Study On Rhodium(Ⅲ)-Catalyzed Thioamide Directed C-H Activated Alkynylation Reaction

Alkynes are significant structural motifs in synthetic chemistry,material science and bioactive compounds and the alkyne group can undergo further transformations to afford diverse functionalized compounds.Thus the selective incorporation of alkyne groups into organic molecules is of great significance.In recent years complementary to the Pd-catalyzed Sonogashira coupling,the direct metal-catalyzed C-H alkynylation has emerged as a highly promising approach to access aryl alkynes directly from arenes because the C-H bond is directly functionalized without preactivation.Thioamide is an important and useful functional group found in vital biological and pharmaceutical molecules,such as potent antitumor agents and enzyme inhibitors.Thioamides,are also a versatile class of building blocks in organic synthesis,which can be used for the convenient construction of nitrogen and sulfur heterocycles.While the C-H bond activation reaction in the presence of an amide as a directing group is well documented,activation assisted by thioamide is still a challenging task due to sulfur’s ability to poison many transition-metal catalysts.This thesis focuses on the C-H alkynylation of thioamides,which consists of three parts as following:Part one:the alkynyl reactions of amides,heterocyclic compounds,carboxylic acids,amines,alcohols,ketones,aldehydes and oxime ethers catalyzed by transition metals were mainly described.Part two:Rh(Ⅲ)-catalyzed C-H mono-and di-alkynylation of thioamides has been developed.This reaction was performed under mild conditions in high yields with a broad substrate scope.Significantly,the versatility of this method was further demonstrated by controlled mono-and di-alkynylation.The strategy was applied to the late stage functionalization of two drug molecules adapalene(treatment of skin disease drug)and amoxapine(anti-depressant drug),which provides a new way to explore new drugs.Part three:Rh(Ⅲ)-catalyzed C-H dialkynylation of ferrocene using thioamides as directing groups has been achieved with good functional group tolerance,and the developed methodology has been applied to the synthesis of the derivatives of drug structure quipazine and anti-depressant drug amoxapine,which further expands the application of this reaction.