Chemoselective and Divergent Synthesis of Chlorohydrins and Oxaheterocycles via Ir-Catalyzed Asymmetric Hydrogenation.

Abstract

Chlorohydrins and oxaheterocycles are synthetically valuable building blocks for diverse natural products and therapeutic substances. A highly efficient Ir/f-phamidol-catalyzed asymmetric hydrogenation of ω-chloroketones was successfully developed, and various chlorohydrins and oxaheterocycles were obtained divergently with excellent yields and enantioselectivities (up to >99% yield and >99% ee). Synthetic utilities of this divergent transformation were demonstrated by gram-scale synthesis of key intermediates of several enantiomerically enriched drugs via this catalytic methodology.