A Visible-Light-Mediated Radical Smiles Rearrangement and its Application to the Synthesis of a Difluoro-Substituted Spirocyclic ORL-1 Antagonist.

ABSTRACT: A visible-light-mediated radical Smiles rearrangement has been developed to address the challenging synthesis of the gem-difluoro group present in an opioid receptor-like?1 (ORL-1) antagonist that is currently in development for the treatment of depression and/or obesity. This method enables the direct and efficient introduction of the difluoroethanol motif into a range of aryl and heteroaryl systems, representing a new disconnection for the synthesis of this versatile moiety. When applied to the target compound, the photochemical step could be conducted on 15?g scale using industrially relevant [Ru(bpy)3Cl2] catalyst loadings of 0.01?mol?%. This transformation is part of an overall five-step route to the antagonist that compares favorably to the current synthetic sequence and demonstrates, in this specific case, a clear strategic benefit of photocatalysis.

SUBMITTER: Douglas JJ 

PROVIDER: S-EPMC4725294 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature