Computational organic chemistry

Cover

Title Page

Contents

Preface

Acknowledgments

Chapter 1 Quantum Mechanics for Organic Chemistry

1.1 Approximations to the Schrodinger Equation

The Hartree

Fock Method

1.1.1 Nonrelativistic Mechanics

1.1.2 The Born

Oppenheimer Approximation

1.1.3 The One-Electron Wavefunction and the Hartree

Fock Method

1.1.4 Linear Combination of Atomic Orbitals (LCAO) Approximation

1.1.5 Hartree

Fock

Roothaan Procedure

1.1.6 Restricted Versus Unrestricted Wavefunctions

1.1.7 The Variational Principle

1.1.8 Basis Sets

1.1.8.1 Basis Set Superposition Error

1.2 Electron Correlation

Post-Hartree

Fock Methods

1.2.1 Configuration Interaction (CI)

1.2.2 Size Consistency

1.2.3 Perturbation Theory

1.2.4 Coupled-Cluster Theory

1.2.5 Multiconfiguration SCF (MCSCF) Theory and Complete Active Space SCF (CASSCF) Theory

1.2.6 Composite Energy Methods

1.3 Density Functional Theory (DFT)

1.3.1 The Exchange-Correlation Functionals: Climbing Jacob's Ladder

1.3.1.1 Double Hybrid Functionals

1.3.2 Dispersion-Corrected DFT

1.3.3 Functional Selection

1.4 Computational Approaches to Solvation

1.4.1 Microsolvation

1.4.2 Implicit Solvent Models

1.4.3 Hybrid Solvation Models

1.5 Hybrid QM/MM Methods

1.5.1 Molecular Mechanics

1.5.2 QM/MM Theory

1.5.3 ONIOM

1.6 Potential Energy Surfaces

1.6.1 Geometry Optimization

1.7 Population Analysis

1.7.1 Orbital-Based Population Methods

1.7.2 Topological Electron Density Analysis

1.8 Interview: Stefan Grimme

References

Chapter 2 Computed Spectral Properties and Structure Identification

2.1 Computed Bond Lengths and Angles

2.2 IR Spectroscopy

2.3 Nuclear Magnetic Resonance

2.3.1 General Considerations

2.3.2 Scaling Chemical Shift Values.

4.1.2 The Nonconcerted Reaction of 1,3-Butadiene with Ethylene

4.1.3 Kinetic Isotope Effects and the Nature of the Diels

Alder Transition State

4.1.4 Transition State Distortion Energy

4.2 The Cope Rearrangement

4.2.1 Theoretical Considerations

4.2.2 Computational Results

4.2.3 Chameleons and Centaurs

4.3 The Bergman Cyclization

4.3.1 Theoretical Considerations

4.3.2 Activation and Reaction Energies of the Parent Bergman Cyclization

4.3.3 The cd Criteria and Cyclic Enediynes

4.3.4 Myers

Saito and Schmittel Cyclization

4.4 Bispericyclic Reactions

4.5 Pseudopericyclic Reactions

4.6 Torquoselectivity

4.7 Interview: Professor Weston Thatcher Borden

References

Chapter 5 Diradicals and Carbenes

5.1 Methylene

5.1.1 Theoretical Considerations of Methylene

5.1.2 The H

C

H Angle in Triplet Methylene

5.1.3 The Methylene and Dichloromethylene Singlet

Triplet Energy Gap

5.2 Phenylnitrene and Phenylcarbene

5.2.1 The Low Lying States of Phenylnitrene and Phenylcarbene

5.2.2 Ring Expansion of Phenylnitrene and Phenylcarbene

5.2.3 Substituent Effects on the Rearrangement of Phenylnitrene

5.3 Tetramethyleneethane

5.3.1 Theoretical Considerations of Tetramethyleneethane

5.3.2 Is TME a Ground-State Singlet or Triplet?

5.4 Oxyallyl Diradical

5.5 Benzynes

5.5.1 Theoretical Considerations of Benzyne

5.5.2 Relative Energies of the Benzynes

5.5.3 Structure of m-Benzyne

5.5.4 The Singlet

Triplet Gap and Reactivity of the Benzynes

5.6 Tunneling of Carbenes

5.6.1 Tunneling control

5.7 Interview: Professor Henry ``Fritz'' Schaefer

5.8 Interview: Professor Peter R. Schreiner

References

Chapter 6 Organic Reactions of Anions

6.1 Substitution Reactions

6.1.1 The Gas Phase SN2 Reaction.

6.1.2 Effects of Solvent on SN2 Reactions

6.2 Asymmetric Induction Via 1,2-Addition to Carbonyl Compounds

6.3 Asymmetric Organocatalysis of Aldol Reactions

6.3.1 Mechanism of Amine-Catalyzed Intermolecular Aldol Reactions

6.3.2 Mechanism of Proline-Catalyzed Intramolecular Aldol Reactions

6.3.3 Comparison with the Mannich Reaction

6.3.4 Catalysis of the Aldol Reaction in Water

6.3.5 Another Organocatalysis Example

The Claisen Rearrangement

6.4 Interview: Professor Kendall N. Houk

References

Chapter 7 Solution-Phase Organic Chemistry

7.1 Aqueous Diels

Alder Reactions

7.2 Glucose

7.2.1 Models Compounds: Ethylene Glycol and Glycerol

7.2.1.1 Ethylene Glycol

7.2.1.2 Glycerol

7.2.2 Solvation Studies of Glucose

7.3 Nucleic Acids

7.3.1 Nucleic Acid Bases

7.3.1.1 Cytosine

7.3.1.2 Guanine

7.3.1.3 Adenine

7.3.1.4 Uracil and Thymine

7.3.2 Base Pairs

7.4 Amino Acids

7.5 Interview: Professor Christopher J. Cramer

References

Chapter 8 Organic Reaction Dynamics

8.1 A Brief Introduction To Molecular Dynamics Trajectory Computations

8.1.1 Integrating the Equations of Motion

8.1.2 Selecting the PES

8.1.3 Initial Conditions

8.2 Statistical Kinetic Theories

8.3 Examples of Organic Reactions With Non-Statistical Dynamics

8.3.1 [1,3]-Sigmatropic Rearrangement of Bicyclo[3.2.0]hex-2-ene

8.3.2 Life in the Caldera: Concerted versus Diradical Mechanisms

8.3.2.1 Rearrangement of Vinylcyclopropane to Cyclopentene

8.3.2.2 Bicyclo[3.1.0]hex-2-ene 20

8.3.2.3 Cyclopropane Stereomutation

8.3.3 Entrance into Intermediates from Above

8.3.3.1 Deazetization of 2,3-Diazabicyclo[2.2.1]hept-2-ene 31

8.3.4 Avoiding Local Minima

8.3.4.1 Methyl Loss from Acetone Radical Cation.

8.3.4.2 Cope Rearrangement of 1,2,6-Heptatriene

8.3.4.3 The SN2 Reaction: HO-+CH3F

8.3.4.4 Reaction of Fluoride with Methyl Hydroperoxide

8.3.5 Bifurcating Surfaces: One TS, Two Products

8.3.5.1 C2

C6 Enyne Allene Cyclization

8.3.5.2 Cycloadditions Involving Ketenes

8.3.5.3 Diels

Alder Reactions: Steps toward Predicting Dynamic Effects on Bifurcating Surfaces

8.3.6 Stepwise Reaction on a Concerted Surface

8.3.6.1 Rearrangement of Protonated Pinacolyl Alcohol

8.3.7 Roaming Mechanism

8.3.8 A Roundabout SN2 reaction

8.3.9 Hydroboration: Dynamical or Statistical?

8.3.10 A Look at the Wolff Rearrangement

8.4 Conclusions

8.5 Interview: Professor Daniel Singleton

References

Chapter 9 Computational Approaches to Understanding Enzymes

9.1 Models for Enzymatic Activity

9.2 Strategy for Computational Enzymology

9.2.1 High Level QM/MM Computations of Enzymes

9.2.2 Chorismate Mutase

9.2.3 Catechol-O-Methyltransferase (COMT)

9.3 De Novo Design of Enzymes

References

Index

Supplemental Images.