Visible-Light-Driven [2+2] Cycloaddition of Coumarins with Diverse Olefins Using a 4CzIPN Photosensitizer: Application to the Total Synthesis of (±)-Lindleyanin

Abstract

Cyclobutane scaffolds represent essential structural motifs in bioactive natural products; however, their synthesis often requires high-energy ultraviolet radiation or costly transition metal catalysts. Herein, we present a sustainable metal-free photosensitized energy transfer strategy for the [2+2] cycloaddition of coumarins with diverse olefins under visible-light irradiation. Employing the organic photocatalyst 4CzIPN in the environmentally benign solvent dimethyl carbonate (DMC), the reaction proceeds efficiently at ambient temperature using a 25 W blue LED, generating cyclobutane-fused chromones in 31–89% yields. The methodology demonstrates an exceptional substrate scope, tolerating diverse styrenes, aliphatic olefins, cycloalkenes (up to eight-membered rings), and heterocycles like benzothiophene. Notably, gram-scale reactions retain a high efficiency, providing the cycloaddition product in 72% yield. Furthermore, implementation of this strategy as a key transformation facilitated the first seven-step total synthesis of the cyclobutane-containing natural product (±)-lindleyanin (5/6/4/6/6/5-fused polycyclic system), underscoring its utility for constructing complex molecular architectures.