三氟甲硫基化反应及亲电环化反应研究

发布时间：2018-03-28 00:33

  本文选题：三氟甲硫基化　切入点：串联环化　出处：《兰州大学》2017年博士论文

【摘要】：本论文对AgSCF3促进的三氟甲硫基化-串联环化反应和酸催化或亲电试剂促进炔的丙醇(酮)串联环化反应进行了系统研究,主要包括以下六个章节:第一章在第一章中,我们主要介绍三氟甲硫基化反应的发展历程,根据所用试剂的性质可将三氟甲硫基化反应分为:自由基型、亲电型、亲核型、过渡金属催化的偶联或C-H活化以及多组分参与的三氟甲硫基化反应等。自由基三氟甲硫基化反应主要是利用AgSCF3与过硫酸盐产生的?SCF3自由基引发的反应。亲电三氟甲硫基化反应主要是一些N-SCF3和O-SCF3试剂参与的反应,包括对硼酸、末端炔烃、烯烃、β-酮酯和羧酸等进行的三氟甲硫基化反应。亲核三氟甲硫基化试剂主要包括一些含SCF3阴离子的盐,它们在Lewis的催化下可将三氟甲硫基引入到目标分子中。在过渡金属的催化下,许多亲核的三氟甲硫基化试剂可与卤代芳烃发生偶联反应,或者在导向基团诱导下通过C-H活化而引入三氟甲硫基。三氟甲硫基中的硫和氟也可以由单质硫和TMSCF3分别提供,即多组分参与的三氟甲硫基化反应。第二章在自由基反应中,烯烃较炔烃更容易捕获自由基从而生成烷基自由基,因此由炔烃引发的自由基反应会更加困难,产率通常也会大幅降低。由于1,6-烯炔具有多个反应位点,因此我们设想将1,6-烯炔底物中的烯烃部分与位阻基团相连,强迫三氟甲硫基自由基从叁键引发反应。在本章中,我们在一个反应历程中成功构建了一个C-SCF3键和两个C-C键,合成了一系列三氟甲硫基取代的芴衍生物,这也是从碳碳叁键引发的三氟甲硫基化-自由基串联环化反应的首例报道。第三章在第三章中,我们利用AgSCF3中的三氟甲硫基负离子直接参与反应,发展了BF3·OEt2?AgSCF3促进的炔丙醇的三氟甲硫基化-串联环化反应。在一步反应中构建了一个C-SCF3键和一个C-O/N键,得到了许多三氟甲硫基取代的2H-色烯和1,2-二氢喹啉衍生物。第四章在第四章中,我们对各种酸催化和亲电试剂促进的炔丙醇(酮)参与的串联环化反应进行了简单归纳。首先介绍了Meyer-Schuster重排反应和基于Meyer-Schuster重排反应的串联环化反应设计。炔丙醇的串联环化反应主要历程包括:(i)炔丙醇的羟基在酸或者亲电试剂作用下离去生成炔丙基碳正离子中间体,(ii)上述中间体紧接着会重排为联烯碳正离子中间体,(iii)体系中亲核性比水强的亲核试剂会进攻该联烯碳正离子中间体得到联烯中间体,(iv)最后在酸或亲电试剂作用下,体系中其他亲核基团进攻原联烯碳原子后成环。炔丙酮中的炔键可在酸或亲电试剂活化下与亲核试剂参与反应。根据亲核试剂的不同,我们主要介绍碳亲核试剂(富电子芳烃、烯烃等)和含杂原子官能团的亲核试剂(氧、硫、氮原子)参与的串联环化反应。第五章在第五章中,我们从同一个二炔酮底物出发,发展了在布朗斯特酸催化下合成4-吡喃酮的反应以及NIS促进的选择性合成4-吡啶酮和3-吡咯酮的反应。这三种产物的分子结构都是某些具有药物活性的天然产物分子的关键骨架。第六章2H-色烯和4-色满酮作为重要的类黄酮骨架结构,其合成方法历来受到有机化学家的广泛关注。在第六章中,我们在两种反应体系中发展了同一炔丙醇底物的两种环化方式,分别构筑了2H-色烯和4-色满酮分子的骨架结构。所得碘代4-色满酮产物还可通过钯催化的交叉偶联反应实现进一步衍生。
[Abstract]:In this paper, three fluorine methylthiolation - AgSCF3 promotes tandem cyclization and acid catalyzed electrophilic reagents or promoting alkyne propyl alcohol (ketone) studied tandem cyclization reaction, mainly includes the following six chapters: the first chapter in the first chapter, we mainly introduce the development process of three fluorine methylthio the reaction, according to the nature of the reagent can be three fluorine methylthiolation divided into: free radical, electrophilic type, pro karyotype, transition metal catalyzed coupling or C-H activation and multiple components involved in three fluorine methylthiolation. Three fluorine free radical methylthiolation reaction with persulfate is mainly produced by AgSCF3? SCF3 free radical reactions. Three electrophilic fluorine methylthiolation is mainly involved in the N-SCF3 and O-SCF3 reagent, including boric acid, terminal alkynes, alkenes, three fluorine methylthiolation beta keto ester and carboxylic acid and so on three fluorine nucleophilic. Methylthiolation reagent mainly includes some SCF3 containing anionic salts, which under the catalysis of Lewis can be three fluorine methylthio into target molecules. In the transition metal catalyzed by many nucleophilic three fluorine methylthiolation reagent reaction with halogenated aromatic hydrocarbons, or in the guide to group induced by C-H activation and the introduction of three fluorine methylthio sulfur and fluorine fluorine. Three methylthio in can also be provided by sulfur and TMSCF3, namely multi components involved in three fluorine methylthiolation. In the second chapter, free radical reaction, is more likely to capture the alkene alkyne free radical the formation of alkyl radicals, so radical reactions caused by alkyne will be more difficult, the yield is usually significantly reduced. Because of 1,6- enyne with multiple reaction sites, so we will assume part of 1,6- olefin enyne in the substrate is connected with the chromophore, forcing three fluorine methylmercapto Free radicals from the triple bond reaction. In this chapter, we successfully constructed a C-SCF3 bonds and two C-C bonds in a reaction process, a series of Fluorene Derivatives and three fluorine methylmercapto substituted were synthesized, which is triggered from a carbon carbon triple bond cyclization tandem three fluorine methyl sulfide base - free radical first report. The third chapter in the third chapter, we use three fluorine methylthio negative ions in AgSCF3 is directly involved in the reaction, the development of BF3 - OEt2? Cyclization of three fluorine series methylthiolation - AgSCF3 promoted propargyl alcohol. In one step reaction in a building a C-SCF3 key and a C-O/N key, 2H- chromen and 1,2- two hydrogen quinoline derivatives many three fluorine methylmercapto substituted is obtained. The fourth chapter in the fourth chapter, we analyze several acid catalyzed electrophilic reagents promoted propargyl alcohol (ketone) tandem cyclization reactions involved are outlined. Firstly Meyer-Schuster Rearrangement and tandem cyclization of Meyer-Schuster rearrangement reaction. Based on the design including the main course of tandem cyclization reaction of propargyl alcohol (I): propargyl alcohol hydroxyl in acid or electrophiles generated under the action of left propargyl carbonium ion (II), the intermediate tight then rearranged into allenes carbonium ion intermediate (III) system in the nucleophilic water than strong nucleophile will attack the allenic carbocation intermediate allene intermediates (IV) in acid or electrophiles under the system of other nucleophiles attack the original allenic carbon atom ring. Alkyne alkyne acetone in the acid or electrophiles and nucleophiles in the activation reaction. According to the different nucleophiles, we introduce carbon nucleophiles (electron rich aromatics, alkenes etc.) and heteroatom containing functional groups of nucleophiles (oxygen, sulfur and nitrogen atoms in the ring series) The reaction. The fifth chapter in the fifth chapter, we start from the same two ynones substrate, development in catalytic synthesis of Bronsted acid 4- pyrone reaction and NIS promote the selective synthesis of 4- pyridone and 3- pyrrolidone reaction. The molecular structure of these three kinds of products are the key frame of natural products some molecules having pharmacological activity. In the sixth chapter, 2H- and 4- chromen chromanone as an important flavonoid skeleton structure, the synthesis method has been widely concerned by organic chemists. In the sixth chapter, we in the two reaction system developed with a propargyl alcohol substrate two cyclization, respectively. To build a framework of 2H- and 4- chromen chromanone. The molecular iodine 4- chromanone products but also through palladium catalyzed cross coupling reactions to achieve further derivatization.

【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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本文编号：1673983