Transition Metal-Catalyzed Nitrogenation of Hydrocarbons

University Of Oklahoma Norman Campus, Norman OK

Investigators

Abstract

This proposal by Prof. Kenneth M. Nicholas of the University of Oklahoma involves using transition metals to form new carbon-nitrogen bonds by developing new, efficient and selective metal catatyzed C-N bond-forming reactions. This methodology will be applicable to the synthesis of amine compounds and nitrogen heterocycles, both as synthetic intermediates and as end-products such as pharmaceuticals. Several of the reactions to be examined include: 1) establishing the synthetic scope and identifying the active nitrogenating species in CpM-catalyzed allylic aminations with nitroarenes, 2) improving the convenience, efficiency and demonstrating the synthetic utility of the CpM-catalyzed reductive cycloaddition of nitroarenes with alkynes and other nitrosophiles, 3) developing effective enantioselective hydroxylamine equivalents and elucidating the mechanism of the Cu-catalyzed allylic aminations, and 4) discovering metal-catalyzed direct amination reactions of saturated and aromatic hydrocarbons. As indicated, not only will the synthetic aspects of these reactions be examined but also the mechanisms of these reactions will be studied. The importance of this study is reflected in the following. The allyl amine unit is found in many natural and unnatural products and is a valuable building block for synthetic elaboration. The indole nucleus is featured in the diverse and biologically potent indole alkaloids as well as in valuable synthetic derivatives, including the specifically targeted indolocarbazole natural products. The direct aminations of aromatic and saturated substrates will also provide novel, synthetically valuable routes to important aliphatic and aromatic amines. Further, the metal-mediated processes leading to these compounds proceed from readily available starting materials and are expected to be highly regio- and chemoselective, functional group tolerant, economical, environmentally-friendly, and complementary or superior to existing methods. Broader Impacts. The new synthetic methods will widen the general scope of the understanding of how metal complexes interact with various classes of organic compounds and they also have the potential for wide applications in synthetic organic chemistry, which can have important implications for making useful materials such as biologically active compounds and polymers. In addition, graduate and undergraduate students in science will be trained along with a disproportionate number of women and members of under-represented minority groups. There will also be continued collaborations with computational and experimental scientists at Ph. D.-granting and undergraduate institutions in the U.S. and Italy.