Ammonium bromides/KF catalyzed trifluoromethylation of carbonyl compounds with (trifluoromethyl)trimethylsilane and its application in the enantioselective trifluoromethylation reaction

The trifluoromethylation of aldehydes and ketones is a potentially powerful method to introduce the CF3 moiety into organic molecules. In general, the trifluoromethylation reaction has been performed by treatment of Me3SiCF3 under initiation by TBAF, TBAT, TMAF as well as CsF. However, these commercially available fluorides are rather expensive and moisture sensitive. Potassium fluoride (KF) is an inexpensive and commonly used fluoride source and can be also used as an initiator for the trifluoromethylation, but the method suffers from the significant limitation that only DMF is available as a solvent. Therefore, novel methods are highly desirable for laboratory-scale as well as large-scale preparations. Here we wish to report a convenient procedure where a KF/TBAB combination acts as a catalyst for trifluoromethylation of aldehydes, ketones, and imides in a variety of organic solvents to provide trimethylsilyl-protected α-trifluoromethyl alcohols in good to high yields. Application of the method in the enantioselective trifluoromethylation is also discussed.