Strained Silanes As Lewis Acids For The Construction Of Carbon-carbon Bonds

This thesis details our efforts to use strained silane reagents as Lewis acids to activate imines and aldehydes towards nucleophilic addition. Part I begins with a summary of prior methods to convert silanes from type II to type I nucleophiles, including activation with Lewis bases and constraining silicon in a small ring. Prior work detailing the development of a diastereoselective tandem aldol-allyation reaction of aldehydes is discussed, followed by our efforts to employ chiral diols and amino alcohols as ligands for silicon. Amino alcohols were found to be competent ligands in the context of the aldol reaction if they were sterically or electronically deactivated.

Part II of this thesis details our efforts to use azoles as directing groups for enantioselective nucleophilic addition to imines. We discovered that imines incorporating imidazole are readily allylated in a highly enantioselective manner by an allylsilane derived from cis-1,2-aminoindanol. A number of substrates were successfully allylated, and several reactions were developed that utilize an in situ ring closing metathesis reaction to quickly access potentially medicinally relevant chiral piperidines and azepines without resorting to protecting group manipulation. The imidazole-directing strategy was extended to the development of an asymmetric Pictet-Spengler reaction in which the aldimine derived from 2-formyl imidazole and tryptamine cyclized in the presence of a strained silane Lewis acid to give the chiral tetrahydro beta-carboline product in high yield and ee. Finally, the initial reports of a strained alkoxysilane-promoted asymmetric aza-Diels-Alder reaction between hydrazones and the Danishefsky diene are disclosed.