Enantioselective Synthesis of Chiral Medium-Sized Cyclic Compounds via Tandem Cycloaddition/Cope Rearrangement Strategy

Abstract

The nine-membered ring-bearing bicyclo[5.2.2]tetrahydrooxonines frameworks have enantioselectively been constructed via a tandem [3 + 2] cycloaddition/Cope rearrangement reaction of vinylethylene carbonates (VECs) with coumalates or pyrones. Under mild conditions, palladium-catalyzed asymmetric tandem reaction of various substituted VECs and coumalates or pyrones proceeds smoothly to produce the corresponding medium-sized heterocyclic compounds in high yields with very high enantioselectivities. Moreover, the reaction on the gram scale and further diverse transformations of the products were workable. The reaction mechanism was investigated through control experiments and DFT calculations, which show the reaction proceeds via a tandem [3 + 2] cycloaddition/Cope rearrangement pathway rather than via a [5 + 4] cycloaddition pathway.