Wiley.com
Print this page Share
E-book

Arene Chemistry: Reaction Mechanisms and Methods for Aromatic Compounds

ISBN: 978-1-118-75498-6
992 pages
November 2015
Arene Chemistry: Reaction Mechanisms and Methods for Aromatic Compounds (1118754980) cover image

Description

Organized to enable students and synthetic chemists to understand and expand on aromatic reactions covered in foundation courses, the book offers a thorough and accessible mechanistic explanation of aromatic reactions involving arene compounds.

•    Surveys methods used for preparing arene compounds and their transformations
•    Connects reactivity and methodology with mechanism
•    Helps readers apply aromatic reactions in a practical context by designing syntheses
•    Provides essential information about techniques used to determine reaction mechanisms
See More

Table of Contents

LIST OF CONTRIBUTORS xxi

PREFACE xxv

PART I ELECTROPHILIC AROMATIC SUBSTITUTION 1

1 Electrophilic Aromatic Substitution: Mechanism 3
Douglas A. Klumpp

1.1 Introduction, 3

1.2 General Aspects, 4

1.3 Electrophiles, 4

1.4 Arene Nucleophiles, 12

1.5 π‐Complex Intermediates, 17

1.6 σ‐Complex or Wheland Intermediates, 22

1.7 Summary and Outlook, 27

Abbreviations, 27

References, 28

2 Friedel–Crafts Alkylation of Arenes in Total Synthesis 33
Gonzalo Blay, Marc Montesinos‐Magraner, and José R. Pedro

2.1 Introduction, 33

2.2 Total Synthesis Involving Intermolecular FC Alkylations, 34

2.2.1 Synthesis of Coenzyme Q10, 34

2.2.2 Total Synthesis of (±)‐Brasiliquinone B, 35

2.2.3 Synthesis of (−)‐Podophyllotoxin, 35

2.2.4 Synthesis of Puupehenol and Related Compounds, 36

2.2.5 Synthesis of (−)‐Talaumidin, 36

2.2.6 Total Synthesis of (±)‐Schefferine, 37

2.3 Total Synthesis Involving Intramolecular FC Alkylations, 37

2.3.1 C─C Bond Formation Leading to Homocyclic Rings, 37

2.3.2 C─C Bond Formation Leading to Oxygen‐Containing Rings, 43

2.3.3 C─C Bond Formation Leading to Nitrogen‐Containing Rings, 44

2.4 Total Synthesis Through Tandem and Cascade Processes Involving FC Reactions, 46

2.4.1 C─C Bond Formation Leading to Homocyclic Rings, 46

2.4.2 C─C Bond Formation Leading to Oxygen‐Containing Rings, 49

2.4.3 C─C Bond Formation Leading to Nitrogen‐Containing Rings, 52

2.5 Total Synthesis Involving ipso‐FC Reactions, 54

2.5.1 Synthesis of (S)‐(−)‐Xylopinine, 54

2.5.2 Synthesis of Garcibracteatone, 55

2.6 Summary and Outlook, 56

2.7 Acknowledgment, 56

Abbreviations, 56

References, 57

3 Catalytic Friedel–Crafts Acylation Reactions 59
Giovanni Sartori, Raimondo Maggi, and Veronica Santacroce

3.1 Introduction and Historical Background, 59

3.2 Catalytic Homogeneous Acylations, 60

3.2.1 Metal Halides, 60

3.2.2 Perfluoroalkanoic Acids, Perfluorosulfonic Acids, and Their (Metal) Derivatives, 62

3.2.3 Miscellaneous, 63

3.3 Catalytic Heterogeneous Acylations, 64

3.3.1 Zeolites, 64

3.3.2 Clays, 69

3.3.3 Metal Oxides, 70

3.3.4 Acid‐Treated Metal Oxides, 70

3.3.5 Heteropoly Acids (HPAs), 71

3.3.6 Nafion, 72

3.3.7 Miscellaneous, 73

3.4 Direct Phenol Acylation, 73

3.5 Summary and Outlook, 77

Abbreviations, 78

References, 78

4 The Use of Quantum Chemistry for Mechanistic Analyses of SEAr Reactions 83
Tore Brinck and Magnus Liljenberg

4.1 Introduction, 83

4.1.1 Historical Overview of Early Quantum Chemistry Work, 83

4.1.2 Current Mechanistic Understanding Based on Kinetic and Spectroscopic Studies, 85

4.2 The SEAr Mechanism: Quantum Chemical Characterization in Gas Phase and Solution, 87

4.2.1 Nitration and Nitrosation, 87

4.2.2 Halogenation, 93

4.2.3 Sulfonation, 96

4.2.4 Friedel–Crafts Alkylations and Acylations, 96

4.3 Prediction of Relative Reactivity and Regioselectivity Based on Quantum Chemical Descriptors, 97

4.4 Quantum Chemical Reactivity Prediction Based on Modeling of Transition States and Intermediates, 100

4.4.1 Transition State Modeling, 100

4.4.2 The Reaction Intermediate or Sigma‐Complex Approach, 101

4.5 Summary and Conclusions, 102

Abbreviations, 103

References, 103

5 Catalytic Enantioselective Electrophilic Aromatic Substitutions 107
Marco Bandini

5.1 Introduction and Historical Background, 107

5.2 Metal‐Catalyzed AFCA of Aromatic Hydrocarbons, 109

5.2.1 Introduction, 109

5.2.2 Metal‐Catalyzed Condensation of Arenes with Carbonyl Compounds and Their Nitrogen Derivatives, 110

5.3 Organocatalyzed AFCA of Aromatic Hydrocarbons, 116

5.3.1 Introduction, 116

5.3.2 Asymmetric Organocatalyzed Condensation of Arenes with Carbonyl Compounds and Their Nitrogen Derivatives, 117

5.3.3 Asymmetric Organocatalyzed Alkylations of Arenes via Michael Additions, 118

5.3.4 Organo‐SOMO‐Catalyzed Asymmetric Alkylations of Arenes, 122

5.3.5 Miscellaneous in Asymmetric Organocatalyzed Alkylations of Arenes, 124

5.4 Merging Asymmetric Metal and Organocatalysis in Friedel–Crafts Alkylations, 125

5.5 Summary and Outlook, 126

Abbreviations, 127

References, 127

PART II NUCLEOPHILIC AROMATIC SUBSTITUTION 131

6 Nucleophilic Aromatic Substitution: An Update Overview 133
Michael R. Crampton

6.1 Introduction, 133

6.2 The SNAr Mechanism, 135

6.2.1 Effects of Activating Groups, 138

6.2.2 Leaving Group Effects, 140

6.2.3 The Attacking Nucleophile, 141

6.2.4 Solvent Effects, 145

6.2.5 Intramolecular Rearrangements, 146

6.3 Meisenheimer Adducts, 150

6.3.1 Spectroscopic and Crystallographic Studies, 150

6.3.2 Range and Variety of Substrates and Nucleophiles, 153

6.3.3 Superelectrophilic Systems, 158

6.4 The SN1 Mechanism, 159

6.4.1 Heterolytic and Homolytic Pathways, 159

6.5 Synthetic Applications, 160

Abbreviations, 167

References, 167

7 Theoretical and Experimental Methods for the Analysis of Reaction Mechanisms in SNAr Processes: Fugality, Philicity, and Solvent Effects 175
Renato Contreras, Paola R. Campodónico, and Rodrigo Ormazábal‐Toledo

7.1 Introduction, 175

7.2 Conceptual DFT: Global, Regional, and Nonlocal Reactivity Indices, 176

7.3 Practical Applications of Conceptual DFT Descriptors, 179

7.3.1 Nucleophilicity and LG Scales, 180

7.3.2 Activation Properties: Reactivity Indices Profiles, 181

7.4 SNAr Reaction Mechanism, 183

7.4.1 Kinetic Measurements, 183

7.4.2 Nucleophilicity, LG, and PG Abilities, 185

7.5 Integrated Experimental and Theoretical Models, 187

7.5.1 Hydrogen Bonding Effects, 187

7.6 Solvent Effects in Conventional Solvents and Ionic Liquids, 188

7.6.1 Preferential Solvation, 188

7.6.2 Ionic Liquids and Catalysis, 189

7.7 Summary and Outlook, 189

Abbreviations, 190

References, 190

8 Asymmetric Nucleophilic Aromatic Substitution 195
Anne‐Sophie Castanet, Anne Boussonnière, and Jacques Mortier

8.1 Introduction, 195

8.2 Auxiliary‐ and Substrate‐Controlled Asymmetric Nucleophilic Aromatic Substitution, 198

8.2.1 Chiral Electron‐Withdrawing Groups, 198

8.2.2 Chiral Leaving Groups, 202

8.2.3 Planar Chiral Arenes, 205

8.2.4 Chiral Tethered Arenes, 207

8.2.5 Chiral Nucleophiles, 209

8.3 Chiral Catalyzed Asymmetric Nucleophilic Aromatic Substitution, 210

8.3.1 Chiral Ligands, 211

8.3.2 Chiral Phase Transfer Catalysts, 211

8.4 Absolute Asymmetric Nucleophilic Aromatic Substitution, 213

8.5 Summary and Outlook, 214

Abbreviations, 214

References, 215

9 Homolytic Aromatic Substitution 219
Roberto A. Rossi, María E. Budén, and Javier F. Guastavino

9.1 Introduction: Scope and Limitations, 219

9.2 Radicals Generated by Homolytic Cleavage Processes: Thermolysis and Photolysis, 223

9.3 Reactions Mediated by Tin and Silicon Hydrides, 225

9.4 Radicals Generated by ET: Redox Reactions, 229

9.4.1 Reducing Metals, 229

9.4.2 Other Reducing Agents, 232

9.4.3 Oxidizing Metals, 233

9.4.4 Base-Promoted Homolytic Aromatic Substitution (BHAS), 236

9.5 Summary and Outlook, 237

Abbreviations, 238

References, 238

10 Radical‐Nucleophilic Aromatic Substitution 243
Roberto A. Rossi, Javier F. Guastavino, and María E. Budén

10.1 Introduction: Scope and Limitations—Background, 243

10.2 Mechanistic Considerations, 245

10.2.1 Initiation Step, 245

10.2.2 Propagation Steps, 246

10.2.3 Termination Steps, 248

10.3 Intermolecular SRN1 Reactions, 248

10.3.1 Nucleophiles from Group 14: C and Sn, 248

10.3.2 Nucleophiles Derived from Group 15: N, P, As, and Sb, 254

10.3.3 Nucleophiles Derived from Group 16: O, S, Se, and Te, 256

10.4 Intramolecular SRN1 Reactions, 258

10.5 Miscellaneous Ring Closure Reactions, 262

10.5.1 Exo or Endo Radical Cyclization Followed by an SRN1 Reaction, 262

10.5.2 Intermolecular SRN1 Reaction Followed by Intramolecular SRN1 or BHAS Reaction, 263

10.6 Summary and Outlook, 264

Abbreviations, 265

References, 265

11 Nucleophilic Substitution of Hydrogen in Electron‐Deficient Arenes 269
Mieczysław Mąkosza

11.1 Introduction, 269

11.2 Oxidative Nucleophilic Substitution of Hydrogen, 270

11.3 Conversion of the σH‐Adducts of Nucleophiles to Nitroarenes into Substituted Nitrosoarenes, 276

11.4 Vicarious Nucleophilic Substitution of Hydrogen, 278

11.4.1 Introduction, 278

11.4.2 Mechanism of VNS Reaction, 279

11.4.3 Scope and Limitation of VNS, 283

11.5 Other Ways of Conversion of the σH‐Adducts, 291

11.6 Concluding Remarks, 293

Abbreviations, 295

References, 295

PART III ARYNE CHEMISTRY 299

12 The Chemistry of Arynes: An Overview 301
Roberto Sanz and Anisley Suárez

12.1 Introduction, 301

12.2 Structure and Representative Reactions of Arynes, 301

12.3 Aryne Generation, 303

12.3.1 Elimination Methods, 303

12.3.2 By Hexadehydro‐Diels–Alder Reaction, 306

12.4 Pericyclic Reactions, 306

12.4.1 Diels–Alder Cycloadditions, 306

12.4.2 [3+2] Cycloadditions, 309

12.4.3 [2+2] Cycloadditions with Alkenes, 311

12.4.4 Ene Reactions, 313

12.5 Nucleophilic Addition Reactions to Arynes, 314

12.5.1 Regioselectivity Issues for Functionalized Arynes, 314

12.5.2 Proton Abstraction: Monosubstitution of the Aryne, 315

12.5.3 Three‐Component Reactions, 317

12.5.4 Aryne Insertion Reactions into σ‐Bonds, 321

12.5.5 Aryne Annulation, 325

12.6 Transition Metal–Catalyzed Reactions of Arynes, 327

12.6.1 Cyclotrimerization of Arynes, 327

12.6.2 Cocyclization of Arynes with Alkynes, 327

12.6.3 Cocyclization of Arynes with Alkenes, 327

12.6.4 Cocyclization of Arynes, Alkenes, and Alkynes, 329

12.6.5 Intermolecular Carbopalladation of Arynes, 329

12.6.6 Catalytic Insertion Reactions of Arynes into σ‐Bonds, 330

12.7 Conclusion, 332

Abbreviations, 332

References, 333

PART IV REDUCTION, OXIDATION, AND DEAROMATIZATION REACTIONS 337

13 Reduction/Hydrogenation of Aromatic Rings 339
Francisco Foubelo and Miguel Yus

13.1 Introduction, 339

13.2 The Birch Reaction, 339

13.2.1 Dissolving Metals, 340

13.2.2 Enzymatic Reactions, 344

13.3 Metal‐Catalyzed Hydrogenations, 345

13.3.1 Homogeneous Conditions, 345

13.3.2 Heterogeneous Conditions, 351

13.4 Electrochemical Reductions, 357

13.5 Other Methodologies, 359

13.6 Summary and Outlook, 361

Abbreviations, 361

References, 362

14 Selective Oxidation of Aromatic Rings 365
Oxana A. Kholdeeva

14.1 Introduction, 365

14.2 Mechanistic Principles, 367

14.2.1 Autoxidation, 367

14.2.2 Spin‐Forbidden Reactions with Triplet Oxygen, 369

14.2.3 Radical Hydroxylation (Addition–Elimination), 370

14.2.4 Electron Transfer Mechanisms, 371

14.2.5 Electrophilic Hydroxylation via Oxygen Atom Transfer, 373

14.2.6 Heterolytic Activation of Substrate, 374

14.3 Stoichiometric Oxidations, 374

14.4 Catalytic Oxidations, 375

14.4.1 Benzene, 375

14.4.2 Polycyclic Arenes, 379

14.4.3 Alkylarenes, 379

14.4.4 Electron‐Poor Aromatic Compounds, 382

14.4.5 ortho‐Hydroxylation Driven by Arene Functional Group, 382

14.4.6 Phenol, 383

14.4.7 Alkylphenols and Alkoxyarenes, 384

14.5 Photochemical Oxidations, 386

14.6 Electrochemical Oxidations, 387

14.7 Enzymatic Hydroxylation, 389

14.8 Summary and Outlook, 390

Acknowledgments, 391

Abbreviations, 391

References, 392

15 Dearomatization Reactions: An Overview 399
F. Christopher Pigge

15.1 Introduction, 399

15.2 Alkylative Dearomatization, 400

15.2.1 C‐Alkylation of Phenolate Anions, 400

15.2.2 Anionic Dearomatization, 401

15.2.3 Radical Dearomatization, 403

15.3 Photochemical and Thermal Dearomatization, 405

15.3.1 Dearomatization by Photocycloaddition, 405

15.3.2 Dearomatization by Thermally Induced Rearrangement, 406

15.4 Oxidative Dearomatization, 408

15.4.1 Oxidative Dearomatization with Formation of Carbon–Heteroatom Bonds, 408

15.4.2 Oxidative Dearomatization with Formation of Carbon–Carbon Bonds, 411

15.5 Transition Metal‐Assisted Dearomatization, 413

15.5.1 Dearomatization Reactions of Metal Carbenoids, 413

15.5.2 Dearomatization Catalyzed by Palladium, Iridium, and Related Complexes, 413

15.5.3 Dearomatization of η2‐Arene Metal Complexes, 416

15.5.4 Dearomatization of η6‐Arene Metal Complexes, 417

15.6 Enzymatic Dearomatization, 418

15.7 Conclusions and Future Directions, 419

Abbreviations, 419

References, 420

PART V AROMATIC REARRANGEMENTS 425

16 Aromatic Compounds via Pericyclic Reactions 427
Sethuraman Sankararaman

16.1 Introduction, 427

16.2 Electrocyclic Ring Closure Reaction, 428

16.2.1 Application of Electrocyclic Ring Closure in Aromatic Synthesis, 429

16.3 Introduction to Cycloaddition Reactions, 433

16.3.1 Application of [4+2] Cycloaddition Method for Synthesis of Aromatic Compounds, 434

16.4 Conclusions, 448

Abbreviations, 448

References, 448

17 Ring‐Closing Metathesis: Synthetic Routes to Carbocyclic Aromatic Compounds using Ring‐Closing Alkene and Enyne Metathesis 451
Charles B. de Koning and Willem A. L. van Otterlo

17.1 Introduction, 451

17.2 Alkene RCM for the Synthesis of Aromatic Compounds, 454

17.2.1 Synthesis of Substituted Benzenes, 454

17.2.2 Synthesis of Substituted Naphthalenes, 458

17.2.3 Synthesis of Substituted Phenanthrenes, 458

17.2.4 Synthesis of Anthraquinones and Benzo‐Fused Anthraquinones, 459

17.2.5 Applications in the Synthesis of Polyarenes, 461

17.2.6 Applications in the Synthesis of Natural Products, 462

17.3 Enyne Metathesis Followed by the Diels–Alder Reaction for the Synthesis of Benzene Rings in Complex Aromatic Compounds, 464

17.3.1 Synthesis of Substituted Benzenes, 464

17.3.2 Synthesis of Substituted Phenanthrenes, 466

17.3.3 Synthesis of Complex Naphthoquinones and Anthraquinones, 466

17.3.4 Applications to the Synthesis of Biologically Active Products, 470

17.4 Cyclotrimerization for the Synthesis of Aromatic Compounds by Metathetic Processes, 470

17.5 Strategies for the Synthesis of Aromatic Carbocycles Fused to Heterocycles by the RCM Reaction, 472

17.5.1 Alkene RCM for the Synthesis of Benzene Rings in Indoles, Carbazoles, Benzo‐Fused Pyridines and Pyridones, and Benzo‐Fused Imidazoles, 472

17.5.2 Enyne RCM for the Synthesis of Benzene Rings in Tetrahydroisoquinolines, Annulated 1,2‐Oxaza‐ and 1,2‐Bisazacycles, and Indoles, 479

17.6 Future Challenges, 481

17.7 Conclusions, 481

Abbreviations, 482

References, 482

18 Aromatic Rearrangements in which the Migrating Group Migrates to the Aromatic Nucleus: An Overview 485
Timothy J. Snape

18.1 Introduction, 485

18.2 Mechanisms by Classification, 486

18.2.1 Intramolecular Reactions: Nucleophilic Aromatic Substitution, 486

18.2.2 Intramolecular: Sigmatropic Rearrangements, 494

18.2.3 Intermolecular Rearrangements, 500

18.3 Summary and Outlook, 508

Abbreviations, 508

References, 508

PART VI TRANSITION METAL‐MEDIATED COUPLING 511

19 Transition Metal‐Catalyzed Carbon–Carbon Cross‐Coupling 513
Anny Jutand and Guillaume Lefèvre

19.1 Introduction, 513

19.2 The Mizoroki–Heck Reaction, 513

19.2.1 General Considerations and Mechanisms, 513

19.2.2 Scope of the Reaction, 520

19.2.3 Synthetic Application, 523

19.3 Cross‐Coupling of Aryl Halides with Anionic C‐Nucleophiles, 523

19.3.1 The Kumada Reactions: Nickel‐Catalyzed Cross‐Coupling with Grignard Reagents, 523

19.3.2 Palladium‐Catalyzed Cross‐Coupling with Grignard Reagents, 524

19.3.3 The Negishi Reaction: Palladium‐Catalyzed Cross‐Coupling with Organozinc Reagents, 525

19.3.4 Palladium‐Catalyzed Cross‐Coupling with Organolithium Reagents, 525

19.3.5 Mechanism of Palladium‐Catalyzed Cross‐Couplings with Rm (m = Li, MgY, ZnY), 526

19.3.6 Nickel‐ and Palladium‐Catalyzed Arylation of Ketone, Ester, and Amide Enolates, 528

19.4 The Sonogashira Reaction, 530

19.4.1 General Considerations and Mechanism, 530

19.4.2 Synthetic Applications, 531

19.5 The Stille Reaction, 532

19.5.1 General Considerations and Mechanism, 532

19.5.2 Synthetic Application, 533

19.6 The Suzuki–Miyaura Reaction, 534

19.6.1 General Considerations and Mechanism, 534

19.6.2 Synthetic Application, 539

19.7 The Hiyama Reaction, 539

19.7.1 General Considerations and Mechanism, 539

19.7.2 Synthetic Applications, 541

19.8 Summary and Outlook, 541

Abbreviations, 541

References, 541

20 Transition Metal‐Mediated Carbon–Heteroatom Cross‐Coupling (C─N, C─O, C─S, C─Se, C─Te, C─P, C─As, C─Sb, and C─B Bond Forming Reactions): An Overview 547
Masanam Kannan, Mani Sengoden, and Tharmalingam Punniyamurthy

20.1 Introduction, 547

20.2 C—N Cross‐Coupling, 550

20.2.1 Palladium‐Catalyzed Reactions, 550

20.2.2 Copper‐Catalyzed Reactions, 555

20.2.3 Other Transition Metal‐Catalyzed Reactions, 559

20.2.4 Synthetic Applications, 560

20.3 C—O Cross‐Coupling, 561

20.3.1 Reactions with Aromatic Alcohols, 561

20.3.2 Reactions with Aliphatic Alcohols, 563

20.3.3 Synthesis of Phenols, 566

20.3.4 Synthetic Applications, 567

20.4 C—S Cross‐Coupling, 569

20.4.1 Palladium‐Catalyzed Reactions, 569

20.4.2 Copper‐Catalyzed Reactions, 569

20.4.3 Other Transition Metal‐Catalyzed Reactions, 570

20.5 C—Se Cross‐Coupling, 571

20.6 C—Te Cross‐Coupling, 571

20.7 C—P Cross‐Coupling, 572

20.7.1 Palladium‐Catalyzed Reactions, 572

20.7.2 Copper‐Catalyzed Reactions, 576

20.7.3 Nickel‐Catalyzed Reactions, 577

20.8 C—As and C—Sb Cross‐Coupling, 578

20.9 C—B Cross‐Coupling, 578

20.10 Summary and Outlook, 579

Abbreviations, 579

References, 579

21 Transition Metal‐Mediated Aromatic Ring Construction 587
Ken Tanaka

21.1 Introduction, 587

21.2 [2+2+2] Cycloaddition, 587

21.2.1 Mechanism, 588

21.2.2 [2+2+2] Cycloaddition of Monoynes, 589

21.2.3 [2+2+2] Cycloaddition of Diynes with Monoynes, 590

21.2.4 [2+2+2] Cycloaddition of Triynes, 598

21.3 [3+2+1] Cycloaddition, 601

21.4 [4+2] Cycloaddition, 602

21.4.1 Diels–Alder Reactions, 602

21.4.2 Reactions of Enynes with Alkynes, 603

21.4.3 Reactions via Pyrylium Intermediates, 606

21.4.4 Reactions via Acylmetallacycles, 607

21.5 Intramolecular Cycloaromatization, 608

21.5.1 Intramolecular Hydroarylation of Alkynes, 608

21.5.2 Cyclization via Transition Metal Vinylidenes, 610

21.6 Summary and Outlook, 612

References, 612

22 Ar–C Bond Formation by Aromatic Carbon–Carbon ipso‐Substitution Reaction 615
Maurizio Fagnoni and Sergio M. Bonesi

22.1 Introduction, 615

22.2 Formation of Ar–C(sp3) Bonds, 616

22.2.1 Ni‐Catalyzed Reactions, 616

22.2.2 Rh‐Catalyzed Reactions, 617

22.2.3 Pd‐Catalyzed Reactions, 619

22.3 Formation of Ar–C(sp2) Bonds, 620

22.3.1 Synthesis of Aryl Ketones and Amidines, 620

22.3.2 Formation of Ar–Vinyl Bonds, 620

22.3.3 Formation of Ar–Ar Bonds, 628

22.3.4 Formation of Benzocondensed Derivatives, 636

22.4 Formation of Ar–C(sp) Bonds, 638

22.5 Summary and Outlook, 639

Abbreviations, 639

References, 640

PART VII C─H FUNCTIONALIZATION 645

23 Chelate‐Assisted Arene C–H Bond Functionalization 647
Marion H. Emmert and Christopher J. Legacy

23.1 Introduction, 647

23.1.1 Mechanisms of Chelate‐Assisted C–H Bond Functionalization and Activation, 648

23.1.2 Weakly and Strongly Coordinating Directing Groups, 651

23.1.3 Common Directing Groups, 651

23.1.4 Transformable and In Situ Generated Directing Groups, 652

23.2 Carbon–Carbon (C–C) Bond Formations, 654

23.2.1 C–CAryl Bond Formations, 654

23.2.2 C–CAlkenyl Bond Formations, 655

23.2.3 C–CAlkyl Bond Formations, 656

23.2.4 C–CAcyl Bond Formations, 657

23.2.5 C–CN Bond Formations, 658

23.2.6 C–CF3 Bond Formations, 659

23.3 Carbon–Heteroatom (C–X) Bond Formations, 660

23.3.1 C–B Bond Formations, 660

23.3.2 C–Si Bond Formations, 661

23.3.3 C–O Bond Formations, 662

23.3.4 C–N Bond Formations, 662

23.3.5 C–P Bond Formations, 664

23.3.6 C–S Bond Formations, 665

23.3.7 C–Halogen Bond Formations, 666

23.3.8 C–D Bond Formations, 667

23.4 Stereoselective C–H Functionalizations, 668

Abbreviations, 669

References, 669

24 Reactivity and Selectivity in Transition Metal‐Catalyzed, Nondirected Arene Functionalizations 675
Dipannita Kalyani and Elodie E. Marlier

24.1 Introduction, 675

24.2 Arylation, 676

24.2.1 Direct Arylations, 677

24.2.2 Cross‐Dehydrogenative Arylations, 684

24.3 Alkenylation, 693

24.4 Alkylation, 699

24.5 Carboxylation, 701

24.6 Oxygenation, 701

24.7 Thiolation, 704

24.8 Amination, 706

24.9 Miscellaneous, 708

24.9.1 Halogenation, 708

24.9.2 Silylation, 708

24.9.3 Borylation, 709

24.10 Summary and Outlook, 710

Abbreviations, 710

References, 710

25 Functionalization of Arenes via C─H Bond Activation Catalysed by Transition Metal Complexes: Synergy between Experiment and Theory 715
Amalia Isabel Poblador‐Bahamonde

25.1 Introduction, 715

25.2 Mechanisms of C─H Bond Activation, 716

25.3 Development of Stoichiometric C─H Bond Activation, 718

25.3.1 Mechanistic Ambiguity: The Power of Theory, 721

25.3.2 C─H Activation Assisted by Carboxylate or Carbonate Bases, 723

25.4 Catalytic C─H Activation and Functionalization, 730

25.4.1 Hydroarylation of Alkenes, 730

25.4.2 Arene Functionalization via a Base‐Assisted Mechanism, 735

25.5 Summary, 738

Abbreviations, 738

References, 738

PART VIII DIRECTED METALATION REACTIONS 741

26 Directed Metalation of Arenes with Organolithiums, Lithium Amides, and Superbases 743
Frédéric R. Leroux and Jacques Mortier

26.1 Introduction, 743

26.2 Preparation and Reactivity of Organolithium Compounds, 744

26.2.1 Bases and Complexing Agents, 744

26.2.2 Solvents, 746

26.2.3 Electrophiles, 747

26.3 Directed ortho-Metalation (DoM), 748

26.3.1 Mechanisms: Complex‐Induced Proximity Effect Process, Kinetically Enhanced Metalation, and Overriding Base Mechanism, 748

26.3.2 Directing Metalation Groups (DMGs), 750

26.3.3 Optional Site Selectivity: Selected Examples, 750

26.3.4 External and In Situ Quench Conditions, 754

26.3.5 Apparent Anomalies in the Reactivity of Certain Electrophiles, 756

26.4 Directed remote Metalation (DreM), 757

26.5 Peri Lithiation of Substituted Naphthalenes, 759

26.6 Lithiation of Metal Arene Complexes, 760

26.7 Lateral Lithiation, 761

26.8 Analytical Methods, 762

26.8.1 Quantitative Determination of Organolithiums, 762

26.8.2 Qualitative Determination of Organolithiums, 763

26.8.3 Crystallography, 763

26.8.4 NMR Spectroscopy, 765

26.9 Synthetic Applications, 765

26.9.1 DoM and C─C Cross‐Coupling, 765

26.9.2 DoM, DreM, and Anionic Fries Rearrangement, 766

26.9.3 Industrial Scale‐Up of Ortho Metalation Reactions, 768

26.9.4 Lateral Lithiation, 768

26.9.5 Superbase Metalation, 769

26.10 Conclusion, 770

Abbreviations, 771

References, 771

27 Deprotonative Metalation Using Alkali Metal–Nonalkali Metal Combinations 777
Floris Chevallier, Florence Mongin, Ryo Takita, and Masanobu Uchiyama

27.1 Introduction, 777

27.2 Preparation of the Bimetallic Combinations and their Structural Features, 778

27.2.1 Preparation of Alkali Metal–Nonalkali Metal Basic Combinations, 778

27.2.2 Ate Compounds, 778

27.2.3 Salt‐Activated Compounds, 779

27.2.4 Contacted and Solvent‐Separated Ion Pairs, 779

27.3 Behavior of Alkali Metal–Nonalkali Metal Combinations, 779

27.3.1 One‐Electron and Two‐Electron Transfers, 779

27.3.2 Base and Nucleophile Ligand Transfers, 780

27.4 Mechanistic Studies on the Deprotometalation Using Alkali Metal–Nonalkali Metal Combinations, 780

27.4.1 Deprotometalation Using Alkali Metal–Amidozincate Complexes, 780

27.4.2 Deprotometalation Using Alkali Metal–Amidoaluminate Complexes, 783

27.4.3 Deprotometalation Using Alkali Metal–Amidocuprate Complexes, 786

27.4.4 Deprotometalation Using Alkali Metal–Amidocadmate Complexes, 789

27.5 Scope and Applications of the Deprotometalation, 790

27.5.1 Using Lithium– or Sodium–Magnesium Mixed‐Metal Bases, 790

27.5.2 Using Lithium–Aluminum Mixed‐Metal Bases, 793

27.5.3 Using Lithium–, Sodium–, or Magnesium–Manganese Mixed‐Metal Bases, 795

27.5.4 Using Lithium–, Sodium–, or Magnesium–Iron Mixed‐Metal Bases, 798

27.5.5 Using Lithium–Cobalt Mixed‐Metal Bases, 799

27.5.6 Using Lithium–Copper Mixed‐Metal Bases, 799

27.5.7 Using Lithium–, Sodium–, or Magnesium–Zinc Mixed‐Metal Bases, 799

27.5.8 Using Lithium– or Magnesium–Zirconium Mixed‐Metal Bases, 804

27.5.9 Using Lithium–Cadmium Mixed‐Metal Bases, 804

27.5.10 Using Lithium– or Magnesium–Lanthanum Mixed‐Metal Bases, 805

27.6 Conclusion and Perspectives, 807

Acknowledgments, 807

Abbreviations, 807

References, 807

28 The Halogen/Metal Interconversion and Related Processes (M = Li, Mg) 813
Armen Panossian and Frédéric R. Leroux

28.1 Introduction, 813

28.2 Generalities, 814

28.2.1 Monometallic Organolithium Reagents, 814

28.2.2 Monometallic Organomagnesium Reagents, 814

28.2.3 Bimetallic Organolithium/Magnesium Reagents, 814

28.3 Mechanism of the Halogen/Metal Interconversion, 815

28.3.1 Reactivity, 815

28.3.2 Mechanism, 816

28.4 Halogen Migration on Aromatic Compounds, 817

28.5 Selective Synthesis via Halogen/Metal Interconversion, 818

28.5.1 Chemo and Regioselectivity of Halogen/Metal Interconversions, 818

28.5.2 Stereoselectivity of Halogen/Metal Interconversions, 821

28.6 The Sulfoxide/Metal and Phosphorus/Metal Interconversions, 822

28.6.1 The Sulfoxide/Metal Interconversion, 822

28.6.2 The Phosphorus/Metal Interconversion, 826

28.7 Aryl─Aryl Coupling Through Halogen/Metal Interconversion, 827

28.7.1 (Re)emerging Methods for Aryl─Aryl Coupling Through Halogen/Metal Interconversion, 827

28.7.2 Aryne‐Mediated Aryl─Aryl Coupling, 828

28.8 Summary and Outlook, 830

Abbreviations, 830

References, 830

PART IX PHOTOCHEMICAL REACTIONS 835

29 Aromatic Photochemical Reactions 837
Norbert Hoffmann and Emmanuel Riguet

29.1 Introduction, 837

29.2 Aromatic Compounds as Chromophores, 838

29.2.1 Photocycloaddition and Photochemical Electrocyclic Reactions Involving Aromatics, 838

29.2.2 Photoinduced Radical Reactions, 842

29.3 Photosensitized and Photocatalyzed Reactions, 849

29.3.1 Metal‐Catalyzed Reactions, 849

29.3.2 Metal‐Free Reactions, 856

29.4 Conclusion, 864

Abbreviation, 865

References, 865

30 Photochemical Bergman Cyclization and Related Reactions 869
Rana K. Mohamed, Kemal Kaya, and Igor V. Alabugin

30.1 Introduction: The Diversity of Cycloaromatization Reactions, 869

30.2 Electronic Factors in Photo‐BC, 870

30.2.1 Substituent Effects, 872

30.2.2 Introducing Strain, 872

30.3 Scope and Limitations of the Photo‐BC, 876

30.3.1 Metal‐Mediated Photochemistry, 876

30.3.2 Diverting from BC Pathway: Direct Excitation and Photoinduced Electron Transfer, 881

30.4 Enediyne Photocyclizations: Tool for Cancer Therapy, 883

30.5 Conclusion, 883

Abbreviations, 885

References, 885

31 Photo‐Fries Reaction and Related Processes 889
Francisco Galindo, M. Consuelo Jiménez, and Miguel Angel Miranda

31.1 Introduction, 889

31.2 Mechanistic Aspects, 889

31.2.1 General Scheme, 889

31.2.2 Experimental Evidence: Steady‐State Photolysis, 890

31.2.3 Experimental Evidence: Time‐Resolved Studies, 891

31.2.4 Experimental Evidence: Spin Chemistry Techniques, 894

31.2.5 Theoretical Studies, 894

31.3 Scope of the Reaction, 894

31.3.1 Esters, 894

31.3.2 Amides, 895

31.3.3 Other, 895

31.4 (Micro)Heterogeneous Systems as Reaction Media, 897

31.4.1 Cyclodextrins, 897

31.4.2 Micelles, 897

31.4.3 Zeolites, 897

31.4.4 Proteins, 897

31.4.5 Other Organized Media, 897

31.5 Applications in Organic Synthesis, 900

31.6 Biological and Industrial Applications, 902

31.6.1 Drugs, 902

31.6.2 Agrochemicals, 902

31.6.3 Polymers, 904

31.7 Summary and Outlook, 905

Abbreviations, 906

References, 906

PART X BIOTRANSFORMATIONS 913

32 Biotransformations of Arenes: An Overview 915
Simon E. Lewis

32.1 Introduction, 915

32.2 Dearomatizing Arene Dihydroxylation, 915

32.3 Dearomatizing Arene Epoxidation, 918

32.4 Arene Alkylation (Biocatalytic Friedel–Crafts), 919

32.5 Arene Deacylation (Biocatalytic Retro Friedel–Crafts), 922

32.6 Arene Carboxylation (Biocatalytic Kolbe–Schmitt), 923

32.7 Arene Halogenation (Halogenases), 925

32.8 Arene Oxidation with Laccases, 925

32.9 Tetrahydroisoquinoline Synthesis (Biocatalytic Pictet–Spengler), 929

32.10 Arene Hydroxylation, 930

32.11 Arene Nitration, 932

32.12 Summary and Outlook, 933

Abbreviations, 934

References, 934

INDEX 939

See More

Author Information

Jacques Mortier, PhD, is Professor of Organic Chemistry at the University of Maine in Le Mans (France), where he teaches classes on Industrial Organic Chemistry and Reaction Mechanisms in Aromatic and Heteroaromatic Chemistry. Dr. Mortier started his career as a research chemist in the crop protection industry. At the University of Maine, his research is focused on various topics dealing with polar organometallics, directed aromatic metalation methodologies, and the study of reaction mechanisms. He has extensive experience as a consultant for the chemical industry. In recognition of his research expertise, he was distinguished as a member of the University Institute of France (IUF).
See More

Related Titles

Back to Top