SYNTHESIS OF (+-)-MESEMBRINE

The nitrostyrene 4 was condensed with butadiene to the nitrocyclohexene 5. Ketone 7, obtained by a Nef reaction on 5 followed by preferential catalytic reduction, was alkylated with allyl bromide to yield olefin 8. Reduction with LAH, followed by acetylation afforded the olefin acetate 11. The acid acetate 13, formed by OsO4-NaIO4 oxidation of 11 to the aldehyde acetate 12 and further oxidation of 12 with silver oxide, was converted to the amide 14. LAH reduction gave the amino alcohols 15. The N-formyl amide 15a was oxidized to the ketone 16. Bromination to 17, followed by dehydrobromination, produced the eneone 18. Epoxidation to 19 was carried out with Clorox, and reduction of 19 using chromous acetate gave the β-hydroxyketone 20. Further reduction with NaBH4 afforded the desired diol 21. Preferential oxidation with Pt/air, followed by acid catalyzed dehydration, finally yielded (±)-mesembrine (1). © 1968.