Higher-order dearomative [10+2] cycloaddition of 2-nitrobenzofurans and 2-alkylidene-1-indanones to access pentacyclic scaffolds

Abstract

Higher-order cycloadditions offer an efficient and atom-economical route to access complex polycyclic frameworks with novel structural motifs. Herein, we report a higher-order dearomative [10+2] cycloaddition between 2-nitrobenzofurans and in situ generated 1-hydroxy isobenzofulvene anions from 2-alkylidene-1-indanones, enabled by phase-transfer catalysis. A diverse array of fused pentacyclic benzofurocyclopenta[b]indanones were obatined in high yields with excellent diastereoselectivities (up to 99% yield and >20:1 dr). The synthetic utility of this methodology was further demonstrated through a scale-up experiment and the late-stage functionalization of complex pharmaceutical molecules.