CAREER: Mechanistic Insights Facilitate the Development of New Bond Forming Processes

Texas A&M University, College Station TX

Investigators

Abstract

With support from the Chemical Structure, Dynamics & Mechanisms-B Program of the Chemistry Division under this CAREER award, Andy Thomas of the Department of Chemistry at Texas A&M University is using newly developed rapid injection NMR (RI-NMR) systems to investigate the fundamental reactivity patterns of unstable intermediates. These new reaction monitoring systems have provided new avenues to explore organolithium (Thrust I) and ozonide (Thrust II) intermediates. The ability to investigate the fundamental reactivity patterns of various systems is providing new and, at times, unexpected mechanistic insights to be obtained, allowing for new reactions to be developed. The newly found mechanistic data are being applied to answer several open synthetic challenges that have considerable importance to the field. Specifically, Thrust I is focused on exploring how chiral Lewis bases can create new avenues for the asymmetric construction of carbon-carbon bonds with organolithium reagents; and Thrust II is developing new oxygenation reactions with ozone by exploring the reactivity patterns of primary ozonides. In addition, this program is well suited to impart a broad set of skills to students as the research requires extensive training in organic synthesis, kinetic analysis, and advanced spectroscopic techniques such as rapid-injection NMR spectroscopy. The crux of the research program has been integrated into an education plan that seeks to expand the scientific literacy of all citizens and places a special emphasis on engaging low-income areas. A chemistry workshop has been established to expose 3rd , 4th, and 5th graders to chemistry early on and inspire them to seek careers in STEM. By using unique RI-NMR reaction monitoring systems, this project is focused on the following two objectives: (Thrust I) development of new asymmetric deprotonation substitution sequences with separated ion pairs and (Thrust II) development of asymmetric constructive ozonolysis for carbon-oxygen bond formation. In Thrust I, a variety of chiral Lewis bases will be synthesized and investigated for the asymmetric capture of carbanions. Specifically, the proposed work endeavors to elucidate the key structural features of chiral Lewis bases and organometallic reagents that engender essential activating and controlling functions for the development of highly general and selective carbon-carbon bond forming reactions. Thrust II of this proposal seeks to gain a detailed mechanistic understanding of the steric and electronic control elements that influence the formation of primary ozonides and their subsequent diversification. Specifically, Thrust II addresses the long-standing synthetic challenge of functionalizing oxygen after it is installed into a carbon skeleton – pursuing new modes for alkyl ether formation. 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.