Organometallic chemistry in industry : a practical approach / edited by Thomas J. Colacot, Carin C.C. Johansson Seechurn ; with a foreword by Robert H. Grubbs.

Format:

Book

Contributor:

Colacot, Thomas, editor.

Johansson Seechurn, Carin C. C., editor.

Language:

English

Subjects (All):

Organometallic chemistry.

Organometallic chemistry--Industrial applications.

Physical Description:

xix, 315 pages : illustrations (some color) ; 25 cm

Place of Publication:

Weinheim, Germany : Wiley-VCH, [2020]

Contents:

1 Industrial Milestones in Organometallic Chemistry p. 1 / Ben M. Gardner and Carin C.C. Johansson Seechurn and Thomas J. Colacot

1.1 Definition of Organometallic and Metal-Organic Compounds p. 1

1.1.1 Applications and Key Reactivity p. 1

1.1.1.1 Electronic Applications p. 1

1.1.1.2 Polymers p. 2

1.1.1.3 Organic Synthesis p. 2

1.2 Industrial Process Considerations p. 7

1.3 Brief Notes on the Historical Development of Organometallic Chemistry for Organic Synthesis Applications Pertaining to the Contents of this Book p. 8

1.3.1 Synthesis of Stoichiometric Organometallic Reagents p. 9

1.3.1.1 Conventional Batch Synthesis p. 9

1.3.1.2 Organometallics in Flow p. 10

1.3.2 Cross-coupling Reactions p. 10

1.3.2.1 C-H Bond Activation p. 12

1.3.2.2 Carbonylation p. 13

1.3.2.3 Catalysis in Water - Micellar Catalysis p. 13

1.3.3 Hydrogenation Reactions p. 14

1.3.4 Olefin Formation Reactions p. 15

1.3.4.1 Wittig Reaction p. 15

1.3.4.2 Metathesis Reactions p. 15

1.3.4.3 Dehydrative Decarbonylation p. 16

1.3.4.4 Olefins as Starting Materials p. 16

1.3.5 Poly- or Oligomerization Processes p. 17

1.3.6 Photoredox Catalysis for Organic Synthesis p. 17

2 Design, Development, and Execution of a Continuous-flow-Enabled API Manufacturing Route p. 23 / Alison C. Brewer and Philip C. Hoffman and Timothy D. White and Yu Lu and Laura McKee and Moussa Boukerche and Michael E. Kobierski and Nessa Mullane and Mark Pietz and Charles A. Alt and Jim R. Stout and Paul K. Milenbaugh and Joseph H. Martinelli

2.1 Continuous-flow-Enabled Synthetic Strategy p. 25

2.2 Design and Scale-up of Chan-Lam Coupling p. 28

2.2.1 Development of Homogeneous Conditions p. 31

2.2.2 Application of a Platform Technology to Aerobic Oxidation p. 32

2.2.3 Optimization of Reaction and Workup Parameters p. 35

2.2.4 Safety Considerations for Aerobic Oxidation on Scale p. 37

2.2.5 Continuous Scale-up and Manufacturing p. 38

2.3 Design and Scale-up of a Buchwald-Hartwig Cross-coupling p. 42

2.3.1 Initial Screening p. 43

2.3.2 Synthesis and Isolation of Pd(dba)DPEPhos Precatalyst p. 45

2.3.3 Workup Procedure, Metal Removal, and Crystallization p. 46

2.3.4 Scale-up and Manufacturing p. 48

2.4 Impurity Control p. 48

2.4.1 Solubility and Impurity Spiking Studies p. 50

3 Continuous Manufacturing as an Enabling Technology for Low-Temperature Organometallic Chemistry p. 61 / Andreas Hafner and Joerg Sedelmeier

3.2 Organo-Li and Mg Processes in Flow Mode p. 62

3.2.1 Technological Advantages of Flow Technology Compared to Traditional Batch Operation p. 62

3.2.2 Temperature Profile of Continuous Flow Reactions p. 64

3.2.3 Flash Chemistry: Functional Group Tolerance p. 65

3.2.4 Flash Chemistry: Selectivity p. 66

3.2.5 Flash Chemistry: Stoichiometry and Chemoselectivity p. 67

3.3 Continuous Flow Technology p. 69

3.3.1 Clogging as a Major Hurdle in Flow Chemistry p. 71

3.3.2 Start-up and Shutdown Operation p. 72

3.3.3 Material of Construction p. 72

3.3.4 Safety Concept and Emergency Strategies p. 73

3.4 Development of a Flow Process p. 73

3.4.1 Screening Phase: Feasibility Study p. 74

3.4.2 Process Development Phase: Extended Evaluations Including Technical Feasibility p. 75

3.5 Literature Examples: Flow Processes on Multi 100 g Scale p. 76

3.5.1 Manufacture of Verubecestat (MK-8931) p. 77

3.5.2 Manufacture of Edivoxetine p. 77

3.5.3 Scale-up of Highly Reactive Aryl Lithium Chemistry p. 80

3.5.4 Synthesis of Bromomethyltrifluoroborates in Continuous Flow Mode p. 81

3.5.5 Two-Step Synthesis Toward Boronic Acids p. 82

3.5.6 Reaction Sequence Toward a Highly Substituted Benzoxazole Building Block p. 84

3.6 Conclusion and Future Prospects p. 86

4 Development of a Nickel-Catalyzed Enantioselective Mizoroki-Heck Coupling p. 91 / Jean-Nicolas Desrosiers and Chris H. Senanayake

4.1.1 Nonprecious Metal Catalysis Advantages for Industry p. 91

4.1.2 Mizoroki-Heck Couplings in Industry with Palladium p. 92

4.1.3 Emergence of Nickel-Catalyzed Mizoroki-Heck Couplings p. 93

4.1.4 Enantioselective Nickel-Catalyzed Couplings p. 94

4.1.5 Synthesis of Oxindoles via Mizoroki-Heck Cyclizations p. 96

4.2 Development of a Nickel-Catalyzed Heck Cyclization to Generate Oxindoles with Quaternary Stereogenic Centers p. 97

4.2.1 Precedents and Challenges p. 97

4.2.2 Optimization of Reducing Agent and Base p. 97

4.2.3 Ligand Screening p. 98

4.2.4 Impact of Aryl Electrophile and of Stereochemistry of Alkene Moiety p. 100

4.2.5 Exploration of the Substrate Scope p. 102

4.2.6 Limitations of the Methodology p. 104

4.2.7 Mechanistic Considerations p. 104

4.3 Development of First Enantioselective Nickel-Catalyzed Heck Coupling p. 107

4.3.1 Ligand Screening p. 107

4.3.2 Impact of Alkene Stereochemistry p. 107

4.3.3 Neutral vs Cationic Pathways p. 108

4.3.4 Nickel Precatalyst Complex Synthesis p. 109

4.3.5 Exploration of the Substrate Scope p. 110

4.3.6 Mechanistic Studies p. 110

5 Development of Iron-Catalyzed Kumada Cross-coupling for the Large-Scale Production of Aliskiren Intermediate p. 121 / Srinivas Achanta and Debjit Basu and Uday K. Neelam and Rajeev R. Budhdev and Apurba Bhattacharya and Rakeshwar Bandichhor

5.2 Optimization of Grade and Equivalents of Mg Metal p. 123

5.3 Optimization of Equivalents of 1,2-Dibromoethane p. 123

5.4 Effect of Solvent Concentration on Preparation of Grignard Reagent and Kumada-Corriu Coupling p. 124

5.5 Effect of Alkyl Chloride 3 Addition Time on the Grignard Reagent Preparation p. 125

5.6 Stability of Grignard Reagent at 0-5°C p. 125

5.7 Iron-Catalyzed Cross-coupling Reaction p. 127

5.8 Optimization of Equivalents of NMP and Fe(acac)₃ p. 129

5.9 Optimization of Equivalents of Substrate 4 and Its Rate of Addition p. 129

5.10 Execution at Pilot Scale and Scale-up Issues p. 129

5.11 Agitated Thin Film Evaporator (ATFE) for Purification of 2 p. 131

6 Development and Scale-Up of a Palladium-Catalyzed Intramolecular Direct Arylation in the Commercial Synthesis of Beclabuvir p. 137 / Collin Chan and Albert J. DelMonte and Choo Hang and Yi Hsiao and Eric M. Simmons

6.2 KOAc/DMAc Process p. 141

6.3 TMAOAc/DMF Process p. 141

6.4 TMAOAc/DMAc Process p. 149

6.4.1 Cyclization Reaction p. 151

6.4.2 Mechanistic Understanding of the Cyclization Reaction and Impurity Formation p. 159

6.4.3 Hydrolysis and Workup p. 162

6.4.4 Crystallization and Drying p. 164

7 Ruthenium-Catalyzed C-H Activated C-C/N/O Bond Formation Reactions for the Practical Synthesis of Heterocycles and Pharmaceutical Agents p. 171 / Anita Mehta and Naresh Kumar and Biswajit Saha

7.2 C-H Activation Followed by C-C Bond Formation p. 172

7.2.1 C-H Activation Followed by C-C Bond Formation: Biaryl/Heterobiaryl Synthesis in Organic Solvents p. 172

7.2.2 C-H Activation Followed by C-C Bond Formation: Biaryl/Heterobiaryl Synthesis in Green Solvents p. 181

7.3 Alkyl/Acyl/Alkenyl Substitution on Heterocycles p. 185

7.4 C-H Activation Followed by C-O/N Bond Formation: Heterocycle Synthesis p. 187

7.4.1 C-H Activation Followed by C-O/N Bond Formation: Heterocycle Synthesis in Organic Solvents p. 187

7.4.2 C-H Activation Followed by C-O and C-N Bond Formation: Heterocycle Synthesis in Green Solvents p. 189

8 Cross-couplings in Water - A Better Way to Assemble New Bonds p. 203 / Tharique N. Ansari and Fabrice Gallou and Sachin Handa

8.2 Transition Metal Catalysis in Organic Solvents vs Micellar Catalysis p. 204

8.2.1 Micellization p. 205

8.2.2 Surfactant Solution - A Highly Organized Reaction Medium to Enhance Reaction Rate p. 206

8.2.3 Reaction Temperature p. 207

8.2.4 Size of Micelles p. 207

8.2.5 Nature of Catalyst p. 208

8.2.6 Increasing the Efficiency in Micellar Catalysis p. 209

8.2.7 Order of Addition p. 210

8.2.8 Product Precipitation or Extraction p. 211

8.2.9 Trace Metal in the Product p. 211

8.3 Highly Valuable Reactions in Water p. 212

8.3.1 Suzuki-Miyaura Couplings p. 212

8.3.2 Heck Couplings p. 217

8.3.3 Negishi Couplings p. 219

8.3.4 C-H Arylations p. 221

8.3.5 Aminations p. 225

8.3.6 Borylation p. 228

8.3.7 Arylation of Nitro Compounds p. 228

8.3.8 Adoption of Micellar Technology by Pharmaceutical Industry p. 229

9 Aspects of Homogeneous Hydrogenation from Industrial Research p. 239 / Stephen Roseblade

9.1 Homogeneous Hydrogenation: A Brief Introduction p. 239

9.2 Catalyst Selection by Effective Screening Approaches p. 240

9.3 Considerations for Reaction Scale-up p. 244

9.4 Notes on Additive Effects p. 247

9.5 A Novel Approach to Aliskiren Using Asymmetric Hydrogenation as a Key Step p. 249

9.6 Efficient Chemoselective Aldehyde Hydrogenation p. 252

9.7 Closing Remarks/Summary p. 253

10 Latest Industrial Uses of Olefin Metathesis p. 259 / John H. Phillips

10.2.1 Non-ruthenium Catalysts p. 260

10.2.2 Ruthenium Catalysts p. 261

10.3 Industrial Uses p. 262

10.3.1 Ring-closing Metathesis (RCM) p. 262

10.3.2 Cross-metathesis (CM) p. 264

10.3.3 Ring-Opening Metathesis Polymerization (ROMP) p. 268

10.4 Reaction Considerations p. 270

10.4.1 Catalyst Choice p. 271

10.4.2 Catalyst Loading p. 273

10.4.3 Solvent p. 273

10.4.4 Reaction Concentration p. 273

10.4.5 Overall Handling p. 274

10.4.6 Application Guide and Availability p. 274

10.5.1 Catalyst Removal p. 275

10.5.2 Functional Group Tolerance p. 276

10.5.3 Substrate Purity p. 276

10.5.4 Catalyst Decomposition - Isomerization p. 277

11 Dehydrative Decarbonylation p. 283 / Alex John

11.2 Use of Sacrificial Anhydride and Catalytic Mechanism p. 285

11.3 Rh-, Pd-, and Ir-Catalysis p. 286

11.3.1 Early Studies p. 286

11.3.2 Recent Studies p. 289

11.4 Milder Temperatures p. 291

11.4.1 PdCl₂/XantPhos/(tBu)₄biphenol System p. 291

11.4.2 Well-Defined Pd-bis(phosphine) Precatalysts p. 294

11.5 Nickel and Iron Catalysis p. 295

11.6 Ester Decarbonylation p. 297

11.7 Synthetic Utility: α-Vinyl Carbonyl Compounds p. 299.

Notes:

Includes bibliographical references and index.

Other Format:

Electronic version: Organometallic chemistry in industry.

ISBN:

9783527345175

3527345175

OCLC:

1144796651