Details

Autor(en) / Beteiligte

• Douglas, James J.
• Albright, Haley
• Sevrin, Martin J.
• Cole, Kevin P.
• Stephenson, Corey R. J.

Titel

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

Ist Teil von

• Angewandte Chemie (International ed.), 2015-12, Vol.54 (49), p.14898-14902

Auflage

International ed. in English

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. A reason for Smiles: A visible‐light‐mediated radical Smiles rearrangement addresses the challenging synthesis of the gem‐difluoro group present in an opioid receptor‐like 1 (ORL‐1) antagonist and enables the introduction of the difluoroethanol motif into a range of aryl and heteroaryl systems. When applied to the target compound, the photochemical step could be conducted on 15 g scale at a [Ru(bpy)3]Cl2 loading of 0.01 mol %.