Palladium-catalyzed asymmetric [4 + 3] cycloaddition of methylene-trimethylenemethane: access to seven-membered exocyclic axially chiral allenes

Abstract

A palladium-catalyzed asymmetric [4 + 3] cycloaddition of the methylene-trimethylenemethane donor with an azadiene has been developed, affording benzofuro[3,2-b]azepine-derived exocyclic chiral allene with control of axial and point chirality. The target compounds were generated in good to excellent yields and with high diastereoselectivities and enantioselectivities (up to >20 : 1 dr, 99% ee). Furthermore, this cycloaddition reaction could be efficiently scaled-up and several synthetic transformations were accomplished for the construction of useful chiral allenol and chiral spirocyclic derivatives.