Construction Of Pyrrole,Thiazole And Quinazoline Compounds By Palladium Catalyzed Cascade Reactions

Nitrogen-containing heterocyclic compounds are a very large part of organic compounds with a wide range of biological activities.They are key components in many fields,such as total synthesis of natural products,pharmaceutical chemistry and multifunctional materials.In particular,pyrrole,thiazole and quinazoline compounds are widely used due to their unique pharmacological activities and chemical properties.Therefore,their synthetic methods have high development value.Without separation of intermediates,palladium catalyzed cascade reactions can afford products with higher yield than traditional methods,which can also easily and efficiently construct complex nitrogen-containing heterocycles.Based on analysis of a large number of literatures,the methods of constructing 1H-pyrrole-3-carbonitriles,2,4-disubstituted thiazoles and 4-arylquinazolines were developed from cyano compounds and arylboronic acids by palladium catalyzed cascade reactions.This paper is divided into four parts:The first part mainly introduces the biological activities and application of pyrrole,thiazole and quinazoline compounds.In the second part,the method of constructing 1H-pyrrole-3-carbonitriles by palladium catalyzed cascade reaction under ligand-free reaction conditions is introduced.The materials are2-(2-oxoalkyl)malononitriles and arylboronic acids.The reaction process involves palladium catalyzed C(sp)-C(sp~2)coupling reaction and intramolecular cyclization.This method features high efficiency,ligand-free reaction conditions,easily available raw materials,simple operations and tolerance of various substrates.In order to verify the substrate scope,17 compounds were synthesized with the yields of 75%-94%.In the third part,a series of 2,4-disubstituted thiazoles were synthesized fromα-thiocyanomethyl ketones and arylboronic acids catalyzed by palladium.The synthesis was carried out efficiently through palladium catalyzed C(sp)-C(sp~2)coupling reaction and intramolecular cyclization under ligand-free reaction conditions.As forα-thiocyanomethyl ketones,this reaction is applicable for both aliphatic and aromatic substrates.14 compounds were synthesized with the yields of 60%-88%.The fourth part mainly introduces the strategy of constructing 4-arylquinazolines from2-aminobenzonitriles,triethyl orthocarboxylates and arylboronic acids by palladium catalyzed three components one-pot method,which features simple operations,high yield,and easily available raw materials.Therefore,this method provides an effective way for the synthesis of quinazoline lead compounds.Moreover,this reaction features broad substrate scope,and it can be expanded to gram scale.24 compounds were synthesized,and the plausible mechanism of this reaction was proposed based on control experiments.