有机膦催化的喹啉氮氧化物脱氧C2-H键官能化反应的研究

2-取代喹啉是一类重要的喹啉衍生物，具有广泛的生物和药理活性。通过亲电试剂活化喹啉氮氧化物,从而提高喹啉C2位亲电性，并进一步接受亲核试剂进攻是当前合成2-取代喹啉的一种重要方法。这种方法存在原子经济性低，需要使用当量亲电试剂以及碱，反应体系产生大量废弃物等问题。针对这些问题，申请人提出以亲电催化代替当量亲电试剂活化喹啉氮氧化物的策略，拟发展有机膦催化的喹啉氮氧化物脱氧C2-H键官能化反应，为2-取代喹啉的绿色合成提供新途径。研究内容包括：（1）考察特定结构有机膦分子催化活性，筛选出1-2类具有高效催化活性的有机膦催化剂。（2）考察喹啉氮氧化物与亲核试剂的反应，实现某些具有生理活性的2-取代喹啉类药物的合成。（3）利用现代分析测试手段，对反应机理进行研究，揭示反应的一般规律。该项目的研究将进一步拓展有机膦分子催化领域，符合现代绿色化学发展的要求，具有重要的科学研究价值和实践意义。

2- Substituted quinolines are versatile quinoline derivatives with a wide range of biological and pharmacological activities. It’s an important strategy for the synthesis of 2-Substituted quinolines via quinoline nitrogen oxides activation with electrophilic reagents to increase the eletrophilicity, following by sequential nucleophilic attack at the C2 position of quinolines. However, this method has some drawbacks, such as low atomic economy, the use of equivalent electrophilic reagents and base, and the production of a large amount of waste in the reaction system. Aiming at the existing problems, this project proposes the strategy of using electrophilic catalysis instead of equivalent electrophilic reagents, intending to develop organophosphorus-catalyzed deoxygenative C2-H bonds functionalization of quinoline nitrogen oxides, which helps to provide a new approach for green synthesis of 2-Substituted quinolines. The research contents include : (1) to investigate the catalytic activity of organophosphorus molecules with specific structures, and to select 1-2 kinds of organophosphorus catalysts with high efficiency in catalyzing the deoxygenative C2-H bonds functionalization of quinoline nitrogen oxides. (2) to investigate the reactions of quinoline nitrogen oxides with various nucleophiles and realize the synthesis of some 2-Substituted quinoline drugs with physiological activities. (3) to study the reaction mechanism and reveal the general law of reactions by means of modern analysis and test. The research of this project will further expand the field of organophosphorus molecular catalysis, which complies with the development of modern green chemistry and has important scientific research value and practical significance.