Asymmetric Synthesis of Methylenetetrahydrofurans by Palladium-Catalyzed [3 + 2] Cycloaddition of Trimethylenemethane with Aldehydes – A Novel Ligand Design

Abstract

The palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane (TMM) with aldehydes is a direct and efficient route to methylenetetrahydrofurans. Herein we describe the first asymmetric synthesis of methylenetetrahydrofurans utilizing a palladium-TMM complex in the presence of a novel phosphoramidite ligand possessing a stereogenic phosphorus. The method allows for the formation of chiral disubstituted tetrahydrofurans in good yields and enantioselectivities.