Exploiting a “Beast” in Carbenoid Chemistry: Development of a Straightforward Direct Nucleophilic Fluoromethylation Strategy

The
first direct and straightforward nucleophilic fluoromethylation
of organic compounds is reported. The tactic employs a “fleeting”
lithium fluorocarbenoid (LiCH2F) generated from commercially
available fluoroiodomethane. Precise reaction conditions were developed
for the generation and synthetic exploitation of such a labile species.
The versatility of the strategy is showcased in ca. 50 examples involving
a plethora of electrophiles. Highly valuable chemicals such as fluoroalcohols,
fluoroamines, and fluoromethylated oxygenated heterocycles could be
prepared in very good yields through a single synthetic operation.
The scalability of the reaction and its application to complex molecular
architectures (e.g., steroids) are documented.

本研究首次报道了有机化合物的直接且简便的亲核氟甲基化反应。该策略采用由商业化可得的氟碘甲烷（fluoroiodomethane）原位生成的“瞬态”氟卡宾锂（lithium fluorocarbenoid, LiCH₂F）。研究人员开发了精准的反应条件，以实现这类不稳定物种的生成与合成应用。该策略的普适性通过约50例涵盖多种亲电试剂的反应案例得到验证。仅需一步合成操作，即可制备氟代醇、氟代胺以及氟甲基化含氧杂环等高价值化合物，且收率优异。本研究还验证了该反应的可放大性，并展示了其在复杂分子骨架（例如类固醇（steroids））修饰中的应用。