铑催化过氧化物与炔烃无外加氧化剂的环化反应

发布时间：2018-04-10 08:41

本文选题：C　切入点：H键活化　出处：《华侨大学》2016年硕士论文

【摘要】：基于过渡金属催化的C H键活化直接构筑C C键,由于其避免底物预活化,减少反应步骤,符合原子经济性,近年来已成为有机合成的一个热点。从机理层面来看,C H键功能团化反应一般需要一个高氧化价态的金属物种作为启动子,还原消除之后得到产物及低氧化价态的金属物种,再经过化学计量或过量的的氧化剂将低氧化价态的金属物种重生为活性金属物种。此过程中,氧化剂的添加往往产生一定量的被还原的氧化剂作为副产物,对环境造成污染。为了克服这个缺点,崔、吴小组提出了新颖的通过氧化导向基团的“内置氧化剂”策略,随后Hartwig,Yu,Glorius,Fagnou,Ackermann及其他课题组发展了其他内置氧化剂体系的脱氢偶联反应。而这些内置氧化剂的研究多集中于N O键,N N键及O N键,其他共价键作为内置氧化剂参与C H键活化反应的研究较少。异香豆素结构是多种具有生物活性的天然产物的主要骨架。随着C H键活化反应的发展,该类化合物的合成方法已从苯甲酸与炔烃的外加氧化剂环化法拓展到了利用N O键作为内置氧化剂N,N-二乙基-O-苯甲酰基羟胺与炔烃的环化策略。过氧酯易于合成且含有较弱的O O键,在有机合成中常被用作氧化剂和自由基激发剂。基于此,我们推测过氧酯中的O O键可以作为内置氧化剂,通过C H键活化反应合成异香豆素衍生物。本方法具有以下创新意义:1)过氧化物作为氧化剂或是自由基引发剂已被广为报道,该反应首次采用过氧化物作为C H键活化反应的底物,拓宽了过氧化物的应用范围。2)氧原子是弱导向原子,其诱导的环化反应一直是C H键活化反应研究领域的一个难点,本文成功的克服了这个困难,为后人的研究提供了有价值的范例。3)本文首次报道了O O键作为内置氧化剂促进过渡金属催化的C H键活化反应,拓宽了内置氧化剂的类型。4)相比之前报道的异香豆素衍生物的合成方法,该方法具有底物易于合成,不需外加氧化剂,副产物(醇类)毒性小等优点。根据实验结果和参考文献,可能的反应机理如下:第一步是活性催化剂[RhIII]的生成。随后,通过环铑化实现过氧苯甲酸叔丁酯的不可逆C H键活化,得到中间体A。中间体A通过与二苯基乙炔的配位及插入形成中间体C,而中间体C再经还原消除形成了C O键及中间体D。最后,中间体D通过自身氧化还原,释放出产物并重生活性催化剂[RhIII](途径I)。另一种可能的途径是,特戊酸辅助的分子内亲核进攻,导致C O键的形成及O O键的断裂,释放出产物,叔丁醇及活性催化剂[Rh III](途径II)。由于叔丁氧基质子化之后形成的中间体E的O O键更易断裂(途径II),且在途径I中[Rh I]迁移到邻近的氧原子需要经过一个三元环过渡态(能垒较高),因此我们认为途径II比途径I更接近于真实反应的机理。
[Abstract]:C / C bond is constructed directly based on transition metal catalyzed C H bond activation. It has become a hot spot in organic synthesis in recent years because it avoids substrate preactivation and reduces reaction steps, which is in line with atomic economy.From the mechanism level, the functional cluster reaction of C H bond usually requires a metal species with high oxidation valence as promoter, and the product and the metal species with low oxidation valence are obtained after reduction and elimination.After stoichiometric or excessive oxidizing agent, the metal species with low oxidation valence were reborn to active metal species.In this process, the addition of oxidants often produces a certain amount of reduced oxidants as by-products, which pollutes the environment.In order to overcome this shortcoming, Cui's team proposed a novel "built-in oxidant" strategy through oxidation-oriented groups. Subsequently, Hartwigi Yugorius Fagnoun Ackermann and other research groups developed the dehydrogenation coupling reaction of other built-in oxidant systems.However, most of the studies focused on N O bond N N bond and N N bond, while other covalent bonds were less involved in C H bond activation.Isocoumarin structure is the main skeleton of many bioactive natural products.With the development of C-H bond activation reaction, the synthesis method of these compounds has been extended from the cyclization of benzoic acid and alkynes to the cyclization strategy of using N-O bond as the built-in oxidant N _ (N) -diethyl-o-benzoyl hydroxylamine and alkynes.Peroxyesters are easy to synthesize and contain weak O-O bonds. They are often used as oxidants and radical activators in organic synthesis.Therefore, we speculate that the O bond in peroxy ester can be used as a built-in oxidant to synthesize isocoumarin derivatives by C-H bond activation reaction.This method has the following innovative significance: 1: 1) peroxide as oxidant or radical initiator has been widely reported. This reaction is the first time that peroxide is used as substrate for C-H bond activation.The oxygen atom is a weakly oriented atom, and the cyclization induced by it has been a difficult point in the field of C-H bond activation, which has been successfully overcome in this paper.In this paper, we report for the first time that O bond acts as a built-in oxidant to promote the C-H bond activation catalyzed by transition metals.Compared with the previously reported method of synthesis of isocoumarin derivatives, this method has the advantages of easy synthesis of substrates, no need of additional oxidants, and less toxicity of byproducts (alcohols).According to the experimental results and references, the possible reaction mechanism is as follows: the first step is the formation of active catalyst [RhIII].Subsequently, the irreversible C-H bond activation of tert-butyl peroxybenzoate was achieved by cyclization of rhodium, and the intermediate A was obtained.Intermediate A forms the intermediate C through the coordination and insertion of diphenyl acetylene, and the intermediate C is reduced to form the C-O bond and the intermediate D.Finally, the intermediate D released the product and reactivated catalyst [RhIII] by self-redox.Another possible approach is the intramolecular nucleophilic attack assisted by pentanoic acid, resulting in the formation of C-O bonds and the breaking of O bonds, resulting in the release of products, tert-butanol and active catalyst [Rh III].Because the O / O bond of the intermediate E formed after the protonation of tert butoxy is easier to break (path II, and [Rh I] migrates to the adjacent oxygen atom in path I, it is necessary to pass through a ternary ring transition state (the energy barrier is high), so we think thatPathway II is closer to the mechanism of real reaction than Pathway I.
【学位授予单位】：华侨大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O621.256.9

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