DIRUTHENIUM CATALYST COMPOSITIONS AND SYNTHETIC PROCESSES

RELATED THERETO

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit ofU.S. Provisional Application No. 63/147,800 filed February 10, 2021. The entirety of this application is hereby incorporated by reference for all purposes.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR

DEVELOPMENT

This invention was made with government support under CHE1956154 and CHE1700982 awarded by the National Science Foundation. The government has certain rights in the invention.

BACKGROUND

The cyclopropane ring is a common structural motif incorporated into many pharmaceutical agents. Elaborate chiral cyclopropanes have been incorporated into therapeutic scaffolds, such as the tri substituted cyclopropanes in beclabuvir, paritaprevir, and glecaprevir. In these cases, three substituents are placed in a defined orientation. The syntheses of these cyclopropanes are challenging because they contain two stereogenic centers which are to be generated in a diastereo selective and enantioselective manner. Thus, there is a need to identify improved synthetic processes.

Davies et al. report asymmetric cyclopropanations by rhodium(II) N- (arylsulfonyl)prolinate catalyzed decomposition of vinyldiazomethanes in the presence of alkenes. J. Am. Chem. Soc. 1996, 118, 6897-6907.

Saha et al. report evaluation of a pair of diruthenium(I) catalysts for carbene-transfer reactions from ethyl diazoacetate. Organometallics, 2011, 30, 2051-2058.

Chepiga et al. report a guide to enantioselective dirhodium(II)-catalyzed cyclopropanation with aryldiazoacetates. Tetrahedron, 2013, 69, 5765-5771. See also US Patent No. 8,975,428. Miyazawa et al. report chiral paddle-wheel diruthenium complexes for asymmetric catalysis. Nature Catalysis, 2020, 3, 851-858.

References cited herein are not an admission of prior art.

SUMMARY

This disclosure relates to compositions comprising diruthenium catalysts and uses related thereto. In certain embodiments, the diruthenium catalyst comprises a cyclopropyl ring substituted with a carboxylic acid ligand. In certain embodiments, the diruthenium catalyst comprises an N-(sulfonyl)pyrrolidine ring substituted with a carboxylic acid ligand. In certain embodiments, the diruthenium catalyst comprises a 2-(l,3-dioxoisoindolin-2-yl)acetic acid ligand. In certain embodiments, this disclosure relates to methods of using catalysts in chemical transformations disclosed herein.

In certain embodiments, the disclosure relates to compositions comprising a catalyst of the following formula, or derivatives or salts thereof wherein, R ¹ , R ² , R ³ and X are defined herein.

In certain embodiments, the disclosure relates to compositions comprising Ru2(N-p-Ph- TPCP) ₄ X , Ru2fV-p-Br-TPCP) ₄ X, Ru ₂ fV-2Cl-5Br-TPCP) ₄ X, Ru2(f?-tris(p-*BuC6H )- TPCP) ₄ X, or a catalyst of formula

or derivatives or salts thereof wherein, Ar and X are defined herein, e.g., X is a covalently bound ligand, such as Cl, or a counterion such as PFs or BARF".

In certain embodiments, the disclosure relates to compositions comprising Ru2(7C D0SP)4 X , or a catalyst of formula or derivatives or salts thereof wherein, R ¹ and X are defined herein, e.g., X is a covalently bound ligand, such as Cl, or a counterion such as PFC or BARF .

In certain embodiments, Ar is p-alkyl-CeFF-.

In certain embodiments, the disclosure relates to compositions comprising Rm(S- catalyst of formula or derivatives or salts thereof wherein, R ¹ , R ² , R ³ , and X are defined herein. In certain embodiments, the disclosure relates to methods of preparing diruthenium catalysts or intermediates disclosed herein by mixing starting materials with catalysts under conditions such that the catalysts or intermediates are formed.

In certain embodiments, the disclosure contemplates enantioselective reactions of donor/acceptor carbenoids, such as cyclopropanations, formal [4 + 3] cycloadditions, C-H functionalizations, and ylide transformations comprising mixing a compound comprising a carbenoid precursor, e.g., a diazo compound, and catalysts disclosed herein and reactive compounds under conditions such that a synthetic compound is formed.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1A illustrates the proposed chemical structure of Ru2(R-p-BrTPCP)4; [Tetrakis[(R)-(-)-[(lR)-l-(4-bromophenyl)-2,2-diphenylcyclop ropanecarboxylato] diruthenium(II/III) with a tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BArF) counter anion.

Figure IB illustrates the proposed chemical structure of Ru2(R-p-BrTPCP)4Cl; [Tetrakis[(R)-(-)-[(lR)-l-(4-bromophenyl)-2,2-diphenylcyclop ropanecarboxylato] diruthenium(II/III)] chi ori de .

Figure 1C illustrates the proposed chemical structure of Ru2(R-p-PhTPCP)4BArF; [Tetrakis[(R)-(-)-[(lR)-l-(4-phenyl(phenyl))-2,2-diphenylcyc lopropanecarboxylato] diruthenium (P/PI)] with a tetrakis(3,5-bis(trifluoromethyl)phenyl)borate counter anion.

Figure ID illustrates the proposed chemical structure of Ru2(R-p-PhTPCP)4Cl; [Tetrakis[(R)-(-)-[(lR)-l-(4-phenyl(phenyl))-2,2-diphenylcyc lopropanecarboxylato] diruthenium(II/III)] chi ori de .

Figure IE illustrates the proposed chemical structure of Ru2(S-2C15BrTPCP)4BArF; [Tetrakis[(S)-l-(5-bromo-2-chlorophenyl)-2,2-diphenylcyclopr opanecarboxylato] diruthenium(II/III)] with a tetrakis(3,5-bis(trifluoromethyl)phenyl)borate counter anion.

Figure IF illustrates the proposed chemical structure of Ru2(S-2C15BrTPCP)4Cl; [Tetrakis[(S)-(5-bromo-2-chlorophenyll)-2,2-diphenylcyclopro panecarboxylato] diruthenium(II/III)] chl ori de .

Figure 1G illustrates the proposed chemical structure of Ru2(R-tris(p-tBuC ₆ H4)- TPCP)4BArF; Tetrakis [(R)-l,2,2-tris[4'-(tert-butyl)-(l, l'-biphenyl]-4-yl]cyclopropane-l- carboxylato] diruthenium(II/III)] with a tetrakis(3,5-bis(trifluoromethyl)phenyl)borate counter anion.

Figure 1H illustrates the proposed chemical structure of Ru2(R-tris(p-tBuC ₆ H4)- TPCP)4C1; Tetrakis [(R)-l,2,2-tris[4"-(tert-butyl)-(l,r:4',l"-terphenyl]-4-yl]c yclopropane-l- carb oxy 1 ato] diruthenium(II/III)] chi on de .

Figure II illustrates the proposed chemical structure of Ru2(R-3,5-di(p-tBuC6H4)- TPCP)4B ArF ; Tetrakis [(R)- 1 -(4,4"-di-tert-butyl-[ 1 , 1 ' : 3 1 "-terphenyl]-5'-yl)-2,2- diphenylcyclopropanecarboxylato] diruthenium(II/III)] with a tetrakis(3,5- bis(trifluoromethyl)phenyl)borate counter anion.

Figure 1J illustrates the proposed chemical structure of Ru2(R-3,5-di(p-tBuC6H4)- TPCP)4C1; T etrakis [(R)- 1 -(4,4"-di-tert-butyl-[ 1 , G : 3 1 "-terphenyl]-5'-yl)-2, 2-diphenyl cyclopropanecarboxylato]diruthenium(II/III)]chloride.

Figure 2A illustrates the proposed chemical structure of Ru2(S-DOSP)4BArF;

[Tetrakis[(S)-(-)-N-(p-dodecylphenylsulfonyl)prolinato]di ruthenium(II/III)] with a tetrakis(3,5-bis(trifluoromethyl)phenyl)borate counter anion.

Figure 2B illustrates the proposed chemical structure of RU2(S-DOSP)4C1; [Tetrakis[(S)-(-)-N-(p-dodecyl phenyl sulfonyl)prolinato]di rutheni um(I I/I I I)chloride.

Figure 3A illustrates the proposed chemical structure of Ru2(S-TPPTTL)4BArF [Tetraki s[N-tetraphenyl phthal oyl-(S)-tert-leucinato]di rutheni um(II/II I)] with a tetrakis(3,5- bis(trifluoromethyl)phenyl)borate counter anion.

Figure 3B illustrates the proposed chemical structure of RU2(S-TPPTTL)4C1;

[Tetraki s[N-tetraphenyl phthal oyl-(S)-tert-leucinato]di rutheni um(I I/I I I)]chloride.

Figure 3C illustrates the proposed chemical structure of Ru2(S-TCPTAD)4BArF; [Tetrakis[(S)-(+)-(l -adamantyl)-(N-tetrachlorophthalimido)acetato]diruthenium(II /III)] with a tetrakis(3,5-bis(trifluoromethyl)phenyl)borate counter anion.

Figure 3D illustrates the proposed chemical structure of RU2(S-TCPTAD)4C1;

[Tetraki s[(S)-(+)-(l -adamantyl)-(N-tetrachlorophthali mi do)acetato]di rutheni um(I I/I II)] chloride.

Figure 3E illustrates the proposed chemical structure of Ru2(S-PTAD)4BArF;

[Tetrakis[(S)-(+)-(l -adamantyl)-(N-phthalimido)acetato]diruthenium(II/III)] with a tetrakis(3,5-bis(trifluoromethyl)phenyl)borate counter anion. Figure 3F illustrates the proposed chemical structure of RU2(S-PTAD)4C1; [Tetrakis[(S)- (+)-(l-adamantyl)-(N-phthalimido)acetato]diruthenium(II/III) ]chloride.

Figure 4 illustrates the use of diruthenium complexes disclosed herein in the synthesis of intermediates for the production pharmaceutical products such as beclabuvir.

DETAILED DESCRIPTION

Terms

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art. The following definitions are provided to help interpret the disclosure and claims of this application. In the event a definition in this section is not consistent with definitions elsewhere, the definition set forth in this section will control.

As used herein, the term “derivative” refers to a structurally similar compound that retains sufficient functional attributes of the identified analogue. The derivative may be structurally similar because it is lacking one or more atoms, substituted, a salt, in different hydration/oxidation states, or because one or more atoms within the molecule are switched, such as, but not limited to, replacing an oxygen atom with a sulfur atom or replacing an amino group with a hydroxy group, or visa versa. Derivatives may be prepared by any variety of synthetic methods or appropriate adaptations presented in synthetic or organic chemistry textbooks, such as those provide in March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Wiley, 6th Edition (2007) Michael B. Smith or Domino Reactions in Organic Synthesis, Wiley (2006) Lutz F. Tietze, hereby incorporated by reference.

The term "substituted" refers to a molecule wherein at least one hydrogen atom is replaced with a substituent. When substituted, one or more of the groups are "substituents." The molecule may be multiply substituted. In the case of an oxo substituent ("=0"), two hydrogen atoms are replaced. Example substituents within this context may include halogen, hydroxy, alkyl, alkoxy, nitro, cyano, oxo, carbocyclyl, carbocycloalkyl, heterocarbocyclyl, heterocarbocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -NRaRb, -NRaC(=0)Rb, - NRaC(=0)NRaNRb, -NRaC(=0)ORb, - NRaS02Rb, -C(=0)Ra, -C(=0)ORa,

-C(=0)NRaRb, -OC(=0)NRaRb, -ORa, -SRa, -SORa, -S(=0)2Ra, -OS(=0)2Ra and -S(=0)20Ra. Ra and Rb in this context may be the same or different and independently hydrogen, halogen hydroxy, alkyl, alkoxy, alkyl, amino, alkylamino, dialkylamino, carbocyclyl, carbocycloalkyl, heterocarbocyclyl, heterocarbocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl.

When used in reference to compound(s) disclosed herein, "salts" refer to derivatives of the disclosed compound(s) where the parent compound is modified making acid or base salts thereof. Examples of salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkylamines, or dialkylamines; alkali or organic salts of acidic residues such as carboxylic acids; and the like.

As used herein, "alkyl" means a noncyclic straight chain or branched, unsaturated or saturated hydrocarbon such as those containing from 1 to 10 carbon atoms. Representative saturated straight chain alkyls include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n- septyl, n-octyl, n-nonyl, and the like; while saturated branched alkyls include isopropyl, sec- butyl, isobutyl, tert-butyl, isopentyl, and the like. Unsaturated alkyls contain at least one double or triple bond between adjacent carbon atoms (referred to as an "alkenyl" or "alkynyl", respectively). Representative straight chain and branched alkenyls include ethylenyl, propylenyl, 1-butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3 -methyl- 1-butenyl, 2- methyl-2-butenyl, 2,3- dimethyl-2-butenyl, and the like; while representative straight chain and branched alkynyls include acetylenyl, propynyl, 1-butynyl, 2-butynyl, 1-pentynyl, 2-pentynyl, 3- methyl- 1-butynyl, and the like.

Non-aromatic mono or polycyclic alkyls are referred to herein as "carbocycles" or "carbocyclyl" groups. Representative saturated carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like; while unsaturated carbocycles include cyclopentenyl and cyclohexenyl, and the like.

"Heterocarbocycles" or heterocarbocyclyl" groups are carbocycles which contain from 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur which may be saturated or unsaturated (but not aromatic), monocyclic or polycyclic, and wherein the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quatemized. Heterocarbocycles include morpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydroprimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, and the like.

"Aryl" or "Ar" means an aromatic carbocyclic monocyclic or polycyclic ring such as phenyl or naphthyl. Polycyclic ring systems may, but are not required to, contain one or more non-aromatic rings, as long as one of the rings is aromatic.

As used herein, "heteroaryl" or “heteroaromatic” refers an aromatic heterocarbocycle having 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and containing at least 1 carbon atom, including both mono- and polycyclic ring systems. Polycyclic ring systems may, but are not required to, contain one or more non-aromatic rings, as long as one of the rings is aromatic. Representative heteroaryls are furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrrolyl, indolyl, isoindolyl, azaindolyl, pyridyl, quinolinyl, isoquinolinyl, oxazolyl, isooxazolyl, benzoxazolyl, pyrazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl, and quinazolinyl. It is contemplated that the use of the term "heteroaryl" includes N-alkylated derivatives such as a l-methylimidazol-5-yl substituent.

As used herein, "heterocycle" or "heterocyclyl" refers to mono- and polycyclic ring systems having 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and containing at least 1 carbon atom. The mono- and polycyclic ring systems may be aromatic, non-aromatic or mixtures of aromatic and non-aromatic rings. Heterocycle includes heterocarbocycles, heteroaryls, and the like.

"Alkylthio" refers to an alkyl group as defined above attached through a sulfur bridge. An example of an alkylthio is methylthio, (i.e., -S-CH3).

"Alkoxy" refers to an alkyl group as defined above attached through an oxygen bridge. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n- butoxy, s-butoxy, t-butoxy, n- pentoxy, and s-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n-propoxy, i- propoxy, n-butoxy, s-butoxy, t-butoxy.

" Alkylamino" refers an alkyl group as defined above attached through an amino bridge. An example of an alkylamino is methylamino, (i.e., -NH-CH3).

"Alkanoyl" refers to an alkyl as defined above attached through a carbonyl bridge (i.e., -(C=0)alkyl). "Alkylsulfonyl" refers to an alkyl as defined above attached through a sulfonyl bridge (i.e., -S(=0)2alkyl) such as mesyl and the like, and "Arylsulfonyl" refers to an aryl attached through a sulfonyl bridge (i.e., - S(=0)2aryl).

"Alkylsulfamoyl" refers to an alkyl as defined above attached through a sulfamoyl bridge (i.e., -S(=0)2NHalkyl), and an "Aryl sulfamoyl" refers to an alkyl attached through a sulfamoyl bridge (i.e., - S(=0)2NHaryl).

"Alkylsulfmyl" refers to an alkyl as defined above with the indicated number of carbon atoms attached through a sulfinyl bridge (i.e. -S(=0)alkyl).

The terms "halogen" and "halo" refer to fluorine, chlorine, bromine, and iodine.

Diruthenium catalysts

In certain embodiments, the disclosure relates to a diruthenium catalyst comprising a cyclopropyl ring substituted with a carboxylic acid ligand.

In certain embodiments, the disclosure relates to compositions comprising a diruthenium complex of the following formula, derivatives or salts thereof wherein,

X is a covalently bound ligand, such as Cl or other halogen, or a counterion such as PFs or BARF ;

R ¹ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ;

R ² is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁴ ;

R ³ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, the disclosure relates to compositions comprising a diruthenium complex of the following formula, derivative or salt thereof wherein,

X is a ligand or a counter anion;

R ¹ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ;

R ² is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁴ ;

R ³ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, the counter anion is tetrakis(3,5- bis(trifluoromethyl)phenyl)borate (BArF).

In certain embodiments, the ligand is a halogen or chlorine (Cl).

In certain embodiments, the diruthenium complex is tetrakis [l-(4-phenyl(phenyl))-2,2- di phenyl cyclopropanecarboxylatojdi ruthenium.

In certain embodiments, the diruthenium complex is tetrakis[l-(5-bromo-2- chlorophenyl)-2,2-diphenylcyclopropanecarboxylato]dirutheniu m.

In certain embodiments, the diruthenium complex is tetrakis [l,2,2-tris[4'-(tert-butyl)- (1,1 '-biphenyl]-4-yl]cyclopropane- 1 -carboxylato] diruthenium] . In certain embodiments, the diruthenium complex is tetrakis [l-(4,4"-di-tert-butyl- [l,l':3',l"-terphenyl]-5'-yl)-2,2-diphenylcyclopropanecarbox ylato] diruthenium.

In certain embodiments, the diruthenium complex is tetrakis[l-(4-bromophenyl)-2,2- di phenyl cy cl opropanecarboxylatojdi ruthenium.

In certain embodiments, the diruthenium complex is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereoisomers:

In certain embodiments, R ¹ is carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, R ¹ is an aryl or an aromatic heterocyclyl.

In certain embodiments, R ¹ is a phenyl optionally substituted with one or more R ⁴ .

In certain embodiments, R ¹ is a phenyl optionally substituted with one or more halogen, alkyl, or alkoxy.

In certain embodiments, R ¹ is hydrogen.

In certain embodiments, R ² is carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, R ² is an aryl or an aromatic heterocyclyl.

In certain embodiments, R ² is a phenyl optionally substituted with one or more R ⁴ .

In certain embodiments, R ² is a phenyl optionally substituted with one or more halogen, alkyl, or alkoxy.

In certain embodiments, R ³ is carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, R ³ is an aryl or an aromatic heterocyclyl.

In certain embodiments, R ³ is a phenyl optionally substituted with one or more R ⁴ .

In certain embodiments, R ³ is a phenyl optionally substituted with one or more halogen, alkyl, or alkoxy.

In certain embodiments, R ³ is a phenyl substituted with a halogen.

In certain embodiments, R ³ is a phenyl substituted with a halogen in the otho or para position.

In certain embodiments, the disclosure relates to compositions comprising a diruthenium complex of the following formula, wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF .

In certain embodiments, the disclosure relates to compositions comprising a diruthenium complex of the following formula, wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF" and

Y is an electron withdrawing group.

In certain embodiments, the catalyst is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereoisomers:

In certain embodiments, Y is a halogen.

In certain embodiments, the disclosure relates to compositions comprising a diruthenium complex of the following formula, wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as

PF5 or BARF . In certain embodiments, the disclosure relates to compositions comprising a diruthenium complex of the following formula, wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF ; wherein Y is an electron withdrawing group; and wherein Z is an electron withdrawing group.

In certain embodiments, Y is a halogen.

In certain embodiments, Z is a halogen.

In certain embodiments, the catalyst is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereoisomers: wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF ; wherein Y is an electron withdrawing group; and wherein Z is an electron withdrawing group.

In certain embodiments, Y is a halogen.

In certain embodiments, Z is a halogen.

In certain embodiments, the disclosure relates to compositions comprising a diruthenium complex of the following formula, wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF ; wherein Y is a halogen; and wherein Z is a halogen.

In certain embodiments, the catalyst is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereoisomers: wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF ; wherein Y is a halogen; and wherein Z is a halogen.

In certain embodiments, Y is a halogen.

In certain embodiments, Z is a halogen.

In certain embodiments, Y is a Br.

In certain embodiments, Z is a Cl.

In certain embodiments, the disclosure relates to a diruthenium catalyst comprising a pyrrolidine-2-sulfonamide substituted with a carboxylic acid ligand.

In certain embodiments, the disclosure relates to compositions comprising Ru2(7C DOSP)4 X , or a diruthenium complex of the following formula of formula or derivatives or salts thereof wherein, wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF ;

R ¹ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, Ar is p-alkyl-Cehk-.

In certain embodiments, this disclosure relates to compositions comprising a diruthenium complex of the following formula, or salt thereof wherein,

X is a ligand or a counter anion;

R ¹ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ; R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, the counter anion is tetrakis(3,5- bis(trifluoromethyl)phenyl)borate (BArF).

In certain embodiments, the ligand is a halogen or chlorine (Cl).

In certain embodiments, R ¹ is (p-alkylphenyl).

In certain embodiments, the diruthenium complex is tetrakis[N-(p- dodecylphenyl sulfonyl)prolinato] diruthenium .

In certain embodiments, the disclosure relates to compositions comprising Ru2fV- TCPTTL) ₄ X _^ Ru ₂ fV-PTAD) ₄ X, Ru ₂ fV-TCPTAD) ₄ X or a diruthenium complex of the following formula of formula or derivatives or salts thereof wherein, wherein X is a covalently bound ligand, such as a halogen, Cl, or a counterion such as PF5 or BARF ;

R ¹ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ;

R ² is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁴ ;

R ³ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, R ² is hydrogen. In certain embodiments, R ³ is hydrogen.

In certain embodiments, R ² and R ³ are hydrogen.

In certain embodiments, R ¹ is tertbutyl.

In certain embodiments, R ¹ is a carbocyclyl. In certain embodiments, R ¹ is adamantly.

In certain embodiments, R ² is phenyl.

In certain embodiments, R ³ is phenyl.

In certain embodiments, R ² and R ³ are phenyl.

In certain embodiments, R ² is halogen. In certain embodiments, R ³ is halogen.

In certain embodiments, R ² and R ³ are halogen.

In certain embodiments, this disclosure relates to composition comprising a diruthenium complex of the following formula, derivative or salt thereof wherein,

X is a ligand or a counter anion;

R ¹ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ; R ² is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁴ ;

R ³ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, the counter anion is tetrakis(3,5- bis(trifluoromethyl)phenyl)borate (BArF).

In certain embodiments, the ligand is a halogen or chlorine (Cl).

In certain embodiments, R ¹ is a carbocyclyl or is adamantly.

In certain embodiments, the diruthenium complex is tetrakis[2-(l,3-dioxo-4, 5,6,7- tetraphenylisoindolin-2-yl)-3,3-dimethylbutanato]diruthenium . In certain embodiments, the diruthenium complex is tetrakis[(l-adamantyl)-(N- tetrachlorophthalimido)acetato]diruthenium.

In certain embodiments, the diruthenium complex is tetrakis[(l-adamantyl)-(N- phthalimido)acetato] diruthenium.

Synthetic Processes

Many enantioselective reactions of donor/acceptor carbenoids may be utilized with diruthenium catalysts disclosed herein. In certain embodiments, the diruthenium complex can be used to make intermediates for pharmaceutical agents as exemplified herein. See Davies & Manning, Nature, 2008, 451, 417-424; Davies & Denton, Chem. Soc. Rev., 2009, 38, 3061- 3071; Davies, et ah, J. Am. Chem. Soc., 2006, 128, 2485-2490; and Davies &. Walji, Angew. Chem., Int. Ed., 2005, 44, 1733-1735, all hereby incorporated by reference.

In certain embodiments, the disclosure contemplates reactions of donor/acceptor carbenoids, such as cyclopropanations, formal [4 + 3] cycloadditions, C-H functionalizations, and ylide transformations comprising mixing a compound comprising a carbenoid precursor, e.g., a diazo compound, and catalysts disclosed herein and reactive compounds under conditions such that a synthetic compound is formed.

In certain embodiments, the disclosure relates to methods of making a synthetic compound comprising mixing a) a diazo compound, b) a compound with a carbon hydrogen bond, and c) a diruthenium catalyst disclosed herein, under conditions such that a synthetic compound is formed comprising a carbon-to-carbon bond between the diazo compound and the compound with a carbon hydrogen bond. The synthetic compound may be the result of an inter or an intra-molecular reaction.

In certain embodiments, the disclosure relates to methods of making a synthetic compound comprising mixing a) a diazo compound, b) a compound with a nitrogen-to- hydrogen bond, and c) a diruthenium catalyst disclosed herein, under conditions such that a synthetic compound is formed comprising a carbon-to-nitrogen bond between the diazo compound and the compound with a nitrogen hydrogen bond. The synthetic compound may be the result of an inter or an intra-molecular reaction.

In certain embodiments, the disclosure relates to cyclopropanation reactions using catalysts disclosed herein. See Davies et ah, J. Am. Chem. Soc. 1996, 118, 6897- 6907, hereby incorporated by reference. In certain embodiments, the disclosure relates to methods of making a synthetic compound comprising mixing a) a diazo compound such as vinyldiazomethane and vinyldiazoactates optionally substituted with one or more substituents, b) a double bond compound such as an alkene or diene optionally substituted with one or more substituent, and c) a compound comprising a diruthenium catalyst disclosed herein under conditions such that a synthetic compound is formed comprising a cyclopropyl ring and carbon-to-carbon bond between the diazo compound and the double bond compound.

In certain embodiments, the diazo compound has the following formula, the double bond compound has the following formula, and the synthetic compound has the following formula, wherein, R ¹ is alkyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ;

R ² is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁴ ;

R ³ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, R ¹ is alkyl optionally substituted with one or more, the same or different, R ⁴ .

In certain embodiments, R ² is an electron donating group selected from cyano, alkenyl, alkynyl, formyl, carbamoyl, carboxy, alkylsulfmyl, alkylsulfonyl, or arylsulfonyl, aryl, or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁴ .

In certain embodiments, R ² is aryl or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁴ .

In certain embodiments, R ³ is an electron donating group selected from cyano, alkenyl, alkynyl, formyl, carbamoyl, carboxy, alkylsulfmyl, alkylsulfonyl, or arylsulfonyl, aryl, or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁴ .

In certain embodiments, R ³ is aryl or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁴ .

In certain embodiments, the synthetic product is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereoisomers: In certain embodiments, the diazo compound has the following formula, the double bond compound has the following formula, and the synthetic compound has the following formula, or salts thereof wherein

R ¹ is phenyl optionally substituted with one or more substituent and R ² is phenyl optionally substituted with one or more substituent. In certain embodiments, the synthetic product is in a composition with greater than 55%,%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereoisomers:

In certain embodiments, the diazo compound has the following formula, the double bond compound has the following formula, r ¹ and the synthetic compound has the following formula, wherein Ar ¹ and Ar ² are each, the same or different, aryl optionally substituted with one or more substituents.

In certain embodiments, the synthetic product is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereioisomers:

In certain embodiments, the disclosure contemplates the use of diruthenium catalysts disclosed herein in [4 + 3] cycloaddition reactions, e.g., mixing a diene and a vinyldiazoacetate and a diruthenium catalyst disclosed herein under conditions such that a cyclic compound is formed. See Davies et al, J. Am. Chem. Soc. 1998, 120, 3326- 3331 and Reddy & Davies, J. Am. Chem. Soc., 2007, 129 (34), 10312-10313.

In certain embodiments, the diazo compound is a vinyldiazoacetate of the following formula, the diene compound has the following formula, and the synthetic compound has the following formula, wherein, R ¹ is alkyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁹ ;

R ² is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁹ ;

R ³ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁹ ;

R ⁴ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁹ ;

R ⁵ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁹ ;

R ⁶ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁶ is optionally substituted with one or more, the same or different, R ⁹ ;

R ⁷ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁷ is optionally substituted with one or more, the same or different, R ⁹ ; R ⁸ is hydrogen, alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁸ is optionally substituted with one or more, the same or different, R ⁹ ;

R ⁹ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁹ is optionally substituted with one or more, the same or different, R ¹⁰ ; and

R ¹⁰ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, the synthetic product is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereoisomers:

In certain embodiments, R ¹ is alkyl optionally substituted with one or more, the same or different, R ⁹ .

In certain embodiments, R ² is an electron donating group selected from cyano, alkenyl, alkynyl, formyl, carbamoyl, carboxy, alkylsulfmyl, alkylsulfonyl, or arylsulfonyl, aryl, or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁹ .

In certain embodiments, R ² is aryl or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁹ . In certain embodiments, R ³ is an electron donating group selected from cyano, alkenyl, alkynyl, formyl, carbamoyl, carboxy, alkylsulfmyl, alkylsulfonyl, or arylsulfonyl, aryl, or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁹ .

In certain embodiments, R ³ is aryl or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁹ .

In certain embodiments, R ⁴ is hydrogen.

In certain embodiments, R ⁵ is hydrogen.

In certain embodiments, R ⁶ is hydrogen.

In certain embodiments, R ⁷ is hydrogen. In certain embodiments, R ⁸ is hydrogen.

In certain embodiments, the diazo compound is a vinyldiazoacetate of the following formula, the diene compound has the following formula, and the synthetic compound has the following formula,

Wherein R is phenyl optionally substituted with one or more substituent.

In certain embodiments, the synthetic product is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereioisomers:

In certain embodiments, the diazo compound has the following formula, t following formula, and the synthetic compound has the following formula, wherein, R ¹ is alkyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁷ ;

R ² is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁷ ;

R ³ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁷ ;

R ⁴ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁷ ; R ⁵ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁷ ; or R ⁴ and R ⁵ form a ring selected from a carbocyclyl, aryl, or heterocyclyl wherein the ring is optionally substituted with one or more, the same or different, R ⁷

R ⁶ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁶ is optionally substituted with one or more, the same or different, R ⁷ ;

R ⁷ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁷ is optionally substituted with one or more, the same or different, R ⁸ ;

R ⁸ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁸ is optionally substituted with one or more, the same or different, R ⁹ ; and

R ⁹ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, R ¹ is alkyl optionally substituted with one or more, the same or different, R ⁷ .

In certain embodiments, R ² is an electron donating group selected from cyano, alkenyl, alkynyl, formyl, carbamoyl, carboxy, alkylsulfmyl, alkylsulfonyl, or arylsulfonyl, aryl, or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁷ .

In certain embodiments, R ² is aryl or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁷ . In certain embodiments, R ³ is an electron donating group selected from cyano, alkenyl, alkynyl, formyl, carbamoyl, carboxy, alkylsulfmyl, alkylsulfonyl, or arylsulfonyl, aryl, or an aromatic heterocyclyl optionally substituted with one or more, the same or different, R ⁷ .

In certain embodiments, R ³ is hydrogen or alkyl optionally substituted with one or more, the same or different, R ⁷ .

In certain embodiments, the disclosure relates to diazo compound of the following formula: 2

EDG A EWG wherein EDG is an electron withdrawing group and EWG is an electron donating group. Such a diazo compound may react with a compound with a C-H bond or a N-H bond as further exemplified below. See Davies & Morton, Chem. Soc. Rev., 2011, 40, 1857-1869, hereby incorporated by reference.

In certain embodiments, the diazo compound has the following formula,

R ¹⁰ is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹⁰ is optionally substituted with one or more, the same or different, R ¹² ;

R ¹¹ is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹² is optionally substituted with one or more, the same or different, R ⁹ ;

R ¹² is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹² is optionally substituted with one or more, the same or different, R ¹³ ;

R ¹³ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, R ¹⁰ is alkyl optionally substituted with one or more halogens.

In certain embodiments, R ¹¹ is aryl or phenyl optionally substituted with an ortho or para substituted with one or more a halogen, hydroxy, alkoxy, thiol, alkylthio, amino, or alkylamino.

In certain embodiments, the method comprises mixing the diazo compound with a compound of the following formula: under conditions such that a synthetic compound of the following formula is formed, wherein X is carbon or nitrogen, wherein R ³ is absent if X is nitrogen,

R ¹ is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹ is optionally substituted with one or more, the same or different, R ⁴ ;

R ² is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkyl sulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ⁴ ; or R ¹ and R ² form a carbocyclyl, aryl, or heterocyclyl ring optionally substituted with one or more, the same or different, R ⁴ ; or when X is carbon R ¹ , R ² , and R ³ form a multicyclic carbocyclyl; R ³ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is alkyl, halogen, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁵ is optionally substituted with one or more, the same or different, R ⁶ ; and

R ⁶ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl;

R ¹⁰ is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹⁰ is optionally substituted with one or more, the same or different, R ¹² ;

R ¹¹ is alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹¹ is optionally substituted with one or more, the same or different, R ¹² ;

R ¹² is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ¹² is optionally substituted with one or more, the same or different, R ¹³ ;

R ¹³ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, the disclosure contemplates the use of diruthenium catalysts disclosed herein for the intra-molecular insertion reactions for the formation of carbon-to- carbon bonds. In certain embodiment, disclosure contemplates a method of making a ring structure comprising mixing a diruthenium catalyst disclosed herein and a compound comprising a diazo group and the same compound comprising a C-H bond configure about the molecule to form a five or six membered ring.

In certain embodiments, the disclosure contemplates the use of diruthenium catalysts disclosed herein in C-H aminations. In certain embodiments, the disclosure contemplates the use of diruthenium catalysts disclosed herein for the insertion reactions for the formation of carbon to nitrogen bonds, e.g., inter and intra-molecular C-H aminations. See Reddy & Davies, Org. Lett., 2006, 8, 5013- 5016, hereby incorporated by reference.

In certain embodiments, the disclosure relates to a method of making a synthetic compound comprising mixing a compound with an aromatic compound, PhI(OAc)2, NsML (4- nitrobenzenesulfonamide , and a diruthenium catalysts disclosed herein under conditions such that a synthetic compound with a C-N bond is formed.

In certain embodiments, the aromatic compound is a has the following formula

R ¹ R ² and the synthetic compound is wherein, Y is 4-nitrobenzenesulfonamide or 2-nitrobenzenesulfonamide; R ¹ is aryl or aromatic heterocyclyl wherein R ¹ is optionally substituted with one or more, the same or different, R ³ ;

R ² is hydrogen alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ² is optionally substituted with one or more, the same or different, R ³ ; or R ¹ and R ² together with the attached atoms form a carbocyclyl, aryl, or heterocyclyl optionally substituted with one or more, the same or different, R ³ ;

R ³ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ³ is optionally substituted with one or more, the same or different, R ⁴ ;

R ⁴ is hydrogen, alkyl, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfmyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R ⁴ is optionally substituted with one or more, the same or different, R ⁵ ;

R ⁵ is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfmyl, ethylsulfmyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N- ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

In certain embodiments, the synthetic product is in a composition with greater than 55%, 75%, 85%, 95%, 98%, or 99% enantiomeric excess of the following stereioisomers:

In certain embodiments, the disclosure relates to a method of making Rasagiline comprising the step of mixing 2,3-dihydro-lH-indene , PhI(OAc)2, YML·, MgO, and a diruthenium catalyst disclosed herein, wherein Y is 4-nitrobenzenesulfonamide or 2- nitrobenzenesulfonamide, under conditions such that a compound of the following formula is formed,

Reaction of this product with propargyl bromide in potassium carbonate provides the N substituted propargyl product. Removal of the nitrobenzenesulfonamide with DBU and HSCH2CH2OH provides Rasagiline. See Reddy & Davies, Org. Lett., 2006, 8, 5013- 5016, hereby incorporated by reference.

EXPERIMENTAL

The following is intended to provide examples on methods of making and using embodiments of the disclosure. It is not intended to limit the scope.

Synthesis and characterization of a diruthenium catalysts

To confirm that the ligands self-assemble to generate the symmetry structures of diruthenium complexes studies were performed with a S-TPPTTL ligand (Figure 3B). Heating the ligand with RU2(OAC)4C1 , results in the formation of a brown solid, that was confirmed by mass-spectrometry to be the desired diruthenium complex. Treatment of RU2(S-TPPTTL)4C1 with NaBArF, displaces the ruthenium bound chloride and generates the diruthenium cationic species [Ru2(S-TPPTTL)4] ⁺ BARF-. The X-ray structure of RU2(TPPTTL)4C1 showed that the complex had adopted a C4-symmetric bowl-shaped structure.

Enantioselective cyclopropanation with donor/acceptor carbenes

25 °G 1 h 76% yield, 77% qb

Results with diazomalonate gave moderate results (44% yield, 46% ee) because the reactions were conducted at 60 °C. However, aryldiazoacetates are more responsive to certain catalysts. As a test reaction a standard cyclopropanation reaction between an aryl di azoacetate and styrene was conducted. The reaction with RU2(S-TPPTTL)4C1 was be conducted at room temperature and generated the cyclopropane in 76% yield and 77% ee. Enantioselective C-H functionalization

25 °C 48 h

85% ee

A reaction of the aryl di azoacetate with cyclohexane was performed. Cyclohexane is a challenging substate and because it is 28,000 times less reactive that styrene in certain reactions with donor/acceptor carbenes. It was observed that cyclohexane was an effective trap, generating the C-H functionalized product in 85% ee. Even more impressive is the reaction with [RU2(TPPTTL)4]+ BArF- as catalyst at 25 °C, which generated the C-H functionalization product in 76% yield and 95% ee.