Photocatalytic synthesis of 3,3-disubstituted cyclobutanols via trifunctionalization of [1.1.1]propellane

Cyclobutanols represent important structural motifs found in numerous bioactive compounds; however, efficient strategies for their synthesis remain scarce. Herein, we report an aqueous-phase trifunctionalization of [1.1.1]propellane via a synergistic approach combining Brønsted acid-promoted hydration-triggered ring-opening and photoredox catalysis, enabling direct access to 3,3-disubstituted cyclobutanol derivatives. Mechanistic studies indicate that Brønsted acids mediate the selective hydration of [1.1.1]propellane to generate a methylenecyclobutanol intermediate that subsequently engages in a photocatalytic radical cascade with alkyl bromides and quinoxalin-2(1H)-ones. In situ oxidation then afforded the corresponding cyclobutanone derivatives in a streamlined one-pot transformation that proceeded under mild conditions. Moreover, our protocol displayed a broad substrate scope and accommodated late-stage functionalization, underscoring its overall applicability in synthetic and medicinal chemistry.