Electron Flow in Organic Chemistry : A Decision-Based Guide to Organic Mechanisms

1 BONDING AND ELECTRON DISTRIBUTION 1

1.1 The Decision-Based Approach To Organic Chemistry 2  

1.2 Ionic And Covalent Bonding 6

1.3 Lewis Structures And Resonance Forms 8

1.4 Curved-Arrow Notation 11

1.5 Nomenclature And Abbreviations 16

1.6 An Orbital View Of Bonding (Supplemental) 18

1.7 The Shapes Of Molecules 21

1.8 Molecular Repulsions, Attractions, And Hydrogen Bonding 25

1.9 Conjugation, Vinylogy, Aromaticity 27

1.10  Summary 30

2  THE PROCESS OF BOND FORMATION 34

2.1 Energetics Control Knowledge 35

2.2 Orbital Overlap In Covalent Bond Formation 35

2.3 Orbital Interaction Diagrams 38

2.4 Polarizability And Hard And Soft Acid-Base Theory 41

2.5 Thermodynamics, Position Of Equilibrium 43

2.6 Kinetics, Rate Of Reaction 47

2.7 Solvent Stabilization Of Ions 53

2.8 Enzymatic Catalysis - Lessons From Biochemistry 55

2.9 Summary 57

3  PROTON TRANSFER AND THE PRINCIPLES OF STABILITY 61

3.1 Introduction To Proton Transfer 62

3.2 Ranking Of Acids And Bases, The pKa Chart 63

3.3 Structural Factors That Influence Acid Strength 66

3.4 Structural Factors That Influence Base Strength 70

3.5 Carbon Acids & Ranking Of Electron-Withdrawing Groups 71

3.6 Calculation Of Keq For Proton Transfer 76

3.7 Proton Transfer Mechanisms 77

3.8 Common Errors 81

3.9 Proton Transfer Product Predictions 82

3.10  Summary 83

4  IMPORTANT REACTION ARCHETYPES  88

4.1 Introduction To Reaction Archetypes 89

4.2 Nucleophilic Substitution At A Tetrahedral Center 89

4.3 Elimination Reactions Create Pi Bonds 110

4.4 Addition Reactions To Polarized Multiple Bonds 124

4.5 Nucleophilic Substitution At A Trigonal Planar Center 133 

4.6 Electrophilic Substitution At A Trigonal Planar Center 140

4.7 Rearrangements To An Electrophilic Carbon 144

4.8 Reaction Archetype Summary 146

5  CLASSIFICATION OF ELECTRON SOURCES 151 

5.1 Generalized Ranking Of Electron Sources 151

5.2 Nonbonding Electrons 152

5.3 Electron-Rich Sigma Bonds 154

5.4 Electron-Rich Pi Bonds 155

5.5 Simple Pi Bonds 156

5.6 Aromatic Rings 159

5.7 Summary Of Generic Electron Sources 160

6  CLASSIFICATION OF ELECTRON SINKS 166

6.1 Generalized Ranking Of Electron Sinks 166

6.2 Electron-Deficient Species 167

6.3 Weak Single Bonds 168

6.4 Polarized Multiple Bonds Without Leaving Groups 170

6.5 Polarized Multiple Bonds With Leaving Groups 172

6.6 Summary Of Generic Electron Sinks 173

7  THE ELECTRON FLOW PATHWAYS 179 

7.1 The Dozen Most Common Pathways 180

7.2 Six Minor Pathways 191

7.3 Common Path Combinations 197

7.4 Variations On A Theme 201

7.5 Twelve Major Paths Summary And Crosschecks 208

8  INTERACTION OF ELECTRON SOURCES AND SINKS 213

8.1 Source And Sink Correlation Matrix 214

8.2 H-A Sinks Reacting With Common Sources 214

8.3 Y-L Sinks Reacting With Common Sources 218

8.4 sp3 C-L Sinks Reacting With Common Sources 222

8.5 C=Y Sinks Reacting With Common Sources 227

8.6 R-C≡Y Sinks Reacting With Common Sources 233

8.7 C=C?Ewg Sinks Reacting With Common Sources 235

8.8 L-C=Y Sinks Reacting With Common Sources 237

8.9 Miscellaneous Reactions 240

8.10  Metal Ions As Electron Sinks 242

8.11  Rearrangements To An Electrophilic Center 243

8.12  Nu-L Reactions 244

8.13  Product Matrix Summary 248

9  DECISIONS, DECISIONS 251 

9.1 Decision Point Recognition 252

9.2 Multiple Additions 252

9.3 Regiochemistry & Stereochemistry Of Enolate Formation 254

9.4 Ambident Nucleophiles 255

9.5 Substitution Vs. Elimination 258

9.6 Ambident Electrophiles 262

9.7 Intermolecular Vs. Intramolecular 263

9.8 To Migrate Or Not To An Electrophilic Center 264

9.8 Summary 266

10 CHOOSING THE MOST PROBABLE PATH  269 

10.1  Problem-Solving In General 270

10.2  General Mechanistic Cross-Checks 274

10.3  The Path-Selection Process 276

10.4  Reaction Mechanism Strategies 278

10.5  Worked Mechanism Examples 279

10.6  Product Prediction Strategies 297

10.7  Worked Product Prediction Examples 297

10.8  Methods For Testing Mechanisms 313

10.9  Lessons from Biochemical Mechanisms 319

10.10 Summary 321

11 ONE-ELECTRON PROCESSES 326 

11.1  Radical Structure And Stability 326

11.2  Radical Path Initiation 329

11.3  Major Paths For Radicals Reacting With Neutrals 330

11.4  Unimolecular Radical Paths 332

11.5  Termination Radical Paths 333

11.6  Radical Path Combinations 333

11.7  Approaches To Radical Mechanisms 336

11.8  Single Electron Transfer, S.E.T., And Charged Radicals 338

11.9  Dissolving Metal Reductions 339

11.10 Electron Transfer Initiated Processes 340

11.11 One-Electron Path Summary 340

12 QUALITATIVE M.O. THEORY & PERICYCLIC REACTIONS  343 

12.1  Review Of Orbitals As Standing Waves 344

12.2  Molecular Orbital Theory For Linear Pi Systems 344

12.3  Molecular Orbital Theory For Cyclic Conjugated PI Systems 348

12.4  Perturbation Of The HOMO And LUMO 351

12.5  Delocalization Of Sigma Electrons (Supplemental) 352

12.6  Concerted Pericyclic Cycloaddition Reactions 353

12.7  Concerted Pericyclic Electrocyclic Reactions 357

12.8  Concerted Pericyclic Sigmatropic Rearrangements 359

12.9  Pericyclic Reactions Summary 361 

APPENDIX (A COLLECTION OF IMPORTANT TOOLS)  364 

General Bibliography 364

Abbreviations Used in This Text 365

Functional Group Glossary 366

Composite pKa Chart 369

Bond Strength Table 372

Generic Classification Guide 373

Flow Charts for the Classification of Electron Sources and Sinks 375

Pathway Summary 375

Trends Guide 380

Major Routes Summary 384

Major Decisions Guide 388

Thermodynamics and Kinetics 390

Generation of Alternate Paths, Reaction Cubes 390

Organic Structure Elucidation Strategies 393

Notes on Nomenclature 399

HINTS TO PROBLEMS FROM CHAPTERS 8, 9, AND 10 404 

INDEX 407