近日，美国纽约州立大学Patricia Z. Musacchio团队报道了通过烯烃自由基阳离子生成烷基C-X合成子的邻二取代。这一研究成果发表在2026年7月9日出版的《科学》杂志上。

在有机化学中，两个相邻碳原子的官能化通常始于烯烃或已双取代的前体。

研究组报道了一种放能活化模式，该模式通过光氧化还原触发的氢原子转移（HAT）和自旋中心迁移（SCS）过程，直接从单官能化的C(sp³)–X手柄生成烯烃自由基阳离子中间体。计算表明，电子离域和氢键溶剂分子网络促进了协同的[HAT+SCS]机制。

利用该催化平台，研究组设计了一种亲电反应性（C–X）从一个碳向另一个碳的转移过程，称之为亲电穿梭。因此，可以从高苄基C–X合成子出发，利用两种亲核试剂构建1,2-双官能化加成物，得到双唑类结构，并展示了与其他亲核试剂类别的兼容性。研究组开发了一系列转化反应，这些反应偏离了传统的合成逻辑，即传统上烷基C–X骨架仅限于单点位取代，而现在将其转变为用于构建邻位复杂性的非直觉性前体。

附：英文原文

Title: Vicinal disubstitution of alkyl C–X synthons via alkene radical cation generation

Author: Yufei Zhang, Tamal Das, Zi Xuan, Mrinmoy Das, Hammed O. Bisiriyu, Alon Nudler, Ben D. Parasch, Matthew D. Resmini, Aubrey E. Graham, David F. Watson, Jennifer S. Hirschi, Patricia Z. Musacchio

Issue&Volume: 2026-07-09

Abstract: In organic chemistry, functionalization of two adjacent carbons often starts from alkenes or already disubstituted precursors. Herein, we report an exergonic activation mode that directly generates alkene radical cation intermediates from monofunctional C(sp3)–X handles through a photoredox-triggered hydrogen-atom abstraction (HAT) and spin-center shift (SCS) process. Computations show that electron delocalization and a network of hydrogen-bonding solvent molecules facilitate a concerted [HAT+SCS] mechanism. The catalytic platform was used to design a transfer of electrophilic reactivity (C–X) from one carbon to another, which we refer to as electrophilic shuttling. Thus, two nucleophiles can be used in the construction of 1,2-difunctionalization adducts from homobenzylic C–X synthons, delivering bisazole architectures and demonstrating compatibility with other nucleophile classes. A suite of transformations is developed that departs from conventional synthetic logic, for which alkyl C–X scaffolds are confined to single-site substitutions, now transforming them into nonintuitive precursors for building vicinal complexity.

DOI: aef0766

Source: https://www.science.org/doi/10.1126/science.aef0766