Synthesis of the Marine Alkaloid Cylindricine C and Serendipitous Synthesis of Its 2,13-Di-epi Stereoisomer.

A new approach to the marine alkaloid cylindricine C afforded its previously unreported (±)-2,13-di-epi stereoisomer as the major product along with a minor amount of the racemic parent alkaloid. Key steps included a stereoselective dianion alkylation of a monoester of 1,2-cyclohexanedicarboxylic acid and an annulation based on the tandem conjugate addition of a primary amine to an acetylenic sulfone, followed by intramolecular acylation of the resulting sulfone-stabilized carbanion. The cis-azadecalin moiety thus formed, comprising the cyclohexane A-ring and enaminone B-ring of the products, was further elaborated by the selenenyl chloride-induced cyclofunctionalization of a pendant butenyl substituent with the enaminone moiety, followed by a seleno-Pummerer reaction. Desulfonylation and enaminone reduction afforded the final products. Molecular modeling and X-ray crystallography provided further insight into these processes.

The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizations.

The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K12Ga4L6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 105, which numbers among the largest magnitudes of transition state stabilization measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity.