A cyclization reaction that can be adapted to the formation of medium ring compounds and will be valuable for the synthesis of various biologically active molecules, including some difficult to synthesize antitumor compounds, is proposed. Because there are relatively few high yield methods of reliably forming carbocycles by a ring closure reaction in which a new carbon-carbon bond is made, the exploration of the transition metal catalyzed coupling of certain organic partners, placed at the termini of an organic fragment, that would produce a ring compound, is a critical problem in the syntheses of many molecules containing medium or large rings. The palladium catalyzed coupled reaction of an organic electrophile with an organotin reagent is such a reaction that gives high yields under mild conditions and will tolerate a wide variety of functional groups. The advantage of such a coupling reaction is that both partners, positioned at the juncture of the new ring, are assembled by the palladium catalyst, binding both ends at one site, and then extruding the formed ring, and producing a high yield cyclization reaction. In order to test the cyclization procedure, cyclization reactions of a series of model compounds which could be expected to yield 11-15 membered rings will be carried out. Following the optimization of these cyclization reactions, the synthesis of cembrenolide, a diterpene containing a 14-membered ring and a fuzed Alpha-methylene lactone, will be carried out. The synthesis of jatrophone, a diterpene containing an 11-membered ring, and exhibiting inhibitory activity in vivo against various carcinomas is also proposed.
