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Advances in Physical Organic Chemistry

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Contents

Contributors

Preface

References

Chapter One: The Factors Determining Reactivity in Nucleophilic Substitution

1. Introduction

2. The Nucleophile in Methyl Transfer Reactions

2.1. Reactions in Solution: Swain and Scott's Nucleophilicity Scale

2.2. Nucleophilicity in Gas Phase Reactions

2.3. Relationship Between Methyl Cation Affinity and Proton Affinity

2.4. Identity SN2 Reactions

2.5. The Double-Well Potential Model

2.6. Marcus Theory: Relating the Intrinsic Barrier and Reaction Enthalpy to Actual Reaction Barriers

2.7. Towards Accurate Models for Methyl Transfer Reactions

2.8. The Alpha Effect

3. The Leaving Group

4. The Substrate

4.1. Alkyl-Substituted Carbon Centres

4.2. Cyclic Substrates

4.3. Benzylic and Allylic Substrates

4.4. Aromatic and Vinylic Nucleophilic Substitution

4.5. SN2 at Centres of Group 14-18 Elements

5. Cationic Reactions and Shift to SN1

6. Kinetic Isotope Effects

7. Understanding SN2 Reactivity

7.1. Correlations Between Barrier Heights and Physical Observables

7.2. VB Theory

7.3. HSAB Theory and Related Approaches

7.4. Energy Decomposition Analysis

8. Reaction Dynamics

9. Role of the Solvent

10. Summary and Outlook

References

Chapter Two: Negative Ion Photoelectron Spectroscopy and Its Use in Investigating the Transition States for Some Organic ...

1. Introduction

1.1. Transition States

1.2. Negative Ion Photoelectron Spectroscopy12,13

1.2.1. Vibrational Bands in NIPE Spectra

1.2.2. Franck-Condon Factors for Vibrational Progressions in NIPE Spectra

1.2.3. The NIPE Spectrum of CO4∙– and Its Simulation

2. Transition State Spectroscopy

2.1. TS Spectroscopy of X∙+H-X Hydrogen Abstraction Reactions

2.1.1. The NIPE Spectrum of I-H-I-

2.1.2. The PES for the Reaction XA∙+H-XBXA-H+XB∙

2.1.3. Antisymmetric Stretching Vibrations on the X-H-X PES

2.1.4. Symmetric Stretching Vibrations on the X-H-X PES

2.2. TS Spectroscopy of Singlet COT

2.2.1. Predicted Violations of Hund's Rule in [4n]Annulenes

2.2.2. PESs for Ring Inversion and Bond Shifting in Singlet and Triplet COT and in COT∙-

2.2.3. NIPE Spectroscopy of COT∙-

2.3. TS Spectroscopy of Singlet OXA

2.3.1. The NIPE Spectrum of OXA∙-

2.4. TS Spectroscopy of Singlet and Triplet (CO)3

2.4.1. The MOs of (CO)3

2.4.2. The PES for Singlet (CO)3

2.4.3. The PES for Triplet (CO)3

2.4.4. Calculated Franck-Condon Factors

2.4.5. The NIPE Spectrum of CO3∙- and Its Simulation

3. Summary

Acknowledgment

References

Chapter Three: Probing Transition State Analogy in Glycoside Hydrolase Catalysis

1. Scope and Purpose for This Review

2. General Introduction

2.1. Transition State Analogy

2.2. Glycoside Hydrolases

2.3. Glycoside Hydrolases: Transition State Analogy

3. Intrinsic Reactivity

3.1. Furanoside Solvolyses

3.2. Pyranoside Solvolyses

4. Catalytic Efficiency and Proficiency

4.1. Measurement of Uncatalysed Rate Constants at High Temperatures

4.2. Extrapolation of Uncatalysed Reaction Rate Constants Using Activated Substrates

5. Evaluation of Transition State Analogy by LFERs

5.1. Experiments Using Site-Directed Mutagenesis

5.2. Experiments Using a Panel of Substrate and Inhibitor Dyads

5.3. Experiments Involving Mechanism-Based Covalent Inhibitors

6. Recent Examples

6.1. Transition State Analogy in GH84 O-GlcNAc Hydrolase

6.2. Covalent Inhibitors of Yeast α-Glucosidase

References

Chapter Four: Phosphate Ester Hydrolysis: The Path From Mechanistic Investigation to the Realization of Artificial Enzymes

1. Introduction

2. Phosphate Ester Hydrolysis

2.1. The Rate of Phosphate Ester Hydrolysis

2.2. The Mechanisms of Phosphate Ester Hydrolysis

2.3. Computational Investigations

2.4. What Controls the Hydrolytic Reactivity of Phosphate Esters

3. Metal Ion Catalysis of Hydrolytic Phosphate Ester Cleavage

3.1. The Mechanism of the Metal-Catalysed Reaction

3.2. Catalytic Roles of the Metal Ions

3.3. Dissection of the Metal Ion Activation Factors

3.4. Strategies to Improve the Lewis Acid Activation Effect

3.5. Strategies to Improve the Nucleophile Activation

4. Comparison Between Enzymes and Artificial Agents Catalysis

5. Conclusions

References

Chapter Five: Physicochemical Aspects of Aqueous and Nonaqueous Approaches to the Preparation of Nucleosides, Nucleotides ...

1. Introduction

2. Physicochemical Properties of Nucleosides, Nucleotides and Polyphosphates

2.1. Acid-Base Properties

2.2. Intermolecular Interactions Between Nucleosides

3. Synthetic Methods

3.1. An Overview of Widely Used Methods for Phosphoanhydride Bond Formation

3.2. New Nonaqueous Solvent-Based Transformations

3.2.1. New Methods for Phosphoanhydride Bond Formation

3.2.1.1. The Development of New P(III) Strategies

3.2.1.2. The Development of New P(V) Strategies

3.2.2. Phosphate Nucleophiles

3.2.3. Sulphurization

3.3. Aqueous Transformations

3.4. Ionic Liquid-Based and Solvent-Free Transformations

3.4.1. Ionic Liquids

3.4.2. Mechanochemical Methods

3.4.2.1. Nucleoside Synthesis

3.4.2.2. Preparation of Phosphorylated Species

4. Conclusions

Acknowledgments

References

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