Organocatalytic Asymmetric Nucleophilic Addition to o-Quinone Methides by Alcohols

The first catalytic asymmetric intermolecular alcohol conjugate addition to o-quinone methides (o-QMs) is disclosed. Due to reversible C-O bond formation and low nucleophilicity of alcohols, catalytic asymmetric oxa-Michael additions with simple alcohol nucleophiles to establish acyclic oxygenated carbon stereocenters remain scarce. The present reaction represents a rare example of this type. With a suitable chiral acid catalyst, the in situ formation of o-QMs and subsequent conjugate addition proceeded with high efficiency and enantioselectivity. The chiral ether products are versatile precursors to other chiral molecules.