Rhodium-Catalyzed Regioselective C3<sub>Ar</sub> Functionalization of Tyrosines with Maleimides and Its Late-Stage Peptide Exemplification
Narendra Dinkar Kharat, Sushma Naharwal, Disha Tank, Siva S. Panda, Kiran Bajaj, Rajeev Sakhuja
Abstract
Pyridyloxy-directed Rh(III)-catalyzed regioselective C3 Ar –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.