Recent advances in trifluoromethylation reactions with electrophilic trifluoromethylating reagents

Abstract

Electrophilic trifluoromethylation reactions have been the latest approach to achieve the fluoroalkylation of compounds with newly-discovered reagents, such as the Togni's (1-trifluoromethyl-1,2-benziodoxol-3-(1 H)-one), Umemoto's (S-(trifluoromethyl)dibenzothiophenium tetrafluoroborate), Yagupolskii's (S-(trifluoromethyldiarylsulfonium salts), Shreeve's (S-(trifluoromethyl)dibenzothiophenium triflate), and Shibata's (trifluoromethylsulfoximine salts) reagents. All these reagents produce an electrophilic trifluoromethylating (CF3 (+) ) species that undergoes reaction with nucleophiles. In addition, these latter reactive species (i.e. CF3 (+) ) can undergo electron-transfer (ET) processes affording CF3 (⋅) radicals that expand the scope to substrates other than conventional nucleophiles that can undergo reaction. In this Review, we shall discuss the trifluoromethylation reactions of diverse families of organic substrates of biological interest as a means to comparing the reagents scope and best reaction conditions. Some, though not all, of these reactions require the assistance of metal or organometallic catalysts. Some require additives and catalysts to promote the fluoroalkylation reaction, but invariably all are initiated and carried out by electrophilic trifluoromethylating species.

Keywords: electrophilic addition; fluorinated compounds; radical reactions; synthetic methods; trifluoromethylation.