Synthesis of cis-fused-oxazolo/oxazino-isoquinolinones via photocascade reaction

Abstract

A method for the selective synthesis of cis-fused-oxazoloisoquinolinones (2-α, 2-β) and cis-fused-oxazinoisoquinolinones (4-α, 4-β) via the visible light photo cascade reaction of (E)-1-(2-hydroxyethyl/propyl)-4-methyl-3-styrylpyridin-2(1H) ones 1/3 was described. In the presence of hydrochloric acid, the dichloromethane solution of 1 and 3 was protected by argon and irradiated with a 50 W LED at 410–415 nm for 2 h, giving 2-α, 2-β and 4-α, 4-β in good yields via a tandem reaction. The transformation involves a sequential E-to-Z photoisomerization, 6π-electrocyclization, and intramolecular nucleophilic addition–cyclization, enabling efficient construction of the dearomatized isoquinolin-1(2H)-one scaffold with high atom economy and bond-forming efficiency. Notably, the reaction exhibits excellent stereoselectivity, favoring cis-fused products, which are otherwise challenging to access via conventional thermal methods.