Electrochemical Benzylic C(sp~3)-H Isothiocyanayion

In the past decade,the high emphasis on resources has made electrochemistry flourish,so the combination of electrochemistry and organic synthesis has become a direction considered by many chemists.The redox reaction is carried out by using an anode and an anode instead of an expensive catalyst,and the compound is activated by the gain and loss of electrons.This method changes the problems of low utilization of traditional organic chemistry resources,cumbersome operation,and great harm to the environment,and brings new ideas for the selective reaction of different sites of inert compounds.As a kind of alkane,benzyl compound has many special properties because it is connected with benzene ring,but the general method to break the carbon-hydrogen bond at the benzylic position is usually to add a large amount of oxidant,which is not in line with the concept of green chemistry.Moreover,the functionalization reaction of the benzylic position often requires pre-functionalization first,and it is rarely possible to directly react through hydrocarbon cleavage.To solve these problems,the electrocatalytic activation of carbon-hydrogen bonds at the benzylic position has attracted extensive attention.Electrocatalysis is an important strategy to solve the direct activation of C(sp~3)-H at the benzylic position,which can use electron transfer to break C-H bonds without guiding groups.This method reduces the influence of the pka value,so that some compounds with a large pka value can also participate in the reaction through the homolytic cleavage of the carbon-hydrogen bond.Although isothiocyanate compounds are widely used,the methods for synthesizing such compounds are all catalyzed by excessive toxic reagents.Especially for benzyl isothiocyanates,the general isothiocyanate reaction is easier to react with the benzene ring than the benzylic position.This makes it difficult to selectively carry out isothiocyanation due to the specificity of its location.Based on the above reasons,our research on electrocatalytic benzylic C(sp~3)-H isothiocyanate was initiated.Selective C(sp~3)-H isothiocyanation represents a significant strategy for the synthesis of isothiocyanate derivatives.Herein,an electrochemical benzylic isothiocyanation in a highly chemo-and site-selective manner under external oxidantfree conditions was reported.The high chemoselectivity is attributed to the facile in situ isomerization of benzylic thiocyanates to isothiocyanates.Notably,the method exhibits high functional group compatibility and is suitable for late-stage functionalization of bioactive molecules.In this paper,33 products with different types of functional groups such as electron withdrawing,electron donating,and halogen,among were synthesized and 7 drug molecule analogs were successfully obtained.The structures of the synthesized compounds were all characterized by ~1H NMR,¹³C NMR,and HRMS.Meanwhile,the possible mechanism of this reaction is proposed through various control experiments:C(sp~3)-H loses two electrons at the anode benzylic position and the C-H bond is broken to form a benzyl cation,the benzyl cation combines with the SCN anion in the system to obtain the intermediate thiocyanate.The thiocyanate intermediate continues to undergo isomerization in anodization to convert to isothiocyanate products.