FIELD OF THE INVENTION

[0001] The present invention pertains to frustrated Lewis pair catalysts and their uses for reduction reactions. More particularly, the present invention pertains to frustrated Lewis pair catalysts comprising a borenium complex, and the use of the borenium-containing frustrated Lewis pair catalysts in direct hydrogenation reactions.

BACKGROUND

[0002] Hydrogenation is one of the most utilized and important reactions in chemistry. Typically, the hydrogenation of organic substrates using H ₂ directly is mediated by a transition metal catalyst. (J. G. de Vries and C. J. Elsevier, The Handbook of Homogeneous Hydrogenation, Wiley-VCH, Weinheim, 2007.) Alternatively, main group hydrides such as NaBH ₄ and LiAlH ₄ afford stoichiometric reductions, with complementary chemo- and regioselectivity to metal catalysis. (M. B. Smith and J. March, in March's Advanced Organic Chemistry, New York, 5th Ed., 2001, pp. 1197-1204 and pp. 1544-1564.) For these reagents in industrial scale reduction processes, cost, chemical efficacy and waste disposal are significant concerns.

[0003] Catalytic hydrogenations employing transition metal-free catalysts could address the cost and waste remediation issues associated with main group hydrides, as well as avoid the expense and potentially toxic nature of precious metal catalysts. A number of transition metal-free hydrogenation reactions are known within the field of organocatalysis. (H. Adolfsson, Angew. Chem., Int. Ed., 2005, 44, 3340; P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed., 2004, 43, 5138; M. Rueping, A. P. Antonchick and T. Theissmann, Angew. Chem., Int. Ed, 2006, 45, 3683; J. B. Tuttle, S. G. Ouellet and D. W. C. MacMillan, J. Am. Chem. Soc, 2006, 128, 12662; J. W. Yang, M. T. Hechavarria Fonseca and B. List, Angew. Chem., Int. Ed., 2004, 43, 6660.) These systems do not use H ₂ directly, but rather a surrogate, such as a Hantzsch ester, as a source of H ₂ .

[0004] Alternatively, as H ₂ is known to react directly with trialkylboranes to give

R ² BH and RH, a hydrogenation cycle by successive hydroboration/ hydrogenolysis reactions can be used to effect the reduction of alkenes. However, the required conditions can be rather forcing (>200 °C, 15 atm). (E. J. DeWitt, F. L. Ramp and L. E. Trapasso, J. Am. Chem. Soc, 1961, 83, 4672; M. W. Haenel, J. Narangerel, U. B. Richter and A. Rufmska, Angew. Chem., Int. Ed., 2006, 45, 1061; R. Koester, G. Bruno and P. Binger, Justus Liebigs Ann. Chem., 1961, 644, 1; F. L. Ramp, E. J. DeWitt and L. E. Trapasso, J. Org. Chem., 1962, 27, 4368.) Similarly, Berkessel et al. reported the catalytic reduction of benzophenone using KOtBu/ H ₂ , although the conditions were again quite harsh (180°C, 50 bar). (A. Berkessel, T. J. S.

Schubert and T. N. Mueller, J. Am. Chem. Soc, 2002, 124, 8693.) The key to developing main group hydrogenation catalysis utilizing H ₂ has been the discovery of main group compounds that can react directly with H ₂ . (A. L. Kenward and W. E. Piers, Angew. Chem., Int. Ed., 2007, 47, 38.)

[0005] The concept of Lewis acidity and basicity and the formation of simple Lewis acid-base adductsis a primary axiom of main group chemistry. (G. N. Lewis, Valence and the Structure of Atoms and Molecules, Chemical Catalogue Company, Inc., New York, 1923.) The combination of Lewis donors and acceptors in which steric demands preclude formation of simple acid-base adducts have been termed "frustrated Lewis pairs" (FLPs). (D. W. Stephan, Org. Biomol. Chem., 2008, 6, 1535-1539.)

Classical Lewis acid/base adduct

"Frustrated

Lewis-pair'

[0006] As a result of the unquenched acidity and basicity, such systems have been shown to prompt non-classical and in some cases unprecedented reactivity. Employing this strategy, it has been demonstrated that the phosphine-borane [(C ₆ H ₂ Me3)2P(C ₆ F4)B(C ₆ F ₅ )2]3 can react reversibly with H ₂ to give the zwitterionic [R ₂ PH(C6F4)BH(C6F5) ₂ ] . (G. C. Welch, R. R. S. Juan, J. D. Masuda and D. W. Stephan, Science, 2006, 314, 1124.) [0007] It has been recently reported that H ₂ can be heterolytically cleaved under ambient conditions by a reaction with a combination of bulky boranes and phosphines. (G.C. Welch, R. San Juan, J.D. Masuda and D.W. Stephan, Science 2006, 314, 1124-1126. G. C. Welch and D. W. Stephan, J. Am. Chem. Soc, 2007, 129, 1880.) Such sterically bulky FLPs provide unquenched acceptor and donor abilities to the acid and base, respectively, opening new modes of reactivity. (G. C. Welch and D. W. Stephan, J. Am. Chem. Soc, 2007, 129, 1880; L. Cabrera, G. C. Welch, J. D. Masuda, P. Wei and D. W. Stephan, Inorg. Chim. Acta, 2006, 359, 3066; G. C. Welch, L. Cabrera, P. A. Chase, E. Hollink, J. D. Masuda, P. Wei and D. W. Stephan, Dalton Trans., 2007, 3407.) Moreover, FLP mixtures of B(C ₆ F ₅ ) ₃ and PR ₃ have been shown to react with alkenes. (J. S. J. McCahill, G. C. Welch and D. W. Stephan, Angew. Chem., Int. Ed., 2007, 46, 4968)

[0008] Compounds wherein the borare and phosphine are present in the same molecule have been shown to catalyze the reduction of imines and nitriles under H ₂ . (P. A. Chase, G. C. Welch, T. Jurca and D. W. Stephan, Angew. Chem., Int. Ed., 2007, 49, 8050) Also, combinations of the Lewis acid B(C ₆ F ₅ ) ₃ with sterically demanding aldimines and ketimines constitute FLPs that react with H ₂ , affording direct and catalytic reduction to amines.

[0009] It has also been demonstrated that the combinations of the Lewis acid

B(C6F5)3 with sterically hindered tertiary phosphines RJP (R = tBu, CeH ₂ Me3) which show no evidence of adduct formation also react spontaneously with 1 atm H ₂ to effect heterolytic H ₂ cleavage to give the salts [R3PH] [HB(C ₆ F ₅ )3]. (G. C. Welch and D. W. Stephan, J. Am. Chem. Soc, 2007, 129, 1880-1881 ; T. A. Rokob, A. Hamza, A. Stirling, T. Soos and I. Papai, Angew. Chem., Int. Ed., 2008, 47, 1-5.) Further, it has been shown that these FLPs can act as catalysts for the hydrogenation of imines. (P. A. Chase, G. C. Welch, T. Jurca and D. W. Stephan, Angew. Chem., Int. Ed., 2007, 49, 8050-8054.)

[0010] 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 OF THE INVENTION

[0011] An object of the present invention is to provide a process for the use of a frustrated Lewis pair catalyst in hydrogenation and reduction reactions. Another object of the present application is to provide a frustrated Lewis pair catalyst comprising a borenium complex, a weakly coordinating anion, and a Lewis base, which can be a frustrated Lewis base.

[0012] In accordance with one aspect, there is provided a process for reducing an unsaturated substrate comprising reacting the substrate with hydrogen in the presence of a catalyst, the catalyst comprising: a borenium complex having the structure of formula (I),

^Rl \©

B R ³

/

R ²

(T)

wherein R ¹ and R ² are alkyl, aryl, -SR ⁴ , -OR ⁴ or -NR ⁴ R ⁴ , and wherein R ⁴ is independently C ₂ -8 alkyl, each of which is optionally substituted, or R ¹ and R ² can form a cyclic structure together with the boron atom to which they are attached; and

R ³ is a strong base,

or a resonance structure thereof;

a weakly coordinating anion; and

a Lewis base.

[0013] In accordance with one embodiment, the Lewis base is NR ₃ , PR ₃ or CR ₃ , wherein R is alkyl or aryl, each of which is optionally substituted.

[0014] In accordance with another embodiment, the weakly coordinating anion is

^~ OTf, NHTf ₂ , or B(R ⁵ ) ₄ ^~ , wherein each R ⁵ is independently phenyl or Ci-s alkyl optionally substituted with halogen, and 'Tf is triflate. In one preferred embodiment, the weakly coordinating anion is B(C ₆ F ₅ ) ₄ ^~ [0015] In accordance with another embodiment, the borenium complex has the structure of formula (I), and R ³ is carbene or phosphene. In one preferred embodiment, R ³ is a carbene, for example an N-heterocyclic carbene, or a mono-amino-carbene (CAAC), or bent allene species.

[0016] In accordance with another embodiment, the borenium complex is chiral.

[0017] In accordance with another embodiment, the compound of formula (I) is

or a resonance structure thereof, wherein each R is alkyl or aryl, each of which is optionally substituted.

[0018] In accordance with another embodiment, the catalyst is

or a resonance structure thereof, wherein each R is independently alkyl or aryl, which is optionally substituted..

[0019] In accordance with another embodiment, the borenium complex is

or a resonance structure thereof, wherein each R ⁷ is independently alkyl or aryl, each of which is optionally substituted.

[0020] In accordance with one embodiment, the substrate is an imine, enamine, aromatic amine, or aromatic N-heterocycle.

[0021] In accordance with another embodiment, the resulting reduced substrate is chiral.

[0022] In accordance with another embodiment, the process is carried out in the presence of a base.

[0023] In another aspect, there is provided a composition comprising: a borenium complex having the structure of formula (I)

B R ³

/

R ²

(T)

wherein R ¹ and R ² are alkyl, aryl, -SR ⁴ , -OR ⁴ or -NR ⁴ R ⁴ , and wherein R ⁴ is independently C ₂ -8 alkyl, each of which is optionally substituted, or R ¹ and R ² can form a cyclic structure together with the boron atom to which they are attached; and

R ³ is a strong base,

or a resonance structure thereof;

a weakly coordinating anion; and

a Lewis base.

[0024] In accordance with one embodiment, the Lewis base is NR ₃ , CR ₃ or PR ₃ , wherein R is alkyl or aryl, each of which is optionally substituted.

[0025] In accordance with another embodiment, the borenium complex has the structure of formula (I), and R ³ is carbene or phosphene. In one preferred embodiment, R ³ is a carbene, for example an N-heterocyclic carbene, or a mono-amino-carbene (CAAC), or bent allene species. [0026] In accordance with another embodiment, the weakly coordinating anion is

OTf, NHTf ₂ , or B(R ) ₄ , wherein each R is independently phenyl or C _1-8 alkyl optionally substituted with halogen. In one preferred embodiment, the weakly coordinating anion is B(C ₆ F ₅ ) ₄ -

[0027] In accordance with another embodiment, the borenium complex is chiral. [0028] In accordance with another embodiment, the borenium complex is

or a resonance structure thereof, wherein each R is independently alkyl, aryl, each of which is optionally substituted.

[0029] In accordance with another embodiment, the composition comprises

or a resonance structure thereof, wherein R and R are as previously defined.

[0030] In accordance with another embodiment, the borenium complex is

wherein R and R ⁷ are as previously defined. [0031] In accordance with another embodiment, the composition is for use in hydrogenation of an unsaturated bond in a substrate.

[0032] In accordance with another aspect, there is provided a complex having structure:

[0033] In accordance with another aspect, there is provided a complex having the structure:

wherein each R is independently alkyl or aryl, each of which is optionally substituted. [0035] In accordance with another aspect, there is provided a complex having the structure:

wherein each R ⁷ is independently alkyl or aryl, each of which is optionally substituted.

[0036] In accordance with another aspect, there is provided a complex having the structure:

BRIEF DESCRIPTION OF THE FIGURES

[0037] For a better understanding of the present application, 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:

[0038] Figures 1 depicts a Persistence of Vision (POV) depiction of the borenium complex [I( Pr)2-BBN] ⁺ having B-C bond lengths (BBN) of 1.554A and 1.561A, , and a B-C (NHC) bond length of 1.585A, and atomic charges on C-(BBN) of -0.657, C-(NHC) of 0.099, and 1.065 on B;

[0039] Figure 2 depicts a POV depiction of the borohydride I(/Pr) ₂ -BBN hydride complex having B-C bond lengths (BBN) of 1.643 A and 1.644 A, and a B-C (NHC) bond length of 1.640A; and [0040] Figure 3 is a photograph of the the borohydride I(7Pr) ₂ -BBN hydride complex in solid form.

DETAILED DESCRIPTION [0041] Definitions

[0042] 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 application belongs.

[0043] As used in the specification and claims, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise.

[0044] 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.

[0045] Terms of degree such as "substantially", "about" and "approximately", as used herein, will be understood to refer to a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the term it modifies.

[0046] In embodiments comprising an "additional" or "second" component, such as an additional or second compound, the second component as used herein is chemically different from the other components or first component. A "third" component is different from the other, first, and second components, and further enumerated or "additional" components are similarly different.

[0047] The term "suitable", as used herein, means that the selection of the particular compound or conditions would depend on the specific synthetic manipulation to be performed, and the identity of the molecule(s) to be transformed, but the selection would be well within the skill of a person trained in the art. All process/method steps described herein are to be conducted under conditions sufficient to provide the product shown. A person skilled in the art would understand that all reaction conditions, including, for example, reaction solvent, reaction time, reaction temperature, reaction pressure, reactant ratio and whether or not the reaction should be performed under an anhydrous or inert atmosphere, can be varied to optimize the yield of the desired product and it is within their skill to do so.

[0048] As used herein, "alkyl" refers to a linear, branched or cyclic, saturated or unsaturated hydrocarbon group, such as a C _1-2 o alkyl, a Ci-io alkyl or a Ci_6 alkyl, 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- 1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-l- propyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl- 1-pentyl, 3-methyl-l-pentyl, 4-methyl- 1-pentyl,

2- methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl- 1-butyl, 3,3- dimethyl- 1-butyl and 2-ethyl- 1-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, bi cyclic or tricyclic hydrocarbon ring system containing at least 3 carbon atoms. Examples of C3-C12 cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, adamantyl, bicyclo[2.2.2]oct-2-enyl, and bicyclo[2.2.2]octyl.

[0049] As used herein, the term "alkenyl" refers to a straight, branched or cyclic hydrocarbon group containing at least one double bond which is unsubstituted or optionally substituted with one or more substituents. For example, an alkenyl can be a C2-20 alkenyl, a C2-10 alkenyl, or a C2-6 alkenyl.

[0050] As used herein, "alkynyl" refers to an unsaturated, straight or branched chain hydrocarbon group containing at least one triple bond which is unsubstituted or optionally substituted with one or more substituents. For example, an alkynyl can be a C2-20 alkynyl, a C2-10 alkynyl, or a C2-6 alkynyl.

[0051] As used herein, "allenyl" refers to a straight or branched chain hydrocarbon group containing a carbon atom connected by double bonds to two other carbon atoms, which is unsubstituted or optionally substituted with one or more substituents.

[0052] 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 which may or may not be a fused ring system. In some embodiments, the aryl group is an unsaturated aromatic carbocyclic group of from 6 to 50, or from 6 to 25, or from 6 to 15 carbon atoms. The aryls can have a single or multiple rings. The term "aryl" as used herein also includes substituted aryls. Examples include, but are not limited to, substituted and unsubstituted phenyl, naphthyl, xylene, phenylethane, 1,2,3,4-tetrahydronaphthyl, indanyl, indenyl, anthracenyl, 1,2-dihydronaphthyl, fluorenyl, and the like. As used herein,

"heteroaryl" refers to an aryl that includes from 1 to 10, or from 1 to 4, heteroatoms selected from oxygen, nitrogen and sulfur, which can be substituted or unsubstituted.

[0053] The term "alkylene", as used herein, means a bivalent alkyl group.

[0054] As used herein, "substituted" refers to the structure having one or more substituents. A substituent is an atom or group of bonded atoms that can be considered to have replaced one or more hydrogen atoms attached to a parent molecular entity. Examples of substituents include aliphatic groups, halogen, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate ester, phosphonato, phosphinato, cyano, tertiary amino, tertiary acylamino, tertiary amide, imino, alkylthio, arylthio, sulfonato, sulfamoyl, tertiary sulfonamido, nitrile, trifluoromethyl, heterocyclyl, aromatic, and heteroaromatic moieties, ether, ester, boron-containing moieties, tertiary phosphines, and silicon-containing moieties. The term "optionally substituted" means unsubstituted or substituted.

[0055] As used herein, "olefin", also called alkene, refers to an unsaturated hydrocarbon containing one or more pairs of carbon atoms linked by a double bond, and includes cyclic or acyclic (aliphatic) olefins, in which the double bond is located between carbon atoms forming part of a cyclic (closed-ring) or of an open-chain grouping, respectively, and monoolefins, diolefins, triolefins, etc., in which the number of double bonds per molecule is, respectively, one, two, three, or some other number. Such olefins can be substituted or unsubsituted . Specific examples of olefins include, but are not limited to, substituted or unsubsituted 1-propene, 1-butene, 1-pentene, 1- hexene, and 1-octene and substituted or unsubstitued norbornene.

[0056] As used herein, the term "electron withdrawing group" refers to an electronegative group capable of polarizing a bond with a carbon atom. Some non-limiting examples of electron withdrawing groups are halogens, CF ₃ , nitro, nitrile, carbonyl and substituted carbonyl. [0057] 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. The term "heteroaromatic" as used herein refers to a five- or six-membered aromatic ring comprising at least one hetermoiety selected from O, S, N, NH and NCi- ₄ alkyl.

Heteroaromatic groups include, for example, furanyl, thiophenyl, pyrrolyl, 1,2- or 1,3- oxazolyl, 1,2- or 1,3-diazolyl, 1,2,3- or 1,2,4-triazolyl, and the like. The term "heteromoiety" as used herein means a heteroatom-containing moiety.

[0058] As used herein, a "heterocycle" is an aromatic or nonaromatic monocyclic or bicyclic ring of carbon atoms and from 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur, and which can be substituted or unsubstituted. Included within the term

"heterocycle" are heteroaryls, as defined above. Examples of 3- to 9-membered heterocycles include, but are not limited to, aziridinyl, oxiranyl, thiiranyl, azirinyl, diaziridinyl, diazirinyl, oxaziridinyl, azetidinyl, azetidinonyl, oxetanyl, thietanyl, piperidinyl, piperazinyl, morpholinyl, pyrrolyl, oxazinyl, thiazinyl, diazinyl, triazinyl, tetrazinyl, imidazolyl, benzimidazolyl, tetrazolyl, indolyl, isoquinolinyl, quinolinyl, quinazolinyl, pyrrolidinyl, purinyl, isoxazolyl, benzisoxazolyl, furanyl, furazanyl, pyridinyl, oxazolyl, benzoxazolyl, thiazolyl, benzthiazolyl, thiophenyl, pyrazolyl, triazolyl, benzodiazolyl, benzotriazolyl, pyrimidinyl, isoindolyl and indazolyl.

[0059] The term "ring system" as used herein refers to a carbon-containing ring system containing the specified number of carbon atoms and includes monocyclic and poly cyclic rings. Ring systems include saturated, unsaturated or aromatic rings, or mixtures thereof. Where specified the ring system is optionally substituted and/or may optionally contain one or more heteromoieties, such as O, S, N, NH and NCi- ₄ alkyl.

[0060] The term "poly cyclic", as used herein, means a group that contains more than one ring linked together and includes, for example, groups that contain two (bicyclic), three (tricyclic) or four (tetracyclic) rings. The rings may be linked through a single bond, a single atom (spirocyclic) or through two atoms (fused and bridged).

[0061] As used herein, "halogen" or "halo" refers to F, CI, Br or I.

[0062] The term "fluoro-substituted",' as used herein, refers to a group in which one or more, including all, of the hydrogen atoms have been replaced with a fluorine atom. [0063] The term "electrophilic activation", as used herein, means to increase reactivity of a specific atom or functional group (e.g., a carbonyl or carboxyl group) by removal of electron density from that atom or functional group.

[0064] The term "lone pair-containing, heteroatom substituent", as used herein, refers to any chemical group that comprises at least heteroatom with one lone pair of electrons and that is capable of donating electron density to neighbouring atoms. Examples of such groups include, but are not limited to, groups comprising, or consisting of, I, CI, Br, S, O, N, and Se. Where necessary, the heteroatom substituent further comprises one or more Ci- ₄ alkyl and/or C6-ioaryl groups that are optionally further substituted by one or more halo, Ci-4alkyl and/or OCi- ₄ alkyl. In one embodiment the heteroatom in the lone pair-containing heteroatom substituent is the point of attachment of the substituent to the remainder of the molecule.

[0065] The terms "protecting group" or "PG" or the like, as used herein, refer to a chemical moiety which protects or masks a reactive portion of a molecule to prevent side reactions in those reactive portions of the molecule, while manipulating or reacting a different portion of the molecule. After the manipulation or reaction is complete, the protecting group is removed under conditions that do not degrade or decompose the remaining portions of the molecule. The selection of a suitable protecting group can be made by a person skilled in the art. Many conventional protecting groups are known in the art, for example as described in "Protective Groups in Organic Chemistry" McOmie, J.F. W. Ed., Plenum Press, 1973, in Greene, T. W. and Wuts, P.G.M., "Protective Groups in Organic Synthesis", John Wiley & Sons, 3 ^rd Edition, 1999 and in Kocienski, P. Protecting Groups, 3rd Edition, 2003, Georg Thieme Verlag (The Americas). Examples of suitable protecting groups include but are not limited to t-BOC, Ts, Ms, TBDMS, TBDPS, Tf, Bn, allyl, Fmoc, Ci-i ₆ acyl and the like, t- BOC, as used herein, refers to the group f-butyloxy carbonyl. Ac, as used herein, refers to the group acetyl. Ts (tosyl) as used herein refers to the group /?-toluenesulfonyl. Ms, as used herein, refers to the group methanesulfonyl. TBDMS, as used herein, refers to the group t- butyldimethylsilyl. TBDPS as used herein refers to the group f-butyldiphenylsilyl. Tf as used herein refers to the group trifluoromethanesulfonyl, also known as triflate. Ns, as used herein, refers to the group naphthalene sulphonyl. Bn, as used herein, refers to the group benzyl. Fmoc, as used herein, refers to the group fiuorenylmethoxy carbonyl

[0066] As used herein, the term "Lewis acid" refers to an electron deficient molecule, complex, fragment or fragment thereof, or ion that can act as an electron-pair acceptor, and is able to react with a Lewis base to form a Lewis adduct, by sharing the electron pair made available from the Lewis base.

[0067] As used herein, the term "Lewis base" refers to a molecule, complex, fragment or fragment thereof, or ion that can act as an electron pair donor, and is able to react with a Lewis acid to form a Lewis adduct by sharing its electron pair.

[0068] As used herein, the term "borenium complex" refers to a cationic organic boron species wherin the boron atom is positively charged. It is understood that the positive charge can be delocalized depending on the structure of the complex. Therefore, though the borenium complex is often depicted with the cationic charge on the boron atom, it is understood that resonance structures can exist.

[0069] As used herein, the term "carbene" refers to a molecule comprising a neutral carbon atom with a valence of two, and two valence electrons available for formation of a bond, for example with a boron atom. Alternatively, the term "carbene" is understood to be a bivalent carbon donor. An "N-heterocyclic carbene" or "NHC" is a type of carbene in which the carbenic carbon is part of a nitrogen-containing heterocycle, such as an imidazole.

[0070] As used herein, the terms "saturated N-heterocyclic carbene", "saturated

NHC", and "sNHC" refer to diamino heterocyclic carbenes in which the carbenic carbon connects the two nitrogen atoms, and the remaining carbon atoms in the heterocycle are saturated (i.e., they are connected via single bonds). In some examples, the sNHC is a five membered or a six membered heterocycle.

[0071] As used herein, the term "weakly coordinating anion" refers to a species that retains a negative charge, in which the charge is delocalized over the fragment and/or sterically protected. This species of anion is a poor donor to a Lewis acidic centre. In the extreme, such anions become non-coordinating anion but typically establish an equilibrium between coordination and non-coordination in which the latter dominates. In the presently described system, the charge derealization and/or sterics of this species prevent it from blocking the reactivity of the borenium complex.

[0072] As used herein, the terms "reducing", "reduction" and "hydrogen reduction" refer to reactions commonly known in the art wherein two hydrogen atoms are added across an unsaturated bond. For example, a double bond can be reduced to generate a single bond. Common double bond types that can serve as substrates for reduction reactions are imines, alkenes, enamines, ketones, olefins, alkynes, and aromatic and heteroaromatic substrates including phenyl and heterocycles.

[0073] As used herein the term "substrate" refers to the chemical species that is the starting material for the present hydrogenation reactions. Substrates used in the presently described reactions are those having at least one reduceable bond that is unsaturated. Some examples of reduceable bonds include imines, alkenes, alkynes, aromatic groups and ketones.

[0074] As used herein the term "strong base" refers to a basic chemical species that is used to form a bond with and stabilize the borenium. The combination of the borenium complex and the strong base forms the borenium complex or Lewis acid species. Non- limiting examples of a strong base are amine, phosphine or carbene.

[0075] Catalyst Activity

[0076] The present application describes a process for catalytic hydrogenation of a variety of organic substrates using the catalysts as described herein. The present reactions do not require the use of an additional metal or metal catalyst to carry out the hydrogenation reactions.

[0077] Also described are frustrated Lewis pair catalysts that can be used in a variety of chemical transformations of organic molecules.

[0078] The presently described catalysts can catalyse the reduction of a variety of different substrates to form hydrogenated products. Some example reduction reactions are summarized in Table 1 below.

Table 1: Examples of Substrate-Product pairs for FLP Cataly

In some specific examples, FLPs have been shown to be capable of performing the hydrogenating reactions shown in Table 2. (Chase, P. A., Welch, G. C, Jurca, T., Stephan, D. W. Angew. Chem. Int. Ed. 2007, 46, 8050 -8053; Spies, P., Schwendemann, S., Lange, S., Kehr, G, Frolich, R, Erker G. Angew. Chem. Int. Ed. 2008, 47, 7543 -7546; Wang, H., Frohlich, R., Kehr G, Erker, G. Chem. Commun., 2008, 5966; Sumerin, V., Schulz, F., Atsumi, M., Wang, C, Nieger, M., Leskela, M., Repo, T., Pyykko P., Rieger, B. J. Am.

Chem. Soc, 2008, 130, 14117; Chase, P. A, Jurca, T., Stephan, D. W. Chem. Commun., 2008, 1701-1703; Chen, D., Klankermayer, J. Chem. Commun., 2008, 2130-2131). The presently described catalysts can also function to perform these hydrogenation reactions.

Table 2: Specific Examples of Substrate-Product pairs for FLP Catalysis

[0079] In one embodiment of the present application, the catalysts are useful for direct reduction of an unsaturated bond reaction in the presence of H ₂ . In this case, the substrate is exposed to the H ₂ reducing reagent in the presence of a presently described catalyst, affording direct hydrogenation of the substrate.

[0080] The present catalysts can assist in the direct hydrogenation of the substrate with molecular hydrogen. The present catalysts can also be employed in stoichiometric, and sub-stoichiometric amounts or catalytic amounts, to arrive at the reduced product.

[0081] Catalyst Structure

[0082] The present catalysts are formed from reaction of a secondary boron with a strong base to form a borohydride zwitterion. Further reaction of this zwitterion with a hydride abstractor results in abstraction of a hydride from the zwitterion to generate the borenium complex. The general reaction scheme is shown in scheme 1.

[hydride abstractor]

[weakly coordinating anion]

coordinating anion]

Scheme 1: General Synthesis of Complex

[0083] The secondary boron species can be any boron atom bound to two non- hydrogen atoms and one hydrogen atom. The non-hydrogen atoms can be any suitable group that forms a bond with boron. Non-limiting examples of the non-hydrogen atoms are alkyl, alkoxy, dialkylamine, alkylsilane, alkylphosphone, and thioalkyl. Some preferred examples of secondary boron species are dialkyl boron hydrides. Abstraction of the hydride from the B- H bond in the boron hydride species generates a borenium, which is the Lewis acid in the frustrated Lewis pair of the active complex. [0084] A strong base, such as but not limited to amine, phosphine or carbene, is used to form a bond with and stabilize the borenium. The combination of the borenium complex and the strong base forms the borenium complex or Lewis acid species. As defined above, a carbene is any species that has a carbon atom with an electron pair capable of forming a bond with the secondary boron species. The carbene can be saturated or unsaturated, acyclic or part of a cyclic structure. If part of a cyclic structure, the cyclic structure can be non- aromatic, aromatic or heteroaromatic. In one preferred embodiment, the carbene is chiral. One example of a strong base that can stabilize the boron is N-heterocyclic carbene (NHC). Other examples of strong bases are mono-amino-carbene (CAAC), and bent allene species.

[0085] A strong hydride abstracting agent is required for abstracting the proton from the secondary boron species to generate the borenium complex. The hydride abstracting agent is a Bronsted or Lewis acid capable of forming a strong bond with hydride, and of abstracting the hydride from the boron zwitterion. Some examples of acceptable hydride removing agents are iminium, carbocations, trialkylphosphonium, or trityl cation. The hydride abstractor with the added hydride subsequent to abstraction from the boron zwitterion is the Lewis base in the frustrated Lewis pair. The abstraction can also be effected by treatment with an acid that provides a weakly coordinating anion. One example of this is triflic acid. This will result in the evolution of H ₂ and formation of the borenium.

[0086] A weakly coordinating anion functions to charge stabilize the borenium complex. This species has an overall negative charge, in which the charge is delocalized to minimize coordination with the borenium complex but maintain charge balance in the composition. Non-limiting examples of these anions are carboranes, bulky

tetraalkoxyaluminates, or B(R ⁵ ) ₄ ^~ , wherein each R ⁵ is independently phenyl or C _1-8 alkyl optionally substituted with halogen Some specific examples of anions are than [B(C ₆ F ₅ ) ₄ ] ^" , ^" OTf or NHTf ₂ . The weakly coordinating anion can be incorporated into the catalyst complex by way of addition of the weakly coordinating anion as a salt with the hydride abstracting agent. One general example of this is [PhsC][BR4]. One preferred, specific example is trityl tetrakis(pentafluorophenyl)borate (also referred to herein as [trityl] [BArF]), where the hydride abstractor trityl is ion-paired with the weakly coordinating anion

tetrakis(pentafluorophenyl)borate. [0087] When the strong base is a carbene, the carbene reacts with the secondary boron to generate a boron hyride zwitterion, as shown in Scheme 2. In the below case, the hydride abstractor is H ⁺ or E ⁺ , and the weakly coordinating anion is X ^" .

H ₂ or E-H

Scheme 2: General Synthesis of Complex from Carbene

[0088] To generate the active catalytic species, an acidic reagent can be used to remove the B-H hydride from the boron hydride species. This generates the active borenium catalyst, which is the Lewis acid partner of the frustrated Lewis catalyst pair. The Lewis acid portion of the complex, specifically the borenium, has a positive charge that is stabilized in the catalyst composition by the weakly coordinating anion.

[0089] In the zwitterionic form as well as the borenium complex, the charges are not point charges, but can be delocalized depending on the strucutre of the complex. It is understood that thought the cationic charge is depicted on the boron atom in the borenium complex, the denoted charge is indicative of the charge of the complex generally, and that the charge may be delocalized in the complex. In one example, in the borenium complex 1 ,3- diisopropylimidazol-2-ylidene-9-borabicyclo[3.3.1]nonane ([I( Pr)2-BBN] ⁺ ), the calculated Natural bond orbital (NBO) charge on C-(BBN) is -0.657, on C-(NHC) is 0.099, and on B is 1.065. The POV molecular structure of this complex is shown in Figure 2.

[0090] In one specific example, the carbene is an N-heterocyclic carbene and the boron formed is an NHC-boreneium complex.

Scheme 3: Formation of NHC-borenium Complex [0091] In one example, a catalyst species is formed by reaction of 9-BBN with an N- heterocyclic carbene (NHC) base. The hydride is then removed to generate the active borenium catalyst. A reaction scheme summarizing one specific example of this reaction is shown below:

9-BBN NHC

Scheme 4: I/Pr ₂ -BBN borenium B(C ₆ F ₅ ) ₄ catalyst formation

[0092] Once the phosphonium salt and zwitterionic borohydride come into contact with an unsaturated bond, such as an imine, their respective proton and hydride are transferred to the unsaturated bond in a stoichiometric hydrogenation. In scheme 4, this also generates free phosphine and the borenium [B(C ₆ F ₅ ) ₄ ] catalyst. As previously described, the borenium complex can then pick up a hydrogen from H ₂ to carry on the catalytic cycle.

[0093] 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

[0094] Example 1 : Synthesis of Catalysts

[0095] General considerations

[0096] All synthetic manipulations were carried out under an atmosphere of dry, 0 ₂ - free N ₂ employing an MBraun glove box and a Schlenk vacuum-line. Solvents were purified with a Grubbs-type column system manufactured by Innovative Technology and dispensed into thick-walled glass Schlenk bombs equipped with Young-type Teflon valve stopcocks (pentane, dichloromethane, toluene). [0097] Deuterated solvents were obtained from Cambridge Isotope Laboratories and used without further purification except where noted. Bromobenzene-c j, chlorobenzene, dichloromethane, and dichloromethane-^ were each dried over CaH ₂ , vacuum-transferred into a Young bomb, and stored over 4 A molecular sieves. Toluene-c¾ was dried over Na/benzophenone, vacuum-transferred into a Young bomb, and stored over 4 A molecular sieves. All solvents were thoroughly degassed after purification (three freeze-pump-thaw cycles). NMR spectra were recorded at 25°C on a Bruker Avance 400 MHz spectrometer or an Agilent DD2 500MHz spectrometer unless otherwise noted.

[0098] Commercially available substrates diisopropylimidazolium chloride, potassium hexamethyldisilazane and 9-BBN dimer were obtained from Sigma- Aldrich and used without further purification. Liquid substrates were stored over 4 A molecular sieves or distilled from triisobuylaluminum and stored in an inert atmosphere glovebox. Solid substrates were dried in vacuo and stored in an inert atmosphere glovebox. Trityl tetrakis(pentafluorophenyl)borate was obtained from Nova Chemicals and used without further purification.

[0099] Hydrogen gas (Grade 5.0) was obtained from Linde and purified through a

Matheson Model 450B or Matheson Nanochem WeldAssure™ gas purifier. Chemical shifts are given relative to SiMe ₄ and referenced to the residual solvent signal ( H, ¹³ C) or relative to an external standard ( ⁿ B: 15% (Et ₂ 0)BF ₃ ; ¹⁹ F: 15% (Et ₂ 0)BF ₃ ; ³¹ P: 85% H ₃ P0 ₄ ). In some instances, signal and/or coupling assignment was derived from two-dimensional NMR experiments. Chemical shifts are reported in ppm and coupling constants as scalar values in Hz. Combustion analyses were performed in house employing a Perkin-Elmer CHN

Analyzer. Mass spectrometry was carried out using and AB/Sciex QStar mass spectrometer with an ESI source. (+)-diispinocampheylborane and 1,3-dimethylimidazolium iodide were prepared by literature procedures (Greszler , S. N.; Malinowski , J. T.; Johnson J. S. Org. Lett., 2011, 13, 3206-3209; Oertel, A. M.; Ritleng, V.; Burr, L.; Chetcuti, M. J.

Organometallics 2011 , 30, 6685 - 6691.) [00100] Synthesis of l,3-diisopropylimidazol-2-ylidene-9-borabicyclo[3.3.1]nonane (IiPr ₂ -BBN)

9-BBN NHC

Scheme 5: Synthesis of IiPr ₂ -BBN

[00101] l,3-Diisopropylimidazol-2-ylidene and [ίΒ¾ΡΗ] [B(C ₆ F ₅ ) ₄ ] were prepared using literature methods. (Schaub, T.; Backes, M.; Radius, U. Organometallics 2006, 25, 4196-4206; International PCT Patent Application No. WO 2006/004376, Filing Date: July 5, 2005)

[00102] In an inert atmosphere glovebox, l,3-diisopropylimidazol-2-ylidene (2 equivalents, 813.8 mg, 5.276 mmol) and 9-BBN dimer (1 equivalent , 707.3 mg, 2.638 mmol) were weighed into vials. 9-BBN was stirred in 7 mL toluene as a solution of 1,3- diisopropylimidazol-2-ylidene in 5 mL toluene was transferred dropwise with 2 x 1 mL additional toluene. The vial was capped and stirred for four hours at room temperature. The solution was concentrated in vacuo to approximately 2 mL and recrystallized in a -35°C freezer. The supernatant was decanted and the colorless crystals were washed with cold pentane (3x1 mL) and dried in vacuo to give 1.1533g I Pr ₂ -BBN (75.8% yield).

[00103] ¾ NMR (400 MHz, C ₆ D ₅ Br, 298 K): δ 6.55 (s, 2H), 5.20 (m(7), 2H, ³ J _HH =

7Hz), 2.40-1.36 (br, 14H), 1.11 (d, 12H, ³ J _HH = 7Hz), No observable B-H peak. ⁿ B NMR (128 MHz, C ₆ D ₅ Br, 298 K): δ -16.64 (d, VBH = 80HZ). "C ^H} NMR (101 MHz, CD ₂ C1 ₂ , 298 K, partial): 125.6, 115.5, 48.2, 38.2, 31.6, 25.5, 24.0, 23.6, 23.4 (br). Elemental Analysis: Calculated: C 74.18%, H 11.72%, N 10.18%; Experimental: C 74.36%, H 11.44%, N 10.16% [00104] Synthesis and Isolation of [l,3-diisopropylimidazol-2-ylidene-9- borabicyclo[3 A]nonane] tetrakis(pentafluorophenyl)borate]([(IiPr2)(BCsHi4)][B(C ₆ F5)4]* 0.66 CeHsCl)

[00105] In an inert atmosphere glovebox, (I Pr ₂ )(HBC ₈ Hi ₄ ) (1.161 g, 4.233 mmol, 1 equiv.) was dissolved in 10 mL dry toluene in a 100 mL Shlenk flask equipped with a stir bar. Trityl tetrakis(pentafluorophenyl)borate (3.904 g, 4.233 mmol, 1 equiv.) was weighed into a vial and transferred with 20 + 10 mL toluene to the solution of LPr ₂ -BBN while stirring. The mixture was stirred overnight during which time a gelatinous precipitate was generated. The solvent was removed in vacuo and the off-white residue redissolved in 20 mL chlorobenzene. This solution was cooled to -35 °C in a glovebox freezer to afford colourless crystals. The chlorobenzene was decanted and the crystals washed with 5 x 1 mL pentane to give an off- white powder. This powder was again dissolved in 20 mL chlorobenzene and cooled to -35 °C in a glovebox freezer to afford colourless crystals. The chlorobenzene was decanted and the crystals washed with 5 x 1 mL pentane. The sample was dried in vacuo at room temperature for 24 hours to give [(LPr ₂ )(BC ₈ Hi ₄ )][B(C6F ₅ ) ₄ ] ^» 0.66 C ₆ H ₅ C1 as a white powder (3.521 g, 81.0% yield).

[00106] Ratio of C ₆ H ₅ C1 to was determined by ¾i NMR and confirmed by elemental analysis. ¾ NMR (400 MHz, CD ₂ C1 ₂ , 298 K) (C ₆ H ₅ C1 omitted): δ 7.55 (s, 2H), 4.65 (m(7), 2H, ³ JHH = 6.7 Hz), 2.34-2.13 (m, br, 6H), 2.08-2.01 (m, br, 2H), 1.99-1.85 (m, br, 4H), 1.62-1.50 (m, br, 2H), 1.58 (d, 12H, ³ J _HH = 6.7 Hz). ⁿ B NMR (128 MHz, CD ₂ C1 ₂ , 298 K): δ 83.8 (br), -16.7. "C^H} NMR (101 MHz, CD ₂ C1 ₂ , 298 K, partial) (C ₆ H ₅ C1 omitted): δ 122.0, 53.5, 34.9, 33.9 (br), 24.1, 22.8. ¹⁹ F NMR (376 MHz, CD ₂ C1 ₂ , 298K): δ -134.1 (o-F, m), -164.7 (p-F, t, ³ J _FF = 20 Hz), -168.6 (m-F, m). Anal. Calcd. for C ₄ iH ₃ oB ₂ F ₂ oN ₂ ^» 0.66(C ₆ H ₅ C1): C 52.61%, H 3.27%, N 2.73%. Found: C 52.56%, H 3.46%, N 2.64%. [00107] Catalyst Activation

[00108] The present catalysts can be activated in situ to form the active borenium complex. The activation is carried out with a hydride abstractor to remove hydride from the boron to yield the borenium complex. The borenium complex is the Lewis acid in the frustrated Lewis pair, and the conjugate base of the hydride abstractor and/or the substrate is the Lewis base in the frustrated Lewis pair.

Scheme 6: Activation of I/Pri-BBN

[00109] Example 2: Reduction of Imines

[00110] Varying reaction conditions

[00111] Reduction of phenyl imines was performed using the substrate N-benzylidene tert-butylamine, and a meta-methoxy variant thereof, according to Scheme 7.

Scheme 7: Example Hydrogenation of an Imine

[00112] Reaction 1

[00113] In a glovebox LPr ₂ -BBN(10.8 mg, 0.0438 mmol, 1 eq), [iBu ₃ PH] [B(C ₆ F ₅ )4]

(38.3 mg, 0.0438, 1 eq) and N-benzylidene-ieri-butylamine (68.2 mg, 0.423 mmol, 10 eq.) were weighed into vials. The contents of the vials were transferred to a J-Young NMR tube with 0.6 niL C ₆ D ₅ Br. The tube was sealed and subjected to three freeze-pump-thaw cycles. The sample was then frozen and the tube was backfilled with hydrogen gas, sealed and carefully thawed. Conversion of N-benzylidene-ferf-butylamine to N-benzyl-ferf-butylamine was observed by ^-NMR.

[00114] Reaction 2

[00115] In a glovebox I;Pr ₂ -BBN(3.9 mg, 0.016 mmol, 1 eq), [iBu ₃ PH][B(C ₆ F ₅ )4]

(14.0 mg, 0.0159 mmol, 1 eq) and N-benzylidene-ferf-butylamine (255.4 mg, 1.584 mmol, 100 eq.) were weighed into vials. N-benzylidene-ieri-butylamine and I Pr ₂ -BBN were transferred to the vial containing [iBu3PH][B(C6Fs)4] using 0.6 mL toluene. The vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm hydrogen and ten times at 102 atm hydrogen. The reactor was sealed under 102 atm hydrogen and placed on a stir plate for 2 hours at room temperature. The reactor was then slowly vented and the sample was concentrated in vacuo. Conversion of N-benzylidene-ieri-butylamine to N-benzyl-ferf-butylamine was determined by ^-NMR in toluene-d ₈ .

[00116] Reactions 3-6

[00117] Reactions 3-6 were carried out in a similar method as described for reaction 2.

For reactions 5 and 6, stock solutions of I Pr ₂ -BBN and [fBu ₃ PH][B(C6F ₅ ) ₄ ] in C ₆ H ₅ C1 were used. Product conversions were determined by ^-NMR comparison to literature values:

N-Benzyl-ferf-butylamine: Froyen, P.; Juvvik, P. Tetrahedron Lett. 1995, 36, 9555-9558;

1,2,3,3-Tetramethylindoline: Tolmachev, A. A. Khim. Geterotsikl. Soedin. 1986, 11, 1474- 1477;

8-Methyl-l,2,3,4-tetrahydoquinoline: Murahashi, S.-I.; Imada, Y.; Hirai, Y. Bull. Chem. Soc. Jpn. 1989, 62, 2968-2976;

N-Benzyl-(diphenylmethyl)amine: Likhar, P. R.; Arundhathi, R.; Kantam, M. L.; Prathima,

P. S. European Journal of Organic Chemistry 2009, 2009, 5383; 2,2,2-trifluoro-l-phenylethanol: Hevia, E.; Kennedy, A. R.; Klett, J.; Livingstone, Z.;

McCall, M. D. Dalton Transactions 2010, 39, 520;

Except :

N-benzyl-phenylsulfonamine: Not detected;

N-ferf-butyl-(3-methoxy)-benzyl amine : ¾ NMR (400 MHz, CD ₂ C1 ₂ , 298 K): δ 7.20 (t, 1H), 6.93-6.88 (m, 2H), 6.77-6.72 (m, 1H), 3.79 (s, 3H), 3.69 (s, 2H), 1.14 (s, 9H), No observable N-H. NMR (101 MHz, CD ₂ C1 ₂ , 298 K): 160.2, 144.3, 129.7, 120.9, 114.2, 112.4,

55.6, 51.0, 47.6, 29.4;

N-cyclopentylpiperidine: ¾ NMR (400 MHz, CD ₂ C1 ₂ , 298 K): δ 2.55-2.30 (m, 5H), 1.90- 1.79 (m, 2H), 1.75-1.30 (m, 12H).

Table 3: Hydrogenation of imines using IiPr ₂ -BB /[iBu3PH][B(C ₆ F5)4]

00118 Pro ression o Reaction

10% conversion

(stoichiometric add ition) 24 h 26% conversion

72 h 58% conversion 120h 73% conversion

Scheme 8: Conversion rates of IiPr ₂ -BBN

[00119] In a glovebox IiPr ₂ -BBN(10.8 mg, 0.0438 mmol, 1 eq), [iBu ₃ PH][B(C ₆ F ₅ )4]

(38.3 mg, 0.0438, 1 eq) and N-benzylidene-ieri-butylamine (68.2 mg, 0.423 mmol, 10 eq.) were weighed into vials. The contents of the vials were transferred to a J-Young NMR tube with 0.6 mL C ₆ D ₅ Br. The tube was sealed and subjected to three freeze-pump-thaw cycles. The sample was then frozen and the tube was backfilled with hydrogen gas, sealed and carefully thawed. Conversion of N-benzylidene-ferf-butylamine to N-benzyl-ferf-butylamine was observed by ^-NMR.

[00120] Example 3: Reduction of Enamines and N-heterocycles

[00121] The following reactions were carried out in a similar method as described for

Example 2.

Table 4: Hydrogenation of enamines using IiPr ₂ -BB /[iBu3PH][B(C ₆ F5)4]

[00122] Example 4: Hvdrogenation reactions with borenium catalyst generated in situ with trityl tetrakis(pentafluorophenyl)borate

[00123] In this series of reactions, trityl tetrakis(pentafluorophenyl)borate was used to abstract the hydride. These experiments show that the substrates can act as the base in the FLP reaction. In this series of experiments, the rates of reaction are improved.

substrate product

Scheme 9: Hydrogenation with borenium complex and trityl

[00124] In a glovebox I/Pr ₂ -BBN(25.0 mg, 0.0912 mmol, 1 eq), [Ph ₃ C] [B(C ₆ F5)4]

(84.1 mg, 0.0912 mmol, 1 eq) and l,3,3-trimethyl-2-methyleneindoline (316.0 mg, 1.824 mmol, 100 eq.) were weighed into vials. [Ph3C][B(C6Fs)4] was transferred to the vial of I/Pr ₂ - BBN with 0.4 mL C6H5CI. This solution was then transferred to the vial containing 1,3,3- trimethyl-2-methyleneindoline. This vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm hydrogen and ten times at 102 atm hydrogen. The reactor was sealed under 102 atm hydrogen and placed on a stir plate for 4 hours at room temperature. The reactor was slowly vented and the sample was concentrated in vacuo. Conversion of N-benzylidene-teri-butylamine to N- benzyl-ferf-butylamine was determined by ^-NMR in toluene-ds or CDCI ₃ . Table 5: In situ Hydrogenation with trityl

[00125] Example 5: Hydrogenation reactions with borenium catalyst generated in situ with Bis(trifluoromethanesulfonyl)imide

[00126] This Example demonstrates successful hydride abstraction from the boron hydride with a strong acid. substrate prod uct

Scheme 10: Strong Acid

[00127] The procedure was as described above for Example 5, except that bis(trifluoro-methanesulfonyl)imide (HNTf ₂ ) was used in place of trityl

tetrakis(pentafluorophenyl)borate.

Table 6: In situ H drogenation with H Tf ₂

[00128] Example 6: Hydrogenation attempt with zwitterionic borohydride

[00129] This Example demonstrates that the borenium complex was required for an active catalyst. Specifically, if a borenium complex is not generated, no catalysis occurred. The zwitterionic borohydride species was therefore the "unactivated" or inactive species in the catalytic cycle.

Scheme 11: Hydride transfer to Unsaturated bond from Zwitterion

[00130] In a glovebox I/Pr ₂ -BBN(5.0 mg, 0.01823 mmol, 1 eq) was transferred to a vial containing N-benzylidene-ferf-butylamine (294 mg, 1.823 mmol, 100 eq.). This vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm hydrogen and ten times at 102 atm hydrogen. The reactor was sealed under 102 atm hydrogen and placed on a stir plate for 4 hours at room temperature. The reactor was slowly vented and the sample was concentrated in vacuo. No conversion of N-benzylidene-ferf-butylamine to N-benzyl-ferf-butylamine was observed by ^-NMR in CDCls.

[00131] Example 7: Hvdrogenation Catalysis in the presence of an Additional Base

[00132] Hydrogenation reactions were carried out on substrate N-piperidine-1- cylcopentene in the presence of a base according to Scheme 12.

base,

0.6 mL C ₆ H ₅ CI,

102 atm. H ₂ ,

r.t.

DABCO: N N TMP:

Scheme 12: Catalysis with Additional Base [00133] The results are shown in Table 7.

Table 7: Catalysis with Additional Base

[00134] Example 8: Chiral Hydrogenation

[00135] Chiral borohydrides were synthesized according to the following general scheme:

Scheme 13: Synthesis of Chiral Borohydrides [00136] Example 9: Catalytic hydrogenation of unsaturated substrates using ra Pr ₇ )ffiC«HM)i rB(C _fi F dl ^« 0.66 C.H.C1

substrate product

102 atm. H ₂

Scheme 14: Catalytic Hydrogenation

[00137] Procedure 1. (Entries 2, 8, 10): In an inert atmosphere glovebox,

(25.0 mg, 0.0912 mmol, 5 equiv. or 5.0 mg, 0.018 mmol, 1 equiv.),

[Ph ₃ C] [B(C ₆ F5)4] (84.1 mg, 0.0912 mmol, 5 equiv. or 16.8 mg, 0.0182 mmol, 1 equiv.) and the unsaturated substrate (1.824 mmol, 100 equiv.) were weighed into vials. [Ph ₃ C] [B(C6F ₅ ) ₄ ] was transferred to the vial of TPr ₂ -BBN with 0.4 mL C ₆ H5CI. This solution was then transferred to the vial containing the unsaturated substrate with an additional 0.2 mL CeHsCl. This vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm with hydrogen gas and ten times at 102 atm with hydrogen gas. The reactor was sealed under 102 atm hydrogen gas and placed on a stir plate for 2 or 4 hours at room temperature. The reactor was slowly vented and an NMR sample was taken in toluene-c g or CDCI ₃ . Conversion of unsaturated substrate to amine product was determined by ¾ NMR spectroscopy.

[00138] Entry 9 was isolated by removal of solvent in vacuo followed by column chromatography using 99: 1 hexanes : EtOAc using silica gel pre-treated with diethylamine.

[00139] Procedure 2. (Entries 1, 4-7, 9, 11): In an inert atmosphere glovebox,

[(LPr2)(BC8Hi4)] [B(C ₆ F5)4h 0.66 C ₆ H ₅ C1 (18.7 mg, 0.0182 mmol, 1 equiv. or 93.6 mg,

0.09115 mmol, 5 equiv.) and the unsaturated substrate (1.824 mmol, 100 equiv.) were weighed into vials. [( ^' Pr ₂ )(BC ₈ H ₁₄ )] [B(C ₆ F ₅ ) ₄ ] ^» 0.66 C ₆ H ₅ C1 was transferred to the vial containing the substrate with 0.6 mL CH2CI2. This vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm with hydrogen gas and ten times at 102 atm with hydrogen gas. The reactor was sealed under 102 atm hydrogen gas and placed on a stir plate for 2 or 4 hours at room temperature. The reactor was slowly vented and an NMR sample was taken in CDCI ₃ . Conversion of unsaturated substrate to amine product was determined by ¾ NMR spectroscopy.

[00140] Entries 2, 5, 6, 7, and 12 were isolated by removal of solvent in vacuo followed by column chromatography using 9: 1 hexanes : EtOAc using silica gel pre-treated with diethylamine.

[00141] Procedure 3. (Entry 4): Procedure 1 was followed with the modification that toluene was used in place of C ₆ H5CI.

[00142] The results of Procedures 1-3 as described above are shown in Table 8, wherein % yield is based on 1H NMR, with isolated yield in parentheses.

Table 9: Catalysis with [(IiPr ₂ XBC ₈ H ₁₄ )] [B(C ₆ F ₅ ) ₄ ] ^« 0.66 C ₆ H ₅ C1

[00143] Isolated products were characterized by H and ¹³ C NMR spectroscopy as well as mass spectrometry and compared to literature values where applicable. Product conversions by H NMR spectroscopy were determined by comparison to literature values for entry 11 : 8-Methyl-l,2,3,4-tetrahydoquinoline: (Murahashi, S.-I.; Imada, Y.; Hirai, Y. Bull. Chem. Soc. Jpn. 1989, 62, 2968-2976.)

[00144] N-benzyl-ferf-butylamine: Froyen, P.; Juvvik, P. Tetrahedron Lett. 1995, 36, 9555-9558. (colourless oil Yield: 0.235 g, 79%) ¾ NMR (CDC1 ₃ , 400 MHz): δ 7.25 and 7.23 (m, 4H, o and m-P -H); 7.15 (tt, lH, /?-Ph-H, ³ J _HH = 6.9 Hz, ⁴ J _HH = 1 6 Hz); 3.65 (s, 2H, CH ₂ ); 1.11 (s, 9Η, 'Bu-CHs). ^C^H} NMR (CDC1 ₃ , 100.7 MHz): δ 141.37 (s, IC, ipso-F - C); 128.21, 128.10, and 126.57 (s, 5C, Ph-C); 50.46 (s, IC, 'Bu-C); 47.14 (s, 2C, H ₂ ); 29.03 (s, 3C, 'Bu- Hs). HR-MS Calcd for CiiH _n N: [M ⁺ ] 164.14392. Found: m/z 164.14460.

[00145] N-ieri-butyl-(3-methoxybenzyl)amine: (colourless oil Yield: 0.309 g, 88%) ^X H NMR (CDCls, 400 MHz): δ 7.22 (dd, 1H, 5-Ph-H, RH = 8.0 Hz, ³ J _HH = 8.0 Hz); 6.93 (s, 1H, 2-Ph-H); 6.93 (m, 1Η, 4-Ph-H); 6.78 (dd, 1Η, 6-Ph-H, RH = 8.3 Hz, RH = 2.2 Hz); 3.80 (s, 1H, OCH3); 3.71 (s, 2Η, CH ₂ ); 1.17 (s, 9Η, 'Bu-CHs). "C^H} NMR (CDC1 ₃ , 100.7 MHz): δ 158.71 (s, IC, ipso-F -COMe); 141.75 (s, IC, ipso-F -Q; 128.35, 119.58, 121.84, and 111.35 (s, 4C, Ph-C); 54.14 (s, IC, OCH ₃ ); 49.88 (s, IC, 'Bu-C); 46.21 (s, 2C, CH ₂ ); 28.00 (s, 3C, 'BU-CHS). HR-MS Calcd for Ci ₂ Hi ₉ NO: [M ⁺ ] 194.15449. Found: m/z

194.15513.

[00146] N-cyclohexylpiperidine: Spies, P.; Schwendemann, S.; Lange, S.; Kehr, G.; Frohlich, R.; Erker, G. Angew. Chem. Int. Ed. 2008, 47, 7543-7546. (colourless oil Yield: 0.259 g, 85%) ¾ NMR (CDC1 ₃ , 400 MHz): δ 2.34 (dd, 4H, CH ₂ N, RH = 5.3, 5.1 Hz); 2.08 (m, 1H, CH); 1.68 and 1.60 (d, 2Η, RH = 5.9 Hz); 1.45 (d, 1H, RH = 6.2 Hz); 1.41 (dd, 4H, 3JHH = 6.1, 5.9 Hz); 1.38 (d, 1H, RH = 6.2 Hz); 1.25 (m, 2H); 1.05 (d, 2H, RH = 8.5 Hz); 1.04 (d, 2H, _HH = 9.4 Hz). "C^H} NMR (CDC1 ₃ , 100.7 MHz): δ 64.17 (s, IC, CH); 49.84 (s, 2C, CH ₂ N); 28.45 (s, 2C, CHCH ₂ ); 26.24 (s, 2C, CH ₂ CH ₂ N); 25.94 (s, 3C,

CHCH ₂ CH ₂ CH ₂ ); 24.70 (s, IC, CH ₂ CH ₂ CH ₂ N). HR-MS Calcd for C11H21N: [M ⁺ ] 168.17522. Found: m/z 168.17514.

[00147] N-cyclopentylpiperidine: (colourless oil Yield: 0.262 g, 94%) ¾ NMR (CDCI ₃ , 400 MHz): δ 2.30 (m, 5H, CH ₂ N and CH); 1.70, 1.53, 1.46, 1.38, and 1.29 (m, 14Η, CH ₂ CH ₂ CH ₂ N and CHCH ₂ CH ₂ ). NMR (CDC1 ₃ , 100.7 MHz): δ 67.95 (s, IC, CH);

53.35 (s, 2C, CH ₂ N); 30.29 (s, 2C, CHCH ₂ ); 25.81 (s, 2C, CH ₂ CH ₂ N); 24.39 (s, IC,

CH ₂ CH ₂ CH ₂ N); 24.05 (s, 2C, CHCH ₂ CH ₂ ). HR-MS Calcd for C10H19N: [M ⁺ ] 154.15957. Found: m/z 154.16002.

[00148] 1,2,3,3-tetramethylindoline: Tolmachev, A. A. Khim. Geterotsikl. Soedin.

1986, 11, 1474-1477. (pale yellow oil Yield: 0.301 g, 94%) ¾ NMR (CDC1 ₃ , 400 MHz): δ 7.28 (ddd, 1H, 3-C ₆ H ₄ -H ³ J _HH = 8.9, 7.8 Hz, HH = 1.1 Hz); 7.21 (dd, 1H, 5-C ₆ H ₄ -H ³ J _HH = 7.8 Hz, _HH = 0.8 Hz); 6.93 (ddd, 1H, 4-C ₆ H ₄ -H V _HH = 8.9, 7.6 Hz, V _HH = 0.8 Hz); 6.70 (d, 1H, 2-C ₆ H ₄ -H _HH = 7.8 Hz); 3.08 (q, 1H, CH, V _HH = 6.6 Hz); 2.90 (s, 3H, NCH ₃ ); 1.52 and 1.26 (s, 6Η, CH ₃ ); 1.14 (d, 3Η, CHCH ₃ , V _HH = 6.6 Hz). ^l3 C{ ^l ] NMR (CDC1 ₃ , 100.7 MHz): δ 152.10 (s, IC, \-ipso-C); 139.26 (s, IC, 6-ipso-C); 127.52 (s, IC, 3-C ₆ H ₄ -CH); 121.60 (s, IC, 5-C ₆ H ₄ -CH); 118.68 (s, IC, 4-C ₆ H ₄ -CH); 107.81 (s, IC, 2-C ₆ H ₄ -CH); 72.37 (s, IC, CH); 42.82 (s, IC, CMe ₂ ); 32.02 (s, IC, NCH ₃ ); 23.02 and 14.77 (s, 2C, CCH ₃ ); 13.55 (s, IC, CHCH ₃ ). HR-MS Calcd for Ci ₂ H _n N: [M ⁺ ] 176.14392. Found: m/z 176.14434.

[00149] N-(1-Phenylethyl)aniline: T. Kawakami, T. Sugimoto, I. Shibata, A. Baba, H. Matsuda and N. Sonoda, J. Org. Chem., 1995, 60, 2677-2682. (colourless oil Yield: 0.325g, 90%) ¾ NMR (CDCI ₃ , 400 MHz): δ 7.65 and 7.61 (m, 4H, o and m-Ph-H); 7.51 (tt, ΙΗ, ρ- Ph-H, VHH = 7.2 Hz, V _HH = 1.3 Hz); 7.41 (dd, 1H, m-N-F -H, V _HH = 8.6 Hz, VHH = 7.3 Hz); 6.98 (tt, 1H, p-N-F -H, V _HH = 7.3 Hz, V _HH = 1.1 Hz); 6.82 (dd, 1H, o-N-Ph-H, V _HH = 8.6 Hz, VHH = 0.9 Hz); 4.77 (q, 3H, CH, VHH = 6.7 Hz); 4.28 (br s, 1H, NH); 1.76 (d, 3H, CH3, V _HH = 6.7 Hz). "C^H} NMR (CDC1 ₃ , 100.7 MHz): δ 147.24 and 145.18 (s, 2C, ipso- Ph-C); 129.04, 128.56, 126.78, 125.78, 117.16, and 113.29 (s, 8C, Ph-C); 53.31 (s, IC, CH); 24.87 (s, IC, CH ₃ ). EI-MS Calcd for Ci ₂ Hi ₉ NO: [M ⁺ ] 198.1. Found: m/z 198.1. [00150] Example 10: Functional group tolerance of borenium-catalyzed

hvdrogenation reactions

[00151] Procedure for surrogate functional group tolerance experiments

Scheme 15: Catalytic Hydrogenation

[00152] In an inert atmosphere glovebox, · 0.66 C ₆ H ₅ C1

(31.2 mg, 0.0303 mmol, 1 equiv.) (2), N-benzylidene-ferf-butylamine (98 mg., 0.6074 mmol, 20 equiv.) and the functional group surrogate (0.6074 mmol, 20 equiv.) were added successively to a vial equipped with a stir bar. The sample was dissolved in 0.2 mL CH2CI2 (in entry 9, 0.4 mL CH2CI2 was required for complete dissolution) and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm with hydrogen gas and ten times at 102 atm with hydrogen gas. The reactor was sealed under 102 atm hydrogen gas and placed on a stir plate for 2 or 4 hours at room temperature. The reactor was slowly vented and an NMR sample was taken in CDCI ₃ .

[00153] Conversion of unsaturated substrate to amine product (yield) was determined by Η NMR spectroscopy. The results are shown in Table 8.

Table 9: Hydrogenation reactions in the presence of a functional group surrog

Scheme 16: Synthesis of chiral borenium ion precursors

[00155] Synthesis of l,3-diisopropylimidazol-2-ylidene-di-(lS,2R,3S,5S)- isopinocampheylborane

[00156] In an inert atmosphere glovebox, (+)-diispinocampheylborane (378.4 mg,

1.322 mmol, 1 equiv.), potassium bis(trimethylsilyl)amide (276.8 mg, 1.388 mmol, 1.05 equiv.) and 1,3-diisopropylimidazolium chloride (249.5 mg, 1.322 mmol, 1 equiv.) were weighed into a flame-dried nitrogen-cooled Shlenk flask. A magnetic stir bar was added and the flask was sealed with a rubber septum. The flask was removed from the glove box and connected to a Shlenk line where it was stirred under nitrogen. Dry tetrahydrofuran (20 mL) was added via cannula and the solution was stirred for 20 hours at room temperature. Solvent was removed in vacuo and the flask was reintroduced to the glovebox. The white residue was washed with pentane (3 x 2 mL). These washings were filtered through a celite plug into a vial. The vial was capped and put in a freezer (-35°C) where colourless crystals formed. The crystals were washed with cold pentane (3 x lmL) and dried in vacuo to give 198 mg 1,3- diisopropylimidazol-2-ylidene-di-(15',2i?,35',55)-isopinocam pheylborane (34% yield).

[00157] ¾ NMR (500 MHz, CDC1 ₃ , 298 K): δ 6.97 (d, 1H, ³ J _HH = 2.0 Hz), 6.92 (d, lH, ³ J _HH = 2.0 Hz), 5.84 (septet, 1H, ³ J _HH = 6.7 Hz ), 5.13 (septet, 1H, ³ J _HH = 6.7 Hz), 2.25 (m, 1H), 2.19-2.04 (m, 4H), 1.85, (m, 1H), 1.75-1.67 (m, 2H), 1.65-1.54 (m, 3H), 1.464 (d, 3H, ³ J _HH = 6.7 Hz), 1.459 (d, 3H, ³ J _HH = 6.7 Hz), 1.459 (d, 3H, ³ J _HH = 6.7 Hz), 1.37 (d, 3H, ³ J _HH = Hz), 1.36 (d, 3H, ³ J _HH = 7 Hz), 1.12 (s, 3H), l. l l(s, 3H), 1.10 (d, 3H, ³ J _HH = 7.0 Hz), 1.08 (s, 3H), 1.06 (s, 3H), 0.95 (d, 1H, 8.5 Hz), 0.84 (d, 1H, 8.5 Hz) 0.48 (d, 3H, 7.2 Hz) (No B-H peak observed. ⁿ B NMR (128 MHz, toluene-d8, 298 K): δ -8.2 (d, ^ _ΒΗ = 862 Hz). "C^H} NMR (125 MHz, CDC1 ₃ , 298 K, partial): δ 115.8 (NHC H), 115.4 (NHC H), 50.6 (CH), 49.9 (CH), 49.3 (NHC 'Pr-CH), 48.9 (NHC T^r-CH), 44.9 (CH), 43.3 (CH), 43.1 (CH), 42.1 (CH), 39.0 (C), 38.9 (C), 37.1 (CH ₂ ), 35.4 (CH ₂ ), 33.8 (CH ₂ ), 32.7 (CH ₂ ), 28.38 (CH ₃ ), 28.36 (CH ₃ ), 24.10 (CH ₃ ), 24.08 (CH ₃ ), 23.82 (CH ₃ ), 23.70 (CH ₃ ), 23.38 (CH ₃ ) 23.33 (CH ₃ ), 23.03 (CH ₃ ), 22.9 (CH ₃ ) (No peaks observed for C-B).

[00158] Synthesis of l,3-dimethylimidazol-2-ylidene-di-(lS,2R,3S,5S)- isopinocampheylborane

[00159] In an inert atmosphere glovebox, (+)-diispinocampheylborane (396.3 mg,

1.384 mmol, 1 equiv.), potassium bis(trimethylsilyl)amide (289.9 mg, 1.453 mmol, 1.05 equiv.) and 1,3-dimethylimidazolium iodide (310.1 mg, 1.384 mmol, 1 equiv.) were weighed into a flame-dried nitrogen-cooled Shlenk flask. A magnetic stir bar was added and the flask was sealed with a rubber septum. The flask was removed from the glove box and connected to a Shlenk line where it was stirred under nitrogen. Dry tetrahydrofuran (20 mL) was added via cannula and the solution was stirred for 20 hours at room temperature. Solvent was removed in vacuo and the flask was reintroduced to the glovebox. The white residue was washed with pentane (3 x 2 mL). These washings were filtered through a celite plug into a vial. The residue was then washed with toluene (3 x 2 mL) and these washings were filtered through the same celite plug into a separate vial. The vials was capped and put in a freezer (- 35°C) where colourless crystals formed. The crystals were washed with cold pentane (3 x lmL) and dried in vacuo to give 198 mg l^-dimethylimidazol^-ylidene-di-ili'^ ^^^Si)- isopinocampheylborane (37% yield) (68 mg were recovered from the pentane washings and 130 mg were recovered from the toluene washings). [00160] ¾ NMR (500 MHz, CDC1 ₃ , 298 K): δ 6.81 (s, 1H), 6.74 (s, 1H), 3.88 (br,

6H), 2.18 (m, 1H, -CH), 2.13-2.07 (m, 2Η, -CHH), 2.05-1.96 (m, 1Η, -CH), 1.92-1.83 (m, 2Η, -CH), 1.75-1.63 (m, 3Η, -CHH, -CH, -CH), 1.59-1.52 (m, 1Η, -CH), 1.43-1.34 (m, 1Η, - CH), 1.32-1.23 (m, 1Η, -CHH), 1.19-1.02 (m, 2Η, -CH), 1.122 (s, 3Η, CH ₃ ) 1.117 (s, 3Η, CH ₃ ), 1.09 (overlapping s, 6Η, 2xCH ₃ ), 1.08 (d, 3Η, ³ JHH = 7.0 Hz, CH ₃ ), 0.95 (br d, 2Η, ³ JHH = 8.5 Hz, CH ₂ ), 0.71 (br d, 2Η, ³ JHH = 8.6 Hz, CH ₂ ), 0.59 (d, 3Η, ³ J _HH = 7.2 Hz, CH ₃ ) (No Β-Η peak found). ⁿ B NMR (128 MHz, toluene-d8, 298 K): δ -9.1 (d, = 86 Hz).

NMR (125 MHz, CDC1 ₃ , 298 K, partial): δ 121.1 (NHC CH), 120.0 (NHC CH), 50.8 (CH), 49.9 (CH), 45.0 (CH), 43.4 (CH), 43.1 (CH), 42.7 (CH), 39.3 (C), 39.1 (C), 37.8 (NHC CH ₃ ), 37.5 (NHC CH ₃ ), 36.2 (CH ₂ ), 35.3 (CH ₂ ), 33.6 (CH ₂ ), 33.3 (CH ₂ ), 28.7 (CH ₃ ), 28.5 (CH ₃ ), 23.8 (CH ₃ ), 23.4 (CH ₃ ), 23.13 (CH ₃ ), 23.11 (CH ₃ ) (No peaks observed for C- B).

[00161] Example 12: Asymmetric induction in borenium-catalyzed hydrogenation reactions

Scheme 17: Asymmetric Catalytic Hydrogenation

[00162] In an inert atmosphere glovebox, a 1,3-disubstituted imidazol-2-ylidene- diispinocampheylborane (0.0285 mmol, 1 equiv.), [Ph ₃ C] [B(C ₆ F ₅ ) ₄ ] (26.3 mg, 0.0285 mmol, 1 equiv. or 16.8 mg, 0.0182 mmol, 1 equiv.) and N-(l-phenylethylidene)aniline (111.3 mg, 0.570 mmol, 20 equiv.) were weighed into vials. [Ph ₃ C] [B(C6F ₅ ) ₄ ] was transferred to the vial of the 1,3 disubstituted imidazol-2-ylidene-diispinocampheylborane with 0.4 mL solvent at which point the reddish trityl solution turns colourless. This solution was then transferred to the vial containing the unsaturated substrate with an additional 0.2 mL solvent. This vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm with hydrogen gas and ten times at 102 atm with hydrogen gas. The reactor was sealed under 102 atm hydrogen gas and placed on a stir plate for 4 hours at room temperature or -30°C. The reactor was slowly vented and an NMR sample was taken in toluene-c s or CDCI3.

[00163] Conversion to N-(l-phenylethyl)aniline was determined by ¾ NMR spectroscopy. The entire sample was then concentrated in vacuo, dissolved in 9: 1 hexanes : ethyl acetate and passed through a short silica plug. The sample was concentrated in vacuo and enantiomeric excess was determined by chiral HPLC (Chiralcel OD-H, 98.9 hexanes : 1 isopropanol : 0.1 diethylamine) by comparison to a racemic standard prepared by a procedure described in Farrell et al. (Farrell, J. M.; Hatnean, J. H.; Stephan, D. W. J. Am. Chem. Soc. 2012, 134: 15728-15731). The results are shown in Table 9, wherein yield was determined by ^-NMR and enantiomeric excess was determined by chiral HPLC.

Table 9: Hydrogenation of N-(a-methylbenzylidene)aniline with in situ generated chiral borenium salts

[00164] 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 application pertains and are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[00165] 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.