Asymmetric hydrogenation of α-keto acid derivatives by rhodium-}amidophosphine-phosphinite{ catalysts

Abstract

The enantioselective hydrogenation of several α-keto esters ( 3a-f, 5a-j), α-keto amides ( 7a-e) and isatine derivatives ( 9a-d) with a set of four representative neutral homogeneous rhodium-amidophosphine-phosphinite catalysts has been investigated. Trifluoroacetato-Rh-AMPP catalytic precursors promoted the rapid, efficient synthesis of aliphatic α-hydroxy esters 4a-f in moderate to high enantioselectivities (66–95% ee), in contrast to most aromatic α-hydroxy esters 6a-j (8–81% ee). Best enantioselectivities for α-hydroxy amides 8a-e (85–95% ee) and dioxindoles 10a-d (80–94% ee) were obtained with chloro-Rh-AMPP precursors. It is proposed that, contrary to α-keto amides, α-keto esters do not chelate onto the rhodium center and that, in such circumstances, the asymmetric induction is mainly controlled by the steric hindrance around the CO function.