Catalytic asymmetric inverse-electron-demand Diels–Alder reaction of 2-pyrones with aryl enol ethers

Chiral aryl cyclohex-3-en ether scaffold is widely present in bioactive natural products and drugs. The exploitation of efficient and enantioselective methods for the construction of aryl cyclohex-3-en ether scaffold is significant. Herein we disclose a chiral N,N’-dioxide/Lewis acid complex-catalyzed asymmetric inverse-electron-demand Diels–Alder (IEDDA) reaction using electron-deficient 3-carboalkoxyl-2-pyrones and less electron-enriched aryl enol ethers as reactants. A wide range of non- and 1,2-disubstituted acyclic aryl enol ethers are applicable to deliver diverse chiral bridged bicyclic lactones in high yields and stereoselectivities (up to 96 % yield, >20:1 dr, 97:3 er). The bridged bicyclic lactone core can be easily converted into chiral aryl cyclohex-3-en ether scaffold. Notably, DFT calculations revealed a stepwise and endo mechanism to explain the high enantioselectivity controlled by the cooperative effect of the steric factors and the dispersion interactions between ligands and enol ethers.