新型手性SPOs配体的合成及其在不对称催化中的应用

氮杂芳香化合物是大量天然产物、药物分子、药物活性分子的母核，但由于其结构特点，经传统化学合成和一般过渡金属催化法制备复杂的缺电子手性杂环化合物往往比较困难低效。近年来发展的Ni-Al双金属催化体系具有经催化C-H官能化构建手性杂环化合物的潜力。仲膦氧化物SPOs比普通膦配体更具特色和广泛应用前景，但目前高效手性SPOs配体还很有限。在文献调研和课题组研究积累的基础上，本项目精心设计并将合成3类新型手性SPOs配体，构建了5类新型氮杂环不对称C-H活化并环化反应，拟通过Ni-Al双金属不对称催化研究，发掘高效SPOs配体和催化体系，考察其构效关系，合成多类常规方法难以获得的新型手性杂环化合物。从而进一步丰富缺电子杂环C-H官能化反应，发展具有自主知识产权的手性配体及非贵金属催化体系，深化对催化机理的认识，为设计发展新型手性催化剂、新反应和构建手性杂环新策略提供理论支持，促进手性化学的发展。

N-heterocyclic compounds are the mother nuclei of a large number of natural products, drug molecules and drug active molecules. However, due to the characteristics of its substrate structure, it is often difficult and inefficient to prepare complex electron-deficient chiral heterocyclic compounds directly by traditional chemical synthesis and general transition metal catalysis. In recent years, a kind of newly developing Ni-Al bimetallic catalytic system has showed the potential to construct chiral heterocyclic compounds efficiently by catalytic C-H functionalization. Compared with ordinary phosphine ligands, secondary phosphine oxides (SPOs) have better characteristics and broad application prospects, but highly efficient chiral SPOs ligands are still limited at present. On the basis of literature review and research accumulation of our group, three kinds of novel chiral SPO ligand skeletons have been carefully designed and will be synthesized in this project, and five kinds of new asymmetric C-H activation and cyclization reactions for the synthesis of chiral heterocyclic compounds have also been constructed. Through the study of Ni-Al bimetallic asymmetric catalysis, it is expected to explore and obtain highly efficient SPO ligands and catalytic systems, and investigate the structure-activity relationship among different substrates, ligands, metals, catalytic activity, regioselectivity and stereoselectivity. Several classes of new chiral heterocyclic compounds, which are difficult to be acquired by conventional methods, will be successfully synthesized. All of these will further enrich C-H functionalization reaction of electron-deficient heterocycles, develop chiral phosphine ligands and non-noble metal catalytic systems with independent intellectual property rights, deepen the understanding of catalytic mechanism, provide theoretical support for the design and development of new chiral catalysts, new reactions and new strategies for the construction of new chiral heterocycles, and promote the development of chiral chemistry.