Enantioselective synthesis of hindered cyclic dialkyl ethers via catalytic oxa-Michael/Michael desymmetrization.

Abstract

An asymmetric oxa-Michael/Michael cascade reaction of p-quinols and α,β-unsaturated aldehydes provides access to hindered dialkyl ethers. A highly enantioselective oxa-Michael addition of a tertiary alcohol precedes an intramolecular cyclohexadienone desymmetrization, which allows for the concomitant formation of four contiguous stereocenters in a single step. The highly functionalized bicyclic frameworks are rapidly obtained from simple starting materials with good diastereoselection and serve as valuable precursors for further manipulation.