Nucleophilic trifluoromethylation of carbonyl compounds and derivatives

Abstract

This review highlights the main methods for the nucleophilic trifluoromethylation of aldehydes, ketones, esters, imines and their analogous compounds published in the literature in the last six years. The focus is on synthetically useful procedures and the work is organized according to the type of carbonyl compound subjected to the trifluoromethylation reaction.

Aqueous Benzylic C–H Trifluoromethylation for Late-Stage Functionalization

“…Excitingly, a number of recent reports describe novel trifluoromethylating reagents that offer the potential for new opportunities to trifluoromethylate organic molecules. The wide availability of the Ruppert–Prakash, Togni, Umemoto, Langlois, Grushin, Chen, Shibata, Baran and other reagents have provided chemists with numerous useful trifluoromethyl synthons with unique properties. Evaluating such reagents under traditional reaction conditions should enable rapid access to new chemical matter.…”

Transition-Metal-Free Trifluoromethylation of Aldehyde Derivatives with Sodium Trifluoromethanesulfinate

“…Trifluoromethyl ketones (TFMKs, RCOCF 3 ) are important components of many biologically active compounds and widely used building blocks in the synthesis of fluorinated molecules. Nucleophilic trifluoromethylation of carbonyl compounds and their nitrogenous derivatives has led to the development of many synthetically useful processes notably based on the use of the Ruppert–Prakash reagent (Me 3 SiCF 3 ) for the synthesis of valuable fluorinated compounds. , Recently, various electrophilic and radical C­(sp 2 )–CF 3 and C­(sp 3 )–CF 3 bond formation protocols have been developed for the trifluoromethylation of carbonyl derivatives. − In this area, particular efforts have been made toward introduction of a CF 3 group at the α-position of carbonyl compounds. Nitrogen-containing derivatives like azomethines may also be used to modify the reactivity of the carbonyl moiety toward trifluoromethylation and open further opportunities for new synthetic strategies or chemical transformations.…”

Asymmetric Synthesis of 3,4-Disubstituted 2-(Trifluoromethyl)pyrrolidines through Rearrangement of Chiral 2-(2,2,2-Trifluoro-1-hydroxyethyl)azetidines

“…In recent years, the search for synthetic strategies enabling the incorporation of a trifluoromethyl group in organic molecules has been expanded considerably, as the presence of this entity is known to provoke a pronounced impact on the physical and chemical properties of the resulting compounds . In particular, hydrogen-by-fluorine replacement has been shown to induce an enhancement of the metabolic stability and a change in lipophilicity of the involved molecules .…”