Red-light-induced high-efficiency oxidation and functionalization of tetrahydroisoquinoline derivatives using chlorophyll as a photocatalyst†

Abstract

A novel, green, and efficient red-light-induced oxidation and functionalization of tetrahydroisoquinoline derivatives (THIQs) has been developed using crude chlorophyll as a photocatalyst extracted from spinach. This green and mild photocatalytic method shows potential for application in medicinal chemistry, enabling not only efficient oxidation at the benzyl position of THIQs, but also rapid diversification of pharmacophoric scaffolds through cross-coupling with a range of nucleophilic reagents, achieving phosphorylation, cyanation, nitro-methylation, and allylation. The synthesis of 40 compounds led to the discovery of compound 4i, which exhibits neuroprotective effects validated in vitro using the neuronal OGD/R model. Further mechanistic investigation suggests that the reaction may involve superoxide anion radicals resulting from photoinduced electron transfer processes.