Synthesis Of Trifluoromethyl-Substituted Nitrogen-Containing Heterocyclic Compounds By Decarboxylative Cyclization Or C-H Bond Activation

As one of the most common structural skeletons,nitrogen-containing heterocyclic compounds exist widely in a variety of natural products,pharmaceuticals,and agrochemicals.Because of the unique properties of fluorine atoms,the introduction of trifluoromethyl group into nitrogen heterocyclic compounds can significantly change the physical and chemical properties of their parent molecules,such as high electronegativity,lipophilicity,metabolic stability,and bioavailability.Therefore,trifluoromethyl substituted nitrogen-containing heterocycles has been widely applied in the fields of pharmaceutical,pesticide and material science.Considering the excellent properties of trifluoromethyl group,the exploration of effective methods to incorporate trifluoromethyl into functionalized nitrogen-containing heterocyclic compounds has become an attractive research field in the past few decades.Trifluoroacetimidohydrazides and CF₃-Imidoyl sulfoxonium ylides derived from trifluoroacetimidoyl chlorides are commonly used as trifluoromethyl synthons,which have notable merits of easy availability,structural stability,good functional group compatibility and high reactivity.Diverse cascade annulation reactions between trifluoromethyl synthons and suitable substrates constitute a kind of efficient strategy for the assembly of trifluoromethyl-containing N-heterocycles.This paper mainly introduces the following works:（1）We have developed a copper-catalyzed intramolecular decarbonylative cyclization reaction of readily available isatins and trifluoroacetimidohydrazides for the synthesis of 2-（5-trifluoromethyl-1,2,4-triazol-3-yl）aniline derivatives.This transformation features simple operation,a wide substrate scope,mild conditions.The obtained 1,2,4-triazole products bearing a free amino group can be converted into other useful compounds with trifluoromethyl-N-heterocyclic frameworks.（2）We have described a simple metal,oxidant and additive-free approach for the assembly of 5-trifluoromethyl-1,2,4-triazoles via only heating-induced decarboxylative cyclization of trifluoroacetimidohydrazides andα-oxocarboxylic acids.In this protocol,the rarely reported tetrahedral carboxylic acids intermediate could be in-situ generated.The protocol provides a facile entry to trifluoromethyl-substituted 1,2,4-triazoles with broad substrate scope.（3）We have achieved a efficient and straightforward approach for the synthesis of trifluoromethyl-decorated benzo[de][1,8]-naphthyridines via the Rh（III）-catalyzed dual C-H activation and cascade annulation of benzimidates and CF₃-imidoyl sulfoxonium ylides.The transformation involves the formation of four new chemical bonds along with the release of two molecules of dimethyl sulfoxide（DMSO）and one molecule each of ethanol and amine.Advantages of this reaction include a broad substrate scope,mild conditions,moderate to good yields.The resulting fused-heterocycles exhibits good fluorescence properties with a large Stokes shift（up to 127 nm）.