Two New Synthesis Methods For 1,4-Dihydropyridine

1,4-Dihydropyridine is a kind of very important nitrogen-containing heterocyclic compound with good physiological activity and has a wide range of applications in biology,medicine and organic catalysis.The most important application is to treat angina pectoris,arrhythmia and other diseases as calcium antagonists in clinic,and it is also a nutritional additive to promote the growth of livestock and poultry in agriculture.In addition,in organic synthesis,it is often used as a hydrogen proton donor or alkylating reagent to participate in the reaction.Therefore,the synthesis of 1,4-dihydropyridine is still one of the research hotspots.In view of the research progress in the synthesis of 1,4-dihydropyridine,it was found that most of the C4 position of its parent structure was derived from aldehydes orα,β-unsaturated carbonyl compounds,while the construction of 1,4-dihydropyridine based on C(sp~3)-H bond substrates(such as alkylamine,ether,alcohol,etc.)as C4sources still faces challenges.Therefore,developing a series reaction based on C(sp~3)-H bond substrates to construct more diverse 1,4-dihydropyridine compounds is a very meaningful workThis paper includes the following three parts:(1).The research progress in the construction of 1,4-dihydropyridine compounds in recent years is reviewed,mainly through the classification of different C4 source types(aldehydes,α,β-unsaturated carbonyl compounds).(2).1,4-Dihydropyridine compounds were synthesized by copper catalytic oxidation[1+2+1+2]cascade cyclization.4-phenyl-1,4-dihydropyridine was successfully constructed by using benzylamine as C4 source and N,N-dimethyleneamine ketone under copper catalytic oxidation.The reaction substrate has a wide range of application,raw materials are easy to obtain,operation is simple,and molecular oxygen is used as oxidant.(3).1,4-Dihydropyridine compounds were synthesized by Fe-catalyzed oxidation cascade cyclization of cyclic ether and enamine ketone.4-alkyl-1,4-dihydropyridine was successfully constructed by using cyclic ether as C4 source and N-aryl enamine ketone under Fe-catalyzed oxidation.The reaction solvent was involved in the reaction,the substrate was widely applicable,the conditions were mild,and the operation was simple.