Investigation On Palladium-catalyzed Conversion Of Isocyanide Nitrogen-carbon Triple Bond

Isocyanide is a class of organic compounds with the general formula R-NC,which is widely used in synthetic chemistry as a highly reactive reaction synthon,such as multi-component reactions,free radical reactions,etc.The terminal carbon atoms of the isocyanide are between divalent and tetravalent.For this special bond structure,it has a good coordination with the metal.In recent years,the transitional-metal-catalyzed,especially the palladium-catalyzed cross-coupling reactions involving isocyanides,have gradually become a research field with great potential in organic synthesis.Due to the high efficiency,high selectivity and diversity of this reaction,it can be used for the synthesis of complex active molecules.Therefore,how to control the orderly and efficient conversion of isocyanide nitrogen-carbon triple bonds is of great significance for the construction of functional molecules.In this paper,based on a review of previous work about the cross-coupling of isocyanides,the transformation of palladium-catalyzed isocyanide nitrogen-carbon triple bonds was explored in depth and systematically.By controlling the reaction initiation mode,reaction process and quenching,a series of carbon-carbon and carbon-heteroatom bonds have been constructed with high efficiency,atomic economy and regioselectivity.In this content,a series of synthetic methods have been developed for the synthesis of maleimides,furans,pyrroles,functional enamines,substituted benzofurans.The specific research content is as follows:(1)Palladium-catalyzed intermolecular cyclization of alkynes with isocyanides:a good method for the synthesis of maleimide derivatives.Carbon-carbon,carbon-nitrogen and two carbon-oxygen double bonds were formed in one step by the successive insertion of isocyanide onto alkyne.A wide range of functional groups were tolerated,for the activation of alkyne and non-activated Alkynes can excellent yields.The deuterium labeling experiments indicated that the two oxygen atoms in the product both come from water.In addition,gram-scale experiments have demonstrated the potential industrial application value of this reaction.(2)Synthesis of 5-iminofuranones and 5-iminopyrrolones via palladiu-catalyzed cyclizations of alkynyl carboxylic acids with Isocyanides.The two products were constructed selectively through different reaction paths by using the same substrate,while different solvents The 5-imine-2-furanone derivatives was synthesized via[4+1]cyclization process in dichloromethane;After decarbonylation and cyclization in N,N-dimethylformamide,the5-imine-2-pyrrolone derivatives was constructed.In addition,the reaction has the advantages of stable raw material properties,cheap availability,simple operation,mild and simple conditions,and good functional group compatibility.We have confirmed that the alkenyl hydrogens in two different products are derived from water through mechanism studies.A possible reaction mechanism was also proposed.(3)Synthesis of(E)-?-carbamoylenamine derivatives through palladium-catalyzed intermolecular oxidative coupling reactions of(Z)-enamines with isocyanides.The products have a unique trans-configuration for the strong intramolecular hydrogen bonds.On the other hand,the coordination anions in the catalytic system have a good regulation effect on the reaction pathway.When a catalytic amount of copper chloride and oxygen is used as the oxidant,the reaction undergo the process of the?-C-H carboxamidation of enamine,when the equivalent copper acetate is used,the reaction proceeds through?-C-H carboxamidation and C=C cleavage/reformation.In addition,the raw materials is easy available and functional group tolerate well,both enamine ester and enaminone are compatible in the catalytic system.(4)Synthesis of functionalized pyrrole derivatives via Palladium-catalyzed tandem cyclizations of aryl oximes with isocyanides.The reaction process involved the activation of unactivated C-O and C(sp~3)-H bond of aryl oximes,one C-N bond and two C-C bonds were constructed in one step.At the same time,we have demonstrated oxime carbamate is the key intermediate and internal oxidant in this reaction and a possible reaction mechanism is proposed.In addition,this transformation also features good functional group tolerance,no use of oxidants,and excellent regioselectivity.(5)Palladium-catalyzed coupling reaction of o-alkynylenyl ethers with isocyanides to construct 2,3-disubstituted benzofurans derivatives.The reaction proceeds under the action of zero-valent palladium,through the oxidative addition of allylic ether oxygen-carbon bonds,cyclization,the insertion of two isocyanides,and the process of hydrolysis and acidolysis to form the middle of 3-benzofurancarboxaldehyde.This intermediate can be converted to a benzofuran compound containing quinoxaline,ketoester,and diketone groups at the3-position under standard conditions.In addition,the reaction does not require the addition of oxidants and the conditions are mild.