Photocatalyzed regioselective arylation of trialkylamines

Abstract

Easily available trialkylamines are increasingly utilized as coupling partners with diverse hydrocarbons to construct various complicated amine frameworks. However, controlling the regioselectivity of these reactions remains a significant challenge. We have developed a method to control arylation reaction sites by modulating the tertiary amine structure in a polar solvent. This approach operates under simple conditions, requiring only a polar solvent to selectively target the methyl group of N-methyl tertiary amines. It facilitates selective arylation across a wide range of trialkylamines substrates, eliminating previous dependencies on restrictive factors such as the use of symmetrical or cyclic trialkylamines, or the need to fine-tune N-alkyl steric hindrance. Notably, a distinct contrast was observed with benzocyclic tertiary amines: the reaction took place at the adjacent methylene group. Nevertheless, this selectivity is reversed upon expansion to an eight-membered ring, wherein the N-methyl group is again favored.