Cheap Metal Copper-Promoted Monoselective C-H Bond Alkynylation Of Ferroceneamide

Due to its special metallocene structure,ferrocene and its derivatives have found many applications in the area of material science,medicinal chemistry as well as in organic synthesis.Traditionally,electrophilic aromatic substitutions such as Friedel-Crafts type reactions,or organometallic reagent ortho-metallization are commonly often employed to generate ferrocene derivatives.However,these traditional reactions have many restrictions,such as anhydrous and anaerobic.Also,the reaction process will produce a large amount of by-products,which will cause serious environmental pollution.Therefore,the transition metal-catalyzed hydrocarbon activation reaction with the advantages of high atom utilization,simple and direct reaction,and environmental friendliness has become the key to solving the above problems.Especially in recent years,the progress made by chemists in the cheap metal catalyzed hydrocarbon activation reactions has made it possible to synthesize ferrocene derivatives efficiently.Herein,we discuss the study on the highly mono-selective synthesis of ferrocenyl alkynes-Cu(I)complexes via Cu-promoted8-aminoquinoline-directed ferrocene C(sp~2)-H bond activations,which can be divided into three parts as follow:(1)The transition metal-catalyzed ortho-C-H activation functionalization reaction of ferrocene and its derivatives,and the background,significance and research contents were introduced,respectively.(2)We attempted to synthesize alkynyl ferrocenes vi a the copper-promoted8-aminoquinoline-directed C-H alkynylation reaction between ferrocenes and terminal alkynes,and its product structure was determined to be a ferrocenyl alkyne-Cu(I)π-complexes by ~1H NMR spectrum,high-resolution mass spectrom and X-crystal diffraction.By screening parameters such as promoters,solvents,bases,temperature and time,the optimal conditions for the reaction were explored.And then,the substrates ranges of the reaction were further expanded under the optimal conditions.The monovalent copper ion of the alkyne-copper complex was removed by ammonia treatment to obtain the final ferrocene monoalkynylation product.(3)According to relevant literature reports and mechanism experiments,a plausible mechanism of the reaction was proposed.First the reaction is initiated by the C–H cyclocupration process of N-(quinolin-8-yl)ferrocene-1-carboxamide 1 with copper salt to afford Cu(Ⅱ)-complex,which subsequently undergoes oxidation by another copper acetate to give Cu(Ⅲ)-complex.Subsequent ligand exchange of Cu(Ⅲ)-complex with metal phenylacetylide which is formed in situ forms alkynyl copper intermediate.Finally,alkynyl-Cu(Ⅰ)π-complex is formed through the reductive elimination of alkynyl copper intermediate.