Modern nucleophilic aromatic substitution \ François Terrier.

Format:

Book

Author/Creator:

Terrier, F.

Contributor:

Anne and Joseph Trachtman Memorial Book Fund.

Lachs-Adler Family Endowed Fund for Collection Development.

Language:

English

Subjects (All):

Nucleophilic reactions.

Aromatic compounds.

Physical Description:

xiii, 472 pages : illustrations ; 25 cm

Place of Publication:

Weinheim : Wiley-VCH, [2013]

Summary:

Nucleophilic Aromatic Substitutions (S

Contents:

1 The S_NAr Reactions: Mechanistic Aspects 1

1.1 Introduction 1

1.2 Activation of the Aromatic System: Driving Force for S_NAi Reactions 5

1.2.1 Benzene and Related Arene Derivatives 5

1.2.2 Pyridine and Related Aza-aromatics 11

1.2.3 Five-Membered Ring Heterocycles 15

1.2.4 Activation by Electron-Withdrawing Heterocyclic Units: The Superelectrophilic Dimension in S_NAt Substitutions 18

1.3 Leaving Group, Nucleophile, Solvent, and Medium Effects 24

1.3.1 The Influence of the Leaving Group 24

1.3.1.1 Halogen Nucleofugality 24

1.3.1.2 The Mobility of the Nitro Group and Other Leaving Groups 28

1.3.2 The Influence of the Nucleophile 31

1.3.2.1 Basicity and Polarizability 31

1.3.2.2 Ritchie and Mayr's Scales 36

1.3.3 The Influence of the Solvent 38

1.3.3.1 S_NAt Reactions Involving Anionic Nucleophiles 38

1.3.3.2 S_NAr Reactions Involving Neutral Nucleophiles 42

1.4 Effects of Specific Structural Variations in the Activated Ring 46

1.4.1 ortho versus para Activation: Hydrogen Bonding and Built-in Solvation 46

1.4.2 Reactivity at Unsubstituted versus Substituted Ring Carbon Atoms: Side Processes 50

1.5 Spectral Evidence for the Intermediacy of c-Complexes in S_NAt Reactions 52

1.6 Base Catalysis in S_NAt Reactions 57

1.6.1 The Specific Base-General Add Mechanism 61

1.6.2 The Rate-limiting Proton-Transfer Mechanism 65

1.7 Regioselectivity in S_NAt Reactions 68

1.8 Asymmetric S_NAr Substitutions 73

1.9 Concerted S_NAr Substitutions 76

1.9.1 Ring Activation and Feasibility of Concerted Substitutions 76

1.9.2 Concerted Substitutions in Triazines 79

1.10 Conclusion 83

References 84

2 Structure and Reactivity of Anionic σ -Complexes 95

2.1 Introduction 95

2.2 Structural Features of σ-Complexes 96

2.2.1 X-Ray Crystallography 96

2.2.2 Gas-Phase Meisenheimer Complexes 100

2.2.3 NMR Spectroscopy 103

2.2.3.1 Complexation at Unsubstituted Carbons 103

2.2.3.2 Complexation at Substituted Carbons 114

2.2.3.3 Complexation versus Proton Abstraction 123

2.3 Thermodynamics and Kinetics of σ-Complex Formation 125

2.3.1 The Nature of the Aromatic System 126

2.3.2 The Effect of Ring Substituents 129

2.3.3 Nucleophilic Reactivity at Substituted versus Unsubstituted Carbons: Steric Effects 135

2.3.3.1 Relative Reactivities and Stabilities of 1-Substituted and 1,1-Disubstituted Complexes 135

2.3.3.2 Isomeric Addition at Substituted and Unsubstituted Carbons of Electron-Deficient Aromatics: Relevance to Nucleophilic Aromatic Substitution Processes 140

2.3.4 Intramolecular Additions: Spiro Complexes 145

2.3.5 Diadduct Formation: Meta Bridging 148

2.3.6 The Effect of the Nucleophile 150

2.3.7 Solvent and Medium Effects 152

References 156

3 The Superelectrophilic Dimension in S_NAr and Related σ-Complexation Processes 163

3.1 Introduction 163

3.2 The Classical Domain of S_NAr and Anionic σ-Complexation Reactivity 164

3.3 Reaching the Superelectrophilic Dimension 167

3.3.1 The Reference Water Reaction 167

3.3.2 σ-Complexation with Weak Carbon Nucleophiles 172

3.3.3 From the pK_aH₂O Scale to Mayr's Electtophilicity (E) Scale 174

3.3.4 Oxidation Potentials as Descriptors of the Superelectrophilic Dimension 180

3.4 The Synthetic Potential of σ-Complexation and S_NAr Reactivity in the Superelectrophilic Dimension 182

3.4.1 σ-Complexation Reactivity 182

3.4.2 The Synthetic Potential of S_NAr Substitutions: Normal (PiCl, NBD-Cl) versus Super (DNBF-Cl, DNBZ-Cl) Electrophiles 186

3.5 Origin of the Superelectrophilicity of Neutral 10π Hetéroaromatics 196

References 198

4 Synthetic Aspects of Intermolecular S_NAr Reactions 205

4.1 Introduction 205

4.2 Intermolecular Displacements of a Nitro Group 206

4.2.1 p-, o-, and m-Dinitrobenzenes- Related Substrates 206

4.2.2 Mononitro-Substituted Benzenes and Heteroarenes 216

4.2.3 Dinitro- and Trinitro-Substituted Benzenes and Related Derivatives 228

4.3 Intermolecular Displacements of Halogen and Other Leaving Groups 236

4.3.1 The Effect of the Leaving Group - Synthetic Implications 236

4.3.2 S_NAr Couplings with Monoactivated Arenes 242

4.3.3 S_NAr Couplings with Polyhaloaromatics 251

4.3.4 S_NAr Couplings with Strongly Activated Arenes 255

4.3.5 S_NAr Couplings with Aza and Polyaza Heteroaromatics 263

4.4 Conclusion 269

References 271

5 Intramolecular S_NAr Reactions 279

5.1 Introduction 279

5.2 S_NAr Cyclizations 280

5.2.1 Substitutions with Oxygen Nucleophiles 280

5.2.2 Substitutions with Nitrogen Nucleophiles 290

5.2.3 Substitutions by Sulfur Nucleophiles 296

5.2.4 Substitutions by Carbon Nucleophiles 298

5.2.5 Intramolecular S_NAr Reactions in Macrocyclization 300

5.3 Smiles Rearrangements 303

5.3.1 O → N and N → O Rearrangements 304

5.3.2 N → N Rearrangements 311

5.3.3 O → O Rearrangements 315

5.3.4 N → S and S → N Rearrangements 318

5.3.5 S → O and Se → O Rearrangements 321

5.3.6 Rearrangements with C-C Bond Formation. Truce-Smiles Rearrangements 325

5.4 Conclusion 331

References 332

6 Nucleophilic Aromatic Substitutions of Hydrogen 337

6.1 Introduction 337

6.2 Reactions Involving Oxidation of a-Complex-Type Intermediates 339

6.2.1 Spontaneous Oxidations 339

6.2.2 Reactions Involving an External Oxidizing Agent (ONSH) 351

6.2.2.1 Oxidation of Oxygen- and Nitrogen-Bonded Adducts 353

6.2.2.2 Oxidation of Carbon-Based σ^H Adducts 357

6.2.2.3 Electrochemical Oxidation 372

6.3 Vicarious Nucleophilic Aromatic Substitutions of Hydrogen (VNS) 374

6.3.1 VNS Animation and Hydroxylation Processes 374

6.3.2 VNS Substitutions with Carbon Nucleophiles 378

6.3.2.1 Effect of the Structure of the Nitroarene 379

6.3.2.2 Effect of the Structure of the Carbanion 384

6.4 Deoxygenative S_NAr^H Substitutions 395

6.5 Cine and Tele Substitutions 397

6.5.1 The Von Richter Rearrangement 398

6.5.2 o-Dinitro Six-Membered Ring Aromatics and Related Derivatives 400

6.5.3 m-Diactivated Arenes and Related Substrates 404

6.5.4 Cine and Tele Substitutions in Heterocyclic Series 407

6.5.4.1 Aza and Polyaza aromatics 407

6.5.4.2 Five-Membered Ring Heteroaromatics 409

1.6.6 Conclusion 414

References 415

7 Other S_NAr Substitution Pathways 423

7.1 S_N(ANRORC) Substitutions 423

7.1.1 Introduction 423

7.1.2 Aza Aromatics without Nitro Activation 423

7.1.3 Nitro-Activated Aza Aromatics 426

7.1.4 Conclusion 429

7.2 Radical Nucleophilic Aromatic Substitutions 430

7.2.1 Introduction 430

7.2.2 Radical Anion Formation in "S_NAr" Systems 431

7.2.3 Representative Radical Nucleophilic Aromatic Substitutions 438

7.2.4 Substitutions via Charge-Transfer Complexes of Anionic Radical Character 445

7.3 Nucleophilic Aromatic Photosubstitutions 448

7.3.1 General Features 448

7.3.2 S_N2Ar* Reactions 450

7.3.3 S_N(ET)Ar* Reactions 453

7.3.4 S_N1Ar* Reactions 455

7.3.5 Regioselectivity and Chemical Theory 456

7.3.5.1 The Frontier Molecular Orbital Theory 456

7.3.5.2 The "Energy Gap" Model and Other Recent Approaches 458

References 459.

Notes:

Includes bibliographical references and index.

Local Notes:

Acquired for the Penn Libraries with assistance from the Lachs-Adler Family Endowed Fund for Collection Development.

Acquired for the Penn Libraries with assistance from the Anne and Joseph Trachtman Memorial Book Fund.

ISBN:

3527318615

9783527318612

OCLC:

823380608

Publisher Number:

99955688922