Cooperative N-heterocyclic carbene/photocatalysis: visible-light-promoted tandem α-sp3 C–H activation and reductive N-alkylation of tetrahydroisoquinoline

Abstract

While N-heterocyclic carbenes (NHCs) play a vital role as organocatalysts due to their umpolung reactivity toward carbonyl or imine carbons, activation of sp³-carbons via single-electron transfer (SET) processes remains challenging and underdeveloped. Recently, the coupling of NHC catalysis with photocatalysis for the SET process has gained attention. Herein, we report visible-light and NHC-catalyzed tandem α-sp³ C–H activation and reductive N-alkylation of tetrahydroisoquinoline (THIQ) with o-hydroxybenzaldehydes. The key step in this process is the formation of a photoactive species between o-hydroxybenzaldehydes and a base, which functions as a self-photocatalyst, eliminating the need for an external photocatalyst or photoactivator. The subsequent reaction of photoactive species with NHCs leads to the Breslow intermediate, followed by intramolecular hydrogen atom transfer (HAT) and benzylic activation to form N-benzylated 3,4-dihydroisoquinolin-1(2H)-ones. The salient features of this work include the use of sunlight as a visible-light source and molecular oxygen as an oxidant under mild reaction conditions, highlighting the green chemistry aspects of this approach.