Domino Reaction For Construction Of Nitrogen-and Oxygen-containing Heterocyclic Medicinal Molecules

The nitrogen-and oxygen-containing heterocyclic compounds such as pyridine and pyran are widely found as privileged framework in many natural products,chemical drugs and biologically active substances as well as various materials.Therefore,the effcieint synthesis of pyridine and pyran derivatives has drawn great attention of chemists.The domino reaction has the advantages of high efficiency,high selectivity,simple isolation and high atomic economy.In this paper,a series of highly efficient,highly selective,high atomic economic domino reactions were successfully designed with highly reactive 2-arylidene-1,3-indanedione and 5-arylidene-l,3 barbituric acid as the key substrates.Thus,several types of potentially phamiaceutically active nitrogen-and oxygen-containing heterocyclic compounds were successfully synthesized in high yields.1.Lewis acid BF3·OEt2 promoted cycloaddition reaction of 2-arylidene-l,3-indanediones with ?-enamino esters generated from addition of arylamines to dimethyl acetylenedicarboxylate to give sixteen densely substituted 1,4-dipheny]-4,5-dihydro-1H-indeno[1,2-b]pyridines in satisfactory yields.When 2-isatylidene-1,3-indanediones were employed under same conditions,the one-pot reaction afforded the thirteen spiro[indeno[1,2-6]pyridine-4,3'-indolines]in high yields.On the other hand,the nine unusual l,2-diphenyl-2,5-dihydro-1H-indeno[l,2-b]pyridines can be obtained in moderate to good yields in the four-component reaction of arylamines,dimethyl acetylenedicarboxylates,aromatic aldehydes and 1,3-indanediones.All products were characterized by IR,1H NMR,13C NMR,HRMS spectroscopy.The single crystal structures of five products were determined by X-ray diffraction method.2.The domino aza-/oxa-hetero-Diels-Alder reactions of ?,?-unsaturated N-aryl-or N-benzyl aldimines with two molecular 5-arylidene-l,3-dimethylbarbituric acids in methylene dichloride at room temperature afforded unique spiro[pyrido[3'2':5,6]pyrano[2,3-d]pyrimidine-7,5'-pyrimidines]in high yields.This reaction has high diastereoselectivity and only one diastereoisomer was produced in the reaction.All thirty-two products were characterized by IR,1H NMR,13C NMR,HRMS spectroscopy.The single crystal structures of two products were determined by X-ray diffraction method.3.The unprecedented reaction of ?,?-unsaturated N-arylaldimines or ?,?-unsaturated N-benzylamine with two-molecule 2-arylidene-1,3-indanediones in a dry acetonitrile at 60?without catalysis under nitrogen protection afforded unique spiro[indene-2,3'-indeno[2',1':5,6]pyrano[2,3-6]pyridine]in good yields and with high diastereoseelctivty.The reaction was believed to proceed with domino aza-/oxa-hetero-Diels-Alder reactions,in which 2-arylidene-l,3-indanediones not only played as reactive dienophiles,but also acted as active oxa-l,4-dienes.On the other hand,catalyst-free domino reaction of ?,?-unsaturated N-arylaldimines with 2,2,-(arylmethylene)bis(1,3-indenediones)afforded a mixture of two diastereoisomeric dispiro[indene-2,1'-cyclohexane-3',2"-indene]derivatives in satisfactory yields.All prepared 54 products were characterized by IR,1H NMR,13C NMR,HRMS spectroscopy.The single crystal structures of four products were determined by X-ray diffraction method.