Studies On The Alkyltion Of Inert C-F Bond And Diaryl Amines Synthesis Via Reductive Coupling Of Nitroarenes

Over the past few decades,transition-metal catalyzed cross-coupling reaction has emerged as a powerful C-C bond forming technique thus has attracted considerable attention by both academia and industry.While generally,the relatively highly reactive species,such as organic halides and/or sulfonates are employed.As is well known that C-F bond,which has a bond dissociation energy as high as 126 Kcal/mol,is the strongest C-based chemical bond.Since the introduction of fluorine atom（s）into the organic molecules often causes the change on physical and chemical properties,therefore,recently has seen rapid development of various efficient synthetic methods toward the fluorinated molecules and their application in different areas,e.g.,material science,pharmaceutical industry,as well as agrochemicals.Consequently,different types of fluorinated molecules with certain quantity have been enriched in nature,while causing the metabolism issue in nature due to the inertness of these fluorinated molecules,thus leading to unexpected side effect on the ecological environment.Moreover,the development of methodologies based on the inert C-F bonds activation lagged far behind due to their formidable challenge.Not surprisingly,the development of methodology toward the chemoselective C-F activation/transformation is significant to not only the sustainable development of the environment,but also the development of corresponding theory from understanding the reactivity of the inert chemical bonds.The wide application of diarylamines in various areas such as pharmaceuticals,agrochemicals,dyes and electronic industry has promoted the development of enabling methods.A close look at the literature precedents revealed that,among all the developed methodologies,downstream intermediates such as aryl amines,aryl halides or aryl boronic acids were inevitably used.Not surprisingly,the operationally simple methods toward the use of accessible upstream aromatic compounds as the starting materials are highly desirable.As the indispensable thus widely used synthetic intermediates,the upstream nitroarenes can be obtained by a direct nitration reaction.As such,an efficient synthetic protocol en route to diarylamines with the use of nitroarenes as the starting material while concurrently avoiding the use of downstream intermediates such as aryl amines,aryl halides or aryl boronic acids,is of not only academically important but also industrially applicable.In view of the abovementioned research background,this thesis includes the following contents:The first chapter mainly focuses on the introduction of methodologies development based on the inert C-F bond activation strategy and recent advancement on the diaryamines synthesis.Then the research projects,including the defluorinative alkylation and the construction of diarylamines based on reductive coupling of nitroarenes,were subsequently proposed.The second chapter mainly describes the reaction development of nickel-catalyzed alkylation of aryl fluorides,vinyl fluorides and vinyl gem-difluorides with trialkylaluminums.Interestingly,the reaction can proceeds chemoselectively when both inert C-F bond and C-O bond are present in the substrate,keeping the C-O bond intact.While intriguingly,all C（sp²）-F bonds,including aryl and Alkenyl C-F bonds undergo the defluorinative alkylation completely.This method provides a de novo catalytic strategy for the synthesis of alkylated analogues from the fluoroarenes and fluoroalkenes via chemoselective C（sp²）-F bond scission,facilitating the investigation of structure-activity relationship of fluorine-containing drugs.The third chapter mainly dictates the investigation of reductive coupling of nitroarenes.Systematic screening of reaction conditions with p-nitrotoluene as a model substrate revealed that Pd（acac）₂ is a suitable catalyst,along with the use of Brettphos as a supporting ligand,B₂（pin）₂ as a enabling reductant,Cs₂CO₃ as the base,18-Crown-6 as an additive,and 1,4-dioxane as the optimum reaction media under 130 ^oC,the reaction proceeded smoothly and afforded the reductive coupling di-p-tolylamine in 90%isolated yield.This reaction characterizes by its good functional group tolerance,constituting an appealing novel method for the construction of value-added diarylamine derivatives from lower-order nitroarenes.