piperidines and deoxynupharidine

In this paper we describe the stereoselective synthesis of functionalized lactam 7 via two enantiospecific piperidine-forming techniques and its employment in a general synthetic approach to Nuphar alkaloids. Specifically, the formation of piperidine 18 by formal [3 + 3] cycloaddition and stepwise annelation processes is described; the latter technique was found to be significantly more efficient than the Pd-catalyzed TMM addition process. Finally, exploitation of the exocyclic alkene installed in the piperidine-forming reaction in the transformation of 18 to (-)-deoxynupharidine ((-)-2), (-)-castoramine ((-)-3), and (-)-nupharolutine ((-)-4) via intermediate lactam 7 is delineated.

Topics: Alkaloids; Catalysis; Combinatorial Chemistry Techniques; Lactams; Molecular Structure; Nuphar; Palladium; Piperidines; Plants, Medicinal; Quinolizines; Stereoisomerism

[reaction: see text] A stereocontrolled route to Nuphar alkaloids is described that employs a formal [3 + 3] cycloaddition strategy to assemble the piperidine nucleus. The addition of Pd-TMM complexes to aziridine 10 was found to be sluggish; however, the addition of a functionalized allyl Grignard reagent followed by a Mitsunobu condensation reaction provided 11 in high yield. The employment of this route in the formal synthesis of (-)-deoxynupharidine 1 is described.

Topics: Alkaloids; Allyl Compounds; Aziridines; Catalysis; Models, Chemical; Nuphar; Palladium; Piperidines; Quinolizines; Stereoisomerism