Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl <i>N</i>-Heteroaryl Ketones with <i>N</i>-Oxide as a Removable <i>ortho</i>-Substituent

Abstract

A highly enantioselective transfer hydrogenation of non-ortho-substituted aryl N-heteroaryl ketones, using readily available chiral diamine-derived iridium complex (S,S)-1f as a catalyst and sodium formate as a hydrogen source in a mixture of H₂O/i-PrOH (v/v = 1:1) under ambient conditions, is described. The chiral aryl N-heteroaryl methanols were obtained with up to 98.2% ee by introducing an N-oxide as a removable ortho-substituent. In contrast, no more than 15.1% ee was observed in the absence of an N-oxide moiety. Furthermore, the practical utility of this protocol was also demonstrated by gram-scale asymmetric synthesis of bepotastine besilate in 51% total yield and 99.9% ee.