CAREER: New Methods for the Synthesis of Nitrogen-Containing Heterocycles

University Of Virginia Main Campus, Charlottesville VA

Investigators

Abstract

With this CAREER Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Michael Hilinski of the University of Virginia. Professor Hilinski is working with graduate and undergraduate students to develop new chemical reactions that allow for reductions in the cost, time, and waste associated with preparing chemical compounds. The targeted compounds have structural features that are found in the majority of Food and Drug Administration-approved drugs, as well as in other types of chemicals such as natural products, agricultural chemicals, and dyes. In addition to improving the ability to make known structures, the Hilinski laboratory is making structures that were previously unable to be made. This allows other scientists to explore potentially, societally-beneficial applications of these new compounds. The scientific approach being employed focuses on ways in which petroleum by-products react with other inexpensive chemicals to form ring structures containing at least one nitrogen atom. The use of catalysts to promote these reactions allows for predictable control of the products and for the synthesis of different ring sizes. The educational activities prepare students to communicate with non-scientists about their research and broader scientific implications. Professor Hilinski is creating and implementing a new science communication workshop for graduate and undergraduate students. He is also establishing a yearly Chemistry department open house event, and he is developing a new outreach activity for an audience of school-age children. Owing to the frequency with which nitrogen-containing heterocycles are found in pharmaceuticals, natural products, agrochemicals, and other bioactive or otherwise useful compounds, overcoming challenges in their synthesis is considered a key goal with broad potential impact. Professor Hilinski is developing new methods for saturated or partially saturated nitrogen-heterocycle synthesis that employ nitrenes as one-atom components in cycloaddition reactions. Several catalytic approaches are being pursued to achieve this underexploited strategy, including two-component formal cycloadditions initiated by nitrene transfer to olefins followed by spontaneous ring expansion or rearrangement, and multi-component formal cycloadditions between olefins, nitrenoid precursors, and a third component. Multiple classes of heterocycles of different ring sizes are being accessed using this strategy. The broader scientific impacts of this synthetic methodology research include the wide potential applicability to the synthesis of a variety of different compound classes. Other broader impacts include an enhancement students' skills in the area of science communication via establishment of a training workshop, and, through the education plan, the exposure of people in the local community to scientific research in a way that is accessible to a non-expert. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.