Study On The Cyclization Of Isocyanides Under The Action Of Transition Metals

Isocyanides compounds are high-activity organic molecules that play an indispensable role in organic chemistry.It can participate in a variety of reaction types including multi-component reactions,radical reactions,and insertion reactions.The cyclization reactions involving isocyanides under the action of transition metals have received widespread attention in recent years.The variety of valencies of each metal make it a lot of changes in the cyclization reaction of isocyanides,which greatly improves the diversity of such reactions.Especially in terms of insertion reactions and radical reactions,transition metals show excellent properties.On the one hand,a variety of transition metals can coordinate with isocyanide groups and achieve insertion reactions.On the other hand,transition metals can promote the generation of radical precursors and cyclization reactions with isocyanides.In the past few decades,organic workers have used the cyclization reaction of isocyanides under the action of transition metals to construct a wide range of nitrogen-containing heterocyclic compounds,including:five-membered nitrogen-containing heterocyclic compounds(pyrrole,imidazole,oxazole,triazole,indole),six-membered nitrogen-containing heterocyclic ring(pyridine,quinoline,isoquinoline,quinazoline,phenanthridine),seven-membered nitrogen-containing heterocyclic ring and other types nitrogen-containing cyclic compounds.These nitrogen-containing heterocyclic compounds exist widely in organic compounds(natural products,drug molecules and so on).Therefore,the reaction involving isocyanides under the action of transition metals has become one of the hot topics in organic chemistry research in recent years.In this thesis,by using a variety of isocyanides to participate in the cyclization reaction under the action of matching transition metals,nitrogen-containing heterocyclic compounds with complex and diverse structures were successfully synthesized.The specific research work is divided into the following three parts:In the first part,we studied the cyclization of palladium-catalyzed carbon dioxide and 2-iodoarylamine with isocyanides,and synthesized a series of quinazoline dione derivatives with moderate to excellent yields.The reaction can efficiently utilize atmospheric carbon dioxide under the conditions of environmental protection,incorporation of two C1 building blocks in the reaction,and conforms to the development direction of green chemistry.In the second part,the cycloaddition reaction of active methylene isocyanides with aryl isocyanides and thiosulfonate under copper catalysis was achieved,and efficiently synthesized sulfur-containing tri-substituted imidazoles.In the reaction,besides catalyzing the cross-cyclization reaction of aryl isocyanides and active methylene isocyanides,the copper salt also achieved the function of activating thiosulfonate and cleverly constructed the C-S bond,avoiding the use of special odor containing sulfur reagent.This strategy provides a concise and efficient method for the synthesis of polysubstituted imidazoles while enriching the research on the cross-cyclization reaction of two different isocyanides.In the third part,we use manganese acetate dihydrate to promote the reaction of phenyl radicals produced by phenylboronic acid with two poly-substituted functional aryl isocyanides to rapidly build a series of pyrroloporphine compounds and pyrroloporoisoquinoline compounds.These reactions provide a good method for the synthesis of fused heterocyclic compounds.Two kinds of multi-substituted functional aryl isocyanides:3-phenyl-2-cyanophenyl isocyanide and 3-alkynyl-2-cyanophenyl isocyanide were designed and synthesized for the first time by us.These new functional isocyanides complete the types of functional aryl isocyanides.