Rhodium-catalyzed regioselective C3ar functionalization of tyrosines with maleimides and its late-stage peptide exemplification

Abstract

Pyridyloxy-directed Rh(III)-catalyzed regioselective C3Ar–H alkenylation of protected tyrosines was achieved with N-aryl and N-alkyl maleimides, furnishing a series of maleimide-appended tyrosine-based unnatural amino acids in good yields. Further, the late-stage exemplification of the strategy was successfully accomplished on tyrosine-containing dipeptides, tripeptides, and tetrapeptides in moderate reactivity. Also, the chemical applications of the strategy were successfully executed toward nailing tyrosine with other amino acids via a maleimide linker and intramolecular hydroarylation to produce tyrosine-centered stapled products and succinimide-glued macrocyclized products, respectively.