【作者】 刘琳；

【导师】 张冬菊；

【作者基本信息】 山东大学 ， 化学， 2023， 硕士

【摘要】 金属有机化学是由无机化学与有机化学相互渗透而成的交叉学科,在有机合成领域具有举足轻重的地位。过渡金属有机化合物由于其稳定性好、选择性高、环境友好等特点在绿色化学和有机合成领域备受关注。几十年来,单一过渡金属催化的有机反应在实验和理论上都取得了重要进展。但单一过渡金属催化剂在化学选择性的控制和原子利用率方面存在一定的局限性,限制了金属有机化合物催化性能的进一步提高。近年来,双金属催化系统的设计和应用得到了快速发展,过渡金属催化系统的催化性能得到了有效提升。开展双金属催化系统的理论研究,对进一步完善催化系统的性能,设计新的双金属催化系统具有重要的指导意义,揭示了其协同催化的分子机制,阐明了提高反应效率的关键因素,掌握了控制反应选择性的微观本质。该论文通过密度泛函理论计算研究了铜/钯和铜/钌双过渡金属有机化合物催化C-C键活化以及交叉偶联等反应,通过理论计算揭示了反应的微观机理,通过对一些关键中间体结构的分析解释了产生化学选择性和立体选择性的本质原因,建立了铜/钯和铜/钌催化循环的理论模型。本论文研究的主要内容和创新性成果如下:一、研究了铜/钯双过渡金属协同催化乙烯基芳烃、CO、芳基卤化物和B2pin2共同参与的四组分硼羰基化反应。对于该反应,实验发现当芳基碘作为反应底物时β-硼基酮是主要产物,而芳基三氟甲磺酸酯作为底物时更容易生成β-硼基乙烯酯。我们系统研究了反应的微观机理,解释了化学选择性的根源,明确了不同底物对反应性能的影响。主要发现可概括为如下三个方面:(1)明确了四组分硼羰基化反应的分子机理。反应涉及两个催化循环,即铜催化循环和钯催化循环;产物的形成主要经历三个基本过程:烷基铜和乙烯烷氧基铜中间体的形成;酰基钯中间体的形成;铜中间体和酰基钯中间体之间的选择偶联。(2)澄清了不同底物产生反应性差异的本质原因。我们发现铜催化循环和钯催化循环中间体的形成速率不同,对于芳基碘底物而言,酰基钯中间体(12.1 kcal/mol)的形成比乙烯烷氧基铜(20.6kcal/mol)更容易,两种中间体发生偶联反应生成β-硼基酮;对于芳基三氟甲酸酯底物而言,烷基铜中间体的形成(20.6 kcal/mol)较酰基钯中间体的形成(21.2 kcal/mol)容易,因此烷基铜中间体与酰基钯中间体偶合形成β-硼基乙烯酯产物。(3)揭示了 C(sp2)-X(X=I,OTf)键的强度是控制活性芳基/酰基钯中间体相对稳定性的关键因素。当底物为芳基碘时,生成酰基钯中间体需要克服12.1 kcal/mol的能垒,而以芳基三氟甲磺酸酯作为反应底物时,则需克服21.1 kcal/mol的能垒形成酰基钯中间体。这是由于C(sp2)-O键的键能大于C(sp2)-I键的键能,前者为21.4 kcal/mol,而后者仅为13.5 kcal/mol,因此活化C(sp2)-O键的能垒更高,使得芳基三氟甲磺酸酯更难发生氧化加成过程,从而造成了反应性的差异。理论结果为改进β-硼羰基化合物的合成提供了一定的理论指导,研究成果在Catalysis Science&Technology 期刊发表。二、探究了铜/钌双过渡金属催化外消旋烯丙醇与酮亚胺酯合成δ-羟基酯的氢烷基化反应。对于该反应,实验发现用手性催化剂催化外消旋的烯丙基醇和酮亚胺酯底物可以得到ee值为99%的(S,R)型δ-羟基酯产物。我们对该体系理论研究的主要结果如下:(1)计算表明,产物的形成主要经历四个基本过程:钌催化烯丙基醇中间体脱氢、铜叶立德的形成、迈克尔加成反应和酮基酯中间体的加氢还原。(2)迈克尔加成过程和加氢还原过程是控制反应立体选择性的关键步骤。迈克尔加成过程中,β-C更容易从Cu(Ⅰ)-亚甲亚胺叶立德中间体平面内发生亲核进攻,形成S-酮基酯中间体;加氢还原过程中,K2HPO4更倾向于在羟基酯中间体平面外发生加氢反应,导致(S,R)型的δ-羟基酯产物。(3)铜催化剂手性磷配体中的苯环与羰基之间存在相对较强的π-π相互作用,有利于第一个手性中心S构型的形成;而羰基氧原子与钌催化剂中氢原子之间的氢键相互作用可以促进第二个手性中心R构型的形成,最终导致(S,R)型产物的形成。理论结果合理解释了实验现象,为1,4-非相邻立体中心化合物的合成提供了一定的理论指导。该结果正在准备中。更多还原

【Abstract】 Metal organic chemistry is an interdisciplinary discipline formed by the interpenetration of inorganic and organic chemistry and occupies an important position in the field of organic synthesis.Transition metal organic compounds have attracted much attention in the field of green chemistry and organic synthesis due to their good stability,high selectivity,and environmental friendliness.Over the past decades,important progress has been made in the experimental and theoretical applications of single transition metal organocatalytic reactions.Single transition metal catalysts have certain limitations in terms of control of chemoselectivity and atomic utilization,which limit the further improvement of the catalytic performance of metal-organic compounds.In recent years,the design and application of dual transition metal catalytic systems have been rapidly developed,effectively improving the catalytic performance of transition metal catalytic systems.The theoretical study of dual transition metal catalytic systems to reveal the molecular mechanism of their synergistic catalysis,elucidate the key factors to improve the reaction efficiency,and grasp the microscopic nature of controlling the reaction selectivity is of great significance for further improving the performance of catalytic systems and designing new dual transition metal catalytic systems.This thesis investigated the reactions of Cu/Pd and Cu/Ru dual transition metal organic compoundscatalyzed by C-C bond activation and cross-coupling through density functional theory calculations,revealed the microscopic mechanism of the reactions through theoretical calculations,explained the essential reasons for the occurrence of chemoselectivity and stereoselectivity through the analysis of the structures of some key intermediates,and the theoretical models of Cu/Pd and Cu/Ru catalytic cycles were established.1.Four-component boron carbonylation reaction joint catalyzed by Cu/Pd dual transition metals involving vinylarenes,CO,aryl halides,and B2pin2 was investigated.For this reaction,it was found experimentally that β-boryl ketone was the main product when aryl iodide was used as the reaction substrate,while β-boryl vinyl ester was more readily produced when aryl triflates was used as the substrate.We systematically investigated the microscopic mechanism of the reaction,explained the root cause of the chemoselectivity,and clarified the effects of different substrates on the reaction performance.The main findings can be summarized in three aspects as follows:(1)The molecular mechanism of the four-component boron carbonylation reaction was clarified.The reaction involves two catalytic cycles,namely the copper-catalyzed cycle and the palladium-catalyzed cycle;the formation of products mainly undergoes three basic processes,such as the formation of alkyl copper and vinyl alkoxide copper intermediates,the formation of acyl palladium intermediates,and the selective coupling of copper intermediates with palladium intermediates.(2)The essential factors leading to the difference in reactivity for different substrates were clarified.We found that the formation rates of intermediates in copper-catalyzed and palladium-catalyzed cycles were different,and for aryl iodide substrates,the formation of acyl palladium intermediates(12.1 kcal/mol)was easier than that of vinyl alkoxide copper(20.6 kcal/mol),and the coupling reaction of the two intermediates led to the formation of β-boryl ketone;while for aryl triflates,the formation of alkyl copper intermediates(20.6 kcal/mol)is easier than that of the acyl palladium intermediate(21.2 kcal/mol),so the coupling of the alkyl copper intermediate with the acyl palladium intermediate leads to the formation of theβ-boryl vinyl ester product.(3)Revealed that the strength of the C(sp2)-X(X=I,OTf)bond is a key factor controlling the relative stability of the reactive aryl/acyl palladium intermediates.When the substrate is aryl iodide,an energy barrier of 12.1 kcal/mol needs to be overcome to produce the acyl palladium intermediate,while an energy barrier of 21.1 kcal/mol needs to be overcome to form the acyl palladium intermediate when aryl triflates is used as the reaction substrate.This is due to the fact that the bond energy of the C(sp2)-O bond is larger than that of the C(sp2)-I bond,which is 21.4 kcal/mol,while the latter is only 3.5 kcal/mol,so the activation energy barrier of the C(sp2)-O bond is higher,which makes the aryl triflates more difficult to undergo the oxidative addition process,thus causing the difference in reactivity.The theoretical results provide some theoretical guidance to improve the synthesis ofβ-boron carbonyl compounds,and the research results were published in Catalysis Science&Technology.2.The Cu/Ru dual transition metal-catalyzed hydroalkylation reaction of secondary allyl alcohols with ketimine esters for the synthesis of δ-hydroxy esters was investigated.It was found that the racemic allyl alcohol and ketimide ester substrates catalyzed by chiral catalysts could yield(S,R)-type δ-hydroxy ester products with an ee value of 99%.The main results of our theoretical study of this system are as follows:(1)The calculations show that the formation of products goes through four basic processes:Ru-catalyzed dehydrogenation of allyl alcohol intermediates,generation of active copper(Ⅰ)-azomethine,Michael addition reaction,and hydrogenation reduction of ketoesters.(2)We found that the Michael addition process and the hydrogenation reduction process are the key steps controlling the stereoselectivity of the reaction.During Michael addition reaction,β-C is more likely to undergo nucleophilic attack from within the plane of Cu(Ⅰ)-methylenimine yelide intermediate to form the intermediate containing S chiral center;during hydrogenation reduction,K2HPO4 is more likely to undergo hydrogenation outside the plane of hydroxyester intermediate,leading to(S,R)-type δ-hydroxyester product.(3)The relatively strong π-π interaction between the benzene ring and the carbonyl group in the chiral phosphorus ligand of the copper catalyst facilitates the formation of the S configuration of the first chiral center,while the hydrogen bonding interaction between the carbonyl oxygen atom and the hydrogen atom in the Ru catalyst can promote the formation of the R configuration of the second chiral center,which eventually leads to the formation of the(S,R)-type product.The theoretical results reasonably explain the experimental phenomena and provide some theoretical guidance for the synthesis of 1,4-nonadjacent stereocentric compounds.The results of the study have been compiled into a research paper,which is currently in submission status.更多还原