手性氮杂环烯烃（NHO）的设计合成及其在不对称催化反应中的应用

N-Heterocyclic olefins (NHOs), as a kind of unique ene-1,1-diamines, are structurally analogous to the deoxy-Breslow intermediates in NHC catalytic chemistry. Due to the donating ability of the two nitrogen atoms and charge separation by unsaturated five-membered backbone, the exocyclic C=C double bond is very electron rich and highly polarized, which leads to three applications of NHOs: as nucleophilic catalyst in organocatalysis，as strong donor ligands for the stabilization of main group element active species and as end-on ligands in transition metal coordination and catalysis. Although the number of research papers concerning on the utility of NHOs increased in the past several years, there are still several limitations: (1) Most of NHOs are C2 symmetric and derived from imidazole. (2) The application of NHO as organocatalysts or end-on ligands in transition metal catalysis is limited and need to be explored furtherly. The synthesis of chiral NHOs and their utility is scare and unsatisfactory. The special charactlization of NHOs along with unsolved problems mentioned above attracted our attention. In this program, we intend to synthesis a serial of chiral amino acid derived-NHOs and investigate their applications as organocatalysts in the activation and catalytic transformation of CO2. Moreover, the newly designed NHOs as the ligands in transition metal catalysis will be explored as well. Next, we will also carry out the control experiments and collaborate with other group to get insight of the reaction mechanism. Based on above work, we hope to develop a new kind of chiral NHOs catalyst for new asymmetric reaction and provide simple but efficient routes to important chiral molecules.

氮杂环烯烃（NHO）是一类1,1-二胺基取代烯烃，结构类似于去氧的Breslow中间体。由于氮原子强的供电作用和杂环有效的电荷分散能力，环外双键富电且被高度极化。使得NHO不但可以用作亲核的有机催化剂，也可通过强供电作用稳定活泼的主族活性物种和作为配体参与络合物催化反应。尽管最近几年，关于NHO的报道逐渐增多，但仍存在如下问题：（1）结构单一，多数是咪唑衍生的C2对称的NHO；（2）作为催化剂或配体在有机合成中的应用还十分有限，且手性NHO应用仅有一例（16% ee）。基于对NHO性质了解以及存在问题的分析，拟设计和合成一类新型的手性氨基酸衍生的NHO，并考察其在催化CO2的不对称转化和作为配体在不对称金属配合物催化中的应用。设计控制实验并展开合作，研究反应机理。通过该项目的开展，希望发展一类新型的手性NHO催化剂，为重要手性分子的合成提供简单、有效的合成途径。

氮杂环烯烃（NHO）是一类1,1-二胺基取代烯烃，由于氮原子强的供电作用和杂环有效的电荷分散能力，环外双键富电且被高度极化。使得NHO不但可以用作亲核的有机催化剂，也可通过强供电作用稳定活泼的主族活性物种以及作为配体参与金属配合物催化反应。尽管近些年关于NHO的报道逐渐增多，但存在如下问题：（1）结构单一，多是咪唑衍生的C2对称的NHO;（2）作为催化剂或配体在不对称合成中的应用少，仅有一例（16% ee）。在项目支持下，我们设计合成了手性芳胺衍生的C2和非C2对称的NHO，建立了手性NHO化合物库，并通过核磁、单晶衍射等表征手段确认了NHO的结构。经过一系列反应筛选和条件优化，发现该类催化剂作为一类新型的有机超强碱，可高效高选择性地催化β-酮酸酯的不对称氨化、硫三氟甲基化反应。以NHO为亲核性的有机小分子催化剂，我们还实现了HBpin对简单酮的还原，并成功拿到关键中间体的单晶，但反应对映选择性有待进一步提高。在上述研究基础上，设计了咪唑啉-2-亚胺（NHI）配体，合成并表征了其前过渡金属配合物结构。研究发现该类配合物能有效催化甲基吡啶和苯甲醚的直接C-H官能化，得到高的收率和中等的对映选择性。除此之外，利用课题组特色催化剂体系，我们发展了新型串联、重排、双金属协同催化等高效催化不对称新反应，实现了药物分子阿莫达非尼、巴氯芬、和天然产物Spirohydantoin (I)和吡咯烷吲哚类生物碱CPC-1的催化不对称合成。上述研究结果很好地完成了既定研究目标，为下一步研究工作打下了坚实基础。项目执行过程中共发表标注项目的SCI论文12篇，培养硕士研究生4名，项目负责人董顺喜获得Thieme Journal Chemistry Award国际学术奖、四川省“青千”资助，入选四川省科学与技术学术带头人后备人选。担任Chin. Chem. Lett.第四届青年编委。