【作者】 赵霞；

【导师】 张冬菊；

【作者基本信息】 山东大学 ， 物理化学， 2021， 博士

【摘要】 金属有机化学作为一门交叉学科,一直是合成化学领域中热门的研究课题之一。过渡金属络合物由于具有抗毒性、热稳定性好、使用寿命长、选择性高以及价格便宜等特点,在生物质降解、有机合成、制药工程、绿色化学等领域有广泛应用。但是这些领域中存在的一些实验现象和结果无法给予合理的解释,一些反应机理尚不清楚,因此这在一定程度上限制了金属有机化学的发展和新型催化剂的开发。通过理论与计算化学研究,从分子层面探索揭示反应的微观机制,解释实验现象,深入理解反应本质,可以为金属有机化学的发展奠定一定的理论基础。本论文基于相关实验研究,选取镍、钌、钯、铜等过渡金属络合物催化的C-X(X=H,C,N)键活化/偶联反应作为研究对象,通过密度泛函理论计算阐明了反应的微观机理,探讨了反应的热力学和动力学性质,解释了反应的化学选择性、区域选择性和对映选择性,分析了配体以及添加剂对反应性能的影响,获得了一些创新性研究成果,为高效催化剂的设计提供了一定的理论指导。本论文的主要研究内容和创新性成果如下:一、研究了铝基lewis添加剂诱导的镍与氮杂环卡宾催化的烯烃吡啶类化合物的环化反应。实验发现,环化反应发生在吡啶环的C4位置,并且具有较高的对映/区域选择性。我们通过DFT计算阐明了反应的详细机理,解释了反应区域选择性和对映选择性的起源,明确了配体和添加剂对反应性能的影响。计算结果表明,反应机理涉及三个基本步骤,即配位、氧化金属化和还原消除,这与实验作者提出的四步机理(配位、C-H氧化加成、烯烃插入和还原消除)明显不同;氧化金属化过程是决定速率和对映选择性的关键步;endo型、R-构型产物为优势产物,与实验结果一致;反应的对映选择性起因于R-构型过渡态中较小的H-H排斥作用,endo型选择性是由于末端烯烃碳原子比内部烯烃碳原子更强的亲核性,C4位置的区域选择性是由于在氧化金属化过程中该位置较小的空间位阻和更有利的电子效应;氮杂环卡宾配体通过增强Ni(0)催化剂的活性来促进反应,而铝基lewis添加剂则通过活化底物来协同催化反应的进行,二者对于吡啶与烯烃的区域和对映选择性C-H环化均有重要影响作用。研究成果在Chemistry-A European Journal(2020,26,5459-5468)期刊发表。二、研究了镍与氮杂环卡宾催化的氟代芳烃和烯烃的烷基化反应,探讨了反应的分子机理,明确了反应的对映选择性、区域选择性和化学选择性的起源,以及氮杂环卡宾配体在反应中的作用。计算结果表明,反应遵循协同的配体-配体氢转移(LLHT)机理,而不是分步氧化加成/烯烃插入机理。反应有利的R型产物是由于在R构型的过渡态中金属有较强的抓氢作用;有利的endo型产物是由于Ni(0)催化剂与烯烃末端碳原子有更强的静电相互作用;与C-F键活化相比,C-H活化更有利是由二者机理不同所致,C-H活化通过协同LLHT机理进行,而C-F键活化则通过分步机理发生。反应的配体增强效应归因于氮杂环卡宾配体较强的供电子性质,提高了催化剂HOMO轨道的能级。研究成果在Organic Chemistry Frontiers(2021,8,1520-1530)期刊发表。三、研究了铜和光氧化还原协同催化的烷基羧酸与氮亲核试剂的交叉偶联反应。实验表明,亲核试剂无论为氯代吲唑还是杂环底物,偶联反应均发生在吲唑仲胺氮位置,而不是在叔胺氮或伯酰胺氮。为了理解控制反应区域选择性的微观机制,我们对反应进行了详细的计算研究。结果表明,反应由三个阶段组成,即烷基自由基的产生、铱(Ⅲ)催化剂的光氧化还原循环和铜(Ⅰ)的催化循环;伯、仲或叔羧酸均可通过与碘化物反应产生烷基自由基;能量最有利的交叉偶联路径由配位、去质子化、单电子转移(SET)、自由基加成和还原消除五个基元步骤组成;氯代吲唑仲胺氮比叔胺氮更容易发生偶联反应起因于1H-异构体比2H-异构体活性更高;杂环底物中吲唑仲胺氮比伯酰胺氮更容易发生偶联反应源于吲唑仲胺N-H键较强的酸性。研究成果在Inorganic Chemistry(2019,58,12669-12677)期刊发表。四、研究了钯(Ⅱ)催化的羧酸乙烯酯与芳基硼酸的交叉偶联反应。钯催化的交叉偶联反应通常通过钯(0)/钯(Ⅱ)机理发生,而近期的一些实验研究表明,一些钯基络合物催化的反应,无需通常需要的碱性条件即可发生,反应中不涉及钯催化剂价态的改变,遵循独特的反应机制。我们以Pd(OAc)2和膦配体催化的羧酸乙烯酯与芳基硼酸的交叉偶联反应为例对这类反应进行了理论研究。我们通过DFT计算,阐明了反应的详细机理,解释了反应区域选择性,弄清了配体调控的反应的分子机制。计算发现,芳基硼酸首先通过分步的转移金属化将芳基基团转移到Pd(Ⅱ)中间体上,继而乙酸乙烯酯的C=C键插入钯-芳基键,形成与α-碳原子键合的Pd(Ⅱ)酮络合物,然后通过1,3-钯迁移发生酮烯醇互变异构化反应,最后,Pd(Ⅱ)和β位的OAc基团发生β-消除反应得到偶联产物,实现活性催化剂的再生。理论计算阐明了水分子在协助质子转移过程中的重要作用;揭示了膦配体的芳基取代基和与Pd(Ⅱ)结合的芳基之间的非共价的π-π相互作用,该作用有利于决定速率和区域选择性的碳钯化过程,是配体调控反应性能的关键。研究成果投稿到A CS Catslysis期刊,目前正在修订。五、研究了[Ru(Cl)(H)(PPh3)3]催化木质素模型化合物的降解机制。实验表明,钌络合物[Ru(Cl)(H)(PPh3)3]可以有效催化木质素模型化合物的降解,即1,3-狄利格醇中Cα-Cβ键的断裂,反应无需外加氧化剂即可顺利进行。理论计算结果表明,反应经历配位、脱氢、C-C键断裂、催化剂再生和产物释放四个阶段。脱氢过程是催化循环的决速步,能垒为29.8 kcal/mol。理论结果合理解释了反应需要在较高温度(160℃)下进行的实验现象。计算发现,木质素模型化合物中的α-OH,γ-OH和Cγ-H对降解反应有重要影响,它们同时存在是Ca-Cβ断裂的必要条件,即底物中缺少α-OH,γ-OH和Cγ-H等任何一个基团,催化反应不能发生。研究成果在Molecular Catolysis(2019,471,77-84)期刊发表。更多还原

【Abstract】 As a new emerging interdiscipline,organometallic chemistry has always been one of the most active research topic in the field of synthetic chemistry.Transition metal complexes have a wide range of applications in the fields of biomass degradation,organic synthesis,pharmaceutical engineering,and green chemistry due to their anti-toxicity,good thermal stability,long service life,high selective oxidation and low price.However,some reaction phenomena and results in these fields cannot be explained reasonably,and the mechanisms of some reactions are still unclear,which limit the development of organometallic chemistry and new catalysts to a certain extent.Exploring and revealing the reaction mechanism at the molecular level,explaining the experimental phenomenon,and deeply understanding the nature of the reaction through theoretical and computational chemistry research can lay a certain theoretical foundation for the development of organometallic chemistry.In this dissertation,we select C-X(X=H,C,N)bond activation/coupling reactions catalyzed by transition metal complexes such as nickel,ruthenium,palladium and copper as the research objects based on the background of relevant experimental literature.DFT calculations have clarified some experimental microscopic mechanisms,discussed the thermodynamic and kinetic properties of the reaction,explained the chemoselectivity,regioselectivity,and enantioselectivity of the reaction,analyzed the effect of ligands and additives on the reaction performance,obtained some innovative research results,and provided some theoretical guidance for the design of efficient catalysts.The main contributions and key innovations of this dissertation are summarized as follows:1.This work presents a DFT-based computational study on the regio-and enantioselective C-H functionalization of pyridines with alkenes at the relatively unreactive C4-position using Ni(0)/N-heterocyclic carbene(NHC)catalysis under the assistance of an aluminum-based Lewis acid additive MAD.The calculations clarified the reaction mechanism,explained the origin of the regio-and enantioselectivity and the effects of ligand and additive.DFT calculations indicate that the selective functionalization involves a three-step mechanism(coordination,HMAOM,and reductive elimination),instead of the four-step mechanism(coordination,C-H oxidative addition,alkene insertion,and reductive elimination)proposed by the experiment author,where a unique H-migration assisted oxidation metalation(HMAOM)step is identified as the rate-and enantioselectivity-determining step.The newly proposed mechanism can well rationalize the experimental observation that the preferred product is the endo-type(vs exo-type),R-configuration(vs S-configuration)product at the C4(vs C2)position,and also unveil the reasons that the NHC ligand and the MAD additive can facilitate the reaction.With the unique mechanism,the enantioselectivity of the reaction towards the desired product is attributed to the smaller H…H repulsion effect in the R-configuration transition state than that in the S-configuration.The favorable endo-type product over the exo-type product is due to the stronger nucleophilicity of the terminal alkene carbon atom than the internal alkene carbon atom.The preferred regioselectivity at the pyridine C4 position stems from both the smaller steric effect and the stronger electronic effect at this position in the HMAOM process than at the C2 position.The NHC ligand facilitates the reaction via enhancing the Ni(0)catalyst activity,while the MAD additive assists the reaction via activating the substrate,and both of them play substantial roles for the regio-and enantioselective C-H cyclization of pyridines with alkenes.This work has been published on Chemistry-A European Journal(2020,26,5459-5468).2.Density functional theory calculations have been carried out to elucidate the mechanism,and clarify enantio-,regio-,and chemoselectivities,and the role of NHC ligand in the Ni/NHC-catalyzed alkylation of fluoroarenes with alkenes.The reaction is found to follow a concerted ligand-ligand hydrogen transfer(LLHT)mechanism instead of the stepwise oxidative addition/alkene insertion mechanism.The high R-enantioselectivity originates from the stronger agostic interaction in the R-configuration than that in the S-type enantiomer,the exclusive endo-regioselectivity is controlled by the stronger electrostatic force of the Ni(0)catalyst with the terminal carbon atom than the internal carbon atom in the alkene,and the excellent chemoselectivity of C-H activation over C-F activation attributed to the more favorable concerted ligand-ligand hydrogen transfer(LLHT)mechanism of C-H activation than the stepwise mechanism of the C-F activation.The enhanced reactivity by NHC ligand is attributed to the raise of the catalyst HOMO level via the highly electron-donating effect of the NHC ligand.This work has been published on Organic Chemistry Frontiers(2021,8,1520-1530.).3.This work presents a DFT-based theoretical study on the cross-coupling reaction of alkyl carboxylic acids and nitrogen nucleophiles via dual copper and photoredox catalysis.It was found that chlorinated indazole nucleophile(R1)prefers the C-N coupling at the indazole secondary amine nitrogen to at the tertiary amine nitrogen,while in the situation of heterocycle(R2),the preferred coupling occurs at the indazole nitrogen rather than at the primary amide nitrogen.The calculations showed the mechanistic details of three subprocesses proposed in the experimental study,including production of alkyl radicals,iridium(Ⅲ)photoredox cycle,and copper(Ⅰ)thermalredox cycle.It is found that alkyl radicals can be easily produced from primary,secondary,or tertiary carboxylic acids through iodonium activation.The energetically most favorable cross-coupling pathway involves coordination,deprotonation,single electron transfer(SET),radical addition,and reductive elimination.For the chlorinated indazole nucleophile(R1),the preferred C-N coupling product from 1H-tautomer are attributed to its higher stability relative to 2H-tautomer and the high barrier involved in the tautomerism from 1H-tautomer to 2H-tautomer.While in the case of heterocycle(R2),the C-N cross coupling preferentially occurs at the indazole nitrogen rather than at the primary amide nitrogen,which is confirmed to be due to the stronger acidity of the indazole N-H unit in comparison with the primary amide N-H unit in the indazole side chain.The theoretical results provide help for understanding the molecular mechanism and regioselectivity of the title reaction.This work has been published on Inorganic Chemistry.(2019,58,12669-12677).4.DFT calculations were performed to investigate the coupling reaction of vinyl carboxylates with arylboronic acids catalyzed by Pd(II).Pd-catalyzed cross-coupling reactions generally occur by the traditional Pd(0)/Pd(II)mechanism.A distinct Pd(Ⅱ)-only mechanism has been suggested recently for the base-free cross-coupling of vinyl carboxylates with arylboronic acids at ambient conditions that is enabled by Pd(OAc)2 along with a phosphine ligand.This computational study elucidates the new Pd(Ⅱ)-only mechanism,explained the regioselectivity of the reaction,and clarified the molecular mechanism of the reaction induced by the ligand..Transmetalation involving the arylboronic acid delivers the aryl group to the Pd(Ⅱ)intermediate,which allows the carbopalladation of the vinyl acetate via C=C insertion into the Pd-aryl bond.The resulting α-carbon-bound Pd(II)keto complex undergoes 1,3-palladatropic shift via keto-enol tautomerism to achieve the epimerization of the α-carbon,in which process transient water molecules play the vital role of proton shuttles.Consequently,the Pd(Ⅱ)center and the β-acetate group are properly oriented for the β-elimination to furnish the coupling product and regenerate the active species.The rate-and regioselectivity-determining carbopalladation via C=C insertion is facilitated by the phosphine ligand’s aryl substituent inducing noncovalent π stacking interactions with the Pd(Ⅱ)-bound aryl group.This reveals the origin of the ligand-controlled catalyst activity.The insights gained by this study can help utilize the Pd(Ⅱ)-only mechanism for a wider range of challenging cross-coupling reactions.This work has submitted to ACS Catslysis and are currently being revised.5.Focusing on the degradation mechanism of lignin model compound catalyzed by[Ru(Cl)(H)(PPh3)3].The experiment show that the degradation of lignin model compounds can effectively catalyzed by the ruthenium complex[Ru(Cl)(H)(PPh3)3],that is,the cleavage of the Cα-Cβ bond in 1,3-dilignol,and the reaction can occur without the addition of oxidants.With the aid of DFT calculations,we have performed the proposed mechanism divides the reaction into four stages:coordination,dehydrogenation,retro-aldol-type C-C bond cleavage,and product and pre-product release with catalyst regeneration.The dehydrogenation process was identified as the bottleneck of the catalytic cycle and the estimated high barrier(29.8 kcal/mol)qualitatively rationalizes the experimental observation that the reactions were carried out under elevated temperature(160 ℃).Calculations show that the α-hydroxyl and γ-hydroxyl groups as well as the y-H in the lignin model compound play substantial roles and their simultaneous presence is necessary for cleavage of the Cα-Cβ bond.This rationalizes the experimental finding that[Ru(Cl)(H)(PPh3)3]/triphos complexes were inactive for cleavage of the Cα-Cβbond cleavage of lignin model compound with any absence of the α-hydroxyl group,y-hydroxyl group,or Cγ-H unit.This work has been published on Molecular Catalysis(2019,471,77-84).更多还原