【作者】 周芳；

【导师】 朱少林；

【作者基本信息】 南京大学 ， 有机化学， 2018， 硕士

【摘要】 过渡金属氢化物络合物在金属有机化学中尤其是涉及到均相催化扮演着重要的角色。它们通常用作分子间氢转移的关键中间体。对于过渡金属氢化物的研究已经有很多的报道。近年来,研究重点主要是这些络合物的结构、成键,尤其是它们在一些还原和还原偶联反应中的催化作用。手性二级醇是用于获得生物活性分子的极其有用的前体,并且也是很有价值的合成中间体。合成它们的最基本的方法之一就是酮的不对称还原。其中酮的不对称氢硼化就是一种有效的策略。频哪醇硼烷是一种有用的硼试剂,官能团兼容性好。频哪醇硼烷和金属钯形成钯氢,将酮还原为醇,相比于氢气作氢源,实验室操作更为安全。反应使用商业可得的手性双膦配体,避免了碱的使用,条件温和,效率高。在过渡金属Pd和Ni催化的偶联反应中,常常伴随着β-氢消除生成烯烃的副反应。如何抑制β-氢消除是这类反应面临的一个问题。近年来,人们将这一不利的反插入反应与金属氢插入结合起来来获得有机金属物种,即有机金属物种发生β-氢消除后生成的金属氢物种继续对碳碳双键插入。相比于原来的有机金属物种发生碳金属键迁移得到一系列有机金属物种,其中某一金属物种选择性发生偶联反应,最终在远程得到单一位点官能团化的产物。通过这种方法,可以将石油化工原料中廉价的烯烃混合物区域归一性地转化为单一的附加值更高的化学品。过渡金属钯、锆、铑、钴等也可以使烯烃发生异构化。其中,镍氢催化的烯烃异构化官能团化相对较少。sp~3-sp~3碳碳键是脂肪有机化合物的结构基础。它们的形成是药物和天然产物合成中的基本操作。使用镍催化的烷基片段的交叉偶联已经被深入研究。然而,从步骤和原子经济的角度来看,需要预先生成有机金属试剂,这点并不够理想。而使用镍氢对稳定以及来源广泛的烯烃进行迭代迁移,可以原位产生有机金属物种,通过链迁移活化脂肪链中原本惰性的碳氢键,实现这些位置的官能团化。本论文主要介绍了钯氢催化的酮的不对称还原以及镍氢催化的烯烃远程烷基化反应。本论文主要包含以下几部分内容:A.钯氢催化的酮的不对称还原。第一章,总结金属氢对酮不对称还原的背景以及二级手性醇的应用、研究进展。第二章,使用频哪醇硼烷作氢源、商业可得的手性双膦配体(S,S)-Ph-BPE,和钯形成钯氢物种,将酮不对称还原为醇。反应催化剂用量少,不用加碱,反应活性、转化率和对映选择性都很高。B.镍氢催化的烯烃远程氢烷基化。第一章,总结过渡金属催化的碳链迁移的背景以及sp3-sp3碳碳键形成的应用、研究进展。第二章,以溴化镍为催化剂,简单的pyrox为配体,三乙氧基硅烷为氢源,氟化钾为碱,DMF为溶剂,室温条件下实现烯烃异构化,接着烷基碘选择性地和端位烷基镍偶联,实现烯烃高选择性的远程sp3碳氢键烷基化。更多还原

【Abstract】 Transition metal hydride complexes play important roles in organometallic chemistry especially related to homogeneous catalysis.They often function as key intermediates for transferring hydrogen between molecules.There have been many reports on the study of transition metal hydrides.In recent years,the research focuses mainly on the structure and bonding of these complexes,especially their catalytic action in some reduction and reductive coupling reactions.Optically active secondary alcohols are extremely useful precursors for obtaining bioactive molecules,as well as valuable synthetic intermediates.One of the most fundamental methods for the synthesis of these compounds is the enantioselective reduction of ketones.The asymmetric hydroboration of ketones is an efficient strategy to achieve optically active alcohols.Pinacolborane is a useful borane reagent,and could tolerate a variety of different functional groups.Compared to the catalytic reduction of hydrogen gas as a hydrogen source and transition metal,palladium hydride formed by pinacolborane and palladium is more safe to reduce the ketone to alcohol.Furthermore,the conditions of the reaction,which are carried out synergistically with palladium hydride and a commercially available chiral bisphosphine ligand,are mild.In addition,the reaction needs no base and the efficiency is high.In the transition-metal-catalyzed reductive coupling reaction,due to theβ-hydride elimination,cross-coupling is often accompanied by β-hydride elimination by-products.To suppress P-hydride elimination has long been a problem when designing reactions.In recent years,by taking advatage of this undesirable reaction,a serials of organometallic species along the hydrocarbon chain could be obtained through chainwalking,one of which could be functionalized with a suitable ligand.Through this method,different isomerized olefin mixtures in the petrochemical feedstock can be reacted with the same electrophile to obtain pure other useful chemical products.The originally low-reactivity alkene substrate can also be converted into a more active olefin through the migration of a carbon-carbon double bond to react with another coupling reagent to realize the construction of different chemical bonds.Transition metals such as palladium,zirconium,rhodium,cobalt,etc.can also cause olefins isomerization.However,researches on nickel-hydride catalyzed olefin isomerization-functionalization have shown an upward trend in recent years.C(sp~3)-C(sp~3)bonds are the structural basis of aliphatic organic compounds,and their formation is a basic operation in the synthesis of pharmaceuticals and natural products.The cross-coupling of alkyl fragments using nickel catalysis has been investigated intensively.However,from the standpoint of step and atom economy,the requirement for pre-generated organometallic reagents is still less than ideal.The use of nickel hydride for iterative migration of the stable and widespread available olefins can generate organometallic species in situ,activate the otherwise inert carbon-hydrogen bonds in the aliphatic chain,and achieve functionalization at these sites.In this paper,we mainly introduce the PdH-catalyzed asymmetric reduction of ketones and NiH-catalyzed remote hydroalkylation of olefins.This thesis includes the following several parts:A.PdH-catalyzed asymmetric reduction of ketones.The chapter 1 summarized the background of the metal hydride catalyzed asymmetric reduction of ketones and the application and research progress of secondary chiral alcohols.The chapter 2 introduced PdH species formed by the pinacolborane and palladium acetate,are together with the commercially available chiral diphosphine ligand(S,S)-Ph-BPE to asymmetrically reduce ketone to alcohol with low catalyst loading,no base,and high reactivity,conversion and enantioselectivity.B.NiH-catalyzed remote hydroalkylation of olefins.The chapter 1 summarized the background of transition-metal-catalyzed carbon chain migration and the application and research progress of sp3-sp3 carbon-carbon bond formation.The chapter 2 introduced a combination of NiBr2,a simple pyrox ligand,an excess of silane and KF can allow for the hydroalkylation of alkenes at the terminal position.更多还原