Catalyzed Coupling of Organostannanes with Electrophiles

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The synthesis of complex molecules requires the development of sensitive, cost-effective new reagents. This grant in the Organic and Macromolecular Chemistry Program supports research leading to new catalytic processes that will facilitate synthesis of the new generation of antibiotics that are characterized by extremely complex stereochemical interrelationships. It is the object of this research to explore synthetically useful palladium-catalyzed coupling reactions utilizing an organotin reagent and an organic electrophile as coupling partners. One goal of the research is the development of an asymmetric synthesis in which a chiral carbon is generated at the coupling site by the use of optically active transition metal catalysts. In order to attain these objectives, a mechanistic understanding of how an organotin reagent transfers an organic group to an organopalladium(II) halide will be sought. The transmetallation reactions of various organotin reagents with alkylpalladium(II) halides bearing a trans-chelating phosphine ligand will be carried out such that the transmetallation product cannot undergo reductive elimination. The synthesis of geometrically pure (E or Z) vinyl triflates and their coupling reactions with organostannanes, particuarly vinylstannanes, will be explored in an effort to synthesize compounds containing the conjugated dienes, an important structural feature in a variety of biologically active products, including certain conjugated polyenes derived from arachadonic acid. The coupling reactions of aryl triflates will be explored, and the reactions of both aryl triflates and aryl halides with vinylstannane will be developed for the synthesis of a number of indole alkaloids. Other useful electrophiles for coupling, such as vinyl epoxides and alpha-halocarbonyls will be sought in order to expand the scope of this reaction. The effective use of a number of untested tin reagents should provide new synthetic pathways to a variety of products including a number of pyrethoids. The utilization of this coupling chemistry in the synthesis of strained ring compounds also will be developed.