Visible Light Mediated Aryl Migration by Homolytic C−N Cleavage of Aryl Amines

Abstract

The photocatalytic preparation of aminoalkylated heteroarenes from haloalkylamides via a 1,4-aryl migration from nitrogen to carbon, conceptually analogous to a radical Smiles rearrangement, is reported. This method enables the substitution of amino groups in heteroaromatic compounds with aminoalkyl motifs under mild, iridium(III)-mediated photoredox conditions. It provides rapid access to thienoazepinone, a pharmacophore present in multiple drug candidates for potential treatment of different conditions, including inflammation and psychotic disorders.

Truce–Smiles Rearrangements by Strain Release: Harnessing Primary Alkyl Radicals for Metal‐Free Arylation

“…The second major approach has been the single‐electron reduction of alkyl/ aryl halides and their equivalents ( 5 ), first demonstrated in seminal work from Speckamp and Motherwell in the synthesis of sp 3 ‐aryls and sp 2 –sp 2 biaryls using tin hydride chemistry [3a–c] . Recent developments in photoredox catalysis have supplanted tin reagents and transformed the scope of the reaction, but do generally require the use of precious metal catalysts to perform the initial reductions [3e–g] …”

“…We hoped that the Truce–Smiles rearrangement could address all three of these shortcomings. In addition, the capture of unstabilized primary radicals is uncommon [3e, 7] in Truce–Smiles systems, enhancing the new reaction space we could explore with the proposed strain‐release system.…”

Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy

“…Restoration of the aromaticity is followed by a presumable hydrogen atom transfer to obtain compound 63 – 6 in 95% yield. 258 …”

Recent Advances in the Smiles Rearrangement: New Opportunities for Arylation

“…The products given in the reaction act as useful precursors to tetrahydrothienoazepinones, an important pharmaceutical scaffold. [60] Accepted Manuscript This article is protected by copyright. All rights reserved.…”