A photoinduced multicomponent intramolecular cyclization/hydroxytrifluoromethylation cascade: facile access to polyfunctionalized 3,4-dihydroquinazolinones

Abstract

Multicomponent reactions (MCRs) have demonstrated enormous potential in the direct and single-step synthesis of chemical entities with structural diversity. However, the photochemical MCR approach for the construction of N-heterocycles, particularly functionalized ones, from non-heterocyclic synthons remains relatively unexplored. Herein, we report a modular assembly of CF₃-modified 3,4-dihydroquinazolinones from basic building blocks using a one-pot light-driven multicomponent approach. In this protocol, the latent capability of 1-(2-acetylphenyl)-3-phenylurea to reach a reactive triplet state upon energy transfer (EnT) activation while successfully triggering intramolecular cyclization is disclosed. Medicinally relevant 3,4-dihydroquinazolinones could be feasibly synthesized from commercially available 2-aminoacetophenone, p-tolyl isocyanate, and Togni's II, offering a metal-free construction with broad functional group tolerance. Mechanistic investigations revealed EnT mediated intramolecular cyclization and single electron transfer (SET) mediated hydroxytrifluoromethylation cascade reactions in this novel process. Density functional theory calculations illustrated the energy landscape of this photoinduced transformation.