| Nitroalkanes are important building blocks for the synthesis of complex molecules. In addition to undergoing a variety of C-C bond forming reactions, the nitro moiety can easily be transformed into a variety of other functional groups, enabling down-stream synthetic manipulations. Despite the extensive research done on nitroalkanes no general, functional group tolerant method had been developed to C-alkylate nitroalkanes using alkyl halide electrophiles.;Herein I will describe the vast reactivity of nitroalkanes as well as give examples of early row transition metals undergoing radical chemistry to forge new C(sp3)-C(sp3) bonds. In the chapter that follows, I will describe the development of a copper-catalyzed method to C-alkylate nitroalkanes using benzyl bromide halide electrophiles. This is the first general example of Calkylation of nitroalkanes using alkyl halide electrophiles. This route enables the rapid construction of complex, and biologically interesting, phenethylamine derivatives.;In Chapter 3, I will describe the C-alkylation of nitroalkanes using alpha-bromocarbonyls, affording a high-yielding and functional group tolerate route to access complex beta-nitrocarbonyl derivatives. This method allows modification of alpha-bromo-esters, -amides, -ketones, and -aldehydes possessing a variety of distal functional groups. Reduction of beta-nitrocarbonyls provides access to beta-amino acid derivatives in excellent yield.;With a route to access complex beta-nitrocarbonyl derivatives, I was able to develop conditions for a diastereoselective Michael addition using this class of reagents as nucleophiles. A variety of different beta-nitrocarbonyls and Michael acceptors participate well in the transformation. I will also discuss a proposed stereochemical rational for the observed diastereoselectivity.;In Chapter 5, I will describe the development of a metal-free synthesis of quaternary alpha-trifluoromethylnitroalkanes. Using a commercially available trifluoromethylating reagent, a variety of complex nitroalkanes can be trifluoromethylated in excellent yield. This route is tolerant of a variety of different nitroalkane scaffolds, sensitive functional groups, and is highly diastereoselective. alpha-Trifluoromethylamines, which are interesting biological compounds, can be accessed in high yield by reduction of this class of nitroalkanes.;In Chapter 6, I will describe the development of on-electrode crosscoupling reactions, which allow for the construction of tailorable molecular wires. In collaboration with the Joel Rosenthal group at the University of Delaware, specifically graduate student Rachel Pupillo, I was able to develop conditions for on-electrode Sonogashira and Glaser reactions. I was then able to translate this chemistry to other carbon electrode surfaces. Studies were performed to ensure efficient immobilization of substrates as well as probe the electrochemical differences between the various molecular wires and carbon electrode. |
