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

这一建议将炔反应性的不寻常方面的研究扩展到一个新的方向。它将集中于控制炔基环化的基本因素，并利用这些知识来设计合成有用的转化。由于烯烃和炔烃自由基环化的立体电子图有很大的不同，了解这些基本的差异对炔烃化学的发展至关重要。在这个项目中，Alabugin小组将利用立体电子和热力学因素来寻找明显有利但实际上尚未开发的自由基过程：5-内切自由基环化，并将此反应和相关反应应用于合成新的碳环和杂环体系。提出的实验将测试关于不同环化模式的相对效率的早期计算预测，发现新的环化拓扑，并测试合作超共轭相互作用在控制自由基反应性方面的效率。同时，该团队将结合有效的自由基环化和自由基易位，以快速构建功能化的多环体系。这些反应通过在C-C键形成步骤中利用炔部分的两个pi键，利用了存在于炔烃中而不存在于烯烃中的合成势。本研究的智力价值在于通过实验和理论研究的结合，揭示了控制自由基过程效率和选择性的电子和结构因素的贡献。对电子效应的潜在关注将增加这些发现的总体重要性，拓宽对这些基本因素的理解，并导致自由基反应性新范式的发展。更广泛的影响将是为炔基自由基反应在合成和材料科学中的成功应用奠定机理、结构和动力学基础。所提出的研究将提高对炔部分反应性和自由基种类的认识。计算和动力学研究的结合将用于验证有机反应研究的理论方法。这项工作的理论和实验部分将允许培训每个领域的专家，并将为本科生，研究生和博士后水平的研究人员提供整合学习和发现的机会。研究结果将在PI的出版物和外联活动中传播，包括参加专题讨论会和在本科和研究生机构演讲。PI和他的学生还将为全球科学、工程和技术教育推广（GEOSET）录制他们的研究报告。GEOSET是一项通过新技术提供优秀的科学、工程和技术（SET）教材的新倡议。录下的研究报告将上载于GEOSET网站，并连结至各项目总监及部门的网站。因为这些录音甚至可以代替工作面试，因此减少了未来雇主的碳足迹和旅行成本，因此，这些录音也将有助于参与学生进一步发展职业机会。

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.