TOTAL SYNTHESIS OF THE UNUSUAL MARINE ALKALOID (-)-PAPUAMINE UTILIZING A NOVEL IMINO ENE REACTION

A concise enantioselective total synthesis of the recently isolated an tibacterial and antifungal marine alkaloid (-)-papuamine (1) is descri bed. The key feature of the synthesis includes the development and sub sequent implementation of a novel pericyclic imino ene reaction. Start ing from readily available enantiomerically pure acid ester 11, alleny l silane N-benzyl imines 24 and 27 were generated in situ from aldehyd es 23a/b. These imines undergo concerted stereospecific imino ene reac tions to afford silyl acetylenes 25 and 28, respectively, in high yiel ds. The ene reactions were found to be promoted both thermally in refl uxing toluene and at lower temperatures using the Lewis acid stannic c hloride as a catalyst. Desilylation of compounds 25 and 28 afforded te rminal alkynes 26 and 29, respectively, whose structures and stereoche mistry were unambiguously established by single crystal X-ray structur e analysis of the corresponding HCl salts. In a more highly convergent approach to the alkaloid 1, aldehyde allenyl silane 23a was treated w ith 0.5 equiv of 1,3-diaminopropane in refluxing toluene to afford hom opropargylic diamine 40 as one stereoisomer via a double imino ene rea ction, which effectively established the remaining four of the eight s tereogenic centers of papuamine in one simple operation. To complete t he route to the natural enantiomer of papuamine, a Pd(II) catalyzed ma crocyclization of bis-E-vinyl stannane 42b was effected in moderate yi eld.