Synthesis Of Vicinal Diamines And Vicinal Diols Via Electrochemical Pinacol Coupling

Vicinal diol and vicinal diamine scaffolds widely exist in natural products,drugs and chiral catalysts.The reductive coupling reaction of aldehydes,ketones and imines,also known as pinacol coupling reaction,is an important means to synthesize vicinal diol and vicinal diamine compounds.The traditional pinacol coupling reaction generally uses more than stoichiometric strongly reducing elemental metal or low valent metal salts as reducing agent,such as Mg,Zn,Yb,Sm I₂,Ti Cl₃,etc.However,due to the relatively harsh reaction conditions,the chemical and stereoselectivity of the reaction is often difficult to control,and the scope of the reaction substrate is quite limited.At the same time,this reaction produces a large amount of metal waste,resulting in low atom economy and difficult product purification.Electrochemical reduction method uses clean electrons as reducing agent without external chemical reducing agent,and selectivity of the reaction can be further optimized by means of current and voltage regulation,use of electrocatalyst,etc.It is a kind of efficient and green synthesis strategy.Therefore,it is of great research value to realize the electrochemical pinacol coupling reaction to synthesize vicinal diamine and vicinal diol compounds.In this thesis we described the pinacol coupling reaction of aromatic aldimines and aromatic aldehydes under electrochemical conditions.Using imine as starting material,we screened the electrode materials（anode and cathode）,solvent,current density,supporting electrolyte,Lewis acid additives and other variables in the reaction optimization.After that,we tried to directly electrolyze N-benzylidene aniline by in-situ formation of aniline and benzaldehyde,omitting the cumbersome procedure for the preparation of imine,and successfully obtained the corresponding vicinal diamine in 92%yield.Under the optimal conditions,we explored the scope of substrates for electrochemical pinacol coupling of imines,and found that the reaction conditions were suitable for aromatic aldehyde imine substrates containing various substituents,and the target coupling product could be obtained in medium to excellent yields.Similarly,we re-screened the conditions using aromatic aldehydes as substrates,expanding the substrate scope of electrochemical homo pinacol coupling reaction of aromatic aldehydes to synthesize vicinal diol compounds.We also studied the mechanism of electrochemical pinacol coupling reaction of imines in detail.By free radical inhibition experiment,we found that the reaction experienced a free radical process is involved.In the divided electrolytic cell experiment,we found that Mn（III）salt can reoxidize the over-reduced product benzylamine to imine without affecting the reaction product vicinal diamine.Cyclic voltammetry experiments suggested that Mn（II）salt can effectively reduce the first reduction potential of imines,which is beneficial to the reduction of imines to imine radical anions.Based on these results,we proposed a plausible mechanism for the electrochemical pinacol coupling reaction of imines,in which Mn（III）additive played a key role in promoting the reaction.In summary,we developed a novel electrochemical homo pinacol coupling of aromatic aldimines,aromatic aldehydes and ketones to synthesize vicinal diamines and vicinal diols.The reaction is highly efficient and environmentally friendly,which can be completed under mild conditions with simple operation.