Enantioselective synthesis of 2,2-disubstituted tetrahydrofurans: palladium-catalyzed [3+2] cycloadditions of trimethylenemethane with ketones

An approach to 2,2-disubstituted 4-methylenetetrahydrofurans has been developed utilizing a cycloaddition of trimethylenemethane with aryl ketones, with formation of the products in up to 96% yield and 95% ee. The reaction is catalyzed by palladium in the presence of a phosphoramidite ligand possessing a stereogenic phosphorus, where only a single epimer at phosphorus yields the active catalyst. The identity of this epimer and the origin of its effect on reactivity are discussed.