Asymmetric Inverse‐Electron‐Demand Hetero‐Diels–Alder Reaction for the Construction of Bicyclic Skeletons with Multiple Stereocenters by Using a Bifunctional Organocatalytic Strategy: An Efficient Approach to Chiral Macrolides

Abstract

We have performed the first bifunctional organocatalytic highly enantioselective inverse-electron-demand hetero-Diels-Alder reaction of cyclic ketones with enones to afford densely functionalized bicyclic skeletons that contain three stereocenters (up 82% yield, 10:1 d.r., and 97% ee). Unlike the previous IEDDAR catalytic strategy, this method features a double HOMO(dienophile)/ LUMO(diene)-activated pathway. Moreover, this process provides a promising method for the construction of enantioenriched macrolides.