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.