Asymmetric Hydrogenation of Oximes Synergistically Assisted by Lewis and Brønsted Acids

Abstract

Due to their low reactivity, difficult enantiocontrol, and proneness to N-O bond cleavage, the catalytic asymmetric hydrogenation of oximes to hydroxylamines has remained a significant challenge. Herein, a Lewis and Brønsted acid cooperation strategy was established for the asymmetric hydrogenation of oximes, providing the corresponding hydroxylamines with up to 95% yield and up to 96% ee. Addition of Lewis and Brønsted acid was crucial to obtain high conversion and enantioselectivity. Mechanistic investigations indicates that the thiourea fragment of the ligand, Lewis acid (In(OTf)₃ or Zn(OAc)₂), as well as the Brønsted acid (l-CSA) played vital roles in the control of reactivity and enantioselectivity of the reaction. In addition, the synthetic elaboration of this transformation was demonstrated by gram scale experiment with retention of the yield and enantioselectivity.