Synthetic studies in the piperidine alkaloid field. Part 1. The 2-azabicyclo[2.2.2]octan-5-one approach to prosopine

Abstract

An approach to the synthesis of the Prosopis alkaloids utilising the Baeyer–Villiger reaction of methyl 2-benzyloxycarbonyl-5-oxo-2-azabicyclo[2.2.2]octane-3-carboxylate (6; R = CO₂Me) is described. The boron trifluoride–ether catalysed cycloaddition to cyclohexadiene of methyl 2-(benzyloxycarbonylimino)acetate (8; R = CO₂ Me), generated in situ from methyl N-benzyloxycarbonyl-2-methoxyglycinate, gave a mixture of bicyclic adducts (9) and (10). Oxymercuriation of (9) gave the alcohol (11; R = H), and subsequent oxidation gave the ketone (6; R = CO₂Me). Baeyer–Villiger oxidations of (6; R = CO₂Me or CH₂·O₂CPh) gave the lactones (14) and (15), respectively, and none of the desired lactone (7).