Radical Arylation And Fluoroalkylselenolation Under Transition-metal-free Conditions

Transition metal-catalyzed cross-coupling reactions are of great significance in chemical science.After decades of research and development,a variety of transition metal-catalyzed coupling reactions have become an indispensable means for the formation of carbon-carbon(C-C)and carbon-heteroatom(C-X)bonds in the field of chemistry.However,the cost of metal catalysts is generally high,especially when high catalyst loading is needed in large-scale industrial production.Some metal complexes are sensitive to water and air.This not only complicates the operation,but also causes security problems.In addition,in the pharmaceutical and materials industries,in order to solve the "transition metal residue problem",some tedious processes and special equipment are often needed to reduce the metal content to a certain level,thus exhausting additional resources.From this point of view,it is particularly important to explore and develop the construction of C-C and C-X bonds that do not depend on transition metals.This dissertation comprises four chapters.The first part summarizes the free radical arylation and fluoroalkylation coupling reactions without the participation of transition metals.Base-promoted homolytic aromatic substitution reaction and oxidative cross-coupling are the main ways of arylation under non-light conditions,as well as the coupling reaction of aryl radicals under the action of light and organic photoredox catalysts.This part also summarizes the free radical fluoroalkylation without the participation of transition metals and the free radical introduction mode of the combination of chalcogenide and fluoroalkyl without transition metals.The second part introduces the radical arylation of benzyl amines with aromatic nitriles under a transition-metal-free condition.2-azaallylketonimine drives single electron transfer under the action of base,activates aromatic nitriles for free radical arylation,and realizes the preparation of diarylmethylamines.This method does not need external light source and transition metal catalyst.At the same time,it has the advantages of simple operation,can be extended to gram scale experiment,and avoids the problem of transition metal residue.The third part describes the photo-promoted fluoroalkylselenolation of 1-enyne without metal participation,which provides a synthetic way for ?-fluoroalkyl selenyl sulfone bienes.Taking advantage of the pyrolysis of trifluoromethyl toluene selenosulfonic acid under light,it was used as a bifunctional reagent to realize the addition reaction of 1,3-enyne.The method has the advantages of mild reaction conditions,wide range of substrates and good tolerance of functional groups.The whole process does not need to use any metal reagents,and the mild and simple operating conditions enable the reaction to be expanded to the gram scale for the preparation of fluoroalkyl selenides with various structures.The fourth part explores the regioselective fluoroalkyl fluoroalkylselenolation of unactivated olefins induced by visible light without metal participation.Eosin Y,a cheap organic photoredox catalyst,was used to introduce two fluoroalkyl groups produced by two different light-induced processes into olefin molecules at the same time.This method has a wide range of substrates and functional group tolerance,and can be used to modify some valuable complex natural products and drug molecules,such as celecoxib derivatives,an inhibitor of cyclooxygenase-2(COX-2).It has a potential application prospect in the construction of compound library.This dissertation mainly introduces some inherent defects of transition metal catalysis and summarizes the free radical arylation and fluoroalkylation coupling reactions without transition metal.This dissertation includes the radical arylation of benzyl amines with aromatic nitriles under a transition-metal-free condition,the photo-promoted fluoroalkylselenolation of 1-enyne without metal participation and regioselective fluoroalkyl fluoroalkylselenolation of unactivated olefins induced by visible light without metal participation.In the future,more novel and practical methodological studies without transition metal participation will be explored,and we will also try to solve the application problems in industrial production and pharmaceutical industry.