Introduction

J.-Q. Yu

The inertness of C—H bonds (excluding acidic C—H bonds) has, since the 1960s, fueled curiosity-driven chemical research. The potential to replace C—H bonds with C—C and C—heteroatom bonds has fascinated chemists in the field of catalysis and synthesis as this offers an untapped avenue for developing new reactions that can be used as new disconnections for making molecules. As a consequence, a number of approaches have been developed to cleave and functionalize C—H bonds: Biomimetic oxidation based on iron, manganese, copper, or cobalt catalysts has led to the accumulation of a vast amount of fundamental knowledge of oxidation chemistry; carbene and nitrene insertion are among the earliest C—H activation reactions that have found their way into synthetic applications; and radical C—H abstraction has also been explored in the past and has recently attracted new interest. That said, based on the sheer number of publications, it is probably fair to say that metal insertions into C—H bonds to form well-defined carbon–metal species and subsequent functionalization of these intermediates is the most extensively investigated of the C—H functionalization techniques. Despite the rich history of C—H activation chemistry, the pace of growth of the field in the past decade is unprecedented. Major advances in two directions are mainly responsible for these new developments: First, many new redox catalytic cycles have been invented or improved to accommodate C—H activation reactions. Second, new reactivity has been obtained through weak coordination of a broad range of substrates with metal catalysts.

Given the advances made in the field of C—H activation, and the breadth of applicability of this technique in modern organic synthesis, the editors of Science of Synthesis consider that the time is ripe for an up to date and focused new addition to the Reference Library on this high-impact topic that is sure to help shape the future direction of chemical science. The organization of this two-volume series is based on the nature of the bond formed to carbon in place of the C—H bond. Each chapter covers a specific methodology so that the hierarchy of the work is kept as flat as possible. As such, experts in the field critically review the state of the art in areas of C—H activation chemistry, and a wide variety of methods by which various bonds to carbon (i.e., C—C, C—Hal, C—N, C—O, and C—B bonds) may be formed are examined. Specific focus is applied to the nature of the substrate, the transition-metal catalyst used, and any specific reagents or techniques that may be applied. To aid practical application of the information contained herein, both for teaching and research, the authors have been encouraged to include typical or general experimental procedures for the best methods.

Volume 1 concerns the formation of C—C bonds by both arene and hetarene C—H activation. For arene C—H activation the material is subdivided by coupling partner (arylation, vinylation, and alkylation) and also by the catalyst system used. The first four sections cover arylation. A chapter by V. Gevorgyan and F. S. Melkonyan (▶ Section 1.1.1) discusses reaction using a palladium(0) catalyst. Both intra- and intermolecular coupling to give various polycyclic and biaryl products, and the effects on reaction of directing groups are described. The second chapter, by C.-H. Cheng and P. Gandeepan (▶ Section 1.1.2), covers arylation using a palladium(II)/palladium(IV) catalyst system, and the role of chelation assistance in reaction is again emphasized. The third contribution, written by W. Su and M. Zhang (▶ Section 1.1.3), discusses arylation using palladium(II) catalysts in the presence of organometallic reagents. The role of palladium in decarboxylative coupling of carboxylic acids is also described. The fourth chapter, by M. Seki (▶ Section 1.1.4), features arylation using ruthenium(II) catalysts; the factors affecting the reaction (including catalyst, ligand, additive, leaving group, and solvent effects) are described in a logical, systematic manner. The next two contributions cover vinylation of arenes. The first of these, by V. M. Dong and P. K. Dornan (▶ Section 1.1.5), discusses vinylation using palladium catalysts, including oxidative Heck-type coupling of arenes (and the effect thereupon of directing groups) and direct arylation of vinyl halides. The second vinylation section, by M. Miura and T. Satoh (▶ Section 1.1.6), covers vinylation using rhodium(III) catalysts and focuses upon both oxidative and non-oxidative coupling of arenes with alkenes and alkynes. This is followed by two chapters on the alkylation of arenes. The first of these, written by C. S. Yi (▶ Section 1.1.7), covers metal-catalyzed alkylation using various electrophiles [RX compounds, where X is a halogen (Cl, Br, I), metalloid (B, Si, Sn), or chalcogen (O, S)]. The second alkylation section, by T. Shibata and K. Tsuchikama (▶ Section 1.1.8), discusses metal-catalyzed alkylation using alkenes; the role of various catalysts (Ru, Rh, Ir, Co, etc.) and substrate-bound directing groups is described. The formation of C—C bonds by hetarene C—H activation is, in contrast, covered by Y. Nakao as a single topic in ▶ Section 1.2. The coupling of hetarenes with a variety of C(sp3) centers (alkylation), C(sp2) centers (arylation, vinylation), and C(sp) centers (alkynylation, cyanation) is described systematically in this sizable contribution in a logical, easily digested fashion.

Volume 2 concerns the formation of C—C bonds by C—H activation of non-(het)arene substrates as well as by C—H activation using special reagents or techniques. The formation of C—heteroatom bonds by (predominantly arene) C—H activation is also included here. For C—C bond formation, the material is initially subdivided by substrate. The first contribution, by G. Liu and P. Chen (Section 2.1), covers allylic C—H activation and the material is categorized systematically depending on the catalyst used. The second chapter, by O. Baudoin (Section 2.2), covers alkyl C—H activation. Various directing effects, including heteroatom direction, and oxidative addition processes are described therein. A number of “special topics” for C—C bond formation are then discussed independently of the substrate used. The first of these techniques, the use of carbenes for C—H activation, is presented by X. P. Zhang and X. Cui (Section 2.3) with both intra- and intermolecular carbene insertion discussed. This is followed by coverage of C—H activation using radicals, as presented by W.-Y. Yu and W.-W. Chan (Section 2.4), which includes discussion of transition-metal-catalyzed acylation, metal-free arylation, and Minisci-type hetarene functionalization. Subsequently, double C—H activation is described by S.-L. You and J.-B. Xia (Section 2.5), who discuss oxidative homocoupling and cross-coupling methods as well less common intramolecular double C—H activation processes. The next contribution, by C. Liu, H. Zhang, and A. Lei (Section 2.6), covers C—C bond formation by carboxylation or carbonylation and, as in several other areas, the effect of directing groups is highlighted.

For C—heteroatom bond formation, the material discussed concerns predominantly arene substrates, and is thus subdivided by the nature of the bond formed. The first chapter on this topic, by M. S. Sanford and A. Cook (Section 2.7), concerns C—halogen bond formation; various ligand effects, as well as reaction in the absence of directing groups, are described. The discussion of the formation of C—N bonds is divided into two parts: The first contribution, by P. Dauban and B. Darses (Section 2.8), concerns C—N bond formation using palladium catalysis. Intramolecular reaction to form five- and six-membered rings is described, as is ortho-amidation in intermolecular processes. The second contribution, by S. B. Blakey and N. Mace Weldy (Section 2.9), covers nitrene insertion; both inter- and intramolecular amination are discussed. Coverage of the formation of C—O bonds is likewise split into two chapters. The first of these, by Y. Hitomi and K. Arakawa (Section 2.10), covers biomimetic and organocatalytic methods for arene C—H oxidation and comments upon the use of various metal complexes (porphyrin, non-heme iron, etc.) and reagents (e.g., phthaloyl peroxide). The second oxidation chapter, by G.-W. Wang and D.-D. Li (Section 2.11), describes arene C—H activation via metal-catalyzed oxidation, and the use of various metal catalysts in inter- and intramolecular processes is discussed systematically. The second volume concludes with discussion of the formation of C—B bonds via arene C—H activation in a chapter by J. M. Lassaletta, A. Ros, and R. Fernández (Section 2.12). Non-directed borylation is covered, as are various directed methods including site-selective, relay-directed, and outer-sphere ortho-C—H borylation. The formation of C—B bonds is of special interest because of the potential applications of aromatic organoboranes in synthesis, not only in cross-coupling (Suzuki–Miyaura) chemistry, but also in many other...