The Cycloaddition Reaction To Construct Quinone Structure Polyheterocycle Compounds Induced By Molecular Ioine

Quinone structures represent one of the most widely distributed structural classes in nature, and compounds belonging to this class can be found in drugs dyes and a large number of important pharmacophores associated with anticancer, antibacterial, antimalarial, fungicidal and antiparasitic agents et al. Among the numerous methods for the preparation of heterocycle, organic transformations induced by iodine have attracted considerable attention in recent years because of its low toxicity, low cost compared with transition metal catalysts, its readily availability, and its utility for a large variety of reactions. In this article, the synthesis of quinone structure polyheterocycle compounds containing symmetrical benzo[f]isoindole, asymmetrical benzo[f]isoindole, pyrrolo[2,1-a]isoquinolines, polysubstituted aromatic core derivatives via the cycloaddition reaction induced by molecular iodine was reported. A series of84compounds were designed and synthesized, among which77structures were new compounds. It could be described as the following four parts:1. I2-mediated1,3-dipolar cycloaddition reaction was developed for the synthesis of a series of24symmetrical benzo[f]isoindoles from quinone and N-substituted amino ester. The reaction was discussed and the parameters were selected. The results showed that the optimal parameters were as follows:3equivalents iodine, DBU and N-substituted amino ester with1equivalent quinone, xylcnc as solvent, the products were obtained in10%-84%yield under refulx. At the same time, a useful method for molecular iodine induced1,3-dipolar cycloaddition/oxidative aromatization sequence to construct the same product was also reported. Under the optimal condition, a scries of17products were obtained in16%-86%yields.2. A scries of asymmetrical benzo[f]isoindole was synthesized from quinone and N-substituted amino ester under different condition directly. The results showed that the optimal parameters were as follows:KF as base,1equivalent iodine, CH2CN as solvent, a series of19products were obtained in31%-72%yields under reflux for8hours. At the same time, a novel iodine induced1,3-dipolar cycloaddition was put forward. And another novel protocol of the synthesis of the same framework via the one-pot,1,3-dipolar cycloaddition of quinone, paraformaldehyde and N-substituted amino ester hydrochloride in the present of iodine at refluxing acetonitrile was also reported. All these reaction proceeded well with a series of20products in36.6%-98.1%yields.3. The novel molecular iodine-catalyzed1,3-dipolar cycloaddition/oxidation/aromatization cascade process with hydrogen peroxide as the terminal oxidant for the construction of pyrrolo[2,1-a]isoquinolines was reported. The reaction was discussed and the parameters were selected. The results showed that the optimal parameters were as follows:0.1equivalent iodine,3equivalents aq H2O2, DMF as solvent, a series of18products were obtained in42%-96%yields under80℃from the reaction between quinone and tetrahydroisoquinoline. Comparing with reported methods, this novel method was simple, economic and metal-free. Moreover, a novel molecular iodine—catalyzed1,3-dipolar cycloaddition/oxidation/aromatization cascade was put forward.4. The unexpected strategy was discovered for the construction of polysubstituted aromatic core derivatives from the reaction of quinone or N-substituted maleimide with β-enaminoester in HOAc by cycloaddition/oxidative aromatization sequence. The reaction was discussed and the parameters were selected. The results showed that the optimal parameters were as follows:3 equivalents β-enaminoester and1equivalent quinone, acetic acid as solvent. A series of22products were obtained in32%-96%yields under70℃. The novel strategy was simple, efficient, metal-free and catalyst-free. According to the captured intermidate, a novel [4+2] reaction process was put forward.