【作者】 李松；

【导师】 李海蓓； 刘磊；

【作者基本信息】 山东大学 ， 药物化学， 2022， 硕士

【摘要】 硅醇和硅氧烷醇是一类非常重要的化合物,其在硅基聚合物材料、有机合成方法学、药物化学等方面有广泛的应用,硅醇的广泛应用促使学术界不断发展其的合成方法,但目前的硅醇合成方法仍然存在底物范围狭窄、使用贵金属催化剂、化学选择性差等不足。铁具有储量丰富、便宜、生物相容性好、对环境友好等优势,比起其他过渡金属,铁催化具有明显的优势,目前也未有铁催化Si-H键氧化的报道。因此,开发铁催化氢硅烷和氢硅氧烷氧化的通用方法具有非常大的理论和实际意义。本文的主要内容如下:在第一章中,综述了现有的硅醇合成方法并具体论述了铁催化的优势。在第二章中,我们先后进行了条件筛选、底物拓展、应用和机理研究。我们先进行了反应条件筛选,确定了最优反应条件为:将氢硅烷(0.1 mmol)和4齿氨基吡啶铁复合物3j(0.1 mol%)溶于1 mL 1,4-二氧六环中,然后加入30%H2O2(0.2 mmol),室温搅拌24 h。接着我们进行了底物拓展研究,我们的方法既能够以优异的产率实现不同骨架的氢硅烷、二氢硅烷、氢硅氧烷到对应的硅醇、偕硅二醇、硅氧醇的转变,也兼容噻吩基、苄基醚、三氟甲基、苯甲酰氧基、烷基氯、烷基溴、炔基、三甲基硅等不同官能团;然后,我们进行了应用研究,能够以优异的产率实现布洛芬、非布索坦、薄荷醇、吲哚、二茂铁等活性分子衍生的氢硅烷到目标硅醇的转化,这进一步证明了我们方法的底物普适性和优异的官能团兼容性。最后,为了获得一些机理细节,我们进行了 KIE、Hammtte曲线、18O掺入、拉曼共振光谱、CHP探针实验,基于上述实验结果和文献调研,我们认为氢原子转移和随后的羟基重组是反应的关键步骤并提出了类似于C-H键氧化的Si-H键氧化机理。在第三章中,我们先详细叙述了反应底物和催化剂的合成方法;接着我们描述了机理研究的细节并提供了相应的谱图证据:开始,我们进行了 KIE实验,1.7的KIE值表明Si-H键断裂可能是反应过程中的决速步骤;通过往反应体系加入溶剂量的H218O,我们进行了 18O整合实验,在反应完成后,体系里面检测到了 12%18O标记的硅醇产生,这说明反应通过硅正离子途径或者通过硅自由基途径进行;Hammtte曲线-0.22的斜率结果表明反应过程中没有明显的电荷分离,即排除硅正离子途径;通过往反应体系里面加入自由基捕捉TEMPO,我们进行了自由基捕捉实验,反应被完全抑制且体系里面检测到氢硅烷结合TEMPO的分子量,这说明反应是通过自由基途径进行;CHP探针实验说明:Fe(Ⅴ)=O是真正的氧化活性中间体;拉曼共振光谱实验说明反应体系里存在Fe(Ⅲ)-OOH中间体,结合上述对照实验结果,Fe(Ⅲ)-OOH作为Fe(Ⅴ)=O的灭活前体存在于反应体系中。最后,我们在章末附上了硅醇产物的表征数据。总之,我们阐述了一种铁催化氢硅烷和氢硅氧烷氧化的方法(0.1 mol%的催化剂负载量),在我们发展的反应条件下,能够以优异的产率获得目标硅醇和硅氧烷醇产物并表现出优异的底物普适性和官能团兼容性,值得注意的是,我们方法也能用于复杂含硅分子的高效氧化修饰。文献调研和机理研究表明Fe(Ⅴ)=O是真正氧化活性物种并且反应通过涉及氢原子转移及随后的羟基重组的自由基过程进行。更多还原

【Abstract】 Silanols and siloxanols are a very important class of compounds,which are widely used in silicon-based polymer materials,organic synthesis methodology,medicinal chemistry,etc.The wide application of silanols forces the academic community to continuously develop their synthetic methods,but the current silanol synthesis methods still have the disadvantages of narrow substrate range,using of noble metal catalysts,and poor chemical selectivity.Iron has the advantages of abundant reserves,cheapness,good biocompatibility,and environmental friendliness.Iron catalysis has obvious advantages over other transition metal catalysis,and there is no report on iron-catalyzed Si-H bond oxidation.Therefore,it is significance in theory and practice to develop a general method for the efficient iron-catalyzed oxidation of hydrosilanes and hydrosiloxanes.The main contents of this thesis are as follows:In the first chapter,the shortcomings of existing silanol synthesis methods are reviewed and the advantages of iron catalysis are discussed in detail.In the second chapter,we performed condition screening,substrate expansion,application and rmechanism studies.We first screened the reaction conditions and determined the optimal reaction conditions:To a solution of hydrosilane(0.1 mmol)and 4-dentate aminopyridine iron complex 3j(0.1 mol%)in 1,4-dioxane(1 mL)was added 30%H2O2(0.2 mmol),and the reaction was stirred at rt for 24 h.We then performed scope of substrate study that achieve hydrosilane,dihydrosilane,and hydrosiloxane with different substituent patterns and backbones to the corresponding silanols,silanediol and siloxaneols in excellent yields.The method is also compatible with different functional groups including thienyl,benzyl ether,trifluoromethyl,benzoyloxy,alkyl chloride,alkynyl,trimethylsilicon,and alkyl bromide;then,we performed application studies,and tranformations of hydrosilanes based on active molecules such as ibuprofen,febuxostat,menthol,indole,ferrocene to target silanols were realized in excellent yields,which further proves our method universality and excellent functional group compatibility.Finally,To gain insight into the oxidation mechanism,we performed KIE,Hammtte plot,18O incorporation,Raman resonance spectroscopy,CHP probe experiments successively,proves that hydrogen atom transfer and subsequent hydroxyl recombination are critical step in the reactions,as a result,a plausilble Si-H bond oxidation mechanism similar to C-H bond oxidation is proposed.In Chapter 3,we first describe synthetic methods of substrates and catalysts;then we describe the details of mechanistic studies and provide the corresponding spectrum.At the beginning,we performed KIE experiment,and the KIE value of 1.7 indicated that Si-H bond cleavage may be the rate-determining step in the reaction process.By adding a solvent amount of H218O to the reaction system,we performed an 18O-integration experiment,after the reaction was completed,12%18O-labeled silanol was detected in the reaction system,indicates that the reaction is carried out either through the silicon cation pathway or through the silicon radical pathway.The result of Hammtte plot indicates that there is no obvious charge separation during the reaction process,that is,the silicon cation pathway is excluded.By adding TEMPO to the reaction system,we performed free radical capture experiment,the transformation of hydrosilane to silanol was completely inhibited and the molecular weight of hydrosilane combined with TEMPO was detected in the system,indicates that the reaction was carried out through the free radical pathway;the probe experiment of cumene hydrogen peroxide indicates:Fe(V)=O is the real oxidation-active intermediate in the reaction process,that is,the reaction proceeds through the free radical pathway initiated by Fe(V)=O;Raman resonance spectroscopy experiments show that Fe(Ⅲ)-OOH intermediate exists in the reaction system,combined with the above control experiment results,indicate that Fe(Ⅲ)-OOH exists in the reaction system as an inactivated precursor of Fe(V)=O.Finally,we attach the characterization data for the silanol product at the end of the chapter.In conclusion,An iron-catalyzed preparative oxidation of hydrosilanes to diversely functionalized silanols with environmentally friendly H2O2 as oxidant at an iron catalyst loading of 0.1 mol%is illustrated here.The generality of the practical and highly selective oxidation is further demonstrated by effective synthesis of oligoand polymeric siloxanols as well as silanediols with diverse substituent patterns.Late-stage application in functional molecule-containing silanols is also illustrated.Mechanistic studies suggest the involvement of high-valent Fe(Ⅴ)=O species and a sequence of hydrogen atom transfer and oxygen rebound.更多还原