted in PhCF 3 (0.1M); Note 3 = neat;

Note 4 = generates ; Note 5 = generates

[00379] Example 6: Intermolecular Thermal Aminocarbonylation with Dialkyl Carbazates

[00380] This Example provides results from successful aminocarbonylation of an alkene using an amino compound of Formula IX according to the following reaction scheme:

[00381] The dialkyl carbazate compound of Formula IX (where LG is Of-Bu, Z is O, and R' and R" are both benzyl) was treated with norbomene in PhCF 3 and heated to 150°C or 180°C for various times. The resulting yields as determined by NMR quantification of the dipole, are shown in the table below:

[00382] X-ray Data

[00383] (±)-cis-l-Diphenylmethylene-3-oxo-tetrahydro-lH-furo[2,3- c]pyrazolidine-l-ium-2-ide (5n)

Table 6. Crystal data and structure refinement for compound 5n

Empirical formula C18 H16 N2 02

Formula weight 292.33

Temperature 200(2) K

Wavelength 0.71073 A

Crystal system, space group Orthorhombic, P2(l)2(l)2(l)

Unit cell dimensions a = 9.2510(13) A alpha = 90 deg

10.0419(15) A beta = 90 deg.

15.538(2) A gamma = 90 deg. Volume 1443.5(4) A A 3

Z, Calculated density 4, 1.345 Mg/m A 3

Absorption coefficient 0.089 mm A -l

F(000) 616

Crystal size 0.11 x 0.06 x 0.04 mm

Theta range for data collection 2.41 to 28.30 deg.

Limiting indices -12<=h<=12, -13<=k<=10, -20<=1<=20 Reflections collected / unique 22561 / 3391 [R(int) = 0.0399]

Completeness to theta = 28.30 95.6 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 0.9964 and 0.9903

Refinement method Full-matrix least-squares on F A 2

Data / restraints / parameters 3391 / 0 / 199

Goodness-of-fit on F A 2 1.017

Final R indices [I>2sigma(I)] Rl = 0.0444, wR2 = 0.0972

R indices (all data) Rl = 0.0573, wR2 = 0.1024

Absolute structure parameter 0.0(13)

Largest diff. peak and hole 0.205 and -0.186 e.A A -3

Table 7. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (A 2 χ

10 3 ) for compound 5n.

U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

U(eq)

N(l) 1466(2) 6594(1) 8739(1) 26(1)

N(2) 2384(2) 7114(1) 9353(1) 29(1)

0(1) 2363(2) 7177(1) 10815(1) 39(1)

0(2) 771(2) 4340(1) 8988(1) 41(1)

C(l) 1822(2) 6814(2) 10131(1) 29(1)

C(2) 443(2) 5972(2) 10068(1) 29(1)

C(3) 600(2) 4576(2) 10471(1) 37(1)

C(4) 1380(2) 3831(2) 9778(1) 42(1)

C(5) 342(2) 5668(2) 9126(1) 31(1)

C(6) 1569(2) 6826(2) 7916(1) 25(1)

C(7) 2738(2) 7626(2) 7525(1) 28(1)

C(8) 2422(2) 8319(2) 6771(1) 36(1)

C(9) 3463(3) 9093(2) 6367(2) 45(1)

C(10) 4848(2) 9150(2) 6704(1) 45(1)

C(l l) 5183(2) 8450(2) 7442(1) 39(1)

C(12) 4139(2) 7703(2) 7856(1) 33(1)

C(13) 442(2) 6252(2) 7337(1) 26(1)

C(14) 851(2) 5284(2) 6739(1) 32(1)

C(15) -147(2) 4768(2) 6170(1) 34(1)

C(16) -1566(2) 5211(2) 6192(1) 32(1) 1979(2) 6167(2) 6779(1)

976(2) 6700(2) 7346(1)

Table 8: Bond lengths [Al and angles idegl for compound 5n.

N(l)-C(6) 1.304(2)

N(l)-N(2) 1.3801(19)

N(l)-C(5) 1.519(2)

N(2)-C(l) 1.349(2)

0(1)-C(1) 1.231(2)

0(2)-C(5) 1.407(2)

0(2)-C(4) 1.445(3)

C(l)-C(2) 1.534(2)

C(2)-C(5) 1.498(3)

C(2)-C(3) 1.542(3)

C(3)-C(4) 1.496(3)

C(6)-C(7) 1.477(2)

C(6)-C(13) 1.493(2)

C(7)-C(8) 1.394(3)

C(7)-C(12) 1.397(2)

C(8)-C(9) 1.387(3)

C(9)-C(10) 1.385(3)

C(10)-C(l l) 1.380(3)

C(l l)-C(12) 1.382(3)

C(13)-C(18) 1.387(2)

C(13)-C(14) 1.396(2)

C(14)-C(15) 1.380(3)

C(15)-C(16) 1.387(3)

C(16)-C(17) 1.378(3)

C(17)-C(18) 1.386(3)

C(6)-N(l)-N(2) 124.43(14)

C(6)-N(l)-C(5) 123.22(14)

N(2)-N(l)-C(5) 112.31(14)

C(l)-N(2)-N(l) 107.32(13)

C(5)-0(2)-C(4) 108.40(14)

0(1)-C(1)-N(2) 123.46(16)

0(1)-C(1)-C(2) 123.84(16)

N(2)-C(l)-C(2) 112.70(14)

C(5)-C(2)-C(l) 103.12(14)

C(5)-C(2)-C(3) 102.59(15)

C(l)-C(2)-C(3) 113.42(14)

C(4)-C(3)-C(2) 101.97(15)

0(2)-C(4)-C(3) 104.26(16)

0(2)-C(5)-C(2) 108.91(15)

0(2)-C(5)-N(l) 109.06(14)

C(2)-C(5)-N(l) 102.64(14)

N(l)-C(6)-C(7) 123.66(15) N(l)-C(6)-C(13) 118.08(15)

C(7)-C(6)-C(13) 118.26(15)

C(8)-C(7)-C(12) 118.44(17)

C(8)-C(7)-C(6) 117.65(15)

C(12)-C(7)-C(6) 123.89(17)

C(9)-C(8)-C(7) 120.97(18)

C(10)-C(9)-C(8) 119.6(2)

C(l l)-C(10)-C(9) 120.08(19)

C(10)-C(l l)-C(12) 120.40(19)

C(l l)-C(12)-C(7) 120.48(19)

C(18)-C(13)-C(14) 119.32(16)

C(18)-C(13)-C(6) 121.93(15)

C(14)-C(13)-C(6) 118.67(15)

C(15)-C(14)-C(13) 120.42(17)

C(14)-C(15)-C(16) 119.77(17)

C(17)-C(16)-C(15) 120.18(17)

C(16)-C(17)-C(18) 120.26(16)

C(17)-C(18)-C(13) 120.03(17)

Symmetry transformations used to generate equivalent atoms:

Table 9. Anisotropic displacement parameters (A 2 χ 10 3 ) for compound 5n.

The anisotropic displacement factor exponent takes the form:

-2 pi 2 [ h 2 a* 2 Ul l + ... + 2 h k a* b* U12 ]

Ul l U22 U33 U23 U13 U12

N(l) 26(1) 26(1) 28(1) -2(1) -4(1) 0(1)

N(2) 30(1) 30(1) 26(1) 2(1) -8(1) -5(1)

0(1) 43(1) 44(1) 29(1) -4(1) -7(1) -4(1)

0(2) 59(1) 31(1) 34(1) -2(1) -2(1) -9(1)

C(l) 29(1) 25(1) 33(1) 0(1) -5(1) 4(1)

C(2) 22(1) 34(1) 30(1) -1(1) 0(1) 2(1)

C(3) 38(1) 37(1) 35(1) 6(1) -2(1) -6(1)

C(4) 48(1) 31(1) 47(1) 3(1) -2(1) 0(1)

C(5) 26(1) 35(1) 32(1) 2(1) -3(1) -6(1)

C(6) 24(1) 25(1) 26(1) 0(1) -3(1) 2(1)

C(7) 27(1) 27(1) 29(1) -6(1) 1(1) 2(1)

C(8) 36(1) 39(1) 33(1) 3(1) -1(1) 2(1)

C(9) 52(1) 43(1) 41(1) 8(1) 6(1) -4(1)

C(10) 47(1) 40(1) 49(1) -4(1) 16(1) -11(1)

C(l l) 29(1) 42(1) 46(1) -11(1) 4(1) -3(1)

C(12) 30(1) 36(1) 35(1) -7(1) 0(1) 1(1)

C(13) 26(1) 28(1) 23(1) 1(1) -2(1) -1(1)

C(14) 27(1) 34(1) 34(1) -2(1) 2(1) 1(1)

C(15) 37(1) 34(1) 31(1) -8(1) 2(1) -1(1) C(16) 32(1) 35(1) 31(1) 0(1) -8(1) -5(1)

C(17) 28(1) 37(1) 37(1) 0(1) -7(1) 4(1)

C(18) 32(1) 32(1) 33(1) -5(1) -3(1) 5(1)

Table 10. Hydrogen coordinates ( x 10 4 ) and isotropic displacement parameters (A 2 χ 10 3 ) for compound 5n.

X y z U(eq)

H(2A) -427 6456 10286 35

H(3A) 1173 4607 11009 44

H(3B) -356 4174 10593 44

H(4A) 2433 4003 9805 50

H(4B) 1211 2860 9831 50

H(5A) -647 5847 8893 37

H(8A) 1481 8261 6530 43

H(9A) 3228 9581 5862 54

H(10A) 5568 9671 6428 55

H(11A) 6138 8481 7667 47

H(12A) 4376 7239 8370 40

H(14A) 1823 4980 6724 38

H(15A) 137 4110 5764 41

H(16A) -2256 4855 5802 39

H(17A) -2954 6462 6796 41

H(18A) -1261 7373 7741 39

Table 11. Torsion angles [degl for compound 5n.

C(6)-N(l)-N(2)-C(l) 171.38(15)

C(5)-N(l)-N(2)-C(l) -10.85(18)

N(l)-N(2)-C(l)-0(1) -177.54(16)

N(l)-N(2)-C(l)-C(2) 2.62(18)

0(1)-C(1)-C(2)-C(5) -173.54(16)

N(2)-C(l)-C(2)-C(5) 6.30(19)

0(1)-C(1)-C(2)-C(3) -63.4(2)

N(2)-C(l)-C(2)-C(3) 116.47(16)

C(5)-C(2)-C(3)-C(4) 30.87(17)

C(l)-C(2)-C(3)-C(4) -79.62(18)

C(5)-0(2)-C(4)-C(3) 29.90(19)

C(2)-C(3)-C(4)-0(2) -37.22(18)

C(4)-0(2)-C(5)-C(2) -9.5(2)

C(4)-0(2)-C(5)-N(l) 101.80(17)

C(l)-C(2)-C(5)-0(2) 104.07(15) C(3)-C(2)-C(5)-0(2) -13.97(18)

C(l)-C(2)-C(5)-N(l) -11.44(16)

C(3)-C(2)-C(5)-N(l) -129.48(14)

C(6)-N(l)-C(5)-0(2) 76.8(2)

N(2)-N(l)-C(5)-0(2) -100.96(16)

C(6)-N(l)-C(5)-C(2) -167.75(15)

N(2)-N(l)-C(5)-C(2) 14.45(18)

N(2)-N(l)-C(6)-C(7) 3.3(3)

C(5)-N(l)-C(6)-C(7) -174.20(15)

N(2)-N(l)-C(6)-C(13) -176.58(14)

C(5)-N(l)-C(6)-C(13) 5.9(2)

N(l)-C(6)-C(7)-C(8) -150.45(17)

C(13)-C(6)-C(7)-C(8) 29.5(2)

N(l)-C(6)-C(7)-C(12) 30.9(3)

C(13)-C(6)-C(7)-C(12) -149.16(16)

C(12)-C(7)-C(8)-C(9) -1.4(3)

C(6)-C(7)-C(8)-C(9) 179.92(18)

C(7)-C(8)-C(9)-C(10) 1.7(3)

C(8)-C(9)-C(10)-C(l l) -0.6(3)

C(9)-C(10)-C(l l)-C(12) -0.9(3)

C(10)-C(l l)-C(12)-C(7) 1.3(3)

C(8)-C(7)-C(12)-C(l l) -0.1(3)

C(6)-C(7)-C(12)-C(l l) 178.50(16)

N(l)-C(6)-C(13)-C(18) 68.8(2)

C(7)-C(6)-C(13)-C(18) -111.11(19)

N(l)-C(6)-C(13)-C(14) -114.61(18)

C(7)-C(6)-C(13)-C(14) 65.5(2)

C(18)-C(13)-C(14)-C(15) -0.8(3)

C(6)-C(13)-C(14)-C(15) -177.43(17)

C(13)-C(14)-C(15)-C(16) -0.1(3)

C(14)-C(15)-C(16)-C(17) 0.2(3)

C(15)-C(16)-C(17)-C(18) 0.6(3)

C(16)-C(17)-C(18)-C(13) -1.4(3)

C(14)-C(13)-C(18)-C(17) 1.5(3)

C(6)-C(13)-C(18)-C(17) 178.05(17)

Symmetry transformations used to generate equivalent atoms:

Table 12. Hydrogen bonds for compound 5n [A and deg.l. d(D-H) d(H .A) d(D .A) <(DHA) [00384] (±)-exo-2-(2,4-Dimethylpentan-3-ylidene)-4-thione-2,3- diazatricyclo [4,3,1 6 ' 9 ,0] decane-2-ium-3-ide (5p)

Table 13. Crystal data and structure refinement for compound 5p.

Empirical formula C15.45 H25.80 N2 00.45 S

Formula weight 278.84

Temperature 200(2) K

Wavelength 0.71073 A

Crystal system, space group Tri clinic, P-l

Unit cell dimensions a = 8.1409(4) A alpha = 91.939(2) deg.

b = 9.9813(5) A beta = 107.230(2) deg.

c = 11.0949(5) A gamma = 111.876(2) deg.

Volume 788.43(7) A A 3

Z, Calculated density 2, 1.175 Mg/m A 3

Absorption coefficient 0.198 mm A -l

F(000) 304

Crystal size 0.22 x 0.19 x 0.16 mm

Theta range for data collection 1.95 to 28.30 deg.

Limiting indices -10<=h<=10, -13<=k<=13, -14<=1<=14 Reflections collected / unique 9891 / 3841 [R(int) = 0.0147]

Completeness to theta = 28.30 97.9 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 0.9690 and 0.9578

Refinement method Full-matrix least-squares on F A 2

Data / restraints / parameters 3841 / 2 / 183

Goodness-of-fit on F A 2 1.027

Final R indices [I>2sigma(I)] Rl = 0.0382, wR2 = 0.1074

R indices (all data) Rl = 0.0424, wR2 = 0.1120

Largest diff. peak and hole 0.463 and -0.190 e.A A -3

Table 14. Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (A ' x 10 3 ) for compound 5p.

U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

y U(eq) S(l) 12638(1) -626(1) 6349(1) 34(1)

N(l) 11295(1) 1258(1) 6934(1) 26(1)

N(2) 9629(1) 1274(1) 7045(1) 22(1)

C(l) 10989(2) -111(1) 6578(1) 24(1)

C(2) 9019(2) -1195(1) 6416(1) 23(1)

C(3) 8962(2) -2260(1) 7393(1) 29(1)

C(4) 6888(2) -3262(1) 7148(1) 36(1)

C(5) 6117(2) -2224(1) 7642(1) 33(1)

C(6) 7821(2) -743(1) 8068(1) 25(1)

C(7) 8124(1) -230(1) 6831(1) 21(1)

C(8) 9435(2) -1229(1) 8620(1) 31(1)

C(33) 9463(2) 2492(1) 7278(1) 25(1)

C(10) 11071(2) 3960(1) 7462(1) 32(1)

C(l l) 12711(2) 4205(2) 8688(1) 45(1)

C(12) 11713(2) 4220(1) 6287(1) 41(1)

C(13) 7623(2) 2460(1) 7333(1) 30(1)

C(14) 6722(2) 3062(2) 6185(1) 40(1)

C(15) 7871(2) 3315(2) 8595(1) 44(1)

0(1) 6443(16) 1560(13) 778(11) 80(3)

C(16) 4820(20) 770(20) -462(15) 78(4)

O(l') 4819(7) -400(4) -24(5) 54(1)

C(16') 5751(9) -1248(7) 504(6) 53(1)

Table 15: Bond lengths [Al and angles [degl for compound 5p.

S(l)-C(l) 1.6843( ;i i)

N(l)-C(l) 1.3182( ;i )

N(l)-N(2) 1.4036( ;i2)

N(2)-C(33) 1.2982( ;i3)

N(2)-C(7) 1.4978( ;i2)

C(l)-C(2) 1.5160( ;i5)

C(2)-C(7) 1.5375( ;i )

C(2)-C(3) 1.5424( ;i5)

C(3)-C(8) 1.536K ;i7)

C(3)-C(4) 1.5414( ;i7)

C(4)-C(5) 1.5544( ;i7)

C(5)-C(6) 1.539K ;i6)

C(6)-C(7) 1.536K ;i )

C(6)-C(8) 1.5350( ;i6)

C(33)-C(13) 1.5059( ;i6)

C(33)-C(10) 1.514K ;i5)

C(10)-C(l l) 1.5336( ;i9)

C(10)-C(12) 1.5377( ;i9)

C(13)-C(14) 1.5327( ;i8) C(13)-C(15) 1.5341(18)

0(1)-C(16) 1.528(15)

0(1')-C(16') 1.373(7)

C(l)-N(l)-N(2) 107.77(9)

C(33)-N(2)-N(l) 121.52(9)

C(33)-N(2)-C(7) 125.68(9)

N(l)-N(2)-C(7) 112.78(8)

N(l)-C(l)-C(2) 113.88(9)

N(l)-C(l)-S(l) 123.43(9)

C(2)-C(l)-S(l) 122.68(8)

C(l)-C(2)-C(7) 103.09(8)

C(l)-C(2)-C(3) 113.22(9)

C(7)-C(2)-C(3) 103.21(8)

C(8)-C(3)-C(4) 101.97(10)

C(8)-C(3)-C(2) 100.71(8)

C(4)-C(3)-C(2) 107.79(10)

C(3)-C(4)-C(5) 103.12(9)

C(6)-C(5)-C(4) 103.27(9)

C(7)-C(6)-C(8) 102.64(9)

C(7)-C(6)-C(5) 105.72(9)

C(8)-C(6)-C(5) 101.32(9)

N(2)-C(7)-C(6) 113.57(8)

N(2)-C(7)-C(2) 102.11(8)

C(6)-C(7)-C(2) 103.71(8)

C(3)-C(8)-C(6) 94.66(9)

N(2)-C(33)-C(13) 119.78(10)

N(2)-C(33)-C(10) 121.42(10)

C(13)-C(33)-C(10) 118.78(9)

C(33)-C(10)-C(l l) 111.68(10)

C(33)-C(10)-C(12) 113.36(10)

C(l l)-C(10)-C(12) 112.05(12)

C(33)-C(13)-C(14) 109.60(10)

C(33)-C(13)-C(15) 111.65(11)

C(14)-C(13)-C(15) 110.98(10)

Symmetry transformations used to generate equivalent atoms:

Table 16: Anisotropic displacement parameters (A 2 χ 10 3 ) for compound 5p.

The anisotropic displacement factor exponent takes the form:

-2 pi A 2 [ h A 2 a* A 2 Ul l + ... + 2 h k a* b* U12 ] Ul l U22 U33 U23 U13 U12

S(l) 30(1) 44(1) 39(1) 7(1) 15(1) 22(1)

N(l) 20(1) 27(1) 32(1) 6(1) 11(1) 10(1)

N(2) 20(1) 19(1) 26(1) 4(1) 8(1) 6(1)

C(l) 24(1) 29(1) 22(1) 6(1) 8(1) 13(1)

C(2) 23(1) 22(1) 25(1) 2(1) 7(1) 11(1)

C(3) 31(1) 23(1) 39(1) 10(1) 12(1) 15(1)

C(4) 36(1) 20(1) 54(1) 9(1) 17(1) 10(1)

C(5) 29(1) 24(1) 49(1) 12(1) 18(1) 9(1)

C(6) 27(1) 22(1) 29(1) 6(1) 13(1) 10(1)

C(7) 20(1) 16(1) 26(1) 3(1) 7(1) 7(1)

C(8) 31(1) 34(1) 28(1) 11(1) 9(1) 15(1)

C(33) 25(1) 20(1) 29(1) 4(1) 9(1) 8(1)

C(10) 31(1) 19(1) 39(1) 2(1) 10(1) 5(1)

C(l l) 38(1) 35(1) 41(1) -2(1) 4(1) 0(1)

C(12) 41(1) 28(1) 45(1) 10(1) 16(1) 3(1)

C(13) 29(1) 24(1) 40(1) 5(1) 14(1) 14(1)

C(14) 41(1) 42(1) 40(1) 4(1) 7(1) 26(1)

C(15) 54(1) 49(1) 41(1) 7(1) 22(1) 30(1)

Table 17: Hydrogen coordinates ( x 10 Λ 4) and isotropic displacement parameters (Α Λ 2 x

10 Λ 3) for compound 5p.

x y z U(eq)

H(2A) 8318 -1718 5516 28

H(3A) 9810 -2783 7444 35

H(4A) 6778 -4090 7631 44

H(4B) 6214 -3652 6227 44

H(5A) 5062 -2162 6953 39

H(5B) 5690 -2559 8368 39

H(6A) 7743 -11 8662 31

H(7A) 6924 -341 6163 25

H(8A) 10687 -413 8853 37

H(8B) 9320 -1750 9354 37

H(10A) 10584 4721 7582 38

H(11A) 12244 4031 9412 67

H(11B) 13641 5214 8844 67 H(11C) 13295 3527 8593 67

H(12A) 10628 4056 5527 61

H(12B) 12284 3540 6165 61

H(12C) 12636 5228 6421 61

H(13A) 6767 1418 7273 35

H(14A) 6578 2500 5392 60

H(14B) 7525 4093 6238 60

H(14C) 5486 2980 6191 60

H(15A) 8441 2907 9314 65

H(15B) 6643 3239 8613 65

H(15C) 8686 4346 8665 65

H(1A) 6918 981 1091 120

H(16A) 3756 67 -261 116

H(16B) 5222 246 -1001 116

H(16C) 4434 1483 -918 116

H(1B) 3657 -906 -285 81

H(16D) 6914 -973 299 79

H(16E) 4952 -2281 156 79

H(16F) 6054 -1094 1435 79

Table 18: Torsion angles [degl for compound 5p.

C(l)-N(l)-N(2)-C(33) -174.04(10)

C(l)-N(l)-N(2)-C(7) 4.37(12)

N(2)-N(l)-C(l)-C(2) -0.42(12)

N(2)-N(l)-C(l)-S(l) -179.23(7)

N(l)-C(l)-C(2)-C(7) -3.37(12)

S(l)-C(l)-C(2)-C(7) 175.44(7)

N(l)-C(l)-C(2)-C(3) -114.17(10)

S(l)-C(l)-C(2)-C(3) 64.65(12)

C(l)-C(2)-C(3)-C(8) 71.90(11)

C(7)-C(2)-C(3)-C(8) -38.82(10)

C(l)-C(2)-C(3)-C(4) 178.30(9)

C(7)-C(2)-C(3)-C(4) 67.58(11)

C(8)-C(3)-C(4)-C(5) 33.48(12)

C(2)-C(3)-C(4)-C(5) -72.04(12)

C(3)-C(4)-C(5)-C(6) 1.80(12)

C(4)-C(5)-C(6)-C(7) 70.29(11)

C(4)-C(5)-C(6)-C(8) -36.45(12)

C(33)-N(2)-C(7)-C(6) -76.88(13)

N(l)-N(2)-C(7)-C(6) 104.79(10)

C(33)-N(2)-C(7)-C(2) 172.14(10) N (1)-N(2)-C(7)-C(2) -6.19(11)

C $)-C(6)-C(7)-N(2) -79.53(10)

C 5)-C(6)-C(7)-N(2) 174.69(8)

c $)-C(6)-C(7)-C(2) 30.47(10)

c 5)-C(6)-C(7)-C(2) -75.31(10)

c i)-C(2)-C(7)-N(2) 5.31(10)

c 3)-C(2)-C(7)-N(2) 123.37(9)

c i)-C(2)-C(7)-C(6) -112.93(9)

c 3)-C(2)-C(7)-C(6) 5.12(10)

c 4)-C(3)-C(8)-C(6) -54.89(10)

c 3)-C(3)-C(8)-C(6) 56.09(10)

c C7)-C(6)-C(8)-C(3) -53.23(10)

c )-C(6)-C(8)-C(3) 55.92(10)

N (1)-N(2)-C(33)-C(13) 177.36(9)

c )-N(2)-C(33)-C(13) -0.82(16)

N (1)-N(2)-C(33)-C(10) -0.93(16)

C C7)-N(2)-C(33)-C(10) -179.11(10)

N (2)-C(33)-C(10)-C(l l) -67.17(15)

C i3)-C(33)-C(10)-C(l l) 114.52(13)

N (2)-C(33)-C(10)-C(12) 60.55(15)

C i3)-C(33)-C(10)-C(12) -117.76(12)

N (2)-C(33)-C(13)-C(14) -111.04(12)

C iO)-C(33)-C(13)-C(14) 67.29(13)

N (2)-C(33)-C(13)-C(15) 125.57(12)

C i0)-C(33)-C(13)-C(15) -56.09(14)

Symmetry transformations used to generate equivalent atoms: Table 19: Hydrogen bonds for compound 5p [A and deg.l.

d(D-H) d(H .A) d(D .A) <(DHA) [00385] (±)-exo-2-(l-methyl-l-(2-furanyl)-methylene)-4-oxo-2,3- diazatricyclo [4,3,1 6 ' 9 ,0] decane-2-ium-3-ide (8)

Table 20: Crystal data and structure refinement for compound 8.

Empirical formula C14 H16 N2 02

Formula weight 244.29

Temperature 200(2) K

Wavelength 0.71073 A

Crystal system, space group Monoclinic, P2(l)/c

Unit cell dimensions a = 9.355(3) A alpha = 90 deg.

b = 10.436(3) A beta = 102.117(17) deg. c = 12.314(4) A gamma = 90 deg.

Volume 1175.4(6) A A 3

Z, Calculated density 4, 1.380 Mg/m A 3

Absorption coefficient 0.094 mm A -l

F(000) 520

Crystal size 0.28 x 0.21 x 0.17 mm

Theta range for data collection 2.23 to 28.66 deg.

Limiting indices -12<=h<=12, -14<=k<=l l, -16<=1<=16 Reflections collected / unique 17491 / 2929 [R(int) = 0.0351]

Completeness to theta = 28.66 96.9 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 0.9843 and 0.9743

Refinement method Full-matrix least-squares on F A 2

Data / restraints / parameters 2929 / 0 / 164

Goodness-of-fit on F A 2 1.023

Final R indices [I>2sigma(I)] Rl = 0.0405, wR2 = 0.1052

R indices (all data) Rl = 0.0519, wR2 = 0.1148

Largest diff. peak and hole 0.289 and -0.201 e.A A -3 Table 21 Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (A 2 χ

10 3 ) for compound 8

U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

X y z U(eq)

N(l) 8306(1) 4760(1) 8531(1) 29(1)

N(2) 8040(1) 4459(1) 9559(1) 25(1)

0(1) 8404(1) 3603(1) 6976(1) 37(1)

0(2) 8456(1) 7409(1) 11070(1) 34(1)

C(l) 8148(1) 3674(1) 7920(1) 28(1)

C(2) 7599(1) 2558(1) 8516(1) 26(1)

C(3) 5991(1) 2210(1) 8002(1) 30(1)

C(4) 5546(1) 1065(1) 8638(1) 36(1)

C(5) 5507(1) 1639(1) 9797(1) 34(1)

C(6) 5867(1) 3058(1) 9664(1) 29(1)

C(7) 7516(1) 3113(1) 9652(1) 25(1)

C(8) 5163(1) 3294(1) 8436(1) 34(1)

C(9) 8191(1) 5297(1) 10366(1) 27(1)

C(10) 8449(1) 6621(1) 10165(1) 29(1)

C(l l) 8652(1) 7351(1) 9284(1) 34(1)

C(12) 8790(1) 8635(1) 9660(1) 39(1)

C(13) 8652(1) 8624(1) 10733(1) 38(1)

C(14) 8119(1) 4868(1) 11519(1) 33(1)

Table 22: Bond lengths [Al and angles idegl for compound 8.

N(l)-C(l) 1.3513(16)

N(l)-N(2) 1.3756(13)

N(2)-C(9) 1.3097(15)

N(2)-C(7) 1.5006(15)

0(1)-C(1) 1.2367(15)

0(2)-C(13) 1.3584(17)

O(2)-C(10) 1.3831(14)

C(l)-C(2) 1.5219(16)

C(2)-C(7) 1.5300(16)

C(2)-C(3) 1.5478(16)

C(3)-C(8) 1.5300(18)

C(3)-C(4) 1.5334(18)

C(4)-C(5) 1.5556(18)

C(5)-C(6) 1.5349(18)

C(6)-C(8) 1.5366(17)

C(6)-C(7) 1.5466(16) C(9)-C(10) 1.4333(18)

C(9)-C(14) 1.5027(16)

C(10)-C(l l1) 1.3713(18)

C(l l)-C(122) 1.4153(19)

C(12)-C(133) 1.354(2)

C(l)-N(i; -N(2) 107 54(9)

C(9)-N(2) -N(l) 122 34(10)

C(9)-N(2) -C(7) 123 51(9)

N(l)-N(2 )-C(7) 114 12(9)

C(13)-0( 2)-C(10) 106 67(10)

o(i)-c(i; -N(l) 123 59(11)

o(i)-c(i; -C(2) 123 98(11)

N(l)-C(l) -C(2) 112 42(10)

C(l)-C(2) -C(7) 103 79(9)

C(l)-C(2) -C(3) 112 30(9)

C(7)-C(2) -C(3) 103 39(9)

C(8)-C(3) -C(4) 100 70(10)

C(8)-C(3) -C(2) 101 73(9)

C(4)-C(3) -C(2) 108 58(10)

C(3)-C(4) -C(5) 103 27(10)

C(6)-C(5) -C(4) 103 05(10)

C(5)-C(6) -C(8) 101 59(10)

C(5)-C(6) -C(7) 106 17(10)

C(8)-C(6) -C(7) 101 95(9)

N(2)-C(7) -C(2) 101 80(9)

N(2)-C(7) -C(6) 112 22(9)

C(2)-C(7) -C(6) 103 71(9)

N(2)-C(9) -C(10) 120 50(10)

N(2)-C(9) -C(14) 119 93(11)

C(10)-C(9)-C(14) 119 56(10)

C(l l)-C(] lO)-0(2) 109 25(11)

C(l l)-C(] 10)-C(9) 136 76(11)

O(2)-C(10)-C(9) 113 95(10)

C(10)-C(] l l)-C(12) 106 52(12)

C(13)-C(] 12)-C(11) 106 91(12)

C(12)-C(] l3)-0(2) 110 64(11)

Symmetry transformations used to generate equivalent atoms:

Table 23. Anisotropic displacement parameters (Α Λ 2 x 10 Λ 3) for compound 8.

The anisotropic displacement factor exponent takes the form:

-2 pi A 2 [ h A 2 a* A 2 Ul l + ... + 2 h k a* b* U12 ]

Ul l U22 U33 U23 U13 U12

N(l) 40(1) 26(1) 23(1) 2(1) 10(1) -3(1)

N(2) 31(1) 23(1) 23(1) 1(1) 8(1) -2(1)

0(1) 51(1) 37(1) 25(1) -2(1) 12(1) -5(1)

0(2) 38(1) 28(1) 37(1) -8(1) 10(1) -3(1)

C(l) 31(1) 27(1) 24(1) 1(1) 5(1) 0(1)

C(2) 29(1) 23(1) 24(1) 0(1) 5(1) 2(1)

C(3) 33(1) 33(1) 24(1) -1(1) 2(1) -3(1)

C(4) 39(1) 29(1) 38(1) -2(1) 6(1) -8(1)

C(5) 39(1) 33(1) 31(1) 4(1) 7(1) -10(1)

C(6) 33(1) 28(1) 29(1) -2(1) 11(1) -3(1)

C(7) 31(1) 22(1) 23(1) 2(1) 5(1) -2(1)

C(8) 30(1) 33(1) 36(1) 6(1) 5(1) 4(1)

C(9) 29(1) 27(1) 26(1) -1(1) 7(1) -2(1)

C(10) 29(1) 27(1) 30(1) -4(1) 6(1) -1(1)

C(l l) 40(1) 27(1) 35(1) 1(1) 7(1) -2(1)

C(12) 40(1) 24(1) 48(1) 3(1) 4(1) -2(1)

C(13) 34(1) 24(1) 55(1) -8(1) 5(1) -2(1)

C(14) 42(1) 33(1) 26(1) -2(1) 12(1) -4(1)

Table 24: Hydrogen coordinates ( x 10 Λ 4) and isotropic displacement parameters (A 2 χ 10 3 ) for compound 8. x y z U(eq)

H(2A) 8261 1798 8579 31

H(3A) 5767 2112 7175 37

H(4A) 6273 364 8701 43

H(4B) 4574 733 8268 43

H(5A) 4529 1537 9973 41

H(5B) 8132 2630 10282 30

H(8A) 4091 3159 8270 40

H(8B) 5399 4149 8173 40

H(11A) 8692 7053 8562 41

H(12A) 8949 9365 9241 46

H(13A) 8687 9363 11187 46 H(14A) 8348 3952 11598 49

H(14B) 7133 5018 11646 49

H(14C) 8829 5353 12063 49

Table 25: Torsion angles [deg] for compound 8.

C(l) -N(l)-N(2; -C(9) 175.95(10)

C(l) -Ν(1)-Ν(2) -C(7) -6.19(12)

N(¾ -N(l)-C(i; -0(1) -175.25(10)

N(2) -N(l)-C(i; -C(2) 5.63(12)

0(1) -C(l)-C(2) -C(7) 177.82(10)

N(l) -C(l)-C(2) -C(7) -3.06(12)

0(1) -C(l)-C(2) -C(3) -71.18(15)

N(l) -C(l)-C(2) -C(3) 107.93(11)

C(l) -C(2)-C(3) -C(8) -75.50(12)

C(7) -C(2)-C(3) -C(8) 35.75(11)

C(l) -C(2)-C(3) -C(4) 178.85(10)

C(7) -C(2)-C(3) -C(4) -69.90(12)

C(8) -C(3)-C(4) -C(5) -37.41(11)

C(2) -C(3)-C(4) -C(5) 68.96(12)

C(3) -C(4)-C(5) -C(6) 2.47(12)

C(4) -C(5)-C(6) -C(8) 33.21(12)

C(4) -C(5)-C(6) -C(7) -73.02(11)

C(9) -N(2)-C(7) -C(2) -178.07(10)

N(l) -N(2)-C(7^ -C(2) 4.10(11)

C(9) -N(2)-C(7) -C(6) 71.63(13)

N(l) -N(2)-C(7; -C(6) -106.20(10)

C(l) -C(2)-C(7) -N(2) -0.58(10)

C(3) -C(2)-C(7) -N(2) -117.97(9)

C(l) -C(2)-C(7) -C(6) 116.08(10)

C(3) -C(2)-C(7) -C(6) -1.31(11)

C(5) -C(6)-C(7) -N(2) -178.33(8)

C(8) -C(6)-C(7) -N(2) 75.70(11)

C(5) -C(6)-C(7) -C(2) 72.59(10)

C(8) -C(6)-C(7) -C(2) -33.38(11)

C(4) -C(3)-C(8) -C(6) 56.83(10)

C(2) -C(3)-C(8) -C(6) -54.91(11)

C(5) -C(6)-C(8) -C(3) -55.45(11)

C(7) -C(6)-C(8) -C(3) 54.05(11)

N(l) -N(2)-C(¾ -C(10) 8.58(16)

C(7) -N(2)-C(9) -C(10) -169.08(10)

N(l) -N(2)-C(¾ -C(14) -170.34(10)

C(7) -N(2)-C(9) -C(14) 12.01(16)

C(13)-0(2)-C(] lO)-C(l l) 0.53(13)

C(13)-0(2)-C(] 10)-C(9) -177.55(10) N(2)-C(9)-C(10)-C(l l) -2.7(2)

C(14)-C(9)-C(10)-C(l l) 176.18(13)

N(2)-C(9)-C(10)-O(2) 174.61(9)

C(14)-C(9)-C(10)-O(2) -6.47(15)

O(2)-C(10)-C(l l)-C(12) 0.02(13)

C(9)-C(10)-C(l l)-C(12) 177.46(13)

C(10)-C(l l)-C(12)-C(13) -0.57(14)

C(l l)-C(12)-C(13)-0(2) 0.93(14)

C(10)-O(2)-C(13)-C(12) -0.91(13)

Symmetry transformations used to generate equivalent atoms:

Table 26. Hydrogen bonds for compound 8 [A and deg.].

D-H...A d(D-H) d(H .A) d(D .A) <(DHA)

[00386] (±)-ex0-2-(2,4-dimethylpentan-3-ylidene)-4-oxo-2,3- diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (3a)

Table 27: Crystal data and structure refinement for compound 3a.

Empirical formula C15 H24 N2 0

Formula weight 248.36

Temperature 296(2) K

Wavelength 0.71073 A

Crystal system, space group Orthorhombic, Pna2(l)

Unit cell dimensions a = 12.8722(2) A alpha = 90 deg.

b = 9.68850(10) A beta = 90 deg. c = 11.38460(10) A gamma = 90

Volume 1419.80(3) A 3

Z, Calculated density 4, 1.162 Mg/m 3

Absorption coefficient 0.073 mm "1 F(000) 544

Crystal size 0.18 x 0.17 x 0.10 mm

Theta range for data collectio n 2.63 to 28.29 deg.

Limiting indices -15≤ h≤ 17, -12≤ k≤ 12, -15≤ 1≤ 15 Reflections collected / unique 13919 / 3463 [R(int) = 0.0220]

Completeness to theta = 28.29 99.7 %

Absorption correction Semi-empirical from equivalents Max. and min. transmission 0.9927 and 0.9870

Refinement method Full-matrix least-squares on F 2

Data / restraints / parameters 3463 / 1 / 163

Goodness-of-fit on F A 2 1.023

Final R indices [I>2sigma(I)] Rl = 0.0346, wR2 = 0.0848 R indices (all data) Rl = 0.0416, wR2 = 0.0895 Absolute structure parameter 0.6(12)

Largest diff. peak and hole 0.119 and -0.123 e.A "3

Table 28: Atomic coordinates ( χ 10 4 ) and equivalent isotropic displacement parameters (A '

x 10 3 ) for compound 3a.

U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

X y z U(eq)

N(l) -1247(1) 1606(1) 4192(1) 43(1)

N(2) -210(1) 1657(1) 4524(1) 35(1)

0(1) -2243(1) 2786(1) 2883(1) 60(1)

C(l) -1397(1) 2564(1) 3361(1) 42(1)

C(2) -424(1) 3388(1) 3080(1) 38(1)

C(3) -526(1) 4896(1) 3475(1) 43(1)

C(4) 480(1) 5652(2) 3156(2) 55(1)

C(5) 1280(1) 5033(2) 4019(2) 57(1)

C(6) 633(1) 4004(1) 4737(1) 44(1)

C(7) 393(1) 2791(1) 3913(1) 36(1)

C(8) -413(1) 4739(1) 4808(1) 46(1)

C(9) 166(1) 833(1) 5313(1) 39(1)

C(10) -529(1) -146(1) 5990(1) 45(1)

C(l l) -1363(1) 612(2) 6694(2) 64(1)

C(12) -1008(1) -1281(2) 5237(2) 59(1)

C(13) 1316(1) 821(2) 5579(1) 50(1)

C(14) 1759(1) -607(2) 5286(2) 69(1)

C(15) 1542(1) 1216(2) 6851(2) 70(1) Table 29: Bond lengths [Al and angles idegl for compound 3a.

N(l)-C(l) 1.3388(17)

N(l)-N(2) 1.3881(13)

N(2)-C(9) 1.2952(15)

N(2)-C(7) 1.5141(14)

0(1)-C(1) 1.2370(15)

C(l)-C(2) 1.5196(18)

C(2)-C(7) 1.5296(17)

C(2)-C(3) 1.5347(18)

C(3)-C(8) 1.5316(19)

C(3)-C(4) 1.5315(19)

C(4)-C(5) 1.545(2)

C(5)-C(6) 1.5350(18)

C(6)-C(8) 1.5251(19)

C(6)-C(7) 1.5344(18)

C(9)-C(13) 1.5105(18)

C(9)-C(10) 1.5150(17)

C(10)-C(12) 1.525(2)

C(10)-C(l l) 1.528(2)

C(13)-C(15) 1.526(3)

C(13)-C(14) 1.533(2)

C(l)-N(l)-N(2) 107.88(10)

C(9)-N(2)-N(l) 121.75(10)

C(9)-N(2)-C(7) 125.06(10)

N(l)-N(2)-C(7) 113.14(9)

0(1)-C(1)-N(1) 123.98(12)

0(1)-C(1)-C(2) 122.81(12)

N(l)-C(l)-C(2) 113.20(10)

C(l)-C(2)-C(7) 103.71(9)

C(l)-C(2)-C(3) 111.59(10)

C(7)-C(2)-C(3) 103.67(10)

C(8)-C(3)-C(4) 101.71(12)

C(8)-C(3)-C(2) 100.84(10)

C(4)-C(3)-C(2) 108.25(11)

C(3)-C(4)-C(5) 103.11(11)

C(6)-C(5)-C(4) 103.23(11)

C(8)-C(6)-C(5) 101.78(10)

C(8)-C(6)-C(7) 102.26(10)

C(5)-C(6)-C(7) 106.36(12)

N(2)-C(7)-C(2) 101.97(9)

N(2)-C(7)-C(6) 112.22(10)

C(2)-C(7)-C(6) 103.18(10)

C(6)-C(8)-C(3) 94.43(10)

N(2)-C(9)-C(13) 120.65(11)

N(2)-C(9)-C(10) 121.24(11)

C(13)-C(9)-C(10) 118.11(11)

C(9)-C(10)-C(12) 113.85(12) C(9)-C(10)-C(l l) 112.36(11)

C(12)-C(10)-C(l l) 110.92(12)

C(9)-C(13)-C(15) 112.02(13)

C(9)-C(13)-C(14) 109.18(13)

C(15)-C(13)-C(14) 111.21(14)

Symmetry transformations used to generate equivalent atoms: Table 30: Anisotropic displacement parameters (A 2 χ 10 3 ) for compound 3a.

The anisotropic displacement factor exponent takes the form:

-2 pi 2 [ h " a* 2 Ul l + ... + 2 h k a* b* U12 ]

Ul l U22 U33 U23 U13 U12

N(l) 35(1 41(1 54(1 11(1) -6(1) -3(1)

N(2) 33(1 31(1 41(1 5(1) 1(1) -1(1)

0(1) 45(1 62(1 74(1 20(1) -19(1) -3(1)

C(l) 41(1 39(1 46(1 3(1) -4(1) 0(1)

C(2) 42(1 39(1 35(1 7(1) 3(1) 2(1)

C(3) 44(1 34(1 52(1 10(1) 0(1) 5(1)

C(4) 61(1 39(1 63(1 17(1) 4(1) -7(1)

C(5) 45(1 43(1 84(1 15(1) -2(1) -9(1)

C(6) 46(1 37(1 48(1 7(1) -8(1) -5(1)

C(7) 34(1 33(1 42(1 8(1) 6(1) 1(1)

C(8) 55(1 38(1 47(1 -2(1) 9(1) 1(1)

C(9) 39(1 34(1 44(1 8(1) 1(1) 0(1)

C(10) 50(1 37(1 48(1 14(1) 1(1) -4(1)

C(l l) 76(1 56(1 60(1 3(1) 24(1) -12(1)

C(12) 67(1 37(1 73(1 5(1) 1(1) -5(1)

C(13) 38(1 49(1 64(1 22(1) -5(1) 0(1)

C(14) 53(1 64(1 91(1 22(1) 4(1) 17(1)

C(15) 64(1 70(1 74(1 17(1) -26(1) -9(1)

Table 31 : Hydrogen coordinates ( x 10 4 ) and isotropic displacement parameters (A 2 χ 10 3 ) for compound 3a. X y z U(eq)

H(2A) -220 3307 2253 46

H(3A) -1164 5358 3219 52

H(4A) 410 6640 3269 66

H(4B) 677 5473 2347 66

H(5A) 1837 4569 3602 69

H(5B) 1575 5742 4520 69

H(6A) 934 3744 5496 52

H(7A) 1010 2448 3502 43

H(8A) -373 5618 5213 56

H(8B) -953 4169 5152 56

H(10A) -83 -611 6566 54

H(11A) -1039 1268 7209 96

H(11B) -1752 -42 7150 96

H(11C) -1822 1085 6165 96

H(12A) -1463 -875 4665 88

H(12B) -1397 -1899 5728 88

H(12C) -467 -1783 4844 88

H(13A) 1654 1499 5068 61

H(14A) 1426 -1292 5766 104

H(14B) 2493 -613 5437 104

H(14C) 1636 -810 4473 104

H(15A) 1241 2102 7016 104

H(15B) 2279 1257 6970 104

H(15C) 1246 538 7367 104

Table 32: Torsion angles Tdeel for compound 3a.

C(l)-N(l)-N(2)-C(9) -179.40(11)

C(l)-N(l)-N(2)-C(7) 3.05(14)

N(2)-N(l)-C(l)-0(1) -179.70(14)

N(2)-N(l)-C(l)-C(2) -1.21(15)

0(1)-C(1)-C(2)-C(7) 177.53(13)

N(l)-C(l)-C(2)-C(7) -0.97(15)

0(1)-C(1)-C(2)-C(3) 66.55(18)

N(l)-C(l)-C(2)-C(3) -111.96(13)

C(l)-C(2)-C(3)-C(8) 73.96(13)

C(7)-C(2)-C(3)-C(8) -37.05(12)

C(l)-C(2)-C(3)-C(4) -179.73(10)

C(7)-C(2)-C(3)-C(4) 69.26(13)

C(8)-C(3)-C(4)-C(5) 35.31(14)

C(2)-C(3)-C(4)-C(5) -70.39(15)

C(3)-C(4)-C(5)-C(6) -0.40(16) C(4)-C(5)-C(6)-C(8) -34.82(15)

C(4)-C(5)-C(6)-C(7) 71.88(14)

C(9)-N(2)-C(7)-C(2) 179.04(11)

N(l)-N(2)-C(7)-C(2) -3.51(12)

C(9)-N(2)-C(7)-C(6) -71.18(15)

N(l)-N(2)-C(7)-C(6) 106.27(12)

C(l)-C(2)-C(7)-N(2) 2.49(12)

C(3)-C(2)-C(7)-N(2) 119.17(10)

C(l)-C(2)-C(7)-C(6) -114.04(11)

C(3)-C(2)-C(7)-C(6) 2.64(12)

C(8)-C(6)-C(7)-N(2) -76.06(12)

C(5)-C(6)-C(7)-N(2) 177.59(10)

C(8)-C(6)-C(7)-C(2) 32.95(12)

C(5)-C(6)-C(7)-C(2) -73.40(12)

C(5)-C(6)-C(8)-C(3) 55.27(13)

C(7)-C(6)-C(8)-C(3) -54.59(11)

C(4)-C(3)-C(8)-C(6) -55.61(12)

C(2)-C(3)-C(8)-C(6) 55.81(11)

N(l)-N(2)-C(9)-C(13) 174.38(12)

C(7)-N(2)-C(9)-C(13) -8.38(18)

N(l)-N(2)-C(9)-C(10) -5.34(18)

C(7)-N(2)-C(9)-C(10) 171.91(11)

N(2)-C(9)-C(10)-C(12) 66.90(16)

C(13)-C(9)-C(10)-C(12) -112.83(15)

N(2)-C(9)-C(10)-C(l l) -60.26(18)

C(13)-C(9)-C(10)-C(l l) 120.01(15)

N(2)-C(9)-C(13)-C(15) 118.74(14)

C(10)-C(9)-C(13)-C(15) -61.53(17)

N(2)-C(9)-C(13)-C(14) -117.62(14)

C(10)-C(9)-C(13)-C(14) 62.11(17)

Symmetry transformations used to generate equivalent atoms:

Table 33: Hydrogen bonds for compound 3a ΓΑ and deg.l

D-H...A d(D-H) d(H . A) d(D . A) <(DHA)

Table 34. Crystal data and structure refinement for (±)-exo-2-[N-(9H-fluoren-9- ylidene)l-4-oxo-2.3-diazatricyclo[4.3.1 6 ' 9 .01decane-2-ium-3-ide:

Empirical formula C21 Η18 Ν2 0

Formula weight 314.37

Temperature 200(2) K

Wavelength 0.71073 A

Crystal system, space group Monoclinic, P2(l)/c

Unit cell dimensions a = 7.1212(5) A alpha = 90 deg. b = 10.1936(6) A beta = 95.486(3) deg.

c = 20.9572(14) A gamma = 90 deg.

Volume 1514.33(17) A 3

Z, Calculated density 4, 1.379 Mg/m 3

Absorption coefficient 0.086 mm "1

F(000) 664

Crystal size 0.17 x 0.08 x 0.08 mm

Theta range for data collection 1.95 to 24.69 deg.

Limiting indices -8≤ h≤ 8, -11≤ k≤ 11, -24≤ 1≤ 24

Reflections collected / unique 17955 / 2552 [R(int) = 0.0626]

Completeness to theta = 24.69 98.8 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 0.9932 and 0.9856

Refinement method Full-matrix least-squares on F 2

Data / restraints / parameters 2552 / 0 / 217

Goodness-of-fit on F A 2 1.052

Final R indices [I>2sigma(I)] Rl = 0.0523, wR2 = 0.1135

R indices (all data) Rl = 0.0809, wR2 = 0.1262

Largest diff. peak and hole 0.153 and -0.267 e.A "3

Table 35: Atomic coordinates ( x 10 4 ) and equivalent isotropic displacement parameters (A 2 x 10 3 ) for (±)-exo-2-rN-(9H-fluoren-9-ylidene)l-4-oxo-2.3-diazatricvcl o-r4.3.1 6 ' 9 .01decane-2- ium-3-ide.

U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

x y z U(eq)

N(l) 1973(2) 4595(2) 1404(1) 26(1)

N(2) 1888(3) 3251(2) 1389(1) 32(1)

0(1) 1493(2) 1667(2) 2135(1) 40(1)

C(l) 1632(3) 2835(2) 1991(1) 30(1)

C(2) 1585(3) 3957(2) 2463(1) 29(1)

C(3) 3339(3) 3967(2) 2950(1) 33(1)

C(4) 3115(4) 5093(2) 3421(1) 36(1)

C(5) 3361(3) 6334(2) 3002(1) 33(1)

C(6) 3710(3) 5755(2) 2346(1) 26(1)

C(7) 1834(3) 5179(2) 2055(1) 27(1)

C(8) 4840(3) 4520(2) 2544(1) 30(1)

C(9) 2167(3) 5273(2) 880(1) 26(1)

C(10) 2403(3) 4699(2) 249(1) 27(1)

C(l l) 2558(3) 3408(2) 43(1) 33(1)

C(12) 2765(3) 3186(2) -603(1) 38(1)

C(13) 2807(3) 4224(2) -1031(1) 39(1)

C(14) 2683(3) 5499(3) -827(1) 37(1) C(15) 2491(3) 5738(2) -185(1) 30(1)

C(16) 2310(3) 6977(2) 157(1) 30(1)

C(17) 2292(4) 8245(2) -73(1) 42(1)

C(18) 2074(4) 9276(2) 347(1) 45(1)

C(19) 1862(3) 9033(2) 985(1) 38(1)

C(20) 1891(3) 7759(2) 1220(1) 33(1)

C(21) 2125(3) 6715(2) 809(1) 28(1)

Table 36: Bond lengths ΓΑ1 and angles ideal for (±)-exo-2-rN-(9H-fluoren-9- ylidene)l-4-oxo-2.3-diazatricvclo-[4.3.1 6 ' 9 .01decane-2-ium-3-ide.

N (1)-C(9) 1.316(3)

N (1)-N(2) 1.371(2)

N (1)-C(7) 1.501(3)

N (2)-C(l) 1.360(3)

0 (l)-C(l) 1.235(3)

C( ;i)-c(2) 1.515(3)

C( ;2)-C(7) 1.530(3)

C( ;2)-C(3) 1.535(3)

C( ;3)-C(4) 1.532(3)

C( ;3)-C(8) 1.535(3)

C( ;4)-C(5) 1.560(3)

C( ;5)-C(6) 1.538(3)

C( ;6)-C(8) 1.530(3)

C( ;6)-C(7) 1.532(3)

C( ;9)-c(io) 1.470(3)

C( ;9)-C(21) 1.478(3)

C( ;io)-c(i i) 1.393(3)

C( ;io)-c(i5) 1.402(3)

C( ;i i)-c(i2) 1.394(3)

C( ;i2)-C(13) 1.389(3)

C( ;i3)-C(14) 1.374(3)

C( ;i4)-C(15) 1.386(3)

C( ;i5)-C(16) 1.465(3)

C( ;i6)-C(17) 1.379(3)

C( ;i6)-C(21) 1.410(3)

C( ;i7)-C(18) 1.389(4)

C( ;i8)-C(19) 1.383(4)

C( ;i9)-C(20) 1.389(3)

C( ;20)-C(21) 1.389(3)

C( ;9)-N(l)-N(2) 120.88(19)

C( ;9)-N(l)-C(7) 124.88(18)

N (2)-N(l)-C(7) 114.24(17)

C( ;i)-N(2)-N(l) 107.45(18)

0 (1)-C(1)-N(2) 123.3(2)

0 (1)-C(1)-C(2) 124.1(2)

N (2)-C(l)-C(2) 112.55(18)

C( ;i)-C(2)-C(7) 103.80(17)

C( ;i)-C(2)-C(3) 111.79(18) c C7)-C(2)-C(3) 103.64(17) c4)-C(3)-C(2) 107.73(19) c4)-C(3)-C(8) 101.68(18) c 3)-C(3)-C(8) 101.53(18) c 3)-C(4)-C(5) 102.74(18) c )-C(5)-C(4) 103.23(17) c $)-C(6)-C(7) 102.01(17) c $)-C(6)-C(5) 101.45(18) c C7)-C(6)-C(5) 107.03(18)

N (1)-C(7)-C(2) 101.93(16)

N (1)-C(7)-C(6) 112.49(17) c 3)-C(7)-C(6) 103.49(17) c )-C(8)-C(3) 94.42(18)

N (1)-C(9)-C(10) 124.9(2)

N (1)-C(9)-C(21) 127.2(2)

C iO)-C(9)-C(21) 107.92(19) c il)-C(10)-C(15) 120.2(2) c il)-C(10)-C(9) 132.4(2) c i5)-C(10)-C(9) 107.45(19) c iO)-C(ll)-C(12) 118.2(2) c i3)-C(12)-C(ll) 121.0(2) c i4)-C(13)-C(12) 120.8(2) c i3)-C(14)-C(15) 118.9(2) c i4)-C(15)-C(10) 120.8(2) c i4)-C(15)-C(16) 130.4(2) c iO)-C(15)-C(16) 108.8(2) c i7)-C(16)-C(21) 121.2(2) c i7)-C(16)-C(15) 129.4(2) c 31)-C(16)-C(15) 109.38(19) c i6)-C(17)-C(18) 119.1(2) c i9)-C(18)-C(17) 120.4(2) c i8)-C(19)-C(20) 120.7(2) c i9)-C(20)-C(21) 119.7(2) c 30)-C(21)-C(16) 118.9(2) c 30)-C(21)-C(9) 134.5(2) c i6)-C(21)-C(9) 106.5(2)

Symmetry transformations used to generate equivalent atoms:

Table 37: Anisotropic displacement parameters (A A 2 x 10 A 3) for (±)-exo-2-rN-(9H-fluoren-9- ylidene)l-4-oxo-2.3-diazatricvclo-r4.3.1 6 ' 9 .01decane-2-ium-3-ide.

The anisotropic displacement factor exponent takes the form: -2 pi 2 [ h 2 a* 2 Ul 1 + ... + 2 h k a* b* U12 ]

Ul l U22 U33 U23 U13 U12

N(l) 27(1) 22(1) 29(1) -2(1) 2(1) 1(1)

N(2) 41(1) 20(1) 34(1) -2(1) 5(1) -2(1)

0(1) 52(1) 24(1) 46(1) 2(1) 10(1) -8(1)

C(l) 28(1) 24(1) 37(1) 1(1) 3(1) -2(1)

C(2) 30(1) 25(1) 33(1) 0(1) 10(1) -2(1)

C(3) 44(1) 24(1) 32(1) 3(1) 4(1) -1(1)

C(4) 46(2) 32(1) 30(1) -3(1) 5(1) -3(1)

C(5) 40(1) 28(1) 31(1) -5(1) 1(1) 1(1)

C(6) 27(1) 22(1) 30(1) 1(1) 3(1) -2(1)

C(7) 30(1) 22(1) 28(1) -2(1) 5(1) 3(1)

C(8) 32(1) 29(1) 29(1) 1(1) 3(1) 2(1)

C(9) 22(1) 26(1) 29(1) 1(1) 0(1) 1(1)

C(10) 22(1) 31(1) 29(1) -2(1) 1(1) 0(1)

C(l l) 33(1) 31(1) 36(1) -5(1) 2(1) 0(1)

C(12) 36(1) 42(2) 37(2) -12(1) 5(1) -1(1)

C(13) 35(1) 53(2) 30(1) -9(1) 7(1) -1(1)

C(14) 34(1) 48(2) 29(1) 3(1) 4(1) -2(1)

C(15) 20(1) 38(1) 31(1) 0(1) 1(1) 0(1)

C(16) 25(1) 30(1) 33(1) 2(1) 0(1) 0(1)

C(17) 48(2) 36(2) 41(2) 10(1) 2(1) 0(1)

C(18) 50(2) 27(1) 55(2) 10(1) -6(1) 1(1)

C(19) 39(1) 28(1) 46(2) -2(1) -6(1) 6(1)

C(20) 32(1) 28(1) 38(1) 0(1) -3(1) 5(1)

C(21) 24(1) 28(1) 32(1) 0(1) -1(1) 3(1)

Table 38: Hydrogen coordinates ( χ 10 4 ) and isotropic displacement parameters (A 2 χ 10 3 ) for (±)-exo-2-[N-(9H-fluoren-9-ylidene)l-4-oxo-2.3-diazatricvcl o-[4.3.1 6 ' 9 .01decane-2-ium-3- ide.

X v z U(ea)

H(2A) 385 3979 2675 35

H(3A) 3661 3099 3155 40

H(4A) 4096 5054 3788 43

H(4B) 1854 5076 3583 43

H(5A) 2209 6883 2970 40

H(5B) 4448 6868 3180 40 H(6A) 4338 6364 2058 32

H(7A) 761 5810 2062 32

H(8A) 6048 4716 2801 36

H(8B) 5061 3952 2176 36

H(11A) 2524 2697 335 40

H(12A) 2879 2313 -752 46

H(13A) 2923 4049 -1471 47

H(14A) 2728 6205 -1120 44

H(17A) 2427 8410 -512 51

H(18A) 2071 10154 194 54

H(19A) 1695 9746 1266 46

H(20A) 1751 7601 1660 39

Table 39: Torsion angles [deal for (±)-exo-2-[N-(9H-fluoren-9-ylidene)l-4-oxo-2.3- diazatricyclo-[4.3.1 6 ' 9 .01 decane-2-ium-3 -ide.

C(9) -N(l) -N(2) -C(l) -178.21(19)

C(7) -N(l) -N(2) -C(l) 2.0(2)

N(i; -N(2; >-c(i; -0(1) 179.81(19)

N(i; -N(2; >-c(i; -C(2) -1.6(2)

o(i; -C(l) -C(2) -C(7) 179.2(2)

N(2) -C(l) -C(2) -C(7) 0.7(2)

0(1) -C(l) -C(2) -C(3) 68.2(3)

N(2) -C(l) -C(2) -C(3) -110.4(2)

C(l) -C(2) -C(3) -C(4) -177.51(18)

C(7) -C(2) -C(3) -C(4) 71.3(2)

C(l) -C(2) -C(3) -C(8) 76.1(2)

C(7) -C(2) -C(3) -C(8) -35.1(2)

C(2) -C(3) -C(4) -C(5) -70.6(2)

C(8) -C(3) -C(4) -C(5) 35.6(2)

C(3) -C(4) -C(5) -C(6) -0.4(2)

C(4) -C(5) -C(6) -C(8) -35.0(2)

C(4) -C(5) -C(6) -C(7) 71.5(2)

C(9) -N(l) -C(7) -C(2) 178.70(19)

N(¾ -N(i; )-C(7 -C(2) -1.5(2)

C(9) -N(l) -C(7) -C(6) -71.1(3)

N(¾ -N(i; )-C(7 -C(6) 108.71(19)

C(l) -C(2) -C(7) -N(l) 0.5(2)

C(3) -C(2) -C(7) -N(l) 117.38(18)

C(l) -C(2) -C(7) -C(6) -116.47(18)

C(3) -C(2) -C(7) -C(6) 0.5(2)

C(8) -C(6) -C(7) -N(l) -74.7(2)

C(5) -C(6) -C(7) -N(l) 179.14(17)

C(8) -C(6) -C(7) -C(2) 34.5(2) C(;5)-C(6)-C(7)-C(2) -71.6(2)

C( ;7)-C(6)-C(8)-C(3) -54.66(19)

C( ;5)-C(6)-C(8)-C(3) 55.74(19)

C( ;4)-C(3)-C(8)-C(6) -56.3(2)

C( ;2)-C(3)-C(8)-C(6) 54.75(19)

N (2)-N(l)-C(9)-C(10) -3.1(3)

C( ;7)-N(l)-C(9)-C(10) 176.64(19)

N (2)-N(l)-C(9)-C(21) 174.60(19)

C( ;7)-N(l)-C(9)-C(21) -5.6(3)

N (1)-C(9)-C(10)-C(11) -2.9(4)

C( ;21)-C(9)-C(10)-C(11) 178.9(2)

N (1)-C(9)-C(10)-C(15) 177.9(2)

C( ;21)-C(9)-C(10)-C(15) -0.3(2)

C( ;i5)-C(10)-C(ll)-C(12) -1.2(3)

C( ;9)-C(10)-C(ll)-C(12) 179.7(2)

C( ;iO)-C(ll)-C(12)-C(13) -0.3(3)

C( ;il)-C(12)-C(13)-C(14) 1.3(4)

C( ;i2)-C(13)-C(14)-C(15) -0.8(4)

C( ;i3)-C(14)-C(15)-C(10) -0.7(3)

C( ;i3)-C(14)-C(15)-C(16) -179.3(2)

C( ;il)-C(10)-C(15)-C(14) 1.7(3)

C( ;9)-C(10)-C(15)-C(14) -179.0(2)

C( ;il)-C(10)-C(15)-C(16) -179.46(18)

C( ;9)-C(10)-C(15)-C(16) -0.1(2)

C( ;i4)-C(15)-C(16)-C(17) -0.4(4)

C( ;iO)-C(15)-C(16)-C(17) -179.1(2)

C( ;i4)-C(15)-C(16)-C(21) 179.2(2)

C( ;iO)-C(15)-C(16)-C(21) 0.5(2)

C( ;21)-C(16)-C(17)-C(18) -0.5(4)

C( ;i5)-C(16)-C(17)-C(18) 179.1(2)

C( ;i6)-C(17)-C(18)-C(19) -0.5(4)

C( ;i7)-C(18)-C(19)-C(20) 1.0(4)

C( ;i8)-C(19)-C(20)-C(21) -0.4(3)

C( ;i9)-C(20)-C(21)-C(16) -0.6(3)

C( ;i9)-C(20)-C(21)-C(9) -177.8(2)

C( ;i7)-C(16)-C(21)-C(20) 1.0(3)

C( ;i5)-C(16)-C(21)-C(20) -178.57(19)

C( ;i7)-C(16)-C(21)-C(9) 178.9(2)

C( ;i5)-C(16)-C(21)-C(9) -0.7(2)

N (1)-C(9)-C(21)-C(20) -0.1(4)

C( ;iO)-C(9)-C(21)-C(20) 178.0(2)

N (1)-C(9)-C(21)-C(16) -177.5(2)

C( ;iO)-C(9)-C(21)-C(16) 0.6(2) [00387] Example 7: Azomethine Imine Production from Aldhydrazones

[00388] Aldehyde-derived hydrazones were reacted with alkenes to produce azomethine imines. For example, the following hydrazone (Rl = i-¥r) was reacted with norbomene to produce an azomethine imine:

Hydrazone Iminoisocyanate Azomethine Imine

[00389] Hydrazones with various R 1 substituents were reacted. In the reaction products below, R 2 and R 3 are derived from the alkene reacted therewith (such as from norbomene as illustrated in the above scheme). OPh was used as the leaving group.

28% isolated yield 53% isolated yield 30% isolated yield 32% isolated yield

23% NMR yield 54% NMR yield 30% NMR yield 33% NMR yield

1 to 2 h 3 h 3 h 1 h

[00390] General Experimental Information

[00391] Infrared spectra were recorded on a Bomem Michelson 100 Fourier transform infrared (IR) spectrometer as neat thin films on NaCl plates and are reported in cm "1 . ¾ NMR and C NMR spectra were recorded in deuterated solvents using Bruker AC-400, AC- 300 spectrometers at ambient temperature, unless otherwise indicated. The data are reported as follows: chemical shift in ppm using solvent as the reference (CDCI 3 at 7.26 ppm, CeD 6 at 7.15 ppm or DMSO-d 6 at 2.50 ppm for 1H NMR and CDC1 3 at 77.0 ppm or DMSO-d 6 at 39.43 for 13C NMR), multiplicity (b = broad, s = singlet, d = doublet, t = triplet, q = quartet, sept = septuplet, m = multiplet), coupling constants (Hz) and integration. High resolution mass spectra (HRMS) were acquired on a Kratos Concept-1 1 A mass spectrometer with an electron beam of 70ev at the Ottawa-Carl eton Mass Spectrometry Centre.

[00392] Materials

[00393] Unless otherwise noted, all commercial materials were purchased from commercial sources and used without further purification.

[00394] Preparation of Starting Materials

[00395] General procdure A (see Berger, R.; Duff, K. ; Leighton, J. L. J. Am. Chem.

Soc. 2004, 126, 5686): To a seal tube (50 mL) were added the corresponding carbazate (lequiv), keton (1 equiv), methanol (0.65 M) and catalytic amount of AcOH (5-15 mol%). The reaction solution was sealed and heated 65 °C for 2-3 hours, then cooled to ambient temperature, concentrated under reduced pressure and purified by direct recrystalization from methanol to give the corresponding products.

[00396] ( s)-Phenyl 2-(2-methylpropylidene)hydrazinecarboxylate

[00397] Synthesized according to general procedure A using isobutyraldehyde (10 mmol, 721 mg), phenyl hydrazinecarboxylate (10 mmol, 1.52 g), methanol (30 mL) and AcOH (10 drops). The title compound was obtained as a white solid (1.34 g, 65% yield). TLC Rf 0.28 in 20% EtOAc in hexanes. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 8.44 (s, 1H), 7.33 (t, J = 7.69 Hz, 2H), 7.22-7.10 (m, 4H), 2.58 (sept, J = 6.74 Hz, 1H), 1.06 (d, J = 6.85 Hz, 6H). 13 C NMR (75 MHz, CDC1 3 ) ppm δ 155.1 (CH), 150.5, 129.3 (CH), 125.6 (CH), 121.5 (CH), 31.4 (CH), 19.9 (CH 3 ). (is)-Phenyl 2-benzylidenehydrazinecarboxylate

[00399] Synthesized according to general procedure A using benzaldehyde (10 mmol, 1.06 g), phenyl hydrazinecarboxylate (10 mmol, 1.52 g), methanol (30 mL) and AcOH (10 drops). The title compound was obtained as a white solid (1.34 g, 65% yield). TLC Rf 0.33 in 20% EtOAc in hexanes. ¾ NMR (300 MHz, CDC1 3 ) ppm δ 8.30-8.25 (m, 2H), 7.47-7.41 (m, 3H), 7.16 (s, 1H), 4.44 (d, J = 6.67 Hz, 1H), 2.81-2.72 (m, 2H), 2.67 (d, J = 2.78 Hz, 1H), 1.76-1.55 (m, 2H), 1.45-1.19 (m, 4H). 13 C NMR (75 MHz, CDC1 3 ) ppm δ 150.6 (C), 146.2 (C), 133.4 (C), 130.3 (CH), 129.4 (CH), 128.7 (CH), 127.5 (CH), 125.8 (CH), 121.5 (CH). ). HRMS(EI): Exact mass calcd for C14H12N2O2 [M] + : 240.0893. Found: 240.0880.

[00400] ( s)-Phenyl 2-(cyclohexylmethylene)hydrazinecarboxylate Ph

[00401] Synthesized according to general procedure A using cyclohexanecarbaldehyde

(10 mmol, 1.12 g), phenyl hydrazinecarboxylate (10 mmol, 1.52 g), methanol (30 mL) and AcOH (10 drops). The title compound was obtained as a white solid (1.75 g, 71% yield). TLC Rf 0.44 in 20% EtOAc in hexanes. ¾ NMR (400 MHz, CDC1 3 ) ppm 5 8.18 (s, 1H), 7.34 (t, J = 7.89 Hz, 2H), 7.23-7.05 (m, 4H), 2.58-2.13 (m, 1H), 1.83-1.61 (m, 5H), 1.34-1.10 (m, 5H). 13 C NMR (75 MHz, CDC1 3 ) ppm δ 154.1 (C), 150.6 (C), 129.4 (2CH), 125.7 (CH), 121.5 (2CH), 40.7 (CH), 30.2 (CH 2 ), 25.8 (CH 2 ), 25.4 (CH 2 ). IR (film) 1711, 1559, 1484, 1366, 1260, 1204, 1047, 954, 910, 756, 688 cm "1 . ). HRMS(EI): Exact mass calcd for Ci 4 Hi 8 N 2 0 2 [M] + : 246.1363. Found: 246.1389. [00402] Intermolecular Aminocarbonylation

[00403] General procedure B: The starting material 1 (0.2 mmol), trifluorotoluene (4 mL), corresponding alkene (2 mmol, 10 equiv) were added to a 2-5 mL μw tube. The tube was then quickly sealed with a microwave cap and heated for 1-3 hours at 120 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by *H NMR using 1,3,5-trimethoxybenzene as an internal standard. The corresponding product was purified using a pipe silica gel column (using EtOAc to wash out byproducts first, then using 10-20% methanol in EtOAc to wash out the target compound).

[00404] (±)-exo-( )-2-(2-Methylpropylidene)-4-oxo-2,3-diazatricyclo[4,3,l 6 9 ,0]decane- 2-ium-3-ide

[00405] Synthesized according to general procedure B using (£)-phenyl 2-(2- methylpropylidene)hydrazinecarboxylate (42 mg, 0.20 mmol), norbornene (188 mg, 2.0 mmol). The reaction time was 2 hours. The title compound (28% isolated yield, 23% NMR yield) was obtained as yellow oil. TLC Rf 0.26 in 20% methanol in EtOAc. H NMR (400 MHz, CDCl 3 ) ppm <5 6.36 (dd, J = 7.57, 1.17 Hz, 1H), 4.19 (d, J = 7.12 Hz, 1H), 3.34-3.24 (m, 1H), 2.72 (s, 1H), 2.69 (d, J = 7.01 Hz, 1H), 2.48 (s, 1H), 1.68-1.57 (m, 2H), 1.39-1.27 (m, 2H), 1.14 (d, J = 6.87 Hz, 6H), 1.13 (d, J = 6.87 Hz, 6H), 1.10-0.97 (m, 2H). 13 C NMR (100 MHz, CDCls) ppm δ 184.7 (C), 144.2 (C), 74.9 (CH), 51.1 (CH), 44.4 (CH), 39.0 (CH), 32.3 (CH 2 ), 28.8 (CH), 27.5 (CH 2 ), 24.8 (CH 2 ), 18.9 (CH 3 ), 18.8 (CH 3 ). IR (film) 2963, 2873, 1716, 1664, 1593, 1465, 1353, 1293, 1002, 917, 729 cm "1 . ). HRMS(EI): Exact mass calcd for Ci 2 Hi 8 N 2 0 [M] + : 206.1414. Found: 206.1417. [00406] (±)-exo-( )-2-Benzylidene-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3- ide

[00407] Synthesized according to general procedure B using (£)-phenyl 2- benzylidenehydrazinecarboxylate (48 mg, 0.20 mmol), norbornene (188 mg, 2.0 mmol). The reaction time was 3 hours. The title compound (53% isolated yield, 54% NMR yield) was obtained as yellow oil. TLC Rf 0.47 in 20% methanol in EtOAc. *H NMR (400 MHz, CDCls) ppm δ 8.31-8.25 (m, 2H), 7.46-7.38 (m, 3H), 7.13 (s, 1H), 4.42 (d, J = 7.02 Hz, 1H), 2.75 (s, 1H), 2.70-2.65 (m, 2H), 1.73-1.56 (m, 2H), 1.40 (d, J = 10.97 Hz, 1H), 1.35-1.25 (m, 2H), 1.21 (d, J = 11.83 Hz, 1H). 13 C NMR (100 MHz, CDCI 3 ) ppm δ 186.2 (C), 132.2 (CH), 131.8 (CH), 131.6 (2CHi), 129.5 (C), 128.8 (2CH), 76.9 (CH), 50.0 (CH), 44.3 (CH), 39.2 (CH), 32.4 (CH 2 ), 27.5 (CH 2 ), 24.9 (CH 2 ). IR (film) 3051, 2961, 2874, 2233, 1659, 1588, 1568, 1451, 1290, 1001, 908, 690 cm "1 . ). HRMS(EI): Exact mass calcd for Ci 5 Hi 6 N 2 0 [M] + : 240.1257. Found: 240.1256.

[00408] (±)-exo-( )-2-Cyclohexylmethylene-4-oxo-2,3-diazatricyclo[4,3,l 6 9 ,0]decane- 2-ium-3-ide

[00409] Synthesized according to general procedure B using (£)-phenyl 2- cyclohexylmethylenehydrazinecarboxylate (49 mg, 0.20 mmol), norbomene (188 mg, 2.0 mmol). The reaction time was 3 hours. The title compound (30% isolated yield, 30% NMR yield) was obtained as yellow oil. TLC Rf 0.24 in 20% methanol in EtOAc. H NMR (400 MHz, CDCI 3 ) ppm δ 6.35 (d, J = 7.71 Hz, 1H), 4.22 (d, J = 7.00 Hz, 1H), 3.23-3.06 (m, 1H), 2.77 (s, 1H), 2.71 (d, J = 6.94 Hz, 1H), 2.50 (s, 1H), 1.94 (d, J = 12.99 Hz, 2H), 1.81- 1.59 (m, 5H), 1.50-1.13 (m, 9H). 13 C NMR (75 MHz, CDC1 3 ) ppm δ 184.6 (C), 142.4 (C), 74.9 (CH), 51.1 (CH), 44.5 (CH 2 ), 39.0 (CH), 37.7 (CH 2 ), 32.3 (CH 2 ), 28.7 (CH 2 ), 28.5 (CH 2 ), 27.5 (CH 2 ), 25.7 (CH 2 ), 24.9 (2CH 2 ), 24.8 (CH 2 ). IR (film) 2998, 2926, 2854, 1165, 1594, 1350, 1004 cm "1 . ). HRMS(EI): Exact mass calcd for Ci 5 H 22 N 2 0 [M] + : 246.1727. Found: 246.1725.

[00410] (±)-cis-(Z)- l-Benzylidene-3-oxotetrahydro- LH-furo [2,3-c] pyrazolidine- 1-ium- 2-ide

[00411] Synthesized according to general procedure B using using (£)-phenyl 2- benzylidenehydrazinecarboxylate (48 mg, 0.20 mmol), norbornene (188 mg, 2.0 mmol). The reaction time was 1 hour. The title compound (32% isolated yield, 33% NMR yield) was obtained as yellow oil. TLC Rf 0.26 in 20% methanol in EtOAc. ¾ NMR (400 MHz, CDC1 3 ) ppm δ 8.31 (dd, J = 7.76, 1.83 Hz, 2H), 7.50-7.43 (m, 3H), 7.34 (s, 1H), 6.11 (d, J = 6.14 Hz, 1H), 4.15 (t, J = 8.30 Hz, 1H), 3.65 (ddd, J = 12.28, 9.05, 5.44 Hz, 1H), 3.37 (dd, J = 9.06, 6.30 Hz, 1H), 2.47 (dd, J = 12.61, 5.32 Hz, 1H), 2.27-2.13 (m, 1H). 13 C NMR (75 MHz, CDCI 3 ) ppm δ 183.7 (C), 134.0 (CH), 132.5 (CH), 132.2 (CH), 129.0 (C), 128.9 (CH), 102.2 (CH), 68.6 (CH 2 ), 45.6 (CH), 29.9 (CH 2 ). IR (film) 2254, 1727, 1700, 1598, 1521, 1253, 1155, 911, 738, 647 cm "1 .

[00412] Table 40 shows the results of different equivalents of norbornene as the alkene in an intermolecular aminocarbonylation reaction. Reactions were performed at 150°C for 3 hours, using 1, 3 or 5 equivalents of norbornene. The yields are provided. Table 40: Yield (%) of aminocarbonylation product using different equivalents of norbornene

Entry Equivalents of Norbornene Temperature (°C) Time (hours) 1 H NMR Yield (%) 1 1 150 3 7 5 3 150 3 0 3 5 150 3 0 a Experiments conducted with 0.4 M of hydrazone in TFT, in microwave sealed tubes, heated in a microwave.

[00413] With excess amounts of alkene, azomethine appears to be highly reactive at 150°C. However, as illustrated in Table 40, very little (if any) product is generated when reacting with lesser amounts of alkene.

[00414] Table 41 shows the results of using different equivalents of norbornene at reaction temperatures lower than 150°C.

Table 41: Yield (%) of aminocarbonylation reaction products at varying norbornene equivalents and temperatures.

Entry Equivalents of Norbornene Temperature (°C) Time (hours) 1 H NMR Yield (%)

6 10 120 2 23 c

a Experiments conducted with 0.4 M of hydrazone in TFT, in microwave sealed tubes, heated in a microwave.

b Thermal heating

[00415] As shown in Table 41, at 100°C, the aminocarbonylation reaction did not generate substantive yields of azomethine imine product, even at longer reaction times. At 120°C, a shorter reaction time appears to generate higher yields of product.

[00416] Example 8: Derivatization of Azomethine Imines to /3-Aminocarbonyl Compounds:

[00417] The dipole products generated in the reactions described herein can be treated to cleave the N-N bond and thereby produce a β-aminocarbonyl-containing compound. It has been found that reductive conditions coupled with elimination facilitate the cleavage of the

N-N bond. Cleavage can be obtained with or without the addition of Raney nickel. [00418] The following scheme illustrates exemplary derivatization of the azomethine imine adducts derived from hydrazone into several β-aminocarbonyl compounds. The fluorenone derived reagent was developed to allow subsequent N-N bond cleavage under mild reducing and basic conditions. Six different aminocarbonylation products provided the desired fluorenyl -protected β-aminoamides upon treatment with KBH 4 and Raney Nickel in MeOH. Subsequent to N-N bond cleavage, a terminal β-aminoamide is formed.

C onditions: Λ ΚΒΗ, . RJ-NI. MeOH. 60 ' - . ih. SOCl : . MeOH.

Γ.ΐ.. jtli. ' ¾Ot l-. Η-ΰ. r. T .. ' DDQ THF. 0 . h. [hen addme

HC] ( 1 M

[00419] General procedure A: To a large sealed flask, azomethine imine was disolved in methanol one pipette of Raney nickel (slurry in water) and KBH 4 (6.0 equiv.) were added. Care must be taken in choosing size of the sealed flask to allow a maximum volume of air to be present once sealed. The bottle was sealed and the reaction mixture was stirred at 60 °C for 12 hours. The mixture was concentrated under reduced pressure and quenched with saturated ammonium chloride solution. Product was extracted with dichloromethane (3 x) and the combined organic layer was dried over sodium sulfate and concentrated under reduced pressure. Crude mixture was purified over column chromatography.

[00420] β-aminoesters and β-aminoacids can also be obtained from the β-aminoamides using literature procedures (Li et al, Eur J. Org. Chem 2007, 1026-30). For example, β- aminoacids can be obtained directly from the β-aminoamide, or can be obtained via the β- aminoester. In certain embodiments, a simple reduction of the dipole provides a

pyrazolidinone, and further reduction to a pyrazolidine. Other derivatization after N-N bond cleavage can include: 1) 1,3 diamines formed upon reduction of the primary amide into an amine (such as reacting with LiAlH 4 to reduce the carbonyl group and obtain a primary amine, for example); 2) nitriles formed upon dehydration of the primary amide; and 3) imidazolidinones, or 1,2 -diamines via Hoffman rearrangement of the primary amide. N-N bond cleavage can be performed as shown in Zupancic et al, J. Heterocyclic Chem, 1999 (36), 607-10, also using KOH.

[00421] Exemplary derivatization products are shown below:

PG . .

J- o PG - NH =G

H i. H i " NH O

X=NH 2 , a 92%, 6aa X=NH 2 , a 62%, 6bb X=NH2, a 91%, 6cc

X=OMe, b 49%, 7aa X=OMe, 50%, 7bb X=OMe, b 89%, 7cc

X=NH 2 , PG=H d X=OH, c 85%, 8a

65%, 9a

X=NH 2 , a 75%, 6ee X=NH 2 , a 72%, 6ff

[00422] Example 9: Equlibration studies on Z and E azomethine imines

[00423] There are very few examples of unsymmetrical azomethine imines in the literature (Taylor, E. C; Haley, N. F.; Clemens, R. J. Am. Chem. Soc. 1981, 103, 7743. (b) Taylor, E. C; Clemens, R. J.; Davies, H. M. L. J. Org. Chem. 1983, 48, 4567. (c)

Tomaschewski, G.; Geissler, G; Schauer, G. J. Prakt. Chem. 1980, 322, 623. (d) Panfil, I.; Urbahczyk-Lipkowska, Z.; Suwmska, K.; Solecka, J.; Chmielewski, M. Tetrahedron 2002, 58, 1199). Seeking to determine if the isomeric mixtures obtained in Table 2 were the result of thermodynamic equilibration or were dependent on the stereisomeric ratio of the imino- isocyanate, each stereoisomer was subjected to the reaction conditions (heating in the presence of the leaving group released under the reaction conditions):

substrate additive Z:E ratio

Z-5c none 2.5:1

Z-5c PhOH 3.2:1

Z-5c PhSH >25:1

E-5c none 2.5:1

E-5c PhOH 3.3:1

E-5c PhSH 8.3:1

[00424] The results in the above scheme show the importance of the leaving group (released during imino-isocyanate formation) on the stereochemical outcome of the reactions. The use of thiophenol as an additive appeared to favour the Z stereoisomer. In contrast, phenol appeared to induce an equilibrium toward a stereoisomer mixture (likely due to the increased ability of E-5c to engage in hydrogen bonding). In E-5c the furyl ring system is aligned to increase the electron density of the amide portion of the dipole, thus increasing its ability to act as H-bond acceptor. Importantly, these results provide the opportunity to access unsymmetrical azomethine imines with high stereocontrol, as illustrated by the use of a modified aminocarbonylation reagent in the following equation:

76% yield

Z:E =12:1

[00425] Conditions allowing for high stereocontrol during the formation of unsymmetrical azomethine imines allow the use of these complex dipoles in stereoselective synthesis. Nucleophilic additions to aldehyde and ketone-derived azomethine imines were investigated, observing high diastereoselectivities:

substrate reagent yield, dr major product

R =H vinyl-MgBr 74%, 14: 1 dr R 1 =H I R2=C 2 H 3 (17a) R 1 =Me K-Selectride 72%, >25: 1 dr R 1 =Me,R 2 =H (17b)

[00426] Preparation of starting material in Example 9

[00427] (E and Z)-S-Phenyl 2-(l-(furan-2-yl)ethylidene)hydrazinecarbothioate (equation 4, 7).

[00428] To a 2-5 mL μνν tube were added t-butyl 2-(l-(furan-2- yl)ethylidene)hydrozinecarboxylate (450 mg, 2.0 mmol), trifluorotoluene (4 mL), and the thiophenol (l. lg, 10 mmol, 5 equiv). The tube was then sealed with a microwave cap and heated for 3 minute at 150 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and purified by silica gel chromatography to give the titled product as a colorless solid (200 mg, 38%) and a mixture of E/Z isomers (ratio = 4: 1 E/Z). TLC Rf = 0.47 in 30% EtOAc/hexanes For E isomer: *H NMR (400 MHz, CDC1 3 ) δ 10.22 (s, 1H), 7.59-7.52 (m, 2H), 7.48 (dd, J = 1.7 and 0.6 Hz, 1H), 7.43-7.34 (m, 3H), 6.75 (dd, J = 3.4 and 0.6 Hz, 1H), 6.43 (dd, J = 3.5 and 1.8 Hz, 1H), 1.97 (s, 3H). 13 C NMR (100 MHz, CDCls) δ 171.9 (C), 151.6 (C), 144.0 (CH), 141.4 (C), 135.8 (CH), 129.1 (CH), 128.8 (CH), 128.6 (C), 111.7 (CH), 110.6 (CH), 12.7 (CH 3 ). IR (film) 1728, 1522, 1496, 1208, 1120, 772 cm "1 . 2 HRMS(EI): Exact mass calcd for C14H22N2O [M] + : 260.3110. Found: 260.3118. [00429] Preparation of products in Example 9

[00430] An oven or flame dried 2-5 mL microwave tube with a stir bar was capped with a septum and purged with argon for 5 minutes. (±)-exo-(E)-2-[(l-Furan-2-yl)ethylidene]-4-oxo- 2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (24 mg, 0.1 mmol) or (±)-exo-(Z)-2-[(l- Furan-2-yl)ethylidene]-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide (24 mg, 0.1 mmol), the corresponding additives phenol (9 mg, 0.1 mmol) or benzenethiol (11 mg, 0.1 mmol) and (trifluoromethyl)benzene (2 mL) were added to the sealed tube. The septum was removed and the tube was then quickly sealed with a microwave cap and heated for 1-3 hours at 130 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by H NMR using 1,3,5-trimethoxybenzene as an internal standard.

[00431] Diastereoselective reduction

[00432] General procedure D: To a flame-dried flask was added at 0°C the nucleophile (1.25 equiv) to a solution of dipole (1 equiv) in THF (0.2 M). The reaction was then stirred overnight at room temperature. Aqueous sat. NH 4 C1 was then added and the aqueous layer was extracted with EtOAc. The organic layer was then dried over MgS04, concentrated under vacuum and was then purified using silica gel chromatography.

[00433] (±)-exo-2,3-Diaza-2-[l-(furan-2-yl)ethyl]-[4,3,l,0]decan-4- one.

[00434] Synthesized according to general procedure D using (±)-exo-(£)-2-[(l-Furan-

2-yl)ethylidene]-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide 6c (0.110 g, 0.45 mmol), K-selectride (1M in THF, 0.54 mL, 0.54 mmol, 1.2 equiv) in THF (3 mL). The title compound was obtained as orange solid (0.092 g, 74% yield) after column chromatography (30/70 Hexane/EtOAc to 100% EtOAc). TLC R f = 0.29 in 100% EtOAc. X H NMR (300 MHz, CDCls) δ 7.37 (d, J = 1.10 Hz, 1H), 6.32 (dd, J= 3.1 and 1.9 Hz, 1H), 6.24 (d, J= 3.2 Hz, 1H), 3.97 (d, J= 7.0 Hz, 1H), 3.26 (d, J= 8.0 Hz, 1H), 2.47 - 2.57 (m, 1H), 2.18 - 2.39 (m, 2 H), 0.96 - 1.70 (m, 10 H). 13 C NMR (75 MHz, CDC1 3 ) δ 174.7 (C), 153.7 (C), 142.1 (CH), 110.2 (CH), 108.3 (CH), 67.70 (CH), 60.07 (CH), 50.4 (CH), 43.6 (CH), 39.2 (CH), 33.4 (CH 2 ), 27.5 (CH 2 ), 25.1 (CH 2 ), 16.6 (CH). IR (film) 3176, 3059, 2963, 2870, 1671, 1502, 1449, 1377 cm "1 . HRMS(EI): Exact mass calcd for Ci 4 Hi 8 N 2 0 2 [M]+:246.1368.

Found: 246.1369.

[00435] (±)-exo-2,3-Diaza-2-[l-(furan-2-yl)allyl]-[4,3,l,0]decan-4- one.

[00436] Synthesized according to general procedure D using (±)-exo-(£)-2-[(l-Furan-

2-yl)ethylidene]-4-oxo-2,3-diazatricyclo[4,3,l 6 ' 9 ,0]decane-2-ium-3-ide 6c (0.110 g, 0.48 mmol), vinylmagnesium bromide (1M in THF, 0.6 mL, 0.60 mmol, 1.25 equiv) in THF (3 mL). The title compound was obtained as yellow solid (0.092 g, 14: 1 isomer, 74% yield) after column chromatography (100% EtOAc). TLC R f = 0.43 in 100% EtOAc. ¾ NMR (300 MHz, CDCls) 8.02 (br. s., 1H), 7.33-7.50 (m, 1H), 6.21-6.43 (m, 2H), 5.90-6.17 (m, 1H), 5.37 (s, 1H), 5.25-5.35 (m, 1H), 4.27 (d, J = 8.0 Hz, 1H), 3.23 (d, J = 8.1 Hz, 1H), 2.41-2.56 (m, 2H), 2.14 (d, J = 3.8 Hz, 1H), 0.96-1.65 (m, 7H). 13 C NMR (100 MHz, CDC1 3 ) 174.1 (C), 151.7 (C), 142.5 (CH), 133.6 (CH), 120.5 (CH 2 ), 110.4 (CH), 108.9 (CH), 68.7 (CH), 67.3 (CH), 50.3 (CH), 43.5 (CH), 39.3 (CH), 33.4 (CH), 27.5 (CH), 24.9 (CH). IR (film) 3172, 2963, 1674, 1494, 1377, 1144 cm "1 . HRMS(EI): Exact mass calcd for Ci 5 Hi 8 N 2 0 2

[M]+:258.1368. Found: 258.13668.

[00437] Example 10: Aminocarbonylation of Alkenes via Imino-Isocyanates: A Concerted Mechanism

[00438] In certain emboidments, a concerted reaction in the aminocarbonylation of alkenes is observed. Without wishing to be bound by theory, it is believed that with a concerted reaction, the stereochemistry of the alkene is conserved in the products of the aminocarbonylation reaction. By contrast, reactions involving chlorosulfonyl isocyanate (a competing aminocarboylation technology which is shown to react in two steps rather than one), alkene stereochemistry is not conserved and the most stable products are typically obtained. [00439] Experimental:

[00440] General procedure : An oven or flame dried 2-5 mL μ-w tube with a stir bar was capped with a septum and purged with argon for 5 minutes. The acyl hydrazone, trifluorotoluene (0.05M) and the corresponding alkene (10 equiv.) were added to the sealed tube. The septum was removed and the tube was then quickly sealed with a microwave cap and heated for 6 hours at 120 °C. The reaction solution was cooled to ambient temperature, concentrated under reduced pressure and analyzed by ¾ NMR using 1,3,5- trimethoxybenzene as an internal standard. The corresponding product was purified using silica gel column chromatography (using EtOAc to wash out by-products first, then using 10- 20% methanol in EtOAc to wash out the target compound) unless noted otherwise.

[00441] Examples of mechanistic determination:

[00442] a) E-alkene

27% traces Results

2-(9H-Fluoren-9-ylidene)-5-oxo-ira«s-2-methyl-3-phenylpyraz olidin-2-

[00446] Synthesized according to general procedure using phenyl 2-(9H-fluoren-9- ylidene)hydrazinecarboxylate (0.0843 g, 0.268 mmol) and irara-jS-methylstyrene (0.35 mL, 2.68 mmol) dissolved in α,α,α-trifluorotoluene (5.37 mL, 0.05M). The target compound was obtained as a yellow solid (0.0475 g, 52%) and a 1 : 1 mixture of regioisomers. TLC R f = 0.61 in 100% EtOAc. ¾ NMR (300 MHz, CDC1 3 ) ppm 9.18 (d, J = 7.3, 1H), 9.12 (d, J = 7.6, 1H), 7.64 (ddd, J = 30.5, 16.4, 7.2, 5H), 7.48-7.21 (m, 18H), 7.05 (s, 1H), 5.91 (s, 1H), 5.36 (q, J = 6.3, 1H), 3.79 (s, 1H), 2.83 (q, J = 7.1, 1H), 1.89 (A, J = 6.6, 3H), 1.60 (d, J = 7.4, 3H); 13 C NMR (CDCI 3 , 75 MHz) δ ppm 186.2, 183.6, 142.3, 141.8, 140.3, 140.0, 138.2, 137.7, 132.3, 131.8, 131.8, 131.8, 131.6, 131.3, 131.1, 129.9, 129.6, 129.5, 129.4, 129.3, 128.8, 128.5, 128.0, 127.9, 127.1, 126.0, 125.5, 124.5, 121.3, 120.9, 119.8, 79.9, 72.5, 56.8, 48.1, 21.8, 18.4; HRMS(EI): Exact mass calcd for C 23 Hi 8 N 2 0 [M] + : 338.1419. Found: 338.1404.

[00447] 2-(9H-Fluoren-9-ylidene)-5-oxo-cis-2-methyl-3-phenylpyrazoli din-2-ium- 1-ide:

[00448] Synthesized according to general procedure using phenyl 2-(9H-fiuoren-9- ylidene)hydrazinecarboxylate (0.105 g, 0.335 mmol) and cw- 3-methylstyrene (0.396 g, 3.35 mmol) dissolved in α,α,α-trifluorotoluene (6.7 mL, 0.05M). The target compound was obtained as a yellow solid (0.0273 g, 24% yield) as a 10: 1 mixture of the target compound and 2-(9H-Fluoren-9-ylidene)-5-oxo-ira« , -2-methyl-3-phenylpyrazolidin-2-ium-l-ide. TLC R f = 0.41 in 100% EtOAc. ¾ NMR (300 MHz, CDC1 3 ) δ ppm 9.17 (d, J= 7.2, 1H), 7.58- 7.55 (m, 2H), 7.47-7.25 (m, 9H), 7.07 (t, J= 7.5, 1H), 6.36 (d, J= 8.8, 1H), 3.43 (quintet, J = 7.6, 1H), 0.90 (d, J= 7.2, 3H); 13 C NMR (CDC1 3 , 75 MHz) δ ppm ; 185.3, 141.6, 140.8, 140.1, 133.9, 132.0, 131.8, 131.7, 130.8, 129.4, 129.4, 129.3, 129.1, 128.9, 127.8, 127.0, 127.0, 126.4, 125.9, 120.7, 119.6, 41.3, 11.4.

[00449] Example 12: Addition of additives to improve reactivity

[00450] General procedure: To an oven dried 2-5 mL microwave vial was added the corresponding hydrazone, trifluorotoluene (0.05M), norbomene (10 equiv.) and catalyst. The vial was then sealed and purged with argon for 1 minute. The reaction solution was then heated for two hours at 70 °C in an oil or wax bath, cooled to ambient temperature, concentrated under reduced pressure and analyzed by H NMR using 1,3,5- trimethoxybenzene as the internal standard.

[00451] For the reactions with 0.02 equivalents of base, diluted solutions of the catalyst were made.

Table 42: Yield and pKa for reactions using various catalysts

Entry Catalyst NMR yield (%) NMR yield (%) pkA

0.3 equiv. cat 0.02 equiv. cat

16-22

Et-,Ν 26 10.75

+ -

13 Na N 25 26 indicates that base is not soluble under the reaction conditions [00452] All publications, patents and patent applications mentioned in this

Specification are indicative of the level of skill of those skilled in the art to which this invention pertains and are herein incorporated by reference to the same extent as if each individual publication, patent, or patent applications was specifically and individually indicated to be incorporated by reference.

[00453] The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.