An organocatalytic domino annulation approach via C(sp2)–OMe cleavage to unlock the synthesis of pyranochromenones enabled by HFIP

Abstract

Fused pyranochromenone derivatives have extensive applications in medicinal chemistry. Herein, we report the first HFIP/TsOH catalyzed, one-pot domino reaction by cleavage of the C(sp²)–OMe bond. Control experiments reveal that 1,3,5-trimethoxybenzene is rapidly protonated in the presence of HFIP to yield a dearomatized cationic diene intermediate. The gram-scale reaction and late-stage functionalization of natural products justified the practicality of this protocol.