| Heteroaromatics such as benzothiazoles and quinolines are commonly found in a variety of marketed drugs,natural products and functional materials.Late-stage modification methods for the construction of N-heteroaromatics have always attracted the attention of organic synthesis researchers.Traditional methodology to hydroxyalkylated N-heteroaromatics was mainly relied on carbonyl nucleophilic addition by preformed highly active heteroaryl metal reagents,but this method has poor functional group compatibility due to harsh reaction condition.In recent years,photoredox chemistry and electrochemistry have attracted broad interest for the development of green and sustainable synthesis.In our work,the photocatalytic,electrocatalytic and electrophotocatalytic Minisci reactions were reviewed.It was found that alkylation,acylation and arylation Minisci reactions were widely reported,but Minisci hydroxyalkylation reactions received less attention.The constructive merging of photochemistry and electrochemistry is the key for the success of this atom-economical Minisci hydroxyalkylation method.Sodium decatungstate(Na DT)and aldehydes are used to obtain acyl radicals through hydrogen atom transfer,and acyl radicals undergo Minisci reaction with N-heteroaromatics to obtain acyl product under electrolysis conditions.On the cathode,the acyl groups are reduced to hydroxyl groups to generate hydroxyalkylazaarenes.Under the promotion of current,the reaction is redox neutral as a whole without adding oxidant.The optimal hydroxyalkylation reaction conditions were obtained by studying the effects of solvent,acid,aldehyde dosage and electrode material on the reaction.Deuterium/hydrogen exchange experiments,radical capture experiments,reaction monitoring,and intermediate conversion experiments were carried out to explore the reaction mechanism,and the results supported the assumed reaction mechanism.The reaction performed well in 5 mmol amplified synthesis and subsequent transformation,reflecting the effectiveness and practicality of hydroxyalkylation reaction.In conclusion,a Minisci reaction using aldehydes as radical precursors with benzothiazoles and quinolines was developed under mild conditions,which can effectively introduce hydroxyalkyl groups on various benzothiazoles and quinolines.It has the advantages of good tolerance of functional groups,scalable synthesis and good atom economy. |
