Electrochemical Radical-radical Cross-coupling And Radical Addition Reactions Based On Imines

Imines are important intermediates in organic synthesis,which are inexpensive and readily available.Generally,the functionalization of imines requires strict conditions such as metal catalysis or strong base activation.Therefore,it is of great significance to develop a more efficient,simple and environmentally-friendly method for the functionalization of imines.Organic electrosynthesis is a mild and practical method.It can obtain a wider reaction window by simply adjusting the reaction current or reaction voltage,effectively improving the efficiency and range of organic chemical conversion.In the past decade,organic electrosynthesis has been regarded as a unique and effective tool for generating active radicals through electrons and protons transfer on the electrodes.However,it is still a great challenge to harness highly active radicals.In this thesis,a series of radical-radical cross-coupling and radical addition reactions were carried out with imines as the starting materials driven by electrochemical reactions.Herein,we have realized three kinds of novel functional group reactions of imines: cyanoalkylation,arylation and hydroxymethylation of imines,respectively.In the first chapter of this thesis,we briefly introduced the organic electrosynthesis reaction.We also outlined the characteristics of radicals and gave examples of the current ways to obtain α-amino radicals,nitrile alkyl radicals and aryl radicals.Then,we discussed the research status of electrochemical radical reactions using imines as raw materials.In the second chapter of this thesis,we have carried out the electrochemical radical-radical cross-coupling reaction between unactivated imines and alkyl nitriles to access β-amino nitriles.We examined N-benzylideneaniline and acetonitrile as model substrates under various electrochemical conditions,such as the types of solvents,electrolytes,mediators and current.Different types of aromatic imines and alkyl nitriles were suitable for this electrochemical reaction with a broad substrate scope of 46examples(yields up to 91%).Gram-scale experiment and derivative experiments proved the practicability of this electrosynthesis.Based on the mechanism exploration experiments,we proposed the radical-radical cross-coupling reaction between α-amino radicals obtained by imines reduction at the cathode and nitrile alkyl radicals obtained by hydrogen atom transfer promotes the formation of β-amino nitriles.What’s more,this strategy provides a new model for activation of alkyl nitriles to nitrile alkyl radicals.In the third chapter of this thesis,we have explored direct reductive arylation of imines with electron-deficient(hetero)nitriles via electrochemical radical-radical cross-coupling reaction to access benzylic amines.We solved the original problems,including inconvenient operation and the limitation on the types of aromatic nitriles and imines,by the electrochemical reductive radical-radical cross-coupling reaction.This transformation proceeded smoothly under mild conditions with 31 examples(36–96%yields),covering various types of aromatic imines,aliphatic imines and electron-deficient(hetero)nitriles.The mechanistic studies proved that the electrochemical reaction produces α-amino radical and aryl radical at the cathode simultaneously,and the coupling of the carbon-carbon bond provides the target product.In the fourth chapter of this thesis,we successfully prepared β-amino alcohols by electroreductive radical addition reaction of imines with ketones.Using electrons as traceless reductants,we successfully synthesized 24 β-amino alcohol derivatives at a yield of 50-89% under open air conditions at room temperature.Chain ketones,cyclic ketones and aromatic aldehydes were good coupling partners of imines.Cyclic voltammetry experiments,radical tapping experiments and electron paramagnetic resonance experiments showed that α-amino radical is the key intermediate of the reaction.Besides,the divided-cell electrolysis experiment confirmed the role of triethylenediamine as a sacrificial reducing agent.Due to the significant difference in reduction potential between imine and ketone,we speculate that the α-amino radical obtained by the cathodic reduction of imine undergoes an addition to the C=O bond of ketone,and the further reduction at the cathode provides the desired product.