Patent ID: 7495123

Claim:
A process for preparing a compound of structural formula I: enantiomerically enriched at the carbon atom marked with an *; wherein Z is OR 2 , SR 2 , or NR 2 R 3 ; R 1 is C 1-8 alkyl, aryl, heteroaryl, aryl-C 1-2 alkyl, or heteroaryl-C 1-2 alkyl; R 2 and R 3 are each independently hydrogen, C 1-8 alkyl, aryl, or aryl-C 1-2 alkyl; or R 2 and R 3 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocyclic ring system optionally containing an additional heteroatom selected from O, S, N, NH, and NC 1-4 alkyl, said heterocyclic ring being unsubstituted or substituted with one to three substituents independently selected from oxo, hydroxy, halogen, C 1-4 alkoxy, and C 1-4 alkyl wherein alkyl and alkoxy are unsubstituted or substituted with one to five fluorines; and said heterocyclic ring system being optionally fused with a 5- to 6-membered saturated or aromatic carbocyclic ring system or a 5- to 6-membered saturated or aromatic heterocyclic ring system containing one to three heteroatoms selected from O, S, N, NH, and NC 1-4 alkyl, said fused ring system being unsubstituted or substituted with one to four substituents selected from hydroxy, amino, fluorine, C 1-4 alkyl, and C 1-4 alkoxy, wherein alkyl and alkoxy are unsubstituted or substituted with one to five fluorines; comprising the step of hydrogenating in the presence of hydrogen gas a prochiral enamine of structural formula II: in a suitable organic solvent in the presence of a rhodium metal precursor complexed to a chiral phosphine ligand selected from the group consisting of: (a) a ligand of the structural formula: wherein R 16 is C 1-4 alkyl or aryl; or an enantiomer thereof; (b) a ligand of the structural formula: or an enantiomer thereof; (c) a ligand of the structural formula: wherein R 12 is C 1-4 alkyl, C 3-6 cycloalkyl, or aryl; or an enantiomer thereof; and (d) a ligand of the structural formula: wherein R 4 is C 1-4 alkyl or aryl; and R 5 and R 6 are each independently C 1-6 alkyl, C 5-12 cycloalkyl, or aryl; and wherein said rhodium metal precursor is [Rh(monoolefin) 2 Cl] 2 , [Rh(diolefin)Cl] 2 , [Rh(monoolefin) 2 acetylacetonate], [Rh(diolefin)acetylacetonate], [Rh(monoolefin) 4 ]X, or [Rh(diolefin) 2 ]X wherein X is selected from the group consisting of methanesulfonate, trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate, and hexafluoroantimonate.