NONCOVALENT INTERACTIONS AND HYPERCONJUGATION IN CONTROL OF RADICAL REACTIVITY: APPLICATION TO 5-ENDO-DIG CYCLIZATIONS

Florida State University, Tallahassee FL

Investigators

Abstract

This proposal extends studies of unusual aspects of alkyne reactivity into a new direction. It will concentrate on fundamental factors controlling radical cyclizations of alkynes and utilize this knowledge for the design of synthetically useful transformations. Because stereoelectronic patterns are significantly different for radical cyclizations of alkenes and alkynes, understanding these fundamental differences is essential for the development of alkyne chemistry. In this project, the Alabugin group will utilize stereoelectronic and thermodynamic factors in search of the apparently favorable but virtually unexplored radical process: 5-endo-dig radical cyclization and apply this and related reactions to the synthesis of new carbo- and heterocyclic systems. Proposed experiments will test earlier computational predictions regarding the relative efficiency of different cyclization patterns, discover new cyclization topologies and test the efficiency of cooperative hyperconjugative interactions in control of radical reactivity. In parallel, the group will combine efficient radical cyclizations with radical translocations for the rapid construction of functionalized polycyclic systems. These reactions take advantage of synthetic potential which is present in alkynes but not in alkenes by utilizing both pi-bonds of the alkyne moiety in the C-C bond forming steps. The intellectual merit of this research is in unraveling the contribution of electronic and structural factors controlling the efficiency and selectivity of radical processes through a combination of experimental and theoretical studies. The underlying focus on electronic effects will increase the general importance of these findings, broaden understanding of these fundamental factors and lead to the development of new paradigms of radical reactivity. The broader impact will be the laying of mechanistic, structural, and kinetic foundations for successful applications of radical reactions of alkynes in synthesis and materials science. The proposed research will enhance understanding of the reactivity of the alkyne moiety as well as radical species. The combination of computations and kinetic studies will be used to validate theoretical approaches for studies of organic reactions. The theoretical and experimental components of this work will allow training of specialists in each area and will provide researchers at the undergraduate, graduate and postdoctoral levels with an opportunity to integrate learning and discovery. The results will be disseminated in the PI's publications and outreach activities, including participation in symposia and lecturing at undergraduate and graduate institutions. The PI and his students will also record their research presentations for the Global Educational Outreach for Science Engineering and Technology (GEOSET), a new initiative to provide outstanding Science, Engineering and Technology (SET) teaching material through the new technology. The recorded research presentations will be posted on the GEOSET website and linked to the the PI's and Departmental websites. This exposure will also help in the development of further career opportunities for participating students since these recordings may even take the place of job interviews, thus reducing carbon footprints and travel costs to prospective employers.