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
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 acidCascade reactionStereoselectivityTransfer hydrogenationNickelRegioselectivityOrganic chemistryCombinatorial chemistryCarboxylic acidRutheniumAsymmetric Hydrogenation and CatalysisCatalytic C–H Functionalization MethodsCarbon dioxide utilization in catalysis