Modular Synthesis of α-Aryl Acrylamido Carboxylic Acids by Triple C-F Bond Cleavage of (Trifluoromethyl)alkenes with Unprotected Amino Acids.

A straightforward and efficient strategy for the construction of tertiary and secondary α-aryl acrylamido carboxylic acids is reported. This N-acrylation protocol of unprotected amino acids is achieved by triple C-F bond cleavage of (trifluoromethyl)alkenes. This method features mild conditions, is operationally simple, is free of transition metals and racemization, can be used on a gram scale, and is compatible with various functional moieties. Mechanistic studies indicate that oxygen atom exchange happens among H 2 O, NaOH, and amino acids, and the oxygen atom of the amide moiety of the product is incorporated by the ipso -defluorooxylation of (trifluoromethyl)alkene.