Pd(0)-Catalyzed Enantioselective Formal Normal-Electron-Demand Cross-[4 + 2] Cycloadditions of Morita–Baylis–Hillman Carbonates with 1,3-Dienes

Abstract

Herein, we describe a palladium(0)-catalyzed cross-[4 + 2] cycloaddition of 2-carboalkoxy-1,3-butadienes, generated in situ from Morita–Baylis–Hillman carbonates, with 1,3-dienes. The use of a palladium(0) catalyst and a side arm-modified chiral phosphoramidite ligand, which contains a dihydroacridine moiety, facilitates the [4 + 2] cycloaddition proceeding in a formal normal-electron-demand pathway with excellent regioselectivity and stereoselectivity. With this method, a wide range of para-substituted cyclohexenes bearing a quaternary chiral center are obtained in high yields and excellent enantioselectivities. The synthetic value of this method is further demonstrated by diverse downstream transformations of the [4 + 2] cycloaddition products into various structurally novel ring systems. DFT calculations show that the [4 + 2] cycloaddition proceeds through a pathway involving highly selective [4 + 4+1] oxidative cyclometalation, allylic isomerization, and 3,3′-reductive elimination steps. It is also suggested that the high level of enantioselectivity is probably due to weak nonbonding interactions from the phenyl group on the side arm of the ligand.