新型杂环膦催化剂的设计合成及其催化反应研究

Phosphorus reagent has a unique reactivity because of the special electronic structure of phosphonic atoms. However, there are some important reactions in which phosphorus reagents were involved, such as Appel and Mitsunobu reaction, due to the production of by-products OPPh3, the atom economy of the reactions are very low and the separation of the product is very difficult. On the other hand, mutual transformation between PV/PIII is difficult owing to the strong P = O (128 kcal/mol) of the by-products OPPh3, and also the activity of phosphorus reagents such as PPh3 is always low. Therefore, the design and synthesis of the new efficiency phosphonic catalyst is an excellent way to solve these problems. This project will design and synthesis new types small ring phosphonic catalysts, research the mutual transformation between PV/PIII, testing and inspecting the catalyst activity and stability. With these phosphonic catalysts in hand, the project will focus on the following research areas: phosphonic catalytic unsaturated bond reduction reaction, the Mitsunobu reaction, the synthesis of natural products or drug molecules, design and development of new reaction. The study of this project will be beneficial to the application of organophosphorus involved reactions and the development of high efficiency, green synthetic methodologies. Preliminary results show that this subject is feasible.

磷试剂中磷原子特殊的电子结构赋予了其独特的反应性能。然而，有些磷试剂参与的重要反应因副产物三苯基氧膦的产生，致使反应原子经济性普遍较低（如Appel反应和Mitsunobu反应等），产物分离困难。另一方面，副产物三苯基氧膦因牢固的P=O双键（键能128kcal/mol）致使PIII/PV间的相互转换较难，且三苯基膦等磷试剂活性较低。设计合成新型高效的膦催化剂是解决这些问题好办法。本项目拟设计合成结构新颖、具有较大环张力的四元杂环有机磷试剂和五元稠杂环有机磷试剂，研究它们之间PIII/PV间的相互转换，测试及检验其催化剂活性和稳定性；并将它们用于催化不饱和键的还原反应、Mitsunobu反应；并应用于天然产物或药物分子的合成，以及用于新反应的设计开发。本项目的实施将促进基于PIII/PV氧化还原的膦催化反应在有机合成中的应用，对发展原子经济性、绿色的合成方法学提供实验依据和理论支撑。

磷催化是有机化学研究的热点领域之一。然而，磷试剂参与的重要反应至今鲜有工业化应用的实例，究其原因是由于副产物三苯基氧膦的产生，致使反应原子经济性普遍较低，产物分离困难，并且三苯基氧膦P=O双键非常稳定致使PIII/PV间的相互转换困难，且三苯基膦等磷试剂活性较低。新型高效的膦催化剂的设计合成是实现高效、高选择性磷催化的关键。本项目从简单原料出发，设计合成新型、活性较高的四元杂环有机磷试剂和五元稠杂环有机磷试剂，重点研究：1）高原子利用率的催化型分子内Wittig反应；2）高原子利用率的催化型分子内氮杂Wittig反应；3）膦催化的分子间氮杂Wittig反应，实现仲胺类衍生物的绿色合成；4）膦参与的多组分串联反应的研究及相关杂环化合物的绿色合成。该项目的实施为快速发展膦催化提供了一定的理论指导和实验依据，并且对发展新的方法学、构建具有潜在应用价值的功能化分子具有重要意义。