无过渡金属和锡参与的卤代芳烃还原脱卤反应研究 ——简单高效氘代芳烃的合成

氘代化合物广泛地应用在化学研究的很多方面，例如有机物的生源合成路径分析、化学反应机理研究和药物分子设计等。来源广泛的卤代芳烃还原脱卤反应是制备氘代芳烃最有效的方法之一，目前报到的路线都具有明显的局限性：主要依赖于使用高活性、易燃的金属试剂，或者高毒性的过渡金属和锡试剂等。本课题拟研究无过渡金属或锡参与的卤代芳香化合物的还原脱卤反应，使用毒性很小的硅试剂在温和条件下产生自由基，随后攫取卤原子生成芳基自由基，再从氘代溶剂中获取氘原子生成目标化合物。将发展一条温和、简单、经济、高效和绿色的合成氘代芳烃的路线。并通过自由基共振谱和自由基中间体的捕获等策略进一步详细研究反应机理。此外，将所发展的这类方法应用到一些复杂分子的进一步修饰中，为药物分子的后期修饰提供简单高效的方法。

Deuterated compounds are widely used in many fields, such as structural studies in biosynthetic analyses, mechanistic investigations of chemical reactions, and deuterated-drugs in pharmaceutics, etc. Deuteration by hydrodehalogenation of readily available aryl halides is one of the most useful methods to access deuterated compounds. However, currently established procedures are mainly limited to the employment of pyrophoric reagents, toxic transition-metal complexes and tin reagents，and expensive deuterium sources. This project aims to study and develop mild, simple, cost-efficient, and environment-friendly hydrodehalogenation reactions to efficiently synthesize the deuterated compounds without the use of stoichiometric organometallic species, transition-metal complexes, and tin reagents. This proposed procedure involves generation of silyl radicals under mild conditions, formation of aryl radicals by dehalogenation, and the abstraction of deuterium from cheap and commercially available deuterated solvent. Concurrently, the mechanism of this chemistry will be studied by ESR and radical trap experiments. Finally, the late-stage modification of drug molecules using this simple and efficient method will be investigated, which highlights the application of this chemistry.