Development of metal-catalyzed silylene transfer to carbonyl compounds and applications in natural product synthesis
Silylene transfer products can undergo stereoselective carbon-carbon bond-forming reactions, including the generation of quaternary carbon stereocenters, which demonstrate their utility in synthetic organic chemistry. Our laboratory has developed a metal-catalyzed method for di-tert-butylsilylene transfer to an alkene, providing silacyclopropane products. This dissertation describes the application of the metal-catalyzed silylene transfer conditions to carbonyl compounds. Metal-catalyzed silylene transfer to a range of a,13-unsaturated esters proved to be a general method for the formation of oxasilacyclopentene products containing a cyclic silyl ketene acetal functionality. These oxasilacyclopentenes are useful synthetic intermediates that can undergo facile and selective aldol addition reactions and Ireland-Claisen rearrangements to provide products with multiple contiguous stereocenters and quaternary carbon centers. By applying this methodology to enantiomerically pure esters, products containing chiral quaternary carbon centers have been accessed, and the total synthesis of (+)-5-epi-acetomycin has been achieved.