RUI: Reaction Acceleration, Mediation, and Catalysis by In Situ Silylation

本研究由化学系化学合成项目资助，Chiles W.里士满大学化学系的唐尼将探索使用甲硅烷基化试剂来加速、调解和催化一系列化学反应。 甲硅烷基化剂如三氟甲磺酸三甲基甲硅烷基酯将起两种作用。 首先，亲电硅中心将充当刘易斯酸，以激活其他亲电体进行亲核攻击。 其次，形成强的硅-氧或其他硅-杂原子键将有助于推动这些化学反应完成，从而提供高产率和更短的反应时间。 特别感兴趣的是羧酸的α-取代反应，这是一类通常受到强碱性反应条件阻碍的反应。 当使用这些反应物时，甲硅烷基化剂可以通过将酸官能团转化为更容易控制的甲硅烷基酯而起到第三种作用。 这项工作可能会导致羧酸的不对称反应的发展，如不对称羧酸羟醛缩合反应。 该项目对基础生物科学、制药和农业工业具有重大影响，因为它将提供直接获得手性羧酸盐构建单元的途径，这些构建单元在生物合成和化学合成具有强大生物活性的复杂分子中非常重要。 对一锅反应性的强调减少了废物的产生，提供了积极的环境影响以及在时间和经济方面的节省。 该项目还为本科研究生提供培训，为科学、卫生领域和学术界的职业生涯做准备。 在这个奖项的过程中，六到八名研究人员将获得资助，除了在正常学年进行的实验外，还将获得为期十周的密集夏季研究经验。

In this project funded by the Chemical Synthesis program of the Chemistry Division, Professor Chiles W. Downey of the Department of Chemistry at the University of Richmond will explore the use of silylating agents for the acceleration, mediation, and catalysis of an array of chemical reactions. Silylating agents such as trimethylsilyl trifluoromethanesulfonate will act in two roles. First, the eletrophilic silicon center will act as a Lewis acid to activate other electrophiles toward nucleophilic attack. Second, the formation of strong silicon-oxygen or other silicon-heteroatom bonds will help drive these chemical reactions to completion, affording high yields and shorter reaction times. Of particular interest are alpha-substitution reactions of carboxylic acids, a class of reactions commonly hampered by strongly basic reaction conditions. When these reactants are employed, the silylating agent can play a third role by transforming the acid functional group into a more easily controllable silyl ester. This work could lead to the development of asymmetric reactions of carboxylic acids, such as an asymmetric carboxylic acid aldol reaction. This project has significant impacts on fundamental biological sciences, pharmaceutical and agricultural industries, as it would provide direct access to chiral carboxylate building blocks important in the biosynthesis and chemical synthesis of complex molecules of potent biological activities. The emphasis upon one-pot reactivity reduces the generation of waste, providing a positive environmental impact as well as savings with respect to time and economics. The project also provides trainings for undergraduate research students in preparation for careers in the science health fields as well as academia. Over the course of this award, six to eight researchers will be funded for an intensive ten-week summer research experience in addition to experiments carried out during the regular academic year.