This project will continue studies involving pericyclic reactions or their equivalents using reactive intermediates. Allylic cations offer a wide range of reactive motives, including cycloadditions and ene reactions. The latter have not been studied extensively and formally offer a process by which C-H activation occurs. Studies to explore the scope of this process, both in an inter- and intramolecular context, will be undertaken. The basic scheme lends itself naturally to an investigation of the homo-Cope rearrangement, which will also be pursued.
Ketenes undergo a cycloaddition reaction with alkenes to form cyclobutanones. Details of the control of regiochemistry in such cycloadditions are incomplete. A study of this process, linked to specifically controlling the outcome of the reaction with vinylcyclopropanes will lead to the synthesis of cyclobutanones substituted regioselectively with cyclopropanes. Such substrates are envisioned to undergo a ring expansion to form seven-membered rings, under the influence of catalytic amounts of certain transition metals.
Finally, the influence of substituents on the rates of certain electrocyclic reactions is a topic of current interest. The electrocyclization of hexatrienes is generally a slow process with a relatively high activation energy. Recent evidence suggests that electronic effects can have a profound influence on the rate of such processes. Carbanions offer the opportunity to develop extremely rapid electrocyclizations in this class that are also diastereoselective and enantioselective, depending on the exact means by which the carbanion is generated, resulting in the preparation of highly substituted six-membered rings. The development of such reactions will be undertaken.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Michael Harmata of the Department of Chemistry at University of Missouri-Columbia. Professor Michael Harmata's research efforts revolve around the development of new carbon-carbon bond forming reactions based on pericyclic reactions of reactive intermediates, especially those of allylic cations and cyclopentadienones, among others. The studies to be undertaken will expand the scope of knowledge of reactive species, resulting in the discovery/invention of new, powerful synthetic processes of use for the synthesis of complex organic chemicals of potential impact to the synthesis of new pharmaceuticals, new materials, and new agrochemicals, as well as new entities of fundamental interest to a broad scientific community.
This work focused on the development and understanding of new synthetic organic reactions. These are the foundation upon which the medicines, materials and other substances used in modern life are built. New reactions are like new tools; understanding how matter behaves, that is, how the tools work, and how we can manipulate what we build to productive ends has been, and continues to be, an important goal for both fundamental science and technology. Our studies focused on a number of different areas but included (1) the invention of a new means of generating allylic organolithium compounds, useful reagents (i.e., tools) that are otherwise not easy to make; (2) the discovery of what is known as an internal redox reaction, which promises to make available a wide variety of complex molecular structures that could have positive impacts in a number of areas, including the life sciences and medicine; (3) the conception of a new means of generating new organoboron compounds, substances that are extremely important in today's world of pharmaceutical chemistry and in the generation of new materials applied to, for example, electronics; (4) the generation and study of strained amides, a portion of molecules that include the clinically important beta-lactam antibiotics; and (5) studies of the catalysis of organic reactions by silver ions. Catalysis general means using less to do more, making the development of catalyzed reactions generally important with respect to their lower environmental impact relative to uncatalyzed processes (use less, waste less). Further, we have investigated leads based on these primary areas of accomplishment either to delve more deeply into what we have uncovered or to complement the main focus of our work. In the course of these studies, we conduct a professional development program that teaches students how to function in a team environment, either as a team leader or a team member. This approach compels one student to literally take charge of a specific project and appropriately engage/inspire his/her colleagues, other students who are members of the team, so that the project can be taken to a conclusion. That generally means the production of a publishable paper. The importance of being able to function both as a team member and leader is, based on our experience, extremely important in the "real" world and we strive to instill the skill and ethos needed for both roles in our students. Students also have the opportunity to present their research at professional meetings in the form of talks and posters and all are required to write at least first drafts of any papers that emanate from the group. For many students, all of these tasks represents true challenges, as it is the first time they have been called upon to both create a "product" (new scientific results) and report on it in a data-based and ethical manner. The broader impact for science and the general public looms large, as professional development is critical to the creation of well-rounded, responsible and ethical scientists who will help move our country through the 21st century.
