Hypercoordinate silicon compounds in organic synthesis: Improved methods for the synthesis of aryl(trialkoxy)silane derivatives; and trimethylsilyl cyanide as a cyanide source for nucleophilic substitution.

摘要

Palladium-catalyzed cross-coupling reactions are versatile methods for the synthesis of carbon-carbon bonds. The Stille and Suzuki cross-coupling protocols have achieved prominence in the synthesis of pharmaceuticals and agrochemicals because of the high yields, tolerance for functional groups, and excellent stereoselectivities. However, there are features associated with each of these processes that limit the generality: the Stille tin reagents and byproducts are toxic; and the Suzuki boron reagents can be difficult to synthesize and purify. Environmentally benign arylsilane derivatives have emerged as powerful alternatives to conventional arylmetalloids for the Pd(0)-catalyzed aryl-aryl coupling reaction with organohalides and organo(pseudo)halides because they avoid the inherent limitations associated with traditional methodologies. It was previously reported that aryl(trialkoxy)silanes (also called siloxanes) are substrates for fluoride-promoted, Pd(0)-catalyzed coupling reactions with allylic ester and aryl derivatives providing cross-coupling products in high yields under mild conditions. However, few detailed studies of the synthesis of these useful cross-coupling reagents have been reported in the literature.; In chapter one of this thesis, two methods for the synthesis of aryl siloxanes are studied and the optimal reaction conditions and the scope determined: (1) general reaction conditions for the synthesis of aryi(trialkoxy)silanes from aryl Grignard and lithium reagents and functional silanes have been developed; and (2) the scope of the palladium-catalyzed silylation of aryl halides with triethoxysilane to generate aryl(trialkoxy)silane derivatives has been expanded. In tandem, these two methods provide ready access to a wide range of aryl siloxane reagents for use in Pd(0)-mediated cross-coupling reactions, including highly functionalized siloxane intermediates in the synthesis of useful biologically active compounds.; In the first part of chapter one, the synthesis of aryl siloxanes from the corresponding aryl organometallic reagent and tetraalkoxysilanes is described.; The second part of chapter one discusses an alternative to the preparation of arylsilanes from organomagnesium or lithium intermediates: the silylation of aryl halide derivatives by triethoxysilane (H-Si(OEt)3) in the presence of a Pd catalyst. (Abstract shortened by UMI.)