高效构建含P-C键的功能有机膦化合物的新方法研究

The increasing importance of phosphorus compounds in organic synthesis, materials, and biology demands new, efficient P-C bond-forming reactions for the construction of structurally sophisticated phosphorus compounds that are not readily available by classic methods. This has stimulated extensive studies of P-C bond-forming reactions via transition-metal catalysis through either couplings with organic reagents or additions to unsaturated C-C. However, the highly-efficient synthesis procedures for organic phosphorous compounds containing P-C bond are limited, which directly restrict the rapid development of phosphorous-containing new ligands, new materials, and new pharmaceuticals. Accordingly, it's a hotspot in organic phosphorous chemistry to develop methodologies that provide P-C bond efficiently and selectively. This program would focus on developing new methods of P-C bond formation, which would fulfill the goal of highly efficient, accurate synthesis of arylphosphonates and α-amino phosphonates. We would design and develop highly efficient copper and nickel catalysts, exploit P-C bond generating procedures that combine the chemically-stable, readily available H-phosphite and series of carbon donating organic substrates (Potassium Aryltrifluoroborates, Aryl Trialkylsiloxane, Arenediazonium Tetrafluoroborates, α, β-unsaturated Imine, Quinoline and their derivatives), realize the highly efficient, selective transformation of C-B bond, C-Si bond, C-N bond, C=C bond, C=N bond to P-C bond. We would further study the effect of organic substrates' chemical and electronic structures on the efficiency and selectivity of P-C bond generation, and investigate the catalysis efficiency and mechanisms of copper and nickel catalysts, thereby deeply realize the mechanism and principle of P-C bond formation and functionalization, then design and develop novel catalysis systems for the P-C bond formation and functionalization, and eventually establish highly efficient, practical new methods using readily available organic reagents, for preparing functional arylphosphonates and α-amino phosphonates.

含P-C键有机膦化合物高效合成法的欠缺，直接制约了含磷新配体、新材料和新药物的发展，因此，开发高效构筑P-C键的方法是有机磷化学中的前沿研究内容。本项目将致力于开拓P-C键的构筑新方法，实现芳基膦酸酯和α-氨基膦酸酯精密高效合成的目标。将发展廉价的铜和镍催化剂，围绕稳定的氢亚磷（膦）酸酯，开发与各种含碳有机底物（芳基氟硼酸钾，芳基三烷氧基硅烷，芳基重氮氟硼酸盐，α,β-不饱和亚胺，喹啉及其衍生物）的P-C键构筑新方法，实现C-B、C-Si、C-N、C=C和C=N键向P-C键的高效高选择性转化；探索含碳有机底物的化学和电性结构对构建P-C键的反应效率和选择性的影响规律；研究铜和镍催化剂的催化效率和反应机理，从而深入认识P-C键生成及官能化的内在机制和基本规律；继而进一步设计和开发新颖的P-C键构筑和官能化的催化体系；最终建立原料易得、实用、高效构建功能性芳基膦酸酯和α-氨基磷酸酯的新方法。

含P-C键的有机膦化合物在有机化学、药物化学和材料科学等领域中广泛应用，但是含P-C键有机膦化合物高效合成法的欠缺，特别是一些复杂的功能化的含P-C键的有机膦化合物往往不能通过传统的方法合成，直接制约了含磷新配体、新材料和新药物的发展，因此，开发高构筑P-C键的精密方法是有机磷化学中的前沿研究课题。本项目基于简单易得的含磷底物成功开发了十几种高效精密构建P-C键的新方法。以钯或廉价的铜和镍作为催化剂，商用的氢亚磷（膦）酸酯为磷源，发展了与各种含碳有机底物（芳基硼酸，芳基丙烯酸，芳基丙炔酸，烯基二溴物，1,2,3,4-四氢异喹啉、1,10-菲罗啉）的P-C键的高效构筑方法，实现了C-B键、C=C键、C=C 键、C-N键和C=N键向P-C键的高效高选择性转化。本项目也探索了含碳有机底物的化学和电性结构对构建P-C键的反应效率和选择性的影响，并揭示了这些方法的反应机理，从而深入认识了P-C键生成及官能化的内在机制。此外，也研究了部分化合物的阻燃性能和电化学性能，发现了3个含磷化合物有望开发为锂离子电池新型阻燃剂。 总之，这些合成新方法具有底物简单易得，催化剂廉价，操作简单，官能团适用性广，化学区域选择性高，立体选择性高，产率高或经济便宜、适用于大量制备等优点，为精密合成功能性的芳基膦酸酯、α-氨基磷酸酯、1-烯基膦酸酯，1-炔基膦酸酯和苯并磷杂环戊二烯衍生物提供了简单高效的合成工具，有效缓解了含P-C键有机膦化合物高效合成方法欠缺的问题，必将有力地促进含磷新配体、新材料和新药物的发展。