Electrochemical sulfonylation/Truce–Smiles rearrangement of N-allylbenzamides: toward sulfone-containing β-arylethylamines and Saclofen analogues

Abstract

The β-arylethylamine pharmacophore is commonly found in medications for central nervous system disorders, prompting the need for safe and efficient methods to endow this motif with relevant functional groups for drug discovery. In this context, herein, we have established electrochemical radical sulfonylation reactions of N-allylbenzamides followed by Truce–Smiles rearrangement to produce sulfone- and sulfonate ester-containing β-arylethylamines. Electricity enables this transformation to occur under mild and oxidant-free conditions. Simple sources of sulfonyl radicals and SO₂ surrogates were employed to form sulfones and sulfonate esters, respectively. This practical and operationally robust method exhibited a broad substrate scope with good to high yields. The prospective pharmaceutical utility of the process was further demonstrated by removing the N-protecting groups and hydrolysing the sulfonate ester moiety to provide γ-sulfonyl-β-arylamines and Saclofen.