A novel synthesis of functionalized tetrahydrofurans by an Oxa-Michael/Michael cyclization of gamma-hydroxyenones.
An approach to highly functionalized tetrahydrofuran derivatives based upon a novel Oxa-Michael/Michael dimerization of cis-gamma-hydroxyenones is presented. The reaction begins with either 1,2-dioxines or trans-gamma-hydroxyenones and proceeds by addition of one molecule of trans-gamma-hydroxyenone to another molecule of cis- or trans-gamma-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 gamma-hydroxyenone is tolerated; however, for 4-substituted gamma-hydroxyenones, selectivity issues arise due to the possibility of heterochiral or homochiral dimerizations. The major products were those with all contiguous groups trans.
Greatrex
Ben W
BW
Department of Chemistry, The University of Adelaide, South Australia 5004, Australia.
Kimber
Marc C
MC
Taylor
Dennis K
DK
Tiekink
Edward R T
ER