Development and application of silyl Bis-enol ether mediated transformations

The oxidative cross-coupling of enolates is a powerful yet under-explored process that provides a direct and convergent means to access 1,4-dicarbonyl structures. The development of these reactions has been significantly limited by several inherent challenges that prevent productive cross-coupling. Our efforts to redefine the limits of this chemistry led us to pursue the use of silyl bis-enol ethers to mediate oxidative cross-coupling reactions.;Initial studies demonstrated that silyl bis-enol ethers are capable of mediating ketone-ketone cross-coupling reactions to generate quaternary stereocenters. These results sparked our interest in developing new silyl bis-enol mediated processes, with a focus on applications in natural product total synthesis.;In line with these goals, we first turned to the prodigiosin alkaloids for inspiration. The structure of these alkaloids keyed the development of a new silyl bis-enol ether mediated fragment coupling strategy that enables the enantioselective and convergent synthesis of trisubstituted pyrroles. This new method was applied to the enantioselective total synthesis of metacycloprodigiosin, prodigiosin R1 and streptorubin B.;Finally, studies towards the synthesis Galbulimima alkaloid GB 17 have led to the enantioselective construction of an advanced intermediate that will eventually make it possible to develop a new aspect of silyl bis-enol ether mediated coupling reactions.