Most reactions in organic chemistry do not proceed in a single step but rather take several steps to yield the desired product. In the course of these multi-step reaction sequences, short-lived intermediates can be generated that quickly convert into other intermediates, reactants, products or side products. As these intermediates are highly reactive, they cannot usually be isolated, but their existence and structure can be proved by theoretical and experimental methods. Using the information obtained, researchers can better understand the underlying reaction mechanism of a certain organic transformation and thus develop novel strategies for efficient organic synthesis.

The chapters are clearly structured and are arranged according to the type of intermediate, providing information on the formation, characterization, stereochemistry, stability, and reactivity of the intermediates. Additionally, representative examples and a problem section with different levels of difficulty are included for self-testing the newly acquired knowledge.

By providing a deeper understanding of the underlying concepts, this is a musthave reference for PhD and Master Students in organic chemistry, as well as a valuable source of information for chemists in academia and industry working in the field. It is also ideal as primary or supplementary reading for courses on organic chemistry, physical organic chemistry or analytical chemistry.

Preface IX

1 Introduction 1

1.1 Reaction Mechanism and Reaction Arrows 4

1.2 Properties and Characteristics of a Reaction 5

1.2.1 Reactants and Reagents 6

1.2.2 Product Selectivity 6

1.2.3 Reaction Characteristics 7

1.2.4 Factors that Influence Reactions 7

1.3 Summary 16

Further Reading 19

2 Carbocations 21

2.1 Introduction 21

2.2 History 22

2.2.1 Carbonium Ions and Carbenium Ions 23

2.3 Structures and Geometry of Carbocations 26

2.4 Generation of Carbocation 28

2.4.1 From a Halide 29

2.4.2 From an Alcohol 29

2.4.3 From an Amine 29

2.4.4 From an Alkene 30

2.4.5 From Carbonyl Compounds 30

2.4.6 Solvent Effects 30

2.5 Carbocation Stability 31

2.6 Detection of Carbocations 36

2.7 Fate of Carbocations 37

2.7.1 Reaction with a Nucleophile 38

2.7.2 Elimination of a Proton 38

2.7.3 Rearrangements of Carbocations 39

2.7.4 Cationic Polymerization 50

2.8 Nonclassical Carbocations 51

2.9 Radical Cations 55

2.10 Summary 60

Further Reading 64

3 Carbanions 65

3.1 Structure and Geometry of Carbanions 65

3.2 Generation of Carbanions 69

3.2.1 Reduction of C–X Bond with Metal 69

3.2.2 Deprotonation from a C–H Bond 70

3.2.3 Reaction of a Metal with an Alkene 70

3.2.4 A Negative Ion Adds to a Carbon–Carbon Double or Triple Bond 71

3.3 Stability of Carbanions 72

3.4 Reactions of Carbanions 77

3.5 Enolate Reactions with Carbonyl Groups 78

3.5.1 Aldol Condensation 78

3.5.2 Enamine Additions 81

3.5.3 Robinson Ring-Forming Reaction 81

3.6 Rearrangements of Carbanions 86

3.6.1 Homoallylic Rearrangements 86

3.7 Chiral Carbanions 90

3.8 Carbanions and Tautomerism 91

3.8.1 Mechanism of Keto-Enol Interconversion 91

3.9 Summary 96

Further Reading 100

4 Radicals 101

4.1 Introduction 101

4.2 Detection and Characterization of Radicals 103

4.3 Structure and Bonding of Radicals 107

4.4 Generation of Free Radicals 111

4.5 Stability of Radicals 114

4.6 Reactions of Free Radicals 116

4.7 Stereochemistry of Radical Reactions 131

4.7.1 Cyclization by Intramolecular Addition Reactions 136

4.8 Biradicals 142

4.9 Summary 146

Further Reading 151

5 Carbenes 153

5.1 Structure and Geometry of Carbenes 153

5.2 Generation of Carbenes 160

5.2.1 Thermolysis or Photolysis of Diazo Compounds 160

5.2.2 Reaction of N-Nitrosoureas with Base 161

5.2.3 Reaction of Tosylhydrazone with Base 162

5.2.4 Carbene Formation by α-Elimination 163

5.2.5 Generation of Carbenoids (Simmons–Smith Reaction) 165

5.2.6 Formation of Carbenes under Neutral Conditions 165

5.2.7 Generation of Carbenes from Small Rings 166

5.3 Reactions of Carbenes 167

5.3.1 Addition Reactions 168

5.3.2 Cycloaddition to 1,2-Dienes (Allenes) 176

5.3.3 Cycloaddition to 1,3-Diene 176

5.3.4 Cycloaddition to Alkynes 177

5.3.5 Insertion Reactions 177

5.3.6 Rearrangement of Carbenes 181

5.3.6.1 Wolff Rearrangement 182

5.3.7 Reactions of Carbenes with Nucleophiles 187

5.4 Carbenes and Carbene Ligands in Organometallic Chemistry 188

5.5 Summary 192

Further Reading 195

6 Nitrenes 197

6.1 Introduction 197

6.2 Structure and Reactivity 198

6.3 Generation of Nitrenes 202

6.3.1 Azides 203

6.3.2 Isocyanates 205

6.3.3 Ylides 205

6.3.4 Small Rings 206

6.3.5 Heterocycles 206

6.3.6 α-Elimination 207

6.3.7 Reduction of Nitro and Nitroso Compounds 207

6.3.8 Oxidation of Amines 208

6.3.9 From Sulfinylamines 208

6.4 Reactions of Nitrenes 209

6.4.1 Cycloaddition Reactions of Nitrenes 209

6.4.1.1 Cycloaddition to Alkenes 209

6.4.1.2 Cycloaddition to 1,3-Dienes 210

6.4.1.3 Cycloaddition to Alkynes 211

6.4.1.4 Cycloaddition to Arenes 212

6.4.2 Insertion Reactions of Nitrenes 212

6.4.3 Rearrangement of Nitrenes 216

6.4.4 Reactions of Nitrenes with Nucleophiles 218

6.5 Summary 220

Further Reading 223

7 Miscellaneous Intermediates 225

7.1 Arynes 225

7.1.1 Introduction 225

7.1.2 Structure and Reactivity 226

7.1.3 Generation of Arynes 230

7.1.4 Reactions of Arynes 236

7.1.4.1 Nucleophilic Addition to Arynes 237

7.1.4.2 Regiochemistry of the Triple Bond Formation 239

7.1.4.3 Cycloaddition Reactions of Arynes (Diels–Alder Reaction) 240

7.1.4.4 1,3-Dipolar Cycloaddition 243

7.1.5 Uses of Arynes in Organic Synthesis 245

7.2 Ketenes and Cumulenes 246

7.2.1 Introduction 246

7.2.2 Generation of Ketenes 248

7.2.3 Photochemical Generation of Ketenes 250

7.2.4 Reactions of Ketenes 251

7.3 ortho-Quinone Methides 253

7.4 Zwitterions and Dipoles 258

7.5 Antiaromatic Systems 262

7.6 Tetrahedral Intermediates 264

7.6.1 Acetals and Hemiacetals 267

7.6.2 Weinreb Amides 269

7.6.3 Applications in Biomedicine 269

7.7 Summary 270

Further Reading 273

Index 275