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

• 成果类型: Article
• 署名作者: Nguyen, Khue N. M.; Mo, Xueling; Demuynck, Bethany M.; Elsayed, Mohamed; Garwood, Jacob J. A.; Ngo, Duong T.; Rana, Ilias Khan; Nagib, David A.
• 署名单位: University System of Ohio; Ohio State University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12583
• DOI: 10.1126/science.adw4177
• 发表日期: 2025-07-10
• 页码: 183-189
• 关键词: stereoselective functionalization; halogen-atom; reactivity; alkyl; cyclopropanes; photoredox; chemistry; agents

摘要

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 alpha-Cl radicals and couples an exceptionally wide array of carbenes in (2+1) cyclopropanations and sigma-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.