催化不对称碳-氢官能团化研究

光学纯的ɑ-取代的氮杂环和氧杂环结构广泛存在于活性天然产物和药物分子中，例如四氢（异）喹啉、哌啶、异色满和四氢呋喃。但到目前为止，还没有通过对氧杂环或N-酰基杂环底物的C-H修饰，构建上述结构的不对称催化体系的报道。本课题拟发展一个以"碳正离子池"和三苯甲基碳正离子介导的C-H修饰为基础的不对称催化体系，通过分别运用"手性亲核试剂"和"手性离子对"两种策略，实现上述一系列氧杂环和氮杂环分别与末端炔和β-二羰基化合物（"手性亲核试剂"策略）以及多种有机硼试剂和C-H亲核试剂（"手性离子对"策略）的不对称偶联，对映选择性的合成结构多样的ɑ-取代杂环衍生物。然后应用此方法，对具有重要抗菌和抗病毒活性的天然产物(+)-deoxyfrenolicin进行不对称全合成研究。拟发展一条比已知最短路线更有效的合成策略，验证该方法在复杂分子合成中的应用潜能，为含上述结构的复杂分子的合成提供新的思路。

Enantiopure ɑ-substituted nitrogen- and oxygen-containing heterocycles, like tetrahydroisoquinolines (THIQs), tetrahydroquinolines (THQs), piperidines, isochromans, and tetrahydrofurans (THFs)， are one of the most common structural motifs spread across biologically active natural products and synthetic pharmaceuticals. However, to the best of our knowledge, no asymmetric catalysis has been reported for the synthesis of such molecules through C-H functionalization of oxygen-containing or N-acyl heterocyclic substrates. In the proposal, two strategies are designed to enantioselectively construct a variety of ɑ-substituted oxygen- and nitrogen-containing heterocycles relying on "cation pool" protocol and triphenylcarbenium ion mediated mild C-H functionalization method. By using "chiral nucleophile" strategy, a variety of heterocycles will be coupled with terminal alkynes and β-dicarbonyl compounds, respectively, in the presence of suitable chiral catalyst. By using "chiral counterion" strategy, the heterocyclic substrates will be coupled with a wide range of organoboranes and C-H nucleophiles, respectively, under the catalysis of suitable chiral Lewis acid. Subsequently, the "chiral counterion" strategy will be applied as the key step in the asymmetric total synthesis of natural product (+)-deoxyfrenolicin possessing potent antifungal and antivirus activities. The synthetic efficiency here is expected to be improved compared to the shortest synthetic route to date for the molecules, indicating that the approach developed herein should have potential applications in complex molecule synthesis, and will open a new synthetic strategy for future efforts in the synthesis of molecules containing such structures.