The search for effective chemotherapeutics depends critically on the selective synthesis of complex organic molecules. These compounds, replete with carbon-carbon, carbon-oxygen and carbon-nitrogen bonds in dazzling stereochemical orientations, are routinely identified as biologically active. Furthermore, the general availability of complex molecules depends on the efficiency with which they may be prepared. As a result, the discovery of new chemical reactions that effect the efficient and stereoselective synthesis of complex molecules impacts drug discovery, development and dissemination. The objective of this proposal is to develop new bond-forming reactions that effect the simultaneous incorporation of several new stereogenic centers into stereochemically complex products. For our goal, we will develop three new rearrangement reactions. Each may be formally characterized as the addition of a nucleophilic group to an electron rich enolsilane. The processes create new opportunities for these readily available intermediates, which have been traditionally exploited for their reactivity towards electrophiles. Rearrangements are particularly attractive reactions for the synthesis of stereochemically complex products because they proceed through well- organized transition states. As a result, we will study the relay of pre-exisiting chirality to newly formed stereogenic centers. In addition, we will explore the de novo introduction of absolute chirality into substrates through the application of chiral catalysts that may be employed in substoichiometric quantities. The results will be new products in which several new bonds are made simultaneously in a regio-, diastereo- and enantioselective fashion. In order to demonstrate the practical utility of these reactions, we will carry out the total asymmetric synthesis of several complex carbohydrates, nucleoside antibiotics and highly modified non- proteinogenic amino acids. These compounds constitute important classes of biologically active small molecules. They are also highly functionalized - frequently every carbon atom along a chain, or within a ring is a stereogenic center. Our objective is to develop reactions that will introduce as many of the stereogenic centers in these systems as possible with single chemical reactions.