Stereo-reversed E2 unlocks Z-selective C-H functionalization

• 成果类型: Article
• 署名作者: Verardi, Peter J.; Ryutov, Elizabeth A.; Mukherjee, Poulami; Lalisse, Remy; Targos, Karina; Inagaki, Tetsuya; Kelly, Megan; Guzei, Ilia A.; Schreier, Marcel; Gutierrez, Osvaldo; Wickens, Zachary K.
• 署名单位: University of Wisconsin System; University of Wisconsin Madison; University of California System; University of California Los Angeles; University of Osaka; University of Wisconsin System; University of Wisconsin Madison
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8079
• DOI: 10.1126/science.adv7630
• 发表日期: 2025-09-18
• 页码: 1239-1245
• 关键词: molecular-orbital methods; heck type reaction; basis-set; mechanism; energies; program; alkenes; trans

摘要

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.