Hyperconjugative assistance in alkyne cyclizations and cycloadditions

点击翻译按钮获取中文摘要

In this project supported by the Chemical Structure, Dynamics and Mechanisms Program of the Division of Chemistry, Professor Igor Alabugin and his research group will extend studies of alkyne reactivity into three new directions. It will use computations to discover stereoelectronic effects capable of controlling anionic cyclizations of alkynes and non-catalyzed alkyne cycloadditions and utilize this knowledge to develop efficient chemical processes. In the first part of this project, the research team will search for the two virtually unexplored alkyne cyclization patterns: 3-exo-dig and 4-exo-dig closures. Proposed experiments will test computational predictions regarding the relative efficiency of different cyclization patterns and utilize cooperative hyperconjugative interactions for the control of reactivity. In the second part, the researchers will use negative hyperconjugation to enable selective endo closures in the delicately poised pairs of competing endo and exo cyclizations. The final part of the project will test hyperconjugative assistance as the new transition state stabilization approach in non-catalyzed alkyne-azide cycloadditions. The intellectual merit of this research is in unraveling the contribution of electronic and structural factors controlling efficiency and selectivity of alkyne cyclizations and cycloaddtions through a combination of experimental and theoretical studies. The underlying focus on orbital interactions will increase the general importance of these findings, broaden our understanding of these fundamental factors and lead to the development of new paradigms of radical and anionic reactivity.The broader impact will be the laying of mechanistic, structural, and kinetic foundations for successful applications of reactions of alkynes in synthesis and materials science. The proposed research will enhance our understanding of the reactivity of the alkyne moiety as well as radical species. The combination of computations with kinetic studies will be used to validate computational 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 publications and through outreach activities, including participation in symposia and lecturing at undergraduate and graduate institutions.