文献类型：期刊文献

英文题名：Cobalt-Catalyzed Asymmetric Reductive Coupling of Isocyanates with Tertiary Alkyl Halides for Sterically Bulky Chiral Amide Synthesis

作者：Zhao, Wenyu[1,2];Shen, Yiwen[1,2];Wu, Xianqing[1,2];Xia, Tingting[1,2];Hu, Jiangtao[1,2];Qu, Jingping[1,2];Chen, Yifeng[1,2,3,4]

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, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Chem & Mol Engn,Joint Int Res Lab Precis Chem, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Organometall Chem, Shanghai 200032, Peoples R China;[4]Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China

年份：2025

卷号：147

期号：31

起止页码：27155

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20261620522791);WOS:【SCI-EXPANDED(收录号:WOS:001534241000001)，CCR-EXPANDED(收录号:WOS:001534241000001)】；

基金：This work was supported by National Natural Science Foundation of China (22171079, 22371071, 92356301, 224011806), Science and Technology Commission of Shanghai Municipality (grant no. 24DX1400200), the Program of Introducing Talents of Discipline to Universities (B16017), Sinopec Seeding Program (C0607-0876), 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：Amides - Carbon - Catalysis - Chemical bonds - Enantioselectivity - Organometallics - Stereocenters - Stereochemistry - Substrates - Synthesis (chemical)

摘要：The ubiquity of amide bonds in pharmaceuticals, agrochemicals, natural products, and peptides underscores the enduring demand for efficient amide synthesis in organic chemistry. Nevertheless, the facile construction of sterically congested chiral amides bearing alpha-quaternary stereogenic centers remains a formidable synthetic challenge. Herein, we report a catalytic reductive addition strategy that leverages readily accessible and stable isocyanates for stereoselective carbon-carbon bond formation. Enabled by earth-abundant chiral cobalt catalysis, this method achieves the enantioconvergent amidation of racemic tertiary alkyl halides, delivering alpha-tetrasubstituted amides with sterically demanding quaternary stereocenters. By circumventing the use of organometallic reagents, this unprecedented enantioselective alkylative reductive addition accommodates a broad substrate scope, including structurally diverse isocyanates and alpha-chloro tertiary amides, while achieving exceptional enantioselectivity (up to 99% ee). Preliminary mechanistic studies demonstrate a radical addition mechanism that is operative in this reductive amidation process.