基于C-H键氧化羰基化反应构筑几类含氮杂环化合物

Oxygen-promoted C-H bond oxidative carbonylation reactions are more environmentally friendly, safe, and economical than that utilizing organic or metallic oxidants. In this research project, we wish to synthesize eight classes of nitrogen-containing heterocycles with important biological activity via oxygen-promoted intramolecular C-H bond oxidative carbonylation reactions oriented by directing groups..Comparing with the traditional synthetic methods, this synthetic strategy contains several advantages as follows: (1) Oxigen, a green and economical oxidant, is used in place of expensive organic or metallic oxidants; (2) Base on the rational substrates design, the reactions need not introduction and modification of any additional directing groups. The N-containing groups in the substrates play the role of nucleophiles as well as directing groups; （3) Pyrroles were explored as new directing groups for C-H bond oxidative carbonylation; (4) There is not a need to introduce halogen atoms or halogen surrogates to the start materials. Thus, the reactions do not produce any halogen-containing waste..We have assembled one such nitrogen-containing heterocyclic compound under 1 atm CO with the use of catalytic amounts of palladium acetate as catalyst and oxygen as sole oxidant. The systematic investigation of this protocol will not only provide a novel route for the synthesis of a variety of nitrogen-containing heterocyclic compounds, but also further expand oxygen, the green and economy oxidant, to apply in the industrial production as well as in the laboratory research.

以氧气为氧化剂促进的C-H键氧化羰基化反应比使用有机或金属氧化剂的C-H键氧化羰基化反应更加环保、安全和经济。本项目拟利用氧气为氧化剂，促使发生分子内C-H键氧化羰基化反应，构筑八类具有重要生物活性的含氮杂环化合物。这一合成策略与传统的合成方法相比，具有如下优点：（1）以绿色经济的氧气作为氧化剂，避免使用昂贵的有机或金属氧化剂；（2）合理设计反应底物，不需要特意进行导向基团的引入和脱除，分子内的含N基团既是导向基，又是亲核试剂；（3）拓展吡咯作为C-H键氧化羰基化反应的新型导向基团；（4）反应底物不需预先引入卤原子或类卤原子，不产生含卤素废料。我们已初步实现了以催化量醋酸钯为催化剂，以空气中氧气为唯一氧化剂在1atm CO下构筑一种含氮杂环化合物。对该合成策略的深入研究，不仅为多种含氮杂环化合物的合成提供新思路，而且将进一步拓展氧气这一绿色经济的氧化剂在实验室研究乃至在工业生产中的应用。

本项目发展出一种室温条件下通过C-H键羰基化一步合成吡啶[2,1-b]喹唑啉酮类化合物的方法；此外，还发展出温和条件下水相Ullmann类型偶联反应的新配体及新催化体系，主要包括以下几方面工作：1）首次发现6,7-Dihydroquinolin-8(5H)-one oxime肟类配体可以有效促进室温铜催化甲胺和二甲胺在纯水相中发生氮芳基化反应；2）发展了三乙醇胺作为配体有效促进铜催化卤代芳烃羟基化合成苯酚的反应；3）发展了一种高效合成N-苯基-2-氨基取代吡啶类化合物的方法。该方法仅用1%的Cu进行催化，不需要添加额外的配体，就可高效合成N-苯基-2-氨基取代吡啶类化合物。