Product Details

Main > ORGANIC CHEMICALS > Coupling Reactions > Buchwald Hartwig Coupling Reaction > Co.: DE. L (Ligand/Etc./Patents) > Patent > Assignee, Claims, No. Etc

Product USA. M. No. 01

PATENT NUMBER This data is not available for free

PATENT GRANT DATE October 23, 2001

PATENT TITLE Ligands for metals and improved metal-catalyzed processes based thereon

PATENT ABSTRACT One aspect of the present invention relates to novel ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency

PATENT INVENTORS This data is not available for free

PATENT ASSIGNEE This data is not available for free

PATENT FILE DATE January 13, 1999

PATENT REFERENCES CITED Hayashi et al. Journal of Am. Chem. Soc. (1995), 117, (35) pp. 9101-9102.*
Vyskocil et al. Tetrahedron Lett. (1998), 39, (50) pp. 9298-9292, 1995.*
Driver M. S. and Hartwig F. J. A Second Generation Catalyst for Aryl Halide Animation: Mixed Secondary Amines From Aryl Halides and Primary Amines Catalyzed by (DPPF) PdCl.sub.2), J. Am. Chem. Soc. 118: 7217-7218 (1996).
Guram S. A. et al.: "A Simple Catalytic Method for the Conversion of Aryl Bromides to Arylamines", Angew. Chem. Int. Ed. Engl. 34: 1348-1350 (1995).
Kang, et al. "Catalytic Asymmmetric Allylic Alkylation With a Novel P.S. Bidentale Ligand", Bull. Korean Chem. Soc. 16(5): 439-443 (1995).
Louie, J. and Hartwig F. J. "Palladium- Catalyzed Synthesis of Arylamines from Aryl Halides. Mechanistic Studies Lead to Coupling in the Absence of tin Reagents", Tetrahedron Letters 36(21): 3609-3611 (1995).
Mann, G. and Hartwig, F. J. Palladium Alkoxides: Potential Intermediary in Catalytic Amination, Reductive Elimination of Ethers, and Catalytic Etheration. Comments on Alcohol Elimination from Ir(III) J. Am. Chem. Soc. 118:13109-13110 (1996).
Wolfe P. J. and Buchwald L. S. "Palladium Catalyzed Amination of Aryl Iodides", J. Org. Chem. 61: 1133-1135 (1996).
Zhao, et al. "Synthesis of Arylpiperazines via Palladium-Catalyzed Aromatic Amination Reaction with Unprotected Piperazines", Tetrahedron Letters 37(26): 4463-4466 (1996).
Aranyos et al., "Novel Electron-Rich Bulky Phosphine Ligands Facilitate the Palladium-Catalyzed Preparation of Diaryl Ethers", J. AM. Chem. Soc. 121: 4369-4378 (1999).
Bronco, S. and Consiglio, G., "Regio- and Stereoregular Copolymerisation of Propene with Carbon Monoxide Catalysed by Palladium Complexes Containing Atropisomeric Diphosphine Ligands", Macromol. Chem. Phys. 197: 355-365 (1996).
Chemical Abstracts vol. 123; No. 15, Oct. 9, 1995, Abstract No. 197945; Colombus, Ohio, US.
Chemical Abstracts vol. 124 No. 25, Jun. 17, 1996; Abstract No. 343650, Colombus Ohio, US.
Chemical Abstracts vol. 127 No. 21; Nov. 24, 1997, Abstract No. 293410, Colombus Ohio.
Cho, Y. S. and Shibasaki, M.; "Synthesis and Evaluation of a New Chiral Ligand: 2-diphenylarsino-2'-diphenylphosphino-1,1'-binaphthyl (BINAPAS)", Tetrahedron Letters 39: 1773-1776 (1998).
Crameri et al., "Pratical Synthesis of (S)-2-(4-fluorophenyl)-3-methylbutanoic acid, key building block for the calcium antagonist Mibefradil", Tetrahedron: Asymmetry 8 (21): 3617-3623 (1997).
Ding, K. et al., "Highly Efficient and Pratical Optical Resolution of 2-Amino-2'-hydroxy-1,1'-binaphthyl by Molecular Complexation with N-Benzylcinchonidium Chloride: A Direct Transformation to Binaphthyl Amino Phosphine", Chem. Eur. J. 5 (6): 1734-1737 (1999).
Empsall, D. H. et al., "Complexes of Platinum and Paladium with Tertiary Dimethoxyphenyl-Phosphines: Attempts to Effect O- or C-Metallation", Journal of the Chemical Society Dalton Transactions No. 3: 257-262 (1978).
Gill, F. D. et al., "Transition Metal-Carbon Bonds. Part XXXIII. .sup.1 Internal Metallations of Secondary and Tertiary Carbon Atoms by Platinum(II) and Palladium (III).", Journal of the Chemical Society, Dalton Transactions No. 3: 270-278 (1973).
Gladiali, S. et al., "Synthesis, Crystal Structure, Dynamic Behavior and Reactivity of Dinaphthol [2,1-b:1',2'-d]phospholes and Related Atropisomeric Phosphacyclic Derivatives", J. Org. Chem. 59 (21):6363-6371 (Oct. 21, 1994).
Gladiali, S. et al., "Novel Heterobidentate Ligands for Asymmetric Catalysis: Synthesis and Rhodium-catalysed Reactions of S-Alkyl(R)-2-Diphenylphosphino-1,1'-binaphthyl-2'-thiol", Tetrahedron: Asymmetry 5 (7): 1143-1146 (1994).
Hayashi Tamio, "Asymmetric Hydrosilylation of Olefins Catalyzed by MOP-Palladium Complexes", Acta Chem. Scand. 50 (3):259-266 (1996).
Hattori, T. et al., "Nucleophilic Aromatic Substitution Reactions of 1-Methoxy-2-(diphenylphosphinyl)naphthalene with C-, N-, and O-Nucleophiles: Facile Synthesis of Diphenyl(1-substituted-2-naphthyl)Phosphines", Synthesis, No. 2: 199-202 (Feb. 1994).
Herrmann, A. et al., "Palladacycles: Efficient New Catalysts for the Hack Vinylation of Aryl Halides", Chemisty, A European Journal, 3 (8):1357-1364 (Aug. 1997).
Langer et al., "Catalytic Asymmetric Hydrosilylation of Ketones Using Rhodium-(I)-Complexes of Chiral Phosphinooxazoline Ligands", Tetrahedron: Asymmetry 7(6):1599-1602 (1996).
Jones et al., "O- and C- Metallation of 2-Alkoxyphenylphosphines by Platinum (II)", Journal of the Chemical Society, Dalton Transactions. No. 9: 992-999 (1974).
Old, W. et al., "A Highly Active Catalyst for Palladium-Catalyzed Cross-Coupling Reactions: Room-Temperature Suzuki Couplings and Amination of Unactivated Aryl Chlorides", J. Am. Chem. Soc. 120: 9722-9723 (1998).
Palucki et al., "Synthesis of Oxygen Heterocycles via a Palladium Catalyzed C-O Bond-Forming Reaction", J. Am. Chem. Soc. 118:10333-10334 (1996).
Palucki et al., "Palladium-Catalyzed Intermolecular Carbon-Oxygen Bond Formation: A New Synthesis of Aryl Ethers", J. Am. Chem. Soc. 119: 3395-3396 (1997).
Vyskocil et al., "Derivatives of 2-Amino-2'-dephenylphosphino-1,1'-binaphthyl (MAP) and Their Application in Asymmetric Palladium(0)- Catalyzed Allylic Substitution", J. Org. Chem. 63 (22): 7738-7748 (1998),
Wolfe, P. J. and Buchwald, L. S. "A Highly Active Catalyst for the Room-Temperature Amination and Suzuki Coupling of Aryl Chlorides", Angewandte Chemie. International Edition 38(16): 2413-2416 (1999).
Wolfe, P. J. et al. "Highly Active Palladium Catalysts for Suzuki Coupling Reactions", J. Am. Chem. Soc. 121(41):9550-9561 (Oct. 20, 1999).
Bei, X. et al., "A Convenient Palladium/Ligand Catalyst for Suzuki Cross-Coupling Reactions of Arylboronic Acids and Aryl Chlorides", Tetrahedron Letters, 40:3855-3858 (1999).
Bei, X. et al., "General and Efficient Palladium-Catalyzed Aminations of Aryl Chlorides", Tetrahedron Letters, 40:1237-1240 (1999).
Bei, X. et al., "Phenyl Backbone-Derived P,O- and P,N-Ligands for Palladium/Ligand-Catalyzed Aminations of Aryl Bromides, Iodides, and Chlorides. Synthesis and Structures of (P,O).sub.n -Palladium(II)Aryl(Br) Complexes", Organometallics, 18:1840-1853 (1999).
Beller, M. et al., "First Palladium-Catalyzed Aminations of Aryl Chlorides", Tetrahedron Letters, 38:2073-2074 (1997).
Beller, M., "Palladacycles as Efficient Catalysts for Aryl Coupling Reactions", Agnew. Chem. Int. Ed. Engl., 34:1848-1849 (1995).
Brenner, E. et al., "New Efficient Nickel(0) Catalysed Amination of Aryl Chlorides", Tetrahedron Letters, 39:5359-5362 (1998).
Bumagin, N. et al., "Ligandless Palladium catalyzed Reactions of Arylboronic Acids and Sodium Tetraphenylborate with Aryl Halides in Aqueous Media", Tetrahedron, 53:14437-14450 (1997).
Cho, S. Y. et al, "The assymetric synthesis of cyclopentane derivatives by palladium-catalyzed coupling of prochiral alkylboron compounds", Tetrahedron:Assymetry, 9:3751-3754 (1998).
Cornils, B., "Industrial Aqueous Biphasic Catalysis: Status and Directions", Org. Proc. Res. Dev., 2:121-127 (1998).
Firooznia, F. et al., "Synthesis of 4-Substituted Phenylalanines by Cross-Coupling Reactions: Extension of the Methodology to Aryl Chlorides", Tetrahedron Letters, 39:3985-3988 (1998).
Galland, J.-C. et al., "Cross-Coupling of Chloroarenes with Boronic Acids using a Water-Soluble Nickle Catalyst", Tetrahedron Letters, 40:2323-2326 (1999).
Hamann, B. et al., "Sterically Hindered Chelating Alkyl Phosphines Provide Large Rate Accelerations in Palladium-Catalyzed Amination of Aryl Iodides, Bromides, and Chlorides, and the First Amination of Aryl Tosylates", J. Am. Chem. Soc., 120:7369-7370 (1998).
Herrmann, W. et al., "Chelating-N-heterocycle carbene ligands in palladium-catalyzed heck-type reactions", J. Organometallic Chem., 557:93-96 (1998).
Indolese, A., "Suzuki-Type Coupling of Chloroarenes with Arylboronic Acids Catalysed by Nickel Complexes", Tetrahedron Lettters, 38:3512-3516 (1997).
Kawatsura, M. et al., "Simple, Highly Active Palladium Catalysts for Ketone and Malonate Arylation: Dissecting the Importance of Chelation and Steric Hindrance", J. Am. Chem. Soc., 121, 1473-1478 (1999).
Littke, A. et al., "A Convenient and General Method for Pd-Cata;yzed Suzuki Cross-Couplings of Aryl Chlorides and Arylboronic Acids", Agnew, Chem. Int. Ed., 37:3387-3388 (1998).
Mann, G. et al., "Palladium-Catalyzed C-N(sp.sup.2) Bond Formation: N-Arylation of Aromatic and Unsaturated Nitrogen and the Reductive Elimination Chemisty of Palladium Azolyl and Methyleneamido Complexes", J. Am. Chem. Soc., 120:827-828 (1998).
Mann, G. et al., "Palladium-Catalyzed C-O Coupling Involving Unactivated Aryl Halides, Sterically Induced Reductive Elimination To Form the C-O Bond in Diary Ethers", J. Am. Chem. Soc., 121-3224-3225 (1999).
Mitchell, M. B. et al., "Coupling of Heteroaryl Chlorides tieh Arylboronic Acids in the Presence of [1,4-Bis-(Diphenylphosphine)Butane]Palladium(II) Dichloride", Tetrahedron Letters, 20:273-2276 (1991).
Muratake, H. et al., "Intramolecular Cyclization Using Palladium-Catalyzed Arylation toward Formyl and Nitro Groups", Tetrahedron Letters, 40:2355-2358 (1999).
Muratake, H. et al., "Palladium-Catalyzed Intramolecular .alpha.-Arylation of Aliphatic Ketones", Tetrahedron Letters, 38:7581-7582 (1997).
Nishiyama, M. et al., "Synthesis of N-Arylpiperazines from Aryl Halides and Piperazine under a Palladium Tri-tert-butylphosphine Catalyst", Tetrahedron Letters, 39:617-620 (1998).
Reddy, N. P. et al., "Palladium-Catalyzed Amination of Aryl Chlorides", Tetrahedron Letters, 27:4807-4810 (1997).
Reirmeier, T. et al., "Palladium-catalyzed C-C- and C-N-coupling reactions of Aryl Chlorides", Topics in Catalysis, 4:301-309 (1997).
Saito, S. et al., "Synthesis of Biaryls via a Nickle(0)-Catalyzed Cross Coupling Reaction of Chloroarenes with Arylboronic Acids", J. Org. Chem., 62:8024-8030 (1997).
Shen, W., "Palladium Catalyzed Coupling of Aryl Chlorides with Arylboronic Acids", Tetrahedron Letters, 38:5575-5578 (1997).
Thompson, W. et al., "An Efficient Synthesis of Arylpyrazines and Bipyridines", J. Org. Chem., 53:2052-2055 (1988).
Uemura, M. et al., "Catalytic asymmetric induction of planar chirality: Palladium-catalyzed asymmetric cross-coupling of meso tricarconyl(arene)chromium complexes with alkenyl- and arylboronic acids", J. Organometallic Chem., 473:129-137 (1994).
Wang, D. et al., "New polymerization catalyzed by palladium complexes: synthesis of poly(p-phenylenevinylene) derivatives", Chem. Commun., 529-530 (1999).
Yamamoto, T. et al., "Palladium-Catalyzed Synthesis of Triarylamines from Aryl Halides and Diarylamines", Tetrahedron Letters, 39:2367-2370 (1998).
Ahman, J., et al., "Asymmetric Arylation of Ketone Enolates," J. Am. Chem. Co., 120, pp. 1918-1919, 1998.
Benincori, T., et al., "(Diphenylphosphino)-biheteroaryls: the First Example of a New Class of Chiral Atropisomeric Chelating Diphosphine Ligands for Transition Metal Catalysed Stereoselective Reactions," J. Chem. Soc., Chem. Commun., pp. 685-686, 1995.
Fiaud, J., et al., "Preparation of Optically Pure 1,2,5-Triphenylphospholane, Use as Ligand for Enantioselective Transition-Metal Catalysis," Tetrahedron Letters, vol. 32, No. 38, pp. 5089-5092, 1991.
Frejd, T., et al., "2,2'-Dimethyl-6,6'-bis(diphenylphosphino)biphenyl (BIPHEMP) as a Chiral Ligand for Transition Metal Catalyzed Asymmetric Synthesis of Binaphthyls and for Asymmetric Hydrogenation. A Comparison with BINAP," Acta Chemica Scandinavica 43, pp. 670-675, 1989.
Hiroi, K., et al., "Asymmetric Induction Reactions. VI. .sup.1,2) Asymmetric Synthesis of a Cyclopentene Derivative by Transition Metal-Catalyzed Asymmetric Vinylcyclopropane-Cyclopentene Rearrangements with Chiral Phosphine Ligands," Chem. Pharm. Bull., 42(3) pp. 470-474 1994.
Shirakawa, E., et al, "Carbostannylation of Alkynes Catalyzed by an Iminophosphine--Palladium Complex," J. Am. Chem. Soc., 120, pp. 2975-2976, 1998.
Sodeoka, M., et al., Stable Diaqua Palladium (II) Complexes of BINAP and Tol-BINAP as Highly Efficient Catalysts for Asymmetric Aldol Reactions, SYNLETT, pp. 463-466, May 1997.
Sodeoka, M., et al., "Asymmetric Synthesis Using Palladium Catalysts," Pure & Appl. Chem., vol. 70, No. 2, pp. 411-414, 1998.
Tamao, K., et al., "Optically Active 2,2'-bis(Diphenylphosphinomethyl)-1,1'-Binaphthyl: A New Chiral Bidentate Phosphine Ligand for Transition-Metal Complex Catalyzed Asymmetric Reactions," Tetrahedron Letters, No. 16, pp. 1389-1392, 1977.
Tanner, D., et al., "C.sub.2 -Symmetric Bis(Aziridines): A New Class of Chiral Ligands for Transition Metal-Mediated Asymmetric Synthesis," Tetrahedron Letters, vol. 35, No. 26, pp. 4631-4634, 1994.
Tokunoh, R., et al., "Synthesis and Crystal Structure of a New C.sub.2 -Symmetric Chiral Bis-sulfoxide Ligand and Its Palladium (II) Complex," Tetrahedron Letters, vol. 36, No. 44, pp. 8035-8038, 1995.
Trost, B., et al., "Asymmetric Ligands for Transition-Metal-Catalyzed Reactions: 2-Diphenylphosphinobenzoyl Derivatives of C.sub.2 -Symmetric Diols and Diamines," Angew. Chem. Int. Ed. Engl. 31 No. 2, 1992.
Trost, B., et al., "Synthesis of 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), an Atropisomeric Chiral Bis(triaryl)phosphine, and Its Use in the Rhodium(I)-Catalyzed Asymmetric Hydrogenation of .alpha.-(Acylamino) acrylic Acids," J. Am. Chem. Soc., 102, pp. 1932-1934, 1980.
Vyskocil, S., et al., "Derivatives of 2-Amino-2'-diphenylphosphino-1,1'-binaphthyl (MAP) and their Application in Pd(0)-Catalyzed Allylic Substitution," Am. Chem. Soc., Newsletter and Abstracts, 216.sup.th ACS National Meeting, Boston, MA Aug. 23-27, 1998, #538.
Wolfe, J., et al., "An Improved Catalyst System for Aromatic Carbon-Nitrogen Bond Formation: The Possible Involvement of Bis(Phosphine)Palladium Complexes as Key Intermediates," J. Am. Chem. Soc., 118, pp. 7215-7216, 1996.
Yoshikawa et al.; "A New Type of Atropisomeric Biphenylbisphosphine Ligand, (R)-MOC-BIMOP and Its Use in Efficient Asymmetric Hydrogenation of .alpha.-Aminoketone and Itaconic Acid .sup.1 ", Tetrahedron Asymmetry, 3(1): 13-16, (1992).
Bayston et al.; "Preparation and Use of a Polymer Supported BINAP Hydrogenation Catalyst", J.Org. Chem. 63:3137-3140, (1998).
Enev et al.; "a Bis-Steroidal Phosphine as New Chiral Hydrogenation Ligand", J. Org. Chem. 62:7092-7093, (1997).
Murata et al.; "Synthesis of Atropisomeric Biphenybisphosphine, 6,6'-Bis (Dicyclohexlphosphino)-3',-Dimethoxy-2,2' 4,4'-Tetramethyl -1,1'-Biphenyl and its Use In Rhodium (I)-Catalyzed Asymmetric Hydrogenation .sup.1 ", Chem. Pharm. Bull. 39(10):2767-2769, (1991).
Schmid et al.; "35. Axially Asymmetric Diphosphines in the Biphenyl Series: Synthesis of (6,6'-Dimethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) ('MeO-BIPHEP') and Analogues via an ortho-Lithiation/ Iodination Ullmann-Reaction Approach", Helvetica Chimica Acta vol. 74: 370-389 (1991).
Uozumi et al.; "Synthesis of Optically Active 2-(Diarylphosphino)-1,1'-bynaphthyls, Efficient Chiral Mondentate Phosphine Ligands", J. Org. Chem. 58: 1945-1948, (1993).
VyskoCil et al.; "Derivatives of 2-amino-2'-diphenylphosphino-1,1'-binaphthl (MAP and Their Application in Asymmetric Palladium (0)-Catalyzed Allylic Substitution", J. Org. Chem. 63: 7738-7748, (1998).
Zhang et al., "Synthesis of Partially Hydrogenated BINAP Variants", Tetrahedron Letters 32(49): 7283-7286, (1991).

PATENT GOVERNMENT INTERESTS GOVERNMENT FUNDING

This invention was made with government support under Grant Number 9421982-CHE awarded by the National Science Foundation. The government has certain rights in the invention.

PATENT PARENT CASE TEXT This data is not available for free

PATENT CLAIMS We claim:

1. The ligand represented by structure 1: ##STR142##

wherein

A and B independently represent fused rings selected from the group consisting of monocyclic or polycyclic cycloalkyls, cycloalkenyls, aryls, and heterocyclic rings, said rings having from 4 to 8 atoms in a ring structure;

X represents NR.sub.2, P(alkyl).sub.2, P(cycloalkyl).sub.2, AsR.sub.2, or OR;

Y represents H, alkyl, NR.sub.2, or AsR.sub.2 ;

X and Y are not identical;

R, R.sub.1, R.sub.2, R.sub.3, and R.sub.4, for each occurrence, independently represent hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.5 and R.sub.6, for each occurrence, independently represent halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or --(CH.sub.2).sub.m --R.sub.80 ;

A and B independently are unsubstituted or substituted with R.sub.5 and R.sub.6, respectively, any number of times up to the limitations imposed by stability and the rules of valence;

R.sub.1 and R.sub.2, or R.sub.3 and R.sub.4, or both, taken together optionally represent a ring having a total of 5-7 atoms in the backbone of said ring; said ring having zero, one or two heteroatoms in its backbone; and said ring is substituted or unsubstituted;

R.sub.80 represents an unsubstituted or substituted aryl, cycloalkyl, cycloalkenyl, heterocycle, or polycycle;

m is an integer in the range 0 to 8 inclusive; and

the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

2. The ligand of claim 1, wherein

R is selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80 ; and

R.sub.5 and R.sub.6 are selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80.

3. The ligand of claim 1, wherein X is P(alkyl).sub.2, or P(cycloalkyl).sub.2 ; and Y is hydrogen.

4. The ligand of claim 3, wherein X is P(tert-butyl).sub.2, or P(cyclohexyl).sub.2.

5. The ligand represented by structure 2: ##STR143##

wherein

X represents PR.sub.2 ;

Y represents H, NR.sub.2, OR, or SR;

R represents, independently for each occurrence, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, or --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, and R.sub.8, for each occurrence, independently represent hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or --(CH.sub.2).sub.m --R.sub.80 ;

one or more pairs of substituent, with an ortho-relationship therebetween, selected from the group consisting of R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, and R.sub.8, taken together optionally represent a ring having a total of 5-7 atoms in the backbone of said ring; said ring having zero, one or two heteroatoms in its backbone; and said ring is substituted or unsubstituted;

R.sub.80 represents an unsubstituted or substituted aryl, cycloalkyl, cycloalkenyl, heterocycle, or polycycle;

m is an integer in the range 0 to 8 inclusive; and

the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

6. amended) The ligand of claim 5, wherein:

R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, and R.sub.8 are selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80.

7. The ligand of claim 5, wherein X is hydrogen; and Y is PR.sub.2.

8. The ligand of claim 7, wherein R is alkyl.

9. The ligand represented by structure 3: ##STR144##

wherein

X represents NR.sub.2, P(alkyl).sub.2, P(cycloalkyl).sub.2, AsR.sub.2, or OR;

Y represents H, alkyl, NR.sub.2, AsR.sub.2, or OR;

X and Y are not identical;

R, R.sub.1, R.sub.2, R.sub.3, and R.sub.4, for each occurrence, independently represent hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.5 and R.sub.6, for each occurrence, independently represent halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or --(CH.sub.2).sub.m --R.sub.80 ;

the B and B' rings of the binaphthyl core independently are unsubstituted or substituted with R.sub.5 and R.sub.6, respectively, any number of times up to the limitations imposed by stability and the rules of valence;

R.sub.1 and R.sub.2, or R.sub.3 and R.sub.4, or both, taken together optionally represent a ring consisting of a total of 5-7 atoms in the backbone of said ring; said ring having zero, one or two heteroatoms in its backbone; and said ring is substituted or unsubstituted;

R.sub.80 represents an unsubstituted or substituted aryl, cycloalkyl, cycloalkenyl, heterocycle, or polycycle;

m is an integer in the range 0 to 8 inclusive; and

the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

10. The ligand of claim 9, wherein:

R is selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80 ; and

R.sub.5 and R.sub.6 are selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80.

11. The ligand of claim 9, wherein X is P(alkyl).sub.2, or P(cycloalkyl).sub.2 ; and Y is hydrogen.

12. The ligand of claim 11, wherein X is P(tert-butyl).sub.2, or P(cyclohexyl).sub.2.

13. The ligand represented by structure 4: ##STR145##

wherein

R is selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and --(CH.sub.2).sub.m --R.sub.80 ;

the A and A' rings of the biphenyl core independently are unsubstituted or substituted with R.sub.1 and R.sub.2, respectively, any number of times up to the limitations imposed by stability and the rules of valence;

R.sub.1 and R.sub.2 are selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.80 represents an unsubstituted or substituted aryl, cycloalkyl, cycloalkenyl, heterocycle, or polycycle;

m is an integer in the range 0 to 8 inclusive; and

the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

14. The ligand of claim 13, wherein:

R.sub.1 and R.sub.2 are absent;

both instances of R in N(R).sub.2 are lower alkyl; and

both instances of R in P(R).sub.2 are cycloalkyl.

15. The ligand represented by structure 5: ##STR146##

wherein

R is selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and --(CH.sub.2).sub.m --R.sub.80 ;

the A, B, A', and B' rings of the binaphthyl core independently are unsubstituted or substituted with R.sub.1, R.sub.2, R.sub.3, and R.sub.4, respectively, any number of times up to the limitations imposed by stability and the rules of valence;

R.sub.1, R.sub.2, R.sub.3, and R.sub.4, are selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.80 represents an unsubstituted or substituted aryl, cycloalkyl, cycloalkenyl, heterocycle, or polycycle;

m is an integer in the range 0 to 8 inclusive; and

the ligand, when chiral, is a mixture of enantiomers or a single enantiomer;

provided that when R is cycloalkyl or aryl, there is at least one instance of R.sub.1, R.sub.2, R.sub.3, or R.sub.4.

16. The ligand of claim 15, wherein:

R.sub.1, R.sub.2, R.sub.3, and R.sub.4, are absent; and

all instances of R are lower alkyl or cycloalkyl.

17. The ligand represented by structure 7: ##STR147##

wherein

R is selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and --(CH.sub.2).sub.m --R.sub.80 ;

P(R).sub.2 represents P(alkyl).sub.2, or P(cycloalkyl).sub.2 ;

the A, B, A', and B' rings of the binaphthyl core independently are unsubstituted or substituted with R.sub.1, R.sub.2, R.sub.3, and R.sub.4, respectively, any number of times up to the limitations imposed by stability and the rules of valence;

R.sub.1, R.sub.2, R.sub.3, and R.sub.4, are selected, independently for each occurrence, from the group consisting of alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, --SiR.sub.3, and --(CH.sub.2).sub.m --R.sub.80 ;

R.sub.80 represents an unsubstituted or substituted aryl, cycloalkyl, cycloalkenyl, heterocycle, or polycycle;

m is an integer in the range 0 to 8 inclusive; and

the ligand, when chiral, is a mixture of enantiomers or a single enantiomer.

18. The ligand of claim 17, wherein:

R.sub.1, R.sub.2, R.sub.3, and R.sub.4, are absent;

both instances of R in N(R).sub.2 are lower alkyl; and

P(R).sub.2 represents P(tert-butyl).sub.2, or P(cyclohexyl).sub.2.

19. The method depicted in Scheme 1: ##STR148##

wherein

Ar is selected from the set consisting of optionally substituted monocyclic and polycyclic aromatic and heteroaromatic moieties;

X is selected from the set consisting of Cl, Br, I, --OS(O).sub.2 alkyl, and --OS(O).sub.2 aryl;

R' and R" are selected, independently for each occurrence, from the set consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, aralkyl, alkoxyl, amino, trialkylsilyl, and triarylsilyl;

R' and R", taken together, may form an optionally substituted ring consisting of 3-10 backbone atoms inclusive; said ring optionally comprising one or more heteroatoms beyond the nitrogen to which R' and R" are bonded;

R' and/or R" may be covalently linked to Ar such that the amination reaction is intramolecular;

the transition metal is selected from the set consisting of the Group VIIIA metals;

the ligand is selected from the set consisting of 1-7 inclusive; and

the base is selected from the set consisting of hydrides carbonates, phosphates, alkoxides, amides, carbanions, and silyl anions.

20. The method of claim 19, wherein:

the ligand is 2;

the transition metal is palladium; and

the base is an alkoxide, amide, phosphate, or carbonate.

21. The method of claim 19 or 20, wherein:

the ligand is 2, wherein X is hydrogen, and Y represents P(alkyl).sub.2 ; and

X represents Cl or Br.

22. The method of claim 19, wherein:

the ligand is 4;

the transition metal is palladium; and

the base is an alkoxide, amide, phosphate, or carbonate.

23. The method of claim 20, wherein:

the ligand is 4, wherein R.sub.1 and R.sub.2 are absent; P(R).sub.2 represents PCy.sub.2, and N(R).sub.2 represents NMe.sub.2 ; and

X represents Cl or Br.

24. The method of claim 19, wherein: HN(R')R" represents an optionally substituted heteroaromatic compound.

25. The method of claim 19, wherein: X represents Cl; the ligand is 4, wherein R.sub.1 and R.sub.2 are absent, P(R).sub.2 represents PCy.sub.2, and N(R).sub.2 represents NMe.sub.2 ; the transition metal is palladium; and the base is an alkoxide, amide, phosphate, or carbonate.

26. The method of claim 19, wherein: X represents Br or I; the ligand is 4, wherein R.sub.1 and R.sub.2 are absent, P(R).sub.2 represents PCy.sub.2, and N(R).sub.2 represents NMe.sub.2 ; the transition metal is palladium; the base is an alkoxide, amide, phosphate, or carbonate; and the transformation occurs at room temperature.

27. The method of claim 19, wherein: the ligand is 5; the transition metal is palladium; and the base is an alkoxide, amide, phosphate, or carbonate.

28. The method of claim 19, wherein: X represents Cl; the ligand is 5, wherein R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are absent, and all occurrences of R are cyclohexyl; the transition metal is palladium; and the base is an alkoxide, amide, phosphate, or carbonate.

29. The method of claim 19, wherein: the ligand is 2, wherein X and Y both represent P; the transition metal is palladium; and the base is an alkoxide, amide, phosphate, or carbonate.

30. The method of claim 19, wherein: X represents Cl; the ligand is 2, wherein X and Y both represent P, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, and R.sub.8 are absent, and all occurrences of R are cyclohexyl; the transition metal is palladium; and the base is an alkoxide, amide, phosphate, or carbonate.

31. The method of claim 19, wherein (alkenyl)X serves as a surrogate for ArX.

32. The method of claim 19, wherein the product is provided in a yield of greater than 50%.

33. The method of claim 19, wherein the product is provided in a yield of greater than 70%.

34. The method of claim 19, wherein the product is provided in a yield of greater than 85%.

35. The method of claim 19, wherein the reaction occurs at ambient temperature.

36. The method of claim 19, wherein the catalyst complex is present in less than 0.01 mol % relative to the limiting reagent.

37. The method of claim 19, wherein the catalyst complex is present in less than 0.0001 mol % relative to the limiting reagent.

38. The method depicted in Scheme 2: ##STR149##

wherein

Ar and Ar' are independently selected from the set consisting of optionally substituted monocyclic and polycyclic aromatic and heteroaromatic moieties;

X is selected from the set consisting of Cl, Br, I, --OS(O).sub.2 alkyl, and --OS(O).sub.2 aryl;

Ar and Ar' may be covalently linked such that the reaction is intramolecular;

the transition metal is selected from the set consisting of the Group VIIIA metals;

the ligand is selected from the set consisting of 1-7 inclusive; and

the base is selected from the set consisting of carbonates, phosphates, fluorides, alkoxides, amides, carbanions, and silyl anions.

39. The method of claim 38, wherein

the ligand is 2;

the transition metal is palladium; and

the base is an alkoxide, amide, phosphate, or carbonate.

40. The method of claim 38 or 39, wherein

the ligand is 2, wherein X is hydrogen, and Y represents P(alkyl).sub.2 ; and

X represents Cl or Br.

41. The method of claim 38, wherein:

the transition metal is palladium;

the ligand is 4; and

the base is an alkoxide, amide, carbonate, phosphate, or fluoride.

42. The method of claim 38, wherein:

the ligand is 4, wherein R.sub.1 and R.sub.2 are absent; P(R).sub.2 represents PCy.sub.2, and N(R).sub.2 represents NMe.sub.2 ;

X represents Cl or Br; and

the reaction occurs at room temperature.

43. The method of claim 38, wherein (alkenyl)X serves as a surrogate for ArX, and/or (alkenyl)B(OH).sub.2 serves as a surrogate for ArB(OH).sub.2.

44. The method of claim 38, wherein the product is provided in a yield of greater than 50%.

45. The method of claim 38, wherein the product is provided in a yield of greater than 70%.

46. The method of claim 38, wherein the product is provided in a yield of greater than 85%.

47. The method of claim 38, wherein the reaction occurs at ambient temperature.

48. The method of claim 38, wherein the catalyst complex is present in less than 0.01 mol % relative to the limiting reagent.

49. The method of claim 38, wherein the catalyst complex is present in less than 0.0001 mol % relative to the limiting reagent.

50. The method depicted in Scheme 3: ##STR150##

wherein

Ar is selected from the set consisting of optionally substituted monocyclic and polycyclic aromatic and heteroaromatic moieties;

R is selected from the set consisting of optionally substituted alkyl, heteroalkyl, and aralkyl;

R' is selected, independently for each occurrence, from the set of alkyl and heteroalkyl; the carbon-boron bond of said alkyl and heteroalkyl groups being inert under the reaction conditions, e.g., BR'.sub.2 taken together represents 9-borobicyclo[3.3.1]nonyl.

X is selected from the set consisting of Cl, Br, I, --OS(O).sub.2 alkyl, and --OS(O).sub.2 aryl;

Ar and R may be covalently linked such that the reaction is intramolecular;

the transition metal is selected from the set consisting of the Group VIIIA metals;

the ligand is selected from the set consisting of 1-7 inclusive; and

the base is selected from the set consisting of carbonates, phosphates, fluorides, alkoxides, amides, carbanions, and silyl anions.

51. The method of claim 50, wherein

the ligand is 2;

the transition metal is palladium; and

the base is an alkoxide, amide, phosphate, or carbonate.

52. The method of claim 50 or 51, wherein:

the ligand is 2 wherein X is hydrogen, and Y represents P(alkyl).sub.2 ; and

X represents Cl or Br.

53. The method of claim 50, wherein

X represents Cl or Br;

the transition metal is palladium;

the ligand is 4; and

the base is an alkoxide, amide, carbonate, phosphate, or fluoride.

54. The method of claim 50, wherein

the ligand is 4, wherein R.sub.1 and R.sub.2 are absent; P(R).sub.2 represents PCy.sub.2, and N(R).sub.2 represents NMe.sub.2 ; and

X represents Cl.

55. The method of claim 50, wherein (alkenyl)X serves as a surrogate for ArX.

56. The method of claim 50, wherein the product is provided in a yield of greater than 50%.

57. The method of claim 50, wherein the product is provided in a yield of greater than 70%.

58. The method of claim 50, wherein the product is provided in a yield of greater than 85%.

59. The method of claim 50, wherein the reaction occurs at ambient temperature.

60. The method of claim 50, wherein the catalyst complex is present in less than 0.01 mol % relative to the limiting reagent.

61. The method of claim 50, wherein the catalyst complex is present in less than 0.0001 mol % relative to the limiting reagent.

62. The method depicted in Scheme 4: ##STR151##

wherein

Ar is selected from the set consisting of optionally substituted monocyclic and polycyclic aromatic and heteroaromatic moieties;

R, R', and R" are selected, independently for each occurrence, from the set consisting of H, alkyl, heteroalkyl, aralkyl, aryl, heteroaryl;

X is selected from the set consisting of Cl, Br, I, --OS(O).sub.2 alkyl, and --OS(O).sub.2 aryl;

Ar and one of R, R', and R" may be covalently linked such that the reaction is intramolecular;

the transition metal is selected from the set consisting of the Group VIIIA metals;

the ligand is selected from the set consisting of 1-7 inclusive; and

the base is selected from the set consisting of carbonates, phosphates, fluorides, alkoxides, amides, carbanions, and silyl anions.

63. The method of claim 62, wherein

the ligand is 2;

the transition metal is palladium; and

the base is an alkoxide, amide, phosphate, or carbonate.

64. The method of claim 62 or 63, wherein

the ligand is 2, wherein X is hydrogen, and Y represents P(alkyl).sub.2 ; and

X represents Cl or Br.

65. The method of claim 62, wherein

X represents Cl or Br;

the transition metal is palladium;

the ligand is 4; and

the base is an alkoxide, or amide.

66. The method of claim 62, wherein

the ligand is 4, wherein R.sub.1 and R.sub.2 are absent; P(R).sub.2 represents PCy.sub.2, and N(R).sub.2 represents NMe.sub.2.

67. The method of claim 62, wherein

X represents Br; and

the reaction occurs at room temperature.

68. The method of claim 62, wherein (alkenyl)X serves as a surrogate for ArX.

69. The method of claim 62, wherein the product is provided in a yield of greater than 50%.

70. The method of claim 62, wherein the product is provided in a yield of greater than 70%.

71. The method of claim 62, wherein the product is provided in a yield of greater than 85%.

72. The method of claim 62, wherein the reaction occurs at ambient temperature.

73. The method of claim 62, wherein the catalyst complex is present in less than 0.01 mol % relative to the limiting reagent.

74. The method of claim 62, wherein the catalyst complex is present in less than 0.0001 mol % relative to the limiting reagent.

75. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to provide the product at room temperature.

76. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to provide the product when X is chloride.

77. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to provide the product utilizing less than 0.01 mol % of the catalyst relative to the limiting reagent.

78. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to provide the product utilizing less than 0.0001 mol % of the catalyst relative to the limiting reagent.

79. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to consume the limiting reagent in less than 48 hours.

80. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to consume the limiting reagent in less than 24 hours.

81. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to consume the limiting reagent in less than 12 hours.

82. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to give the product in a yield of greater than 50% in less than 48 hours.

83. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to give the product in a yield of greater than 50% in less than 24 hours.

84. The method of claim 19, 38, 50, or 62, wherein the transition metal and ligand are selected to give the product in a yield of greater than 50% in less than 12 hours.
--------------------------------------------------------------------------------

PATENT DESCRIPTION BACKGROUND OF THE INVENTION

Transition metal catalyst complexes play important roles in many areas of chemistry, including the preparation of polymers and pharmaceuticals. The properties of these catalyst complexes are recognized to be influenced by both the characteristics of the metal and those of the ligands associated with the metal atom. For example, structural features of the ligands can influence reaction rate, regioselectivity, and stereoselectivity. Bulky ligands can be expected to slow reaction rate; electron-withdrawing ligands, in coupling reactions, can be expected to slow oxidative addition to, and speed reductive elimination from, the metal center; and electron-rich ligands, in coupling reactions, conversely, can be expected to speed oxidative addition to, and slow reductive elimination from, the metal center.

In many cases, the oxidative addition step in the accepted mechanism of a coupling reaction is deemed to be rate limiting. Therefore, adjustments to the catalytic system as a whole that increase the rate of the oxidative addition step should increase overall reaction rate. Additionally, the rate of oxidative addition of a transtion metal catalyst to the carbon-halogen bond of an aryl halide is known to decrease as the halide is varied from iodide to bromide to chloride, all other factors being equal. Because of this fact, the more stable, lower molecular weight, and arguably more easy to obtain, members of the set of reactive organic halides--the chlorides--are the poorest substrates for traditional transition metal catalyzed coupling reactions and the like.

To date, the best halogen-containing substrates for transtion metal catalyzed carbon--heteroatom and carbon-carbon bond forming reactions have been the iodides. Bromides have often been acceptable substrates, but typically required higher temperatures, longer reaction times, and gave lower yields of products.

SUMMARY OF THE INVENTION

One aspect of the present invention relates to novel bidentate ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon--carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, number of catalyst turnovers, reaction conditions, and efficiency.

Unexpected, pioneering improvements over the prior art have been realized in transition metal-catalyzed: aryl amination reactions; Suzuki couplings to give both biaryl and alkylaryl products; and .alpha.-arylations of ketones. The ligands and methods of the present invention enable for the first time, the efficient use of aryl chlorides, inter alia, in the aforementioned reactions. Additionally, the ligands and methods of the present invention enable for the first time transformations utilizing aryl bromides or chlorides to proceed efficiently at room temperature. Furthermore, the ligands and methods of the present invention enable the aforementioned reactions to occur at synthetically useful rates using extremely small amounts of catalyst, e.g., 0.000001 mol % relative to the limiting reagent.

PATENT EXAMPLES available on request

PATENT PHOTOCOPY available on request

Want more information ?
Interested in the hidden information ?
Click here and do your request.

back