文献类型：期刊文献

英文题名：Cobalt-Catalyzed Enantioselective Reductive α-Chloro-Carbonyl Addition of Ketimine to Construct the β-Tertiary Amino Acid Analogues

作者：Xia, Tingting[1];Wu, Wenwen[1];Wu, Xianqing[1];Qu, Jingping[1];Chen, Yifeng[1]

机构：[1]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Chem & Mol Engn,Key Lab Adv Mat & Joint Int Re, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2024

卷号：63

期号：25

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20242016092868);WOS:【SCI-EXPANDED(收录号:WOS:001221919300001)，CCR-EXPANDED(收录号:WOS:001221919300001)】；

基金：This work was supported by the National Natural Science Foun-dation of China (22171079, 22371071, 92356301), Natural Science Foundation of Shanghai (21ZR1480400), Shanghai Municipal Science and Technology Major Project (Grant No.2018SHZDZX03), the Program of Introducing Talents of Discipline to Universities (B16017), the China Postdoctoral Science Foundation (2021M701197, 2023T160215), Shanghai Sailing Program (23YF1408800) and the Fundamental Research Funds for the Central Universities. The authors thank the Analysis and Testing Center of East China University of Science and Technology for help with NMR and HRMS analysis.

语种：英文

外文关键词：amino acid; asymmetric catalysis; reductive addition; alpha-chloro carbonyls; cobalt

摘要：beta-Tertiary amino acid derivatives constitute one of the most frequently occurring units in natural products and bioactive molecules. However, the efficient asymmetric synthesis of this motif still remains a significant challenge. Herein, we disclose a cobalt-catalyzed enantioselective reductive addition reaction of ketimine using alpha-chloro carbonyl compound as a radical precursor, providing expedient access to a diverse array of enantioenriched beta-quaternary amino acid analogues. This protocol exhibits outstanding enantioselectivity and broad substrate scope with excellent functional group tolerance. Preliminary mechanism studies rule out the possibility of Reformatsky-type addition and confirm the involvement of radical species in stereoselective addition process. The synthetic utility has been demonstrated through the rapid assembly of iterative amino acid units and oligopeptide, showcasing its versatile platform for late-stage modification of drug candidates. Cobalt-catalyzed enantioselective reductive addition reaction of ketimine using alpha-chloro carbonyl electrophile has been developed to access diversified enantioenriched beta-tertiary amino acid with excellent enantioselectivity and broad functional group tolerance. The synthetic utility of this protocol includes the efficient assembly of iterative amino acid units and oligopeptide. image