Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2001-02-26
2002-05-07
Davis, Brian J. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S305000, C564S408000, C356S402000, C356S408000
Reexamination Certificate
active
06384282
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process for addition of amines to carbon-carbon double bonds, and more particularly to a process of adding amines to carbon-carbon double bonds in an enantioselective manner. The method of the invention utilizes a transition metal catalyst made from a Group 8 metal and a ligand containing one or more 2-electron donor atoms. The present invention is also directed to a colorimetric assay to evaluate potential catalysts in these reactions.
2. Brief Description of the Related Art
The metal-catalyzed addition of amines to carbon-carbon double bonds is an unsolved, synthetically important problem (Muller, T. E.; Beller, M.
Chem. Rev
. 1998, 98, 675-703; Han, L.-B.; Tanaka, M.
Chem Commun
1999, 395-402; Gasc, M. B.; Lattes, A.; Perie, J. J. Tetrahedron 1983, 39, 703-731). Recent advances have been made using lanthanide (Tian, S.; Arredondo, V. M.; Stern, C. L.; Marks, T. J.
Organometallics
1999, 18, 2568-2570; Arredondo, V. M.; Tian, S.; McDonald, F. E.; Marks, T. J.
J. Am. Chem Soc
. 1999, 121, 3633-3639; Li, Y. W.; Marks, T. J.
J. Am. Chem. Soc
. 1996, 118, 9295-9306) and precious metal complexes, (Coulson, D. R.
Tetrahedron Lett
. 1971, 429-430; Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Herwig, J.; Muller, T. E.; Thiel, O. R. Chem. Eur. J. 1999, 5, 1306-1319; Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Müller, T., E. Eur.
J. Inorg. Chem
. 1999, 1121-1132; Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D.
J. Am. Chem. Soc
. 1988, 110, 6738-6744; Dorta, R.; Egli, P.; Zurcher, F.; Togni, A.
J. Am. Chem. Soc
. 1997, 119, 10857-10858) but a catalyst that displays broad functional group tolerance, useful rates, and high turnover numbers for an intermolecular addition has been reported only recently. Specifically, the present inventors reported the addition of aromatic amines to both vinylarenes (Kawatsura, M.; Hartwig, J. F.
J. Am. Chem. Soc
. 2000, 122, 9546-9547) and dienes (Loeber, O.; Kawatsura, M.; Hartwig, J. F.
J. Am. Chem. Soc
. 2000, in press), and this chemistry included asymmetric additions.
The present inventors have also been interested in developing catalysts for the addition of amines to acrylic acid derivatives. Some of these reactions can be conducted in protic solvents under relatively mild conditions without a catalyst, but some cases do occur slowly, and most examples occur slowly in aprotic solvents. Thus, one could develop enantioselective additions of amines to acrylic acid derivatives if transition metal catalysts could be found for these transformations. The products of these additions would be &bgr;-amino acid derivatives that can be used in peptide analogs, or as precursors to optically active aminoalcohols, diamines, and lactams.
Lewis acids and bases catalyze the addition of azide and derivatives of hydroxylamine to substituted acrylates, and some of the catalysts provide nonracemic products in high enantiomeric excess (Sibi, M. P.; Shay, J. J.; Liu, M.; Jasperse, C. P.
J. Am. Chem. Soc
. 1998, 120, 6615-6616; Guerin, D. J.; Horstmann, T. E.; Miller, S.
J. Org. Lett
. 1999, 1, 1107; Myers, J. K.; Jacobsen, E. N.
J. Am. Chem. Soc
. 1999, 121, 8959). However, these catalysts are likely to be poisoned by alkyl- and arylamine reagents. Trogler reported the addition of anilinium salts to acrylonitrile catalyzed by palladium alkyl complexes ligated by either the PCP ligand (t-Bu)
2
P(CH
2
)
2
CH(CH
2
)
2
P(t-Bu)
2
or the chelating phosphine Me
2
PCH
2
CH
2
PMe
2
.(Seligson, A. L.; Trogler, W. C.
Organometallics
1993, 12, 744). However, this work did not extend successfully beyond acrylonitrile as Michael acceptor
Accordingly, what is needed in the art is a facile method for addition of amines to carbon-carbon double bonds under mild conditions, and catalysts to catalyze such reactions. The present invention is believed to be an answer to that need.
SUMMARY OF THE INVENTION
In one aspect, the present invention is directed to a process for addition of amines to carbon-carbon double bonds in a substrate, comprising: reacting an amine compound comprising a primary or a secondary amine with a compound containing at least one carbon-carbon double bond in the presence a transition metal catalyst and in the absence of an alkylaluminum co-catalyst under reaction conditions effective to form a product having a covalent bond between the primary or secondary amine and the one carbon atom of the former carbon-carbon double bond; wherein the reaction time is less than 40 hours, and wherein the reaction produces more than 20 moles of product per mole of said transition metal in said catalyst and consumes more than 30% of either of the amine compound or the compound containing at least one carbon-carbon double bond, and wherein the product contains at least 80% of one regioisomer, the transition metal catalyst comprising a Group 8 metal and a ligand containing one or more 2-electron donor atoms.
In another aspect, the present invention is directed to a process for enantioselective addition of amines to carbon-carbon double bonds in a substrate, comprising: reacting an amine compound comprising a primary or a secondary amine with a compound containing at least one carbon-carbon double bond in the presence a chiral and nonracemic transition metal catalyst under reaction conditions effective to form a product having a covalent bond between the primary or secondary amine and one carbon atom of the former carbon-carbon double bond; the transition metal catalyst comprising a Group 8 metal and a ligand containing one or more 2-electron donor atoms; and wherein the product is formed in greater than 20% yield, and with greater than 50% enantioselectivity.
In yet another aspect, the present invention is directed to a method for determining the activity of a catalyst useful in a reaction that adds primary or secondary amine compounds to compounds containing at least one carbon-carbon double bond, comprising: (1) reacting in a reaction vessel an amine compound comprising a primary or a secondary amine with a compound containing at least one carbon-carbon double bond in the presence a transition metal catalyst under reaction conditions effective to form a product containing a covalent bond between the primary or secondary amine and one carbon atom of the former carbon-carbon double bond, the transition metal catalyst comprising a Group 8 metal and a ligand containing one or more 2-electron donor atoms; (2) adding a calorimetric agent to the reaction vessel, the calorimetric agent reactive with the amine compound or the product; and (3) evaluating the degree of color in the reaction vessel to determine the activity of the catalyst.
These and other aspects will become apparent upon reading the following detailed description of the invention.
REFERENCES:
patent: 4120901 (1978-10-01), Hobbs
patent: 4307250 (1981-12-01), Peterson
patent: 5929265 (1999-07-01), Dorta et al.
patent: 5977361 (1999-11-01), Hartwig et al.
patent: 6048993 (2000-04-01), Grubbs et al.
patent: 6057456 (2000-05-01), Hartwig et al.
patent: 6072073 (2000-06-01), Kawatsura et al.
patent: 6100000 (2000-08-01), Hartwig et al.
Muller et al., “Metal-Initiated Amination of Alkenes and A;kynes”,Chem. Rev.1988, 98, pp. 675-703.
Gasc et al., “Amination of Alkenes”,Tetrahedron Report No. 144, vol. 19, No. 5, pp. 703-731, (1982).
Li-Biao Han et al., “Transition metal-catalyzed addition reactions of H-heteroatom and inter-heteroatom bonds to carbon-carbon unsaturated linkages via oxidative additions”,Chem. Commun, 1999, pp. 395-402.
Tian et al., “Constrained Geometry Organolanthanide Catalysts. Synthesis, Structural Characterization, and Enhanced Aminoalkene Hydroamination/Cyclization Activity”,OrganometallicsI 1999, 18, pp. 2568-2570.
Arredondo et al., “Organolanthanide-Catalyzed Hydroamination/Cyclization. Efficient Allene-Based Transformations for the Synthesis of Naturally Occurring Alkaloids”,J. Am. Chem. Soc., 1999, 121, pp. 3633-3639.
Li et al., “Organolanthanide-Catalyzed Intramolecular Hydroamination
Hartwig John F.
Kawatsura Motoi
Loeber Oliver
Davis Brian J.
Garabedian Todd E.
Wiggin & Dana
Yale University
LandOfFree
Transition metal-catalyzed process for addition of amines to... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Transition metal-catalyzed process for addition of amines to..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transition metal-catalyzed process for addition of amines to... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2908982