| abstract |
The present invention provides a process for the preparation of acyl amines of formula (I), enantiomerically enriched at the carbon atom marked with an *; wherein Y is N or CH; R1 and R2 are independently selected from H, halogen, Cl-4alkyl, OH, OC1-4alkyl, OSO2CH3, OSO2CF3, NO2, and phenyl optionally substituted with 1 to 3 substituents independently selected from CN, halogen, Cl-4alkyl optionally substituted with 1 to 5 halogen atoms, OH, OCl-4alkyl, CO2 Cl-4alkyl, and OC1-4alkyl optionally substituted with 1 to 5 halogen atoms; and R3 is C(O)H, C(O)C1-4alkyl optionally substituted with 1 to 5 halogen atoms, C(O)aryl, C(O)CH2-aryl, C(O)O-C1-10alkyl, C(O)O-aryl, or C(O)OCH2-aryl; which comprises hydrogenating in the presence of hydrogen gas a prochiral enamide of formula (II), in a suitable organic solvent in the presence of a rhodium metal precursor complexed to a chiral mono- or bidentate phosphine ligand. A process for the preparation of an enamide of formula (II) which comprises reaction an aryl nitrile of formula (III), with a methylating agent selected from methylmagnesiumbromide, methylmagnesium-chloride, methyllithium and methyllithium-lithium bromide complex, in a suitable organic solvent and in the presence of R3-Cl or (R3)2O, wherein RI, R2 and R3 areas defined in Claim 1. |