Catalytic Enantioselective Protonation of Monofluorinated Silyl Enol Ethers towards Chiral α-Fluoroketones

Described herein is an organocatalytic enantioselective protonation of monofluorinated silyl enol ethers, affording an array of optically active α-secondary α-fluoroketones in good to high yields and enantioselectivities, under the catalysis of bifunctional cinchonidine derived squaramide C4. It represents a rare example of facile synthesis of enantioenriched α-secondary α-fluoroketones. With D₂O as the deuterium source and MeOD as the solvent, the first highly enantioselective preparation of chiral α-deuterated α-fluoroketones in >92% deuteration is developed.