Research On Synthesis Of N/s-Containing Compounds Involving Isocyanides Catalyzed By Transition Metal Or Rare Earth Metal

As an important class of active synthons in organic synthesis,isocyanides are used to efficiently synthesize natural products,drug molecules and nitrogen-containing molecules or heterocyclic compounds with potential biological activity.In recent years,palladium-catalyzed various reactions involving isocyanide,especially the insertion reactions of isocyanide,have been widely concerned,studied and applied,which are of great practical significance.In this paper,we mainly focus on the synthesis of N-aryl dialkynylimines,thiadiazole dithiazoles,diamine thioethylenebenzamide and other nitrogen-containing compounds by palladium/copper synergistic catalysis or rare earth metal catalyzed reaction of isocyanide.It provides a variety of effective strategies for the efficient construction of nitrogen-containing molecules or heterocyclic derivatives and the synthesis of their related drugs,which further enriches the types of reactions involved in isocyanides and the research and development of isocyanide chemistry.Part 1,Pd（dppf）Cl₂/Cu（OAc）₂ synergistically catalyzes the double coupling reaction of terminal alkynes and isocyanides at room temperature to obtain a series of N-aryl dialkynylimines.Then,the N-aryl dialkynylimines were further converted into2-iodobenzo[f]quinoline compounds by electrophilic cyclization.This method has the advantages of mild conditions,simple operation and high efficiency of atom economy,which provides a new and efficient way to be used as building blocks for elaborated synthesis.Part 2,using Pd（dppf）Cl₂ as the catalyst,under the promotion of copper salt,a series of thiadiazole dithiazole double heterocyclic derivatives were synthesized by using benzyl isocyanide and thiobenzamide as the reaction substrates,through the strategy of double insertion/tandem cyclization of benzyl isocyanide,a one-step efficient construction Two heterocyclic rings,including the formation of C-N,C-O,S-S and S-N bonds.The possible mechanism of the reaction has been proved by isotope labeling method and control experiment.The mechanism study shows that the oxygen in the target product comes from water.This method has the advantages of mild conditions,simple operation and easy availability of raw materials.This project provides a novel and effective strategy for the efficient construction of thiazole compounds and the synthesis of their related drugs.Part 3,due to the unique chemical activity of rare earth metals compared with other transition metals,in recent years,rare earth metal catalyzed reactions involving isocyanide have been widely used in organic synthesis.In the presence of a catalytic amount of the rare earth catalyst La（OTf）₃,one molecule of thioamide and two molecules of isocyanide undergo a rearrangement reaction.The reaction process involves the cleavage of the C-S bond and the formation of new C-N,C-O and C-S bonds.A series of diamine thioethylidene benzamide derivatives were obtained.The mechanism study shows that the oxygen in the target product comes from water.This scheme has the advantages of high chemical selectivity,good atomic economy,low catalyst loading,low cost and easy availability.It further expands the types of reactions involving amide groups and reveals the reaction mechanism of these reactions.