自由基反应在构建含氟中环/大环内酰胺和内酯化合物的研究

中环/大环内酰胺和内酯是有机化学中一类有重要合成意义和挑战性的化合物,广泛存在于很多天然产物和有生物活性的分子中。基于含氟化合物在材料和医药研发方面的重要性，本项目结合申请人在自由基反应和中环/大环化合物合成的学科背景，拟设计和发展全新的自由基酰胺和酯的迁移化学实现含氟中环/大环内酰胺和内酯的构建。研究理念是以简单易得的烯基和炔基酰胺或者酯为原料，利用现场产生的含氟烷基自由基进攻非活性的烯烃或炔烃，产生的烷基或者烯基自由基引发远程的酰胺和酯的迁移，通过分子的结构重组构建含氟中环/大环内酰胺和内酯化合物。同时，通过一系列控制实验对反应机理进行详细研究。项目的成功实施将为含氟中环内酰胺和内酯化合物的合成提供新的工具，开辟自由基反应在中环和大环化合物合成中的应用。

Medium-/Large-sized lactams and lactones are important and synthetically challenging structural motifs in a range of natural products and biologically active molecules. Due to the importance of organic fluorine compounds in material science and medicinal chemistry, we will focus on the development of a novel remote radical amidyl and ester migration chemistry for the synthesis of a library of fluoro-containing medium-/large-sized lactams and lactones based on our knowledge in radical chemistry and synthesis of medium-/large-sized molecules. We assume that the in situ generated fluoroalkyl radicals would attack the unactivated alkene or alkyne of readily available substrates to generate a higher-energy radical intermediate, which would initiate the remote amidyl or ester group migration to provide structurally diverse fluoro-containing medium-/large-sized lactams or lactones via skeletal reorganization. Furthermore, we will study the detailed reaction mechanism through a series of control experiment. The implementation of this project would provide a versatile tool for synthesis of fluoro-containing medium-/large-sized lactams and lactones as well as exploit the application of radical reaction in assembly of skeletally complex medium-/large-sized molecules.