Mild LiOMe-Catalyzed Trifluoromethylation of Carbonyl Compounds

We report a mild lithium methoxide (LiOMe)-catalyzed protocol for the trifluoromethylation of aldehydes, acyclic and cyclic ketones, and α,β-unsaturated carbonyl compounds. This method avoids the use of fluorinated or strong bases that promote enolization, offering broad functional group tolerance, including silyl, Boc, Cbz, nitrile, and benzyl groups, enabling its application to diverse complex substrates. Additionally, LiOMe catalyzes the diastereoselective addition of CF3 to chiral keto esters derived from (1R,2S)-1-(methylamino)-2,3-dihydro-1H-inden-2-ol, affording products with diastereomeric ratios up to 84:16.