Multicomponent Reaction Synthesis Of Spirocyclic And Heterocyclic [3.3.3] Spiral Alkane Compounds

The target of this paper is to study the synthesis of functionalized heterocyclic spiro compounds and heterocyclic[3.3.3]propellanes. On the basis of a summary of the synthesis and development of these compounds and a combination of our recent research work, we successfully developed multicomponent domino reactions containing cheap and readily available starting materials to synthesize a wide range of biological and pharmaceutical active heterocyclic spiro compounds and heterocyclic[3.3.3]propellanes under mild conditions.1. The domino reactions of isatin, malononitrile (ethyl cyanoacetate), primary amine, methyl propiolate in ethanol in the presence of triethylamine showed interesting molecular diversity. When malononitrile participated in the reaction, a series of spiro[indoline-3,4’-pyridines] were obtained in good yields. Under the same condition, the reactions of ethyl cyanoacetate afforded different result:Anilines bearing with p-chloro, m-chloro or p-bromo groups afforded spiro[indoline-3,4’-pyridines] as main products. On the other hand,p-methoxyaniline and p-methylaniline gave spiro[indoline-3,4’-pyridinones] as main products. Benzylamine and2-phenylethylamine could also be used in the domino reaction to give the corresponding spiro[indoline-3,4’-pyridinones]. All of the38new compounds have been identified by IR, NMR LC-MS, HRMS spectra, and the single crystal structures of three products were determined by X-ray diffraction method. 2. The domino reactions of ninhydrin, malononitrile, and cyclic enaminones derived from condensation of cyclic1,3-dicarbonyl compounds with primary aromatic amines in ethanol in the presence of triethylamine gave diverse heterocyclic compounds. When5,5-dimethyl-1,3-cyclohexanedione (1,3-cyclohexanedione) was used in the reaction, the novel heterocyclic [3.3.3]propellanes were synthesized in satisfactory yields. When1,3-cyclopentadione was utilized in the reactions, the functionalized spiro[cyclopenta[b]pyridine-4,2’-indenes] were obtained as main products. We successfully synthesized23new heterocyclic compounds, which were identified by IR, NMR, HRMS spectroscopic methods. The single crystal structures of three products were determined by X-ray diffraction method.3. The three-component reaction of isatins, N-substituted benzimidazole and dialkyl actylenedicarboxylates afforded benzimidazol[2.1-6][1,3]oxazine spirooxindoles in good yields. The similar complex spiro compounds were also obtained by replacing N-substituted isatin with acenaphthenequinone. Under similar conditions, the multicomponent reactions of N-substituted isatins, malononitrile, N-substituted benzimidazole and dialkyl actylenedicarboxylates unexpectedly resulted in a mixture of diastereoisomeric pyrido[1,2-a]benzimidazole spirooxindole derivatives. Totally,36new spiro compounds were synthesized and their structures were characterized by IR, NMR, HRMS methods. Five single crystal compounds were determined by X-ray diffraction.