Dipartimento di tienze F armaceutiche -Via Fossato di Mortara 19, I-44100 Ferrara Abstmett An enantioselective approach to the synthesis of non nahual (-)-meroquinene 1 based on sequential into-and intramolecular Michael reaction between (L)-menthyl N-bcnzyl-S-amino-2E-pcntecloate 3 and 1-acetyloxy-4-methoxymethyloxy-2nitmbutaue lob. acting as surrogate of 2-nitro-l3-butadiene 4. is described. The hetemcydization process led to the formation of the piperkline ring system 12, obtained as an umqarable 80:20 mixture of diastereamers at the newly created chiral centres at C-3 and C-4, which became easily separable by column chromatography afta tmasformation of the nitrogen protective benzyl group into the corresponding carbamate.s 14 and 15. Both compounds. aftter elaboration of the chain geminal to the nitro group into a vinyl appendage, underwent regio-and stereo-selective removal of the nitro group by palladium-catalyztd displacement with hydride generated by formate to give the precursor 19. easily converted by treatment with hydrochloric acid to l.isolated as hydrochloride. A tandem reaction is usually defined as a sequence involving two or more consecutive reactions in which the functionalities created by bond formation in the initial step allow further reactions. Although by no means new, the field of tandem reaction has witnessed a striking progress over the last years. In fact, the variety of elegant and convenient synthetic applications based on this strategy have been recently reviewed1 and a useful classification of the different sequences has been suggested.
Accordingly, the tandem Michael reaction methodology, which we have developed for employment in a program directed at the synthesis of biologically active compounds with a pyrrolidine ring system as the salient structuml feature, is an anionic-anionic process; the primary step being the intermolecular addition of a nitrogen nucleophile to an electrophilic olefin to form a new anionic functionality which is subsequently captured by a built-in electrophile acceptor.
Recent applications of this stmtegy from our laboratories have resulted in concise enantioselective syntheses of (+)-and (-)-a-allokainic,2 (-)-a-kainic acid2 and acromelic acid A.3