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The Pauson-Khand Reaction: Scope, Variations and Applications

ISBN: 978-0-470-97076-8
328 pages
April 2012
The Pauson-Khand Reaction: Scope, Variations and Applications (0470970766) cover image
The Pauson-Khand reaction is an important reaction in the field of organic chemistry. It involves the transition-metal catalysed cycloaddition of an alkyne, an alkene and carbon monoxide, to produce cyclopentenones.   The importance of this reaction originates from its high value in transforming simple components into the synthetically useful cyclopentenone unit, in which a high degree of molecular complexity can be achieved in a single step, with impressive stereochemical and regiochemical control.

The Pauson-Khand Reaction investigates the nature and many variations of this reaction.

Topics covered include: 

  • the mechanisms of Pauson‐Khand-type reactions
  • non chiral  intramolecular and intermolecular versions of Pauson‐Khand reactions
  • asymmetric Pauson‐Khand reaction using chiral auxiliaries
  • the enantioselective Pauson‐Khand reaction
  • Pauson‐Khand reactions catalysed by metals other than cobalt
  • unconventional Pauson‐Khand reactions
  • the Pauson‐Khand reaction in total synthesis

Presenting a comprehensive overview of this fundamental reaction, The Pauson-Khand Reaction will find a place on the bookshelves of any organic or organometallic chemist. 

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List of Contributors xi

Foreword xiii

Preface xv

1. The Pauson-Khand Reaction – an Introduction 1
William J. Kerr

1.1 The Discovery and Early Evolution of the Khand Reaction 1

1.2 The Intermolecular Pauson-Khand Reaction 4

1.2.1 Regioselectivity of Alkyne Insertion 5

1.2.2 Regioselectivity of Alkene Insertion 6

1.3 The Intramolecular Pauson-Khand Reaction 8

1.4 Enhancing the Pauson-Khand Annulation by Reaction Promotion 9

1.4.1 Dry State Adsorption 9

1.4.2 Ultrasound Techniques 10

1.4.3 Microwave Promotion 10

1.4.4 Amine N-Oxide Additives 11

1.4.5 Sulfide Promoters 13

1.5 Catalytic Pauson-Khand Protocols 15

1.6 Concluding Remarks 16

Acknowledgements 17

References 17

2. The Mechanism of the Pauson-Khand Reaction: Hypothesis, Experimental Facts, and Theoretical Investigations 23
Xacobe C. Cambeiro and Miquel A. Pericás

2.1 Introduction 23

2.2 Stoichiometric Pauson-Khand Reaction 25

2.2.1 The Ligand Substitution Steps 25

2.2.2 Cobaltacycle Formation 29

2.2.3 CO Insertion 31

2.2.4 Reductive Elimination 32

2.3 Catalytic Pauson-Khand Reaction 32

2.4 Theoretical Studies 33

2.4.1 General Approach to the Mechanism 33

2.4.2 Regioselectivity. Early Steps of the Pauson-Khand Reaction 37

2.4.3 Stereoselectivity 41

2.5 Conclusions 46

References 46

3. Non Chiral Pauson-Khand Reaction 49
Takanori Shibata

3.1 History of Co-Mediated Pauson-Khand Reaction 49

3.2 Mechanism of the Pauson-Khand Reaction 50

3.3 An Early Example of Catalytic Reaction 51

3.4 Catalytic Reactions by Aid of Additives 52

3.5 Catalytic Reaction Using in-situ Generated Low-Valent Cobalt Complex 55

3.6 Catalytic Reaction Using Multinuclear Cobalt Carbonyl Catalysts 59

3.7 Catalytic Reaction Using Heterogeneous Catalysts 61

3.8 Catalytic Reaction in Other Than Conventional Solvents 63

3.9 Intramolecular Reaction of Carbodiimides with Alkynes 65

References 66

4. Diastereoselective Pauson-Khand Reaction using Chiral Pool Techniques (Chiral Substrates) 69
Martin Kamlar, Jan Vesely, and Ramon Rios Torres

4.1 Introduction and Background 69

4.2 Intramolecular Diastereoselective Pauson-Khand Reaction 70

4.3 Intermolecular Diastereoselective Pauson-Khand Reaction 87

4.4 Conclusion 90

References 91

5. Asymmetric Intra- and Intermolecular Pauson-Khand Reactions: The Chiral Auxiliary Approach 95
Albert Moyano

5.1 Introduction 96

5.2 Asymmetric Intramolecular PKRs with the Aid of Chiral Auxiliaries 99

5.2.1 Chiral Alkoxyacetylenes 99

5.2.2 Chiral Acetylene Thioethers 104

5.2.3 Chiral 2-alkynoate Derivatives 106

5.2.4 Chiral O-alkyl Enol Ethers 108

5.2.5 Alkenyl sulfoxides 113

5.2.6 Asymmetric Intramolecular PKRs Mediated by Chiral Auxiliaries Located in the Enyne Tether 114

5.3 Asymmetric Intermolecular PKRs with the Aid of Chiral Auxiliaries 116

5.3.1 Chiral Alkoxyacetylenes 116

5.3.2 Chiral Acetylene Thioethers 124

5.3.3 Alkynyl Sulfoxides 125

5.3.4 Chiral Ynamines and Ynamides 126

5.3.5 Chiral 2-alkynoates 128

5.3.6 Alkenyl Sulfoxides 135

5.4 Chiral Reagents for the Kinetic Resolution of PK Cycloadducts 138

5.5 Conclusion 140

Acknowledgements 140

References 140

6. The Enantioselective Pauson-Khand Reaction 147
Agustí Lledó, Xavier Verdaguer and Antoni Riera

6.1 Introduction 148

6.2 Mechanistic Considerations. Topology of Alkyne-Dicobalt Clusters 148

6.3 Intrinsically Chiral Dicobalt Clusters 150

6.3.1 Resolution of Monophosphine Complexes 150

6.3.2 Synthesis of Chiral Monophosphine Complexes Using Chiral N-Oxides 151

6.3.3 Heterobimetallic Complexes 151

6.4 Chiral Promoters 153

6.4.1 Sulfoxides 153

6.4.2 Chiral N-Oxides 153

6.5 Chiral Ligands 155

6.5.1 Sulfides 155

6.5.2 Cyclopentadienes (Heterobimetallic) 156

6.5.3 C-Chiral and Axially Chiral Phosphines 156

6.5.4 C2-Symmetric Bridging Bis-phosphines 161

6.5.5 C-Chiral Bidentate (P,S) Ligands 162

6.5.6 S-Chiral Bidentate (P,S) Ligands 167

6.6 Synthetic Applications 171

6.7 Conclusion 176

References 176

7. Recent Advancement of Catalytic Pauson-Khand-type Reactions 181
Fuk Loi Lam, Hang Wai Lee, Jun Wang and Fuk Yee Kwong

7.1 Introduction 181

7.2 Rhodium-Catalyzed Pauson-Khand-Type Cyclizations 182

7.3 Iridium-Catalyzed Pauson-Khand-Type Cyclizations 194

7.4 Titanium-Catalyzed Pauson-Khand-Type Cyclizations 198

7.5 Ruthenium-Catalyzed Pauson-Khand-Type Cyclizations 200

7.6 Nickel- and Palladium-Catalyzed Pauson-Khand-Type Cyclizations 201

7.7 Tandem Reactions and Miscellaneous (other than Co complex) 204

7.8 Conclusion 206

Acknowledgements 206

References 206

8. Recent Adventures with the Pauson-Khand Reaction in Total Synthesis 211
Scott G. Van Ornum, Sarah Hoerner and James M. Cook

8.1 Introduction 212

8.2 (+)-Epoxydictymene 212

8.3 (±)-Pentalenene and (-)-Pentalenene 214

8.4 The Tandem Pauson-Khand Reaction Directed Towards the Synthesis of Dicyclopentapentalenes 215

8.5 Enantioselective Total Synthesis of (-)--Kainic Acid 219

8.6 The Total Synthesis of Paecilomycine A 220

8.7 The Total Synthesis of (+)-Achalensolide 221

8.8 The Total Synthesis of (-)-Alstonerine 222

8.9 The Total Synthesis of (±)-8-Hydroxystreptazolone 224

8.10 The Formal Total Synthesis of (±)-- and -Cedrene 226

8.11 Additional Applications of the Pauson-Khand Reaction in Total Synthesis 227

8.12 Conclusions 230

Acknowledgements 231

References 231

9. Heterogeneous Catalytic Pauson-Khand Reaction 239
Young Keun Chung

9.1 Introduction 240

9.2 Development of Heterogeneous Catalysts for PKR 240

9.2.1 Polymer-Supported Catalytic Systems 241

9.2.2 Bulk Cobalt as a Catalyst 242

9.2.3 Raney Cobalt 243

9.2.4 Mesoporous Organized Zirconium Oxide Silica Powders as Catalyst 244

9.2.5 Mesoporous Graphitic Carbon as a Promoter 245

9.3 Transition Metal Nanoparticle Catalyst 246

9.3.1 Colloidal Cobalt Nanoparticles 247

9.3.2 Cobalt Nanoparticles on Charcoal 247

9.3.3 Poly(ethylene glycol)-Stabilized Cobalt Nanoparticles 249

9.4 Bimetallic Nanoparticle Catalysts 250

9.4.1 Immobilized Heterobimetallic Ru/Co Nanoparticle 250

9.4.2 Heterobimetallic Co/Rh Nanoparticles 251

9.5 Sequential Action of Two Different Catalysts in One-Pot Reactions 261

9.5.1 Chiral Pd(II) Complex and Bulk Cobalt on Charcoal-Catalyzed Tandem Asymmetric Allylic Alkylation and PK Annulation Reactions 262

9.5.2 Pd(II) Complex and Cobalt Nanoparticle-Catalyzed Three-Step One-Pot Synthesis of Fenestranes 262

9.5.3 Palladium and Cobalt Nanoparticles-Catalyzed Tandem Allylic Alkylation and PKRs 264

9.6 Conclusion 265

References 266

10. Other Transition Metal-Mediated Cyclizations Leading to Cyclopentenones 275
Ramon Rios Torres and Jan Vesely

10.1 Introduction and Background 276

10.2 [4+1] Strategies for the Synthesis of Cyclopentenones 278

10.3 [3+2] Strategies for the Synthesis of Cyclopentenones 283

10.3.1 Iron Promoted Reactions 283

10.3.2 Synthesis of Cyclopentenones via [3+2] Cycloadditions of Fisher Alkenyl Complexes 284

10.4 Nickel(0) and Palladium(0) Synthesis of Cyclopentenones 285

10.5 Metal Carbine Strategies for the Synthesis of Cyclopentenones 289

10.5.1 Cyclopropylcarbene Chromium Complexes 289

10.5.2 Rhodium(II)-Catalyzed Strategies 291

10.6 Other Methodologies 292

10.7 Conclusions 298

Experimental 299

References and Notes 299

Index 307

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