Lewis Base Catalyzed Trifluoromethylation of Carbonyl Compounds with Trialkyl(trifluoromethyl)silanes

Strategies for nucleophilic, electrophilic, and radical trifluoromethylations

“…Furthermore, these initiators are very sensitive to moisture. In 1997, Fuchikami and co-workers studied the trifluoromethylation reaction of aldehydes by using a variety of Lewis bases [33]. Following this pioneering work, Prakash's group employed trimethylamine N-oxide as a recoverable nucleophilic catalyst for the activation of Me 3 SiCF 3 [34].…”

“…Other initiators. Nucleophilic trifluoromethylation of aldehydes and certain activated ketones with Me 3 SiCF 3 have also been studied using other nucleophilic catalysts, such as amines, AsPh 3 and SbPh 3 , [33,43] as well as DMF or DMSO in the presence of molecular sieves [44]. It is noteworthy that carbonate and phosphate salts such as K 2 CO 3 and (MeO) 2-P(O)O À NBu 4 + also showed efficient catalytic activity in nucleophilic trifluoromethylation reactions [35].…”

“…Triphenylphosphine is a widely used catalyst for trifluoromethylation reactions with Me 3 SiCF 3 . The yields are relatively low and longer reaction times are required possibly owing to the poor nucleophilicity of PPh 3 [30,33]. Recently, Shibata and co-workers developed an efficient Lewis base-catalysed system for nucleophilic trifluoromethylation of a variety of aldehydes and ketones through the use of tri-tert-butylphosphine P(t-Bu) 3 (0.1-10 mol%) in dimethylformamide [42].…”

How to Reach Stereogenic Trifluoromethylated Carbon? En Route to the “Grail” of the Asymmetric Trifluoromethylation Reaction

“…Thus, attempts to enantioselectively trifluoromethylate benzaldehyde with quinine activation have been realized. [28] However, only modest yields and low ee's were observed ( Table 3). The best observed ee is only 21 % and required a more hindered trifluoromethylated reagent (Entry 4).…”

Nucleophilic trifluoromethylation

“…Indeed, if high diastereoselectivity can be obtained during trifluoromethylation of chiral substrates, such as chiral sulfinimides, with Ruppert-Prakash reagent [22], trifluoromethylation of prochiral substrates with chiral trifluoromethyl-containing systems usually leads to medium enantiomeric excesses. Until now, the best results have been obtained with CF 3 SiMe 3 , activated by chiral fluorides, especially N-substituted cinchonium fluoride [23], or chiral Lewis bases [24] based on quinquina alkaloids, but enantiomeric excesses exceeding 50% are rarely reached, except when the substrate is very hindered or when its conformation is such that any nucleophile would add in a stereoselective way [25].…”