Enantioselective Synthesis of Chiral Carboxylic Acids from Alkynes and Formic Acid by Nickel‐Catalyzed Cascade Reactions: Facile Synthesis of Profens. (18th November 2021)

• Record Type: Journal Article
• Authors: Yang, Peng; Sun, Yaxin; Fu, Kaiyue; Zhang, Li; Yang, Guang; Yue, Jieyu; Ma, Yu; Zhou, Jianrong Steve; Tang, Bo
• Is Part Of: Angewandte Chemie. Volume 134:Number 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-18
• Subjects: cascade reaction -- chiral carboxylic acid -- hydrocarboxylation -- Nickel -- transfer hydrogenation; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202111778
• Languages: English
• ISSNs: 0044-8249

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. Abstract : A simple nickel catalyst converts terminal alkynes and formic acid to α‐chiral carboxylic acids in high enantioselectivity. The reaction proceeds via the hydrocarboxylation of alkynes and enantioselective transfer hydrogenation of acrylic acids.