Reaction On The Electrochemically Catalyzed Synthesis Of 3,4-dihydroquinolinones And 2-oxazolidinones From Unsaturated Amines

The 3,4-dihydroquinolinones and 2-oxazolidinones skeletons are widely available in natural products and drug molecules with a variety of biological effects which are important structural substrates in clinical drugs and industrial production.Therefore,the development of an efficient,green and environmentally friendly synthesis method is a significant work of research.Electrochemical catalytic synthesis technology achieves the redox process by constant electron transfer,which can avoid the excessive use of expensive or toxic metal catalysts and has environmentally friendly,green and efficient characteristics.In this study,we propose to achieve efficient synthesis of 3,4-dihydroquinolinones and 2-oxazolidinones,respectively,by electrochemical catalysis under mild conditions using unsaturated amines as substrates.It also introduced CO₂ as an important C1 source to achieve the synthesis of 2-oxazolidinones,which provides a new way to realize the development of chemical carbon sequestration technology.The details are as follows:（1）A new efficient and green method for the electrochemically catalyzed selective 6-endo cyclization of o-haloarylacrylamides for the synthesis of 3,4-dihydroquinolinones was established.N-benzyl-N-（2-bromophenyl）methacrylamide was used as the substrate for the model reaction,and the conditions of electrode,current,temperature,reducing medium and reaction time were optimized for this reaction by using the one-factor method.The optimal reaction conditions were:In an undivided electrolytic cell with aluminum as the anode,platinum as the cathode,20 mol%addition of phenanthrene as the indirect reduction mediator,ⁿBu₄NBF₄ as the electrolyte,and DMF as the solvent,the model reaction yield was 82%at a constant current of 5 m A and 50°C for 5 hours of electrolytic reaction.Twenty-two 3,4-dihydroquinolinone derivatives were synthesized in yields ranging from 31%to 85%.The reaction mechanism was thoroughly investigated by cyclic voltammetry,controlled experiments and density flooding theory calculations,and it was determined that the reaction mechanism was:phenanthrene as an indirect reduction mediator to achieve two-electron reduction after dehalogenation,followed by Michael addition to obtain the 6-endo cyclization products;Gram-scale experiments were carried out for the model reaction and 71%yield was obtained,which indicates that the method has potential for application.The established method can selectively achieve the reaction of 6-endo cyclization,which effectively avoids the generation of 5-exo cyclization by-products,and the used phenanthrene is economical and easy to obtain and can be recovered,and the recovery rate is 90%,with the characteristics of excellent selectivity,mild conditions and green.A new efficient and green method was developed for synthesis of tellurium-containing2-oxazolidinones by a three-component reaction of propargylamine/propargylamide,ditellurium and CO₂ under electrocatalysis.Using electro-copper bromide synergistic catalysis,N-benzylpropyl-2-yn-1-amine and diphenyl ditellurium were used as substrates for the model reaction.The conditions of copper,electrode,current,base and reaction time for the reaction were optimized using the single-factor method.The optimal reaction conditions were:Under one atmosphere pressure of pure CO₂,the reaction was carried out with 20 mol%Cu Br₂ as copper catalyst,ⁿBu₄NPF₆ as electrolyte,platinum as anode,stainless steel as cathode,Cs₂CO₃ as base,DMSO as solvent,and a constant current of 20m A for 3 hours at room temperature with optimal yields up to 80%.Thirty tellurium-containing 2-oxazolidinone derivatives were synthesized in 40%-84%yields.A series of controlled experimental studies have proposed the possible reaction mechanism was:propargylamine and CO₂ form carbamate anionic intermediates under the action of base,the ditelluride is oxidized to tellurium radicals at the anode and attacks the carbon-carbon triple bond of the propargylamine,then cyclized to obtain tellurium-containing substituted2-oxazolidinones.The effect of low CO₂ concentration on the reaction was investigated,and the results showed that the product could be obtained in 56%yield even at 30%concentration of CO₂.Also,the antitumor pharmacological activity of the products was investigated.The results showed that 10 final products have excellent inhibition of four tumor cell line types,MDA-MB-231（human breast cancer）,MGC-803（human gastric cancer）,T-24（human bladder cancer）and MIA Pa Ca-2（human pancreatic cancer）.The efficient insertion of telluride was achieved,featuring excellent product pharmacological activity and mild and green reaction conditions.