DANIEL E. LEVY, PhD, is the owner of DEL BioPharma LLC, USA. He previously worked at Glycomed, COR Therapeutics, Scios, and Intradigm. Dr. Levy developed, with Dr. Péter Fügedi, short courses entitled "Modern Synthetic Carbohydrate Chemistry" and "The Organic Chemistry of Sugars." He has three books to his credit, including the rst edition of Arrow-Pushing in Organic Chemistry (Wiley, 2008). He received his bachelors in chemistry from the University of California– Berkeley and his doctorate in organic chemistry from the Massachusetts Institute of Technology.

• PREFACE xiACKNOWLEDGEMENTS xiiiABOUT THE AUTHOR xv1. Introduction 11.1 Definition of Arrow-Pushing 11.2 Functional Groups 51.3 Nucleophiles and Leaving Groups 71.4 Summary 8Problems 92. Free Radicals 192.1 What Are Free Radicals? 192.2 How Are Free Radicals Formed? 212.2.1 Free Radical Initiators 222.2.2 Electron Transfer 232.3 Free Radical Stability 232.4 What Types of Reactions Involve Free Radicals? 252.4.1 Halogenation Reactions 262.4.2 Polymerization Reactions 282.4.3 Oxidation Reactions 302.5 Summary 31Problems 323. Acids 373.1 What Are Acids? 373.2 What Is Resonance? 383.3 How Is Acidity Measured? 413.4 Relative Acidities 423.5 Inductive Effects 473.6 Inductive Effects and Relative Acidities 493.7 Relative Acidities of Hydrocarbons 503.8 Summary 51Problems 524. Bases and Nucleophiles 614.1 What Are Bases? 614.2 What Are Nucleophiles? 664.3 Leaving Groups 704.4 Summary 70Problems 715. SN2 Substitution Reactions 815.1 What Is An SN2 Reaction? 815.2 What Are Leaving Groups? 835.3 Where Can SN2 Reactions Occur? 845.4 SN2′ Reactions 855.5 Summary 88Problems 896. SN1 Substitution Reactions 976.1 What Is An SN1 Reaction? 976.2 How Are SN1 Reactions Initiated? 986.3 The Carbocation 996.3.1 Molecular Structure and Orbitals 1006.3.2 Stability of Carbocations 1036.4 Carbocation Rearrangements 1056.4.1 1,2-Hydride Shifts 1056.4.2 1,2-Alkyl Shifts 1066.4.3 Preventing Side Reactions 1096.5 Summary 109Problems 1107. Elimination Reactions 1157.1 E1 Eliminations 1157.2 E1cB Eliminations 1187.3 E2 Eliminations 1207.4 How Do Elimination Reactions Work? 1217.5 E1cB Eliminations Versus E2 Eliminations 1247.6 Summary 124Problems 1268. Addition Reactions 1338.1 Addition of Halogens to Double Bonds 1338.2 Markovnikov’s Rule 1358.3 Additions to Carbonyls 1378.3.1 1,2-Additions 1378.3.2 1,4-Additions 1388.3.3 Addition–Elimination Reactions 1418.4 Summary 143Problems 1449. Carbenes 1539.1 What Are Carbenes? 1539.2 How Are Carbenes Formed? 1549.3 Reactions with Carbenes 1569.3.1 Carbene Dimerization 1569.3.2 Cyclopropanation Reactions 1579.3.3 O-H Insertion Reactions 1619.4 Carbenes Versus Carbenoids 1629.5 Summary 163Problems 16410. Pericyclic Reactions 17110.1 What Are Pericyclic Reactions? 17110.2 Electrocyclic Reactions 17210.3 Cycloaddition Reactions 17510.3.1 The Diels–Alder Reaction 17510.3.2 The Ene Reaction 17810.3.3 Dipolar Cycloaddition Reactions 18010.4 Sigmatropic Reactions 18210.4.1 The Cope Rearrangement 18310.4.2 The Claisen Rearrangement 18410.5 Summary 187Problems 18911. Moving Forward 19511.1 Functional Group Manipulations 19511.2 Name Reactions 19611.3 Reagents 20811.4 Final Comments 208Problems 209Appendix 1. pKa Values of Protons Associated with Common Functional Groups 219Appendix 2. Answers and Explanations to Problems 223Chapter 1 Solutions 224Chapter 2 Solutions 234Chapter 3 Solutions 241Chapter 4 Solutions 258Chapter 5 Solutions 270Chapter 6 Solutions 285Chapter 7 Solutions 293Chapter 8 Solutions 303Chapter 9 Solutions 318Chapter 10 Solutions 334Chapter 11 Solutions 347Appendix 3. Student Reaction Glossary 369Index 373Periodic Table of Elements 401

DANIEL E. LEVY, PhD, is the owner of DEL BioPharma LLC, USA. He previously worked at Glycomed, COR Therapeutics, Scios, and Intradigm. Dr. Levy developed, with Dr. Péter Fügedi, short courses entitled "Modern Synthetic Carbohydrate Chemistry" and "The Organic Chemistry of Sugars." He has three books to his credit, including the rst edition of Arrow-Pushing in Organic Chemistry (Wiley, 2008). He received his bachelors in chemistry from the University of California– Berkeley and his doctorate in organic chemistry from the Massachusetts Institute of Technology.

• PREFACE xiACKNOWLEDGEMENTS xiiiABOUT THE AUTHOR xv1. Introduction 11.1 Definition of Arrow-Pushing 11.2 Functional Groups 51.3 Nucleophiles and Leaving Groups 71.4 Summary 8Problems 92. Free Radicals 192.1 What Are Free Radicals? 192.2 How Are Free Radicals Formed? 212.2.1 Free Radical Initiators 222.2.2 Electron Transfer 232.3 Free Radical Stability 232.4 What Types of Reactions Involve Free Radicals? 252.4.1 Halogenation Reactions 262.4.2 Polymerization Reactions 282.4.3 Oxidation Reactions 302.5 Summary 31Problems 323. Acids 373.1 What Are Acids? 373.2 What Is Resonance? 383.3 How Is Acidity Measured? 413.4 Relative Acidities 423.5 Inductive Effects 473.6 Inductive Effects and Relative Acidities 493.7 Relative Acidities of Hydrocarbons 503.8 Summary 51Problems 524. Bases and Nucleophiles 614.1 What Are Bases? 614.2 What Are Nucleophiles? 664.3 Leaving Groups 704.4 Summary 70Problems 715. SN2 Substitution Reactions 815.1 What Is An SN2 Reaction? 815.2 What Are Leaving Groups? 835.3 Where Can SN2 Reactions Occur? 845.4 SN2′ Reactions 855.5 Summary 88Problems 896. SN1 Substitution Reactions 976.1 What Is An SN1 Reaction? 976.2 How Are SN1 Reactions Initiated? 986.3 The Carbocation 996.3.1 Molecular Structure and Orbitals 1006.3.2 Stability of Carbocations 1036.4 Carbocation Rearrangements 1056.4.1 1,2-Hydride Shifts 1056.4.2 1,2-Alkyl Shifts 1066.4.3 Preventing Side Reactions 1096.5 Summary 109Problems 1107. Elimination Reactions 1157.1 E1 Eliminations 1157.2 E1cB Eliminations 1187.3 E2 Eliminations 1207.4 How Do Elimination Reactions Work? 1217.5 E1cB Eliminations Versus E2 Eliminations 1247.6 Summary 124Problems 1268. Addition Reactions 1338.1 Addition of Halogens to Double Bonds 1338.2 Markovnikov’s Rule 1358.3 Additions to Carbonyls 1378.3.1 1,2-Additions 1378.3.2 1,4-Additions 1388.3.3 Addition–Elimination Reactions 1418.4 Summary 143Problems 1449. Carbenes 1539.1 What Are Carbenes? 1539.2 How Are Carbenes Formed? 1549.3 Reactions with Carbenes 1569.3.1 Carbene Dimerization 1569.3.2 Cyclopropanation Reactions 1579.3.3 O-H Insertion Reactions 1619.4 Carbenes Versus Carbenoids 1629.5 Summary 163Problems 16410. Pericyclic Reactions 17110.1 What Are Pericyclic Reactions? 17110.2 Electrocyclic Reactions 17210.3 Cycloaddition Reactions 17510.3.1 The Diels–Alder Reaction 17510.3.2 The Ene Reaction 17810.3.3 Dipolar Cycloaddition Reactions 18010.4 Sigmatropic Reactions 18210.4.1 The Cope Rearrangement 18310.4.2 The Claisen Rearrangement 18410.5 Summary 187Problems 18911. Moving Forward 19511.1 Functional Group Manipulations 19511.2 Name Reactions 19611.3 Reagents 20811.4 Final Comments 208Problems 209Appendix 1. pKa Values of Protons Associated with Common Functional Groups 219Appendix 2. Answers and Explanations to Problems 223Chapter 1 Solutions 224Chapter 2 Solutions 234Chapter 3 Solutions 241Chapter 4 Solutions 258Chapter 5 Solutions 270Chapter 6 Solutions 285Chapter 7 Solutions 293Chapter 8 Solutions 303Chapter 9 Solutions 318Chapter 10 Solutions 334Chapter 11 Solutions 347Appendix 3. Student Reaction Glossary 369Index 373Periodic Table of Elements 401