Science of Synthesis

Science of Synthesis is the authoritative and comprehensive reference work for the entire field of organic and organometallic synthesis.

Science of Synthesis presents the important synthetic methods for all classes of compounds and includes:

Methods critically evaluated by leading scientists

Background information and detailed experimental procedures

Schemes and tables which illustrate the reaction scope

Preface

As the pace and breadth of research intensifies, organic synthesis is playing an increasingly central role in the discovery process within all imaginable areas of science: from pharmaceuticals, agrochemicals, and materials science to areas of biology and physics, the most impactful investigations are becoming more and more molecular. As an enabling science, synthetic organic chemistry is uniquely poised to provide access to compounds with exciting and valuable new properties. Organic molecules of extreme complexity can, given expert knowledge, be prepared with exquisite efficiency and selectivity, allowing virtually any phenomenon to be probed at levels never before imagined. With ready access to materials of remarkable structural diversity, critical studies can be conducted that reveal the intimate workings of chemical, biological, or physical processes with stunning detail.

The sheer variety of chemical structural space required for these investigations and the design elements necessary to assemble molecular targets of increasing intricacy place extraordinary demands on the individual synthetic methods used. They must be robust and provide reliably high yields on both small and large scales, have broad applicability, and exhibit high selectivity. Increasingly, synthetic approaches to organic molecules must take into account environmental sustainability. Thus, atom economy and the overall environmental impact of the transformations are taking on increased importance.

The need to provide a dependable source of information on evaluated synthetic methods in organic chemistry embracing these characteristics was first acknowledged over 100 years ago, when the highly regarded reference source Houben–Weyl Methoden der Organischen Chemie was first introduced. Recognizing the necessity to provide a modernized, comprehensive, and critical assessment of synthetic organic chemistry, in 2000 Thieme launched Science of Synthesis, Houben–Weyl Methods of Molecular Transformations. This effort, assembled by almost 1000 leading experts from both industry and academia, provides a balanced and critical analysis of the entire literature from the early 1800s until the year of publication. The accompanying online version of Science of Synthesis provides text, structure, substructure, and reaction searching capabilities by a powerful, yet easy-to-use, intuitive interface.

From 2010 onward, Science of Synthesis is being updated quarterly with high-quality content via Science of Synthesis Knowledge Updates. The goal of the Science of Synthesis Knowledge Updates is to provide a continuous review of the field of synthetic organic chemistry, with an eye toward evaluating and analyzing significant new developments in synthetic methods. A list of stringent criteria for inclusion of each synthetic transformation ensures that only the best and most reliable synthetic methods are incorporated. These efforts guarantee that Science of Synthesis will continue to be the most up-to-date electronic database available for the documentation of validated synthetic methods.

Also from 2010, Science of Synthesis includes the Science of Synthesis Reference Library, comprising volumes covering special topics of organic chemistry in a modular fashion, with six main classifications: (1) Classical, (2) Advances, (3) Transformations, (4) Applications, (5) Structures, and (6) Techniques. Titles will include Stereoselective Synthesis, Water in Organic Synthesis, and Asymmetric Organocatalysis, among others. With expertevaluated content focusing on subjects of particular current interest, the Science of Synthesis Reference Library complements the Science of Synthesis Knowledge Updates, to make Science of Synthesis the complete information source for the modern synthetic chemist.

The overarching goal of the Science of Synthesis Editorial Board is to make the suite of Science of Synthesis resources the first and foremost focal point for critically evaluated information on chemical transformations for those individuals involved in the design and construction of organic molecules.

Throughout the years, the chemical community has benefited tremendously from the outstanding contribution of hundreds of highly dedicated expert authors who have devoted their energies and intellectual capital to these projects. We thank all of these individuals for the heroic efforts they have made throughout the entire publication process to make Science of Synthesis a reference work of the highest integrity and quality.

The Editorial Board

July 2010

E. M. Carreira (Zurich, Switzerland)

C. P. Decicco (Princeton, USA)

A. Fuerstner (Muelheim, Germany)

G. Koch (Basel, Switzerland)

G. A. Molander (Philadelphia, USA)

E. Schaumann (Clausthal-Zellerfeld, Germany)

M. Shibasaki (Tokyo, Japan)

E. J. Thomas (Manchester, UK)

B. M. Trost (Stanford, USA)

Science of Synthesis Reference Library

Catalytic Transformations via C—H Activation (2 Vols.)

Biocatalysis in Organic Synthesis (3 Vols.)

C-1 Building Blocks in Organic Synthesis (2 Vols.)

Multicomponent Reactions (2 Vols.)

Cross Coupling and Heck-Type Reactions (3 Vols.)

Water in Organic Synthesis

Asymmetric Organocatalysis (2 Vols.)

Stereoselective Synthesis (3 Vols.)

Abstracts

2.1 C−C and C−X Bond Formation by Allylic C−H Activation

G. Liu and P. Chen

This chapter documents recent studies into allylic functionalization via C−H activation processes catalyzed by metals such as palladium, rhodium, ruthenium, copper, and iron. The focus is on the formation of C−C, C−N, and C−O bonds reported in the last two decades, but more recent developments involving the formation of other C−X bonds, such as C−F and C−Si are also highlighted.

Keywords: allylic C−H activation • alkenes • palladium • rhodium • ruthenium • copper • iron • allylic amines • allylic acetates

2.2 C−C Bond Formation by Alkyl C−H Activation

O. Baudoin

In comparison to the wealth of methods recently developed for the catalytic functionalization of the C(sp²)−H bonds of arenes and hetarenes, relatively little work has focused on the functionalization of the unactivated C(sp³)−H bonds of alkyl fragments. This chapter highlights selected examples of the fast-growing literature on the catalytic functionalization of unactivated C(sp³)−H bonds through organometallic C−H activation, with an emphasis on the most synthetically useful methods. It covers heteroatom-directed C(sp³)−H activation with regard to cross coupling with alkenes, alkynes, and carbon monoxide, organoboron reagents, diaryliodonium salts, and organic halides. Also included is C(sp³)−H activation/intramolecular C−C coupling induced by oxidative addition and non-directed intermolecular C(sp³)−H arylation.

Keywords: C(sp³)−H bond activation • carbon−carbon coupling • transition metals • palladium catalysis • ruthenium catalysis • alkylation

2.3 C−C Bond Formation Using Carbenes

X. Cui and X. P. Zhang

Transition-metal-catalyzed carbene C−H insertion has been developed as one of the most direct and effective methods for the construction of C−C bonds from C−H bonds. During the past two decades, a number of transition-metal-based catalytic systems have been established for asymmetric C−H functionalization via carbene insertion. Synthetically useful systems have been developed to functionalize C−H bonds in both intermolecular and intramolecular fashions. In this chapter, highly selective and practical catalytic systems for stereoselective C−H functionalization via catalytic carbene transfer are summarized. Literature reports are classified and discussed according to the type of C−H bond. This review focuses mainly on the issue of stereoselectivity, particularly on enantioselectivity.

Keywords: asymmetric synthesis • C−H functionalization • transition-metal catalysis • diazo reagents • metal carbenes • dirhodium(II) complexes

2.4 C−C Bond Formation Using Radicals

W.-W. Chan and W.-Y. Yu

Direct C−H carbo-functionalization of (hetero) aromatic rings, as an atom-efficient route for regioselective C−C bond formation, is receiving current attention. In this review, radical coupling of unfunctionalized (het) arenes for C−C bond formation is described. Recent progress on the palladium-catalyzed regioselective C−H acylation of arenes with acyl radicals, as well as the transition-metal-free C−H arylation using aryl radicals, are presented. Some remarkable advances in the Minisci-type radical C−H alkylation of heterocycles are also discussed.

Keywords: C−H functionalization • organocatalysis • palladium • cross coupling • radicals • heterocycles

2.5 C−C Bond Formation by Double C−H Activation

J.-B. Xia and S.-L. You

This chapter focuses on transition-metal-catalyzed aryl−aryl bond-forming reactions via double C−H activation. Biaryl scaffolds have received much attention as a privileged structure broadly found in biologically active natural products, pharmaceuticals, agrochemicals, and functional molecules in material sciences, etc. Transition-metal-catalyzed cross-coupling reactions are the most general and efficient methods to synthesize biaryls, but both coupling partners need to be preactivated in transition-metal-catalyzed cross-coupling reactions when compared with simple arenes. Over the past decade, significant advances have been made in transition-metal-catalyzed biaryl synthesis using simple arenes as substrates via C−H activation. This chapter summarizes representative examples of transition-metal-catalyzed biaryl synthesis using two simple arenes as substrates via double C−H activation.

Keywords: transition-metal catalysis • double C−H activation • biaryl synthesis • directing groups

2.6 C−C Bond Formation by C−H Carboxylation or Carbonylation

H. Zhang, C. Liu, and A. Lei

The direct C−H carbonylation or carboxylation involving carbon monoxide is an ideal and environmentally friendly method toward the synthesis of carboxylic acids and derivatives. Within this emerging area, a number of significant examples have been reported, which are summarized in this chapter. Additionally, the recent progress on C−H carboxylation utilizing carbon dioxide is included in this review.

Keywords: C−H carbonylation • C−H carboxylation • carbon monoxide • carbon dioxide • directing groups • transition-metal catalysis • carboxylic acids • carboxylic esters • carboxylic amides • carbonyl compounds

2.7 C−Hal Bond Formation by Arene C−H Activation

M. S. Sanford and A. Cook

Caryl−H bonds are transformed into Caryl−halogen bonds via transition-metal-catalyzed C−H activation. Fluorination, chlorination, bromination, and iodination are discussed and a wide variety of arenes bearing various directing groups are competent substrates.

Keywords: halogens • carbon−halogen bonds • carbon−hydrogen bonds • regioselectivity • arenes • transition metals • pyridines • amides • quinoxalines • oximes • benzothiazoles • esters • benzonitriles • ketones • carboxylic acids

2.8 C−N Bond Formation by Arene C−H Activation Using a Palladium Catalyst

P. Dauban and B. Darses

The search for methodologies allowing C(sp²)−N bond formation is of utmost interest as the arylamine motif is ubiquitous in nature and life and material sciences. This chapter focuses on palladium-catalyzed arene C−H activation for the direct amination of C(sp²)—H bonds, generally under oxidizing conditions. These processes mainly allow the efficient introduction of carboxamides and sulfonamides, but the insertion of an amino group is also possible. Intramolecular transformations lead to the formation of either five-membered rings, such as carbazoles, indole derivatives, and benzo-fused nitrogen heterocycles, or six-membered rings, such as quinolinones and phenanthridinones. On the other hand, intermolecular reactions occur with complete regioselectivity, generally ortho to an appropriate directing group, which can be an oxime, a ketone, a carboxylic acid, or an amide.

Keywords: palladium • arylamines • amination • intramolecular • intermolecular • regioselectivity • chemoselectivity • directing groups • carboxamides • sulfonamides • oxidants • heterocycles • carbazoles • indoles • dihydroindoles • oxindoles • benzimidazoles • benzotriazoles • quinolinones • phenanthridinones

2.9 C−N Bond Formation by C−H Functionalization via Metal-Catalyzed Nitrene Insertion

N. Mace Weldy and S. B. Blakey

New routes for the formation of C−N bonds are important due to the prevalence of these bonds in complex natural products and molecules of pharmaceutical interest. Metallonitrene amination requires pre-oxidation of an amine, using precursors such as azides, N-(tosyloxy) carbamates, and iminoiodinanes. Binding of a transition-metal catalyst to the nitrene source gives the metallonitrene, which is capable of inserting into C−H bonds. Insertion may be made enantioselective in some systems by the use of a chiral metal complex. Most early examples of metallonitrene C−H amination focused on insertion into benzylic C−H bonds, but recently the substrate scope has been expanded to include aryl, vinyl, and even unactivated tertiary, secondary, and primary bonds.

Keywords: amination • nitrenes • C−N bonds • enantioselectivity • rhodium catalysts • ruthenium catalysts • iridium catalysts • cobalt catalysts • iron catalysts

2.10 C−O Bond Formation by Arene C−H Activation via Biomimetic and Organocatalytic Oxidation

Y. Hitomi and K. Arakawa

This chapter is a summary of selected reactions for C−O bond formation via arene C−H bond activation by biomimetic and organocatalytic oxidation catalysts, which include manganese, iron, copper, and vanadium complexes as well as photocatalysts.

Keywords: arene complexes • arenes • hydroxylation • oxidation • oxygenation • quinones • phenols • porphyrins • iron catalysts • iron complexes • manganese catalysts • manganese complexes • ruthenium catalysts • ruthenium complexes • hydroperoxides • hydroquinones • copper catalysts • copper complexes

2.11 C−O Bond Formation by Arene C−H Activation via Metal-Catalyzed Oxidation

D.-D. Li and G.-W. Wang

This chapter highlights significant achievements in metal-catalyzed selective oxidation processes of arene C−H bonds to construct C−O bonds. A directing group is usually required to achieve high ortho-regioselectivity. Various functional groups have been fruitfully exploited as the directing groups for the acyloxylation, alkoxylation, hydroxylation, and intramolecular C−O cyclization of arenes by the palladium-, copper-, and rutheniumcatalyzed C−H activation. These transition-metal-catalyzed C−H/C−O processes can be efficiently achieved by utilizing either a monodentate or bidentate directing group.

Keywords: arene C−H bond activation • C−O bond formation • palladium catalysis • copper catalysis • ruthenium catalysis • acyloxylation • alkoxylation • hydroxylation • intramolecular C−O cyclization

2.12 C−B Bond Formation by Arene C−H Activation

A. Ros, R. Fern ndez, and J. M. Lassaletta

This chapter provides a survey of the most useful available methodologies for the direct borylation of arenes and hetarenes, which proceed in all cases via a C−H activation event mediated by transition metals such as rhodium, iridium, or palladium. The borylation reactions have been organized into two main groups: (1) direct borylations with regioselectivity mainly controlled by steric factors, and (2) site-selective borylation, with regioselectivity driven by directing effects.

Keywords: C−H activation • organoboron compounds • borylation • arenes • hetarenes • synthetic methods • rhodium • iridium • palladium • directing groups

Catalytic Transformations via C—H Activation 2

Preface

Abstracts

Table of Contents

2.1 C−C and C−X Bond Formation by Allylic C−H Activation

G. Liu and P. Chen

2.2 C−C Bond Formation by Alkyl C−H Activation

O. Baudoin

2.3 C−C Bond Formation Using Carbenes

X. Cui and X. P. Zhang

2.4 C−C Bond Formation Using Radicals

W.-W. Chan and W.-Y. Yu

2.5 C−C Bond Formation by Double C−H Activation

J.-B. Xia and S.-L. You

2.6 C−C Bond Formation by C−H Carboxylation or Carbonylation

H. Zhang, C. Liu, and A. Lei

2.7 C−Hal Bond Formation by Arene C−H Activation

M. S. Sanford and A. Cook

2.8 C−N Bond Formation by Arene C−H Activation Using a Palladium Catalyst

P. Dauban and B. Darses

2.9 C−N Bond Formation by C−H Functionalization via Metal-Catalyzed Nitrene Insertion

N. Mace Weldy and S. B. Blakey

2.10 C−O Bond Formation by Arene C−H Activation via Biomimetic and Organocatalytic Oxidation

Y. Hitomi and K. Arakawa

2.11 C−O Bond Formation by Arene C−H Activation via Metal-Catalyzed Oxidation

D.-D. Li and G.-W. Wang

2.12 C−B Bond Formation by Arene C−H Activation

A. Ros, R. Fernández, and J. M. Lassaletta

Keyword Index

Author Index

Abbreviations

Table of Contents

2.1 C−C and C−X Bond Formation by Allylic C−H Activation

G. Liu and P. Chen

2.1 C−C and C−X Bond Formation by Allylic C−H Activation

2.1.1 C−C Bond Formation by Allylic C−H Activation

2.1.1.1 Reaction Using a Palladium Catalyst

2.1.1.2 Reaction Using Rhodium and Ruthenium Catalysts

2.1.1.3 Reaction Using Copper, Iron, and Cobalt Catalysts

2.1.2 C−N Bond Formation by Allylic C−H Activation

2.1.2.1 Reaction Using a Palladium Catalyst

2.1.2.2 Reaction Using Rhodium and Ruthenium Catalysts

2.1.2.3 Reaction Using Copper and Iron Catalysts

2.1.3 C−O Bond Formation by Allylic C−H Activation

2.1.3.1 Reaction Using a Palladium Catalyst

2.1.3.2 Reaction Using Copper and Iron Catalysts

2.1.4 Other C−X Bonds Formed by Allylic C−H Activation

2.2 C−C Bond Formation by Alkyl C−H Activation

O. Baudoin

2.2 C−C Bond Formation by Alkyl C−H Activation

2.2.1 Heteroatom-Directed C(sp³)−H Activation

2.2.1.1 Cross Coupling with Alkenes, Alkynes, and Carbon Monoxide

2.2.1.2 Cross Coupling with Organoboron Reagents

2.2.1.3 Cross Coupling with Diaryliodonium Salts and Organic Halides

2.2.2 Oxidative Addition Induced C(sp³)−H Activation/Intramolecular C−C Coupling 51

2.2.2.1 Palladium(0)-Catalyzed Synthesis of Polycyclic Systems

2.2.2.2 Asymmetric Reactions

2.2.3 Nondirected Intermolecular C(sp³)−H Arylation

2.3 C−C Bond Formation Using Carbenes

X. Cui and X. P. Zhang

2.3 C−C Bond Formation Using Carbenes

2.3.1 Stereoselective Intramolecular Carbene C−H Insertion

2.3.1.1 Insertion into Secondary C−H Bonds

2.3.1.1.1 Insertion Using Alkyl Diazoacetates

2.3.1.1.2 Insertion Using Cycloalkyl Diazoacetates

2.3.1.1.3 Insertion into C−H Bonds Adjacent to Oxygen Atoms

2.3.1.1.4 Insertion into C−H Bonds Adjacent to Nitrogen Atoms

2.3.1.1.5 Insertion Using Aryldiazoacetates

2.3.1.1.6 Insertion Using Alkyldiazoacetates

2.3.1.1.7 Insertion Using Acceptor/Acceptor-Substituted Diazo Reagents

2.3.1.2 Insertion into Tertiary C−H Bonds

2.3.1.2.1 Insertion Using Aryldiazoacetates

2.3.1.2.2 Sequential Insertion Reactions

2.3.1.3 Insertion into Primary C−H Bonds

2.3.1.4 Insertion into C(sp²)−H Bonds

2.3.2 Stereoselective Intermolecular Carbene C−H Insertion

2.3.2.1 Insertion into Secondary C−H Bonds

2.3.2.1.1 Insertion into Cycloalkanes

2.3.2.1.2 Insertion into Cycloalkenes

2.3.2.1.3 Insertion into Cyclohexa-1,4-diene

2.3.2.1.4 Insertion into Tetrahydrofuran

2.3.2.1.5 Insertion into Silyl Ethers

2.3.2.1.6 Insertion into Cyclic Amines

2.3.2.1.7 Insertion into Benzylic C−H Bonds

2.3.2.2 Insertion into Tertiary C−H Bonds

2.3.2.3 Insertion into Primary C−H Bonds

2.3.2.3.1 Competitive Insertion between Primary and Secondary C−H Bonds

2.3.2.3.2 Competitive Insertion between Primary and Benzylic C−H Bonds

2.3.2.4 Insertion into C(sp²)−H Bonds

2.3.2.4.1 Insertion of Alkyldiazoacetates into Indoles

2.3.2.4.2 Insertion of Aryldiazoacetates into Indoles

2.3.3 Conclusions

2.4 C−C Bond Formation Using Radicals

W.-W. Chan and W.-Y. Yu

2.4 C−C Bond Formation Using Radicals

2.4.1 Palladium-Catalyzed ortho-Selective Oxidative Acylation of Arenes with Aldehydes

2.4.1.1 Acylation of Aryloximes with Aldehydes

2.4.1.2 Acylation of Anilides with Aldehydes

2.4.1.3 Acylation of N-Benzyltrifluoromethanesulfonamides with Aldehydes

2.4.1.4 Acylation of Aryldiazenes with Aldehydes

2.4.2 Transition-Metal-Free Direct Arylation of Arenes with Aryl Halides

2.4.3 Direct Functionalization of N-Heterocycles (Minisci-Type Radical Coupling)

2.4.3.1 Arylation of N-Heterocycles with Boronic Acids

2.4.3.2 Alkylation of N-Heterocycles with Zinc(II) Sulfinates

2.4.3.3 Acylation of Isoquinolines and Pyridines with Aldehydes

2.5 C−C Bond Formation by Double C−H Activation

J.-B. Xia and S.-L. You

2.5 C−C Bond Formation by Double C−H Activation

2.5.1 Oxidative Homocoupling

2.5.1.1 Palladium-Catalyzed Homocoupling of Benzene

2.5.1.2 Palladium-Catalyzed Homocoupling of Thiophenes

2.5.1.3 Palladium-Catalyzed Homocoupling of Indolizines

2.5.1.4 Palladium-Catalyzed Directed Homocoupling of 2-Arylpyridines

2.5.2 Oxidative Cross Coupling

2.5.2.1 Direct Coupling

2.5.2.1.1 Palladium-Catalyzed Coupling of Hetarenes with Arenes

2.5.2.1.2 Palladium-Catalyzed Coupling of Polyfluoroarenes with Arenes

2.5.2.1.3 Transition-Metal-Catalyzed Heterocoupling of Hetarenes

2.5.2.2 Directed Coupling

2.5.2.2.1 Palladium-Catalyzed Coupling of Benzo[h]quinoline with Arenes

2.5.2.2.2 Palladium-Catalyzed Coupling of 2-Ferrocenyl-4,5-dihydrooxazoles with Arenes

2.5.2.2.3 Palladium-Catalyzed Coupling of Anilides with Arenes

2.5.2.2.4 Palladium-Catalyzed Coupling of O-Phenyl Carbamates with Arenes

2.5.2.2.5 Palladium-Catalyzed Coupling of Benzamides with Arenes

2.5.2.2.6 Rhodium-Catalyzed Coupling of Benzamides with Arenes

2.5.2.2.7 Transition-Metal-Mediated Coupling of 2-Arylpyridines with Hetarenes

2.5.3 Intramolecular Oxidative Coupling

2.5.3.1 Palladium-Catalyzed Coupling of Arenes

2.5.3.2 Palladium-Catalyzed Coupling of Arenes with Hetarenes

2.6 C−C Bond Formation by C−H Carboxylation or Carbonylation

H. Zhang, C. Liu, and A. Lei

2.6 C−C Bond Formation by C−H Carboxylation or Carbonylation

2.6.1 C−C Bond Formation by C−H Carboxylation

2.6.1.1 C−H Carboxylation Using Carbon Monoxide

2.6.1.1.1 C(sp²)−H Carboxylation without Directing Groups

2.6.1.1.2 C(sp²)−H Carboxylation Assisted by Directing Groups

2.6.1.1.2.1 Carboxy Directing Groups

2.6.1.1.2.2 Acylamino Directing Groups

2.6.1.1.2.3 Sulfonamide Directing Groups

2.6.1.2 C−H Carboxylation Using Carbon Dioxide

2.6.1.2.1 C(sp²)−H Carboxylation without Directing Groups

2.6.1.2.1.1 Synthesis of Carboxylic Acids

2.6.1.2.1.2 Synthesis of Esters

2.6.1.2.2 C(sp²)−H Carboxylation Assisted by Directing Groups

2.6.1.2.2.1 N-Hetarene Directing Groups

2.6.2 C−C Bond Formation by C−H Carbonylation

2.6.2.1 C(sp²)−H Carbonylation

2.6.2.1.1 Intramolecular C(sp²)−H Carbonylation without Directing Groups

2.6.2.1.1.1 Synthesis of Xanthones

2.6.2.1.2 Intramolecular C(sp²)−H Carbonylation Assisted by Directing Groups

2.6.2.1.2.1 Aminoalkyl Directing Groups

2.6.2.1.2.2 Aminoaryl Directing Groups

2.6.2.1.2.3 Hydroxyalkyl Directing Groups

2.6.2.1.2.4 N-(2-Pyridylmethyl) amido Directing Group

2.6.2.1.2.5 N-Alkoxy- and N-Alkylamido Directing Groups

2.6.2.1.2.6 Alkylamino Directing Groups

2.6.2.1.2.7 Amidine Directing Groups

2.6.2.1.2.8 Sulfonamide Directing Groups

2.6.2.1.3 Intermolecular C(sp²)−H Carbonylation without Directing Groups

2.6.2.1.3.1 Synthesis of Esters

2.6.2.1.4 Intermolecular C(sp²)−H Carbonylation Assisted by Directing Groups

2.6.2.1.4.1 N-Hetarene Directing Groups

2.6.2.1.4.2 Urea Directing Groups

2.6.2.1.4.3 (Dimethylamino) methyl Directing Group

2.6.2.2 C(sp³)−H Carbonylation

2.6.2.2.1 Intramolecular C(sp³)−H Carbonylation Assisted by Directing Groups

2.6.2.2.1.1 N-(Aryl) amido Directing Groups

2.6.2.2.1.2 N-(2-Pyridylmethyl) amido Directing Groups

2.6.2.2.2 Intermolecular C(sp³)−H Carbonylation without Directing Groups

2.6.2.2.2.1 Synthesis of Esters

2.7 C−Hal Bond Formation by Arene C−H Activation

M. S. Sanford and A. Cook

2.7 C−Hal Bond Formation by Arene C−H Activation

2.7.1 C(sp²)−H Fluorination

2.7.1.1 Ligand-Directed Fluorination

2.7.2 C(sp²)−H Chlorination

2.7.2.1 Ligand-Directed Chlorination

2.7.2.1.1 Chlorination with N-Chlorosuccinimide

2.7.2.1.2 Chlorination with Other Chlorine-Containing Oxidants

2.7.2.1.3 Chlorination with an Oxidant and a Nucleophilic Chloride Source

2.7.3 C(sp²)−H Bromination

2.7.3.1 Ligand-Directed Bromination

2.7.3.1.1 Bromination with N-Bromosuccinimide

2.7.3.1.2 Bromination with an Oxidant and a Nucleophilic Bromide Source

2.7.3.2 Non-Directed Bromination

2.7.3.2.1 Bromination with N-Bromosuccinimide

2.7.4 C(sp²)−H Iodination

2.7.4.1 Ligand-Directed Iodination

2.7.4.1.1 Iodination with N-Iodosuccinimide

2.7.4.1.2 Iodination with Acetyl Hypoiodite

2.7.4.1.3 Iodination with Molecular Iodine

2.7.4.2 Non-Directed Iodination

2.7.4.2.1 Iodination with N-Iodosuccinimide

2.8 C−N Bond Formation by Arene C−H Activation Using a Palladium Catalyst

P. Dauban and B. Darses

2.8 C−N Bond Formation by Arene C−H Activation Using a Palladium Catalyst 221

2.8.1 Intramolecular C−N Bond Formation

2.8.1.1 Synthesis of Five-Membered Rings

2.8.1.1.1 Preparation of Carbazoles

2.8.1.1.2 Preparation of Oxindoles

2.8.1.1.3 Preparation of Dihydroindoles

2.8.1.1.4 Preparation of Indoles

2.8.1.1.5 Preparation of Benzimidazoles

2.8.1.1.6 Preparation of Benzotriazoles

2.8.1.2 Synthesis of Six-Membered Rings

2.8.1.2.1 Preparation of Quinolinones

2.8.1.2.2 Preparation of Phenanthridinones

2.8.2 Intermolecular C−N Bond Formation

2.8.2.1 Synthesis by ortho-Amidation

2.8.2.1.1 Reaction of Aromatic Oximes

2.8.2.1.2 Reaction of Aromatic Ketones

2.8.2.1.3 Reaction of Anilides

2.8.2.1.4 Reaction of Benzoic Acids

2.8.2.1.5 Reaction of Amides

2.9 C−N Bond Formation by C−H Functionalization via Metal-Catalyzed Nitrene Insertion

N. Mace Weldy and S. B. Blakey

2.9 C−N Bond Formation by C−H Functionalization via Metal-Catalyzed Nitrene Insertion

2.9.1 Amination of C(sp³)−H Bonds

2.9.1.1 Intramolecular Amination Reactions

2.9.1.1.1 Amination with Carbamates To Give 1,2-Amino Alcohol Derivatives

2.9.1.1.2 Propargylic Amination with Carbamates To Give 1,2-Amino Alcohol Derivatives

2.9.1.1.3 Amination with Sulfamates To Give 1,3-Amino Alcohol Derivatives

2.9.1.1.4 Enantioselective Amination with Sulfamate Esters To Give 1,3-Amino Alcohol Derivatives

2.9.1.1.5 Benzylic Amination with Phosphoryl Azides To Give 1,3-Amino Alcohol Derivatives

2.9.1.1.6 Amination with Ureas and Guanidines To Give 1,2-Diamine Derivatives

2.9.1.1.7 Amination with Hydroxylamine-Based Sulfamate Esters To Give 1,2-Diamine Derivatives

2.9.1.1.8 Amination with N-Alkyl-N-(tert-butoxycarbonyl) sulfamides To Give 1,3-Diamine Derivatives

2.9.1.1.9 Amination with Sulfamoyl Azides To Give 1,3-Diamine Derivatives

2.9.1.1.10 Benzylic Amination with Sulfonyl Azides To Give Sultams

2.9.1.1.11 Benzylic Amination with Aryl Azides To Give 2-Aryldihydroindoles

2.9.1.1.12 Alkyl Amination with Aryl Azides To Give Functionalized Dihydroindoles

2.9.1.1.13 Aliphatic Amination with Alkyl Azides To Give Pyrrolidines

2.9.1.2 Intermolecular Amination Reactions

2.9.1.2.1 Benzylic and Tertiary C−H Amination with 2,2,2-Trichloroethyl Sulfamate and 2,6-Difluorophenyl Sulfamate

2.9.1.2.2 Stereoselective Amination with N-(Mesyloxy)- and N-(Tosyloxy) carbamates

2.9.1.2.3 Directed Primary Amidation with Sulfonyl Azides

2.9.1.2.4 Enantioselective Benzylic Amination with 4-Nitrobenzenesulfonamide

2.9.1.2.5 Enantioselective Benzylic and Allylic Amination with 2-(Trimethylsilyl) ethanesulfonyl Azide

2.9.2 Amination of C(sp²)−H Bonds

2.9.2.1 Intramolecular Amination Reactions

2.9.2.1.1 Aryl Amination with Vinyl Azides To Give Substituted Indoles

2.9.2.1.2 Vinyl Amination with Aryl Azides To Give Indoles

2.9.2.1.3 Amination with Biaryl Azides To Give Carbazoles

2.9.2.2 Intermolecular Amination Reactions

2.9.2.2.1 Directed Aryl Amidation with Azides

2.9.2.2.2 Directed Amidation of Alkenes with Acyl Azides

2.10 C−O Bond Formation by Arene C−H Activation via Biomimetic and Organocatalytic Oxidation

Y. Hitomi and K. Arakawa

2.10 C−O Bond Formation by Arene C−H Activation via Biomimetic and Organocatalytic Oxidation

2.10.1 Biomimetic Oxidation

2.10.1.1 Catalysis by Porphyrin Complexes

2.10.1.1.1 Reaction with Iron–and Manganese–Porphyrins

2.10.1.1.2 Reaction with Ruthenium–Porphyrins

2.10.1.2 Catalysis by Non-heme Iron Complexes

2.10.1.3 Catalysis by Copper Complexes

2.10.2 Organocatalytic Oxidation

2.10.2.1 Reaction with Phthaloyl Peroxide

2.11 C−O Bond Formation by Arene C−H Activation via Metal-Catalyzed Oxidation

D.-D. Li and G.-W. Wang

2.11 C−O Bond Formation by Arene C−H Activation via Metal-Catalyzed Oxidation

2.11.1 Palladium-Catalyzed C−O Bond Formation

2.11.1.1 Intermolecular C−O Bond Formation

2.11.1.1.1 Acyloxylation of Arenes

2.11.1.1.2 Alkoxylation of Arenes

2.11.1.1.3 Hydroxylation of Arenes

2.11.1.2 Intramolecular C−O Bond Formation

2.11.2 Copper-Catalyzed C−O Bond Formation

2.11.2.1 Intermolecular C−O Bond Formation

2.11.2.2 Intramolecular C−O Bond Formation

2.11.3 Ruthenium-Catalyzed C−O Bond Formation

2.11.3.1 Intermolecular C−O Bond Formation

2.11.4 Conclusions

2.12 C−B Bond Formation by Arene C−H Activation

A. Ros, R. Fernández, and J. M. Lassaletta

2.12 C−B Bond Formation by Arene C−H Activation

2.12.1 Direct Borylation of Arene C−H Bonds

2.12.1.1 Rhodium-Catalyzed Borylation

2.12.1.2 Iridium-Catalyzed Borylation

2.12.2 Site-Selective Directed Borylation of Arenes

2.12.2.1 Chelate-Directed ortho-C−H Borylation

2.12.2.1.1 Iridium-Catalyzed Borylation

2.12.2.1.2 Rhodium-Catalyzed Borylation

2.12.2.1.3 Palladium-Catalyzed Borylation

2.12.2.1.4 Ruthenium-Catalyzed Borylation

2.12.2.2 Relay-Directed ortho-C−H Borylation

2.12.2.3 Outer-Sphere-Directed ortho-C−H Borylation

2.12.3 Conclusions

Keyword Index

Author Index

Abbreviations

2.1 C—C and C—X Bond Formation by Allylic C—H Activation

G. Liu and P. Chen

General Introduction

Transition-metal-catalyzed C—H bond cleavage and functionalization are attractive processes because of the demands of green chemistry, including atom economy and step economy.[1–4] Over the past half century, massive efforts have been made to activate specific “inert” C—H bonds, and these efforts have combined mechanistic studies and synthetic applications.[5–8] Among these studies, the activation of allylic C—H bonds with the assistance of an alkenyl group has received much attention, as alkenyl groups can efficiently coordinate with transition metals. Many transition metals have been discovered to participate in this process. Palladium, arguably the most powerful transition metal in organic synthesis,[9] has been found to be capable of catalyzing various C—H bond activation reactions, including activation of allylic C—H bonds.[10] Other metals such as rhodium, ruthenium, copper, and iron are also used for allylic C—H bond functionalization.

Although various transition metals can be used to catalyze the functionalization of allylic C—H bonds, the reactions operate under only three different mechanistic scenarios. The first scenario (▶ Scheme 1) involves cleavage of a C—H bond with the assistance of a metal to afford an allylic metal species. This is followed by two possible processes: (1) attack by either an external or internal nucleophile at the carbon center to give the linear or branched product, with [M]n regenerated in the presence of an oxidant; or (2) attack at the metal center in the presence of an oxidant, followed by reductive elimination to give the allylic product and regenerate [M]n. Most palladium-catalyzed allylic C—H functionalization reactions and ruthenium-catalyzed allylic C—C bond-forming reactions follow these pathways.

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