Asymmetric Remote Leaving Group-Promoted Propargylic Substitution

IF 11.3 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2025-05-29 DOI:10.1021/acscatal.5c01798

Yuan-Xiang Yang, Yi-Fan Wang, Guo-Qiang Lin, Zhi-Tao He

引用次数: 0

Abstract

Propargylic substitution is a basic type of transformation in organic synthesis but relies on the existence of an α-leaving group. Thus, alkyne bearing an alkyl-linked remote leaving group is not considered as a suitable substrate for propargylation, and related remote substitution is unexplored. Here, we show that such a remote propargylation model can be established stereoselectively via copper catalysis. By combining the positive effects of d-orbital electron donation of alkynyl copper, ring strain release, and the cleaving tendency of the remote leaving group, propargylic cyclopropane fragmentation and functionalization is achieved in good yield and with high enantioselectivity. A set of modified chiral PPBOX ligands are developed to guarantee stereocontrol of the transformation. Both the amination and alkylation processes have been established to demonstrate the reliability of the design. Mechanistic studies show the necessity of Cu metal, ring strain, and remote leaving group in promoting C–C bond cleavage and that propargylic substitution might be the turnover-limiting step.

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不对称远离离去基促进丙炔取代

丙炔取代是有机合成中一种基本的转化类型，但它依赖于α-离去基的存在。因此，带有烷基连接的远端离去基的炔不被认为是丙基化的合适底物，相关的远端取代尚未探索。在这里，我们证明了这种远程丙基化模型可以通过铜催化立体选择性地建立。结合炔基铜的d轨道给电子、环应变释放和远端离去基的劈裂倾向的积极作用，以良好的收率和高的对映选择性实现了丙基环丙烷的裂解和功能化。开发了一组修饰的手性PPBOX配体，以保证转化的立体控制。建立了胺化和烷基化工艺，以证明设计的可靠性。机理研究表明，Cu金属、环应变和远端离去基是促进C-C键解理的必要条件，丙炔取代可能是限制翻转的步骤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.