Rhodium‐Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of 1,3‐Dipolar Nitrones

Abstract

Owing to their distinctive 1,3‐dipolar structure, the catalytic asymmetric hydrogenation of nitrones to hydroxylamines has been a formidable and longstanding challenge, characterized by intricate enantiocontrol and susceptibility to N‐O bond cleavage. In this study, the asymmetric hydrogenation and transfer hydrogenation of nitrones were accomplished with a tethered TsDPEN‐derived cyclopentadienyl rhodium(III) catalyst (TsDPEN: p‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine), the reaction proceeds via a novel 7‐membered cyclic transition state, producing chiral hydroxylamines with up to 99% yield and >99% ee. The practical viability of this methodology was underscored by gram‐scale catalytic reactions and subsequent transformations. Furthermore, mechanistic investigations and DFT calculations were also conducted to elucidate the origin of enantioselectivity.