1,2-Asymmetric induction in intramolecular Michael reaction. A novel and enantioselective route to (+)-Geissman lactone

Abstract

The Horner-Emmons reaction of the hemiacetal (19), derived from L-(+)-diethyl tartrate, was found to give the pyrrolidine (21)via an intramolecular Michael reaction as a mixture of diastereoisomers which, after treatment with ethanethiol and boron trifluoride–diethyl ether, was converted into the lactone (22) and the ester (23). The lactone (22), a minor component, could then be transformed into the Geissman lactone (10), a potential precursor for retronecine synthesis, via a three-step sequence. Alternatively, the hemiacetal (41), prepared from S-(–)-malic acid, was converted into the Z-α,β-unsaturated ester (49) whose intramolecular Michael reaction followed by cleavage of the corresponding methoxymethyl ether afforded the pyrrolidine (51) as a major product in a highly diastereoselective manner. The three-step conversion of (51) into (–)-ethyl 3-oxo-2-oxa-6-azabicyclo[3.3.0]octane-6-carboxylate (32) provided an efficient and stereocontrolled route to the Geissman lactone in optically active form.