A novel synthesis of functionalized tetrahydrofurans by an Oxa-Michael/Michael cyclization of γ-hydroxyenones

Abstract

An approach to highly functionalized tetrahydrofuran derivatives based upon a novel Oxa-Michael/ Michael dimerization of cis-γ-hydroxyenones is presented. The reaction begins with either 1,2-dioxines or trans-γ-hydroxyenones and proceeds by addition of one molecule of trans-γ-hydroxyenone to another molecule of cis- or trans-γ-hydroxyenone catalyzed by an alkoxide or hydroxide base. Subsequent intramolecular Michael addition of the keto-enolate gives the observed tetrahydrofurans. Substitution at both the 2- and 4-positions of the γ-hydroxyenone is tolerated; however, for 4-substituted γ-hydroxyenones, selectivity issues arise due to the possibility of heterochiral or homochiral dimerizations. The major products were those with all contiguous groups trans.