Dynamic Kinetic Cross-electrophile Arylation Of Benzyl Alcohols By Nickel Catalysis

Transition metal-catalyzed coupling reactions have been successful in the precise construction of carbon-carbon bonds and carbon-heterobonds.Halogenated hydrocarbon is usually used as the basic raw material to synthesize all kinds of carbon chemical bonds.At present,the effective utilization of C-O bond electrophiles mainly focuses on the coupling reactions involving Csp~2-O bond.Because of the high energy barrier,Csp~3-O bond is not easily activated,and the related research on Csp~3-O bond is still relatively lagging behind.As a kind of chemical raw materials with wide existence,low price and stable property,alcohol compounds have great research value for their high added value transformation.In the past decades,great progress has been made in coupling reactions based on Csp~3-O bond participation,extending from classical coupling to reductive coupling,which not only expands the range of reaction substrates,but also improves reaction conditions and enhances functional group compatibility.This paper focuses on the nickel catalyzed coupling reaction involving Csp~3-O bond,which is mainly discussed in the following three parts:Chapter 1:This chapter mainly introduces the research status of Csp~3-O bond activation from four aspects.We have divided this chapter into four modules:the carbon-oxygen bond activation of allyl alcohols,propargyl alcohols,benzyl alcohols,and alkyl alcohols and their derivatives.In each module,the development and research status of Csp~3-O bond activation were discussed according to the suitability of substrates and reaction mechanism,starting from ester,ether and alcohol(activation difficulty from easy to difficult).Chapter 2:In this chapter,the deoxyarylation reaction of benzyl alcohol is studied based on the dynamic kinetics strategy.In this paper,a series of structural fragments of diaryl methanes were synthesized using benzyl alcohol as raw material,dimethyl oxalate as additive and aryl trifluoromethesulfonate as aryl reagent,and the concept of dynamic mechanism was first proposed.This method has great application value,not only can be used in the synthesis of drug molecules,but also can realize the modification of bioactive molecules and peptide compounds.The results of in situ NMR experiments show that transesterification is initiated by low metal and catalyzed by alkali.Chapter 3:In this chapter,we continue to use the dynamic kinetics strategy to synthesize diaryl methane compounds using aryl halides as arylating reagents.The application range of this method was improved through the study of substrate expansion and synthesis application.The mechanism experiment showed that benzyl radical was formed in the reaction.The possible reaction mechanism was proposed by means of intermediate experiments.It provides a new idea for transition metal catalytic activation of inert Csp~3-O bond.