Can a Ketone Be More Reactive than an Aldehyde? Catalytic Asymmetric Synthesis of Substituted Tetrahydrofurans

Abstract

O-heterocycles bearing tetrasubstituted stereogenic centers are prepared via catalytic chemo- and enantioselective nucleophilic additions to ketoaldehydes, in which the ketone reacts preferentially over the aldehyde. Five- and six-membered rings with both aromatic and aliphatic substituents, as well as an alkynyl substituent, are obtained. Moreover, 2,2,5-trisubstituted and 2,2,5,5-tetrasubstituted tetrahydrofurans are synthesized with excellent stereoselectivities. Additionally, the synthetic utility of the described method is demonstrated with a three-step synthesis of the side chain of anhydroharringtonine.

Keywords: Lewis acid catalysis; enantioselective nucleophilic addition; oxygen heterocycles; tetrasubstituted stereogenic centers.