ASYMMETRIC HYDROGENATION OF ENAMIDES

摘要

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; R<SUP>1</SUP> and R<SUP>2</SUP> are independently selected from H, halogen, C<SUB>l-4</SUB>alkyl, OH, OC<SUB>1</SUB>-4alkyl, OSO<SUB>2</SUB>CH<SUB>3</SUB>, OSO<SUB>2</SUB>CF<SUB>3</SUB>, NO<SUB>2</SUB>, and phenyl optionally substituted with 1 to 3 substituents independently selected from CN, halogen, C<SUB>l-4</SUB>alkyl optionally substituted with 1 to 5 halogen atoms, OH, OC<SUB>l-4</SUB>alkyl, CO<SUB>2</SUB>­ C<SUB>l-4</SUB>alkyl, and OC<SUB>1-4</SUB>alkyl optionally substituted with 1 to 5 halogen atoms; and R<SUP>3</SUP> is C(O)H, C(O)C<SUB>1-4</SUB>alkyl optionally substituted with 1 to 5 halogen atoms, C(O)aryl, C(O)CH<SUB>2</SUB>-aryl, C(O)O-C<SUB>1-10</SUB>alkyl, C(O)O-aryl, or C(O)OCH<SUB>2</SUB>-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 R<SUP>3</SUP>-Cl or (R<SUP>3</SUP>)<SUB>2</SUB>O, wherein R<SUP>I</SUP>, R<SUP>2</SUP> and R<SUP>3</SUP> areas defined in Claim 1.