Ni- and Pd-based homogeneous catalyst systems for direct oxygenation of C(sp3)-H groups

Developing catalytic approaches to selective activation and functionalization of C–H bonds in hydrocarbons and complex organic molecules has been considered as a challenging goal. Recently, significant efforts have been aimed at the search for efficient nickel- and palladium-based catalyst systems, capable of conducting direct aliphatic C–H oxygenation with high and predictable chemoselectivity and regioselectivity. The present review focuses on the advances in homogeneous oxidation of hydrocarbon C(sp³)–H groups, catalyzed by nickel and palladium complexes, and covers the publications of the past 15 years. Correlations between the structure of the metal-based catalyst, steric and electronic properties of the ligands, catalytic conditions, and the catalytic reactivity (efficiency, chemoselectivity, and regioselectivity) are discussed.     

Metal–Organic Framework (MOF)-Based Materials as Heterogeneous Catalysts for C−H Bond Activation

Converting light hydrocarbons such as methane, ethane, propane, and cyclohexane into value-added chemicals and fuel products by means of direct C−H functionalization is an attractive method in the petrochemical industry. As they emerge as a relatively new class of porous solid materials, metal–organic frameworks (MOFs) are appealing as single-site heterogeneous catalysts or catalytic supports for C−H bond activation. In contrast to the traditional microporous and mesoporous materials, MOFs feature high porosity, functional tunability, and molecular-level characterization for the study of structure–property relationships. These virtues make MOFs ideal platforms to develop catalysts for C−H activation with high catalytic activity, selectivity, and recyclability under relatively mild reaction conditions. This review highlights the research aimed at the implementation of MOFs as single-site heterogeneous catalysts for C−H bond activation. It provides insight into the rational design and synthesis of three types of stable MOF catalysts for C−H bond activation, that is, i) metal nodes as catalytic sites, ii) the incorporation of catalytic sites into organic struts, and iii) the incorporation of catalytically active guest species into pores of MOFs. Here, the rational design and synthesis of MOF catalysts that lead to the distinct catalytic property for C−H bond activation are discussed along with the post-synthesis of MOFs, intriguing functions with MOF catalysts, and microenvironments that lead to the distinct catalytic properties of MOF catalysts.     

Improving the efficiency and sustainability of catalysts for direct arylation polymerization (DArP)

In the past decade, direct arylation polymerization (DArP) has rapidly developed as a sustainable synthetic protocol for cost-effective, atom-economical preparation of conjugated polymers. By circumventing monomer functionalization with toxic transmetallating reagents such as organostannane and organoboron required for Stille-Migita and Suzuki-Miyaura polymerization methods, DArP proceeds through a metal-catalyzed C H activation pathway for the preparation of high-performance conjugated polymer materials. This review evaluates the development of several classes of efficient catalysts/catalytic systems from small-molecule studies to polymerizations, including the mechanisms involved in these transformations and how they inspire catalyst and monomer design for defect-free conjugated polymer synthesis. Recent advances in developing more sustainable first-row transition metal catalysts for DArP are also highlighted, and the fundamental understanding of these efficient and sustainable catalysts should motivate the pursuit for the next generation of catalytic design to enable more effective and environmentally friendly conjugated polymer synthesis.     

Polymer‐ and Silica‐Supported Iron BPMEN‐Inspired Catalysts for CH Bond Functionalization Reactions

Direct catalytic C? H bond functionalization is a key challenge in synthetic chemistry, with many popular C? H activation methodologies involving precious‐metal catalysts. In recent years, iron catalysts have emerged as a possible alternative to the more common precious‐metal catalysts, owing to its high abundance, low cost, and low toxicity. However, iron catalysts are plagued by two key factors: the ligand cost and the low turnover numbers (TONs) typically achieved. In this work, two approaches are presented to functionalize the popular N¹,N²‐dimethyl‐N¹,N²‐bis(pyridin‐2‐ylmethyl)ethane‐1,2‐diamine (BPMEN) ligand, so that it can be supported on porous silica or polymer resin supports. Four new catalysts are prepared and evaluated in an array of catalytic C? H functionalization reactions by using cyclohexane, cyclohexene, cyclooctane, adamantane, benzyl alcohol, and cumene with aqueous hydrogen peroxide. Catalyst recovery and recycling is demonstrated by using supported catalysts, which allows for a modest increase in the TON achieved with these catalysts.     

低碳烷烃与二氧化碳催化转化研究进展

页岩气革命为低碳经济发展提供了重要契机.在低碳烷烃(甲烷和乙烷)催化转化过程中,以二氧化碳作为氧化剂参与反应,通过C-H键的选择性活化可将页岩气转化为优质化工原料——合成气和乙烯,是一种低碳烷烃转化与二氧化碳资源化利用的工艺路线.本文总结了近年来甲烷干重整与乙烷和二氧化碳反应中与C-H键活化相关的研究进展,分析了甲烷干...     

弱碱柔能克刚:动力学去质子官能化反应

碳氢键的去质子官能化反应是碳碳键构建最常用的方法,是一种重要的碳氢键活化方式.近年来,碱催化碳碳键形成反应在含弱酸性碳氢键化合物作为亲核试剂的底物拓展方面取得了重要进展.强碱性试剂或催化剂是实现这些弱酸性碳氢键官能化反应的关键.根据酸碱平衡理论,相对较强的碱才能够对弱酸性碳氢键发生去质子化反应,形成较大浓度的碳负离子中间体,进而发生亲核反应.相对较弱的碱不足以对弱酸性碳氢键进行去质子化反应,然而尽管碳负离子中间体可能浓度很低,但应该仍然存在于反应体系中.如果可以选择性地进行热力学有利的化学转化,碳负离子中间体的浓度将会下降并引起去质子化平衡的重新构建.结合碳负离子中间体不可逆的转化和去质子平衡的重新构建,弱酸性碳氢键就可以在弱碱条件下实现缓慢却持续不断的去质子官能化反应.为区别于强碱条件下、通过热力学稳定碳负离子中间体的传统碳氢键去质子官能化反应,我们将这种在弱碱条件下、通过热力学不利的碳负离子中间体转化和酸碱平衡重新构建实现的弱酸性碳氢键的官能化反应称为动力学去质子官能化反应.本文总结了碳氢键去质子官能化反应研究现状和本研究团队近年来在弱碱条件下的动力学去质子官能化反应研究进展.     

N-Tosylhydrazone as an oxidizing directing group for the redox-neutral access to isoquinolines via Cp1Co(III)-Catalyzed C–H/N–N activation

Herein, an efficient and economic access has been revealed for the synthesis of isoquinolines via C–H bond activation strategy by using comparatively inexpensive and versatile cobalt catalyst. A hardly investigated directing group, N-tosylhydrazone has been effectively applied as an internal oxidant for an annulation reaction with internal alkynes via C–H/N–N bond functionalization. This catalytic protocol works for the extensive variety of substrates in moderate to excellent yields under external oxidant-free conditions. Additionally, the proposed protocol has advantages such as broad substrate coverage with significant product yields, readily synthesized substrates as well as scalability up to the gram quantity which further improves the competency of the methodology.     

Porous Organic Phenanthroline-Based Polymer as an Efficient Transition-Metal-Free Heterogeneous Catalyst for Direct Aromatic C−H Activation

Direct C−H bond transformation has been regarded as one of the most important areas in organic synthesis in both academia and industry. However, the heterogeneous transition-metal-free catalysis of direct C−H bond transformation has remained a contemporary challenge. To tackle this challenge, we designed and constructed a porous phenanthroline-based polymer (namely POP-Phen) via free radical polymerization of vinyl-functionalized phenanthroline monomers. POP-Phen shows excellent catalytic performances in transition-metal-free catalyzed C−H arylation, even better than those of the corresponding homogeneous catalyst, which is mainly attributed to the high density of catalytically active sites in the heterogeneous catalyst. Kinetic isotope experiments and spectral characterizations demonstrate the electron-transfer between the heterogeneous catalyst and the base (t-BuOK), a key step for C−H activation. We believe that this porous organic phenanthroline polymer could open a new door for the design of novel heterogeneous transition-metal-free catalysts for direct C−H activation.     

Metal-catalyzed alkyne oxidation/C?H functionalization: Effects of oxidant,temperature, and metal catalyst on chemoselectivity

Gold-catalyzed intermolecular alkyne oxidation has attracted much synthetic attention, but mostly suffering undesired over-oxidation. Recent experiments demonstrated that over-oxidation could be dramatically suppressed in zinc(II)-catalyzed intermolecular alkyne oxidation/C H functionalization. By means of first-principle density functional theory calculations, we explored the mechanism of the M-catalyzed intermolecular alkyne oxidations (M = Zn(OTf)₂ and Au⁺PR₃) as well as the effects of oxidants, temperature, and metal catalysts on chemoselectivity, in an effort to disclose the origin of the extraordinary chemoselectivity pertaining to zinc catalysis. Our calculations indicate that the Zn-catalyzed intermolecular alkyne oxidation/C H functionalization proceeds by a Friedel–Crafts alkylation mechanism rather than metal carbene insertion mechanism. The chemoselectivity of C H functionalization against over-oxidation in Zn catalysis, in comparison with gold catalysis, can be jointly controlled by four factors: (1) the use of less nucleophilic N-oxide, (2) the enhanced electrophilicity and carbocationic nature of the carbenic site in the α-oxo metal carbenoid intermediate, (3) enhanced steric repulsion to incoming oxidant exerted by bulky ancillary ligand in the close nearby of the carbenic site to disfavor intermolecular over-oxidation and (4) the large negative value of activation entropy in the intermolecular over-oxidation pathway, that jointly give rise to lower activation free energy for the intramolecular cyclization/C H functionalization pathway than for the intermolecular over-oxidation pathway. © 2018 Wiley Periodicals, Inc.     

Synthesis of Chiral Aldehyde Catalysts by Pd‐Catalyzed Atroposelective C−H Naphthylation

Chiral aldehyde catalysis opens new avenues for the activation of simple amines. However, the lack of easy access to structurally diverse chiral aldehyde catalysts has hampered the development of this cutting‐edge field. Herein, we report a Pd‐catalyzed atroposelective C?H naphthylation with 7‐oxabenzonorbornadienes for the preparation of axially chiral biaryls with excellent enantioselectivities (up to >99 % ee). This reaction is scalable and robust, which serves as a key step to provide a rapid access to axially chiral aldehyde catalysts through a three‐step C?H functionalization sequence. These chiral aldehydes exhibit better activities and enantioselectivities than the previously reported organocatalysts in the asymmetric activation of glycine derived amides and dipeptides. Moreover, preliminary investigation also discloses that the aldehyde catalyst can effectively override the intrinsic facial selectivity of chiral dipeptide substrates, showcasing the strong chiral induction ability of this type of novel aldehyde catalysts.     

Controlling Regioselectivity in Palladium-Catalyzed C−H Activation/Aryl–Aryl Coupling of 4-Phenylamino[2.2]paracyclophane

Selective activation/functionalization of C−H bonds has emerged as an atom- and step-economical process at the forefront of modern synthetic chemistry. This work reports palladium-catalyzed exclusively para-selective C−H activation/aryl–aryl bond formation with a preference over N-arylation under the Buchwald–Hartwig amination reaction of 4-phenylamino[2.2]paracyclophane. This innovative synthetic strategy allows a facile preparation of [2.2]paracyclophane derivatives featuring disparate para-substitutions at C-4 and C-7 positions in a highly selective manner, gives access to a series of potential candidates for [2.2]paracyclophane-derived new planar chiral ligands. The unprecedented behavior in reactivity and preferential selectivity of C−C coupling over C−N bond formation via C−H activation is unique to the [2.2]paracyclophane scaffold compared to the non-cyclophane analogue under the same reaction conditions. Selective C−H activation/aryl–aryl bond formation and sequential C−N coupling product formation is evidenced unambiguously by X-ray crystallography.     

Synthesis of 3-(quinolin-2-yl)indolizines through iodine-mediated sp3C–H functionalization of azaarenes

An efficient approach toward C–H bond activation using iodine-mediated sp³C–H bond functionalization for the synthesis of dialkyl 3-(quinolin-2-yl)indolizine-1,2-dicarboxylates and dialkyl 3-(quinolin-2-yl)pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylates through 1,3-dipolar cycloaddition reaction of nitrogen ylides with acetylenic esters is described.     

Oxidation-induced <Emphasis Type="Italic">ortho</Emphasis>-selective C–H bond functionalization of 2-naphthylamine derivative

Selective C–H bond functionalization has been emerged as a versatile strategy for the construction of new chemical bonds. In the past decades, the directing group (DG)-assisted C–H bond activation has been developed as one of the most efficient methods for selective C–H functionalization. Although a great progress has been made by utilizing this traditional method, developing new strategy for selective C–H bond functionalization is still highly demanded. Hence, a novel oxidation-induced C–H bond functionalization method was demonstrated in this work. By this new method, ortho-C(sp₂)–H chlorination of N-substituted 2-naphthylamine was realized in a highly selective manner.     

meta-Selective C−H Functionalization of Pyridines

The pyridine moiety is an important core structure for a variety of drugs, agrochemicals, catalysts, and functional materials. Direct functionalization of C−H bonds in pyridines is a straightforward approach to access valuable substituted pyridines. Compared to the direct ortho- and para-functionalization, meta-selective pyridine C−H functionalization is far more challenging due to the inherent electronic properties of the pyridine entity. This review summarizes currently available methods for pyridine meta-C−H functionalization using a directing group, non-directed metalation, and temporary dearomatization strategies. Recent advances in ligand control and temporary dearomatization are highlighted. We analyze the advantages as well as limitations of current techniques and hope to inspire further developments in this important area.     

光/电化学氧化诱导C–H键官能团化

C–H键活化及其官能团化一直被认为是合成化学的圣杯,光/电氧化诱导C–H键官能团化反应为追求更为绿色、原子经济性、步骤经济性更高的现代合成化学提供了新思路.我们借助可见光或电化学氧化诱导策略实现了直接C–H键官能团化,即底物无需预官能团化,无需外加氧化剂,可直接实现碳–碳以及碳–杂键的构建.通过光/电化学氧化诱导策略使得反应在更为温和的条件下进行,能够兼容更多官能团,并且为合成化学提供一条新的途径.近些年,该策略已经应用于不同化学环境C–H官能团化构建多种化学键.本文结合该领域的代表性工作,重点介绍本课题组近些年在光/电氧化诱导C–H键官能团化反应上的研究进展,并对这一领域的前景进行了展望.     

Cp*Co(III) catalyzed annulation of N-Cbz hydrazones for the redox-neutral synthesis of isoquinolines via C–H/N–N bond activation

Abstract

A new cascade oxidative cyclization reaction of N-Cbz hydrazones with internal alkynes has been explored for the preparation of isoquinoline derivatives using Cp*Co^III-catalyst through C–H and N–N bond functionalization. N-Cbz hydrazones are rarely explored as directing group for redox-neutral [4?+?2] cyclization reaction through the cyclometallation and this catalyst system does not require any external oxidizing agent, as well as, silver or antimony salt. The current efficient approach has been utilized for the synthesis of different isoquinoline derivatives with good regioselectivity and yields.     

过渡金属-配体σ键键能在碳-氢键活化中的应用

过渡金属催化的碳-氢(C-H)键活化因其优异的原子经济性及步骤简便性在过去几十年间蓬勃发展,已成为当前构建复杂化合物最常用的策略之一.对该过程中活性中间体的热力学研究有助于加深人们对反应机理的理解,指导新催化剂、新反应的理性设计.然而,近年来该领域的发展颇为缓慢,相应的报道十分零散,缺少系统的归纳和总结.本综述简要梳理...     

Nickel/NHC‐Catalyzed Asymmetric C−H Alkylation of Fluoroarenes with Alkenes: Synthesis of Enantioenriched Fluorotetralins

Chiral polyfluoroarene derivatives are an important scaffold in chemistry. An unprecedented enantioselective C?H alkylation of polyfluoroarenes with alkenes is described. The reaction employs bulky chiral N‐heterocyclic carbene (NHC) ligands for nickel catalysts to enable exclusive activation of C?H bonds over C?F bonds and complete endo‐selective C?H annulation and excellent enantioselectivity. A wide variety of chiral fluorotetralins, compounds otherwise difficultly accessed but serve as important bioisosteric analogs of both tetralin and heterocycle units for drug design, are expediently synthesized from easily available substrates. To our knowledge, this is the first example of catalytic enantioselective C?H functionalization of polyfluoroarenes.     

Catalytic Gold Chemistry: From Simple Salts to Complexes for Regioselective C−H Bond Functionalization

Gold coordinated to neutral phosphines (R₃P), N-heterocyclic carbenes (NHCs) or anionic ligands is catalytically active in functionalizing various C−H bonds with high selectivity. The sterics/electronic nature of the studied C−H bond, oxidation state of gold and stereoelectronic capacity of the coordinated auxiliary ligand are some of the associated selectivity factors in gold-catalyzed C−H bond functionalization reactions. Hence, in this review a comprehensive update about the action of different types of gold catalysts, from simple to sophisticated ones, on C−H bond reactions and their regiochemical outcome is disclosed. This review also highlights the catalytic applications of Au(I)- and Au(III)-species in creating new opportunities for the regio- and site-selective activation of challenging C−H bonds. Finally, it also intends to stress the potential applications in selective C−H bond activation associated with a variety of heterocycles recently described in the literature.