Palladium-catalyzed Cascade Annulation Reactions For The Construction Of Trifluoromethyl-substituted Nitrogen-containing Heterocycles Using Trifluoromethyl Synthons

Due to the special biologically activity,nitrogen-containing heterocyclic compounds widely exist in natural products,pharmaceuticals,agrochemicals,and functional materials.According to statistics,more than 60% of drug molecules contain at least one nitrogen heterocyclic skeleton,and the unsaturated nitrogen-containing heterocycle with excellent stability is the common unit of drug molecules,such as triazole,pyridine,pyrimidine and so on.Because of the unique properties of fluorine atoms,the introduction of trifluoromethyl group to heterocycle could obviously enhance the lipophilicity and metabolic stability of the parent molecules.Our group focuses on the development of green and efficient methods for the construction of structurally diverse nitrogen-containing heterocycles using different trifluoromethyl synthons.The main contents of this thesis are as follows:(1)We have developed a palladium-catalyzed cascade carbonylative reaction of trifluoroacetimidohydrazides and aryl iodides for the synthesis of biologically active5-trifluoromethyl-1,2,4-triazoles with high efficiency.The reaction is characterized by a low catalyst loading amount,readily available starting materials,a broad substrate scope,no participation of CO gas.The method has been successfully applied to prepare the bioactive molecule Gly T1 inhibitor.(2)We have developed a palladium/norbornene synergistically catalyzed Catellani reaction to enable cascade dehydrogenative annulation of readily accessible3-iodochromones and trifluoroacetimidoyl chlorides for the synthesis of a variety of biologically and pharmaceutically active trifluoromethyl-substituted chromeno[2,3-c]quinolin-12-ones.The reaction provides a direct and facile route to functionalized fused-heterocycles.The gram-scale reaction demonstrates the good application prospect of the reaction.Palladium catalyst has a significant role in the above reactions,and extends the application range of construction of trifluoromethyl-substituted N-heterocycles employing trifluoromethyl synthons.The research contents of this thesis contribute to the field of efficient synthesis of trifluoromethyl-substituted N-heterocycles.