Ru-BICP-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones

Abstract

The design and synthesis of effective enantioselective catalysts for hydrogenation of simple ketones remains a challenging problem.1 Recently, Noyori2 disclosed a ternary catalyst system consisting of Ru-BINAP-chiral diamine-KOH, which is highly efficient in the asymmetric hydrogenation of a variety of simple ketones lacking a secondary coordinating functional group. We have developed rhodium complexes with a conformationally rigid, electron-rich bidentate phosphine ligand (PennPhos)3 as highly enantioselective catalysts for hydrogenation of both aryl alkyl and dialkyl ketones. In a related study, we have designed and synthesized a new conformationally rigid 1,4-bisphosphine, (2R,2′R)-bis(diphenylphosphino)-(1R,1′R)-dicyclopentane (BICP). Rh-BICP gives excellent enantioselectivity upon asymmetric hydrogenation of 2-(acylamino)acrylic acids.4 Prompted by these encouraging results, we were interested in exploring the Ru-BICP-catalyzed hydrogenation of simple ketones using Noyori’s protocol (Scheme 1). Our experimental results on a Ru-BICP catalytic system indicate an important finding of possible multipoint interactions between a chiral chelating diamine and acetylthiophene derivatives.