Synthesis of Heterocyclic Natural Products

A novel variation of the Heck palladium catalyzed intramolecular coupling of a vinyl halide with an alkene will be developed for construction of a variety of nitrogen heterocycles. The process allows concurrent formation of a C-C and a C-N bond, producing a bicyclic ring system. The basic methodology will be explored further and then applied in concise syntheses of the Lycopodium alkaloid phlegmarine and the spirocyclic alkaloid perhydrohistrionicotoxin. The chemistry will also be extended to allow formation of two new C-C bonds, leading to a range of carbocyclic systems. This methodological variation will be applied to construction of the pseudoguaiane ring system and will be a key step in total syntheses of the magellanine/paniculatin group of Lycopodium alkaloids as well as the spirocyclic sesquiterpene beta-chamigrene. %%% With this award, the Organic Synthesis Program will support the research of Dr. Steven M. Weinreb at Pennsylvania State University. The research explores new ramifications and applications of a new palladium catalyzed reaction to construct complex structures by new synthetic methodology that should benefit research in biochemistry and medicine, as well as in the chemical industry.