Cross‐Coupling of Organolithium with Ethers or Aryl Ammonium Salts by C−O or C−N Bond Cleavage

Various aryl‐, alkenyl‐, and/or alkyllithium species reacted smoothly with aryl and/or benzyl ethers with cleavage of the inert C?O bond to afford cross‐coupled products, catalyzed by commercially available [Ni(cod)₂] (cod=1,5‐cyclooctadiene) catalysts with N‐heterocyclic carbene (NHC) ligands. Furthermore, the coupling reaction between the aryllithium compounds and aryl ammonium salts proceeded under mild conditions with C?N bond cleavage in the presence of a [Pd(PPh₃)₂Cl₂] catalyst. These methods enable selective sequential functionalizations of arenes having both C?N and C?O bonds in one pot.     

Exploiting Strained Rings in Chelation Guided C−H Functionalization: Integration of C−H Activation with Ring Cleavage

Strained ring systems are regarded as privileged coupling partners in directed C?H bond functionalization and have emerged as a potential research area in organic synthesis. The inherent ring strain in these systems acts as a driving force, allowing the facile construction of diversified structural scaffolds via integrating C?H activation and ring‐scission. The mechanistic underpinnings allows the implementation of a plethora of C?H bonds across plentiful organic substrates, including the less reactive alkyl ones. Considering the synthetic space, this area will foster developments of novel synthetic methods in chelation guided C?H functionalization. This review will focus on recent developments in transition‐metal catalyzed chelation assisted concomitant C?H activation and ring scission of strained rings to attain molecular complexity.     

Copper Catalyzed C−H Activation

Activation of C?H bonds and their application in cross coupling chemistry has received a wider interest in recent years. The conventional strategy in cross coupling reaction involves the pre‐functionalization step of coupling reactants such as organic halides, pseudo‐halides and organometallic reagents. The C?H activation facilitates a simple and straight forward approach devoid of pre‐functionalization step. This approach also addresses the environmental and economical issues involved in several chemical reactions. In this account, we have reported C?H bond activation of small organic molecules, for example, formamide C?H bond can be activated and coupled with β‐dicarbonyl or 2‐carbonyl substituted phenols under oxidative conditions to yield carbamates using inexpensive copper catalysts. Phenyl carbamates were successfully synthesized in moderate to good yields by cross dehydrogenative coupling (CDC) of phenols with formamides using copper catalysts in presence of a ligand. We have also prepared unsymmetrical urea derivatives by oxidative cross coupling of formamides with amines using copper catalysts. Synthesis of N,N‐dimethyl substituted amides, 5‐substituted‐γ‐lactams and α‐acyloxy ethers was carried out from carboxylic acids using recyclable CuO nanoparticles. Copper nanoparticles afforded N‐aryl‐γ‐amino‐γ‐lactams by oxidative coupling of aromatic amines with 2‐pyrrolidinone. Reusable transition metal HT‐derived oxide catalyst was used for the synthesis of N,N‐dimethyl substituted amides by the oxidative cross‐coupling of carboxylic acids and substituted benzaldehydes. Overview of our work in this area is summarized.     

Activating a Peroxo Ligand for C−O Bond Formation

Dioxygen activation for effective C?O bond formation in the coordination sphere of a metal is a long‐standing challenge in chemistry for which the design of catalysts for oxygenations is slowed down by the complicated, and sometimes poorly understood, mechanistic panorama. In this context, olefin–peroxide complexes could be valuable models for the study of such reactions. Herein, we showcase the isolation of rare “Ir(cod)(peroxide)” complexes (cod=1,5‐cyclooctadiene) from reactions with oxygen, and then the activation of the peroxide ligand for O?O bond cleavage and C?O bond formation by transfer of a hydrogen atom through proton transfer/electron transfer reactions to give 2‐iradaoxetane complexes and water. 2,4,6‐Trimethylphenol, 1,4‐hydroquinone, and 1,4‐cyclohexadiene were used as hydrogen atom donors. These reactions can be key steps in the oxy‐functionalization of olefins with oxygen, and they constitute a novel mechanistic pathway for iridium, whose full reaction profile is supported by DFT calculations.     

Cobalt‐Catalyzed Tandem C−H Activation/C−C Cleavage/C−H Cyclization of Aromatic Amides with Alkylidenecyclopropanes

A cobalt‐catalyzed chelation‐assisted tandem C?H activation/C?C cleavage/C?H cyclization of aromatic amides with alkylidenecyclopropanes is reported. This process allows the sequential formation of two C?C bonds, which is in sharp contrast to previous reports on using rhodium catalysts for the formation of C?N bonds. Here the inexpensive catalyst system exhibits good functional‐group compatibility and relatively broad substrate scope. The desired products can be easily transformed into polycyclic lactones with m‐CPBA. Mechanistic studies revealed that the tandem reaction proceeds through a C?H cobaltation, β‐carbon elimination, and intramolecular C?H cobaltation sequence.     

Carboxylic Acids as Directing Groups for C−H Bond Functionalization

The selective transformation of C?H bonds is one of the most desirable approaches to creating complexity from simple building blocks. Several directing groups are efficient in controlling the regioselectivity of catalytic C?H bond functionalizations. Among them, carboxylic acids are particularly advantageous, since they are widely available in great structural diversity and at low cost. The carboxylate directing groups can be tracelessly cleaved or may serve as the anchor point for further functionalization through decarboxylative couplings. This Minireview summarizes the substantial progress made in the last few years in the development of reactions in which carboxylate groups direct C?H bond functionalizations with formation of C?C, C?O, C?N, or C?halogen bonds at specific positions. It is divided into sections on C?C, C?O, C?N, and C?halogen bond formation, each of which is subdivided by reactions and product classes. Particular emphasis is placed on methods that enable multiple derivatizations by combining carboxylate‐directed C?H functionalization with decarboxylative couplings.     

A Visible‐Light‐Driven Iminyl Radical‐Mediated C−C Single Bond Cleavage/Radical Addition Cascade of Oxime Esters

A room‐temperature, visible‐light‐driven N‐centered iminyl radical‐mediated and redox‐neutral C?C single bond cleavage/radical addition cascade reaction of oxime esters and unsaturated systems has been accomplished. The strategy tolerates a wide range of O‐acyl oximes and unsaturated systems, such as alkenes, silyl enol ethers, alkynes, and isonitrile, enabling highly selective formation of various chemical bonds. This method thus provides an efficient approach to various diversely substituted cyano‐containing alkenes, ketones, carbocycles, and heterocycles.     

纤维素及其衍生物催化脱氧转化制化学品

纤维素是木质纤维素生物质中最为丰富的组分,将其催化转化制备高附加值化学品在生物质资源化利用中占据极为重要的一席之地。由于纤维素中氧含量过高,需选择性地脱除部分氧原子才可获得满足当前化学工业对各类高值化学品的要求。近年来,针对纤维素以及由其衍生的关键平台分子葡萄糖和5-羟甲基糠醛(HMF)等催化脱氧的研究已引起广泛关注,并取得诸多重要进展。在此,我们总结了具有代表性的多相催化剂体系,讨论了利用氢解或脱水脱氧策略分别将纤维素和葡萄糖等分子中一个或多个C―O键裁剪制备乙醇、烯烃或己二酸等的研究。我们还着重介绍了HMF和其衍生的呋喃化合物选择性剪切C―OH/C＝O键或呋喃环中的C―O―C键分别制备二甲基呋喃和1, 6-己二醇等催化体系。此外,对各多相催化剂的作用机制和特定C―O断键机理也分别进行了探讨,以期深入理解纤维素及其衍生物的催化脱氧反应。     

纤维素及其衍生物催化脱氧转化制化学品

Biomass, as a renewable carbon resource in nature, has been considered as an ideal starting feedstock to produce various valuable chemicals, fuels, and materials, and thus, can help build a sustainable chemical industry. Because cellulose is one of the richest components in lignocellulosic biomass, the efficient transformation of cellulose plays a crucial role in biomass utilization. However, there are many oxygen-containing groups in cellulose, and therefore, the selective removal of particular functional groups from cellulose becomes an essential step in the synthesis of the chemicals or fuels that can meet the requirements set by current chemical industries. In the past decades, several efficient catalytic systems have been developed to selectively split the C―O bonds inside cellulose and its derivatives, thereby producing various valuable chemicals. In this review article, we highlight recent progress made in the selective deoxygenation of cellulose and its derived key platforms such as glucose and 5-hydroxymethyl furfural (HMF) into ethanol, dimethyl furfural (DMF), 1, 6-hexanediol (1, 6-HD), and adipic acid. The selection of these reactions is primarily because these chemicals are of great significance in chemical industries. More importantly, the formation of these chemicals represents the cleavage of different C―O bonds in biomass molecules. For instance, the synthesis of ethanol requires cleaving of only one C―O bond and two C―C bonds of the glucose unit inside cellulose. If two or more C―O bonds in the sugar or sugar acids are cleaved, olefins, oxygen-reduced sugars, and adipic acid will be attained. HMF has a furan ring linked by hydroxyl/carbonyl groups, and hence, either a furanic compound (e.g., DMF) or linear products (e.g., 1, 6-HD and adipic acid) can be synthesized by selective removal of hydroxyl/carbonyl oxygen or ring oxygen atoms. This article focuses on the selective cleavage of particular C―O bonds via heterogeneous catalysis. Efficient catalytic systems using hydrogenolysis and/or deoxydehydration strategies for these transformations are discussed. Moreover, the functions of typical catalysts and reaction mechanisms are presented to obtain insight into the C―O bond cleavage in these biomass molecules. Additionally, other factors such as reaction conditions that also influence the deoxygenation performance are analyzed. We hope that these knowledge gained on the catalytic deoxygenation of cellulose and its derived platforms will promote the rational design of effective strategies or catalysts in the future utilization of lignocellulosic biomass.     

Rh‐Catalyzed Direct Carboxylation of Alkenyl C−H Bonds of Alkenylpyrazoles

The Rh‐catalyzed direct carboxylation of alkenyl C?H bonds was achieved by using pyrazole as a removable directing group. In the presence of 5 mol% RhCl₃ ? 3H₂O, 6 mol% P(Mes)₃, and 2 equiv. of AlMe₂(OMe), the alkenyl C?H bond of various alkenylpyrazoles was directly carboxylated in good yields under CO₂ atmosphere. Furthermore, several useful transformations of the pyrazole moiety of the product were achieved to afford synthetically useful carboxylic acid derivatives in good yields.     

Site‐Selective C−H Oxygenation via Aryl Sulfonium Salts

Herein, we report a two‐step process forming arene C?O bonds in excellent site‐selectivity at a late‐stage. The C?O bond formation is achieved by selective introduction of a thianthrenium group, which is then converted into C?O bonds using photoredox chemistry. Electron‐rich, ‐poor and ‐neutral arenes as well as complex drug‐like small molecules are successfully transformed into both phenols and various ethers. The sequence differs conceptually from all previous arene oxygenation reactions in that oxygen functionality can be incorporated into complex small molecules at a late stage site‐selectively, which has not been shown via aryl halides.     

C−H and C−N Activation at Redox‐Active Pyridine Complexes of Iron

Pyridine activation by inexpensive iron catalysts has great utility, but the steps through which iron species can break the strong (105–111 kcal mol⁻¹) C−H bonds of pyridine substrates are unknown. In this work, we report the rapid room‐temperature cleavage of C−H bonds in pyridine, 4‐tert‐butylpyridine, and 2‐phenylpyridine by an iron(I) species, to give well‐characterized iron(II) products. In addition, 4‐dimethylaminopyridine (DMAP) undergoes room‐temperature C−N bond cleavage, which forms a dimethylamidoiron(II) complex and a pyridyl‐bridged tetrairon(II) square. These facile bond‐cleaving reactions are proposed to occur through intermediates having a two‐electron reduced pyridine that bridges two iron centers. Thus, the redox non‐innocence of the pyridine can play a key role in enabling high regioselectivity for difficult reactions.     

Carbon Monoxide Activation by a Molecular Aluminium Imide: C−O Bond Cleavage and C−C Bond Formation

Anionic molecular imide complexes of aluminium are accessible via a rational synthetic approach involving the reactions of organo azides with a potassium aluminyl reagent. In the case of K₂[( NON )Al(NDipp)]₂ ( NON =4,5‐bis(2,6‐diisopropylanilido)‐2,7‐di‐tert‐butyl‐9,9‐dimethyl‐xanthene; Dipp=2,6‐diisopropylphenyl) structural characterization by X‐ray crystallography reveals a short Al?N distance, which is thought primarily to be due to the low coordinate nature of the nitrogen centre. The Al?N unit is highly polar, and capable of the activation of relatively inert chemical bonds, such as those found in dihydrogen and carbon monoxide. In the case of CO, uptake of two molecules of the substrate leads to C?C coupling and C≡O bond cleavage. Thermodynamically, this is driven, at least in part, by Al?O bond formation. Mechanistically, a combination of quantum chemical and experimental observations suggests that the reaction proceeds via exchange of the NR and O substituents through intermediates featuring an aluminium‐bound isocyanate fragment.     

Site‐Selective Remote Radical C−H Functionalization of Unactivated C−H Bonds in Amides Using Sulfone Reagents

A general and practical strategy for remote site‐selective functionalization of unactivated aliphatic C?H bonds in various amides by radical chemistry is introduced. C?H bond functionalization is achieved by using the readily installed N‐allylsulfonyl moiety as an N‐radical precursor. The in situ generated N‐radical engages in intramolecular 1,5‐hydrogen atom transfer to generate a translocated C radical which is subsequently trapped with various sulfone reagents to afford the corresponding C?H functionalized amides. The generality of the approach is documented by the successful remote C?N₃, C?Cl, C?Br, C?SCF₃, C?SPh, and C?C bond formation. Unactivated tertiary and secondary C?H bonds, as well as activated primary C?H bonds, can be readily functionalized by this method.     

Construction of Fused Pyrrolidines and β‐Lactones by Carbene‐Catalyzed C−N,C−C,and C−O Bond Formations

A carbene‐catalyzed intermolecular C−N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused β‐lactones, is disclosed. The nitrogen‐containing bicyclic β‐lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene‐catalyzed asymmetric carbon–heteroatom bond‐forming reactions.     

Construction of Fused Pyrrolidines and β‐Lactones by Carbene‐Catalyzed C−N,C−C,and C−O Bond Formations

A carbene‐catalyzed intermolecular C−N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused β‐lactones, is disclosed. The nitrogen‐containing bicyclic β‐lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene‐catalyzed asymmetric carbon–heteroatom bond‐forming reactions.     

Asymmetric Desymmetrization via Metal‐Free C−F Bond Activation: Synthesis of 3,5‐Diaryl‐5‐fluoromethyloxazolidin‐2‐ones with Quaternary Carbon Centers

We disclose the first asymmetric activation of a non‐activated aliphatic C?F bond in which a conceptually new desymmetrization of 1,3‐difluorides by silicon‐induced selective C?F bond scission is a key step. The combination of a cinchona alkaloid based chiral ammonium bifluoride catalyst and N,O‐bis(trimethylsilyl)acetoamide (BSA) as the silicon reagent enabled the efficient catalytic cycle of asymmetric C_sp3?F bond cleavage under mild conditions with high enantioselectivities. The ortho effect of the aryl group at the prostereogenic center is remarkable. This concept was applied for the asymmetric synthesis of promising agrochemical compounds, 3,5‐diaryl‐5‐fluoromethyloxazolidin‐2‐ones bearing a quaternary carbon center.     

Combined Photoredox/Enzymatic C−H Benzylic Hydroxylations

Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value‐added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single‐flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.     

生物质转化中C―O/C―C键的活化断裂

生物质作为自然界中唯一可持续的有机碳来源,在解决环境和能源问题、创建一个碳中和的社会方面展现出巨大的潜力。木质生物质是由具有C―O/C―C键的基本结构单元构成的高分子化合物,活化、断裂这些C―O/C―C键是生物质高值化利用的关键,因此在过去十年中受到了广泛的关注。本文首先简要综述了生物质转化中C―O/C―C键催化断裂的现状,主要关注C―O/C―C键断裂的关键挑战和现有策略。我们的目标不是全面概述C―O/C―C键活化断裂的现况,而是提出与C―O/C―C键断裂相关的核心问题并且对未来的研究作出展望。我们选择了碳水化合物和木质素中几种具有代表性的C―O/C―C键来讨论它们在不同情况下协同催化断裂的机理,然后对未来的研究提出自己的见解。     

生物质转化中C―O/C―C键的活化断裂

Sustainable fuels and chemicals are receiving unprecedented attention worldwide in the context of achieving global carbon neutrality. Biomass, as the only natural and sustainable carbon-based source, shows great potential in addressing our current environmental/energy problems and in creating a carbon-neutral society. Lignocellulosic biomass is made up of basic structural units containing C―O/C―C bonds, and the catalytic cleavage of these C―O/C―C bonds is the key for biomass valorization; thus, garnering considerable attention in the past decade. This viewpoint begins with a brief report on the current status of catalytic activation/cleavage of C―O/C―C bonds during biomass conversion, and then goes on to discuss the key challenges experienced and possible strategies that can be implemented using cooperative catalysis. Our goal is not to provide a comprehensive overview of the activation/cleavage of the C―O/C―C bonds in biomass, but rather to highlight the core questions and challenges related to this process and the requirements for future investigations. We selected several representative C―O/C―C bonds in carbohydrates and lignin to discuss their catalytic mechanism in terms of total/selective bond cleavage, and then present our own insights for future studies. Therefore, this article mainly discusses the following two aspects: (1) The activation and cleavage of C―O bonds, which includes total and selective C―O bond cleavage in furan-based fuel precursors and lignin. When aiming to produce liquid fuels, including alkanes and arenes from biomass, the total cleavage of C―O bonds is essential. During the hydrodeoxygenation (HDO) of furan-based fuel precursors, various C―O bonds need to be cleaved, especially the C―O bond of each tetrahydrofuran ring, which has the highest bond energy. When compared with the total HDO of fuel precursors, the removal of the phenolic hydroxyl groups in lignin to produce arenes is more challenging because of the competition between the over-hydrogenation of the benzene rings and the cleavage of phenolic C―O bonds. The selective or partial cleavage of C―O/C―C bonds to form highly functionalized chemicals has recently attracted great interest and is believed to be a dynamic future research avenue. For example, the production of phenol from lignin or lignin-model compounds, through the selective removal of methoxy groups and para-side-chain groups, while preserving the phenolic hydroxyl groups, has been extensively explored in the past few years. (2) The other important aspect of this article is the cleavage of the C―C bonds in carbohydrates and lignin. The cleavage of carbohydrate C―C bonds occurs via retro-aldol condensation, which produces propylene glycol, ethylene glycol, ethanol, and lactic acid. The cleavage of C―C bonds in lignin is challenging because the bond energy of the C―C bonds is generally higher than that of the C―O bonds in lignin. Therefore, in this section, we discuss the cleavage of the strongest 5―5' bond in lignin. Finally, some subjective perspectives and future directions are provided, also highlighting several major challenges in this field.