Harnessing carbene polarity: Unified catalytic access to donor, neutral, and acceptor carbenes

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-07-10 DOI:10.1126/science.adw4177

Khue N. M. Nguyen, Xueling Mo, Bethany M. DeMuynck, Mohamed Elsayed, Jacob J. A. Garwood, Duong T. Ngo, Ilias Khan Rana, David A. Nagib

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引用次数: 0

Abstract

Metal carbenes are highly useful intermediates in organic synthesis. However, not all classes of carbene polarity are catalytically accessible, nor are there common precursors known to synthesize all of these electronically diverse carbene types. Here, we report a unified strategy to access a full range of carbenes, including those with donor substituents (EDG: OMe, NR₂, alkyl), acceptor substituents (EWG: CN, CO₂R), and electronically neutral or nonpolar substituents (H, BR₂, SiR₃, halide, aryl, heteroaryl). This Fe-catalyzed method harnesses α-Cl radicals and couples an exceptionally wide array of carbenes in (2+1) cyclopropanations and σ-bond insertions. This mild, robust, and electronically tunable synthetic method facilitated the development of a better classification system for catalytic metal carbenes (validated by both kinetic and thermodynamic quantification), as well as a carbene “click-like” reaction and aqueous adaptation for chemical biology applications.

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利用碳烯极性：对供体、中性和受体碳烯的统一催化途径

金属碳烯是有机合成中非常有用的中间体。然而，并不是所有种类的碳烯极性都可以催化获得，也没有已知的共同前体来合成所有这些电子多样化的碳烯类型。在这里，我们报告了一个统一的策略来获取全范围的碳，包括那些具有供体取代基（EDG: OMe, NR 2，烷基），受体取代基（EWG: CN, CO 2 R）和电子中性或非极性取代基（H, BR 2, SiR 3，卤化物，芳基，杂芳基）的碳。这种铁催化的方法利用α-Cl自由基，在（2+1）环丙烷和σ-键插入中偶联了大量的碳烯。这种温和、稳健、电子可调的合成方法促进了催化金属卡宾的分类系统的发展（通过动力学和热力学量化验证），以及卡宾“点击式”反应和化学生物学应用的水适应。

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

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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