A combination of oxidation methods and CH bond functionalization, this book emphasizes mechanistic understanding and critical analysis of synthetic reactions to offer a guide or manual for practicing chemists.
* Combines oxidation methods and CH bond functionalization, two of the most important aspects of organic synthesis
* Deals with CH bonds, an area of dynamic and continuous research across chemistry and catalysis
* Helps readers understand the fundamental and applied differences among various oxidation methods and reactions
* Covers mechanistic details, conditions, oxidation reagents, and practical aspects of different reactions
weitere Ausgaben werden ermittelt
Wenjun Lu, D.Eng., is a Professor of Organic Chemistry at Shanghai Jiao Tong University.
Lihong Zhou, PhD, is a Research Associate at Shanghai Jiao Tong University.
1 Introduction 1
1.1 What Is Oxidation of C??H Bonds? 1
1.2 Chemical Synthesis and Oxidation of C??H Bonds 2
1.3 C??H Bonds 6
1.4 Concepts in This Book 15
2 Oxidation of Methane 19
2.1 Methane 19
2.2 Methyl sp3 C??H Bond 20
2.3 Oxidations of Methyl sp3 C??H Bond 21
2.4 Summary 35
3 Oxidation of Alkyl sp3 C??H Bond 39
3.1 Alkane 39
3.2 Alkyl sp3 C??H Bonds 40
3.3 Oxidations of Alkyl sp3 C??H Bond 42
3.4 Summary 61
4 Oxidation of Alkyl sp3 C??H Bond Assisted by Directing Group 65
4.1 Directing Group 65
4.2 Alkyl sp3 C??H Bonds with Directing Groups 66
4.3 Directed Oxidations of Alkyl sp3 C??H Bond 67
4.4 Summary 97
5 Oxidation of Alkyl sp3 C--H Bond Adjacent to Unsaturated Carbon Atom 101
5.1 Alkyl alpha?]sp3 C??H Bond 101
5.2 Alkyl sp3 C??H Bonds Adjacent to Unsaturated Carbon Atoms 102
5.3 Oxidations of Alkyl sp3 C??H Bond Adjacent to Unsaturated Carbon Atom 103
5.4 Summary 138
6 Oxidation of Alkyl sp3 C??H Bond Adjacent to Heteroatom 143
6.1 Alkyl sp3 C??H Bonds Adjacent to Heteroatoms 143
6.2 Oxidations of Alkyl sp3 C??H Bond Adjacent to Heteroatom 144
6.3 Summary 166
7 Oxidation of Alkenyl or Carbonyl sp2 C??H Bond 171
7.1 Alkenyl and Carbonyl sp2 C??H Bonds 171
7.2 Oxidations of Alkenyl and Carbonyl sp2 C??H Bonds 172
7.3 Summary 203
8 Oxidation of Alkynyl spC??H Bond 209
8.1 spC??H Bonds 209
8.2 Oxidations of spC??H Bond 210
8.3 Summary 232
9 Oxidation of Benzene 235
9.1 Introduction 235
9.2 Oxidations of Phenyl sp2 C??H Bond 237
9.3 Summary 277
10 Oxidation of Aryl sp2 C??H Bond on Substituted Benzene 283
10.1 Introduction 283
10.2 Formation of C??C Bond 284
10.3 Formation of C??N Bond 313
10.4 Formation of C??O Bond 316
10.5 Formation of C??S Bond 322
10.6 Formation of C??Halogen Bond 323
10.7 Summary 331
11 Oxidation of Aryl sp2 C??H Bond Assisted by Directing Group 337
11.1 Introduction 337
11.2 Formation of C??C Bond 337
11.3 Formation of C??N Bond 400
11.4 Formation of C??O Bond 406
11.5 Formation of C??S Bond 412
11.6 Formation of C??Halogen Bond 414
11.7 Summary 424
12 Oxidation of Aryl sp2 C??H Bond on Heteroarene or Perfluoroarene 433
12.1 Introduction 433
12.2 Formation of C??C Bond 434
12.3 Formation of C??N Bond 459
12.4 Formation of C??O Bond 461
12.5 Formation of C??Halogen Bond 462
12.6 Cross?]Coupling of Dual Aryl sp2 C??H Bonds on Directing?]Group?]Containing Arenes, Heteroarenes,
or Polyfluoroarenes 468
12.7 Summary 477
13 Oxidative Cross?]Coupling of Aryl sp2 C??H Bond with Inert C??H Bond 483
13.1 Introduction 483
13.2 Oxidative Coupling of Simple Arenes with Alkanes (Alkylation of Arenes) 484
13.3 Oxidative Coupling of Simple Arenes with Alkenes (Alkenylation of Arenes) 486
13.4 Oxidative Cross?]Coupling of Simple Arenes (Arylation of Arenes) 490
13.5 Summary 498
1.1 What Is Oxidation of C─H Bonds?
Oxidation of C─H bonds is to transform the C─H bonds to various C─X bonds, in which X is a nonmetal atom with higher electronegativity than hydrogen, including carbon, nitrogen, oxygen, sulfur, selenium, fluorine, chlorine, bromine, iodine, etc. in this book . In a typical oxidation process, it usually involves a cleavage of the covalent C─H bond and an oxidative functionalization of the carbon by a reagent (Scheme 1.1).
Scheme 1.1 Oxidation of C─H bond.
1.2 Chemical Synthesis and Oxidation of C─H Bonds
1.2.1 Transformation of Organic Compounds
Organic compounds are a kind of carbon molecules containing at least one C─H, C─C, or single C─heteroatom bond, which are very important substances to provide chemical energy, to construct organisms, to act as the functional materials in human life, and so on. Actually, many transformations are happening spontaneously among these organic compounds and other carbon-containing compounds every day, leading to a big carbon cycle on the Earth. Meanwhile, man-made organic compounds including agrochemicals, pharmaceuticals, and various organic functional materials are prepared enormously through a series of reactions from the raw materials such as methane, ethylene, and benzene, affecting the human being's daily life and human beings themselves remarkably. The preparation of target products (complex molecules) from substrates (simple molecules) is called chemical synthesis normally involving multiple-step reactions in one way (Scheme 1.2).
Scheme 1.2 Carbon cycle and chemical synthesis.
1.2.2 Ideal Chemical Synthesis
An ideal chemical synthesis is a process with minimal impact on external environment. There are two simple aspects in the process: mass and energy. In theory, at the end of the most ideal process, there are no other substances transformed except the desired products generated from substrates and no other energy consumed except the reaction heat ?H for product generation. Although there is a large gap between the current chemical processes and the ideal ones in most cases, it is necessary to give some concise suggestions on the estimation of a practical process. Five rules for a HELLO process are listed as follows:
- High Yield When the product is obtained in high yield, it indicates that the utilization of substrate is highly sufficient and effective during the transformation.
- Efficient Pathway In an efficient pathway of chemical synthesis, a multiple-step process is usually replaced by a one-step reaction, a few reactions in one pot, or a cascade reaction to avoid or reduce the consumption of both substance and energy in the reactions and posttreatments. Furthermore, the substrates, intermediates, and products should be tolerant to the reaction systems without protection treatment on functional groups, and no external substances are consumed to initiate, accelerate, or control any reactions in the process.
- Low Loading If it is possible, to save substance, energy, and space, quantitative reactants are employed, and other necessary materials including catalysts, additives, and solvents are used at a minimum during the whole chemical process.
- Low Complexity in Operation It is highly required that a chemical process is carried out easily without special protection and caution, under normal pressure in air, and at an ambient temperature. In such a process, all expenses are reduced on safety, equipment, energy, and so on.
- Only Target Products In some cases, high selectivity such as high stereoselectivity is more important than high yield. Thus, it is the key symbol for an excellent and elegant process to obtain target products only. In other words, a HELLO process could become a HELL one with a poor selectivity because the wastes or by-products generated could decrease obviously the quantity and/or quality of products and increase largely the cost of substance and energy in the reactions as well as in the product purifications.
To set up such a HELLO process, it mainly depends on the discovery and development of every single perfect reaction, that is, an ideal chemical synthesis is an ideal reaction indeed or consists of a series of ideal reactions.
1.2.3 Oxidation of C─H Bonds for Ideal Chemical Synthesis
According to the aforementioned description, oxidation of C─H bonds should be one of the most promising reactions in an ideal chemical synthesis. There are three main factors as follows to support it strongly:
- Rich Resources Since the C─H bonds are fundamental, ubiquitous, and substantial in the saturated and unsaturated organic compounds, especially in the raw materials such as simple alkanes, olefins, and arenes, the oxidation of C─H bonds to form the C─C bonds or C─heteroatom bonds is the most popular method in organic synthesis. For example, aryl sp2C─H bonds are very common and abundant in various aromatic compounds, so it is the most convenient method for the direct oxidative coupling of two aryl sp2C─H bonds to give a new aryl sp2C─sp2C bond in the preparation of biaryls.
- High Mass Efficiency A direct oxidation of C─H bonds to give the desired product is a process in a high mass efficiency (ME). The ME is the ratio of the mass of products to the mass of all transformed substances including reactants, reagents, oxidants or reductants, additives, etc. in the synthetic process. Obviously, the highest ME must be 100% in all addition or rearrangement reactions, like the atom economy . In the substitution or elimination reactions, however, the highest ME can be achieved just when hydrogens, the lightest elements, are replaced or eliminated from the substrates and the wastes or by-products are produced at a minimum. The oxidations of C─H bonds via the cleavage of C─H bonds belong to these reactions giving the highest ME values, which may be close to the ideal processes.
When the transformed substances are just the reactants, the ME is equal to the atom efficiency (AE).
For example, in the formation of biphenyl from benzene, the highest ME is 99% in the dehydrogenative coupling reaction, in which the by-product is only H2. When dioxygen is employed as an oxidant, the ME is 90% with H2O generated in the direct oxidative coupling reaction. In contrast, the total ME is decreased sharply to just 39% because of more wastes produced in the sequentially oxidative bromination of benzene using dioxygen as the terminal oxidant and the reductive coupling (Ullmann coupling) of bromobenzene using zinc as reductant (Scheme 1.3).
It is notable that the preparations of different products cannot be compared with each other by their ME values because one process in synthesis has its own highest ME values. For instance, the highest ME is 99% in the formation of biphenyl (C6H5─C6H5) from benzene (C6H6), but that is 94% in the formation of ethane (CH3─CH3) from methane (CH4).
- High Energy Efficiency A direct oxidation of C─H bonds to give the desired product is also a process with a high energy efficiency (EE). The EE is the ratio of the reaction heat just for the products (?H) to all consumed energy (SE) in the synthetic process. The EE is a small value in a practical one due to all consumed energy including not only the reaction heat but also a large part for keeping reaction temperature, mechanical stirring, purifying substances, treating wastes, and so on though it is close to 100% in an ideal reaction. Thus, if the process is just a one-step reaction running under mild conditions, especially to generate no or less wastes like a HELLO process, it usually shows a high EE. The aerobic oxidation of C─H bonds expresses a unique merit in EE when its by-product is only H2O which should not be considered to deal with specially. In contrast, since the multiple-step synthesis often requires the external energy consumption in the separation of intermediates and/or the regeneration of some important additives to enhance the ME, it is not a process in good EE.
Energy Efficiency For example, in the cases of biphenyl prepared from benzene mentioned earlier, if the regeneration of Zn and Br2 from ZnBr2 is carried out after the oxidative bromination/reductive coupling reaction, the total ME can be up to 90% as in the aerobic oxidative coupling reaction (Scheme 1.4). However, the three-step process apparently requires more energy consumption for the treatments of intermediates and wastes than that one-step process, a direct oxidation of C─H bonds, even though their total reaction heats for the products could be the same.
Overall, it is undoubted that direct oxidation of C─H bonds is the simplest and most effective method to form the carbon backbones and to introduce a lot of functional groups or heteroatoms in the synthesis. However, at present, either the realization or the application of direct oxidation of C─H bonds is insufficient, and it is far away to be a HELLO process with high ME and EE. For example, the preparation of biphenyl by the coupling of aryl C─halogen bonds and aryl reagents is very effective and...
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