Recent Advances in Radical‐Mediated C—C Bond Fragmentation of Non‐Strained Molecules

The carbon‐carbon (C—C) σ‐bonds construct the fundamental frameworks of organic molecules. The direct functionalization of C—C bonds represents one of the most efficient and step‐economical transformations in synthetic chemistry. The past few decades have witnessed the fast development of transition‐metal mediated C—C bond activation. In contrast, the radical‐promoted C—C bond cleavage has received relatively less attention. As the occurrence of ring strain significantly facilitates the fission of cyclic C—C bonds via radical approaches, the strain relief‐driven C—C bond activation mostly relies on the three‐ and four‐membered rings. The C—C activation of non‐strained molecules such as medium‐ or large‐sized rings and linear alkanes remains challenging. In this review, we will focus on the recent advances in radical‐mediated C—C bond activation of non‐strained molecules. Herein, the alkoxy‐ and iminyl‐radical triggered scission of non‐strained C—C bonds and C—C cleavage via the strategy of remote functional group migration is summarized.     

Unstrained CarbonCarbon Bond Cleavage

This Focus Review presents recent developments in the cleavage of C? C bonds in organic molecules. Significant progress in C? C activation, including the development of a variety of new synthetic strategies, has contributed to the development of this field over the past few decades. Transition‐metal‐mediated C? C bond cleavage has been shown to be a quite efficient process and several elegant metal‐free methods have also recently been developed. Strained rings have been widely used in C? C cleavage transformations; however, unstrained C? C activation has increasingly caught the attention of organic researchers, which inspired us to clarify the developments in this field.     

Dry synthesis of triple cumulative double bonds (C=C=C=N) on Si(111)-7 x 7 surfaces

The interactions of cyanoacetylene and diacetylene with a Si(111)-7 x 7 surface have been studied as model systems to mechanistically understand the chemical binding of unsaturated organic molecules to diradical-like silicon dangling bonds. Vibrational studies show that cyanoacetylene mainly binds to the surface through a diradical reaction involving both cyano and C[triple bond]C groups with an adjacent adatom-rest atom pair at 110 K, resulting in an intermediate containing triple cumulative double bonds (C=C=C=N). On the other hand, diacetylene was shown to the covalently attached to Si(111)-7 x 7 only through one of its C[triple bond]C groups, forming an enynic-like structure with a C=C-C[triple bond]C skeleton. These chemisorbed species containing triple cumulative double bonds (C=C=C=N) and C=C-C[triple bond]C may be employed as precursors (or templates) for further construction of bilayer organic films on the semiconductor surfaces.     

Interaction of niobium and tantalum pentahalides with O-donors: coordination chemistry and activation reactions

The chemistry of niobium and tantalum pentahalides, MX(5), with oxygen compounds is reviewed herein. The polynuclear structure of MX(5) is readily broken by addition of oxygen-containing organic molecules, L, to give either mononuclear or ionic dinuclear coordination adducts. Then activation of the organic ligand may take place favoured by several factors, i.e. low M-X bond energy, high temperature, presence of more than one oxygen function within L, L/M molar ratio ≥ 2. The activation reactions are often uncommon in the context of metal halides; they include the cleavage of C(sp3)-O, C(sp2)-O, C-H and C-C bonds, and eventual successive rearrangements proceeding with C-O or C-C couplings. The recently elucidated reactivity of MX(5) with limited amounts of oxygen compounds will be presented, and possible connections with the relevant MX(5)-directed syntheses reported in the literature will be outlined.     

Catalytic reactions involving the cleavage of carbon-cyano and carbon-carbon triple bonds

The catalytic reactions that involve the cleavage of C-CN bonds and carbon-carbon triple bonds are described in this tutorial review. Regarding the cleavage of a C-CN bond, the catalytic reaction can proceed by two different mechanisms: oxidative addition and deinsertion of silyl isocyanide. A carbon-carbon triple bond can be cleaved in the absence of an organic promoter via the formation of unique organometallic species, such as allenylidene and cyclopropyl carbenoid complexes.     

Pd nanoparticles for C-C coupling reactions

The catalytic formation of C-C bonds is one of the most useful transformations in organic synthesis. Over the last decade, the use of transition metal nanoparticles (NPs) in catalysis has attracted much interest and their use in C-C bond formation reactions constitutes one of their most important applications, including the Suzuki, Heck, and Sonogashira reactions. This tutorial review highlights recent work in this active area, considering the stabilising agents used to prepare the NPs, the catalytic results and the recycling possibilities.     

Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

The activation of carbon–fluorine (C?F) bonds is an important topic in synthetic organic chemistry. Metal‐mediated and ‐catalyzed elimination of β‐ or α‐fluorine proceeds under milder conditions than oxidative addition to C?F bonds. The β‐ or α‐fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations through these elimination processes (C?F bond cleavage), which are typically preceded by carbon–carbon (or carbon–heteroatom) bond formation, have been increasingly developed in the past five years as C?F bond activation methods. In this Minireview, we summarize the applications of transition‐metal‐mediated and ‐catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective with early studies and from a systematic perspective with recent studies.     

过渡金属配合物催化乙腈碳碳单键断裂的研究进展

有机化合物中的碳碳单键断裂反应是一类非常重要而且具有挑战性的反应,过去的几十年中,关于有机腈类化合物中碳碳单键的催化断裂反应研究受到了很多的关注。而乙腈作为常用的有机溶剂之一,其分子是有机腈类中的最小分子。本文结合最近几年国内外及本课题组关于乙腈分子的碳碳单键活化断裂的研究,综述了各类过渡金属配合物催化乙腈分子碳碳单键断裂的研究进展,分析了当前存在的问题,提出了对今后研究的展望。     

过渡金属配合物催化乙腈碳碳单键断裂的研究进展

有机化合物中的碳碳单键断裂反应是一类非常重要而且具有挑战性的反应,过去的几十年中,关于有机腈类化合物中碳碳单键的催化断裂反应研究受到了很多的关注。而乙腈作为常用的有机溶剂之一,其分子是有机腈类中的最小分子。本文结合最近几年国内外及本课题组关于乙腈分子的碳碳单键活化断裂的研究,综述了各类过渡金属配合物催化乙腈分子碳碳单键断裂的研究进展,分析了当前存在的问题,提出了对今后研究的展望。     

Chiral nonracemic late-transition-metal organometallics with a metal-bonded stereogenic carbon atom: development of new tools for asymmetric organic synthesis

Transition-metal-catalyzed cross-coupling reactions and the Heck reaction have evolved into powerful tools for the construction of carbon-carbon bonds. In most cases, the reactive organometallic intermediates feature a carbon-transition-metal sigma bond between a sp(2)-hybridized carbon atom and the transition metal (Csp(2)--TM). New, and potentially more powerful approach to transition-metal-catalyzed asymmetric organic synthesis would arise if catalytic chiral nonracemic organometallic intermediates with a stereogenic sp(3)-hybridized carbon atoms directly bonded to the transition metal (C*sp(3)--TM bond) could be formed from racemic or achiral organic substrates, and subsequently participate in the formation of a new carbon-carbon bond (C*sp(3)-C) with retention of the stereochemical information. To date, only a few catalytic processes that are based on this concept, have been developed. In this account, both "classical" and recent studies on preparation and reactivity of stable chiral nonracemic organometallics with a metal-bonded stereogenic carbon, which provide the foundation for the future design of new synthetic transformations exploiting the outlined concept, are discussed, along with examples of relevant catalytic processes.     

过渡金属参与C―H键切断模式的理论研究进展

过渡金属催化活化C―H键来构建新共价键因具有原子经济和合成简捷的特点,已成为合成化学中最为有效策略之一。本文中,我们总结了过渡金属参与的C―H键切断的理论研究进展,并系统性提出了C―H键切断的相关模式,包括:C―H键对金属的氧化加成、碱协助的去质子化、σ-复分解、Friedel-Crafts型亲电芳香取代、α-或β-氢消除以及夺氢活化等。理论计算表明,当使用还原性较强的零价金属催化剂时,反应可按照氧化加成模式进行。当使用金属羧酸盐作为催化剂时,通常以协同金属化-去质子化机理模式实现C―H键切断。当使用阳离子金属催化剂,富电子芳烃比缺电子芳烃优先反应时,C―H键切断则会经历碱协助的内部亲电取代模式。σ-复分解是协同金属化-去质子化机理的另一种模式。如果亲电体对芳烃进行加成时,则可按照Friedel-Crafts型亲电芳香取代方式活化C―H键。α-或β-氢消除也是比较常见的活化C―H键模式。此外,夺氢活化可通过自由基过程实现C―H键活化。本文通过对过渡金属参与的C―H键活化模式的论述旨在为实验提供理论指导。     

Recent progress in transition metal catalysed hydrofunctionalisation of less activated olefins

The electrophilic activation(C-H activation) of alkenes by transition metal catalysts is a fundamental step in a rapidly growing number of catalytic processes since it would provide simple, clean, and economic methods for making controlled and selectively functionalized organic moieties directly from simple olefins. Also catalytic activation of C-H bonds leading to useful organic reactions such as new C-C, C-N and C-O bond formation is of considerable interest for the chemical and pharmaceutical industries and remained a long-term challenge to chemists. A substantial progress has made in the last decade in this area. Contrary to traditional belief, it is nowadays possible to control the regiochemistry of various additions of nucleophiles to alkenes by the choice of transition metal catalysts. Atom economy, an inevitable factor of current research also can be accomplished in these reactions. Developments in this area of selective hydrofunctionalisation of alkenes by taking into consideration of the mechanistic aspects and the role of organometallic catalyst or active species formed during the reaction on the outcome of the reactions are reviewed.     

Direct Sp3α-C-H activation and functionalization of alcohol and ether

Seven kinds of sp(3)α-C-H activation/C-C formation reactions of alcohols and ethers have been reviewed in this tutorial review, from the viewpoint of both methodology and synthetic application, towards the efficiency, chemo-, regio- and stereoselectivity, catalytic system, substrate scope and mechanistic study. Section 2 describes radical-mediated α-C-H activation and addition/elimination of ethers with unsaturated (C=C and C[triple bond]C) species. Sections 3-8 discuss the α-C-H activation and additions of alcohols and/or ethers with unsaturated (C=C, C[triple bond]C, C=O and C=N) compounds, which involve the key processes of radical mediation, carbenoid insertion, 1,5-H-migration, oxidative dehydrogenation coupling, transfer hydrogenative coupling, and metal-mediated C=C insertion into the C-H bond.     

Cross- and Multi-Coupling Reactions Using Monofluoroalkanes

Carbon-fluorine bonds are stable and have demonstrated sluggishness against various chemical manipulations. However, selective transformations of C−F bonds can be achieved by developing appropriate conditions as useful synthetic methods in organic chemistry. This review focuses on C−C bond formation at monofluorinated sp³-hybridized carbons via C−F bond cleavage, including cross-coupling and multi-component coupling reactions. The C−F bond cleavage mechanisms on the sp³-hybridized carbon centers can be primarily categorized into three types: Lewis acids promoted F atom elimination to generate carbocation intermediates; nucleophilic substitution with metal or carbon nucleophiles supported by the activation of C−F bonds by coordination of Lewis acids; and the cleavage of C−F bonds via a single electron transfer. The characteristic features of alkyl fluorides, in comparison with other (pseudo)halides as promising electrophilic coupling counterparts, are also discussed.     

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.     

Synthesis of Conjugated Polymers via Transition Metal Catalysed C−H Bond Activation

Transition metal catalysed C−H bond activation chemistry has emerged as an exciting and promising approach in organic synthesis. This allows us to synthesize a wider range of functional molecules and conjugated polymers in a more convenient and more atom economical way. The formation of C−C bonds in the construction of pi-conjugated systems, particularly for conjugated polymers, has benefited much from the advances in C−H bond activation chemistry. Compared to conventional transition-metal catalysed cross-coupling polymerization such as Suzuki and Stille cross-coupling, pre-functionalization of aromatic monomers, such as halogenation, borylation and stannylation, is no longer required for direct arylation polymerization (DArP), which involve C−H/C−X cross-coupling, and oxidative direct arylation polymerization (Ox-DArP), which involves C−H/C−H cross-coupling protocols driven by the activation of monomers’ C(sp²)−H bonds. Furthermore, poly(annulation) via C−H bond activation chemistry leads to the formation of unique pi-conjugated moieties as part of the polymeric backbone. This review thus summarises advances to date in the synthesis of conjugated polymers utilizing transition metal catalysed C−H bond activation chemistry. A variety of conjugated polymers via DArP including poly(thiophene), thieno[3,4-c]pyrrole-4,6-dione)-containing, fluorenyl-containing, benzothiadiazole-containing and diketopyrrolopyrrole-containing copolymers, were summarized. Conjugated polymers obtained through Ox-DArP were outlined and compared. Furthermore, poly(annulation) using transition metal catalysed C−H bond activation chemistry was also reviewed. In the last part of this review, difficulties and perspective to make use of transition metal catalysed C−H activation polymerization to prepare conjugated polymers were discussed and commented.     

Highly stable organic monolayers for reacting silicon with further functionalities: the effect of the C-C bond nearest the silicon surface

Crystalline Si(111) surfaces have been alkylated in a two-step chlorination/alkylation process using various organic molecules having similar backbones but differing in their C-C bond closest to the silicon surface (i.e., C-C vs C=C vs C[triple bond]C bonds). X-ray photoelectron spectroscopic (XPS) data show that functionalization of silicon surfaces with propenyl magnesium bromide (CH3-CH=CH-MgBr) organic molecules gives nearly full coverage of the silicon atop sites, as on methyl- and propynyl-terminated silicon surfaces. Propenyl-terminated silicon surface shows less surface oxidation and is more robust against solvent attacks when compared to methyl- and propynyl-terminated silicon surfaces. We also show a secondary functionalization process of propenyl-terminated silicon surface with 4'-[3-Trifluoromethyl-3H-diazirin-3-yl]-benzoic acid N-hydroxysuccinimide ester [TDBA-OSu] cross-linker. The Si-CH=CH-CH3 surfaces thus offer a means of attaching a variety of chemical moieties to a silicon surface through a short linking group, enabling applications in molecular electronics, energy conversion, catalysis, and sensing.     

Activation of N−O σ Bonds with Transition Metals: A Versatile Platform for Organic Synthesis and C−N Bonds Formation**

N−O σ bonds containing compounds are versatile substrates for organic synthesis under transition metal catalysis. Their ability to react through both polar (oxidative addition, formation of metallanitrene, nucleophilic substitution) and radical pathways (single electron transfer, homolytic bond scission) have triggered the development of various synthetic methodologies, particularly toward synthesizing nitrogen-containing compounds. In this review, we discuss the different modes of activation of N−O bonds in the presence of transition metal catalysts, emphasizing the experimental and computational mechanistic proofs in the literature to help to design new synthetic pathways toward the synthesis of C−N bonds.     

Factors influencing the reductive cleavage of C-x multiple bonds in their reactions with meal-meal multiple bonds (X = C, N, O, S)

Though metal-metal multiple bonds of the transition elements are redox active, their reactivity towards C-X multiple bonds (X = C, N, O, S) vary greatly depending principally on: 1. The coordination geometry of the metal. 2. The oxidation state of the metal and the electronic configuration of the M-M bond. 3. The nature of the attendant ligands. Specific examples of C-X multiple bond activation at dimolybdenum and ditungsten centers are presented that illustrate the importance of these factors. Evidence is presented to support the view that reductive cleavage of a C-X multiple bond can be considered to be equivalent to an intramolecular redox reaction within a [M2CX] "cluster complex," for which the frontier orbital energies of the C-X and M-M multiple bonds are of paramount importance. Some applications of these C-X reductive cleavage reactions toward organic synthesis are described.