Development of transition-metal catalyzed methods utilizing silicon-containing compounds and nitroalkanes

Abstract

Watson, Donald A.Organosilanes and nitroalkanes are important synthetic intermediates in organic synthesis. Nitroalkanes can be transformed to medicinally relevant functional groups, such as tertiary amines. Organosilanes can participate in C–C bond formation via the Hiyama-Denmark cross-coupling or be converted to alcohols via the TamaoFleming oxidation. Silicon bioisosteres are also of interest in the medicinal chemistry community. Despite their significance, general methods to synthesize organosilanes, particularly those that are chiral, and nitroalkanes have proven challenging. Our group uses transition metal-catalyzed strategies to access these interesting compounds. ☐ In Chapter 1, I will describe a Hiyama-Denmark cross-coupling of tetrasubstituted vinylsilanes to stereospecifically access tetrasubstituted alkenes, which are an important motif in medicinal chemistry and organic synthesis. A general method was developed to cross couple a variety of highly substituted vinylsilanes with aryl halides under mild conditions using KOSiMe3 as the base and THF/DMA as the solvent, without the need for any extraneous additives. The identification of dimethyl- (5-methylfuryl)vinylsilanes as an easily synthesized, bench stable, yet reactive coupling partner was essential. Mechanistic investigations and byproduct analysis have revealed a unique and unexpected role for DMA, namely that it serves as a reagent for the slow release of water into the solution over the course of the reaction. Details of the optimization, scope, and the investigations that led to our mechanistic understanding are described. ☐ In Chapter 2, the development of a light-mediated nickel-catalyzed Calkylation of nitroalkanes will be described. The direct photoactivation of nickel complexes to enable catalysis has only recently been explored and is not well documented for C–C bond formation reactions. In previous work from our group, a dual photoredox nickel-catalyzed C-alkylation of nitroalkanes was reported. Control experiments revealed the nickel complex can catalyze the reaction without the need for a rare-earth metal photocatalyst. The scope of this transformation has been extensively studied and a benchtop protocol for this transformation has been developed.University of Delaware, Department of Chemistry and BiochemistryPh.D