New Avenues in Smiles Arylation

Abstract

The Smiles rearrangement is an ipso-aryl transfer that can be integrated into intermolecular reaction cascades to enable the efficient formation of valuable bonds and complex products under mild and operationally simple conditions. Herein, four transformations are described that explore new avenues in Smiles arylation. Firstly, a desulfinylative diarylamine synthesis is described. This reaction uncovers distinct aryl-transfer reactivity of underexplored diarylsulfinamide linkers, synthesising various diarylamines through a 3-exo-trig Smiles rearrangement. Secondly, archetypal bifunctional sulfonamides are reacted with electrophilic cyclopropanes, enacting a Smiles-Truce cascade which results in the synthesis of pharmaceutically relevant pyrrolidinone scaffolds. The reaction is characterised by its operational simplicity, using commercially available starting materials and simple base treatment to furnish highly complex pyrrolidinones. Thirdly, a C-N arylation of anilines is described. This reaction uses benzyne to activate and arylate the C-N bond of anilines through a 4-exo-trig Smiles-Truce rearrangement. This reaction unveils the C-N bond of anilines as functional handles for arylation and is used to synthesise a wide variety of biaryls. The reaction can also be applied to ring-expansion, furnishing highly complex tricyclic scaffolds. Finally, a Halogen-Atom Transfer (XAT) mediated intramolecular biaryl synthesis is described. This reaction uses an underexplored and readily synthesised benzanilide scaffold and XAT-mediated photoredox catalysis to synthesise a range of biaryls. The reaction is also effectively integrated into a telescoped C-N arylation of anilines.

Date of Award	6 Jan 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Sam Butterworth (Supervisor) & Michael Greaney (Supervisor)