The Art of Problem Solving in Organic Chemistry

Preface xi

Preface to the First Edition xvii

Acknowledgments xix

1 Problem Analysis in Organic Reaction Mechanism 1

1.1 Overview, 1

1.2 Introduction, 1

1.2.1 "Pushing Forward" a Solution in Formal and Exhaustive Terms, 2

1.2.2 Lessons from this Example, 7

1.3 Avoiding the Quagmire, 7

1.4 The Basic Steps of Problem Analysis, 8

1.4.1 Recognizing the Problem, 8

1.4.2 Analyzing Problems by Asking the Right Questions, Discarding the Irrelevant, 11

1.4.3 Drawing a First Outline for Guidance, 12

1.4.4 Asking the Right Questions and Proposing the Right Answers . . . is enough?, 13

1.5 Intuition and Problem Solving, 14

1.6 Summing Up, 17

References and Notes, 17

2 Electron Flow in Organic Reactions 19

2.1 Overview, 19

2.2 Introduction, 19

2.3 Practical Rules Governing Electron Redeployment, 22

2.3.1 Issue 1: Electrons within Orbitals, 22

2.3.2 Issue 2: Electron Transfer and Stereochemistry, 23

2.3.3 Issue 3: Electron Energy Level and Accessibility, 24

2.3.4 Issue 4: Electron Flow and Molecular Active Sectors, 26

2.3.4.1 Case A: π–π Interactions, 26

2.3.4.2 Case B.: π → σ Interactions, 27

2.3.4.3 Case C: When Reactivity Patterns Seem to Break Down, 27

2.3.5 Issue 5: Electron Traffic and Electronic Density Differences, 31

2.3.5.1 M0 Metals as Electron Source, 31

2.3.5.2 Metal Hydrides and Organic Hydrides as Electron Source, 32

2.3.6 Issue 6: Creating Zones of High Electron Density, 34

2.3.6.1 The Natural Polarization, 35

2.3.6.2 Reversing the Natural Polarization: Umpolung, 35

2.3.7 Issue 7: Electron Flow and Low Electron Density Zones, 36

2.3.7.1 Identifying LEDZs, 36

2.3.7.2 Creating a New LEDZ in the Substrate, 37

2.3.7.3 Finding Unsuspected LEDZs among the Other Reagents in the Mixture, 41

2.3.7.4 When Compounds Show Double Personality, 42

2.4 Summing Up, 42

2.5 A Flowchart of Organized Problem Analysis, 44

References and Notes, 45

3 Additional Techniques to Postulate Organic Reaction Mechanisms 49

3.1 Overview, 49

3.2 Take Your Time, 50

3.3 Clear and Informative Molecular Renderings, 50

3.3.1 The Value of Molecular Sketches, 50

3.3.2 Two- Versus Three-Dimensional Renderings and the "Flat" Organic Compounds, 52

3.4 Element and Bond Budgets, 53

3.5 Looking at Molecules from Various Perspectives, 55

3.6 Separate the Grain from the Chaff, 58

3.7 Dissecting Products in Terms of Reactants: Fragmentation Analysis, 59

3.7.1 The Fundamental Proposition, 59

3.7.2 Adding Potentially Nucleophilic or Electrophilic Character to Fragments, 61

3.7.3 When Fragmentation Analysis Fails, Getting Help from Atom Labels, 63

3.8 Oxidation Levels and Mechanism, 65

3.8.1 Methods to Estimate Oxidation Status, 65

3.9 The Functionality Number, 66

3.9.1 What Exactly Is FN?, 66

3.9.2 Properties of FN, 67

3.10 Combining Fragmentation Analysis and Functionality Numbers, 72

3.11 Summing Up, 74

References, 75

4 Solved Problem Collection 77

Problem 1 to 60. See Graphical Problem Index, 79

Glossary 405

Subject/Reaction Index 409

Reagent Index 425

Author Index 433

Graphical Problem Index 445