文献类型：期刊文献

英文题名：Enantioselective Redox-Neutral Radical Addition of α-Imino Esters with Sulfonyl Hydrazides

作者：Xia, Tingting[1];Wang, Zihan[1];Zhang, Xiaochen[1];Hu, Jiangtao[1];Zhang, Shengyu[1];Zhang, Yangyang[1];Gu, Honglei[1];Wu, Xianqing[1];Zhu, Wei-Hong[1];Qu, Jingping[1];Chen, Yifeng[1,2,3]

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, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Organometall Chem, Shanghai 200032, Peoples R China;[3]Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China

年份：2025

卷号：147

期号：44

起止页码：41149

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20254519451947);WOS:【SCI-EXPANDED(收录号:WOS:001600381300001)，CCR-EXPANDED(收录号:WOS:001600381300001)】；

基金：This work was supported by National Natural Science Foundation of China (22171079, 22371071, 92356301, 2240011806), 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：Addition reactions - Amino acids - Catalysis - Cobalt - Covalent bonds - Drug discovery - Drug products - Esters - Methyl ester - Organometallics - Stereochemistry

摘要：The construction of chiral sp3-sp3 carbon-carbon bonds represents a central challenge in organic synthesis, critically enabling 3D molecular complexity for drug discovery. While transition metal-catalyzed asymmetric alkylation of unsaturated bonds offers a powerful route to these motifs, conventional strategies face inherent limitations: nucleophilic additions require preformed organometallic reagents via an external synthetic sequence, and recent flourishing reductive methods with alkyl halides demand stoichiometric terminal reductants. Herein, we disclose a cobalt-catalyzed, enantioselective redox-neutral radical addition that directly couples bench-stable unactivated alkyl sulfonyl hydrazides with various imines. This strategy eliminates external reductants while accommodating a broad substrate scope, delivering valuable alpha-amino esters in high yields and enantioselectivities. Crucially, the redox-neutral conditions enable the first asymmetric radical addition of N-TMS iminoesters, providing unprotected alpha,alpha-disubstituted amino acids directly without deprotection sequences. Mechanistic studies confirm alkyl radical intermediates in the stereoselective C-C bond formation. This method overcomes key limitations of existing approaches, offering a step-economical route to medicinally relevant chiral building blocks.