Supported group II transition metal catalysts in liquid phase reactions using borrowing hydrogen methodology 1

TABLE OF CONTENTS PAGE Acknowledgement i Table of Contents ii Summary vi List of publications viii List of Tables ix List of Schemes xi List of Figures xiii CHAPTER 1 Introduction

ACKNOWLEDGEMENT

It has been a truly memorable learning journey in completing the research work and I would like to take this opportunity to acknowledge those who have been helping and supporting me along the way

First of all, I would like to express my gratitude to my supervisor, Associate Professor Dr Stephan Jaenicke for giving me the opportunity to work on the project in the research lab I truly appreciate his help, stimulating suggestions and encouragement throughout the project

I specially thank Associate Professor Dr Chuah Gaik Khuan for her untiring help and invaluable advice throughout the time of research and writing of this thesis

The support by Madam Toh of the Applied Chemistry lab and all the other members of the technical staff at NUS was indispensable for the success of my work I am very grateful for their help

I also acknowledge Miss Nie Yuntong, Mr Do Dong Minh, Mr Fan Ao,

Mr Wang Jie, Miss Gao Yanxiu, Miss Toy Xiu Yi, Miss Han Aijuan, Mr Goh Sook Jun, Mr Sun Jiulong and all the members of our research group, for their kind help and encouragement during my candidature

Especially, I would like to give my special thanks to my husband for believing in me and giving me the inspiration and moral support when it was most required I am also grateful to my parents, for their unconditional love, encouragement and motivation

Lastly, I am indebted to the National University of Singapore for providing me with a valuable research scholarship and for funding the project

TABLE OF CONTENTS

PAGE

Acknowledgement i

Table of Contents ii

Summary vi

List of publications viii

List of Tables ix

List of Schemes xi

List of Figures xiii

CHAPTER 1 Introduction 1.1 Supported group 11 nanosized transition metal catalysts in fine chemical synthesis 1

1.1.1 Synthesis of supported group 11 catalysts 1.1.2 Group 11 based catalysts in liquid phase reactions 1.2 Borrowing Hydrogen methodology in fine chemical synthesis 21 1.2.1 Activation of alkanes 1.2.2 Activation of alcohols 1.2.3 Activation of amines 1.3 Aims and outline of this thesis 36 References

CHAPTER 2 Catalyst Characterization Techniques

2.1 Nitrogen Porosimetry 46

2.2 XRD 50

2.3 TEM 53

2.4 X-ray photoelectron Spectroscopy 55

2.5 Temperature Programmed Desorption 58

2.6 Inductively Coupled Plasma Atomic Emission Spectroscopy 59

2.7 CO-adsorption IR 61

References CHAPTER 3 Oxidation of alcohols over supported Ag catalysts 3.1 Introduction 64

3.2 Experimental and Catalytic Testing 67

3.3 Results & Discussion 68

3.4 Conclusion 95

References CHAPTER 4 Alumina-entrapped Ag catalysts for N-alkylation of amines with alcohols via borrowing hydrogen methodology 4.1 Introduction 101

4.2 Experimental and Catalytic Testing 104

4.3 Results & Discussion 106

4.4 Conclusion 125 References

CHAPTER 5 Alumina-entrapped Ag catalysts for reductive amination

of alcohols using nitroarenes via borrowing hydrogen methodology

5.1 Introduction 130

5.2 Experimental and Catalytic Testing 132

5.3 Results & Discussion 133

5.4 Conclusion 146

References CHAPTER 6 Self-coupling of benzylamines over highly active and selective alumina-entrapped Cu catalysts to produce secondary benzylamines using borrowing hydrogen methodology 6.1 Introduction 150

6.2 Experimental and Catalytic Testing 154

6.3 Results & Discussion 155

6.4 Conclusion 171

References CHAPTER 7 Magnesia supported Ni catalysts modified with silver for the selective hydrogenation of benzonitrile 7.1 Introduction 174

7.2 Experimental and Catalytic Testing 178

7.3 Results & Discussion 179

7.4 Conclusion 197

References

CHAPTER 8 Conclusions

Summary

The borrowing hydrogen methodology is an interesting protocol for the activation of alcohols and amines towards nucleophilic substitution reactions The reaction sequence usually starts with the abstraction of a hydrogen molecule from the starting reagent R1-XH (X = O, NH,…) by a catalyst This generates an unsaturated species R1=X which can condense with R2 to form an unsaturated intermediate The abstracted hydrogen is then returned and hydrogenates this intermediate to generate the final product It is a very “green” and highly atom efficient protocol for C-C and C-N bond formation with very little byproducts and waste production This methodology had been developed with homogeneous catalysts for reactions such as N-alkylation, indirect Wittig reactions, and C-C bond formation reactions Heterogeneous catalysts have many advantages over homogenous ones such as easy separation and recovery The aim of this thesis was to investigate suitable heterogeneous catalysts for liquid phase reactions using the hydrogen borrowing methodology

Heterogeneous group 11 transition metals (Au, Ag and Cu) had been shown to be active in many liquid phase reactions like catalytic oxidation, catalytic hydrogenation and catalytic C-C coupling We developed a heterogeneous silver catalyst which is very active for the oxidative dehydrogenation of alcohols, with good selectivity to the corresponding aldehyde or ketone This hydride removal is the crucial step in the activation

of alcohols for subsequent coupling with suitable nucleophiles In the course

of this Thesis, catalysts were prepared based on well dispersed supported group 11 metals (Ag and Cu), and their activities were tested in a number of catalytic reactions including the N-alkylation of amines by alcohols, reductive

N-alkylation of nitroarenes by alcohols, and self-coupling of aromatic amines,

in all cases using the borrowing hydrogen methodology In these reactions, the group 11 metal was the active species We also investigated a hydrogenation reaction, where Ag by itself was essentially inactive However, when Ag was incorporated in a formulation with nickel, it was found to be able to greatly enhance the selectivity in the catalytic hydrogenation of benzonitrile to benzylamine

LIST OF PUBLICATIONS

(1) Journal papers

1 H H Liu, G K Chuah, S Jaenicke*, N-alkylation of amines by alcohols over alumina-entrapped Ag catalysts using “borrowing hydrogen” methodology, J Catal 292.(2012) 130

(2) Conference papers

1 Aerobic Alcohol Oxidation by supported Ag catalysts

H H Liu, G K Chuah, S Jaenicke*

(Poster at the 6th Asian-European Symposium on Metal Mediated Efficient Reactions, June 7-9, 2010, Singapore)

2 Investigation of hydrogen produced from the dehydrogenative oxidation of alcohols over Ag catalysts

H H Liu, G K Chuah, S Jaenicke*

(Poster at the 3rd Singapore Catalysis Forum, May 17, 2010, Singapore)

3 Selective hydrogenation of nitriles to primary amines over hetergeneous Nickel-silver catalyst in liquid phase

H H Liu, G K Chuah, S Jaenicke*,

(Poster at the 14th Asian Chemical Conference (ACC), Sep 5-8, 2011, Bangkok, Thailand)

4 Role of oxygen in dehydrogenation of alcohols over Ag/Al2O3

H H Liu, S Jaenicke, G K Chuah*

, (Poster at the 6th Asia-Pacific Congress on Catalysis (APCAT), Oct 13-17, 2013, Taipei, Taiwan)

5 Reduction amination of Reductive N-alkylation of nitro compounds with alcohols over entrapped Ag catalysts

H H Liu, G K Chuah, S Jaenicke, *

, (Poster at the 6th Asia-Pacific Congress on Catalysis (APCAT), Oct 13-17, 2013, Taipei, Taiwan)

LIST OF TABLES

Table 1-1 Basic physical properties of group 11 transition metals Table 1-2 Isoelectric point (IEP) of commonly used inorganic supports Table 1-3 Examples of group 11 metal catalysed oxidation reactions

Table 1-4 Examples of supported group 11 metal catalysed

hydrogenation reactions

Table 2-1 Parameters of XPS measurements

Table 3-1 Textural properties of screened supported Ag catalysts in the

benzyl alcohol oxidation

Table 3-2 Effect of hydrogen pre-treatment time at 300 °C on Ag

crystallite size for 10 wt % Ag/Al2O3

Table 3-3 XPS results for calcined and H2-treated 10 wt % Ag/Al2O3

Table 3-4 Catalytic dehydrogenation of benzyl alcohol to benzaldehyde

under oxygen flow

Table 3-5 Oxidation of various primary and secondary alcohols

catalysed by 10 wt % Ag/γ-Al2O3

Table 3-6 Effect of catalyst pre-treatment on hydrogen formation during

benzyl alcohol oxidation in the open system

Table 3-7 Conversion of benzyl alcohol and H2 detection under different

reaction conditions and catalyst pre-treatments

Table 4-1 Textural properties of the catalysts in the N-alkylation of

benzyl alcohols with anilines

Table 4-2 N-alkylation of aniline with benzyl alcohol over various

Table 4-5 Reaction studies and conditions in the N-alkylation of benzyl

alcohols with anilines

Table 5-1 N-alkylation of nitroarenes using alcohols

Table 5-2 Effect of the ratio benzyl alcohol/nitrobenzene on the yields

after 19 h

Table 5-3 Results of the reductive alkylation of nitroarenes with alcohols

Table 5-4 Reaction studies and conditions in the N-alkylation of

nitroarenes using alcohols

Table 6-1 Textural properties of the catalysts in the self-coupling of

benzyl amines tested

Table 6-2 Self-coupling of benzyl amine in the presence of different

catalysts

Table 6-3 Self coupling of various amines

Table 6-4 Reaction studies and conditions in the self-coupling of

benzylamines

Table 7-1 Chemical and textural properties of the catalysts used in

benzonitrile hydrogenation

Table 7-2 Total basicity of NixAgy/MgO catalysts

Table 7-3 XPS Binding energies for Ni-Ag catalysts on MgO supports

Table 7-4 Summary of the activities of catalysts in the benzonitrile

hydrogenation

LIST OF SCHEMES

Scheme 1-1 Proposed mechanism of nitroaromatic hydrogenation over

an Ag nanocluster

Scheme 1-2 Metal catalysed cross coupling

Scheme 1-3 Borrowing hydrogen scheme in fine chemical synthesis Scheme 1-4 Activation of alkane by borrowing hydrogen

Scheme 1-5 Activation of alcohol by borrowing hydrogen

Scheme 1-6 Types of reactions applied by the activation of alcohols

using borrowing hydrogen

Scheme 1-7 General strategy for the formation of N-heterocycles from

primary amine

Scheme 1-8 α-Alkylation of ketones by an oxidation/aldol/reduction

sequence

Scheme 1-9 Borrowing hydrogen in the β-functionalisation of alcohols

Scheme 1-10 C-C bond formation between two alcohols

Scheme 1-11 Activation of amines by borrowing hydrogen

Scheme 3-1 Proposed mechanism by Shimizu et al for the alcohol

dehydrogenation by Ag/Al2O3[40]

Scheme 3-2 Transformation of benzyl alcohol to benzaldehyde via (1)

reaction with oxygen and formation of water and (2) removal of hydrogen

Scheme 3-3 Surface restructuring and redispersion model of silver

crystallites under oxidation/reduction cyclic treatment

Scheme 3-4 Proposed pathways for (a) nonreduced and (b) reduced Ag

surface

Scheme 4-1 Hydroamination of an alkene or alkyne

Scheme 4-2 Hydrogen autotransfer process from alcohol

Scheme 4-3 N-alkylation of aniline with benzyl alcohol

alcohols catalysed by Ag/Al2O3

Scheme 5-1 Bifunctions of alcohols in the reductive N-alkylation of

nitroarenes with alcohols (1) hydrogen source for the reduction of nitro group (2) hydrogen source for the reduction of secondary imine

Scheme 5-2 Pathway of transfer hydrogenation of nitrobenzene by

benzyl alcohol

Scheme 5-3 A tentative pathway for the direct alkylation of nitroarenes

Scheme 6-1 (a) hydrogen autotransfer process for alcohols as

electrophiles (top) (b) hydrogen autotransfer process for amines as electrophiles (below)

Scheme 6-2 Proposed reaction pathway of the Cu/Al2O3 catalysed

self-coupling of amines

Scheme 7-1 Reaction scheme of benzonitrile hydrogenation after von

Braun [23]

Scheme 7-2 Stoichiometric equation of benzonitrile hydrogenation

Scheme 7-3 Proposed surface reaction mechanism for the hydrogenation

of benzonitrile

LIST OF FIGURES

Figure 1-1 Size effect observed for the oxidation of alcohols on the

surface of Pd nanoclusters

Figure 1-2 Steps leading to the preparation of gold nanoparticles

embedded inside spheres with double or single shells

Figure 1-3 TEM images of Au/AlOOH and crystallite size distribution

of Au in Au/AlOOH

Figure 1-4 Decarboxylative cross-coupling reaction mediated by silver

oxide

Figure 1-5 Alkane metathesis reaction

Figure 1-6 N-methylation of primary and secondary amines

Figure 1-7 N-alkylation of an amide

Figure 1-8 Cyclisation reactions of amino alcohols

Figure 1-9 Examples of ruthenium-catalysed N-heterocyclisation

reaction

Figure 1-10 Indirect Witting reaction on alcohols

Figure 1-11 Example of Ru catalysed indirect Wittig reaction on alcohols Figure 1-12 Palladium catalysed α-alkylation of ketones

Figure 1-13 Bromination of alcohols via temporary oxidation

Figure 1-14 Examples of alkylation of alcohols with other alcohols

Figure 1-15 Transamination of Primary Amines catalysed by the Shvo

Complex

Figure 2-1 BET plot

Figure 2-2 Different types of adsorption isotherms

Figure 2-3 Bragg condition for an incident plane wave of wavelength λ,

inclined at angle θ, illuminating a crystal structure with d hkl spacing

Figure 2-4 TEM principle: (a) diffracting mode and (b) imaging mode

Both modes can be interchanged by adjusting the objective and SAED

Figure 2-5 Example of XPS chemical shift for Si with different

Figure 3-1 (a) Adsorption-desorption isotherms and (b) pore size

distribution of Al2O3-supported samples with different silver loadings

Figure 3-2 XRD patterns of (a) Al2O3 and Al2O3-supported samples with

(b) 2 (c) 4 (d) 5 (e) 8 (f) 10 and (g) 12 wt % Ag

Figure 3-3 Powder XRD of 10 wt % Ag/Al2O3 after hydrogen treatment

at 300 °C for different times

Figure 3-4 TEM images of (a) calcined 10 wt.% Ag /Al2O3 (b) reduced

10 wt.% Ag /Al2O3 for 15 min (c)reduced 10 wt % Ag/Al2O3 for 30 min (d) reduced 10 wt.% Ag /Al2O3 for 60 min (e) reduced 10 wt.% Ag /Al2O3 for 120 min Histogram

of the particle sizes for (f) calcined sample (g) reduced sample -15 min (h) reduced sample 30 min (i) reduced sample 60 min (j) reduced sample 120 min

Figure 3-5 TEM images of 2 wt % Ag/Al2O3 (a) before and (b) after

annealing at 500 oC Histogram of the particle sizes for

2 wt % Ag/Al2O3 (c) before and (d) after annealing

Figure 3-6 Al 2p XPS spectra of Al2O3 support and 10 wt % Ag/Al2O3

catalyst after calcination in air and H2 pre-treatment for 30 min

Figure 3-7 Ag 3d XPS spectra of 10 wt % Ag/Al2O3 after calcination in

air and after H2 pre-treatment

Figure 3-8 O 1s XPS spectra of 10 wt % Ag/Al2O3 after calcination in

air and after H2 pre-treatment

Figure 3-9 Monitor of CO2 (a) and CO (b) signals during the CO TPR

of (i) air-calcined (ii) H2-treated 10 wt % Ag/Al2O3 catalysts for 15 min (iii) H2-treated 10 wt % Ag/Al2O3 catalysts for

30 min (iv) H2-treated 10 wt % Ag/Al2O3 catalysts for 60 min (v) H2-treated 10 wt % Ag/Al2O3 catalysts for 120 min

Figure 3-10 Determination of rate constant by plotting –ln(1-C) versus

time (a) treduction = 0 min (b) treduction = 5 min (c) treduction = 15 min (d) treduction = 30 min (e) treduction = 60 min (f) treduction =

120 min (g) treduction = 180 min

Figure 3-11 Effect of Ag crystallite size on catalytic dehydrogenation of

benzyl alcohol

Figure 4-1 (a) Nitrogen adsorption-desorption isotherms and (b) pore

size distribution of Ag/Al2O3 with (i) 0.29 (ii) 0.59 (iii) 1.2 (iv) 2.4 (v) 6.2 and (vi) 13 wt % Ag

Figure 4-2 TEM images of the (a) 0.59 (b) 2.4 wt %

(c) 6.2 wt % Ag/Al2O3

Figure 4-3 XRD diffractograms (a) γ-Al2O3 and Ag/Al2O3 with (b) 0.29

(c) 0.59 (d) 1.2 (e) 2.4 (f) 6.2 and (g) 13 wt % Ag

Figure 4-4 XRD diffractogram (i) commercial Al2O3 (ii) 2.4 wt % Ag/

commercial Al2O3 from wet impregnation method (crystallite size calculated to be 5.4 nm) (iii) 2.4 wt % Ag/ Al2O3 from sol-gel method

Figure 4-5 (a) Silver loading of Ag/Al2O3 catalysts on N-alkylation of

aniline by benzyl alcohol TOF values for the conversion of aniline given as the ratio of moles of aniline per mole Ag per hour (measured at t = 1 h) versus the loading of silver (b) TOF based on the number of surface Ag atoms for conversion of aniline to secondary amine/imine at 120 oC as

a function of average particle size of Ag in Ag/Al2O3catalysts

Figure 4-6 N-alkylation of aniline with benzyl alcohol in the presence

(▲) and absence () of 2.4 wt % Ag/Al2O3 (catalyst was removed by filtration after 2 h)

Figure 4-7 Reaction profile for the N-alkylation of aniline by benzyl

alcohol in the presence of 2.4 wt % Ag/ Al2O3 () Aniline

mmol, xylene 5 ml, catalyst 2.4 wt % Ag/Al2O3 165 mg,

Cs2CO3 100 mg, reaction time

GC conditions: starting temperature 80 oC, ramp 20 oC/min

Figure 5-1 Activities of the catalyst with the addition of fresh substrate

Reaction conditions as described in Table 5-1

Figure 5-2 (a) Silver loading of Ag/Al2O3 catalysts on N-alkylation of

nitrobenzene by benzyl alcohol TOF values for the conversion of aniline given as the ratio of moles of aniline per mole Ag per hour (measured at t = 1 h) versus the loading of silver (b) TOF based on the number of surface Ag atoms for conversion of nitrobenzene to secondary

amine/imine at 140 oC as a function of average particle size

of Ag in Ag/Al2O3 catalysts Reaction conditions as described in Table 5-1

Figure 5-3 N-alkylation of nitrobenzene with benzyl alcohol in the

presence (■) and absence (▲) of 2.4 wt % Ag/Al2O3

(catalyst was removed by filtration after 2 h) Reaction conditions: nitrobenzene 1 mmol, benzyl alcohol 6 mmol, catalyst 100 mg (metal 2.2 mol%), Cs2CO3 100 mg, 140 oC, flowing N2, 19 h

Figure 5-4 Time-yield plots for the N-alkylation of nitroarenes with

benzyl alcohol in the presence of Ag/Al2O3 Reaction conditions: nitrobenzene 1 mmol, benzyl alcohol 6 mmol, p-xylene 5 ml, catalyst Ag/Al2O3 100 mg, (■) conversion (◊) N-benzylaniline (▲) N-benzylideneaniline ()

Azobenzene (+) Aniline

Figure 6-1 (a) N2 adsorption isotherm of 5 wt % Cu/ Al2O3 and (b) the

corresponding pore size distribution

Figure 6-2 XRD (a) 5 wt % Cu/Al2O3 (b) 5 wt % Cu/Al2O3-WI

(c) 5 wt % Cu/ SiO2 (d) 5 wt % Cu/ ZrO2

Figure 6-3 TEM images of 5 wt % Cu/Al2O3 (avg size ~ 2.6 nm)

Figure 6-4 Self coupling of benzylamines in the presence (■) and

absence (□) of 2.4 wt % Ag/Al2O3 (catalyst was removed by filtration after 3 h)

Figure 6-5 Time-yield plots for the self-coupling of benzylamine in the

presence of 5 wt % Cu/Al2O3 (2.6 nm) Reaction conditions:

amine 2 mmol, p-xylene 5 ml, catalyst Cu/Al2O3 150 mg, conversion and selectivity obtained from a series of reactions (3, 6, 16, 20, 24 h) (■) conversion (□) dibenzylamine

(◊)N-benzylidene-1-phenylmethanamine

Figure 6-6 GC spectrum of self-coupling of benzylamines

Reaction conditions: amine 2 mmol, xylene 5 ml, catalyst

48 %; Selectivity (DBA) 10 %

GC conditions: starting temperature 80 oC, ramp 20 oC/min

Figure 6-7 GC spectrum of self-coupling of benzylamines

Reaction conditions: amine 2 mmol, xylene 5 ml, catalyst

5 wt % Cu/Al2O3 150 mg, reaction time 24 h Conversion

96 %; Selectivity(DBA) 94 %

GC conditions: starting temperature 80 oC, ramp 20 oC/min

Figure 7-2 N2 adsorption/desorption curves (a) and pore size distribution

(b) of (i) Ni2Ag18/MgO (ii) Ni4Ag16/MgO (iii) Ni10Ag10/MgO (iv) Ni15Ag5/MgO (v) Ni20/MgO (vi) MgO (a) N2 isotherm (b)

pore size distribution

Figure 7-3 (a) XRD patterns of (i) Ni2Ag18/MgO (ii) Ni4Ag16/MgO (iii)

Ni10Ag10/MgO (iv) Ni15Ag5/MgO (v) Ni20/MgO (b) TEM images of Ni10Ag10/MgO(Avg alloy size ~ 7 nm) (c) size distribution obtained from Fig 7-2(b)

Figure 7-4 CO2 TPD spectra of (i) MgO (ii) Ni2Ag18/MgO (iii)

Ni4Ag16/MgO (iv) Ni10Ag10/MgO (v) Ni15Ag5/MgO (vi)

Ni20/MgO

Figure 7-5 XPS spectra of (a) Ni 2p (b) Ag 3d and (c) Mg 2p for the

samples of (i) H2-reduced Ni2Ag18/MgO (ii) untreated

Ni10Ag10/MgO (iii) H2-untreated Ni10Ag10/MgO (iii) H2

reduced Ni20/MgO

Figure 7-6 Effect of composition on the activity for the benzonitrile

hydrogenation Reaction condition: BN 2 mmol, catalyst: 100 mg, ethanol:

10 ml, temp 100 oC, PH2 = 10 bar, 5 h

Figure 7-7 Effect of pressure and temperature on the activities of the

benzonitrile hydrogenation Reaction condition: (a) BN 2 mmol, catalyst: 100 mg, ethanol: 10 ml, temp 100 oC, 5 h (b) BN: 8 mmol, ethanol : 40 ml, catalyst: 400 mg, PH2 = 5 bar, temp 100 oC, 5 h (c) BN: 2 mmol, catalyst: 100 mg, ethanol

10 ml, PH2 = 10 bar, 5 h

Figure 7-8 Hydrogenation of benzonitrile with and without

Ni10Ag10/MgO (catalyst was removed by filtration after 1 h)

Figure 7-9 Reaction profile for the N-alkylation of aniline by benzyl

alcohol in the presence of Ni10Ag10/MgO Reaction conditions: BN 2 mmol, catalyst: 100 mg, ethanol: 10 ml, temp 100 oC, PH2 = 10 bar, 5 h, reaction was stopped at 1 h, 2

h , 3 h , 4 h and 5 h

Chapter 1

General Introduction

1.1 Supported nanosized transition metal catalysts in fine chemical synthesis

A catalyst is a material which can enhance the rate of the catalysed reaction; while it

is intimately involved in the reaction sequence and regenerated at the end of the reaction [1] Certain reaction steps can be accelerated, but no gain on the equilibrium can be achieved by the addition of a catalyst because the forward and reverse reactions are accelerated in the same magnitude (principle of microscopic reversibility) Catalysis is a vital technology in today’s world Approximately 90 % of our chemicals and materials are produced using catalysis at one stage or another The catalyst can either be dissolved in the reaction medium (homogeneous catalysis), or it can be a separate, normally solid, phase (heterogeneous catalysis) [1]

Industrially, heterogeneous catalysis is preferred The primary advantages of using a heterogeneous catalyst are ease of separation from the products, reusability of the catalyst, and improved efficiency due to stable active sites Heterogeneous catalysts are mostly applied in the form of bulk oxides or as supported metal catalysts, and they are used in the fabrication of a wide range of products like petrochemicals, fine chemicals, plastics, and fertilizers, or reduction of environmental pollution The comparatively high stability of a catalyst on a solid support makes the reactions less sensitive to ambient conditions, and the reactions are in most cases compatible with air, or water as reaction medium Heterogeneously catalysed reactions are therefore environmentally benign Many transition metal catalytic systems rely on homogeneous catalysts because of their high catalytic activity and selectivity However, homogeneous metal catalysis suffers from serious draw-backs such as metal contamination in the product due to lack of efficient separation, which is highly

undesirable from an industrial and environmental point of view Moreover, the homogeneous metal catalysts cannot be reused, which results in loss of expensive metals and is a serious economical disadvantage, whereas the heterogeneous catalyst can be recovered and reused by simple filtration, decantation and recently by magnetic separation [1] Simple work up protocols, easy handling of catalysts, metal contaminant free products and easy but effective reuse of the catalyst make heterogeneous catalysts the preferred alternative to the analogous homogeneous counterparts

In heterogeneous catalysis the reactants interact at the surface of the solid catalytically active phase Boudart formulated the definition for “structure sensitivity” [2,3]: a heterogeneously catalysed reaction is structure sensitive if its rate, referred to the number of active sites and thus expressed as turnover frequency, depends on the particle size of the active component or a specific crystallographic orientation of the exposed catalyst surface For a supported catalyst with particles of the active metal in the nanorange (<100 nm) (Figure 1-1), the surface metal atoms may occupy different types of sites, namely atoms with a high coordination number in the terraces and with

a low coordination number in edges and corners The relative proportion of these sites with respect to the total number of surface atoms will vary with the metal particle size Coordinatively saturated (terrace) and coordinatively unsaturated (edge and corner) surface atoms usually have different catalytic activities Kaneda et al observed that in the alcohol oxidation over Pd nanoclusters, only the low-coordinated Pd atoms were responsible for the catalysis [4] Similar observations were reported in the Heck [5] and Suzuki coupling [6] with polyvinylpyrrolidone (PVP)-stabilized Pd nanoparticles

Figure 1-1 Size effect observed for the oxidation of alcohols on the surface of Pd

where r is the radius of the particle The extreme limit would be to use single atoms,

but there is a strong thermodynamic driving force towards aggregation into larger entities, such that the existence of very small clusters is experimentally unconfirmed except at low temperatures or when stabilization is effected by suitable ligands or by

an environment not conducive to atomic movement Thus it would be a high demanding to prepare supported metal catalysts with the smallest possible metal

crystallites

Academic interest into the catalytic activities of supported nanosized transition metals is flourishing Many transition metals can adsorb the reactant easily so that they can participate in a surface reaction A good catalyst should not absorb the reactants so strongly that they are irreversibly bound to the metal rather than reacting with other molecules on the surface The transition metals most frequently used in catalysts belong to the groups 8 to 11, and particularly the group 11 transition metals

Au, Ag and Cu are receiving more and more attention due to their increasing applications in catalysis

1.1.1 Synthesis of supported group 11 catalysts

The Group 11 of the periodic table, also called the copper group or in the older nomenclature Group IB, includes the transition metals copper, silver, and gold All the elements of the group have been known since prehistoric times and are all relatively inert, corrosion-resistant metals Table 1-1 lists the basic physical properties of group

11 transitional metals Gold has a distinctive yellow colour and is extremely malleable and ductile Gold is the most electronegative of all metals, making it hard to be oxidized and very resistant to corrosion It is a very good conductor and is often used

to plate electrical contacts since it resists corrosion so well Silver is about twenty more abundant than gold At ambient temperature, pure silver metal is the best conductor of heat and of electricity Pure silver is too soft for jewellery and utensils,

so it is usually alloyed with at least one other metal Copper is the most abundant and least corrosion resistant of the three elements It has a characteristic ‘copper red’ colour, but due to surface oxidation, tarnishes quickly Its hardness can be improved

by alloying with other metals, making it a source for reliable tools and weapons

Table 1-1 Basic Physical Properties of Group 11 transition metals

Because of the relatively high cost of group 11 metals, they are often supported

on a carrier in order to utilize the atoms more efficiently The preparation of heterogeneous catalysts usually consists of three steps:

1 Contact of a metal precursor with the support material

2 Calcination of the resultant precatalyst precursor/support material

3 Formation of the active catalyst species via reduction

Introduction of metal precursors onto a suitable support can be accomplished by several established methods Commonly used methodologies for deposition of group

11 metals onto the support include impregnation, co-precipitation, deposition, ion exchange and steric stabilization strategies

Impregnation

The supported catalyst can be prepared by starting with a high surface area porous support, such as alumina, which is then dosed with a precursor for the active phase The impregnation can be achieved by various ways It can be done by adsorption from solution, that is, by adding the support to a solution of the active ingredient This

method can be modified by precipitation impregnation, in which the active phase is precipitated onto the support by, for instance, a sudden pH change in the mixture, or

by a chemical reaction The catalyst has then to be separated by filtering, and much of the solution may be wasted

In many ways a more controllable method is the “incipient wetness” technique The active phase is added as a solution to the dry powdered support until the mixture becomes slightly tacky This occurs when the pores of the support are filled with the liquid For example the Ag/γ-Al2O3 [7,9] catalyst prepared by Shimizu et al for a series of C-H activation reactions was prepared by impregnating γ-Al2O3 with a solution of AgNO3

Coprecipitation

The soluble precursor components for both the support and the active phase are mixed, and co-precipitation occurs by adjusting the pH or by addition of other salts, acids or bases One example of this method is the production of the Cu/ZnO/Al2O3 catalyst [10] for low temperature methanol synthesis Here, the Cu/ZnO/Al2O3 catalyst synthesis starts with a solution of the nitrates of copper, zinc and aluminum, followed by addition of Na2CO3 to allow the co-precipitation to occur The resulting gel is left to age, a process during which the chemical and physical structure of the solid changes slowly, and finally, the precipitate is recovered and washed thoroughly to remove Na+ions The catalyst is then dried and calcined The final active product is an intimate mix of copper oxide, zinc oxide and alumina as the support phase

Deposition-Precipitation

This procedure is somewhat similar to the coprecipitation method: it consists in the precipitation of a metal hydroxide or carbonate on the particles of a solid support

through the reaction of a base with the precursor of the metal By this method, metal hydroxide particles can be deposited inside the pores of the support, and the nucleation and growth on the support surface will therefore result in a uniform distribution of small particles However, rapid nucleation and growth in the bulk of the solution will lead to large crystallites and inhomogeneous distribution, since the large particles will be unable to enter into the pores, but will deposit only on the external surface Thus, to obtain the best results, an efficient mixing should be used together with slow addition of the alkaline solution in order to avoid the build up of local oversaturation The best base was reported to be urea [11] which is usually added at room temperature and slowly hydrolyzed generating ammonium hydroxide homogeneously through the solution by rising the temperature to 90 oC Besides urea, other bases such as KOH or NaOH can also be used The Au/TiO2 [12] catalyst reported by Cao’s group was prepared by a deposition of Au onto TiO2 at pH = 8 adjusted by addition of 0.2 M NaOH solution

Ion exchange

Inorganic oxides such as Al2O3, SiO2, TiO2, and MgO which are commonly used as support materials tend to polarize and their surfaces become charged once they are suspended in an aqueous solution The degree of charging is controlled by the pH of the solution according to these schematic equations:

In acidic media, the adsorption surface site (M-OH) is positively charged and will be surrounded by anions (Eq 1), while in basic media the acidic surface site (M-OH)

M-OH + H+A- M-OH2+ + A

-M-OH + OH- M-O- + H2O

(1) (2)

particular pH exists at which the surface will not be charged, and this pH is called PZC (point of zero charge) or IEP (isoelectric point) (Table 1-2) [13] If we immerse a material with PZC = 8 in a solution with a pH above its PZC, its surface will be negatively polarized and will adsorb cations, while the opposite will happen if the pH

of the solution is below the PZC: it will be positively charged and anionic species will adsorb on the surface

Table 1-2 Isoelectric point (IEP) of commonly used inorganic supports

Thus, the ions that adsorb on the support can be controlled by tuning (i) the type and concentration of metal precursor (ii) the pH of the aqueous solution, and (iii) the type of support For example, the Cu/SiO2 reported by Kohler et al [14] was prepared

by ion-exchange of [Cu(NH3)4]]2+ with silanol sites under basic conditions (normally

pH 11)

Steric stabilization strategies (yolk-shell or core-shell, entrapped)

Besides the methods discussed previous for the deposition of the active metal on the surface of the solid, strategies of encapsulation of the metal into the micro-meso-porous hosts such as metal oxides and metal organic framework (MOF) have been developed [15,16] For example, gold nanoparticles can be embedded within mono-disperse spheres that have double shells of porous silica and zirconia [17] After dissolving the middle silica shell, then gold nanoparticles are left floating inside the zirconia shell to form a yolk-shell structure (Figure 1-2) The free space between the nanoparticles and the ZrO2 shell prevents the metal from sintering but also helps the diffusion of substrates and products

Figure 1-2 Steps leading to the preparation of gold nanoparticles embedded inside

spheres with double or single shells [17]

Another strategy involves the entrapment or encapsulation of dissolved metal ions by gelation of the support material The method starts with the mixing of precursors for the support and active metal together to obtain a clear gel Then water

is added into the gel and the support precursor is hydrolysed to form a matrix structure The active metal was thus entrapped into the support matrix For example, Park et al used this method to entrapped Au [18] and Cu [19] catalysts for C-H activation reactions The active Au and Cu metals were entrapped into a fibrous

support, resulting in nanoparticles with a quite narrow crystallite size distribution (Figure 1-3)

Figure 1-3 (a) and (b) TEM images of Au/AlOOH (c) crystallite size distribution of

Au in Au/AlOOH [18]

After impregnation, the material undergoes a drying treatment which is generally performed at temperatures between 80 oC to 200 oC in order to eliminate the solvent used in the previous impregnation step Depending on the nature of the catalyst, the pre-catalyst is then subjected to a calcination process This treatment consists of heating the catalysts in an oxidizing atmosphere at a temperature usually as high or a little higher than that encountered during reaction During calcination, the metal precursor decomposes, and most organic molecules are removed as gaseous products (usually water, CO2) Volatile cations or anions which have been previously introduced will also be removed In most cases, the metal remains in the form of an oxide During calcination, some other processes can also take place: (i) sintering of the precursor or of the oxide to form bigger aggregates, and (ii) reaction of the latter

with the support In fact, in case of alumina as the support, calcination at temperatures around 500 oC – 600 oC can give rise to a chemical reaction with divalent metal (Ni,

Co, Cu) oxides which results in the formation of a catalytically inactive surface phase

of metal aluminates Sometimes, this thermal treatment step leads to well dispersed catalysts after reduction due to a textural effect For example, in the case of the group

8 transition metal Pt/Al2O3, a volcano type correlation was found between the metal dispersion and the catalytic properties vs the calcination or reduction temperature [13] and the optimal dispersion was obtained at about 400 – 500 oC A higher calcination temperature above 600 oC leads to a catalyst with lower dispersion because the Pt oxychloride complex decomposes to Pt oxide species that are mobile on the surface and tend to sinter at the high temperature

The final step in the preparation of supported nanoparticle heterogeneous catalysts is the transformation of the precatalyst to the active catalyst, typically by reduction under H2 The reducing gas or gas mixture is very important Particularly, it

is necessary to keep the water vapour pressure as low as possible because water formed during the reduction can be detrimental for a high dispersion of the metal High hydrogen flow rates help to remove the water from the support as soon as it is formed [20] The experimental conditions, such as the temperature or H2 pressure, can change the product, and the reduction step needs to be optimized for each individual supported metal precatalyst

1.1.2 Group 11 based catalysts in liquid phase reactions

The application of copper-group based heterogeneous catalysts in fine chemicals synthesis can be generally divided into: catalytic oxidation, catalytic hydrogenation and catalytic C-C bond formation The following sections give an overview of

reactions catalysed by group 11 metals

Table 1-3 Examples of oxidation reactions catalysed by Group 11 metals

Until 25 years ago, gold was considered to be catalytically inert [15,22] Haruta’s breakthrough discovery [23] that gold nanoparticles (NP) on reducible oxides were effective catalysts for CO oxidation at very low temperature initiated increasing interest in Au NPs After gold had been established as an powerful CO oxidation

metal Examples of oxidation reactions Catalyst used reference

Au CO oxidation to CO 2

cyclohexane oxidation to mixture of

cyclohexanol and cyclohexanone

propylene epoxidation to alcohols

Au/Ti-HMM Au/TS-1

Au/TiO 2

Au/ hydrotalcite Au/TiO 2

Au/C Au/CeO 2

Alcohol oxidation to carbonyls

Benzene oxidation to phenol

phenol oxidation

methanol synthesis from H 2 /CO

Ammonia oxidation to N 2 and N 2 O

CuO/CeO 2

Cu/hydrotalcite Cu/MCM-41, Cu/Zeolite, Cu/Al 2 O 3

CuO/C, CuO/ZSM-5 CuO/ZnO/Al 2 O 3

catalyst, it was also found to be active in the oxidation of alcohols, aldehydes, amines, hydrocarbons, and in the epoxidation of alkenes utilizing oxygen or air as oxidant [24-26]

Silver is a good catalyst for selective oxidation, and is used on a large scale for the controlled oxidation of ethylene to ethylene oxide and of methanol to formaldehyde While there is no detectable O2 adsorption on the Au surface at room temperature [27], oxygen diffuses readily into the silver lattice and forms different types of subsurface oxygen It is generally accepted that the particularly high activity and selectivity of silver for these reactions is due to its ability to activate molecular oxygen in a variety

of ways leading to the creation of different types of silver-bound oxygen species, which differentiate themselves in their electronic properties as well as in their location

on and in the silver catalyst [28] The first species is Oα, which is chemisorbed atomic oxygen catalysing the oxi-dehydrogenation of methanol to formaldehyde as well as the complete oxidation to CO2 and water It is highly reactive and exhibits a strongnucleophilic character It is characterized by a thermal desorption temperature at 573

K and a XPS binding energy of 530 eV The second species is bulk-dissolved oxygen

Oβ, which desorbs at 773 K and has a XPS binding energy centred at 530.3 eV The last species is referred to as strongly bound, intercalated oxygen species Oγ, with the thermal desorption starting at 973 K and an XPS binding energy of 529 eV It was reported that catalyst restructuring and the formation of different types of subsurface oxygen species can modify the silver surface electronically, which then affects the olefin adsorption, leading to high activity and selectivity [29] Silver has also been applied in various other oxidation reactions, such as the oxidation of alcohols [30], acceptorless dehydrogenation of alcohol [7] and CO oxidation to CO2 [31]

Copper-based catalysts are active in a wide range oxidation reaction as listed in

Table 1-3 Copper-containing zeolites have been used in the direct oxidation of benzene to phenol [32,33] Because of the high stability of benzene, the direct oxygenation of benzene to form phenol is one of the most challenging reactions from the point of view of industrial synthetic chemistry CuAlPO4-5 reported by Cheng’s group was identified an efficient catalyst in hydroxylation of alkyl-substituted benzenes The authors reported a phenol selectivity of near 100% using hydrogen peroxide as the oxidant over Cu-substituted molecular sieves [32] and the catalyst was resistant to leaching

Table 1-4 Hydrogenation reactions catalysed by supported group 11 metals

Au Alkynes hydrogenation

carbonyl compounds hydrogenation

nitro compounds hydrogenation

Ag carbonyl compounds hydrogenation

Nitro compounds hydrogenation

Ag/SiO 2

Ag/ γ-Al 2 O 3

[40,44] [8]

hydrogenation

As a challenging topic in chemistry, selective hydrogenation of α,β-unsaturated aldehydes (R1R2C=CH–CH=O) to unsaturated alcohols (R1R2C=CH–CH2OH) has been studied for a long time However, when conventional hydrogenation catalysts were used, the major products were almost always the saturated aldehydes or saturated alcohols because hydrogenation of the C=C bond of R1R2C=CH–CH=O is thermodynamically favoured over the hydrogenation of the C=O bond [38] Moreover, the C=C bond is more reactive than the C=O group due to kinetic reasons Claus et al synthesized a series of supported Au catalysts (Au/TiO2 and Au/ZrO2) which were active in the catalytic hydrogenation of acrolein [39] They prepared catalysts with gold particle size varying from 1.1 to 3.8 nm and found that the activity and selectivity to the desired allyl alcohol increased over the catalysts with the bigger particles The authors proposed that the increased fraction of dense (111) planes on the larger gold particles offers more favourable adsorption sites for the carbonyl group

of the α,β-unsaturated aldehyde, and thereby enhances the allyl alcohol formation Previously, silver had drawn less attention as a catalyst for hydrogenation

[8,40-45] than platinum group metal (PGM) catalysts It is known from experiments and has been confirmed by theoretical studies [46-48] that hydrogen interacts only very weakly with extended silver surfaces (single crystals, polycrystalline surfaces), and dissociative chemisorptions does not occur at low temperature This was attributed to the completely filled d-band of silver as well as the position of the d-band centre relative to the Fermi level [46] However, supported silver was predicted to show some hydrogenation capabilities The group of Claus in Darmstadt were the first to report excellent selectivity of silver nanoparticle catalysts for the hydrogenation of a C=O group in the presence of a C=C bond [45] They studied the selective hydrogenation of crotonaldehyde over silver supported on titania or silica Different catalysts were prepared with metal particles of a size of 1 to 7 nm, and as in the case of gold, the larger particles gave higher selectivity to the unsaturated alcohol Shimizu [8] recently reported that silver clusters on θ-Al2O3 catalyse the reduction of nitro groups with high chemoselectivity in the reduction of substituted nitroaromatics They suggested that nitrobenzene interacts with the catalyst surface through the nitro group, and the silver clusters play an important role in the H2 activation step (Scheme 1-1)

Scheme 1-1 Proposed mechanism of nitroaromatic hydrogenation over an Ag

nanocluster [8]

Supported copper catalysts are an interesting option to perform selective hydrogenation reactions due to the low cost of the metal combined with advantageous catalytic properties of copper for selective hydrogenation reactions [49-54] Copper catalysts were also used in the selective hydrogenation of unsaturated carbonyls, and the selectivity can be tuned by adding different promoters From kinetic studies performed over Pt, Cu and Pd catalysts supported on silica, Pham et al [52] observed that over Cu/SiO2 catalysts, the hydrogenation of the C=O bond in 2-methyl-2-pentenal is faster than that of the C=C bond, though this effect is masked

at high conversion levels On the other hand, Marchi et al [55] studied the liquid phase hydrogenation of cinnamaldehyde, and concluded that Cu/SiO2 and binary Cu-Al catalysts were unselective, producing predominantly hydro-cinnamaldehyde However, they observed that ternary Cu–Zn–Al and quaternary Cu–Ni(Co)–Zn catalysts were more selective than Cu/SiO2 They proposed that cationic species of the promoter (Zn, Ni, Co) were responsible for the creation of selective sites for the hydrogenation of C=O

1.1.2.3 Carbon-carbon bond formation or cleavage

The cross-coupling reactions represent a class of synthetic transformations that involve the combination of an organometallic reagent (in most of cases containing a main group metal atom) with an organic electrophile in the presence of groups 8–10 metal catalysts to achieve a C–C, C–H, C–N, C–O, C–S, C–P, or C–M bond formation [56,57] In general, the reaction occurs through the sequence: oxidative addition – transmetallation – reductive elimination (Scheme 1-2) The group X in the reacting nucleophilic reagent R1-X can be different main group metals and metalloids

as indicated in Scheme 1-2 Group 11 metals except Au were not active for this type

catalytic system were found to have a promotional effect in the reactions

Scheme 1-2 Metal catalysed cross coupling

Homocoupling of arylboronic acids – Suzuki cross coupling

After Miyaura, Yamada, and Suzuki reported the Pd - catalysed coupling reaction of alkenyl boronates with alkenyl bromide, this type of reaction, known as the Suzuki–Miyaura reaction, has been widely studied [58,59] The coupling of organoboron reagents with various organic halides has broadened its scope, becoming one of the most important transformations leading to the formation of a C–C bond, since organoboron reagents are (i) readily available by hydroboration and transmetallation, (ii) inert to water and related solvents, as well as oxygen, (iii) generally thermally stable, (iv) tolerant toward various functional groups Another advantage is (v) the low toxicity of the starting materials and byproducts

Guo and co-workers reported a clean Suzuki-Miyaura cross-coupling in the presence of reusable poly(2-aminothiophenol) (PATP) stabilized Au NPs (0.05 mol%) The reactions were run in aqueous medium at 80 oC with the aid of 4 equiv of KOH

[M] : Fe, Ni, Pd, Rh, Au

[M'] : Li, Mg, B, Al, Si, Zn, Cu, Ag, Zr, Sn

and gave high yields of 50 – 95% [60] More recently, Stevens and co-workers showed that biodeposited Pd/Au bimetallic nanoparticles (2 wt % Au) catalyse efficiently the Suzuki coupling between aryl iodides and a series of aryl boronic acids [61]

Sonogashira cross-coupling

The Sonogashira reaction [62] of terminal alkynes with aryl and alkenyl (pseudo)halides is a straightforward method for the preparation of acetylene derivatives, which are highly useful building blocks in organic synthesis The Sonogashira reactions are most frequently carried out by palladium catalysts together with a copper co-catalyst using an amine as solvent [62]

Besides copper as the co-catalysts, Ag also was used as the co-catalysts for this type of reactions Palladium-catalysed decarboxylative sp-sp2 cross-coupling reactions

of aryl and vinyl halides and triflates with α,β-ynoic acids using silver oxide as the co-catalysts was reported by Lee and his co-workers (Figure 1-4) [63] A variety of

α,β-ynoic acids are readily decarboxylated in the presence of silver oxide, and the in situ generated silver acetylides then coupled with electrophiles in the presence of a

palladium(0) catalyst under neutral conditions, producing either symmetrical or unsymmetrical diarylacetylenes, arylalkylacetylenes and arylvinylacetylenes in good

FG

R+

cat Pd

Ag 2 O -CO2

FG = Me, n-Bu, MeO, Ac, CHO, EtO2 C, CN, Ph

R = H, alkyl, aryl X = Br, I, OTf

1.2 Borrowing hydrogen methodology in fine chemical synthesis

Borrowing hydrogen catalysis is an important catalytic concept It is based on the intermediate oxidation of a non-reactive starting substrate to the corresponding reactive substrate by the catalyst (which "borrows" hydrogen from the substrate); the intermediate species reacts with a second species producing a coupling product, which

is then reduced by the catalyst in the next step to yield the final product A number of characteristics are common to the reactions discussed In each case a less reactive species, such as an alkane or alcohol, is converted to a more reactive one, an alkene or organic carbonyl compound, that then reacts further in a tandem ‘one-pot’ procedure The first step is catalysed by a transition-metal complex and involves a C−H bond cleavage; the following steps may or may not be catalytic depending on the case This type of reaction offers benefits of atom economy and sustainable “green” chemistry:

by using unfunctionalized alkanes and alcohols, it avoids the need to introduce activating groups such as bromide or tosylate The types of reaction involved are illustrated in Scheme 1-3

Scheme 1-3 Borrowing hydrogen scheme in fine chemical synthesis

Here, ‘cat’ refers to the dehydrogenation/hydrogenation catalyst Where the initial dehydrogenation is endothermic, particularly in the case of alkane dehydrogenation,

the resulting arrangement has a great thermodynamic advantage The third step is necessarily exothermic to approximately the same extent as the first step is endothermic The third step can therefore help to drive the first step This type of transformation has been referred to as “hydrogen borrowing methodology” [64], the

“hydrogen autotransfer process” [65], or simply “hydrogen transfer” [66]

Alkanes, amines and alcohol substrates can all be used as the source of the electrophile Alkanes are dehydrogenated to alkenes, which then react to give the final products In the case of alcohols, dehydrogenation leads to aldehydes or ketones that then react further with nucleophiles Amines have also figured in dehydrogenative activation reactions, in which case reactive imines are generated as intermediates

1.2.1 Activation of alkanes

In 1973, Burnett and Hughes found that butane can be converted to lower and higher alkanes in contact with a combination of a dehydrogenation catalyst, platinum on alumina, and an olefin metathesis catalyst, tungsten oxide on silica [67] Basset and co-workers [68-70] found that supported Ta and W hydride catalysts also bring about this reaction but by a more complex mechanism Selective dehydrogenative activation

of alkanes is particularly challenging because an initial C−H activation is required in

an unreactive substrate to associate with the metal species in the catalytic cycle Once

an alkene is formed, the alkene metathesis reaction (Scheme 1-4) efficiently permutes alkylidene groups and leads to higher hydrocarbons

Scheme 1-4 Activation of alkane by borrowing hydrogen

Early work showed the feasibility of homogeneous alkane dehydrogenation to alkenes by a reverse hydrogenation pathway [71] The earliest report of such a dehydrogenation described the reaction of alkanes with [Ir(H2(Me2CO)2(PPh3)2]BF4

in the presence of a hydrogen acceptor [72] It was proposed that the oxidative addition of an alkane C−H bond to the complex is followed by β-elimination to give final products derived from an intermediate alkene; the key oxidative addition was later shown experimentally by Janowicz and Bergman [73] Subsequent work by Felkin [74], Jensen [75], Goldman [76-78], Saito [79,80], and Crabtree [81] established that several low-valent metal complexes were capable of this type of activation Then Goldman, Brookhart, and co-workers were able to bring about homogeneous alkane metathesis by a three-step one-pot process (Scheme 1-4) [82] In step 1, alkane dehydrogenation to the corresponding alkenes by one of Goldman’s Ir-based alkene dehydrogenation catalysts produces a small equilibrium concentration

of alkenes A Schrock Mo-based alkene metathesis catalyst, also present in the medium, converts these alkenes to alkenes of higher and lower carbon number in step

2 In the third step, the resulting alkenes are hydrogenated by the Ir catalyst to form the higher and lower alkanes By using the two hydrogen atoms formally liberated in step 1 as the reductant for step 3, the system beats the usual thermodynamic limitation for alkane dehydrogenation, since the overall process is nearly thermodynamically

2H

H2C CH2