Synthesis of substituted heterocycles via electrophile addition - 1,2-silyl shift - cyclization domino process

Overview & Synopsis

The work is dedicated to the development of new synthetic methodology, which allows to get various heterocyclic compounds with highly functionalized olefin side chain. Such compounds has potential application in pharmacy. The methodology is based on 1,2-migration of silicon in propargyl silanes attacked by electrophiles. After electrophilic addition to triple bond and consequent silyl group shift, the relatively stable allylic cation is formed. It can further react with inner nucleophiles providing cyclic compounds. This research is focused on the formation of chiral products what is crucial for biological activity of the potential drug. Three strategies to enantioselective cyclization were proposed:Desymmetrization strategy. Starting material is symmetric and contains 2 nucleophilic groups which are differentialized by chiral catalysis.Enantiospecific hypothesis. Attempt to synthesis of chiral starting material with assumption that cyclization proceeds by a concerted mechanism.Enantioselective strategy. Synthesis of racemic starting material and accent on stabilization of allyl cation transition state - if cyclization proceeds by a stepwise mechanism.