Silylboranes, New Reagents for Tin-free Radical Mediated Processes – SILABOR

Free radicals are nowadays of paramount importance in organic chemistry and many synthesis of complex natural products have been achieved recently by incorporating one or several steps involving such reactive species. Free-radical reactions using Bu3SnH or (Bu3Sn)2 respectively in reduction processes and formations of C-C bonds are the most useful tools in the armory of organic chemists and any radical chemistry practitioner will find very difficult to get away from Bu3Sn and other tin reagents to sustain a radical chain. Tin derivatives however suffer from several drawbacks including an acute toxicity and often, tedious purifications and contamination of final products. The Environmental Protection Agency (EPA) has recently restricted their use, prompting chemists to envision valuable alternatives for these compounds. In organic radical chemistry, although several elegant solutions have been proposed recently, efforts remain to be done to provide a simple, non toxic, easily available tributyltin surrogate. Silicon radicals possess attractive features which parallel those of tin radicals, and maybe viewed as non toxic candidates to replace tin, providing a valuable and environmentally benign solution to this long standing problem. Although limited in scope, some recent reports clearly establish that silyl radicals can promote radical chain reactions, which has prompted us to look more carefully in this direction. We propose in this project a tin-free methodology relying on the use of silyl radicals as initiators for a number of radical transformations, including powerful chain transfer processes. Our approach is based on intramolecular homolytic substitutions at silicon, namely aryl and silyl group migrations or homolytic ring closure, two processes which have been little exploited so far. The required silyl-centered radical would be generated from a carbon-centered radical through a 5- or a 6-exo cyclization process. The carbon radical would in turn be generated from a borane precursor, itself prepared in situ from readily available arylsilyl- or disilyl- alkenes. We thus plan, within this project, to design first silyl radical precursors, having both a boron moiety at one end of a carbon chain (as a source of carbon radical) and a silicon group at the other end of the chain, the required silyl radical being generated upon a cyclization process. These silyl radicals will then be used to initiate various chain transfer processes, allowing these reactions to be performed under tin-free conditions, extending further their range of application. Thus, this chemistry is not restricted to reduction of alkyl or aryl halides, the focus of most studies involving silicon radical chemistry so far, but is directed toward the more challenging and more useful C-C bond formation through chain transfer reactions.The utility of such silicon-centered radicals will finally be illustrated in the synthesis of biologically relevant substituted piperidinones, using a novel multi-component radical chain transfer strategy. Theoretical studies will be performed in parallel, including ab initio calculations of the cyclization reaction pathways and calculations of bond dissociation energies of disilane precursors. These investigations will provide useful informations for a more efficient rational design of the structure of silyl radical precursors. The project will involve partners, which expertise has been recognized in boron (P. Renaud, Berne) and silicon chemistry (Y. Landais, Bordeaux) as well as in theoretical chemistry (F. Castet, Bordeaux). We believe that this strategy should open new avenues in radical chemistry with clean processes free of toxic alkyltin residues.