五氧化二碘促进的自由基三氟甲基化反应研究

发布时间：2018-04-24 21:15

本文选题：三氟甲基化 + 自由基　；参考：《兰州大学》2017年博士论文

【摘要】：本文首先概述了有机分子引入三氟甲基的研究进展,随后详细阐述了我们研究发展的一种经五氧化二碘促进的安全绿色的自由基三氟甲基化策略,该方法可顺利地实现四类有机化合物的高效三氟甲基化。全文分为以下五部分内容:第一部分概述了含氟化合物在医药、农药、新型材料领域具有广泛应用,并对近年来有机分子引入三氟甲基的研究进展进行了概括。同时从反应机理出发,总结了这些三氟甲基化方法的特点,并指出了这些研究体系存在的问题。第二部分详细阐述了我们发展的一种安全高效的烯烃三氟甲基碘化方法。该策略使用廉价安全的五氧化二碘作为单电子氧化试剂,氧化三氟亚磺酸钠成相应的CF3自由基,随后顺利地实现了各种活泼以及非活化的烯烃双官能团化。该方法有效地弥补了传统实用三氟碘甲烷这一有毒气体的不足。此外,我们运用自旋捕截技术以及电子自旋共振仪,对该反应的机理细节进行了深入地研究。有力地证实该过程经历自由基历程。第三部分细致描述了五氧化二碘单电子氧化三氟亚磺酸钠策略实现炔烃的双官能团化反应。运用同样的策略,在类似的反应条件下,一系列炔烃也能顺利地发生三氟甲基碘化反应,生成相应的三氟甲基碘代烯烃。碳碳双键的保留以及碘原子的引入为进一步的合成转化提供了更多的可能。第四部分陈述了杂环类化合物在三氟亚磺酸钠和五氧化二碘的作用下,也能发生高区域选择性的芳环三氟甲基化。一系列杂环化合物如呋喃、噻吩、吡咯、苯并呋喃、苯并噻吩、吲哚等均能高选择性地实现三氟甲基化。该方法为大量的含氟药物分子的合成提供了一种绿色安全的方法。第五部分论述了在五氧化二碘与三氟亚磺酸钠的作用下,一系列肉桂酸及其衍生物,能发生自由基加成消除脱羧反应,双键顺反专一性地生成三氟甲基取代的苯乙烯类化合物。综上所述,我们以三氟亚磺酸钠作为三氟甲基源,廉价五氧化二碘作为单电子氧化剂,二氯甲烷与水作为混合溶剂,可实现烯烃、炔烃、杂环及肉桂酸等四大类有机化合物的高效三氟甲基化反应。该三氟甲基化策略使用的原料廉价易得、安全稳定,而且该方法操作简单,体系环境友好,预计将在有机合成尤其是含氟药物分子的合成中被广泛应用。
[Abstract]:In this paper, the progress of introducing trifluoromethyl into organic molecules is reviewed, and a safe and green free radical trifluoromethylation strategy promoted by iodine pentoxide is described in detail. This method can successfully realize the high efficiency trifluoromethylation of four kinds of organic compounds. The paper is divided into five parts as follows: in the first part, the applications of fluorinated compounds in medicine, pesticide and new materials are summarized, and the research progress of introducing trifluoromethyl into organic molecules in recent years is summarized. At the same time, based on the reaction mechanism, the characteristics of these trifluoromethylation methods are summarized, and the problems of these research systems are pointed out. In the second part, we developed a safe and efficient method of trifluoromethyl iodization of olefin. In this strategy, the cheap and safe iodine pentoxide was used as a single electron oxidation reagent to oxidize sodium trifluorosulfonate into corresponding CF3 free radicals, and then various active and non-activated olefin difunctional groups were successfully realized. This method can effectively make up for the deficiency of trifluoromethane, a toxic gas. In addition, the mechanism of the reaction is studied in detail by using spin trapping technique and electron spin resonance instrument. It has been proved that the process goes through the free radical process. In the third part, the difunctional reaction of alkynes is described. Using the same strategy, a series of alkynes can also be successfully reacted with trifluoromethyl iodization under the same reaction conditions, resulting in the corresponding trifluoromethyl iodide alkenes. The retention of carbon and carbon double bonds and the introduction of iodine atoms provide more possibilities for further synthesis and conversion. In the fourth part, it is stated that heterocyclic compounds can also produce high region-selective aromatic trifluoromethylation under the action of sodium trifluorosulfonate and iodine pentoxide. A series of heterocyclic compounds, such as furan, thiophene, pyrrole, benzofuran, benzothiophene and indole, can achieve highly selective trifluoromethylation. This method provides a green and safe method for the synthesis of a large number of fluorine-containing drugs. In the fifth part, under the action of iodine pentoxide and sodium trifluorosulfonate, a series of cinnamic acid and its derivatives can occur free radical addition to eliminate decarboxylation, and double bond cis-anti-specific to form trifluoromethyl substituted styrene compounds. To sum up, we can realize alkenes and alkynes by using sodium trifluorosulfonate as trifluoromethyl source, cheap iodine pentoxide as single electron oxidant, dichloromethane and water as mixed solvents. High efficiency trifluoromethylation of heterocyclic and cinnamic acid compounds. The trifluoromethylation strategy uses cheap, safe and stable raw materials, and the method is simple and environmentally friendly. It is expected to be widely used in organic synthesis, especially in the synthesis of fluorine-containing drugs.
【学位授予单位】：兰州大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.25

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