THE ART OF PROBLEM SOLVING IN ORGANIC CHEMISTRY
CONTENTS PART I THE TOOLBOX 1 INTRODUCTION TO PROBLEM ANALYSIS IN ADVANCED ORGANIC REACTION MECHANISM 1 1 OVERVIEW, 1 2 THE FIRST THREE STEPS IN PROBLEM ANALYSIS, 1 2 1 A BIRD’S EYE OVERVIEW, 1 2 2 CHANGE THE MOLECULAR RENDERING TO A FAMILIAR FRAMEWORK, 1 2 3 GO FOR THE RELEVANT, SKIP THE SUPERFICIAL INFORMATION, 1 3 MOVING BEYOND THE PRIMARY ANSWERS, 1 4 DRAWING A PRELIMINARY OUTLINE FOR GUIDANCE, 1 5 INTUITION AND PROBLEM SOLVING, 1 6 SUMMING UP, 1 7 SOLUTION TO THE 14 ? 16 CONVERSION IN SCHEME I 5, REFERENCES AND NOTES, 2 ELECTRON FLOW IN ORGANIC REACTIONS 2 1 OVERVIEW, 2 2 INTRODUCTION, 2 2 1 A WORD OR TWO ON NOTATION, 2 2 1 1 LEWIS NOTATION AND LINE RENDERINGS, 2 2 1 2 CURVED OR “CURLY” ARROWS, 2 3 ELECTRONS IN COVALENT BONDING AND REDEPLOYMENT, 2 3 1 A PRELIMINARY REVIEW OF THE ESSENTIALS, 2 3 1 1 ELECTRONS AND COVALENT BONDS: THE STILL UNSOLVED FUNDAMENTAL QUESTIONS, 2 4 PRACTICAL RULES GOVERNING ELECTRON REDEPLOYMENT, 2 4 1 ISSUE 1: ELECTRONS RESIDE WITHIN ORBITALS, 2 4 1 1 THE QUESTION OF ORBITAL RESTRICTIONS AND ELECTRON DEPLOYMENT, 2 4 2 ISSUE 2: THE ELECTRON SHIELD CONCEPT CONTRIBUTES TO COVALENT BONDS, 2 4 2 1 CARBOCATIONS, 2 4 2 2 CARBON DICATIONS, 2 4 3 ISSUE 3: AO/MO OVERLAP IS A REQUIREMENT FOR ? AND ? BOND FORMATION, 2 4 3 1 AO/MO LIMITS AND THE QUANTUM TUNNELING EFFECT, 2 4 4 ISSUE 4: ELECTRON TRAFFIC AND STEREOCHEMISTRY, 2 4 5 ISSUE 5: ELECTRON ENERGY LEVEL AND ACCESSIBILITY, 2 4 6 ISSUE 6: ELECTRON FLOW AND MOLECULAR ACTIVE SECTORS, 2 4 7 ISSUE 7: ELECTRON FLOW AND COMPATIBLE AO TYPES, 2 4 7 1 ?–? INTERACTIONS, 2 4 7 2 ?–? INTERACTIONS, 2 4 7 3 ?–? INTERACTIONS, ISSUE 8: ELECTRON FLOW, DELOCALIZATION OF BONDING AND NON-BONDING ELECTRONS, RESONANCE STABILIZATION, 2 4 8 1 NON-BONDING ELECTRON PAIRS (NBPS), ISSUE 9: ELECTRON TRAFFIC AND ELECTRONIC DENSITY DIFFERENCES, 2 4 9 1 DETECTING POTENTIAL DONORS AND ACCEPTORS, 2 4 9 2 WHAT MAKES A GIVEN FUNCTIONAL GROUP A NATURAL HEDZ OR LEDZ?, 2 4 9 3 A REMINDER TAKEAWAY, 2 4 9 4 QUANTUM-MECHANICAL COMPUTATIONS AND MECHANISM, 2 4 10 ISSUE 10: ELECTRON TRAFFIC ON ACCOUNT OF LEDZ ALONE, 2 4 10 1 HIDDEN LEDZS TRIGGERING DEEP-ROOTED SKELETAL REARRANGEMENTS, 2 4 10 2 REMOTE C–H ACTIVATION BY LEDZ AND RADICALS, 2 4 11 ISSUE 11: INVERTING THE NATURAL ELECTRON FLOW, UMPOLUNG, 2 4 11 1 UMPOLUNG SUCCESSFUL ACCOMPLISHMENTS, 2 4 11 2 THE NITROGEN HETEROCYCLE CARBENES (NHC) IN CARBONYL UMPOLUNG, 2 4 11 3 UMPOLUNG OF C=O THROUGH IMINE DERIVATIVES, 2 4 11 4 THE HYDRAZONE WAY TO C=O UMPOLUNG, 2 4 12 ISSUE 12: ONE-ELECTRON FLOW, 2 4 12 1 RADICALS, REMINDER TAKEAWAYS, 2 4 12 2 CARBENES, OVERVIEW, AND ELECTRON REDEPLOYMENT, 2 5 SUMMING UP, 2 6 ORGANIZED PROBLEM ANALYSIS WITH THE TOOLS DESCRIBED SO FAR, 2 7 SUPPLEMENTARY SCHEMES: SOLUTIONS TO PROBLEMS EMBEDDED IN THIS CHAPTER, NOTES, 3 STEREOCHEMISTRY AND MECHANISM OF MOLECULAR TRANSFORMATIONS 3 1 OVERVIEW, 3 2 INTRODUCTION, THE QUESTION OF PLANAR MOLECULES AND DEVIATIONS, AN APPROACH TO STERIC EFFECTS, 3 2 1 1 PLANAR 2D VERSUS 3D, 3 2 1 2 PERTURBATION OF PLANARITY BY SUBSTITUENTS; APPROACHING STERIC EFFECTS, 3 2 1 3 INTERACTION OF DISTANT C=C BONDS BY STEREOCHEMICAL PROXIMITY, 3 3 MEASURING STERIC HINDRANCE, THE ROADBLOCKS AHEAD, STERIC REQUISITES FOR BUILDING ? BONDS, REACTION RATE RETARDATION DUE TO STERIC HINDRANCE, THE SAGA OF PURELY STERIC EFFECTS, 3 3 4 1 STUDY CASE 1: SUBSTITUTION (SN2) OF ALKYL BROMIDES BY SODIUM METHOXIDE, 3 3 4 2 STUDY CASE 2: HYDROLYSIS OF ESTERS AND ESTERIFICATION OF CARBOXYLIC ACIDS, 3 3 4 3 STUDY CASE 3: CONNOLLY’S MOLECULAR VOLUME, 3 3 4 4 STUDY CASE 4: THE ANILINES ARYLSULFONYL CHLORIDE MODEL, 3 3 4 5 STUDY CASE 5: OTHER SOURCES OF EVIDENCE, STERIC ACCELERATION OF REACTION RATES, 3 3 5 1 STERIC ACCELERATION IN SN1/E1 COMPETITION DURING SOLVOLYSIS, 3 3 5 2 STERIC ACCELERATION IN THE GAS PHASE, SUMMARY OF STERIC HINDRANCE AND REACTIVITY TAKEAWAYS, 3 4 APPLICATIONS TO STEREOCHEMICALLY COMPETENT REACTION MECHANISMS, A CASE OF REGIO AND STEREOSELECTIVE REACTION IN A STERICALLY SIMPLE COMPOUND, THE ROLE OF STERIC UMBRELLAS, 3 5 STEREOCHEMISTRY IN BIMOLECULAR REACTIONS: CYCLOADDITIONS, THE DIELS–ALDER CYCLOADDITION: THE CA PROTOTYPE, 3 5 1 1 DACA STERIC DOMAIN: ESSENTIAL TAKEAWAYS, 3 5 1 2 DACA STEREOELECTRONIC DOMAIN: ESSENTIAL TAKEAWAYS, 3 5 1 3 ASSESSING STERIC EFFECTS (SES) THROUGH PRODUCTS CONFIGURATION: THE ENDO ALDERS RULE, 3 5 1 4 THE EXO : ENDO RATIO AND LEWIS-ACID CATALYSIS, 3 5 1 5 CURRENT AND FUTURE PROSPECTS FOR DACA AND OTHER CYCLOADDITIONS, 3 6 THE ULTIMATE STEREO- AND ENANTIO-CONTROL: ORIENTED EXTERNAL ELECTRIC FIELDS (OEEFS), 3 6 1 HOW OEEF WORKS, 3 6 2 OEEF AND DACA STEREOCONTROL, 3 6 3 THE EXPERIMENTAL ARRAY, 3 7 SUMMING UP, 3 8 SUPPLEMENTARY SCHEMES, REFERENCES, 4 ADDITIONAL TECHNIQUES TO POSTULATE ORGANIC REACTION MECHANISMS OVERVIEW, TAKE YOUR TIME, USE CLEAR AND INFORMATIVE MOLECULAR RENDERINGS, ELEMENT AND BOND BUDGETS, LOOKING AT MOLECULES FROM DIFFERENT PERSPECTIVES, REDRAW REACTANTS SUCH THAT THEY RESEMBLE PRODUCTS, FRAGMENTATION ANALYSIS (FA): DISSECTING PRODUCTS IN TERMS OF REACTANTS, 4 7 1 THE FUNDAMENTAL PROPOSITION, 4 7 2 STUDY CASE 1, 4 7 3 STUDY CASE 2, 4 7 4 LEARNING LESSONS AND TAKEAWAYS FROM FA, OXIDATION LEVELS AND MECHANISM, THE FUNCTIONALITY NUMBER (FN), 4 9 1 WHAT EXACTLY IS FN?, 4 9 2 ORGANIZING CARBON FUNCTIONALITIES IN FN GROUPS, 4 9 3 MAIN FN GROUPS PROPERTIES, 4 9 4 STUDY CASE 1, 4 9 5 STUDY CASE 2, 4 9 6 STUDY CASE 3: HETEROLYTIC C–C CLEAVAGE AND THE ELECTRON SINK, 4 10 COMBINING FRAGMENTATION ANALYSIS AND FUNCTIONALITY NUMBERS, 4 11 A FLOWCHART TO ORDERLY EXPLOIT THE STRATEGIES OF THIS CHAPTER, 4 12 SUMMING UP, 4 13 SOLUTION TO PROBLEMS EMBEDDED IN THIS CHAPTER, PART II THE PROBLEM CHEST