Synthesis Of 1,4-dihydropyridines Via Iodine-mediated Annulations Of N-cyclopropylenamine

1,4-Dihydropyridines(1,4-DHPs)are an important class of six-membered Nheterocyclic compounds.Their derivatives can be used as calcium ion channel antagonists for the treatment of cardiovascular diseases including hypertension,and they also possess antibacterial,anti-oxidant,anti-tuberculosis,anti-cancer biological activities.These compounds display aggregation-induced fluorescence emission properties and mechanochromism properties,and can be used as fluorescent probes to detect the concentration of metal ions.1,4-DHPs also have a wide range of applications in organic synthesis as reductants.To date,1,4-DHPs are mainly prepared via two-or multi-component reactions or synthesized using pyridines as substrates.Therefore,the development of new reactions for 1,4-dihydropyridine synthesis are of great significance for research in the fields such as medicinal chemistry.Cyclopropylamine derivatives have been widely employed in the construction of Ncontaining skeletons,as they are more reactive due to the ring strain of the cyclopropane in their structures.In this dissertation,a new synthetic strategy for the formation of 1,4-dihydropyridines from N-cyclopropylenamine has been established.Under the action of cheap and easily available molecular iodine,the Ncyclopropylenamine substrate undergoes cyclopropyl ring opening and further intermolecular cyclization reaction to produce 1,4-DHP product.This reaction has good substrate applicability,and twenty-four 1,4-dihydropyridine products were successfully synthesized.The features of the present reaction include simple operation,mild conditions,no use of transition metals,and gram-scale synthesis.Through further research on the conversion reactions of 1,4-DHP products,a series of nitrogencontaining heterocyclic compounds can be synthesized.Upon the formation of 1,4DHPs,the reaction system was directly treated with DDQ and the aromatization pyridines were formed in a one-pot manner.In the presence of potassium carbonate,1,4-DHP products could be further transformed into azabicyclic compounds and their corresponding pyridine products.The structures of 1,4-DHP,pyridine,azabicyclic compound were further confirmed by X-ray crystallography.