催化不对称反电子需求环化反应合成双杂原子环状化合物研究

含两个杂原子的手性六元和五元环状化合物在天然产物和药物分子中占有重要地位。双杂原子二烯的反电子需求杂Diels-Alder反应可以有效构建含两个杂原子的六元杂环，而烯丙型偶极子的反电子需求1,3-偶极环加成反应可以有效构建含两个杂原子的五元杂环化合物。然而，到目前为止，对反电子需求成环反应有效的不对称催化体系十分有限。基于课题组特色的手性双氮氧/金属配合物催化杂Diels-Alder反应和正常电子需求1,3-偶极环加成反应的研究基础，申请者拟利用手性双氮氧催化剂，高效催化双杂原子二烯的不对称反电子需求杂Diels-Alder反应、烯丙型偶极子的反电子需求1,3-偶极环加成反应以及两者的串联反应，高效高对映选择性的合成含两个杂原子的光学活性六元和五元环状化合物。 本项目还将加强机理研究，并将发展的不对称催化体系应用到生物活性天然产物和药物分子的全合成中。

Chiral hexa- and penta-cyclocompounds with two heteroatoms play an important role in the bioactive natural products and drugs. The hexa-cyclocompounds can be synthesized by the inverse-electron-demand heter Diels-Alder reaction of dienes containing two heteroatoms with alkenes, while the penta-cyclocompounds can be synthesized by the inverse-electron-demand 1,3-dipolar cycloaddition of allylic dipoles with electron-rich dipolarophiles. However, to the best of our knowledge, there are very few catalysts that are efficient for the inverse-electron-demand reactions. Based on our research on the N,N'-dioxide/metal complexes-catalyzed hetero Diels-Alder reactions and the normal-electron-demand 1,3-dipolar cycloadditions，the applicant and coworkers plan to develope new catalyst systems based on the N,N'-dioxides to realize some inverse-electron-demand heter Diels-Alder reactions of dienes containing two heteroatoms, 1,3-dipolar cycloadditions and their tandem reactions. The program will also strengthen the mechanism research, as well as applying the developed methods to the total synthesis of bioactive natural products and drugs.