Discovery and mechanistic study of a photocatalytic indoline dehydrogenation for the synthesis of elbasvir.

ABSTRACT: Elbasvir is a potent NS5A antagonist for the treatment of chronic hepatitis C. A seemingly trivial indoline oxidation en route to the target compound was complicated by epimerization of a stereogenic hemiaminal center under most standard oxidation conditions. To address this issue, a novel visible light photoredox process for indoline oxidation was developed involving an iridium photosensitizer and environmentally-benign perester oxidant. The reaction was discovered through a high-throughput experimentation campaign and the optimized process was demonstrated on 100 g scale in flow to afford a key intermediate towards the target compound. A battery of kinetic, electrochemical, and spectroscopic studies of this process indicates a radical chain mechanism of dehydrogenation involving selectiv

SUBMITTER: Yayla HG 

PROVIDER: S-EPMC5968518 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature