streamlining free radical green chemistry - gbv · 9.6 phosphinoyl radicals 206. streamliningfree...

Streamlining Free Radical Green

Chemistry

V. Tamara PerchyonokVTPCHEM PTY LTD, Melbourne, Victoria, Australia

Ioannis LykakisDepartment of Chemistry, University of Crete, Voutes-Heraklion, Greece

AI PostigoFaculty of Science, University of Belgrano, Buenos Aires, Argentina

RSC Publishing

Contents

Chapter 1 Development of Free Radical Green Chemistry and

Technology: Journey through Times, Solvents, Causes,

Effects and Assessments

1.1 Introduction 1

1.2 The Major Use of Free Radical Green Chemistry

from the Beginning 4

1.3 Alternative Feedstocks 4

1.3.1 Innocuous or More Innocuous 5

1.3.2 Renewable 5

1.3.3 Light 5

1.3.4 Solve Other Environmental Problems 6

1.3.5 Biocatalysis 6

1.4 Benign Reagents/Synthetic Pathways 7

1.4.1 Innocuous or More Innocuous 7

1.4.2 Generates Less Waste 7

1.4.3 Selective 8

1.4.4 Catalytic 8

1.5 Biomass: Utilization and Sustainability 8

1.6 Green Chemical Syntheses and Processes 9

1.7 Basic Radical Chemistry: Structure, Reactions

and Rates 10

1.7.1 General Aspects of Synthesis with Radicals:

Advantages and Traditions 10

1.7.2 Reactions Between Radicals 10

1.7.3 Reaction Between a Radical and a Non-radical 10

1.7.4 Reactivity and Selectivity 11

1.7.5 Enthalpy: In Brief 11

1.7.6 Entropy13

1.7.7 Steric Effects 14

1.7.8 Stereoelectronic Effects 15

Streamlining Free Radical Green Chemistry

V. Tamara Perchyonok, Ioannis Lykakis and Al Postigo

© V. Tamara Perchyonok, Ioannis Lykakis and AI Postigo 2012

Published by the Royal Society of Chemistry, www.rsc.org

ix

X Contents

1.7.9 Polarity 17

1.8 Solvent Effect and Free Radical Transformations:

General Understanding 17

1.9 Why Water as a Solvent? Reasons and Advantages 22

1.9.1 Solubility of Organic Compounds in Water 23

1.9.2 Organic Cosolvents 23

1.9.3 Ionic Derivatization (pH Control) 24

1.9.4 Surfactants 24

1.9.5 Hydrophilic Auxiliaries 25

1.9.6 Summary 25

1.10 Classical Synthesis in Modern Solvents 25

1.10.1 Perfluorinated Solvents—a Novel Reaction

Medium in Organic Chemistry: General

Introduction 26

1.10.2 Benzotrifluoride and Derivatives: Useful

Solvents for Organic Synthesis and

Fluorous Synthesis 28

1.10.3 Reactions in Supercritical Carbon Dioxide

(SCCO2) as a Novel Reaction Medium 29

1.10.4 Solvent-free Reactions as an Alternative:

General Interest for Solvent-free Processes 29

1.11 Methods of Generating Free Radicals 31

1.11.1 Thermal Cracking 31

1.11.2 Homolysis of Peroxides and Azo Compounds 32

1.11.3 Photolytic Bond Homolysis 32

1.11.4 Electron Transfer 32

1.11.5 Hydrogen and Halogen Atom Abstraction 33

1.11.6 The Configuration of Free Radicals 33

1.11.7 Elementary Reaction Steps between

Radicals and Non-radicals: Reactions of

Free Radicals 34

1.12 Sustainable Chemistry Metrics and Radical

Chemistry: Comparative Approach 35

1.12.1 Classical Metrics of Chemical Reactions 36

1.12.2 How do Contemporary Free Radical

Transformations Hold Up? Focus on

Sustainability, Atom Efficiency and

Advantages 38

1.13 Classics and Catalysis in Free Radical Chemistry:

Reagents, Reactants and Protocols 45

1.14 Radical cascades and Free Radical Green Chemistry 46

1.15 Artificial Enzymes in Free Radical Synthetic

Chemistry: the Chemist's Perspective 47

1.16 Future Challenges and Opportunities for the

Chemical Profession and the Science of Chemistry 48

Streamlining Free Radical Green Chemistry xi

1.17 An Environmentally Friendly Economy from

Green Chemistry 49

1.17.1 Renewable Energy Sources 49

1.17.2 Renewable Feedstocks 50

1.17.3 Pollution Reduction 50

1.17.4 Interdisciplinary Approach 50

1.18 Conclusion and Future Direction 51

References 51

Chapter 2 Classical Synthetic Free Radical Transformations in

Alternative Media: Supercritical C02, Ionic Liquids and

Fluorous Media

2.1 Introduction 58

2.2 Radicals in Synthetic Chemistry in the Nutshell 58

2.3 Reactions between Radicals 59

2.4 Elementary Reaction Steps between Radicals and

Non-radicals 60

2.4.1 Additions 61

2.4.2 Substitution (Abstraction) Reactions 63

2.4.3 Elimination Reactions 64

2.4.4 Rearrangement Reactions 64

2.4.5 Termination/Electron Transfer Reactions 65

2.5 Reactivity and Selectivity 65

2.6 Chain vs. Non-chain Free Radical Processes:

Reasons, Relevance and Outlook 66

2.7 Radical Reactions in Supercritical Fluids 66

2.7.1 Radical Reactions and Supercritical C02: Is

There a Hidden Advantage? 66

2.7.2 Radical Reactions in Supercritical Carbon

Dioxide in Detail 68

2.7.3 Future Directions 70

2.8 Radical Reactions in Ionic Liquids 72

2.8.1 Ionic Liquids and Alternative Media:

General Introduction 72

2.8.2 Radical Chain Reactions in Ionic Liquids:Triethylborane-induced Radical Reactions 72

2.8.3 Radical Additions of Thiols to Alkenes and

Alkynes in Ionic Liquids 73

2.9 Radical Non-Chain Reactions in Ionic Liquids 75

2.9.1 Formation of Radicals by Oxidation with

Transition Metal Salts: General Perspective 75

2.9.2 Oxidations involving Mn(in) in Ionic Liquids 75

xii Contents

2.9.3 Supported Ionic Liquids: Versatile Reaction

and Separation Media—the Latest

Developments 79

2.9.4 Conclusions and Future Directions 80

2.10 Fluorous Chemistry as an Alternative Reaction

Medium for Free Radical Transformations 81

2.10.1 Fluorous Separation Techniques: from

"Liquid-Liquid" to "Solid-Liquid" and

"Light Fluorous" 81

2.10.2 Fluorous Chemistry and Radicals—

Combined Efforts to the Rescue 83

2.10.3 Fluorous Radical CarbonylationReactions: from Synthetic Approach to

Practical Applications 83

2.11 Ishii Oxidation in Detail 89

2.12 From Phase-separation to Phase-vanishingMethods based on Fluorous-phase Screen: a SimpleWay for the Efficient Execution of Organic Synthesis 91

2.13 Conclusions and Future Directions in Fluorous

Chemistry 93

2.14 General Conclusion 93

References 94

Chapter 3 Solvent-Free Carbon-Carbon Bond Formations in Ball Mills

and in the Solid State

3.1 Introduction 99

3.2 Radical Additions to Imines Mediated by Mn(m) 102

3.3 Solid-phase Homolytic Substitution in Action 102

3.4 Future Directions 104

References 104

Chapter 4 Microwaves in Synthesis: How do Microwaves Promote the

Reaction in Conventional and Alternative Media?

4.1 Introduction 106

4.2 Microwave-assisted Fluorous Synthesis 107

4.3 Nitroxide-mediated Radical Cyclization and

Intramolecular Addition Reactions In Microwaves 107

4.3.1 The Persistent Radical Effect: General

Introduction 107

4.4 Radical Addition to C=N bonds in the Microwave 110

4.5 Microwave-assisted Generation of AlkoxylRadicals and their Use in Additions, P-Fragmentations and Remote Functionalization 113

Streamlining Free Radical Green Chemistry xiii

4.6 Atom-transfer Reactions as Efficient and Novel

Benzannulation Reactions in the Microwave 114

4.7 Conclusions and Future Directions 115

References 115

Chapter 5 Asymmetric Free-Radical Reductions Mediated by Chiral

Stannanes, Germanes, and Silanes


5.2 Stoichiometric Free Radical Reductions 118

5.3 Scope and Limitations 120

5.4 Examples Relevant to the Fine Chemical Industry 121

5.5 Strategies for the Avoidance of Tin Waste 121

5.6 Immobilization of Tin Reagents 122

5.7 Catalytic Reductions in Tin 123

5.8 Reducing Agents based on Germanium and Silicon 123

5.9 Summary 125

References 125

Chapter 6 Organic Radical Reductions in Water: Water as a HydrogenAtom Source


6.2 Water-soluble Organosilanes and Synthesis 128

6.3 rrw(trimethylsilyl)silane in Water and "on Water" 129

6.4 Triethylborane-Water Complex as a Reducing Agent 134

6.5 Titanium(m)-Water as a Reducing Agent 135

6.6 Summary 136

References 137

Chapter 7 Tin-Free Radical Reactions Mediated by Organoboron

Compounds


7.2 Organoboranes as Radical Initiators 141

7.3 In Reductive Processes 141

7.3.1 Reduction of Halides and Related Compounds 141

7.3.2 Reductive Addition of Heteroatom-centered

Radicals to Alkynes and Alkenes 143

7.3.3 In Fragmentation Processes 144

7.4 In Atom-transfer Processes 145

7.4.1 Iodine Atom Transfer 145

7.4.2 Bromine Atom Transfer 148

7.4.3 Chlorine Atom Transfer 149

7.5 Organoboron Compounds as a Source of Carbon-

centered Radicals 150

7.5.1 Conjugated Additions to Enones and Enals 150

xiv Contents

7.5.2 Conjugate Addition to Activated Olefins 155

7.5.3 Addition to Imine Derivatives 158

7.5.4 C-C Bond Formation via P-FragmentationProcesses 158

7.6 Organoboranes as Chain-transfer Reagents 162

7.6.1 Via Iodine Atom Transfer 163

7.6.2 Via Hydrogen Atom Transfer 165

7.7 Organoboron Compounds as Radical-reducing Agents 166

7.7.1 Complexes with Tertiary Amines 166

7.7.2 Complexes with Water and Alcohols 166

7.8 Conclusions 167

References 169

Chapter 8 Thiols as Efficient Hydrogen Atom Donors in Free Radical

Transformations in Aqueous Media


8.2 The Tris(trimethylsilyl)silane (TMS3SiH)/thiol

System is an Efficient Radical Hydrogen Donor

"on Water" 176

8.3 Thiol/Azo Initiator System in cis-trans

Isomerization of Double Bonds in Aqueous Media 177

8.4 Thiols in Peptides: Degradation in Aqueous Media 181

8.5 Thiols in C-C Bond Formation in Water 182

8.6 Thiol-Ene Coupling as a Click Process for

Materials and Bioorganic Chemistry 184

8.7 Hydrogen Sulfide in Oxidation and/or Reduction of

Organic Compounds 185

8.8 Thiyl Radicals and the Influence of

Antioxidants/Vitamins 186

8.9 Conclusions 189

References 189

Chapter 9 Advances in the Use of Phosphorus-centered Radicals in

Organic Synthesis in Conventional Flasks: Advantages,

Reasons and Applications


9.2 Physical Organic Aspects 196

9.3 Use of P-centered Radicals as Mediators 197

9.4 Synthetic Applications of P-centered Radical Additions 202

9.4.1 Phosphinyl Radicals 203

9.4.2 Phosphonyl Radicals 204

9.5 Radicals from Hypophosphites and Phosphinates 204

9.6 Phosphinoyl Radicals 206

Streamlining Free Radical Green Chemistry xv

9.6.1 Thiophosphonyl and Other Sulfur-

containing Radicals 206

9.7 Elimination of Organophosphorous Radicals 207

9.7.1 Phosphoranyl Radicals 207

9.7.2 P-Elimination of P-centered Radicals 208

9.8 Conclusion and Perspectives 209

References 210

Chapter 10 Metal-based Homogeneous Catalysis and Free Radical

Synthesis: Advantages, Developments and Scope

10.1 Introduction

10.2 Metal-mediated Reduction and Oxidation

Reactions in Water

10.3 Metal-radical-mediated Carbon-Carbon Bond

Formation Reactions in Water

10.3.1 Metal-mediated Radical Cyclizations in Water

10.3.2 Reformatzky Reactions in Water

10.3.3 Alkylation of Carbonyl Compounds, Imine

Derivatives and Electron-deficient Alkenes

in Water

10.3.4 Allylation of Carbonyl Compounds and

Imine-derivatives in Water

10.3.5 Radical Conjugate Additions to a,|3-

Unsaturated Carbonyl Compounds in Water

10.3.6 Synthesis of a,(3-Unsaturated Ketones

10.3.7 Metal-mediated Mannich-type Reactions

in Water

10.3.8 Pinacol and Other Coupling Reactions

in Water

10.4 Conclusion and Future Direction

AcknowledgmentsReferences

Chapter 11 Radicals and Transition-metal Catalysis: a ComplementarySolution to Increase Reactivity and Selectivity in Organic

Chemistry


11.2 Radical Cyclizations Terminated by Ir-catalyzed

Hydrogen-atom Transfer 302

11.3 Conclusion 306

References 307

212

212

228

228

238

240

248

268

275

277

278

286

287

287

xvi Contents

Chapter 12 Reagent Control in Transition-metal-initiated Radical

Reactions


12.2 Reagent Control in Transition-metal-initiated

Radical Reactions 311

12.3 Carbonyl Compounds as Radical Sources: Pinacol

Couplings 312

12.3.1 Stoichiometric Reagent-controlled Couplings 312

12.3.2 From Stoichiometric to Catalytic Pinacol

Couplings 316

12.4 Protonation of Metal-Oxygen Bonds in CatalyticRadical Reactions 320

12.5 Carbonyl Compounds as Radical Precursors:

Additions of Ketyl Radicals to C-C and C-X Bonds 322

12.6 Epoxides as Radical Precursors 328

12.6.1 Stoichiometric Reagents 328

12.6.2 Titanocene-catalyzed Epoxide Openings 333

12.6.3 Catalytic Enantioselective Epoxide Openings 336


References 340

Chapter 13 Enantioselective Radical Reactions and Organocatalysis


13.2 Organic Reagents and Organocatalysts in

Stereoselective Radical Chemistry 349

13.2.1 Chiral Lewis Acid Activation 349

13.3 Enantioselective Hydrogen Atom Transfer 353

13.4 Aminocatalysis/Enamine Activation 355

13.5 Future Directions for Organocatalysis in Radical

Chemistry 362

13.6 Conclusion 364

References 364

Chapter 14 The Sunny Side of Chemistry: Green Synthesis by Solar

Light


14.2 Historical Background 368

14.3 Synthesis using Non-concentrated Sunlight 370

14.4 Photocatalytic/Photomediated Processes 370

14.5 Photodimerization 372

14.6 Cycloadditions 374

14.7 Cyclizations 375

14.8 Photopinacolization (Photoreduction) 376

Streamlining Free Radical Green Chemistry xvii

14.9 Synthesis via Elimination of a Group 377

14.10 Arylation Reactions 379

14.11 Isomerizations 379

14.12 Halogenations 380

14.13 Synthesis of Endoperoxides 381

14.14 Oxidations/Oxygenations 382

14.15 Concentrated Sunlight 384

14.15.1 General Remarks 384

14.15.2 Photooxidations and Photooxygenations 385

14.15.3 Cycloadditions 387

14.16 Photocatalytic Reactions 387

14.17 Photoacylations 389

14.18 E/Z Isomerizations 389

14.19 Potential Industrial Applications 390


References 391

Chapter 15 Sonochemistry: Ultrasound Application in Radical Synthesis


15.2 Energy Efficiency 403

15.3 Sonochemical Initiation of Radical Chain

Reactions: Hydrostannation and

Hydroxystannation of C-C Multiple Bonds 404

15.4 Homogeneous Sonochemistry of Hydrostannationin Detail 406

15.5 Sonication-induced Halogenative Decarboxylationof Thiohydroxamic Esters 411

15.6 Aerobic Conversion of Organic Halides to

Alcohols: an Oxygenative Radical Cyclization 412

15.7 A New Method for Nitration of Alkenes to

a,p-Unsaturated Nitroalkenes 413


References 414

Chapter 16 Black-light-initiated Free Radical Reactions for Synthetic

Applications, Micro-reactors and Modified Nucleoside

Synthesis

16.1 Introduction: Why Black Light is so Important 416

16.2 C2',3'-Cyclic Carbonates Derived from

Nucleosides Why They are Important 417

16.3 C5' General Comments and History 417

16.4 Black-light induced Radical Cyclization Approach

to Cyclonucleosides: an Independent Approach 418

xviii Contents

16.5 Radical Cyclization "Tin-free" Approach to

C2',C3'-Cyclic Carbonates Derived from

Nucleosides: an Independent Approach 422

16.6 Black-light-induced Direct Generation of C2'-

Nucleosidyl Radicals in Adenosine, Thymidine and

Uridine in Organic and Aqueous Media 426

16.7 Black-light-induced Radical/Ionic

Hydroxymethylation of Alkyl Iodides with

Atmospheric CO in the Presence of

Tetrabutylammonium Borohydride 428

16.8 Towards the Synthesis ofAlkyl Alkynyl Ketones by

Pd/Light-induced Three-component CouplingReactions of Iodoalkanes, CO, and 1-Alkynes 431

16.9 Vicinal C-Functionalization of Alkenes: Pd/Light-induced Multicomponent Coupling Reactions

Leading to Functionalized Esters and Lactones 433

16.10 Closing the Gap: from Single Molecule Synthesisthe Conventional Way to Microreactors—the

Power of Black Light 434

16.11 Synthesis in Microchemical Systems 436

16.12 Microflow Photo-radical Chlorination of

Cycloalkanes 436

16.13 Continuous Microflow Chlorination of

Cyclohexane with Molecular Chlorine in Detail 437

16.14 Microflow Chlorination with Sulfuryl Chloride and

Black Light 438

16.15 The Barton Reaction Using a Microreactor and

Black Light: Continuous-flow Synthesis of a KeySteroid Intermediate for an Endothelin Receptor

Antagonist 439

16.16 Conclusion 442

References 442

Chapter 17 Photo-catalysis and Metal-Oxygen-anion Cluster

Decatungstate in Organic Chemistry: a Manifold Conceptfor Green Chemistry


17.2 C-C Bond Formation via C-H Bond

Fragmentation under Anaerobic Conditions 458

17.2.1 Functionalization of Alkanes by HomolyticC-H Bond Cleavage 458

17.2.2 Functionalization of Aldehydes byHomolytic C-H Bond Cleavage 461

17.2.3 Functionalization of Amides by HomolyticC-H Bond Cleavage 462

Streamlining Free Radical Green Chemistry xix

17.2.4 Functionalization of Toluenes, Anisoles

and Thioanisole by Homolytic C-H Bond

Cleavage 463

17.3 Homogeneous Oxidation of Organic Compounds

by Decatungstate 463

17.3.1 Oxidation ofAliphatic Alcohols and Alkanes 464

17.3.2 Oxidation of Aromatic Alcohols and Alkanes 465

17.3.3 Oxidation ofAliphatic and Aromatic Alkenes 466

17.4 Heterogeneous Oxidation of Organic Compounds

by Decatungstate 467

17.4.1 Immobilization on a Solid Support 468

17.4.2 Immobilization inside the Silica or Zirconia

Network 472

17.4.3 Immobilization on Silica containingAmmonium Cations 472

17.4.4 Immobilization onto Organic Ion-exchange

Resins 473

17.4.5 Immobilization with Organic Sensitizers 475

17.4.6 Immobilization in Polymeric Membranes 476

17.5 Degradation of Organic Pollutants by Decatungstate 478

17.6 Conclusion and Future Directions 483

References 483

Chapter 18 Radical Domino Reactions: Intermolecular TelescopicReactions

18.1 Introduction: Advantages and Limits 486

18.2 Radical/Radical Domino Processes in Synthesis 490


References 509

Chapter 19 Telescopic Reactions and Free Radical Synthesis: Focus on

Radical and Radical-Ionic Multicomponent Processes

19.1 General Introduction: Advantages and Limitations 513

19.2 Mnemonic Classification 514

19.3 Three-component Radical Reactions 516

19.3.1 3-CR-ADA 516

19.3.2 3-CR-DAD 519

19.3.3 3-CR-DAA 521

19.3.4 3-CR-DDA 522

19.4 Four- and Five-Component Radical Reactions 524

19.4.1 4-CR-DAAD 524

19.4.2 4-CR-ADAA 525

19.4.3 4-CR-AADA 525

19.5 Multicomponent Radical-Ionic Reactions 527

XX Contents

19.5.1 Multicomponent Radical-Anionic Reactions 527

19.5.2 Multicomponent Radical-Cationic Reactions 529

19.5.3 Sequential Multicomponent Radical-Polar

Crossover Reactions 531


References 532

Chapter 20 Radical-Radical-Radical Telescopic Reactions: from Rules

through Reasons to Applications


20.2 The "Round Trip" Strategy in Action 537


References 551

Chapter 21 Applications of Conventional Free Radicals and Advances in

Total Synthesis: from the Bench to the Future through the

Vinyl Radical

21.1 The Vinyl Radical, a Precious Tool for Radical

Cascades in 5-exo-dig Cyclizations 553

21.2 Linear Triquinanes from Acyclic Precursors 555

21.3 First Total Synthesis of Natural Protoilludane,

epz-Illudol 556

21.4 Asymmetric Intramolecular Radical Vinylation

using Enantiopure Sulfoxides as Temporary Chiral

Auxiliaries 559

21.5 Conclusion and Summary 561

References 561

Chapter 22 Streamlining Organic Free Radical Synthesis throughModem Molecular Technology: from Polymer-supported

Synthesis to Microreactors and Beyond

22.1 Free Radicals: a Brief Introduction and Why theyare Important 563

22.2 Polymer-supported Reagents and Free Radical

Synthesis: a Few Initial Remarks and Approaches 564

22.2.1 PEG-bound Reagents and Free Radical

Transformations to Date: the Journey

Has Begun 564

22.2.2 Solid-state Radical Reactions 565

22.3 Ultraporous Materials as Possible Microreactors

and Free Radical Synthesis 567

22.3.1 A Few Words About Polarity Reversal

Catalysis and its Advantages in Free

Radical Transformations in PolyHIPEs 569

Streamlining Free Radical Green Chemistry

22.4 Microreactor-controlled Selectivity in OrganicPhotochemical Reactions: Molecular Sieve Zeolites

to the Rescue

22.4.1 Photochemistry of Phenyl PhenylacetatesIncluded Within Zeolites and Nafion

Membranes

22.4.2 Zeolites and LDPE Films as Hosts for the

Preparation of Large Ring Compounds:Intramolecular Photocycloaddition of

Diaryl Compounds22.4.3 Summary

22.5 Microflow Systems for Practical Free Radical

Synthesis and Polymerization

22.6 Free Radical Polymerization in Microreactors:

New Advantages and Extra Control

22.7 Conclusion

References

Chapter 23 Radical Reactions and fl-Cyclodexrrin as a Molecular

Ferrari: Is There a Hidden Advantage of Speed, Power and

Class? From Fundamental Reactions to Potential

Applications

23.1 Introduction

23.2 The Cyclodextrin Reaction Media

23.3 P-Cyclodextrin-based Molecular Reactors for Free

Radical Chemistry in Aqueous Media and Chain

Reactions

23.4 On the Use of P-Cyclodextrins as Molecular

Reactors for the Radical Cyclizations under Tin-

free Conditions: Chain and Non-chain Reactions

23.5 Radical Cyclizations in P-Cyclodextrins in AqueousMedia under Photolytic Conditions

23.6 Mn(OAc)3 Radical Cyclizations in P-Cyclodextrin23.7 Cu(OAc)2 Radical Cyclizations in P-Cyclodextrins23.8 On the Scope of P-Cyclodextrin-Ionic Liquid-based

Molecular Reactors for Free Radical Chemistry in

Bio-compatible and Alternative Media

23.9 P-Cyclodextrin-Ionic Liquids and Conventional

Free Radical Reactions: Hydrogen Atom Transfer

Reactions

23.10 P-Cyclodextrin-Ionic Liquid (MIM-P-CDOTs) and

Conventional Free Radical Reactions: Radical

Additions, Atom Transfer, Hydrosilylation and

Hydrostannylation Reactions in Aqueous Media

xxii Contents

23.11 Potential Practical Application: Towards the

Development of Novel Drug Delivery PrototypeDevices for Targeted-Delivery Drug Therapy at the

Molecular Level in Aqueous Media 605

23.11.1 Path A in Detail: P-Cyclodextrin-Pro-

drug as an Efficient Prototype Molecular

Carrier in Water Aimed at TransportingRadical-affording Species (RAS) in

Aqueous Media 607

23.11.2 Path B in Detail: Investigation of Free

Radical-quenching Species (RQS) from a

p-Cyclodextrin-Phenol "Molecular

Antioxidant Prototype" in Water as

Antioxidant Delivery to the Radical

Reaction Mixture 608

23.12 Towards Streamlining Conventional Radical

Reactions through the Development of

|3-Cyclodextrin-based Batch, Flow-through and

"Teabag" Prototype Molecular Reactors 609

23.12.1 P-Cyclodextrins as Molecular Batch Reactors610

23.12.2 p-Cyclodextrin Molecular Flow-throughReactor for Streamlining Organic

Synthesis in a Continuous and Reusable

Fashion 611

23.12.3 "Teabag" Methodology and Radical

Reactions: Screening the Scope and

Flexibility 612


References 614

Chapter 24 Artificial Enzymes and Free Radicals: the Chemist's

Perspective


24.2 Transition State Theory: a Brief Introduction 626

24.3 The "Design Approach" 629

24.3.1 Cyclodextrins as Enzyme Mimics 629

24.3.2 Vitamin B12 Functions: Enzymatic Reactions 630

24.3.3 Model Reactions with Apoenzyme Functions 632

24.4 The "Transition State Analogue Selection" Approach 633

24.4.1 The Transition State Analogue Selection

Approach: General Introduction 633

24.4.2 Molecular-imprinted Polymers as a

Method in the Transition State AnalogueSelection Approach 634

24.4.3 Imprinting an Artificial Proteinase 636

Streamlining Free Radical Green Chemistry xxiii

24.4.4 Bioimprinting24.5 The "Catalytic Activity Selection Approach":

General Introduction

24.5.1 Combinatorial Polymers as Enzyme Mimics

24.5.2 Directed Evolution of Enzymes24.5.3 Catalysis with Imprinted Silicas and Zeolites

24.5.4 Catalytic Antibodies and a Few Examplesof Radical Transformations

24.6 Conclusion

References


Total Synthesis: from the Bench to Nature through Sml2

Radicals as an Efficient Trigger for Radical Cascades, a

Journey from Orsay to the 21st Century

25.1 Mechanisms of Sml2-mediated Reactions: the Basics 658

25.2 Radicals and Anions from Organohalides 659

25.3 Sml2-mediated Cyclizations in Natural Product

Synthesis 663

25.4 Four-membered Ring Formation Using Sml2 663

25.4.1 A Synthesis of Paeoniflorin 663

25.4.2 An Approach to the Pestalotiopsin and

Taedolidol Skeletons 664

25.5 Five-membered Ring Formation Using Sml2: the

Synthesis of (-)-Hypnophilin and the Formal

Synthesis of (-)-Coriolin 664

25.5.1 A Synthesis of Grayanotoxin HI 664

25.5.2 A Synthesis and Structural Revision of (-)-Laurentristich-4-ol 667

25.5.3 An Approach to (-)-Welwitindolinone A

Isonitrile 667

25.6 Six-membered Ring Formation Using Sml2: an

Approach to Marine Polycyclic Ethers 667

25.6.1 A Synthesis of Pradimicinone 669

25.6.2 A Synthesis of (+)-Microcladallene B 669

25.6.3 A Synthesis of Botcinins C, D and F 670

25.7 Seven-membered Ring Formation Using Sml2:

Syntheses of (-)-Balanol 671

25.8 Eight-membered Ring Formation Using Sml2:A Synthesis of Paclitaxel (Taxol) 673

25.8.1 A Synthesis of (+)-Isoschizandrin 673

25.9 Nine-membered Ring Formation Using Sml2: An

Approach to Ciguatoxin 674

25.10 Forming Larger Rings Using Sml2: A Synthesis of

Diazonamide A 674

xxiv Contents

25.10.1 A Synthesis of (3-Araneosene 674

25.10.2 A Synthesis of Kendomycin 675

25.11 Modifying Biomolecules Using Sml2 676

25.11.1 Introduction 676

25.11.2 Modifying Carbohydrates Using Sml2 678

25.11.3 Modifying Amino Acids and Peptides

Using Sml2 683

25.12 Summary 685

References 685

Chapter 26 Innovative Reactions Mediated by Zirconocene: Advantages

and Scope

26.1 Background of Zirconium in Organic Synthesis 689

26.2 Triethylborane-induced Radical Reaction with

Schwartz Reagent 690

26.3 Radical Cyclization Reactions with a

Zirconocene(alkene) Complex as an Efficient SingleElectron Transfer Agent 694

26.4 Triethylborane-induced Radical AllylationReaction with a Zirconocene(alkene) Complex 695

26.5 Conclusion 696

References 697


Total Synthesis: Radical Cascades in Bio-inspired Terpene

Synthesis


27.2 Antecedents 701

27.3 Recent Developments 703

27.3.1 Acyclic Terpenes 703

27.3.2 Radical Polyprene Cyclizations 704

27.3.3 Photo-induced Electron Transfer (PET)Reactions as Initiation 704

27.3.4 Acylselenium Derivatives as Substrates 707

27.4 Transition-metal-mediated Transformations 709

27.4.1 Manganese(m)-mediated Cyclizations 709

27.4.2 Ti(m)-mediated Epoxypolyprene Cyclizations 712

27.5 SOMO Organocatalysis and Terpenes 721

27.6 Conclusions 722

References 722

Subject Index 726

streamlining free radical green chemistry - gbv · 9.6 phosphinoyl radicals 206. streamliningfree...

Documents