【作者】 王鹏；

【导师】 李辉林；

【作者基本信息】 兰州大学 ， 化学·有机化学， 2023， 硕士

【摘要】 过渡金属催化重氮化合物的卡宾转移反应是现代有机合成中最重要的化学转化之一。利用过渡金属活化重氮化合物产生的金属卡宾物种,与不同的亲核试剂发生诸多的化学反应类型中,其中X-H键插入反应在这一领域中占据着至关重要的地位。然而,过渡金属催化剂往往存在着价格高昂、毒性和对人体有害等固有的缺点,这对于医药研发、食品行业是极其不友好的。非金属催化的化学反应则正好避免了以上存在的问题。本论文以Lewis酸性B(C6F5)3为非金属催化剂,通过设计反应底物和优化反应条件,成功发展了几种对重氮化合物的X-H键插入反应。本论文分为以下四个部分:第一章:绪论简要介绍了重氮化合物的合成方法及参与的化学反应,重点综述了三芳基硼烷催化重氮化合物的研究进展,特别是B(C6F5)3催化重氮化合物参与的有机反应,如:环加成反应、X-H键插入反应、碳碳键形成反应等。第二章:B(C6F5)3催化α-重氮酯与羧酸及衍生物的O-H插入反应研究重氮化合物与羧酸的O-H键插入反应是合成各种α-含氧羧酸衍生物的直接方法之一。以B(C6F5)3为催化剂,通过系统的反应条件优化,在最优条件下考察了不同的重氮化合物和羧酸及衍生物的底物范围,高产率、高效率合成了多种类型的O-H键插入产物。该方法操作简便、条件温和、具有较好的底物普适性和官能团兼容性。另外,通过氘代标记实验结果,我们提出了可能的反应机理。第三章:B(C6F5)3催化α-重氮酯与酰胺及衍生物的N-H插入反应研究非金属催化重氮化合物与酰胺的N-H键插入反应是合成非天然α-氨基酯的直接途径之一。我们简要综述了非天然α-氨基酯的合成方法,并引出利用非金属催化剂B(C6F5)3催化重氮化合物与酰胺及衍生物来构筑C-N键的合成策略。该反应在中性条件下进行,高产率、高效率获得了一系列N-H键插入产物,并且能在克级实验上保持较高的反应效率。另外,通过氘代标记实验结果,我们提出了可能的反应机理。该方法为非天然α-氨基酯的合成提供了一种新的思路。第四章:无溶剂、B(C6F5)3催化α-重氮酯与硫醇和硫酚的S-H插入反应研究α-重氮酯与巯基化合物的S-H键插入反应是合成α-硫酯最直接的方法之一。我们以B(C6F5)3为催化剂,实现了重氮化合物与硫醇和硫酚间的S-H键插入反应。通过系统的反应条件优化,确定了该反应在无溶剂条件下进行。根据既定的方案,以中等至良好的产率合成了一系列α-硫酯产物,具有广泛的底物范围和良好的官能团耐受性。另外,该反应在克级实验中保持较高的反应效率,并且所得的α-硫酯产物易于转化为其他有用的化合物。该反应在室温下在无溶剂条件下进行,在磁力搅拌下通常在20分钟内完成,这为药物分子的后期修饰、含硫化合物的合成提供了一种方便的方法。更多还原

【Abstract】 The transition metals catalyzed carbene transfer reactions of diazo compounds is one of the most important chemical transformations in modern organic synthesis.The metal carbene species produced by using transition metals to activate diazo compounds have many types of chemical reactions with diverse nucleophiles,among which the XH bond insertion reactions occupy a critical position in this field.However,transition metal catalysts often have inherent disadvantages such as high price,toxicity and harm to human body,which is extremely unfriendly to pharmaceutical research and food industry.Non-metallic catalytic chemical reactions just avoid the above problems.In this thesis,several X-H bond insertion reactions for diazo compounds were successfully developed by designing reaction substrates and optimizing reaction conditions using Lewis acidic B(C6F5)3 as a non-metallic catalyst.This thesis is divided into the following four chapters:Chapter 1:introductionThe synthetic methods and chemical reactions involved in diazo compounds are briefly introduced,with emphasis on reviewing the research progress of triarylboranecatalyzed diazo compounds,especially the organic reactions involved in B(C6F5)3catalyzed diazo compounds,such as:cycloaddition reactions,X-H bond insertion reactions,carbon-carbon bond formation reactions,etc.Chapter 2:study on the O-H insertion reactions of α-diazoesters with carboxylic acids and derivatives catalyzed by B(C6F5)3The O-H bond insertion reactions between diazo compounds and carboxylic acids is one of the direct methods to synthesize various α-oxycarboxylic acid derivatives.With B(C6F5)3 as the catalyst,various types of O-H bond insertion products have been synthesized with high yield and high efficiency by systematically optimizing the reaction conditions and investigating the substrate range of different diazo compounds,carboxylic acids and derivatives under the optimal conditions.The method is simple,mild,and has good substrate universality and functional group compatibility.In addition,through the results of deuterium labeling experiment,we propose a possible reaction mechanism.Chapter 3:study on N-H insertion reactions of α-diazoesters with amides and derivatives catalyzed by B(C6F5)3The N-H bond insertion reactions of diazo compounds and amides catalyzed by nonmetals is one of the direct ways to synthesize unnatural α-amino esters.We briefly reviewed the synthesis methods of unnatural α-amino esters,and introduced the synthesis strategy of using non-metallic catalyst B(C6F5)3 to catalyze diazo compounds,amides and derivatives to construct C-N bonds.The reaction was carried out under neutral conditions,and a series of N-H bond insertion products were obtained with high yield and high efficiency,and high reaction efficiency could be maintained in gram scale experiment.In addition,through the results of deuterium labeling experiment,we propose a possible reaction mechanism.This method provides a new idea for the synthesis of unnatural α-amino esters.Chapter 4:study on the S-H insertion reactions of α-diazoesters with thiols and thiophenols catalyzed by B(C6F5)3 without solventThe insertion reactions of S-H bond between α-diazoesters and mercapto compounds is one of the most direct methods to synthesize α-thioesters.We used B(C6F5)3 as catalyst to realize the S-H bond insertion reactions between diazo compounds and thiols and thiophenols.By optimizing the reaction conditions of the system,it was determined that the reaction was carried out under solvent-free conditions.According to the established scheme,a series of α-thioester products were synthesized in moderate to good yields,with a wide range of substrates and good functional group tolerance.In addition,the reaction maintains a high reaction efficiency in the gram scale experiment,and the α-thioester products obtained is easy to be converted into other useful compounds.The reaction is carried out under solvent-free conditions at room temperature,and usually completed within 20 minutes under magnetic stirring,which provides a convenient method for the later modification of drug molecules and the synthesis of sulfur-containing compounds.更多还原