The Handbook of Homogeneous Hydrogenation 3527311610

Edited byJohannes G. de Vriesand Cornelis J. Elsevier

The Handbookof HomogeneousHydrogenation

The Handbook of Homogeneous Hydrogenation.Edited by J.G. de Vries and C. J. ElsevierCopyright 2007 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimISBN: 978-3-527-31161-3

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Edited byJohannes G. de Vries and Cornelis J. Elsevier

The Handbook of HomogeneousHydrogenation

The Editors

Prof. Dr. Johannes G. De VriesDSM Pharmaceutical ProductsAdvanced Synthesis, Catalysis, and DevelopmentP.O. Box 186160 MD GeleenThe Netherlands

Prof. Dr. Cornelis J. ElsevierUniversiteit van AmsterdamHIMSNieuwe Achtergracht 1661018 WV AmsterdamThe Netherlands

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2007 WILEY-VCH Verlag GmbH & Co. KGaA,Weinheim, Germany

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Foreword XIX

Preface XXIII

List of Contributors XXV

Part I Introduction, Organometallic Aspectsand Mechanism of Homogeneous Hydrogenation

1 Rhodium 3Luis A. Oro and Daniel Carmona

1.1 Introduction 31.1.1 Monohydride Hydrogenation Catalysts 41.1.2 Dihydride Hydrogenation Catalysts 41.2 The Early Years (19391970) 51.3 The [RhH(CO)(PPh3)3] Catalyst 61.4 The [RhCl(PPh3)3] Complex and Related Catalysts 81.5 The Cationic[Rh(diene)(PR3)X]

+ Catalysts 111.6 Enantioselective Rhodium Catalysts 141.6.1 Hydrogenation of Alkenes 141.6.2 Hydrogenation of Ketones 191.6.3 Hydrogenation of Imines 201.6.4 Mechanism of Rhodium-Catalyzed Enantioselective

Hydrogenation 211.7 Some Dinuclear Catalyst Precursors 261.8 Concluding Remark 26

Abbreviations 26References 27

2 Iridium 31Robert H. Crabtree

2.1 Introduction 312.2 Historical Aspects 312.3 Organometallic Aspects 36

V


Contents

2.4 Catalysis 392.4.1 Enantioselective Versions of the Iridium Catalyst 392.4.2 Mechanism 402.4.3 Practical Considerations 42

Acknowledgments 43Abbreviations 43References 43

3 Ruthenium and Osmium 45Robert H. Morris

3.1 Introduction 453.2 Ruthenium 463.2.1 The First Catalysts for Alkene Hydrogenation:

Mechanistic Considerations 463.2.2 Synthesis of Ruthenium Precatalysts and Catalysts 503.2.3 Dihydrogen Complexes and Non-Classical Hydrogen Bonding

in Catalysis 523.2.4 Toward the Reduction of Simple Ketones, Nitriles, Esters

and Aromatics with Monodentate Phosphine Systems 553.2.5 Enantiomeric Hydrogenation of Alkenes with Bidentate Ligand

Systems 583.2.6 Enantiomeric Hydrogenation of Carbonyl Compounds 603.3 Osmium 64

Acknowledgment 66Abbreviations 67References 67

4 Palladium and Platinum 71Paolo Pelagatti

4.1 Introduction 714.2 Palladium 724.2.1 Phosphorus-Containing Catalysts 724.2.2 Nitrogen-Containing Catalysts 764.2.3 Other Catalysts 784.2.4 Mechanistic Aspects 794.3 Platinum 844.3.1 Platinum Complexes Activated with Sn(II) Salts 844.3.1.1 Phosphorus-Containing Catalysts 844.3.1.2 Other Catalysts 854.3.2 Platinum Complexes not Activated with Sn(II) Salts 864.3.3 Mechanistic Aspects 87


ContentsVI

5 Nickel 93Elisabeth Bouwman

5.1 Introduction 935.2 Coordination Chemistry and Organometallic Aspects of Nickel 945.2.1 NickelHydride Complexes 945.2.2 Nickel-Alkene and Nickel-Alkyl Complexes 965.2.3 Mechanistic Aspects of Hydrogen Activation 975.3 Hydrogenation Catalysis 985.3.1 Ziegler Systems 985.3.2 Nickel Complexes of Oxygen- or Nitrogen-Containing Ligands 995.3.3 Nickel Complexes of Triphenylphosphane 1005.3.4 Nickel Complexes of Didentate Phosphane Ligands 1015.4 Concluding Remarks 107


6 Hydrogenation with Early Transition Metal, Lanthanideand Actinide Complexes 111Christophe Copret

6.1 Introduction 1116.2 Mechanistic Considerations 1126.3 Group IV Metal Hydrogenation Catalysts 1136.3.1 Hydrogenation of Alkenes 1136.3.2 Hydrogenation of Alkynes and Dienes 1146.3.3 Enantioselective Hydrogenation of Alkenes 1166.3.4 Enantioselective Hydrogenation of Imines and Enanimes 1186.4 Hydrogenation Catalysts Based on Group III, Lanthanide,

and Actinide Complexes 1266.4.1 Hydrogenation of Alkenes with Group III Metal and Lanthanide

Complexes 1266.4.2 Hydrogenation of Dienes and Alkynes with Group III

and Lanthanide Complexes 1296.4.3 Hydrogenation of Imines with Group III and Lanthanide

Complexes 1316.4.4 Hydrogenation of Alkenes with Actinide Complexes 1326.4.5 Enantiomeric Hydrogenation of Alkenes 1346.5 Hydrogenation Catalysts Based on Groups VVII Transition-Metal

Complexes 1366.5.1 Hydrogenation of Alkenes and Dienes with Groups VVII

Transition-Metal Complexes 1366.5.2 Hydrogenation of Aromatics with Well-Defined Nb and Ta Aryloxide

Complexes 1386.6 Supported Early Transition-Metal Complexes

as Heterogeneous Hydrogenation Catalysts 1406.6.1 Supported Homogeneous Catalysts 140

Contents VII

6.6.2 Heterogeneous Catalysts Prepared via Surface OrganometallicChemistry 142

6.7 Conclusions 145Acknowledgments 146Abbreviations 146References 146

7 Ionic Hydrogenations 153R. Morris Bullock

7.1 Introduction 1537.2 Stoichiometric Ionic Hydrogenations 1547.2.1 Stoichiometric Ionic Hydrogenations using CF3CO2H

and HSiEt3 1547.2.2 Stoichiometric Ionic Hydrogenations using Transition-Metal

Hydrides 1577.2.2.1 General Aspects 1577.2.2.2 Transition-Metal Hydrides as Proton Donors 1577.2.3 Transition Metal Hydrides as Hydride Donors 1597.2.4 Stoichiometric Ionic Hydrogenation of Alkenes with Metal Hydrides

as the Hydride Donor 1647.2.5 Stoichiometric Ionic Hydrogenation of Alkynes 1667.2.6 Stoichiometric Ionic Hydrogenation of Ketones and Aldehydes

using Metal Hydrides as Hydride Donors and Added Acidsas the Proton Donor 167

7.2.7 Stoichiometric Ionic Hydrogenation of Acyl Chlorides to Aldehydeswith HOTf/Metal Hydrides 171

7.2.8 Stoichiometric Ionic Hydrogenation of Ketoneswith Metal Dihydrides 173

7.3 Catalytic Ionic Hydrogenation 1747.3.1 Catalytic Ionic Hydrogenation of C=C Bonds 1747.3.2 Catalytic Ionic Hydrogenation of Ketones by Anionic Cr, Mo,

and W Complexes 1747.3.3 Catalytic Ionic Hydrogenation of Ketones by Molybdenocene

Complexes 1767.3.4 Catalytic Ionic Hydrogenation of Ketones by Cationic Mo

and W Complexes 1787.3.4.1 In Solution 1787.3.4.2 Solvent-free 1817.3.4.3 N-Heterocyclic Carbene Complexes 1827.3.5 Use of a Pd Hydride in Hydrogenation of C=C Bonds 1847.3.6 Catalytic Hydrogenation of Iminium Cations by Ru Complexes 1847.4 Ruthenium Complexes Having an OH Proton Donor and a RuH

as Hydride Donor 1867.4.1 The Shvo System 1867.4.2 Hydrogenation of Imines by Shvo Complexes 189

ContentsVIII

7.4.3 Dehydrogenation of Imines and Alcohols by Shvo Complexes 1917.4.4 Catalytic Hydrogenations with MetalLigand Bifunctional

Catalysis 1937.5 Catalytic Hydrogenation of Ketones by Strong Bases 1937.6 Conclusion 194


8 Homogeneous Hydrogenation by Defined Metal Clusters 199Roberto A. Snchez-Delgado

8.1 Introduction 1998.1.1 Is a Cluster the Real Catalyst? Fragmentation and Aggregation

Phenomena 2008.2 Hydrogenation of CC Bonds 2018.3 Hydrogenation of CC Bonds 2068.4 Hydrogenation of Other Substrates 2118.5 Concluding Remarks 212


9 Homogeneous Hydrogenation:Colloids Hydrogenation with Noble Metal Nanoparticles 217Alain Roucoux and Karine Philippot

9.1 Introduction 2179.2 Concepts 2179.2.1 Electrostatic Stabilization 2189.2.2 Steric Stabilization 2199.3 Hydrogenation of Compounds with CC Bonds 2209.3.1 Use of Polymers as Stabilizers 2209.3.2 Use of Non-Usual Polymers as Stabilizers 2219.3.3 Use of Dendrimers as Stabilizers 2259.3.4 Use of Surfactants as Stabilizers 2269.3.5 Use of Polyoxoanions as Stabilizers 2279.3.6 Use of Ligands as Stabilizers 2289.3.7 Biomaterial as a Protective Matrix 2329.3.8 Ionic Liquids used as Templates for the Stabilization

of Metal Nanoparticles 2339.3.9 Supercritical Microemulsions Used as Templates for the Stabilization

of Metal Nanoparticles 2369.3.10 Conclusion 2389.4 Hydrogenation of Compounds with CC Bonds 2389.5 Arene Hydrogenation 2419.6 Hydrogenation of Compounds with CO Bonds 2459.7 Enantioselective Hydrogenation 249

Contents IX

9.8 Conclusion 252Abbreviations 252References 253

10 Kinetics of Homogeneous Hydrogenations:Measurement and Interpretation 257Hans-Joachim Drexler, Angelika Preetz, Thomas Schmidt, and Detlef Heller

10.1 Introduction 25710.2 The Basics of Michaelis-Menten Kinetics 25910.3 Hydrogenation From a Kinetic Viewpoint 26310.3.1 Measurement of ConcentrationTime Data

and Possible Problems 26310.3.1.1 Monitoring of Hydrogenations via Hydrogen Consumption 26410.3.1.2 Monitoring of Hydrogenations by NMR and UV/Visible

Spectroscopy 27210.3.2 Gross-Kinetic Measurements 27710.3.2.1 Derivation of Michaelis-Menten Kinetics with Various

Catalyst-Substrate Complexes 27710.3.2.2 Data from Gross Kinetic Measurements 280


Part II Spectroscopic Methods in Homogeneous Hydrogenation

11 Nuclear Magnetic Resonance Spectroscopyin Homogeneous Hydrogenation Research 297N. Koen de Vries

11.1 Introduction 29711.1.1 Nuclear Magnetic Resonance (NMR) 29711.1.2 NMR in Homogeneous Hydrogenation Research 29811.2 NMR Methods 29911.2.1 General 29911.2.2 Chemical Shift 30011.2.2.1 General 30011.2.2.2 Chemical Shifts in Homogeneous Hydrogenation Research 30011.2.3 Coupling Constant 30111.2.4 2D-NMR 30211.2.4.1 General 30211.2.4.2 2D-NMR in Homogeneous Hydrogenation Research 30211.2.5 Variable Temperature and Variable Pressure Studies 30711.2.5.1 General 30711.2.5.2 Variable-Temperature Studies in Homogeneous Hydrogenation

Research 30711.2.5.3 Variable-Pressure Studies in Homogeneous Hydrogenation

Research 308

ContentsX

11.2.6 PGSE NMR Diffusion Methods 30911.3 Outlook 309


12 Parahydrogen-Induced Polarization: Applicationsto Detect Intermediates of Catalytic Hydrogenations 313Joachim Bargon

12.1 In-Situ Spectroscopy 31312.1.1 In-Situ NMR Spectroscopy 31312.1.2 In-Situ PHIP-NMR Spectroscopy 31412.2 Ortho- and Parahydrogen 31512.2.1 Magnetic Field Dependence of the PHIP-Phenomenon:

PASADENA and ALTADENA Conditions 31612.2.2 PHIP, CIDNP, and Radical Mechanisms 31812.2.3 Preparation of Parahydrogen 31912.2.3.1 Parahydrogen Enrichment 31912.2.3.2 High-Pressure Apparatus for Parahydrogen Enrichment 32012.2.3.3 Enrichment of Parahydrogen using Closed-Circuit

Cryorefrigeration 32112.2.4 Preparation of Orthohydrogen 32212.2.5 Thermal Conductivity Cells for Ortho/Para Determination 32212.2.6 Determination of the Ortho/Para Ratio 32312.2.7 Enrichment of Ortho- or Paradeuterium 32312.3 Applications of PHIP-NMR Spectroscopy 32412.3.1 In-Situ PHIP-NMR Spectroscopy of Homogeneous

Hydrogenations 32412.3.1.1 Activation of Dihydrogen 32412.3.1.2 Concepts of Reaction Mechanisms 32412.3.2 In-Situ PHIP-NMR Observation of Mono- and Binuclear Rhodium

Dihydride Complexes 32512.3.2.1 Reactions of [RhCl(NBD)]2 with Parahydrogen in the Presence

of Tertiary Phosphines 32512.3.2.2 Formation of the Binuclear Complexes

[(H)(Cl)Rh(PMe3)2(-Cl)(-H)Rh(PMe3)]and [(H)(Cl)Rh(PMe2Ph)2(-Cl)(-H)Rh(PMe2Ph)] 328

12.3.2.3 General Procedure for the Generation of the Complexes [Rh(H)2ClL3](L=Phosphine) 329

12.3.3.3 Intermediate Dihydrides of Cationic Rh Catalysts 32912.3.3.4 Obtaining Structural Information using 13C-Labeled Substrates 33212.4 Catalyst-Attached Products as Observable Intermediates 33512.4.1 Enantioselective Substrates 33612.4.2 Chiral Catalysts 33612.4.3 Determination of Kinetic Constants 338

Contents XI

12.4.4 Computer-Assisted Prediction and Analysisof the Polarization Patterns: DYPAS2 341

12.5 Colloidal Catalysts 34212.5.1 In-Situ PHIP-NMR Investigation of the Hydrogenation

of Ethynylbenzene by Pdx[N(octyl)4Cl]y 34212.6 Transfer of Proton Polarization to Heteronuclei 34412.6.1 General Aspects 34412.6.2 Polarization Transfer to 13C 34612.6.3 Polarization Transfer to 19F 35212.6.4 Parahydrogen-Assisted Signal Enhancement for Magnetic Resonance

Imaging 35312.7 Catalysts Containing other Transition Metals 35412.8 Summary and Conclusions 354

Acknowledgment 355Abbreviations 355References 356

13 A Tour Guide to Mass Spectrometric Studiesof Hydrogenation Mechanisms 359Corbin K. Ralph, Robin J. Hamilton, and Steven H. Bergens

13.1 Introduction 35913.2 A General Description of ESI-MS 36013.3 Mechanistic Hydrogenation Studies 36413.4 Conclusions 369


Part III Homogeneous Hydrogenation by Functional Groups

14 Homogeneous Hydrogenation of Alkynes and Dienes 375Alexander M. Kluwer and Cornelis J. Elsevier

14.1 Stereoselective Homogeneous Hydrogenation of Alkynesto Alkenes 375

14.1.1 Introduction 37514.1.2 Chromium Catalysts 37614.1.3 Iron Catalysts 37714.1.4 Ruthenium Catalysts 37814.1.5 Osmium Catalysts 38214.1.6 Rhodium Catalysts 38414.1.7 Iridium Catalysts 38614.1.8 Palladium Catalysts 38814.1.9 Conclusions 39414.2 Homogeneous Hydrogenation of Dienes to Monoenes 39414.2.1 Introduction 394

ContentsXII

14.2.2 Zirconium Catalysts 39514.2.3 Chromium Catalysts 39714.2.4 Ruthenium Catalysts 40014.2.5 Cobalt Catalysts 40214.2.6 Rhodium Catalysts 40214.2.7 Palladium and Platinum Catalysts 40614.2.8 Conclusions 408


15 Homogeneous Hydrogenation of Aldehydes, Ketones, Iminesand Carboxylic Acid Derivatives: Chemoselectivityand Catalytic Activity 413Matthew L. Clarke and Geoffrey J. Roff

15.1 Introduction 41315.2 Hydrogenation of Aldehydes 41415.2.1 Iridium Catalysts 41415.2.2 Rhodium Catalysts 41715.2.2.1 Rh-amine Catalysts 41715.2.2.2 Cationic Rhodium Phosphine Catalysts 41815.2.2.3 Water-Soluble Rh Catalysts 41915.2.3 Ruthenium Catalysts 42015.2.3.1 Ru-PPh3 Catalysts 42015.2.3.2 Polydentate Ru Catalysts 42115.2.3.3 Diamine-Modified Ru Catalysts 42215.2.3.4 Ru-TPPMS/TPPTS Catalysts 42315.2.4 Other Metal Catalysts 42515.2.4.1 Copper 42515.2.4.2 Osmium 42515.3 Hydrogenation of Ketones 42615.3.1 Iridium Catalysts 42615.3.2 Rhodium Catalysts 42815.3.2.1 Rh-Phosphine Catalysts 42815.3.2.2 Water-Soluble Rh Catalysts 43015.3.3 Ruthenium Catalysts 43115.3.3.1 Ruthenium Carbonyl Clusters 43115.3.3.2 RuPPh3 Complexes 43115.3.3.3 Diamine-Modified Ru Catalysts 43315.3.3.4 Other Ru Catalysts 43415.3.4 Other Metal Catalysts 43515.3.4.1 Copper 43515.3.4.2 Metal Carbonyls 43615.4 Domino-Hydroformylation-Reduction Reactions 43615.4.1 Cobalt Catalysts 43615.4.2 Rhodium Catalysts 437

Contents XIII

15.5 Reductive Amination of Ketones and Aldehydes 43715.6 Hydroaminomethylation of Alkenes

(Domino Hydroformylation-Reductive Amination) 43915.7 Hydrogenation of Carboxylic Acid Derivatives 44115.7.1 Hydrogenation of Acids and Anhydrides 44215.7.2 Hydrogenation of Esters 44515.8 Summary and Outlook 450


16 Hydrogenation of Arenes and Heteroaromatics 455Claudio Bianchini, Andrea Meli, and Francesco Vizza

16.1 Introduction 45516.2 Hydrogenation of Arenes 45616.2.1 Molecular Catalysts in Different Phase-Variation Systems 45616.2.2 Molecular Catalysts Immobilized on Support Materials 46616.3 Hydrogenation of Heteroaromatics 47016.3.1 Molecular Catalysts in Different Phase-Variation Systems 47016.3.1.1 S-Heteroaromatics 47016.3.1.2 N-Heteroaromatics 47416.3.1.3 O-Heteroaromatics 47916.3.2 Molecular Catalysts Immobilized on Support Materials 47916.4 Stereoselective Hydrogenation of Prochiral Heteroaromatics 48116.4.1 Molecular Catalysts in Homogeneous Phase 48116.4.2 Molecular Catalysts Immobilized on Support Materials 484


17 Homogeneous Hydrogenation of Carbon Dioxide 489Philip G. Jessop

17.1 Introduction 48917.2 Reduction to Formic Acid 49017.2.1 Insertion Mechanisms 49417.2.2 Ionic Hydrogenation 49717.2.3 Concerted Ionic Hydrogenation 49817.2.4 Bicarbonate Hydrogenation 49817.2.5 Other Mechanisms 49917.3 Reduction to Oxalic Acid 49917.4 Reduction to Formate Esters 50017.4.1 In the Presence of Alcohols 50017.4.2 In the Presence of Alkyl Halides 50217.4.3 In the Presence of Epoxides 50317.5 Reduction to Formamides 50417.6 Reduction to Other Products 50617.7 Concluding Remarks 507

ContentsXIV


18 Dehalogenation Reactions 513Attila Sisak and Ott Balzs Simon

19 Homogeneous Catalytic Hydrogenation of Polymers 547Garry L. Rempel, Qinmin Pan, and Jialong Wu

20 Transfer Hydrogenation Includingthe Meerwein-Ponndorf-Verley Reduction 585Dirk Klomp, Ulf Hanefeld, and Joop A. Peters

21 Diastereoselective Hydrogenation 631Takamichi Yamagishi

22 Hydrogen-Mediated CarbonCarbon Bond Formation Catalyzedby Rhodium 713Chang-Woo Cho and Michael J. Krische

Part IV Asymmetric Homogeneous Hydrogenation

23 Enantioselective Alkene Hydrogenation:Introduction and Historic Overview 745David J. Ager

24 Enantioselective Hydrogenation: Phospholane Ligands 773Christopher J. Cobley and Paul H. Moran

25 Enantioselective Hydrogenation of Alkeneswith Ferrocene-Based Ligands 833Hans-Ulrich Blaser, Matthias Lotz, and Felix Spindler

26 The other Bisphosphine Ligands for Enantioselective AlkeneHydrogenation 853Yongxiang Chi, Wenjun Tang, and Xumu Zhang

27 Bidentate Ligands Containing a HeteroatomPhosphorus Bond 883Stanton H.L. Kok, Terry T.-L. Au-Yeung, Hong Yee Cheung,Wing Sze Lam, Shu Sun Chan, and Albert S.C. Chan

28 Enantioselective Alkene Hydrogenation: Monodentate Ligands 995Michel van den Berg, Ben L. Feringa, and Adriaan J. Minnaard

Contents XV

29 P,N and Non-Phosphorus Ligands 1029Andreas Pfaltz and Sharon Bell

30 Enantioselective Hydrogenation of Unfunctionalized Alkenes 1049Andreas Pfaltz and Sharon Bell

31 Mechanism of Enantioselective Hydrogenation 1073John M. Brown

32 Enantioselective Ketone and -Keto Ester Hydrogenations(Including Mechanisms) 1105Takeshi Ohkuma and Ryoji Noyori

33 Rhodium-Catalyzed Enantioselective Hydrogenationof Functionalized Ketones 1165Andr Mortreux and Abdallah Karim

34 Enantioselective Hydrogenation of C=N Functionsand Enamines 1193Felix Spindler and Hans-Ulrich Blaser

35 Enantioselective Transfer Hydrogenation 1215A. John Blacker

36 High-Throughput Experimentation and Ligand Libraries 1245Johannes G. de Vries and Laurent Lefort

37 Industrial Applications 1279Hans-Ulrich Blaser, Felix Spindler, and Marc Thommen

Part V Phase Separation in Homogeneous Hydrogenation

38 Two-Phase Aqueous Hydrogenations 1327Ferenc Jo and gnes Kath

39 Supercritical and Compressed Carbon Dioxide as Reaction Mediumand Mass Separating Agent for Hydrogenation Reactionsusing Organometallic Catalysts 1361Walter Leitner

40 Fluorous Catalysts and Fluorous Phase Catalyst Separationfor Hydrogenation Catalysis 1377Elwin de Wolf and Berth-Jan Deelman

ContentsXVI

41 Catalytic Hydrogenation using Ionic Liquids as Catalyst Phase 1389Peter Wasserscheid and Peter Schulz

42 Immobilization Techniques 1421Imre Tth and Paul C. van Geem

Part VI Miscellaneous Topics in Homogeneous Hydrogenation

43 Transition Metal-Catalyzed Regenerationof Nicotinamide Cofactors 1471Stephan Ltz

44 Catalyst Inhibition and Deactivationin Homogeneous Hydrogenation 1483Detlef Heller, Andr H.M. de Vries, and Johannes G. de Vries

45 Chemical Reaction Engineering Aspectsof Homogeneous Hydrogenations 1517Claude de Bellefon and Nathalie Pestre

Subject Index 1547

Contents XVII











V


Contents











ContentsVI


18.1 Introduction 51318.2 Catalytic Dehalogenation with Various Reducing Agents 51718.2.1 Molecular Hydrogen 51718.2.2 Simple and Complex Metal Hydrides 52018.2.3 Hydrosilanes and Hydrostannanes 52418.2.4 Hydrogen Donors other than Hydrides 52618.2.5 Biomimetic Dehalogenations 52818.2.6 Electrochemical Reductions 53218.2.7 Miscellaneous Reducing Methods 53318.3 Mechanistic Considerations 53418.3.1 Activation of the CX Bond 53518.3.1.1 Oxidative Addition 53518.3.1.2 -Bond Metathesis 53718.3.1.3 SN2 Attack of the Hydride Ligand 53818.3.1.4 1,2-Insertion 53818.3.2 Reaction Steps Involving the Reducing Agents 53818.3.3 Formation of the Product 53918.4 Concluding Remarks 540



19.1 General Introduction 54719.1.1 Diene-Based Polymers 54719.1.2 Hydrogenation of Diene-Based Polymers 54819.1.2.1 Heterogeneous Catalysts 54919.1.2.2 Homogeneous Catalysts 55019.2 Reaction Art 55119.2.1 Catalyst Techniques 55119.2.2 Hydrogenation Kinetic Mechanism 56519.2.2.1 Rhodium-Based Catalysts 56519.2.2.2 Ruthenium-Based Catalysts 56819.2.2.3 Osmium-Based Catalysts 57119.2.2.4 Palladium Complexes 57219.2.3 Kinetic Mechanism Discrimination 57319.3 Engineering Art 57319.3.1 Catalyst Recovery 57419.3.1.1 Precipitation 57519.3.1.2 Adsorption 57519.3.2 Solvent Recycling 57619.3.3 Reactor Technology and Catalytic Engineering Aspects 577

Contents VII

19.4 A Commercial Example: Production of HNBR via a HomogeneousHydrogenation Route 578

19.5 Future Outlook and Perspectives 579Abbreviations 579References 579


20.1 Introduction 58520.2 Reaction Mechanisms 58720.2.1 Hydrogen Transfer Reduction of Carbonyl Compounds 58820.2.1.1 Meerwein-Ponndorf-Verley Reduction and Oppenauer

Oxidation 58820.2.1.2 Transition Metal-Catalyzed Reductions 59020.2.2 Transfer Hydrogenation Catalysts for Reduction of CC Double

and Triple Bonds 59520.3 Reaction Conditions 59720.3.1 Hydrogen Donors 59720.3.2 Solvents 60020.3.3 Catalysts and Substrates 60120.3.4 Selectivity 60320.4 Related Reactions and Side-Reactions 60920.4.1 Aldol Reaction 60920.4.2 Tishchenko Reaction 60920.4.3 Cannizzaro Reaction 60920.4.4 Decarbonylation 61020.4.5 Leuckart-Wallach and Eschweiler-Clarke Reactions 61020.4.6 Reductive Acetylation of Ketones 61020.4.7 Other Hydrogen Transfer Reactions 61120.5 Racemizations 612


21 Diastereoselective Hydrogenation 631Takamichi Yamagishi

21.1 Introduction 63121.2 Hydrogenation of Alkenes, Ketones, and Imines 63121.3 Substrate-Directive Diastereoselective Hydrogenation 63821.3.1 Hydrogenation of Cyclic Alcohols with Endo- or Exo-Cyclic Olefinic

Bond 63821.3.2 Hydrogenation of Acyclic Allyl and Homoallyl Alcohols 65321.3.3 Ester Unit- or Amide-Directive Hydrogenation 66721.4 Hydrogenation of Dehydrooligopeptides 67121.5 Diastereoselective Hydrogenation of Keto-Compounds 676

ContentsVIII

21.5.1 Substrate-Directive Hydrogenation of Keto-Compounds 68121.5.2 Hydrogenation of Diketo Esters and Diketones 68421.6 Kinetic Resolution to Selectively Afford Diastereomers

and Enantiomers 69121.7 Kinetic Resolution of Keto- and Imino-Compounds 69421.8 Dynamic Kinetic Resolution 69721.9 Conclusions 701



22.1 Introduction and Mechanistic Considerations 71322.2 Reductive Coupling of Conjugated Enones and Aldehydes 71622.2.1 Intramolecular Reductive Aldolization 71622.2.2 Intermolecular Reductive Aldolization 72022.3 Reductive Coupling of 1,3-Cyclohexadiene and -Ketoaldehydes 72322.4 Reductive Coupling of Conjugated Enynes and Diynes

with Activated Aldehydes and Imines 72622.5 Reductive Cyclization of 1,6-Diynes and 1,6-Enynes 73322.6 Conclusion 736




23.1 Introduction 74523.2 Development of CAMP and DIPAMP 74623.3 DIOP 74923.4 Ferrocene Ligands 75323.4.1 Ferrocene Hybrids 75623.5 Atropisomeric Systems 75623.6 DuPhos 75823.7 Variations at Phosphorus 76023.8 Monophosphorus Ligands 76223.9 A Return to Monodentate Ligands 76223.10 Summary 763

References 764

Contents IX


24.1 Introduction and Extent of Review 77324.2 Phospholane Ligands: Synthesis and Scope 77424.2.1 Early Discoveries and the Breakthrough with DuPhos and BPE 77424.2.2 Modifications to the Backbone 77824.2.3 Modifications to the Phospholane Substituents 77924.2.4 Other Phospholane-Containing Ligands 78324.2.5 Related Phosphacycle-Based Ligands 78624.3 Enantioselective Hydrogenation of Alkenes 78824.3.1 Enantioselective Hydrogenation of -Dehydroamino Acid

Derivatives 78824.3.2 Enantioselective Hydrogenation of -Dehydroamino Acid

Derivatives 80124.3.3 Enantioselective Hydrogenation of Enamides 80624.3.4 Enantioselective Hydrogenation of Unsaturated Acid

and Ester Derivatives 81024.3.5 Enantioselective Hydrogenation of Unsaturated Alcohol

Derivatives 81624.3.6 Enantioselective Hydrogenation of Miscellaneous C=C Bonds 81924.4 Enantioselective Hydrogenation of C=O and C=N Bonds 82024.4.1 Enantioselective Hydrogenation of Ketones 82024.4.2 Enantioselective Hydrogenation of Imines and C=NX Bonds 82224.5 Concluding Remarks 823



25.1 Introduction 83325.2 Ligands with Phosphine Substituents Bound

to One Cyclopentadiene Ring 83525.3 Ligands with Phosphine Substituents Bound

to both Cyclopentadiene Rings 83525.3.1 Bppfa, Ferrophos, and Mandyphos Ligands 83625.3.2 Miscellaneous Diphosphines 83725.4 Ligands with Phosphine Substituents Bound

to a Cyclopentadiene Ring and to a Side Chain 83925.4.1 Josiphos 83925.4.2 Immobilized Josiphos and Josiphos Analogues 84125.4.3 Taniaphos 84225.4.3 Various Ligands 84325.5 Ligands with Phosphine Substituents Bound

only to Side Chains 844

ContentsX

25.6 Major Applications of Ferrocene Diphosphine-Based Catalysts 84725.6.1 Hydrogenation of Substituted Alkenes 84825.6.2 Hydrogenation of C=O and C=N Functions 848



26.1 Introduction 85326.2 Chiral Bisphosphine Ligands 85326.2.1 Atropisomeric Biaryl Bisphosphine Ligands 85326.2.2 Chiral Bisphosphine Ligands Based on DIOP Modifications 86026.2.3 P-Chiral Bisphosphine Ligands 86126.2.4 Other Bisphosphine Ligands 86226.3 Applications in Enantioselective Hydrogenation of Alkenes 86426.3.1 Enantioselective Hydrogenation of -Dehydroamino Acid

Derivatives 86426.3.2 Enantioselective Hydrogenation of Enamides 86626.3.3 Enantioselective Hydrogenation of (-Acylamino) Acrylates 86826.3.4 Enantioselective Hydrogenation of Enol Esters 87026.3.5 Enantioselective Hydrogenation of Unsaturated Acids and Esters 87226.3.5.1 ,-Unsaturated Carboxylic Acids 87226.3.5.2 ,-Unsaturated Esters, Amides, Lactones, and Ketones 87426.3.5.3 Itaconic Acids and Their Derivatives 87426.3.6 Enantioselective Hydrogenation of Unsaturated Alcohols 87526.4 Concluding Remarks 877

References 877


27.1 Introduction 88327.2 Aminophosphine-Phosphinites (AMPPs) 88327.3 Bisphosphinamidite Ligands 90727.4 Mixed Phosphine-Phosphoramidites and Phosphine-Aminophosphine

Ligands 91827.5 Bisphosphinite Ligands (One PO Bond) 92427.6 Bisphosphonite Ligands (Two PO Bonds) 97827.7 Bisphosphite Ligands (Three PO Bonds) 98027.8 Other Mixed-Donor Bidentate Ligands 98127.9 Ligands Containing Neutral S-Donors 983


Contents XI


28.1 Introduction 99528.2 Monodentate Phosphines 99728.3 Monodentate Phosphonites 100028.4 Monodentate Phosphites 100028.5 Monodentate Phosphoramidites 100528.6 Monodentate Phosphinites, Aminophosphinites,

Diazaphospholidinesand Secondary Phosphine Oxides 1010

28.7 Hydrogenation of N-Acyl--Dehydroamino Acids and Esters 101128.8 Hydrogenation of Unsaturated Acids and Esters 101428.9 Hydrogenation of N-Acyl Enamides, Enol Esters

and Enol Carbamates 101628.10 Hydrogenation of N-Acyl--Dehydroamino Acid Esters 102028.11 Hydrogenation of Ketones and Imines 102128.12 Conclusions 1023



29.1 Introduction 102929.2 Oxazoline-Derived P,N Ligands 103029.2.1 Phosphino-oxazolines 103029.2.2 Phosphite and Phosphinite Oxazolines 103329.2.3 Oxazoline-Derived Ligands Containing a PN Bond 103629.2.4 Structurally Related Ligands 103829.3 Pyridine and Quinoline-Derived P,N Ligands 104029.4 Carbenoid Imidazolylidene Ligands 104229.5 Metallocenes 104329.6 Other Ligands 104429.7 Conclusions 1046





ContentsXII










41 Catalytic Hydrogenation using Ionic Liquids as Catalyst Phase 1389Peter Wasserscheid and Peter Schulz


Contents XIII





Subject Index 1547

ContentsXIV











V


Contents














ContentsVI

21 Diastereoselective Hydrogenation 631Takamichi YamagishiReferences 708










Contents VII


30.1 Introduction 104930.2 Terminal Alkenes 105030.2.1 2-Aryl-1-Butenes 105030.2.2 Other Terminal Alkenes 105430.3 Trisubstituted Alkenes 105630.3.1 Introduction 105630.3.2 Ir Catalysts 105730.3.3 Standard Test Substrates 105730.3.4 Other Substrates 106330.4 Tetrasubstituted Alkenes 106630.4.1 Substrates 106630.5 Dienes and Trienes 106730.6 Conclusions 1069



31.1 Introduction 107331.2 Rhodium-Catalyzed Hydrogenations 107431.2.1 Background 107431.2.2 More Recent Developments 107631.2.3 Transient and Reactive Intermediates in Rhodium Enantioselective

Hydrogenation 107831.2.4 Mnemonics for the Sense of Enantioselective Hydrogenation 108231.2.5 Status of the Computational Study of Rhodium-Complex-Catalyzed

Enantioselective Hydrogenation 108231.2.6 Monophosphines in Rhodium-Complex-Catalyzed Enantioselective

Hydrogenation 108631.2.7 Mechanism of Hydrogenation of -Dehydroamino Acid

Precursors 108731.2.8 Current Status of Rhodium Hydrogenations 108831.3 Ruthenium-Complex-Catalyzed Hydrogenations 109331.3.1 Reactive Intermediates in Ruthenium-Complex-Catalyzed

Hydrogenations 109331.3.2 Kinetic Analysis of Ruthenium-Complex-Catalyzed

Hydrogenations 109331.4 Iridium-Complex-Catalyzed Hydrogenations 109431.4.1 Background 109431.4.2 Mechanistic and Computational Studies 109531.4.3 Counter-Ion Effects 109731.5 Summary and Conclusions 1098

Acknowledgments 1099

ContentsVIII



32.1 Chiral Ligands 110532.2 -Keto Esters and Analogues 110732.2.1 -Keto Esters 110732.2.2 1,3-Diketones 112232.2.3 -Keto Phosphonates, Sulfonates, and Sulfones 112532.2.4 Dynamic Kinetic Resolution 112732.3 Simple Ketones 113132.3.1 Alkyl Aryl Ketones 113132.3.2 Hetero-Substituted Aromatic Ketones 114132.3.3 Diaryl Ketones 114432.3.4 Heteroaromatic Ketones 114432.3.5 Dialkyl Ketones 114732.3.6 Unsaturated Ketones 114832.3.7 Kinetic Resolution and Dynamic Kinetic Resolution 115032.3.8 Enantioselective Activation and Deactivation 1154



33.1 Introduction 116533.2 Basic Principles of Ketone Hydrogenation

on Rhodium Catalysts 116633.3 Enantioselective Hydrogenation of Ketoesters 116633.3.1 Enantioselective Hydrogenation of Ketopantoyllactone (KPL) 116633.3.2 Hydrogenation of Ketoesters and Ketoamides 117233.3.2.1 -Ketoesters and Ketoamides 117233.3.2.2 ,-Diketoesters 117633.3.3 Hydrogenation of Amino Ketones 117733.3.3.1 -Amino Ketones 117733.3.3.2 - and -Amino Ketones 118433.4 Enantioselective Hydrogenation of Fluoroketones 118633.5 Conclusions 1188

Abbreviations and Acronyms 1189References 1189

Contents IX


34.1 Introduction 119334.2 Chiral Ligands 119534.3 N-Aryl Imines 119734.4 N-Alkyl Imines 120034.5 Cyclic Imines and Heteraromatic Substrates 120234.6 Miscellaneous C=NX Systems 120434.7 Enamines 120634.8 Mechanistic Aspects 120734.9 Alternative Reduction Systems 120934.10 Assessment of Catalysts and Conclusions 121034.10.1 Iridium Complexes 121034.10.2 Rhodium Complexes 121134.10.3 Ruthenium Complexes 121134.10.4 Titanium Complexes 1211



35.1 Introduction 121535.2 Homogenous Metal Catalysts 121635.2.1 Early studies 121635.2.2 Group VIII Metal Catalysts 121735.2.3 Chiral Ligands 121835.2.4 Immobilized Ligands 122035.2.5 Water-Soluble Ligands 122135.2.6 Catalyst Selection 122135.2.7 Catalyst Preparation 122235.2.8 The Reaction Mechanism 122335.3 Hydrogen Donors 122435.3.1 The IPA System 122435.3.2 The TEAF System 122535.3.3 Other Hydrogen Donors 122935.4 Substrates and Products 122935.4.1 Aldehydes 122935.4.2 Ketones 122935.4.3 Aldimines 123135.4.4 Ketimines 123235.4.5 Alkenes 123535.5 Solvents 123535.6 Reaction Conditions, Optimization, and Scale-Up 123635.6.1 Temperature 1236

ContentsX

35.6.2 Productivity 123735.6.3 Reaction Control 123835.6.4 Large-Scale Processes 123935.7 Discussion 1239



36.1 Introduction 124536.2 High-Throughput Experimentation 124836.2.1 Serial Mode 124836.2.2 Parallel Experimentation 124936.2.3 Combinatorial Protocols 124936.3 Generating and Testing Libraries of Catalysts and Ligands 125036.3.1 Libraries of Individually Synthesized Ligands 125036.3.2 Automated Synthesis of Ligand Libraries 125836.3.3 Mixtures of Chiral Monodentate Ligands 126336.3.4 Mixtures of Chiral Monodentate Ligands

and Nonchiral Ligands 126736.3.5 Supramolecular Approaches to Ligand Libraries 127036.4 Methodology for Testing Catalysts 127236.5 High-Throughput Analysis 127336.6 Conclusions 1274



37.1 Introduction and Scope of the Chapter 127937.2 Requirements for Technical-Scale Applications 128037.2.1 Catalyst Performance 128137.2.2 Availability and Cost of the Catalyst 128137.2.3 Development Time 128237.3 Process Development and Equipment 128337.4 Industrial Processes: General Comments 128437.5 Chemo- and Diastereoselective Hydrogenations 128637.6 Enantioselective Hydrogenation of C=C Bonds 128737.6.1 Dehydro -Amino Acid Derivatives 128737.6.1.1 L-Dopa (Monsanto, VEB Isis-Chemie) 128837.6.1.2 Aspartame (Enichem/Anic, Degussa) 128937.6.1.3 Various Pilot- and Bench-Scale Processes for -Amino

Acid Derivatives 128937.6.2 Dehydro -Amino Acid Derivatives 129237.6.3 Simple Enamides and Enol Acetates 1293

Contents XI

37.6.4 Itaconic Acid Derivatives 129337.6.5 Allylic Alcohols and ,-Unsaturated Acids 129437.6.5.1 Allylic Alcohols 129537.6.5.2 ,-Unsaturated Acids 129637.6.6 Miscellaneous C=C Systems 129837.6.6.1 Hydrogenation of a Biotin Intermediate (Lonza) 129937.6.6.2 Synthesis of (+)-Methyl cis-Dihydrojasmonate (Firmenich) 130037.6.6.3 Intermediate for Tipranavir (Chirotech) 130037.6.6.4 Various C=C Substrates 130237.7 Enantioselective Hydrogenation of C=O Bonds 130237.7.1 -Functionalized Ketones 130237.7.2 -Functionalized Ketones 130537.7.3 Aromatic Ketones 130737.8 Enantioselective Hydrogenation of C=N Bonds 130837.9 Ligands and Metal Complexes for Large-Scale Applications 131137.9.1 Companies Offering Services, Technology, Ligands

and Catalysts 131237.9.2 Chiral Ligands with Established Industrial Performance 131337.9.3 Metal Complexes and Anions 131337.9.4 Intellectual Property Aspects 131737.10 Conclusions and Future Developments 1317




38.1 Introduction 132738.2 Two-Phase Hydrogenation of Alkenes, Alkynes, and Arenes 133438.3 Enantioselective Hydrogenation of Alkenes in Two-Phase Aqueous

Systems 133838.4 Aqueous Two-Phase Hydrogenation of Aldehydes and Ketones 134438.5 Aqueous Two-Phase Hydrogenations of Nitro-Compounds, Imines,

Nitriles, Oximes, and Heteroaromatics 135238.6 Conclusions 1354


ContentsXII


39.1 Introduction 136139.2 The Molecular and Reaction Engineering Basis

of Organometallic-Catalyzed Hydrogenations using Compressedand scCO2 1362

39.2.1 Control of Hydrogen Availability 136239.2.2 Catalyst Recycling and Immobilization 136339.2.2.1 Solubility Control for Separation 136439.2.2.2 Membrane Separation 136439.2.2.3 Biphasic Liquid/Supercritical Systems 136439.2.2.4 Inverted Biphasic Systems 136439.2.2.5 Solid-Supported Catalysts 136539.2.3 Catalytic Systems for Hydrogenation using SCFs,

and their Synthetic Applications 136539.2.4 Mechanistic Aspects 137139.3 Conclusions and Outlook 1373



40.1 Introduction 137740.2 Catalysts Based on Fluorous Alkylphosphines, -Phosphinites,

-Phosphonites, and -Phosphites 137840.3 Catalysts Based on Perfluoroalkyl-Substituted Arylphosphines 138040.4 Fluorous Anions for the Separation of Cationic Hydrogenation

Catalysts 138440.5 Catalysts Based on Nonphosphorus Ligands 138640.6 Enantioselective Hydrogenation Catalysts 138640.7 Conclusions 1386

Abbreviations 1387References and Notes 1387

41 Catalytic Hydrogenation using Ionic Liquidsas Catalyst Phase 1389Peter Wasserscheid and Peter Schulz

41.1 Introduction to Ionic Liquids 138941.2 Homogeneous Catalyzed Hydrogenation in Biphasic LiquidLiquid

Systems 139441.2.1 Hydrogenation of Olefins 139441.2.2 Hydrogenation of Arenes 1397

Contents XIII

41.2.3 Hydrogenation of Polymers 140041.2.4 Stereoselective Hydrogenation 140141.2.5 Ketone and Imine Hydrogenation in Ionic Liquids 140741.2.6 Imine Hydrogenation 141141.3 Homogeneous Catalyzed Hydrogenation

in Biphasic Ionic Liquid/Supercritical (sc)CO2 System 141241.4 Supported Ionic Liquid Phase Catalysis 141341.5 Conclusion 1416



42.1 Introduction 142142.2 Engineering and Experimental Aspects 142242.3 Immobilization Methods 142442.3.1 Physical Methods of Immobilization 142642.3.1.1 Physisorption of Metal Complexes 142742.3.1.2 Weak Chemisorption: Supported Hydrogen-Bonded (SHB)

Catalysts 142742.3.2 Encapsulated Homogeneous Catalysts 143042.3.2.1 Synthesis of SIB Catalysts 143142.3.2.2 Application of SIB Catalysts 143342.3.3 Catalysts Entangled in a Polymer 143442.3.4 Catalyst Dissolved in a Supported Liquid-Phase 143542.3.4.1 Supported Aqueous-Phase Catalysis 143642.3.4.2 Hybrid SLP Systems 143742.3.5 Covalently Bound Metal Centers 143842.3.6 Covalent Attachment of Ligands 143942.3.6.1 Grafting to Oxide Supports 144042.3.6.2 SolGel Method 144142.3.6.3 Anchoring with Organic Phosphonates 144242.3.6.4 Attachment to Polymer Supports 144442.3.6.4.1 Functionalized Polymers as Supports 144442.3.6.4.2 Enzymes as Support 144842.3.6.4.3 Functionalized Monomers 144842.3.6.4.4 Dendrimers as Supports: Membrane Filtration 145342.3.6.4.5 Grafting to Polymers 145442.3.7 Ionic Bonding of Metals to Supports 145542.3.7.1 Ionically Bound Metal Centers on Inorganic Supports 145542.3.7.2 Ionically Bound Metal Centers on Polymer Supports 145642.3.8 Attachment of Ligands via Ion Exchange 145742.4 Catalyst Deactivation 146142.5 Conclusions 146242.6 Outlook 1462

ContentsXIV




43.1 Introduction 147143.2 Enzymatic Cofactor Regeneration 147443.3 Electrochemical Cofactor Regeneration 147543.4 Chemical Cofactor Regeneration 147743.5 Other Chemical Cofactor Regeneration Procedures 147943.6 Conclusions and Outlook 1479



44.1 Introduction 148344.2 Mechanisms of Catalyst Inhibition 148444.3 Induction Periods 148544.3.1 Introduction 148544.3.2 Induction Period Caused by Slow Hydrogenation of COD

or NBD 148644.4 Substrate and Product Inhibition 149444.5 Reversible Inhibition Caused by Materials that can Function

as Ligand 149944.5.1 Catalyst Deactivation Caused by Solvents 150044.5.2 Catalyst Inhibition Caused by Compounds Containing

Heteroatoms 150344.5.3 Inhibition by CO and sources of CO 150444.5.4 Inhibition by Acids and Bases 150544.6 Irreversible Deactivation 150744.6.1 Inhibition by Anions 150744.6.2 Inhibition by Oxidation and by Ligand Modification 150744.6.3 Formation of Dimers, Trimers, Clusters, Colloids, and Solids 150944.7 Conclusions 1512


Contents XV


45.1 Introduction 151745.2 Fundamentals 151845.2.1 Basics of Mass Transfer in GasLiquid Systems 151845.2.2 Physical and Chemical Data for Hydrogenations 152145.2.2.1 Heat of Reaction 152245.2.2.2 Solubility 152245.2.2.3 Diffusivity 152545.2.3 Coupling Between Mass Transfer and a Single Homogeneous

Irreversible Reaction 152645.2.4 Coupling of Reaction and Mass Transfer in Ideal Reactors 153345.2.4.1 Mass Balance for a Batch Reactor 153445.2.4.2 Mass Balance for a CSTR Reactor 153545.2.4.2.1 Simplified Mass Balances 153545.2.4.3 Mass Balance for a Plug Flow Reactor 153645.3 Industrial Reactor and Scale-Up Issues 153645.4 Future Developments 1541

Nomenclature 1542Abbreviations 1544References 1544

Subject Index 1547

ContentsXVI

Homogeneous hydrogenation of organic compounds catalyzed by metal com-plexes is undoubtedly the most studied of the entire class of homogenously cat-alyzed reactions. Indeed, advances in hydrogenation systems have contributedsignificantly to progress in homogeneous catalysis more generally, mainly be-cause of the involvement of intermediate metal hydrides in a wider range of cat-alytic processes. The historical development of homogeneous hydrogenation isdocumented in my 1973 text on this topic, which was intended to represent anexhaustive treatise on the subject (the process, prior to the computer era, wascertainly exhausting as over 1900 multi-language references were compiled).

Before outlining the content of The Handbook of Homogeneous Hydrogenation,I will briefly note here a few early facts chronologically for the appropriate con-text. Melvin Calvin first used the term homogeneous hydrogenation in 1938for some non-aqueous, Cu-based systems, and a year later an M. Iguchi was thefirst to record the use of Rh species for hydrogenations in aqueous media. JackHalpern was the first to study (in the mid-1950s) the kinetics and detailedmechanisms of such hydrogenations, while notably R. J.P. (Bob) Williams wasthe first (in 1960) to suggest in an equation the possibility of an M(H2) species,long before their true characterization in the early 1980s! The majority of thesystems studied up to the early 1960s (for homogeneous catalysis generally, aswell as hydrogenations) were in aqueous media a fact frequently overlookedby current researchers but developments at that time in the isolation andcharacterization of transition metal hydrides (pioneered especially by JosephChatts group), including their stabilization by tertiary phosphines, led to in-creased studies in non-aqueous systems. Cleaner and greener aqueous sys-tems are preferred for industrial processes, and intense interest remains in theincorporation of, for example, water-solubility enhancing, polar groups (sulfo-nate, carboxylate, hydroxide, etc.) into phosphine-containing ligands, protona-tion of N-atoms in P-N donor ligand, and more general use of cationic or anion-ic species for catalysis. The completion of the cycle back to aqueous systems isnow in progress.

The classic 1961 paper by Halpern et al. (the al. being John Harrod and myself)on the catalytic hydrogenation of unsaturated acids using chlororuthenium(II)species in aqueous acid solutions certainly motivated the work of Geoffrey Wilk-insons group on Ru- and Rh-triphenylphosphine hydrogenation catalysts; these

XIX


Foreword

findings, published in the mid-1960s, are now legendary. The next highly signifi-cant step was the use of chiral phosphines with Rh precursors, first reported in1968 by the groups of Knowles and Horner, the work providing the first examplesof catalytic enantioselective hydrogenation (of unsaturated acids and -substitutedstyrenes). Thousands of subsequent publications have recorded the developmentof catalyst systems containing chiral ligands (such as phosphines, sulfoxides, ox-azolines, nitrogen-ligands, combinations of P/N/O/S-donors, carbenes, etc.) forhydrogenation of a wide range of prochiral substrates including alkenes, ketones,and ketimines. Processes reaching close to 100% enantiomeric excess (e.e.) are nolonger uncommon, and, in a few cases, a remarkable degree of understanding ofthe mechanistic pathways has been achieved. About one dozen industrial, catalyticenantioselective homogeneous hydrogenation processes are now operating, andthe potential for chiral catalyst systems within fine chemical industries (particular-ly for pharmaceuticals and agrochemicals) remains enormous. The first such pro-cess, that went on-line in 1970, was for the synthesis of L-dopa, a drug for treat-ment of Parkinsons disease; the system involved hydrogenation of a prochiral en-amide using a Rh-chiral phosphine catalyst. In the production of the herbicide Me-tolachlor, a process that went on-line in 1996, a chiral amine is generated byhydrogenation of a ketimine using an Ir catalyst, and this currently provides thelargest scale industrial process for an enantioselective synthesis of any type. Thediscovery and explanation of non-linear effects in enantioselective reactions, firstreported by Kagans group in 1986, are also noteworthy, and should lead to im-proved applications in enantioselective synthesis and, more importantly, a betterunderstanding of the origins of enantioselectivity.

Advances thus far in experimental enantioselective hydrogenation havestemmed largely from empirical studies. More trendy and certainly more effec-tive is high-throughput experimentation using ligand libraries, a methodologythat is being increasingly promoted by researchers in the fine-chemical indus-tries. Novel attempts to find the best catalyst by purely theoretical work that in-volves screening virtual catalyst libraries are also being published.

Hydrogenation catalysis in the petrochemical and related industries remainsin the domain of heterogeneous systems, because of the practicality of separat-ing and recycling the catalyst, although advances in the use of multiphase sys-tems might find eventually use in relatively small-scale systems where a re-quirement is high selectivity, a vital property that can be engineered with ahomogeneous catalyst. The design of supported metal complexes, includingdendrimers, the use of size-exclusion filtration methodology, and the use of bi-phasic systems with all their ramifications (fluorous solvents, ionic liquids, andsupercritical fluids), continue to be areas of intense current interest, and thefindings should lead to further industrial uses of homogeneous catalysts, partic-ularly in the small-scale synthesis of high value products.

The classic division between heterogeneous and homogeneous catalysts ap-pears to becoming increasingly blurred and, in some cases involving colloidal/nanoparticle and metal cluster catalysts, the difference is difficult to determineexperimentally. The large majority of reported homogeneous hydrogenation cat-

ForewordXX

alysts for aromatic residues now appear to be colloidal systems; in terms of ac-tivity within a particular reaction, the true nature of a catalyst may be con-sidered somewhat irrelevant, but this is key when catalyst separation/removalfor the purposes of recycling and residual toxicity levels is considered.

The exponential increase in the homogeneous hydrogenation literature overthe last three decades shows no sign of abatement, and indeed, with the re-placement of phosphine ligands by the increasingly popular carbenes, and theuse of various two- and multi-phase systems, a further endemic literature ex-pansion in homogeneous catalysis, and especially in the most understood areaof hydrogenation, is guaranteed.

There is no question that much general knowledge on homogeneous catalysishas stemmed from studies on homogeneous hydrogenation, and it is fitting thatThe Handbook of Homogeneous Hydrogenation is published about 50 years afterHalperns first reports on the mechanistic aspects of such reactions. The editorshave assembled an impressive list of eighty-one international experts that reviewthe field from several aspects noted above. The first six chapters are categorizedaccording to the catalyst metal used (most often the more traditional group 810 noble metals, although data on the early transition metals are presented),and there are chapters on the use of metal clusters and nanoparticles. A sepa-rate chapter appears on the kinetics commonly observed in hydrogenation sys-tems, and there is one chapter on ionic hydrogenations. Three well-known tech-niques for studying homogeneous hydrogenation are then each presented in achapter that discuss: NMR methods in general, the PHIP (parahydrogen in-duced polarization) NMR method, and the application of mass spectrometry.There are chapters on hydrogenation of organic substrates that are generally as-sembled according to the nature of the unsaturated function present in the or-ganic, while separate chapters describe hydrogen transfer processes, CO2 hydro-genation, and Rh-catalyzed, hydrogen-mediated, carbon-carbon bond formation.A large number of the chapters appropriately cover the many aspects of enantio-selective hydrogenation, including a synopsis of current industrial applications.The final chapters deal with the fundamental problem associated with applica-tions of homogeneous catalysis: deactivation, separation and recovery of the cat-alyst, and related engineering aspects.

The editors and authors are to be congratulated on assembling what is des-tined to become a classic in the area of Homogeneous Hydrogenation, whichover the years has earned its title in capital letters.

Brian R. James(University of British Columbia)

Foreword XXI

It is truly astonishing that such a simple reaction as the addition of one mole-cule of hydrogen to a double or triple bond can have so many facets.

When we had chosen the title of Handbook of Homogeneous Hydrogenationfor our book we meant it to be a comprehensive work of reference. In this re-spect we are quite satisfied. We only had to skip the chapter on dehydrogena-tions, for which we could not find an author. We are extremely grateful to theother 88 authors for dedicating so much of their valuable time to writing the 81marvellous chapters included in these volumes. We had envisaged an average of30 pages per chapter but in the end this was not enough, necessitating an ex-pansion of the two projected volumes to three.

One may wonder how long this handbook remains up-to-date. Indeed manyareas are continuously undergoing new developments. In addition, new topicsthat were hardly emerging five years ago seem to develop at a very fast pace.Colloidal hydrogenation catalysts, for instance, which until recently were seenas the Cinderella of both homogeneous and heterogeneous catalysis too solu-ble to be heterogeneous and too ill-defined to be homogeneous have becomequite respectable since they were recognized to be part of nanotechnology. Re-ductive coupling reactions can be considered as a green method to constructcarbon-carbon bonds without taking resort to leaving groups. Indeed, not onlythis class of reactions, but all hydrogenations are of course extremely environ-mentally benign. Also the number of substrates is continuously expanding; car-boxylic acid derivatives and heteroarenes are good examples of substrates re-cently added to the existing pool.

Just when everyone thought the chiral-ligand-boom was coming to an end, ex-tremely simple monodentate ligands turned out to be quite effective, also allow-ing a combinatorial approach using mixtures of ligands. There is now a bewil-dering choice of chiral ligands available, increasing the chances of application.Indeed, the number of industrial applications is steadily increasing; an impor-tant breakthrough in this area was the advent of high throughput experimenta-tion, which allowed for the first time to find a chiral ligand with good perfor-mance within a matter of weeks.

Our insight into the mechanisms of hydrogenation reactions has grown tre-mendously, thanks to advances in spectroscopic techniques, but also thanks tothe hard work of many organometallic chemists. Many authors now also recog-

XXIII


Preface

nise the importance of the rate of these reactions. Turnover frequencies of hy-drogenations are listed throughout the book.

One aspect that remains underdeveloped is the insight in deactivation path-ways. Our knowledge in this area is growing, but the pace is slow. We have de-voted an entire chapter to this topic, since the economics of many processescould benefit a lot from more insight in ways to reduce catalyst deactivation.

So far none of the industrial processes recycle the catalyst. Yet the number ofways to do this has grown far beyond simple immobilization. Two-phase cataly-sis now comes in many flavours.

Looking into the future, we expect that hydrogenation reactions will also betremendously important for the conversion of renewable resources. Going fromcarbohydrates to valuable chemicals will require deoxygenating reactions. Thus,hydrogenation of alcohols, aldehydes and carboxylic acids will become very im-portant topics.

We hope the readers will appreciate as well as enjoy the contents of this book.Any comments you may have are of course very welcome.

Hans de Vries September 2006Kees Elsevier

PrefaceXXIV

XXV


List of Contributors

David AgerDSM Pharma Chemicals9650 Strickland Road, Suite 103Raleigh NC 27615-1937USA

Terry T.-L. Au-YeungOpen Laboratory of ChirotechnologyInstitute of Molecular Technologyfor Drug Discovery and SynthesisDepartment of Applied Biologyand Chemical TechnologyThe Hong Kong PolytechnicUniversityHong Kong

Joachim BargonInstitute of Physical and TheoreticalChemistryUniversity of BonnWegelerstrae 1253115 BonnGermany

Sharon BellUniversity of BaselDepartment of ChemistrySt.-Johanns-Ring 194056 BaselSwitzerland

Claude de BellefonLaboratoire de Gnie des ProcdsCatalytiquesCNRS-ESCPE Lyon69616 VilleurbanneFrance

Steven H. BergensDepartment of ChemistryUniversity of AlbertaEdmontonAlbertaCanada T6G 2G2

Claudio BianchiniICCOM-CNRArea della Ricerca CNRVia Madonna del Piano snc500019 Sesto Fiorentina/FirenzeItaly

A. John BlackerAvecia Pharma (UK) Ltd.Research and DevelopmentLeeds RoadHuddersfieldHD1 9GAUK

List of ContributorsXXVI

Hans-Ulrich BlaserSolvias AGWRO-1055.6.28Klybeckstrasse 1914002 BaselSwitzerland

Elisabeth BouwmanLeiden Institute of ChemistryLeiden UniversityP.O. Box 95022300 RA LeidenThe Netherlands

John M. BrownChemical Research LaboratoryOxford UniversityOxford OX1 3TAUK

R. Morris BullockBrookahven National LaboratoryChemistry DepartmentUptonNew York 11973-5000USA

Daniel CarmonaDepartamento de Qumica InorgnicaInstituto Universitario de CatlisisHomogneaUniversidad de ZaragozaInstituto de Ciencia de Materialesde AragnC.S.I.C.-Universidad de ZaragozaZaragoza 50009Spain

Shu Sun ChanOpen Laboratory of ChirotechnologyInstitute of Molecular Technologyfor Drug Discovery and SynthesisDepartment of Applied Biologyand Chemical TechnologyThe Hong Kong PolytechnicUniversityHong Kong

Albert S.C. ChanOpen Laboratory of ChirotechnologyInstitute of Molecular Technologyfor Drug Discovery and SynthesisDepartment of Applied Biologyand Chemical TechnologyThe Hong Kong PolytechnicUniversityHong Kong

Yongxiang ChiDepartment of Chemistry104 Chemistry BuildingThe Pennsylvania State UniversityUniversity ParkPA 16802USA

Chang-Woo ChoUniversity of Texas at AustinDepartment of Chemistryand BiochemistryAustinTexas 78712USA

Hong Yee CheungOpen Laboratory of ChirotechnologyInstitute of Molecular Technologyfor Drug Discovery and SynthesisDepartment of Applied Biologyand Chemical TechnologyThe Hong Kong PolytechnicUniversityHong Kong

List of Contributors XXVII

Matthew L. ClarkeSchool of Chemistry,University of St. AndrewsSt. AndrewsFife KY16 9STUK

Christoper J. CobleyDowpharmaChirotech Technology LimitedThe Dow Chemical Company321 Cambridge Science ParkMilton Road,Cambridge CB4 0WGUK

Christophe CopretLaboratoire de ChimieOrganomtallique de SurfaceUMR 9986 CNRS CPE LyonCPE Lyon Bt. 30869616 Villeurbanne CedexFrance

Robert H. CrabtreeYale UniversityChemistry Department350 Edwards StreetNew HavenCT 06520-8107USA

Berth-Jan DeelmanArkema Vlissingen B.V.P.O. Box 704380 AB VlissingenThe Netherlands

Andr H.M. de VriesDSM Pharmaceutical ProductsAdvanced Synthesis, Catalysis,and DevelopmentP.O. 186160 MDGeleenThe Netherlands

Johannes G. de VriesDSM Pharmaceutical ProductsAdvanced Synthesis, Catalysis,and DevelopmentP.O. Box 186160 MD GeleenThe Netherlands

N. Koen de VriesDSM Research GeleenP.O. Box 186160 MD GeleenThe Netherlands

Elwin de WolfDebye InstituteDept. of Metal-Mediated SynthesisUtrecht UniversityPadualaan 83584 CH UtrechtThe Netherlands

Hans-Joachim DrexlerLeibniz-Institut fr OrganischeKatalyse an der Universitt Rostock e.V.Albert-Einstein-Str. 29a18059 RostockGermany

Cornelis J. ElsevierInstitute of Molecular ChemistryUniveristy of AmsterdamNiewe Achtergracht 1661018 WV AmsterdamThe Netherlands

Ben L. FeringaStratingh InstituteUniversity of GroningenNijenborgh 49747 AG GroningenThe Netherlands

List of ContributorsXXVIII

Robin J. HamiltonDepartment of ChemistryUniversity of AlbertaEdmontonAlbertaCanada T6G 2G2

Ulf HanefeldOrganic ChemistryDelft University of TechnologyJulianalaan 1362628 BL DelftThe Netherlands

Detlef HellerLeibniz-Institut fr Katalysean der Universitt RostockAlbert-Einstein-Str. 29a18059 RostockGermany

Philip G. JessopDepartment of ChemistryQueens University90 Bader LaneKingstonOntarioCanada K7L 3N6

Ferenc JoInstitute of Physical ChemistryUniversity of Debrecen1, Egyetem tr4010 DebrecenHungary

Abdallah KarimLaboratoire de Chimiede CoordinationFacult des Sciences SemlaliaUniversit Cadi AyyadBP 2390MarrakechMorocco

gnes KathInstitute of Physical ChemistryUniversity of Debrecen1, Egyetem trDebrecen4010 DebredenHungary

Dirk KlompOrganic ChemistryDelft University of TechnologyJulianalaan 1362628 BL DelftThe Netherlands

Alexander M. KluwerVant Hoff Institute for MolecularSciencesNieuwe Achtergracht 1661018 WV AmsterdamThe Netherlands

Stanton H.L. KokOpen Laboratory of ChirotechnologyInstitute of Molecular Technologyfor Drug Discovery and SynthesisDepartment of Applied Biologyand Chemical TechnologyThe Hong Kong PolytechnicUniversityHong Kong

Michael J. KrischeUniversity of TexasDepart. of Chemistryand Biochemistry1 University Station A5300Austin TX 78712-0165USA

List of Contributors XXIX

Wing Sze LamOpen Laboratory of ChirotechnologyInstitute of Molecular Technologyfor Drug Discovery and SynthesisDepartment of Applied Biologyand Chemical TechnologyThe Hong Kong PolytechnicUniversityHong Kong

Laurent LefortDSM Pharmaceutical ProductsAdvanced SynthesisCatalysis & DevelopmentP.O. Box 166160 MD GeleenThe Netherlands

Walter LeitnerLehrstuhl fr Technische Chemieund PetrolchemieInstitut fr Technischeund Makromolekulare ChemieRWTH AachenWorringer Weg 152070 AachenGermany

Matthias LotzSolvias AGP.O. Box4002 BaselSwitzerland

Stephan LtzInstitute of Biotechnology 2Research Centre Jlich52425 JlichGermany

Andrea MeliICCOM-CNRArea della Ricerca CNRVia Madonna del Piano snc500019 Sesto Fiorentina/FirenzeItaly

Adriaan J. MinnaardStratingh InstituteUniversity of GroningenNijenborgh 49747 AG GroningenThe Netherlands

Paul H. MoranDowpharmaChirotech Technology LimitedThe Dow Chemical Company321 Cambridge Science ParkMilton RoadCambridge CB4 0WGUK

Robert H. MorrisDepartment of ChemistryUniversity of Toronto80 St. George St.Toronto M5S 3H6Canada

Andr MortreuxLaboratoire de Catalyse de LilleUMR 8010 CNRS, USTL, ENSCLBP 9010859652, Villeneuve dAscq CedexFrance

Ryoji NoyoriDepartment of Chemistryand Research Centerfor Materials ScienceNagoya University ChikusaNagoya 464-8602Japan

List of ContributorsXXX

Taheshi OhkumaGraduate School of EngineeringHokkaido UniversityLaboratory of Organic SynthesisDivision of Molecular ChemistrySapporo 060-8628Japan

Luis A. OroDepartamento de Qumica InorgnicaInstituto Universitario de CatlisisHomogneaUniversidad de ZaragozaInstituto de Ciencia de Materialesde AragnC.S.I.C.-Universidad de ZaragozaZaragoza 50009Spain

Qinmin PanUniversity of WaterlooDepartment of Chemical EngineeringWaterlooOntarioCanada N2L 3G1

Paolo PelagattiDipartimento di Chimica Generale edInorganicaChimica Analitica, Chimica FisicaUniversit degli Studi di ParmaParco Area Scienze 17/A43100 ParmaItaly

Nathalie PestreLaboratoire de Gnie des ProcdsCatalytiquesCNRS-ESCPE Lyon69616 VilleurbanneFrance

Joop A. PetersOrganic ChemistryDelft University of TechnologyJulianalaan 1362628 BL DelftThe Netherlands

Andreas PfaltzUniversity of BaselDepartment of ChemistrySt.-Johanns-Ring 194056 BaselSwitzerland

Karine PhilippotLaboratoire de Chimiede Coordination du CNRSUPR 8241205, route de Narbonne31077 Toulouse Cedex 04France

Angelika PreetzLeibniz-Institut frKatalyse an der Universitt Rostock e.V.Albert-Einstein-Str. 29a18059 RostockGermany

Corbin K. RalphDepartment of ChemistryUniversity of AlbertaEdmontonAlbertaCanada T6G 2G2

Garry L. RempelUniversity of WaterlooDepartment of Chemical EngineeringWaterlooOntarioCanada N2L 3G1

List of Contributors XXXI

Geoffrey J. RoffClarke Research GroupSchool of ChemistryUniversity of St. AndrewsSt. AndrewsFife KY16 9STUK

Alain RoucouxUMR CNRS 6052Synthses et Activationsde BiomolculesEcole Nationale Suprieure de Chimiede RennesInstitut de Chimie de RennesAve. du Gnral Leclerc35700 RennesFrance

Roberto A. Snchez-DelgadoBrooklyn College and the GraduateCenter of the City Universityof New YorkNew YorkUSA

Thomas SchmidtLeibniz-Institut fr OrganischeKatalyse an der Universitt Rostock e.V.Albert-Einstein-Str. 29a18059 RostockGermany

P. SchulzLehrstuhl fr ChemischeReaktionstechnikUniversitt ErlangenEgerlandstrae 391058 ErlangenGermany

Ott Balzs SimonDepartment of Organic Chemistry,University of VeszprmP.O. Box 158VeszprmHungary

Attila SisakResearch Group for Petrochemistry ofthe Hungarian Academy of SciencesP.O. Box 158VeszprmHungary

Felix SpindlerSolvias AGP.O. Box4002 BaselSwitzerland

Wenjun TangDepartment of Chemistry104 Chemistry BuildingThe Pennsylvania State UniversityUniversity ParkPA 16802USA

Marc ThommenSolvias AGP.O. Box4002 BaselSwitzerland

Imre TothDSM ResearchDepartment of Industrial Chemicals-Chemistry and TechnologyUrmonderbaan 226167 RD GeleenThe Netherlands

List of ContributorsXXXII

Michel van den BergStratingh InstituteUniversity of GroningenNijenborgh 49747 AG GroningenThe Netherlands

Paul C. van GeemDSM ResearchDepartment of Industrial Chemicals-Chemistry and TechnologyUrmonderbaan 226167 RD GeleenThe Netherlands

Francesco VizzaICCOM-CNRArea della Ricerca CNRVia Madonna del Piano snc500019 Sesto Fiorentina/FirenzeItaly

Peter WasserscheidRWTH AachenInstitut fr Technischeund Makromolekulare ChemieWorringer Weg 152056 AachenGermany

Jialong WuUniversity of WaterlooDepartment of Chemical EngineeringWaterlooOntarioCanada N2L 3G1

Takamichi YamagishiDepartment of Applied ChemistryGraduate School of EngineeringTokyo Metropolitan UniversityTokyoJapan

Xumu ZhangDepartment of Chemistry152 Davey LaboratoryUniversity ParkPennsylvania, PA 16802-6300USA


Part IIntroduction, Organometallic Aspectsand Mechanism of Homogeneous Hydrogenation

Luis A. Oro and Daniel Carmona

1.1Introduction

Homogeneous hydrogenation constitutes an important synthetic procedure andis one of the most extensively studied reactions of homogeneous catalysis. Thehomogeneous hydrogenation of organic unsaturated substrates is usually per-formed with molecular hydrogen, but it is also possible to derive hydrogen fromother molecules acting as hydrogen donors, such as alcohols; these are termedhydrogen transfer reactions. The impressive developments of coordination andorganometallic chemistry have allowed the preparation of a wide variety of solu-ble metal complexes active as homogeneous hydrogenation catalysts under verymild conditions. These complexes are usually derived from transition metals,especially late transition metals with tertiary phosphine ligands, having partiallyfilled d electron shells. These transition metal complexes present the ability tostabilize a large variety of ligands with a variability of the coordination numberand oxidation state. Among those ligands are unsaturated substrates containing-electron systems, such as alkenes or alkynes, as well as key -bonded ligandssuch as hydride or alkyl groups.

Although the reaction of hydrogen with alkenes is exothermic, the high acti-vation energy required constrains the reaction. Thus, the concerted addition ofhydrogen to alkenes is a forbidden process according to orbital symmetry rules.In contrast, transition metals have the appropriate orbitals to interact readilywith molecular hydrogen, forming metal hydride species, allowing the transferof the hydride to the coordinated alkene. Rhodium is a good example of suchtransition metals, and has played a pivotal role in the understanding of homoge-neous hydrogenation, providing clear examples of the two types of homoge-neous hydrogenation catalysts that formally can be considered, namely monohy-dride and dihydride catalysts.

3


1Rhodium

1.1.1Monohydride Hydrogenation Catalysts

Monohydride (MH) catalysts, such as [RhH(CO)(PPh3)3], react with substratessuch as alkenes, according to Scheme 1.1, yielding rhodiumalkyl intermediateswhich, by subsequent reaction with hydrogen, regenerate the initial monohy-dride catalyst. This mechanism is usually adopted by hydrogenation catalystswhich contain an MH bond.

1.1.2Dihydride Hydrogenation Catalysts

Many of these catalysts are derived from metal complexes which, initially, donot contain metal hydride bonds, but can give rise to intermediate MH2 (al-kene) species. These species, after migratory insertion of the hydride to the co-ordinated alkene and subsequent hydrogenolysis of the metal alkyl species, yieldthe saturated alkane. At first glance there are two possibilities to reach MH2 (al-kene) intermediates which are related to the order of entry of the two reactionpartners in the coordination sphere of the metal (Scheme 1.2).

1 Rhodium4

Scheme 1.1

Scheme 1.2

The hydride route involves the initial reaction with hydrogen followed by coor-dination of the substrate; the well-known Wilkinson catalyst [RhCl(PPh3)3] is arepresentative example. A second possible route is the alkene (or unsaturated)route which involves an initial coordination of the substrate followed by reactionwith hydrogen. The cationic catalyst derived from [Rh(NBD)(DIPHOS)]+

(NBD=2,5-norbornadiene; DIPHOS=1,2-bis(diphenyl)phosphinoethane) is awell-known example. The above-mentioned rhodium catalysts will be discussed,in the detail, in the following sections.

Homogeneous hydrogenation reactions by metal complexes have been investi-gated extensively during previous years. The first authoritative book on this sub-ject, containing interesting and detailed historical considerations, was written byJames, and appeared in 1973 [1]. Following this, other monographs [2, 3] werepublished, as well as several reviews and book chapters [4], reporting on the rap-id and impressive development of this field.

1.2The Early Years (19391970)

Calvin made the first documented example of homogeneous hydrogenation by me-tal compounds in 1938, reporting that quinoline solutions of copper acetate, at100 C, were capable of hydrogenating unsaturated substrates such as p-benzoqui-none [5]. One year later, Iguchi reported the first example of homogeneous hydro-genation by rhodium complexes. A variety of organic and inorganic substrates werehydrogenated, at 25 C, by aqueous acetate solutions of RhCl3, [Rh(NH3)5(H2O)]Cl3,or [Rh(NH3)4Cl2]Cl, whilst more inert complexes [Rh(NH3)6]Cl3 and [Rh(en)3]Cl3,were inactive [6]. The initial hydrogen reduction of these and other related rhodi-um(III) complexes with nitrogen donor ligands seems to proceed via hydride rho-dium intermediates formed by the heterolysis of hydrogen [1, 7]. In the case of theIguchi rhodium(III) catalysts, however, after some time, partial autoreduction torhodium metal occurred. Another seminal contribution of Iguchi, which appearedfew years later in 1942, was the observation of the ready absorption of hydrogen bycobalt cyanide aqueous solutions; the formed cobalt hydride, [CoH(CN)5]

, was seento be highly selective for the hydrogenation of conjugated dienes to monoenes [8].

During this period, the most significant advances in homogeneous hydrogena-tion catalysis have been the discovery of rhodium phosphine complexes. The hy-dridocarbonyltris(triphenylphosphine)rhodium(I) complex, [RhH(CO)(PPh3)3],was reported in 1963 [9], and its catalytic activity was studied in detail by Wil-kinson and coworkers a few years later [1013]. The most important rhodium cat-alyst, the chlorotris(triphenylphosphine)rhodium(I) complex, was prepared dur-ing the period 19641965 by several groups [14]. It is easily synthesized by treatingRhCl33H2O with triphenylphosphine in ethanol. It can also be prepared by dis-placement of the coordinated diene 1,5-cyclooctadiene from [RhCl(diene)]2 com-plexes [15]. Wilkinson and coworkers extensively studied the remarkable catalyticproperties of this complex, which is usually known as Wilkinsons catalyst. It was

1.2 The Early Years (19391970) 5

the first practical hydrogenation system to be used routinely under very mild con-ditions usually room temperature and atmospheric pressure of hydrogen. Thiscompound catalyzes the chemospecific hydrogenation of alkenes in the presenceof other easily reduced groups such as NO2 or CHO, and terminal alkenes in thepresence of internal alkenes [14b, 16]. The remarkable success of this catalyst in-spired the incorporation of chiral phosphines, which in turn prompted the birth ofthe catalytic enantioselective hydrogenation with pioneering contribution from thegroups of Knowles and Horner (see [38, 39, 45b] in Section 1.1.6).

The synthesis of cationic rhodium complexes constitutes another importantcontribution of the late 1960s. The preparation of cationic complexes of formula[Rh(diene)(PR3)2]

+ was reported by several laboratories in the period 19681970[17, 18]. Osborn and coworkers made the important discovery that these com-plexes, when treated with molecular hydrogen, yield [RhH2(PR3)2(S)2]

+ (S=sol-vent). These rhodium(III) complexes function as homogeneous hydrogenationcatalysts under mild conditions for the reduction of alkenes, dienes, alkynes,and ketones [17, 19]. Related complexes with chiral diphosphines have been veryimportant in modern enantioselective catalytic hydrogenations (see Section 1.1.6).

Rhodium(II) acetate complexes of formula [Rh2(OAc)4] have been used as hy-drogenation catalysts [20, 21]. The reaction seems to proceed only at one of therhodium atoms of the dimeric species [20]. Protonated solutions of the dimericacetate complex in the presence of stabilizing ligands have been reported as ef-fective catalysts for the reduction of alkenes and alkynes [21].

It is noteworthy to comment that the remarkable advances of experimentaltechniques made during the past few decades has allowed, in many cases, infor-mation to be obtained about key intermediates. As a consequence, detailed me-chanistic studies have now firmly established reaction pathways.

1.3The [RhH(CO)(PPh3)3] Catalyst

This complex was first prepared by Bath and Vaska in 1963 [9], and studied indetail by Wilkinson and coworkers some years later [10] as an active catalyst forhydrogenation [11], isomerization [12], and hydroformylation [13] reactions.

The crystal structure of the [RhH(CO)(PPh3)3] complex [22] shows a bipyrami-dal structure with equatorial phosphines. This coordinatively saturated 18-elec-tron complex should be considered strictly as a precatalyst (or catalyst precursor)which, after dissociation of PPh3 and creation of a vacant coordination site,yields the real catalytic species, [RhH(CO)(PPh3)2]. It should be remembered atthis point that homogeneous mechanisms involve multistep processes, charac-teristic of coordination and organometallic chemistry (e.g., ligand dissociationor substitution, oxidative addition, reductive elimination), and therefore severaltypes of intermediates are involved. The intermediates proposed by Wilkinsonand coworkers in 1968 [11], based on kinetic studies, are shown in Scheme 1.3.Thus, the first step is the ligand dissociation of PPh3 (step a), yielding

1 Rhodium6

[RhH(CO)(PPh3)2]. A vacant coordination site has been created and coordinationof the 1-alkene substrate to the [RhH(CO)(PPh3)2] catalyst is feasible (step b).This is followed by the migratory insertion of the hydride to the coordinated al-kene (step c), and then hydrogenolysis of the metal alkyl species to yield the satu-rated alkane. This hydrogenolysis proceeds, in this case, through two steps oxidative addition of H2 (step d), followed by reductive elimination to regeneratethe [RhH(CO)(PPh3)2] catalyst (step e). Further support for steps c and d hasbeen obtained by studying the reaction of [RhH(CO)(PPh3)2] with tetrafluoro-ethylene that yields the stable trans-[Rh(C2F2H)(CO)(PPh3)2] that, under reactionwith hydrogen and in the presence of phosphine, gives C2F2H2 and[RhH(CO)(PPh3)3] [13].

Rhodium species in oxidation states I and III are involved in the process. Rho-dium-catalyzed hydrogenations generally involve oxidative addition reactions, fol-lowed by the reverse process of reductive elimination in the final step. Anothercommon elimination process is the so-called -elimination, which accounts forthe frequent side reaction of isomerization of alkenes, according to Eq. (1):

1.3 The [RhH(CO)(PPh3)3] Catalyst 7

Scheme 1.3

RCH2CH2CH2 RCH2CH CH2 RCH2CHMe RCH CHMe 1M MH M MH

This reversibility explains the frequent isomerization of alkenes by metal hy-dride complexes, even in the absence of hydrogen. The formation of the second-ary alkyl should be unfavored when bulky ligands are present. This steric argu-ment explains why internal alkenes are isomerized by [RhH(CO)(PPh3)2] butare not competitively hydrogenated, as well as the high selectivity of this catalystfor the hydrogenation of terminal alkenes compared to 2-alkenes due to the low-ered stabi

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The Handbook of Homogeneous Hydrogenation 3527311610