The Art of Problem Solving in Organic Chemistry

Contents

Preface

Text Organization

Reference

Preface to the First Edition

Acknowledgments

1 Problem Analysis in Organic Reaction Mechanism

1.1 Overview

1.2 Introduction

1.2.1 “Pushing Forward” a Solution in Formal and Exhaustive Terms

1.2.2 Lessons from this Example

1.3 Avoiding the Quagmire

1.4 The Basic Steps of Problem Analysis

1.4.1 Recognizing the Problem

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

1.4.3 Drawing a First Outline for Guidance

1.4.4 Asking the Right Questions and Proposing the Right Answers… is enough?

1.5 Intuition and Problem Solving

1.6 Summing Up

References and Notes

2 Electron Flow in Organic Reactions

2.1 Overview

2.2 Introduction

2.3 Practical Rules Governing Electron Redeployment

2.3.1 Issue 1: Electrons within Orbitals

2.3.2 Issue 2: Electron Transfer and Stereochemistry

2.3.3 Issue 3: Electron Energy Level and Accessibility

2.3.4 Issue 4: Electron Flow and Molecular Active Sectors

2.3.4.1 Case A: n–π Interactions

2.3.4.2 Case B: π – σ Interactions

2.3.4.3 Case C: When Reactivity Patterns Seem to Break Down

2.3.5 Issue 5: Electron Traffic and Electronic Density Differences

2.3.5.1 M0 Metals as Electron Source

2.3.5.2 Metal Hydrides and Organic Hydrides as Electron Source

2.3.6 Issue 6: Creating Zones of High Electron Density

2.3.6.1 The Natural Polarization

2.3.6.2 Reversing the Natural Polarization

2.3.7 Issue 7: Electron Flow and Low Electron Density Zones

2.3.7.1 Identifying LEDZs

2.3.7.2 Creating a New LEDZ in the Substrate

2.3.7.3 Finding Unsuspected LEDZs among the Other Reagents in the Mixture

2.3.7.4 When Compounds Show Double Personality

2.4 Summing Up

2.5 A Flowchart of Organized Problem Analysis

References and Notes

3 Additional Techniques to Postulate Organic Reaction Mechanisms

3.1 Overview

3.2 Take Your Time

3.3 Clear and Informative Molecular Renderings

3.3.1 The Value of Molecular Sketches

3.3.2 Two- Versus Three-Dimensional Renderings and the “Flat” Organic Compounds

3.4 Element and Bond Budgets

3.5 Looking at Molecules from Various Perspectives

3.6 Separate the Grain from the Chaff

3.7 Dissecting Products in Terms of Reactants: Fragmentation Analysis

3.7.1 The Fundamental Proposition

3.7.2 Adding Potentially Nucleophilic or Electrophilic Character to Fragments

3.7.3 When Fragmentation Analysis Fails, Getting Help from Atom Labels

3.8 Oxidation Levels and Mechanism

3.8.1 Methods to Estimate Oxidation Status

3.9 The Functionality Number

3.9.1 What Exactly Is FN?

3.9.2 Properties of FN

3.10 Combining Fragmentation Analysis and Functionality Numbers

3.11 Summing up

References

4 Solved Problem Collection

Problem 1

Prolem 1: Discussion

Part I: Explaining Products 2 and 3

References

Problem 2

Problem 2: Discussion

References and Notes

Problem 3

Problem 3: Discussion

Part 1: Explaining Compound 3

Part II: Explaining Product 4

References and Notes

Problem 4

Problem 4: Discussion

References and Notes

Problem 5

Problem 5: Discussion

References and Notes

Problem 6

Problem 6: Discussion

References and Notes

Problem 7

Problem 7: Discussion

Part I: Explaining the Thermolysis of 1

Part II. Explaining the Thermolysis of 3

Part III. Comments on the Stereochemistry of 4

References and Notes

Problem 8

Problem 8: Discussion

References

Problem 9

Problem 9: Discussion

Part I: Solving Reaction I

Part II: Solving Reaction II

References

Problem 10

Problem 10: Discussion

References

Problem 11

Problem 11: Discussion

References

Problem 12

Problem 12: Discussion

References and Notes

Problem 13

Problem 13: Discussion

References and Notes

Problem 14

Problem 14: Discussion

Part I: Explaining 1 (Condition i) → 2(S)

Part II: Explaining 1 (Condition ii) → 2(R)

References and Notes

Problem 15

Problem 15: Discussion

Part I: Explaining 1 → 2

Part II: Explaining Products 3 and 6

References and Notes

Problem 16

Problem 16: Discussion

Part I: Explaining Product 2, the Easy Part

Part II: Explaining Product 3

References and Notes

Problem 17

Problem 17: Discussion

References and Notes

Problem 18

Problem 18: Discussion

Part I: Reaction A: Explaining Product 2 (and 3 as likely offshoot)

Part II: Explaining Reaction B

References and Notes

Problem 19

Problem 19: Discussion

Part I: Explaining Product 2

Part II: Explaining Product 3

References and Notes

Problem 20

Problem 20: Discussion

Part I: Solving 1 → 2

Part II: Solving 1 → 3

References and Notes

Problem 21

Problem 21: Discussion

Part I: Explaining 1 → 2

Part II: Explaining 1 → 3

References and Notes

Problem 22

Problem 22: Discussion

Part I: Explaining Product 2

Part II: Explaining Product 3, a Separate Problem in Itself

References and Notes

Problem 23

Problem 23: Discussion

Part I: Explaining 1 → 2 and Maybe 3

Part II: Explaining 4 → 5

References

Problem 24

Problem 24: Discussion

Part I: Explaining 1 → 2

Part II: Explaining Products from 3

References and Notes

Problem 25

Problem 25: Discussion

References and Notes

Problem 26

Problem 26: Discussion

Part I: Explaining Products 2 and 3 as a Warm-Up

Part II: Explaining Product 4

Part III: Solving 5 → 6 + 7

References and Notes

Problem 27

Problem 27: Discussion

Part I: Exploring 1 + 2 → 5

Part II: Explaining 1 → 6 [3]

References and Notes

Problem 28

Problem 28: Discussion

References

Problem 29

Problem 29: Discussion

Reference

Problem 30

Problem 30: Discussion

References and Notes

Problem 31

Problem 31: Discussion

Part I: Unveiling Compound 3

Part II: Assembling Adducts 4 and 5

Part III: How Does 5 Arise?

Part IV: Explaining Product 6

References and Notes

Problem 32

Problem 32: Discussion

Part I: The General Picture

Part II. Putting Together the South Western End (Rings A and B)

Part III. Building the Orthoacetate Southeastern Section

References

Problem 33

Problem 33: Discussion

Part I. Explaining 1 → 4:

Reference

Problem 34

Problem 34: Discussion

References and Notes

Problem 35

Problem 35: Discussion

Part I. Explaining Product 3

Part II. Explaining product 4

References

Problem 36

Problem 36: Discussion

References and Notes

Problem 37

Problem 37: Discussion

References and Notes

Problem 38

Problem 38: Discussion

References and Notes

Problem 39

Problem 39: Discussion

Part I: Overview

Part II: Solving the Most Likely Ugi Product X

Part III. Submitting 9 to H3PO4

Part IV. In Search for Effective Stereocontrol in 5

Part V. Attempting to Explain 5 Stereospecifically from 16

References and Notes

Problem 40

Problem 40: Discussion

Part I: Putting 3 Together

Part II. Understanding Catalyst 4

Part III. Understanding Mechanistic Enantioselectivity to Obtain 3

References and Notes

Problem 41

Problem 41: Discussion

Part I: Explaining Compound 4

Part II: Explaining Target 5

References and Notes

Problem 42

Problem 42: Discussion

References and Notes

Problem 43

Problem 43: Discussion

Part I: Bond Connections

Part II. Accounting for Observed Diastereoselectivity

References and Notes

Problem 44

Problem 44: Discussion

Part I. Explaining Product 3

Part II.- Explaining Product 4:

Part III. Stereochemistry of 4

Part IV. Explaining 4 → 5 → 6

References and Notes

Problem 45

Problem 45: Discussion

Reference

Problem 46

Problem 46: Discussion

Part I. Explaining Targets 2 and 3 and Their Stereochemistry

Part II. Deciding which Mechanism Prevails

References and Notes

Problem 47

Problem 47: Discussion

Part I. Establishing the Basic Premises

Part II. Turning the Premises into Real Chemistry to Explain 1 → 2 + 3

Part III. Explaining the 2:3 Diastereoselectivity

Part IV. Explaining 1 → 4

References and Notes

Problem 48

Problem 48: Discussion

References and Notes

Problem 49

Problem 49: Discussion

Part I. Solving 1 → X

Part II. Moving on from X to 2

References and Notes

Problem 50

Problem 50: Discussion

References and Notes

Problem 51

Problem 51: Discussion

References and Notes

Problem 52

Problem 52: Discussion

References and Notes

Problem 53

Problem 53: Discussion

Part I: Explaining 1 → 2

Part II: Stereochemistry of 2EZ

References and Notes

Problem 54

Problem 54: Discussion

Part I: Explaining 1 → 2

Part II: Explaining 3 → 4

References and Notes

Problem 55

Problem 55: Discussion

Part I: Explaining 1 → 3 + 4

Part II: Explaining 1 + 2 → 6

References and Notes

Problem 56

Problem 56: Discussion

Part I: Explaining 1 → 3

Part II: Explaining 1 → 2

References and Notes

Problem 57

Problem 57: Discussion

References and Notes

Problem 58

Problem 58: Discussion

References and Notes

Problem 59

Problem 59: Discussion

Part I: Preliminary Clarifications

Part II: Solving 1 → 2

Part III: Solving 1 → 3

References and Notes

Problem 60

Problem 60: Discussion

Part I: Explaining 1 → 3

Part II: Understanding Stereochemistry of 1 → 3

Part III: Explaining 4 → 5

References and Notes

Glossary

Subject/Reaction Index

Reagent Index

Author Index

Graphical Problem Index

EULA