Catalytic C(sp3)-H Trifluoroethylation of Amino Acids and Carboxylic Acids.

Abstract

Integrating of the trifluoroethyl (-CH2CF3) group into the organic compounds by activating the distal C(sp3)-H bond is a challenging but crucial task in organic chemistry. This transformation imparts unique physicochemical properties to the compounds, such as enhanced lipophilicity, metabolic stability, and altered electronic characteristics. In this study, we unveil a new palladium-catalyzed method to directly introduce the trifluoroethyl group into amino acid and carboxylic acid derivatives. Remarkably, this method effectively activates the β-C(sp3)-H bond across various substrates at room temperature. Utilizing mesityl(2,2,2-trifluoroethyl)iodonium triflate as a trifluoroethyl source, our approach selectively targets the distal β-C(sp3)-H bonds of amino and carboxylic acids, ensuring high chemoselectivity and enabling the straightforward synthesis of a diverse array of important γ-trifluoromethyl amino acid and carboxylic acid derivatives. Furthermore, the practical applicability of this methodology is demonstrated through its scalability for gram-scale synthesis.