Palladium-catalyzed Divergent Imidoylative Cyclization Of Multi-functionalized Isocyanides

Isocyanide is a special bivalent carbene compound with the general formula R-NC.It is widely used in synthetic chemistry as a highly reactive synthon such as free radical reaction,multi-component reaction and so on.It can also participate in transitionalmetal-catalyzed reactions,especially palladium-catalyzed insertion reactions,and has developed a lot of synthesis methods.In recent years,palladium-catalyzed insertion involving isocyanides in organic synthesis has become a promising research field.Organic heterocycles,especially nitrogen-containing heterocycles,play an important role in modern drug research and development.The construction and modification of nitrogen-containing heterocycles are of vital importance,which are ubiquitous in natural products,pharmaceutical chemistry,and material sciences.In this regard,divergent heterocycles could be accessed by conditions-controlled selective reactions from the same molecules,which could facilitate the assembly of complex compounds.Because of the adjustable R group of isocyanides,an effiffifficient access to N-heterocycles by the strategy of functionalized isocyanide was successfully developed,in which multiple atoms(including both nitrogen and carbon atoms of isocyanide)were introduced to the formed cycle,demonstrating the advantage over carbon monoxide-participated carbonylation reactions.In Chapter 1,the properties,structural characteristics and development of isocyanides were reviewed.And we also focus our attention on the recent progress of the construction of nitrogen-containing heterocyclic compounds by palladium-catalyzed insertion reaction involving isocyanides.In Chapter 2,a palladium-catalyzed tunable imidoylative cyclization of multi-functionalized isocyanides to construct diverse imine-containing heterocycles has been developed.Oxazol-5(4H)-one derivatives were obtained exclusively when allyl-2-benzyl(or allyl)-2-isocyanoacetates were used in the reaction with aryl triflates as electrophiles,whereas cyclic ketoimines were generated in the presence of aryl iodides with the allyl ester group remaining unreacted.The cyclic ketoimine scaffolds could be accessed as well with isocyanides bearing an ethyl ester group with aryl triflates.The reactions proceeded smoothly under mild conditions with a wide functional group tolerance.In Chapter 3,a intramolecular imidoylative Heck reaction was developed to prepare 1,4-diazaphrone derivatives by functionalized isocyanides bearing alkenes.In addition,the reaction has the advantages of stable raw materials,simple operation,mild and simple conditions and excellent functional group tolerance.The product can be further transformed into kinds of valuable functional molecules.