Professor Aaron L. Odom of Michigan State University is supported by the Chemical Catalysis (CAT) Program in the Division of Chemistry to explore the properties and reactivity of titanium complexes with a focus on new reactions for the catalytic production of heterocyclic compounds. The main focus will be on the hydroamination of alkynes and alkenes, which are atom-economical synthetic methodologies for the generation of C?N bonds. Multi-component coupling reactions that yield complex organic compounds in a single synthetic step as well as routes to surface-tethered catalyst systems for multicomponent coupling chemistry will be investigated. The advantages of titanium-based chemistry include titanium?s high natural abundance and lack of toxicity.
The development of new atom-economical reaction chemistry and catalysts for C?N bond formation is critical for the efficient, green synthesis of a variety of nitrogen-based heterocycles. These nitrogen heterocycles have applications in many areas that impact our daily lives. For example, around 80% of the pharmaceuticals on the market contain nitrogen, many in the form of nitrogen heterocycles. This research is expected to have an immediate impact on the pharmaceutical and fine chemicals industry. Graduate and undergraduate students and postdoctoral associates involved in this research will receive excellent training in chemical catalysis and synthetic chemistry.
One of the great challenges facing society from a chemical perspective is the production of the compounds we need in an environmentally conscious and efficient manner. Multicomponent coupling chemistry (MCC) is a method where chemists can put together more than two molecules at a time, which can build molecular complexity very quickly. MCC in general, and catalyzed MCC in particular, may play a large role in our ability to synthesize complex molecules in an efficient manner in the future. These strategies can reduce the energy, man-hours, and environmental cost of producing important compounds. In this project, we explored applications of earth-abundant and nontoxic titanium to the synthesis of important classes of nitrogen-based heterocycles. Nitrogen heterocycles are, quite simply, ring compounds bearing at least one nitrogen in a ring of carbons, and they are common structures found in biologically active materials. For example, nitrogen heterocycles are found in a large portion of the pharmaceuticals; in fact, it is estimated that more than 90% of new drugs contain heterocycles, most as nitrogen heterocycles. We designed easily prepared catalyst architectures for titanium-catalyzed MCC. These MCC products are easily adapted to one-pot procedures to produce a variety of different heterocyclic cores as shown below. The hope is that this environmentally friendly chemistry will lead to rapid methods for screening new compounds for a variety of applications. Specifically during this program period we accomplished several goals. First, we were able to develop new one-pot strategies for isoxazoles, 2-aminopyridines, and pyrroles using the titanium MCC approach. Second, we also developed a new catalyst architecture amenable to monosubstituted hydrazine, isonitrile, and alkyne multicomponent coupling chemistry, which generates pyrazoles in a single efficient step. Third, we began developing new tools for catalyst optimization for earth abundant transition metals that will allow parameterization of ligand donor abilities towards these metals in high oxidation states. In the course of this research we also discovered an interesting molybdenum-mediated N–N bond cleavage, which gave some insight into the mechanism of this important reaction. Another important outcome of this research is the education and training of postdoctoral, graduate, and undergraduate students during the course of the research. Postdoctoral students who participated where Dr. Ross Bemowski, Dr. Amrendra Singh, and Dr. Dushyanthi Hoole. The graduate students who received support were Steve DiFranco, Amila Dissanayake, Nick Maciulis, and Tanner McDaniel. In addition, a large number of undergraduate students received training, including Danielle Eppen, Jake Claes, Matt Oliver, Evan Beaumier, Michael Costa, Kaylee Laudick, Yvonne DePorre, and Bailey Bajorek.
