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Arene Chemistry

Reaction Mechanisms and Methods for Aromatic Compounds
1. Aufl.

von: Jacques Mortier
173,99 €
Verlag:	Wiley
Format:	EPUB
Veröffentl.:	30.11.2015
ISBN/EAN:	9781118754986
Sprache:	englisch
Anzahl Seiten:	992

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Titelbeschreibung

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

Inhaltsverzeichnis

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

Rezension

"The broad covering of topics, made possible by the collaboration of world-renowned experts in different fields of organic chemistry and by a good balance in depth of coverage, positions [this book] as a deskbook that would be extremely useful for students of advanced courses of organic chemistry, instructors and professors, as well as experienced chemists in both academy and industry, and to those interested in arene chemistry and its application." -- Chemistry International " ... Jacques Mortier has brought together contributions from leading practitioners in universities and research institutes from around the world to create a concise but comprehensive text on aromatic chemistry. ... They have effectively condensed the essential material, and made an ideal source of information ..." -- Applied Organometallic Chemistry

Autorenportrait

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).

Back cover copy

Arenes, or aromatic compounds, have tremendous importance in industrial chemical applications – used across such diverse industries as pharmaceuticals, dyes, and polymers. Given the utility of aromatic reactions, there is real need for a book focusing on mechanisms and strategies for aromatic reactions. Stepping up to meet that demand, Arene Chemistry: Reaction Mechanisms and Methods for Aromatic Compounds surveys the main methods used for preparing these compounds and their transformations. Organized to enable students and synthetic chemists to understand and expand on aromatic reactions, the book helps those readers apply aromatic reactions in a practical context by designing syntheses. The book has 10 parts, divided into 32 chapters organized according to the types of mechanisms rather than by the conditions under which a reaction is executed. The topics covered include electrophilic aromatic substitution, nucleophilic aromatic substitution, aryne chemistry, reduction, oxidation, and dearomatization reactions, aromatic rearrangement reactions, transition metal mediated coupling, C-H bond functionalization, directed metalation and photochemical reactions, and biotransformations. Featuring the perspectives and expertise of leading researchers from around the world, Arene Chemistry offers a valuable reference and resource for the organic chemistry community. Key benefits include: • A thorough and accessible mechanistic explanation of aromatic reactions of arene compounds • Connection of reactivity and methodology with mechanism, at the interface of synthesis and physical organic chemistry • Essential information about techniques used to determine reaction mechanisms • Synthetic applications