Iron-Catalyzed Asymmetric Cross-Electrophile Alkylation of Imines

IF 13.1 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2025-08-15 DOI:10.1021/acscatal.5c04547

Jiahao Bai, Qinglin Wang, Wenyu Zhao, Yiwen Shen, Yuquan Xin, Xianqing Wu, Jingping Qu and Yifeng Chen*,

引用次数: 0

Abstract

Transition metal-catalyzed asymmetric cross-electrophile coupling has emerged as a synthetically useful strategy for the stereoselective construction of a carbon–carbon bond. Herein, we report an iron-catalyzed enantioselective cross-electrophile alkylation of α-imino esters with unactivated alkyl halides by employing a chiral NPN ligand. This method delivers α-tetrasubstituted amino esters in high yields (up to 93%) and enantioselectivity (up to 97:3 er), accommodating diverse substrates, including primary, secondary, and tertiary alkyl iodides, with broad functional group tolerance. The system is extended to asymmetric benzylation using benzyl chlorides, yielding chiral phenylalanine derivatives bearing quaternary stereocenters (up to 97.5:2.5 er), including bioactive motifs. Mechanistic studies suggest alkyl radical intermediates and a low-valent iron catalytic cycle initiated by a single-electron transfer.

Abstract Image

查看原文本刊更多论文

铁催化亚胺不对称交叉亲电烷基化反应

过渡金属催化的不对称交叉亲电偶联已成为碳-碳键立体选择性构建的一种有用的综合策略。在此，我们报道了铁催化的α-亚胺酯与未活化的烷基卤化物的对映选择性交叉亲电烷基化，采用手性NPN配体。该方法以高收率（高达93%）和对映选择性（高达97:3 er）递送α-四取代氨基酯，可容纳多种底物，包括初级、二级和叔烷基碘化物，具有广泛的官能团耐受性。该系统扩展到使用苯氯化物的不对称苄基化，产生具有季立体中心的手性苯丙氨酸衍生物（高达97.5:2.5 er），包括生物活性基序。机理研究表明，烷基自由基中间体和一个由单电子转移引发的低价铁催化循环。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.