近日，美国威斯康星州麦迪逊大学Zachary K. Wickens团队研究了立体反转E2解锁Z选择性C-H官能化。相关论文于2025年9月18日发表在《科学》杂志上。

C-H键的立体选择性官能化是现代有机合成中的一个核心挑战。尽管C-H活化化学已历经几十年的创新，但合成化学家仍未实现烯烃的Z选择性官能化策略。末端烯烃对Z选择性构成了最大的挑战，因其需要选择性裂解两个几乎相同的C-H键中位阻更大的键。

研究组描述了烯烃转化为经过Z选择性消除的瞬态1,2-双锍中间体，通过稳定相互作用颠覆了教科书级的E2立体选择性规则。他们将配对电解确定为一种使能策略，既可以选择性地产生所需的双锍中间体，又可将其在原位快速消除。由此产生的Z-烯基锍关键体通过稳健的交叉偶联反应，从廉价的原料中获得广泛的Z-烯烃目标。

附：英文原文

Title: Stereo-reversed E2 unlocks Z-selective C–H functionalization

Author: Peter J. Verardi, Elizabeth A. Ryutov, Poulami Mukherjee, Remy Lalisse, Karina Targos, Tetsuya Inagaki, Megan Kelly, Ilia A. Guzei, Marcel Schreier, Osvaldo Gutierrez, Zachary K. Wickens

Issue&Volume: 2025-09-18

Abstract: The stereoselective functionalization of C–H bonds represents a central challenge in modern organic synthesis. Despite decades of innovation in C–H activation chemistry, methods for Z-selective functionalization of alkenes have eluded synthetic practitioners. Terminal alkenes present the biggest challenge for Z-selectivity as they require selective cleavage of the more hindered of two otherwise virtually identical C–H bonds. Herein, we describe the transformation of alkenes into transient 1,2-bis-sulfonium intermediates found to undergo Z-selective elimination, overturning a textbook E2 stereoselectivity rule through stabilizing interactions. We identify paired electrolysis as an enabling strategy to both selectively generate the requisite bis-sulfonium intermediate and drive its rapid elimination in situ. The resultant Z-alkenyl sulfonium linchpins provide access to a wide array of Z-alkene targets from inexpensive feedstocks through robust cross-coupling reactions.

DOI: adv7630

Source: https://www.science.org/doi/10.1126/science.adv7630