美国普林斯顿大学David W. C. MacMillan揭示了四元sp3-碳形成的仿生SH2交叉耦合机制。相关研究成果于2021年11月11日发表于国际一流学术期刊《科学》。

双分子均溶取代（SH2）是一种开壳机制，涉及许多生物化学烷基化途径。然而，令人惊讶的是，该自由基取代歧管在合成C–C键形成中并没有被普遍用作设计元素。

该文中，研究人员证明了SH2机制可以用来实现仿生sp3-sp3交叉耦合平台，该平台提供四元sp3-碳中心，这是有机分子结构中的一个长期挑战。该异选择性自由基偶联结合了铁卟啉易于区分开壳一级和三级碳的SH2键形成作用的能力，以及从广泛丰富的官能团同时生成两类自由基的光催化作用。机理研究证实了偶联前一级烷基-Fe（III）物种的中间性，并为关键的四元sp3-碳键形成步骤中的SH2置换途径提供了证据。

附：英文原文

Title: A biomimetic SH2 cross-coupling mechanism for quaternary sp3-carbon formation

Author: Wei Liu, Marissa N. Lavagnino, Colin A. Gould, Jesús Alcázar, David W. C. MacMillan

Issue&Volume: 2021-11-11

Abstract: Bimolecular homolytic substitution (SH2) is an open-shell mechanism that is implicated across a host of biochemical alkylation pathways. Surprisingly, however, this radical substitution manifold has not been generally deployed as a design element in synthetic C–C bond formation. Here, we demonstrate that the SH2 mechanism can be leveraged to enable a biomimetic sp3-sp3 cross-coupling platform that furnishes quaternary sp3-carbon centers, a longstanding challenge in organic molecule construction. This heteroselective radical-radical coupling combines the capacity of iron porphyrin to readily distinguish between the SH2 bond-forming roles of open-shell primary and tertiary carbons, and photocatalysis to generate both radical classes simultaneously from widely abundant functional groups. Mechanistic studies confirm the intermediacy of a primary alkyl–Fe(III) species prior to coupling and provide evidence for the SH2 displacement pathway in the critical quaternary sp3-carbon bond formation step.

DOI: abl4322

Source: https://www.science.org/doi/10.1126/science.abl4322#con5