Pd-catalyzed C-H Functionalization Of Quinoline And The Sonogashira-type Coupling In Transition-metal-free System

Biaryls constitute the basic skeleton of many agrochemicals,pharmaceuticals,natural products,organic functional materials,ligands,and organic synthetic intermediates.The biaryl C-C bond-forming reactions through two aromatic units is the most important subjects in organic chemistry and have attracted great attention.Quinoline,as an important skeleton motif involved in many biologically active compounds and functional materials,was often employed for the formation of diversiform heterocycles.As a consequence,the selective functionalization of quinolines in the different active sites has received considerable attention over the past decades.In the cases reported,transition-metal catalyzed C-H activation into C-C bond formation,as one of promising approaches,makes the inactive sites of quinolines more simple and easy to be tailored.On the basis of the above research,we have developed a novel protocol for synthesis of 3-arylated quinoline derivatives using silver carbonate(Ag2CO3)and dioxygen(O2)as the oxidants.In this method,quinolines acting as parent reagent react with arenes under Palladium acetate(Pd(OAc)2)catalysis along with1-adamantane carboxylic acid(Adm).Beyond that,a relevant mechanism is proposed.This strategy provides a simple and efficient method for quinoline C3-H bond activation.The resulting C-3 arylated quinolines can be used as building blocks for synthesis of bioactive alkaloid natural products and drug molecules.We then discoverd an interesting method of Pd-catalyzed direct homocoupling of unactivated quionlines/heterocyclic aromatic bromides.In this method,KF was found to be an essential factor in achieving high activity and selectivity,allows2,2'-biquinolines and bipyridines obtained in high yields.In this method,prefunctionalization is not required,mild reaction conditions is used,and a relevant mechanism via double C-H activation is proposed,our protocol offer a new strategy for organic synthesis.Beyond that,We developed an efficient transition metal-free(PPh3/base)system for the cross-coupling reactions of heteroaryl halides with terminal alkynes/Phenylboronic acid.Various phenylethynyl heterocycles and phenyl heterocycles were achieved in excellent yields.The mild and economical reaction conditions and high reactivity deliver promising applications in drug discovery and functional materials.