Radical α-Trifluoromethylation of Ketones via Lithium Enolates

Significance

So far the trifluoromethylation of ketones was known only via preparation of some derivatives, which makes the whole process lengthy. Although, perfluoroalkylation is known to give products in good yields (K. Miura, Y. Takeyama, K. Oshima, K. Utimoto Bull. Chem. Soc. Jap. 1991, 64, 1542-1553). Interestingly, this radical trifluoromethylation reaction was found to be extremely fast and is completed often within seconds at -78 ºC. Prolonged reaction times often decrease the yields of the products probably due to base-induced decomposition. Only cyclic ketones were studied as substrates. The lithium enolate can be generated from a ketone by a direct metalation (‘kinetic’ enolate) or from its tri­methylsilyl enol ether by reaction with BuLi (‘thermodynamic’ enolate). Since even 20 mol% of Et₃B is sufficient for good yields, a radical chain mechanism involving formation of the CF₃ radical and its attack on the enolate is proposed. No reaction was observed in the absence of Et₃B.