ABSTRACT
A stepwise [3 + 3] annelation reaction has been developed that allows access to pyrans from epoxides. This process involves the addition of an allylmagnesium reagent, itself readily prepared from methallyl alcohol, and a Pd-catalyzed cyclodehydration reaction. The potential of this process to be employed in natural product synthesis has been exemplified by its use in the preparation of rhopaloic acid A.
Subject(s)
Magnesium/chemistry , Pyrans/chemistry , Cyclization , Magnetic Resonance Spectroscopy , Oxidation-Reduction , Palladium/chemistry , Pyrans/chemical synthesis , Spectrometry, Mass, Electrospray Ionization , Spectroscopy, Fourier Transform InfraredABSTRACT
A general and enantiospecific [3 + 3] reaction toward functionalized pyrans is reported that has been employed in the first enantioselective synthesis of (+)-rhopaloic acid B.
Subject(s)
Acids/chemistry , Pyrans/chemistry , Epoxy Compounds/chemistry , Molecular StructureABSTRACT
[reaction: see text] A stepwise formal [3 + 3] cycloaddition sequence via a Grignard addition-cyclization reaction leads to a much improved piperidine synthesis. This methodology provides improved flexibility in both the aziridine substrate and TMM equivalent.
ABSTRACT
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.
Subject(s)
Alkaloids/chemical synthesis , Combinatorial Chemistry Techniques , Nuphar/chemistry , Quinolizines/chemical synthesis , Catalysis , Lactams/chemistry , Molecular Structure , Palladium/chemistry , Piperidines/chemical synthesis , Piperidines/chemistry , Plants, Medicinal/chemistry , StereoisomerismABSTRACT
[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.