Fluorocarbyne Insertion into Benzene Skeletons

作者：C. H. Wu, Mingyang Wang, Cheng Wang, Jun-Jie Zhi, Lin Chen, Y. Zou, Hao-Song Wang, Xin Hong, Wei Li · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c16875 · 被引用次数：9 · 研究领域：Fluorine in Organic Chemistry、Chemical Synthesis and Analysis、Innovative Microfluidic and Catalytic Techniques Innovation

Innovative fluorinated synthons essentially advance the organofluorine chemistry. However, the fundamental fluorocarbon synthon, metal-fluorocarbyne, remains largely unexplored, in contrast to its well-established trifluoromethyl and difluorocarbene counterparts. Here, we report a fluorocarbyne-promoted skeletal editing that transforms simple benzenes into precious monofluorinated cycloheptatrienes. This fluorocarbyne insertion features broad functional-group tolerance, exclusive meta -insertion selectivity, and compatibility with arene substrates ranging from benzene to per-substituted derivatives. The selective benzene activation within polyaromatics and successful applications to late-stage drug modifications further demonstrate its utility. Pharmaceutical application to the antiviral agent tecovirimat yielded a fluorinated derivative with an approximately 3-fold increase in aqueous solubility. Mechanistic studies involving intermediate capture and DFT calculations support the fluorocarbyne intermediate and elucidate the origin of meta -insertion and the ring expansion pathway. This work presents the first application of metal-fluorocarbyne in organic synthesis, enabling concurrent fluorine incorporation and scaffold editing.