Diastereo- and Enantioselective Inverse-Electron-Demand Diels-Alder Cycloaddition between 2-Pyrones and Acyclic Enol Ethers

Abstract

A broadly applicable diastereo- and enantioselective inverse-electron-demand Diels-Alder reaction of 2-pyrones and acyclic enol ethers is reported herein. Using a copper(II)-BOX catalytic system, bridged bicyclic lactones are obtained in very high yields (up to 99 % yield) and enantioselectivities (up to 99 % ee) from diversely substituted 2-pyrones and acyclic enol ethers. Mechanistic experiments as well as DFT calculations indicate the occurrence of a stepwise mechanism. The synthetic potential of the bridged bicyclic lactones is showcased by the enantioselective synthesis of polyfunctional cyclohexenes and cyclohexadienes, as well as a carbasugar unit.

Keywords: Asymmetric Catalysis; Copper; Cycloaddition; Diastereoselectivity; Enantioselectivity.