Merging Hydrogen-Atom-Transfer and the Truce-Smiles Rearrangement for Synthesis of β-Arylethylamines from Unactivated Allylsulfonamides

Abstract

Arylethylamines are crucial elements in pharmaceutical molecules, making methods for their synthesis highly significant. The Truce-Smiles rearrangement is a well-developed strategy to synthesize arylethylamine motifs via aryl migration. However, most examples require amide substrates to activate the alkene to attack by a radical precursor. This strategy both limits the product scope to amide-containing compounds as well as necessitating the incorporation of specific functional groups arising from the initial radical addition. In this work, we overcome these limitations, delivering a hydrogen-atom transfer from a cobalt catalyst to unactivated alkenes to yield β-arylethylamines with simple alkyl chains. DFT studies reveal that increasing the steric hindrance in at least one of the ortho positions on the migrating aromatic group promotes ipso over ortho addition, a selectivity that contrasts with previous methods.

Keywords: Arylation; Cobalt; Density functional calculations; Hydrogen‐atom‐transfer; Reaction mechanisms.