Enantioselective Synthesis of Chiral Carboxylic Acids from Alkynes and Formic Acid by Nickel‐Catalyzed Cascade Reactions: Facile Synthesis of Profens
Peng Yang, Yaxin Sun, Kaiyue Fu, Li Zhang, Guang Yang, Jieyu Yue, Yu Ma, Jianrong Steve Zhou, Bo Tang
Abstract
We report a stereoselective conversion of terminal alkynes to α-chiral carboxylic acids using a nickel-catalyzed domino hydrocarboxylation-transfer hydrogenation reaction. A simple nickel/BenzP* catalyst displayed high activity in both steps of regioselective hydrocarboxylation of alkynes and subsequent asymmetric transfer hydrogenation. The reaction was successfully applied in enantioselective preparation of three nonsteroidal anti-inflammatory profens (>90 % ees) and the chiral fragment of AZD2716.
Topics & Concepts
Enantioselective synthesisChemistryCatalysisFormic acidStereoselectivityCascade reactionTransfer hydrogenationNickelRegioselectivityCombinatorial chemistryOrganic chemistryCarboxylic acidRutheniumAsymmetric Hydrogenation and CatalysisCarbon dioxide utilization in catalysisCatalytic C–H Functionalization Methods