An organocatalytic domino annulation approach C(sp)-OMe cleavage to unlock the synthesis of pyranochromenones enabled by HFIP.

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(sp)-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.