Synthesis of Aryl α,α-Difluoroalkyl Ketones as Potent Inhibitors of Cholesterol Esterase

Aryl α,α-difluoroalkyl ketones were synthesized from the reaction of ethyl α,α-difluoroacylate with aryl lithium at ?78°C or from the coupling of aryl iododifluoromethyl ketone with 1-alkene in the presence of tetcrakis(triphenylphosphine)palladium(0). These compounds were potent inhibitors of pancreatic cholesterol esterase with K_i values in the range 15 μM-20 nM.