Asymmetric Weitz−Scheffer Epoxidation of α,β-Enones by Optically Active Hydroperoxides: Control of Enantioselectivity through Metal-Coordinated or Hydrogen-Bonded Templates

Abstract

The enantioselective epoxidation of the α,β-enones 1 with the optically active hydroperoxides (−)-(S)-2, catalyzed by the bases KOH or DBU, affords the enantiomerically enriched oxo epoxides 3 in high yields and with good enantioselectivities (up to 90% ee for KOH and up to 72% ee for DBU). The preparatively useful feature of this asymmetric epoxidation is the fact that opposite senses of enantioselectivity are observed with the same optically active hydroperoxide and the same prochiral enone substrate. Thus, whereas KOH in CH3CN affords the (αS,βR)-epoxide 3a from chalcone 1a, through preferential Si-face attack, DBU in toluene selectively provide the (αR,βS)-epoxide 3a from this alkene, through favored Re-face attack. It is proposed that template structures, held together by octahedrally ligating K+ or the hydrogen-bonding DBUH+ ammonium ion, account for the observed enantioselectivities. The sense and degree of enantioselectivity are determined by steric interactions between the base-derived, templating K+ and DBUH+ agents, the chiral peroxide anion oxygen donor, and the prochiral enone substrate.