Enantioselective, Organocatalytic Oxy-Michael Addition to γ/δ-Hydroxy-α,β-enones: Boronate-Amine Complexes as Chiral Hydroxide Synthons

An organocatalytic, enantioselective oxy-Michael addition to achiral γ- and δ-hydroxy-α,β-enones was developed. The key transformation is an unprecedented, asymmetric conjugate addition triggered by complexation between an in situ generated boronic acid hemiester and a chiral amine catalyst. Functionally, the intermediate amine−boronate complex acts as a chiral hydroxide surrogate or synthon. The resultant chiral β-hydroxy-ketones are obtained in good to excellent yields and high ee following mild oxidative removal of the cyclic boronate. Natural products (R,12Z,15Z)-2-hydroxy-4-oxohenicosa-12,15-dienyl acetate and (+)-(S)-streptenol A were synthesized to demonstrate the utility of this reaction.