The hydration of olefins and the reduction of ketones play an important role in the synthetic strategies for the construction of biologically active molecules. The current methods of hydration of olefins by, for example, hydroboration or oxymercuration and reduction of ketones by, for example, boron or aluminum hydrides are, in the main, stoichiometric transformations. Although many of these reactions have been carried out enantioselectively to produce enantiomeric products, the chemoselectivity is poor in that ester and amide groups are generally reduced in competition. Moreover, there are few examples of asymmetric catalysis. Intramolecular asymmetric catalytic hydrosilation provides an attractive solution to the chemoselective hydration of olefins and the reduction of ketones. This proposal is directed at developing new chiral catlysts for asymmetric catalytic hydrosilation. A mechanistic rationalization is offered which suggests that certain readily available substrates will generate high optical yields by an intramolecular process. The strategy employs familiar concepts of discrimination by preferred cyclic conformations in the enantioseleetive transition sites. The products of hydrosilation are readily converted into optically active 1,4-, 1,3 and 1,2-diols. These diols are key starting materials in the synthesis of macrolide and ionophore antibioties. The proposal is also directed at an important methodological issue. This concerns the problem of selecting the correct catalyst and substrate which will give high optical yields. For this purpose, it is proposed to investigate the mechanism of the reaction in order to determine the origins of the enantioselection. Such studies will provide a basis for the design of catalysts for other transformations.
