Distal C(sp3)-H Amidation via Ind*RhIII Catalysed Nitrene Transfer using 1,4,2-Dioxazol-5-ones

Building on our discovery that Ind*Rh(III) catalysts accelerated C(sp2)–H amidation, the Ind*Rh(III) catalysed amidation of C(sp3)–H sites was explored harnessing amides as weakly-coordinating directing groups. The combined use of an indenyl-derived catalyst and 2-pyridone additive proved critical in providing the enhanced catalytic activity required to achieve the amidation of both primary and secondary C(sp3)–H sites, affording a diversity of valuable structures. The late-stage amidation and peptide conjugation of pharmaceutical derivatives using the Ind*RhIII/2-pyridone catalytic system was also demonstrated.