Brønsted acid catalyzed, conjugate addition of β-dicarbonyls to in situ generated ortho-quinone methides--enantioselective synthesis of 4-aryl-4H-chromenes

Abstract

We describe herein a catalytic, enantioselective process for the synthesis of 4H-chromenes which are important structural elements of many natural products and biologically active compounds. A sequence comprising a conjugate addition of β-diketones to in situ generated ortho-quinone methides followed by a cyclodehydration reaction furnished 4-aryl-4H-chromenes in generally excellent yields and high optical purity. A BINOL-based chiral phosphoric acid was employed as a Brønsted acid catalyst which converted ortho-hydroxy benzhydryl alcohols into hydrogen-bonded ortho-quinone methides and effected the carbon-carbon bond-forming event with high enantioselectivity.

Keywords: asymmetric synthesis; benzhydrylic alcohols; chiral phosphoric acids; chromenes; xanthenones.