Distal C(sp <sup>3</sup> )-H Amidation via Ind*Rh <sup>III</sup> Catalyzed Nitrene Transfer
Hannah J. Ross, Yang Yu, Liselle Atkin, Milad Ghorbani, Kelly Mint, Nicole M. Warne, Kristian Kempe, Daniel L. Priebbenow
Abstract
The Ind*Rh III catalyzed distal amidation of C(sp 3 )–H sites was explored, harnessing amides as weakly coordinating directing groups. The combined use of an Ind*Rh III complex and 2-pyridone ligand delivered the enhanced catalytic activity required to functionalize both primary and secondary β-C(sp 3 )–H sites. The accelerated nitrene transfer catalysis facilitated the late-stage functionalization of pharmaceutical derivatives and the synthesis of drug conjugates bearing peptides, biotin, or E3-ligase binders. The post-polymerization modification of poly(2-alkyl-2-oxazoline)s and poly(2-alkyl-2-oxazine)s using Ind*Rh III nitrene transfer catalysis involving the site-selective C–H amidation of polymer side chains was also achieved.