Pd-Catalyzed Remote Site-Selective and Stereoselective C(Alkenyl)-H Alkenylation of Unactivated Cycloalkenes

A palladium-catalyzed alkenylation involving remote delta-position C(alkenyl)-H activation of cycloalkenes reacting with electron-deficient alkenes is described. This method features excellent site selectivity and stereoselectivity to efficiently afford only E-selective highly substituted 1,3-diene derivatives with extra-ligand-free and good functional group tolerance including estrone and free N-H tryptamine under weakly alkaline conditions. Mechanistic studies suggest that picolinamide as a bidentate directing group enables the formation of unique alkenyl palladacycle intermediates.