Preface xix

Acknowlegments xxi

CHAPTER 1 Synthetic Toolbox 1: Retrosynthesis and Protective Groups 1

1.1 Retrosynthetic Analysis 3

1.2 Protective Groups 11

CHAPTER 1 Problems Protective Groups 19

CHAPTER 2 Synthetic Toolbox 2: Overview of Organic Transformations 21

2.1 Nucleophiles and Electrophiles 23

2.2 Oxidation and Reduction Reactions 27

CHAPTER 2 Problems Nucleophiles, Electrophiles, and Redox 41

CHAPTER 3 Synthesis of Monofunctional Target Molecules (1-FG TMs) 45

3.1 Synthesis of Alcohols (ROH) and Phenols (ArOH) 47

3.2 Synthesis of Alkyl (RX) and Aryl Halides (ArX) 61

3.3 Synthesis of Ethers (ROR') 67

3.4 Synthesis of Thiols (RSH) and Thioethers (RSR´) 73

3.5 Synthesis of Amines (RNH2) and Anilines (ArNH2) 77

3.6 Synthesis of Alkenes (R2C?TCR2) 85

3.7 Synthesis of Alkynes (RC identical to CR') 93

3.8 Synthesis of Alkanes (RH) 97

3.9 Synthesis of Aldehydes and Ketones (RCHO, R2C?TO) 105

3.10 Synthesis of Carboxylic Acids (RCO2H) 117

3.11 Synthesis of Carboxylic Acid Derivatives 125

CHAPTER 3 Problems 1-FG TMs 139

CHAPTER 4 Synthesis of Target Molecules with Two Functional Groups (2-FG TMs) 143

4.1 Synthesis of ß?Hydroxy Carbonyls and alpha,ß?Unsaturated Carbonyls 145

4.2 More Enolate Reactions: Synthesis of 1,3?Dicarbonyls, 1,5?Dicarbonyls, and Cyclohexenones 157

4.3 "Illogical" 2?Group Disconnections: Umpolung (Polarity Reversal) 171

CHAPTER 4 Problems 2-FG TMs 183

CHAPTER 5 Synthesis of Aromatic Target Molecules 187

5.1 Electrophilic Aromatic Substitution (ArH + E+ --> ArE) 189

5.2 Synthesis of Aromatic TMs via Diazonium Salts (ArN2 + + Nu: --> ArNu) 201

5.3 Nucleophilic Aromatic Substitution (ArX + Nu: --> ArNu) 205

CHAPTER 5 Problems Aromatic TMs 209

CHAPTER 6 Synthesis of Compounds Containing Rings 211

6.1 Synthesis of Cyclopropanes 213

6.2 Synthesis of Cyclobutanes 215

6.3 Synthesis of Five?Membered Rings (Radical Cyclization Reactions) 217

6.4 Synthesis of Six?Membered Rings (Diels-Alder Reaction) 221

CHAPTER 6 Problems Cyclic TMs 231

CHAPTER 7 Predicting and Controlling Stereochemistry 235

7.1 Reactions that Form Racemates 237

7.2 SN2 Mechanism: Backside Attack 243

7.3 Elimination Mechanisms 245

7.4 Additions to Alkenes and Alkynes 247

7.5 Additions to Carbonyls 251

7.6 Additions to Enolates: Aldol Stereochemistry 257

7.7 Enantioselectivity and Asymmetric Syntheses 261

CHAPTER 7 Problems Stereochemistry 269

CHAPTER 8 Transition Metal-Mediated Carbon-Carbon Bond Formation 273

8.1 Transition Metal Coordination Complexes 275

8.2 Organometallic Reaction Mechanisms 283

8.3 Carbonylation and Decarbonylation 291

8.4 (ArX + Alkene --> Ar?Alkene) 295

8.5 Palladium?Catalyzed Cross?Coupling Reactions (RX + R'M --> R?R') 297

8.6 Olefin Metathesis Reactions 303

8.7 Retrosynthesis: Disconnections Based on Metal-Mediated Reactions 307

CHAPTER 8 Problems Transition Metal-Mediated Synthesis 309

SOLUTIONS TO PROBLEMS 313

Index 389