Alkyl-Trifluoromethylation of Glycine Derivatives

We present a three-component, successive radical addition-coupling strategy for the synthesis of complex alkyl-trifluoromethylated noncanonical α-amino acids. This method utilizes readily available glycine derivatives, alkenes, and trifluoromethyl thianthrenium triflate, all under a metal-free, photoredox-neutral catalytic cycle. The effectiveness of this approach is further demonstrated through its application in late-stage, site-selective modifications of glycine residues in short peptides. Notably, only 2 mol % of the nonmetal catalyst, Eosin Y, is required, highlighting the high catalytic efficiency of this reaction.