A formal [4 + 1] annulation incorporating styrylogous aldol condensation to access functionalized 2-styryl-benzofurans†

Abstract

Despite the well-established aldol reaction and its vinylogous variants, the styrylogous version has been scarcely reported. Herein, we have introduced a styrylogous aldol condensation reaction. A novel base-mediated formal [4 + 1] annulation, integrating O-allylation and styrylogous aldol condensation, has been disclosed. This transformation involves ortho-hydroxyaryl aldehydes/ketones in conjunction with distally-activated cinnamyl (pseudo)halides. The presented transition metal-free process forms C–O and CC bonds, enabling the synthesis of functionalized 2-styryl-benzofuran derivatives in moderate to good yields. The application potential of the developed method has been demonstrated in the efficient syntheses of 2-aminostyryl-benzofuran derivatives, which have proven to act as potent inhibitors for Aβ fibril formation related to Alzheimer's disease (AD).