Eindhoven University of Technology

MASTER

Mechanochemical activation of latent Gold(I)-NHC catalyst

Niu, Y.

Award date: 2015

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Mechanochemical activation of latent Gold(I)-NHC catalyst

Graduation report of

Yong Niu

Supervisor:

Dr. E. Schwartz

Ir. A. Balan

Supervising professor:

Prof. dr. R.P. Sijbesma

Advising committee:

Dr. L.G. Milroy

Dr. A.R.A. Palmans

Dr. T. Noel

Eindhoven, August 2015

Laboratory Molecular Science and Technology

Department of Chemical Engineering and Chemistry

Eindhoven University of Technology

Summary:

Chemical reactions are commonly initiated by absorbing energy from heat, light, or electricity as energy sources. Another alternative way to induce chemical reaction is to apply mechanical energy. The mechanical force from mechanical energy sources such as from ultrasound can be used to activate chemical bonds. By embedding a mechanophore with sensitive trigger structure to a polymer chain, the trigger bond can selectively break by applying mechanical force along the polymer chain. Different specifically designed mechanophores by chemists can magically show various structure- function relationships, resulting in different kinds of chemical properties. With mechanical force, selectively break bond in a latent catalyst may result in activating the catalytic property.

The main goal of this project is to synthesize a latent Au(I)-bisNHC catalyst. Aim to use mechanoforce, ultrasound power, to activate the latent Au(I)-bisNHC catalyst, and compare the difference of mechanoscission between Au(I)-NHC mechanophore and Pd(II)-NHC mechanophore.

In chapter 1, we give a short review of mechanochemistry history and describe several recent research results on polymer mechanochemistry area.

In chapter 2, the NHC chemistry and organogold chemistry were first reviewed. The successful synthesis of Au(I)-NHC mechanophore, model Au(I)-NHC catalysts were reported. The mechanoscission experiments successfully show the scission happen at the Au-NHC bond. The furtherly research on the property of the latent Au(I) mechanocatalyst indicated that the gold catalytic property can be activated by applying mechanic force under sonication. This discovery represents a new, as the third, method of activating organogold catalyst, besides the commonly used silver salt method for chemical activation and the more recently reported silver free protocol.

In chapter 3, Two amazing discovery on colloidal gold nanoparticles and a possible gold cluster were described.

In chapter 4, the successful synthesis of Pd(II) mechanophore with steric hinder structures were reported. The following mechanoscission experiments indicate a fast mechanoscission happen under sonication.

I

Abbreviation List

δ chemical shift (NMR spectroscopy) v wavenumber (IR spectroscopy) br broad (NMR spectroscopy) COGEF constrained geometry optimization cm-1 inverse centimetre d doublet (NMR spectroscopy) DMS dimethylsulfide DMSO dimethylsulfoxide equiv. equivalents et al. et alia FMPES force-modified potential energy surface FT-IR Fourier-transform infrared g grams h hours HRMS high resolution mass spectrometry Hz Hertz J coupling constant (NMR spectroscopy) KHMDS bis(trimethylsilyl)amide LC-MS liquid chromatography mass spectrometry m medium intensity (IR spectroscopy) m multiplet (NMR spectroscopy) M moles per litre MALDI matrix-assisted laser desorption and ionisation (mass spectrometry) Mes mesityl, 2,4,6-trimethylphenyl MW moleular weight min minutes mL millilitres mol moles nm nanometres NHC N-heterocyclic NMR nuclear magnetic resonance ppm parts per million q quartet (NMR spectroscopy) RCM ring closing metathesis ROMP ring-opening metathesis polymerization

Rt retention time r.t. room temperature s strong intensity (IR spectroscopy) SMFM single-molecule force microscopy t triplet (NMR spectroscopy) TABS thermally activated barrier to scission THF w weak intensity (IR spectroscopy) II

Table of Contents

Summary: ...... I

Abbreviation List ...... II

Chapter 1 Introduction ...... 1

1.1 Overview of mechanochemistry ...... 1

1.2 Fundamental aspects of polymer mechanochemistry ...... 1

1.3 Methods and techniques of applying mechanical stress...... 3

1.31 Ultrasound ...... 4

1.32 Elongational Flow ...... 5

1.4 Mechanoresponsive materials ...... 7

1.41 Mechanochromism ...... 7

1.42 Mechanoluminescence ...... 7

1.43 Mechanocatalysis ...... 8

1.5 Aims of this project ...... 9

1.6 References ...... 11

Chapter 2 Mechanochemical activation of a Gold(I)-bis(NHC) catalyst and scission rate determination with trapping agents...... 13

2.1 Introduction ...... 13

2.11 and N-heterocyclic carbenes (NHCs) ...... 13

2.12 Gold and organogold chemistry ...... 15

2.13 -NHC and Gold(I)-NHC ...... 16

2.3 Results and discussion: the synthesis of Gold-NHC complexes ...... 19

2.31 The synthesis of model Au(I)-bis(NHC) molecule ...... 19

2.32 The synthesis of Au(I) mono-NHC complex...... 21

2.32 The synthesis of Au(I)-bis(NHC) mechanophore ...... 23

2.4 Results and discussion: mechanoscission of Gold(I)-bis(NHC) mechanophore ...... 23 III

2.43 Mechanochemical activation of Au(I)-NHC catalyst ...... 26

2.5 Conclusion ...... 27

2.6 Experimental section ...... 27

2.7 References ...... 33

Chapter 3 Colloidal gold nanoparticles and a potential gold cluster ...... 35

3.1 Introduction ...... 35

3.2 Results and discussion ...... 35

3.21 Colloidal gold nanoparticles ...... 35

3.22 A potential ‘hexamer’ gold cluster ...... 38

3.4 Conclusion ...... 39

3.3 Experiment Section ...... 39

3.5 References ...... 40

Chapter 4 Mechanochemical scission of Pd(II)-NHC complex ...... 41

4.1 Introduction ...... 41

4.2 Results and discussion ...... 41

4.21 Synthesis of Pd(II)-NHC model complex...... 41

4.22 Synthesis of Pd(II)-NHC mechanophore ...... 43

4.23 Mechanochemical scission of Pd(II)-NHC complex ...... 44

4.3 Conclusion ...... 45

4.4 Experimental section ...... 45

4.5 References ...... 47

Conclusions and Outlook ...... 48

Acknowledgements ...... 49

Appendix ...... 50

IV

Chapter 1 Introduction

1.1 Overview of mechanochemistry

Mechanochemical reactions are defined as chemical reactions induced by the direct absorption of mechanical energy.1 Different sources of mechanical force, such as shearing, stretching, grinding, and ultrasonication are typical methods for inducing mechanochemical reactions. The first record of a mechanochemical reaction is reported in a book by Theophrastus of Ephesus (371-286 B.C.), named “De Lapidibus” or “On stones”, which described the phenomenon that in the presence of vinegar, rubbing native cinnabar ( (II) sulfide) in a brass mortar with a brass pestle, generates metallic mercury.2

In nature, many phenomena can be described as the responses of mechanochemical reactions such as sense of hearing or touching,3 and enzyme activity inhibition, which is caused by mechanical force induced enzyme conformational change. 4 Numerous common changes are also accompanied with mechanochemical reactions, for example, grinding and milling grains or minerals to powder, cutting or elongating polymer material,5 etc.

The phenomena in macroscale that the fractures of material under mechanical manipulation reflect the scission of chemical bonds on a molecular scale. Mechanical force used to induce mechanochemical reactions is an alternative to the common energy sources, such as thermal energy for reactions that proceed by heating, light energy for photochemical reactions or electric energy for electrochemical reactions.

1.2 Fundamental aspects of polymer mechanochemistry

In the early 1930s, German scientist Hermann Staudinger discovered that under mastication condition the molecular weight (MW) of rubber reduced resulting in polymer degradation. This report represents the first description of polymer mechanochemistry. 6 Later theoretical work confirmed that the decrease in MW can be attributed to the scission of polymer chains under mechanical force. The thermally activated barrier to scission (TABS) theory was developed by American scientists

Figure 1.1 (dash-dotted line) Morse potential of a covalent bond, with dissociation energy D at equilibrium r0. (real line) Morse potential deformed by external force F, resulting in a low barrier D for bond dissociation.8

1

Kauzmann and Eyring six years after Staudinger’s discovery,7 and describes the energy changes in different bond activation pathways.

The TABS theory can be well interpreted by Figure 1.1. As a result of external stretching force, bond length increases from equlibrium r0 to r’. The potential energy of the bond is decreased by the work of the external force W(r) = F × (r’- r0). Consequently, the bond dissociation barrier energy (D’) in the new Morse potential ( U’(r) = U(r) – W(r), the real line in Figure 1.1) is lower than that of before (D). Mechanoscission will eventually occur when the external force is enough to reduce the dissociation energy,8 given by the new barrier (D’) to such an extent that it can be crossed by energy from thermal fluctuations (kBT) at room temperature.

In recent years, the principle of decreasing Morse potential in mechanochemical reactions has been well illustrated by both theoretical calculations and experimental studies. For example, To simulate the

Figure 1.2 Left: the potential energy surface of the Ag–C bond cleavage under the external force. Right: the potential energy diagrams at various selected external forces: (○) no external force, (▲) 82 nN, (▼) 165 nN, (◆) 247 nN, (■) 329 nN, (●) 412 nN, and (★) 823 nN.8

experimental results of mechanoscission in a silver(I)-bis(NHC) polymer complexes (Ag-(NHCx)2PF6), a DFT calculation was first used to estimate the value of external force for breaking the silver(I)-NHC coordination bond, and a series of ab initio molecular dynamics (MD) simulations combined with constrained geometry optimization (COGEF) were performed to calculate the potential energy surface under varied external forces.8 The results demonstrate that with the increase of external force, the activation energy for breaking the silver carbene bond (Ag-C bond) significantly decreases (Figure 1.2).

Another profound example is the mechanoactived ring-opening reaction of cyclobutanes. Moore et al. found that under mechanoforce the ring-opening reactions of both trans- and cis- cyclobutanes isomers only yield the E,E isomer as the product (Figure 1.3).9 This result means that both conrotatory and disrotatory pathways of electrocyclic ring opening reaction can happen under mechanoforce without obeying the Woodward-Hoffman rules,10 which is that the conrotatory pathway or disrotatory pathway can only alternatively happen either in a thermal condition or a photochemical condition determined by the electron number in the conjugated π-system.

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Figure 1.3 Activation of benzocyclobutenes by mechanical forces yield only E,E-isomer9

These interesting results were further investigated by calculations. A series of ab initio steered molecular dynamics calculations were used to simulate the mechanically induced ring opening of cyclobutene. The resulting force-modified potential energy surface (FMPES) (Figure 1.4) from dynamic study shows that the activation energy for two possible competing conrotatory and disrotatory ring-opening reactions is affected by external force. The energy barrier for the ring- opening reaction of which the rotational direction is in line with the direction of the external force can is decreased with the increase of external force.11 The results of these calculations also match with TABS theory. Both experimental and theoretical results show that the results of mechanochemical reactions can be totally different with those under thermal or photochemical conditions.

Figure 1.4 Force-modified potential energy diagram for cyclobutene ring opening by cis- pulling (left) and trans-pulling (right)11

1.3 Methods and techniques of applying mechanical stress

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Several commonly used mechanical manipulations, such as grinding, milling, mastication and stretching etc. can be used for introducing mechanical stress in nature or in artificial ways. Besides these, in the field of polymer mechnochemistry, several advanced techniques for applying mechanical stress in or in solid state have been developed, supplying forces and strain rates ranging from a low strain rate by the technique of single-molecule force microscopy (SMFM) to high strain rate from laser-induced acoustic waves (Figure 1.5).12

Figure 1.5 Schematic summary of varied experimental methods to generate mechanical activation on a material at the single molecule level, in solution, and in a solid polymer.12

1.31 Ultrasound

Ultrasound can be divided into two types in terms of intensity and frequency: (1) high-intensity (min. 10 W/cm2) with low-frequency (20 kHz to 2 MHz) and (2) low-intensity (max. 0.5 W/cm2) with high- frequency (2 - 10 MHz) ultrasound. 13 The latter type of ultrasound is widely used for medical diagnostics applications, and the former type of ultrasuond with more extreme ultrasonic intensities are generally used for sonochemistry.15

High intensity ultrasound is a powerful tool to promote chemical reactions. Ultrasound causes longitudinal sound waves passing through liquid phase, causing acoustic cavitation when the molecular attractive force is exceeded by the ultrasonic power. The caviation bubbles grow with the negative half of the sound waves cycle and collapse with the positive half of the sound waves cycle. Rarefaction of the bubbles is followed by compression alternatingly. Since the bubbles grow more than they shrink in each cycle, the growing bubbles at some point reach a maximum critical diameter and eventually collapse violently (Figure 1.6 a).12 The shear force occurring during this imploding process can be used to promote various chemical reactions.

The violent collapse causes solvent molecules that rush into the void to pull along the nearby dissolved polymer chains. An elongational flow field is generated as the molecules near to the collapsing bubble

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move faster than those further from the bubble. The drag forces elongate the polymer chain and eventually causes cleavage of a chemical bond in the polymer chain (Figure 1.6 b).

Besides the mechanical effects, the forming of hotspots during the rapidly implosion of cavitation bubbles can pyrolyze solvent molcules, resulting in the formation of highly reactive species. The high temperatures up to 5000K and pressures up to 500 bar in the induced hotspot may also cause a plasma formed during bubble collapse and eventually result in a phenomenon of sonoluminescence.14,15

Figure 1.6 Schematic overview of ultrasound-induced polymer chain scission: (a) The cavitation mechanism in acoustic field; (b) bubble collapse results in polymer elongation and mechanoscission; (c) Radical byproducts formed by pyrolyzing small molecules12

1.32 Elongational Flow

The continuous flow techniques with prominent advantages of strong mass transfer and heat transfer have found wide utilization in many research fields of chemistry. 16, 17, 18 The application of flow techniques can also be used to generate forces in polymer mechanochemistry area. The opposed jets and cross slots are techniques to generate elongational flow, and were introduced by Odell and Keller for the study of polymer mechanochemistry.19 The flow reactor consists of two opposing orifices. When the polymer solution flows through the opposing orifices, a zero velocity region at stagnation point (marked as X in Figure 1.7) 20, 21 is created. The mechanoforce that is induced by the high velocity gradient can pull the polymer which gets trapped in this region in an opposite direction. The key parameter to control this technique is the strain rate which can be adjusted by the velocity of the solution in flow. Increasing the velocity results in an increase of strain rate ε. Above the critical strain rate ε, the polymer will be efficiently elongated, reflecting a significant change in birefringence (figure 1.7 b).20 With continued increase of flow velocity and the corresponding strain rate, at some point the mechanoscission of polymer will occur.

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a b

Figure 1.7 (a) Diagram of flow field created in a cross slot reactor. (b) Representation of birefringence versus strain rate under flow-induced polymer elongation.20,21

Another technique for creating mechanoforce in polymer mechanochemistry area is the contraction flow described by Nguyen and Kausch. 22 The differential in pressures drives a polymer solution through a narrow contraction. The contraction promotes the increase of fluid passing speed and suddenly induces a flow field with high strain rate (Figure 1.8).23 By using this apparatus, the polymer elongation can be controlled by two parameters: the flow rates of the fluid and the relaxation time of the polymer. The simple experimental set-up is an obvious advantage of this technique.

Figure 1.8 Diagram of flow field generated in a simple contraction apparatus21

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1.4 Mechanoresponsive materials

In recent years, many interesting results were reported in the frontier area of polymer mechanochemistry of materials.15 Under external force, selective bond scission in a polymer chain has two possible origins. If the polymer chain contains a weak bond, it selectively breaks at the weaker bond. On the other hand, even when all bonds have the same strength, forces on the polymer molecule accumulated in the center of the chain can promote preferential midchain scission. The term ‘mechanophore’ refers to a force-sensitive molecular unit containing labile bonds. With sufficient external force applied to materials chemical transformation can happen in the mechanophore.24 By introducing polymer embedded mechanophores, mechanoscission selectively cleaves the weak bond at the specific point of mechanophore along the polymer chain. Different mechanophore-functionalized polymers provide various mechanochemical properties and applications such as chromism, luminescence, , self-healing, etc.

1.41 Mechanochromism

Mechanoforce induced reactions can be visualized by color changes. 25 For example, a series of polymer linked spiropyrans was reported to be mechanochromic.26 Under mechanical force, the weak bond between the ethereal and nodal carbon breaks, resulting in ring opening to a highly conjugated zwitterionic merocyanine dye moiety and a color change from colorless to red (Figure 1.9).

Figure 1.9 Mechanochromic response of spiropyran embedded PMA26

1.42 Mechanoluminescence

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Mechanoluminescence is light emission resulting from any mechanical action on a solid. It can be produced through ultrasound or by applying tensile force. The polymer based mechanoluminescence, mechanical cycloreversion of 1,2-dioxetane which is embedded in linear and cross-linked PMA films, was reported by the Sijbesma .27,28 A series of bis(adamantyl)-1,2-dioxetane linked poly(methyl acrylate) (PMA) polymer film were made by co-polymerizing methyl acrylate with small amount bisacrylate linked bis(adamantyl)-1,2-dioxetane. The strained four-membered 1,2-dioxetane ring broken by ultrasound or tensile deformation generates one ground state ketone and one ketone in its excited state. The latter relaxes to the ground state via blue chemiluminescence. By the addition of acceptors to the polymeric matrix, the total quantum yield of mechanoluminescence can be improved. Energy transfers occur from the excited ketone to varied sensitizers, the excited sensitizers decay to ground state resulting in light emission with different wavelengths (Figure 1.10).

polymer polymer Force polymer O + OO polymer polymer bright blue chemiluminescence

O* O

Figure 1.10 Mechanoluminescence by 1,2-dioxetane linked poly (methyl acrylate) (PMA) with different sensitizers27

1.43 Mechanocatalysis

Previous studies in the Sijbesma group of polymer embedded transition metal mechanophores have shown that the Palladium (II) - (Pd-P) bond or the Platinum(II) – phosphine (Pt-P) bond selectively break in ultrasound induced polymer chain scission, (Figure 1.11),29 and they do so in a reversible manner.30,31 These results show the possibility that scission of a bond by mechanical force may activate catalytic properties of metals or , switching a latent catalyst to an active catalyst.

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Figure 1.11 sonication results in polymer chain scission with metal coordination bond break.29

Inspired by theses interesting results, in 2009, the Sijbesma group first successfully developed polymer-functionalized mechanocatalysts,32 latent catalyst activated by mechanoforce. The reported a silver (I) complex coordinated by two N-heterocyclic carbene (NHC) ligands embedded in two polymer chains, which can be activated mechanochemically. Upon sonication, the carbene-silver coordination bond breaks, dividing the coordinated complex into two parts, a highly nucleophilic free NHC part with another silver-mono NHC complex part. The free NHC can catalyze an esterification reaction converting vinyl acetate to Benzyl acetate in the presence of benzyl alcohol. Subsequent research indicated that activation of related Grubbs-type (II)-NHC complex by mechanical force can result in ring closing metathesis (RCM) and ring-opening metathesis polymerization (ROMP).33,34

a

O + OH N N O b O n Ultrasonication PF6Ag N N O n O O NN O n + O

Ar N N c n O Ar N Cl N n Ru Ultrasonication O Cl Ph Cl Ru O Cl Ph nNN Ar m

Figure 1.12 Overview of latent mechanocatalyst (a) a cartoon model of mechanocatalyst (b) ultrasound activates mechanocatalyst for transesterification reaction (c) ultrasound activates mechanocatalyst for ROMP reaction

1.5 Aims of this project

Since the first polymer-functionalized mechanocatalyst was successfully reported in 2009,32 one of our group’s research lines focuses on latent catalysts which can be activated by mechanoforce, such as ultrasound and external force. A series of latent catalysts based on metal-bis(NHC) mechanocatalysts have been reported in recent years such as the polymer linked silver (I)-bis(NHC) mechanocatalyst 9

and polymer linked Grubbs-type ruthenium (II)-bis(NHC) mechanocatalyst, mentioned above. It is believed that under mechanical force, the metal-bis-NHC complexes are teared into two parts: 1) a NHC moiety and 2) metal mono-NHC complex. For the silver NHC mechanocatalyst, the liberated carbene is the activated catalyst. The silver-bis-NHC complex is, however not very stable at - room temperature, especially when the anion is changed from PF6 to chloride. Furthermore, for the related palladium (II)-bisNHC contained mechanophore, no catalysis is observed.

We expect the gold-carbene bond to be stronger than silver-carbene bond but weaker than palladium- carbene bond. The initial goal of this project is to synthesize and test the properties of a polymer- linked gold(I)-NHC mechanocatalyst (Figure 1.12). We proposed that under sonication the Gold(I) mechanocatalyst can be activated to catalyze reactions of . We also aim to test and compare the mechanochemical scission of Gold(I) mechanophore and Pd(II) mechanophore.

N N N N Carbene Catalyst O n Sonication O n

Au PF6 PF6 O Au N N n O Gold(Ι) Catalyst N N n

Figure 1.12 Proposed mechanoactivation of gold-bis(NHC) complex

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1.6 References

1 IUPAC. Compendium of Chemical Terminology, 2nd ed. (the "Gold Book"). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). XML on-line corrected version: http://goldbook.iupac.org (2006-) created by M. Nic, J. Jirat, B. Kosata; updates compiled by A. Jenkins. ISBN 0-9678550-9-8. doi:10.1351/goldbook. http://goldbook.iupac.org/MT07141.html 2 M.K. Beyer, H. Clausen-Schaumann, Chem. Rev. 2005, 105, 2921–2948 3 a) Orr, A. W.; Helmke, B. P.; Blackman, B. R.; Schwartz, M. A. Dev. Cell 2006, 10, 11-20; b) Gillespie, P. G.; Walker, R. G. Nature 2001, 413, 194-202; 4 R.K. Murray, D.K. Granner, P.A. Mayes, V.W. Rodwell, In Harper’s Illustrated Biochemistry (26th Ed.); Lange Medical Books/McGraw-Hill: New York, 2003 5 Casale, A.; Porter, R. S. Polymer Stress Reactions; Academic Press: New York, 1978; Vol. 1 and 2. 6 Staudinger, H.; Heuer, W. Ber. Dtsch. Chem. Ges. A/B 1934, 67, 1159-1164. 7 Kauzmann, W.; Eyring, H. J. Am. Chem. Soc. 1940, 62, 3113-3125. 8 Ramon Groote; Bartłomiej M. Szyja; Evgeny A. Pidko; Emiel J. M. Hensen; Rint P. Sijbesma; Macromolecules 2011, 44, 9187-9195. 9 Hickenboth, C. R.; Moore, J. S.; White, S. R.; Sottos, N. R.; Baudry, J.; Wilson, S. R. Nature 2007, 446 (7134), 423–427. 10 Woodward, R. B.; Hoffmann, R. Angew. Chem. Int. Ed. Engl. 1969, 8 (11), 781–853. 11 Ong, M. T.; Leiding, J.; Tao, H.; Virshup, A. M.; Martínez, T. J. J. Am. Chem. Soc. 2009, 131 (18), 6377–6379. 12 Caruso, M. M.; Davis, D. A.; Shen, Q.; Odom, S. A.; Sottos, N. R.; White, S. R.; Moore, J. S. Chem. Rev. 2009, 109 (11), 5755–5798. 13 Suslick, K. S.; Price, G. J. Annual Review of Materials Science 1999, 29 (1), 295–326. 14 Nakamura, E.; Machii, D.; Inubushi, T. J. Am. Chem. Soc. 1989, 111 (17), 6849–6850. 15 Groote, R.; Jakobs, R. T. M.; Sijbesma, R. P. Polym. Chem. 2013, 4 (18), 4846–4859. 16 McQuade, D. T.; Seeberger, P. H. J. Org. Chem. 2013, 78 (13), 6384–6389. 17 Newman, S. G.; Jensen, K. F. Green Chem. 2013, 15 (6), 1456–1472. 18 Wegner, J.; Ceylan, S.; Kirschning, A. Chem. Commun. 2011, 47 (16), 4583–4592. 19 Keller, A.; Odell, J. A. Colloid & Polymer Sci 1985, 263 (3), 181–201. 20 Odell, J. A.; Keller, A. J. Polym. Sci. B Polym. Phys. 1986, 24 (9), 1889–1916. 21 May, P. A.; Moore, J. S. Chem. Soc. Rev. 2013, 42 (18), 7497–7506. 22 Nguyen, T. Q.; Kausch, H. H. Adv. Polym. Sci. 1992, 100, 74 23 Yu, G.; Nguyen, T. Q.; Kausch, H.-H. J. Polym. Sci. B Polym. Phys. 1998, 36 (9), 1483–1500. 24 Li, J.; Nagamani, C.; Moore, J. S. Acc. Chem. Res. 2015. In pressing 25 Potisek, S. L.; Davis, D. A.; Sottos, N. R.; White, S. R.; Moore, J. S. J. Am. Chem. Soc. 2007, 129, 13808-13809. 26 Davis, D. A.; Hamilton, A.; Yang, J.; Cremar, L. D.; Van Gough, D.; Potisek, S. L.; Ong, M. T.; Braun, P. V.; Martinez, T. J.; White, S. R.; Moore, J. S.; Sottos, N. R. Nature 2009, 459, 68–72. 27 Chen, Y.; Spiering, A. J. H.; Karthikeyan, S.; Peters, G. W. M.; Meijer, E. W.; Sijbesma, R. P. Nat. Chem. 2012, 4, 559. 28 Ducrot, E.; Chen, Y.; Bulters, M.; Sijbesma, R. P.; Creton, C. Science 2014, 344 (6180), 186–189. 29 Paulusse, J. M. J.; Sijbesma, R. P. Chem. Commun. 2008, No. 37, 4416–4418.

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30 Paulusse, J. M. J.; Sijbesma, R. P. Angewandte Chemie International Edition 2004, 43 (34), 4460– 4462. 31 Paulusse, J. M. J.; van Beek, D. J. M.; Sijbesma, R. P. J. Am. Chem. Soc. 2007, 129 (8), 2392–2397. 32 Piermattei, A.; Karthikeyan, S.; Sijbesma, R. P. Nature Chem. 2009, 1, 133–137. 33 R.T.M. Jakobs, R.P. Sijbesma, Organometallics 2012, 31, 2476–2481 34 R. Groote, R.T.M. Jakobs, R.P. Sijbesma, ACS Macro Lett. 2012, 1, 1012–1015

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13

though the carbene is in a singlet state, with the lowest energy among the three states (Figure 2.2).

However, when the carbine carbon atom is substituted with heteroatoms, particularly , stable carbenes are obtained, called or N-heterocyclic carbene.2,3 The existence of NHC was first proposed by Breslow in 1957 as an intermediate involving a catalytic cycle of vitamin B1.4 To explore an isolable, stable carbene, extensive studies on NHC dimers were carried out by Wanzlick in the 1960s. However, only a mecury(II)-bis(NHC) and a NHC- adduct were synthesized and isolated.5 In 1988, the first isolated carbine - with adjacent and substituents - was reported by Bertrand.6 Three years later, inspired by the earlier work of Wanzlick and Ofele7 on metal-carbenes, an air-stable adamantyl-linked NHC was successfully prepared and isolated by Arduengo (Figure 2.3). 8 This landmark discovery greatly encouraged and promoted developments in the field of NHC’s. From then on, a huge amount of research on NHCs has been reported.

NN NaH NN + H2 + NaCl Cl THF cat. DMSO

Figure 2.3 The synthesis of Arduengo NHC8

Different from traditional carbenes, NHCs are relatively stable with many advantages over traditional carbenes. As a general representative structure of NHCs shown in Figure 2.4, the ring forces the angle of N-C-N to be smaller than 180⁰. A bent carbene geometry favors sp2 hybridization of the carbene carbon in the lowest energy as a singlet state. In the electronic effects, the two pair electron from the p orbitals of two adjacent nitrogen atoms donate electron to the unoccupied p-orbital of the carbene carbon. This π-electron- donating effect generates a ‘five center six electron conjugated π system’ having aromatic properties, stablizing the p orbital of carbene carbon. The electronic effects of the ring skeleton is reflected in the σ bonds. Due to the higher electronegativity of nitrogen compared to carbon, an withdraws electrons from from the central carbene carbon toward the two adjacent nitrogen atoms, further lowering the energy of the sp2 hybridized electrons on carbene carbon. These dual effects from the nitrogen heteroatom(s) play a role in stablizing the carbene.

Figure 2.4 The electronic effects in a general NHC structure2

Another advantage of NHc’s is the easy modification of N-substituent(s) – the ‘R’ group on Figure 2.3. Applying different substituents on nitrogen can adjust the properties of NHCs, such as introduction of bulky groups on nitrogen which give rise to a steric effect , kinetically stabilizing NHCs, while application of electron rich or poor substituents can bring an electronic influence modulating the electron orbitals energy the on NHC ring, and introducing asymmetric centers may result in stereoselectivity when the NHC is used as organocatalyst/ligand in

14

catalysis9 NHCs are most commonly obtained by from the precursor imidazolium salts under basic conditions.

The major applications of NHCs focus on two main areas. They can be directly use as nucleophilic or basic organocatalysts,10,11,12 or as versatile ligands to coordinate with metal to form catalytically active13,14,15 metal- NHC complexes16,17 NHCs can also bond with Lewis from p-block elements to form adducts,18, 19 for several uses such as stabilization of reactive species.20,21

After the first report of the stable NHC in 1991,8 many kinds of NHCs have been developed showing versatile properties and utilizations in many aspects.22 Several typical classes of NHCs are shown in the Figure 2.5.

R' NX R NN R' R NN R' R N R R'

Imidazolylidene Imidazolinylidene Pyrrolidinylidene Thiazolylidene (X=S) Oxazolylidene (X=O)

R'' R'' R''' R'' R''' N N O O NN R R' R N R' R NN R' R R' 'Abnormal' Triazolylidene Benzimidazolylidene imidazolylidene N,N'-Diamidocarbene

Figure 2.4 Different typical classes of NHCs

2.12 Gold and organogold chemistry

Gold is a late transition metal element. It has atomic number of 79 in group 11. The electronic configuration for metallic gold at zero is 5d106s1. Gold can also commonly exist as cation with electronic configuration of 5d10 for Au(I) and 5d8 for Au(III). It also can exist as a aurate anion Au(-1) with 5d106s2 electronic configuration due to the stabilization of the 6s orbital.

Gold as a post- element has a large number of in the atomic nuclei. Therefore, the electrons move in the field with very high nuclear charge, leading to electron velocities approaching light speed. According to Einstein’s principle of relativity, the mass of electron will consequently increase and the Bohr radius will decrease. These relativistic effects result in significant larger contraction of the 6s orbital23,24 than the p-orbital and d-orbital (Figure 2.5), because the s orbitals have wavefunctions with a finite electron density at the atomic nucleus.

The strong relativistic effects on gold determine many peculiar properties. Concerning physical properties, the energy for transition from the 5d band to the contracted 6s band (the Fermi level) equals around 2.4 eV, which give a strong absorption of blue light and purple light, and reflects red and yellow light. With respect to chemical properties, the contracted 6s orbital promote a better shield (expands) for the 5d orbitals.25,26 For the gold cation, on one hand, the contracted 6s orbital enhances the π- acidity; on the other hand, the expanded 5d orbital increases electron delocalization, and promotes π- backbonding. This results in a soft π- Lewis property of gold.

15

Figure 2.5 The calculated relativistic effects on the contraction of the 6s orbital

The π-acidity of gold - used to activate the compounds with π-bonds - dominates its catalytic properties. The utilization of gold catalysis can be divided into two major areas: supported gold nanoparticles for heterogeneous catalysis, and ligand-coordinated organogold(I) or organogold(III) complexes for homogeneous catalysis. Instead of using inorganic gold halide salts such as gold(I) chloride (AuCl), gold(III) chloride (AuCl3) or chloroauric acid (HAuCl4), which were used in the early stage of gold catalysis research, most of recently developed organogold catalysts are designed and synthesized containing a gold-organic ligand bond and a gold- bond. Commonly chloride bound to gold is used as catalyst precursor. To activate the latent organogold catalysts, a soluble silver salt with a non-nucleophilic anion, such as silver hexafluorophosphate (AgPF6),

(AgBF4) or hexafluoroantimonate (AgSbF6) is usually added to abstract the halogen. The resulting ‘naked’ gold(I) cation has catalytic activity as π-Lewis acid to activate organic molecules with a π- electron system.

In particular gold(I) catalysts represent highly efficient catalysts to functionalize the carbon-carbon multiple bonds. Many functional groups with conjugated π- bonds can be activated, 27 such as ,28, 29 , 30, 31 allenes,32, 33 arenes,34 and dienes35. The general mechanism for gold(I) π- activation catalysis is shown in Figure 2.6.27 In general, after removal of the halide ‘X’ from the ‘L- Au-X’ structure, the gold cation coordinates to a π-bond, the two coordinated π-complex followed a nucleophlic addition by to finish the catalytic cycle.

Figure 2.6 The general mechanism for π-activation of gold catalyst27

2.13 Transition metal-NHC and Gold(I)-NHC

In general, the use of proper ligands is necessary to promote the catalytic properties of transition metal. There are two classes of ligands commonly used ligands in gold catalysis, phosphines36,37 and N-

16

heterocyclic carbenes (NHC). 38 Both of them can assist and promote the catalysis of the central transition metal. However, NHCs have many advantages over classical . Generally, phosphines are air sensitive since the phosphorus atom is easily oxidized, and handling these ligands requires special treatment. Furthermore, the P-C bond in the ligand usually suffers cleavage by its coordinated transition metal center. These factors shorten the lifetime of the phosphines and the corresponding organometallic catalyst. On the other hand, NHCs not only overcome these drawbacks but have other advantages as excellent ligands. For example, the easy modification of substituents on the nitrogen atoms of NHC, and the close distance between substituent and the NHC ring can dramatically affect and modulate steric hindrance and the electronic effects of the ligands further influence the coordinated transition metal center.

NHCs are nucleophilic because they can use the lone pair in the p orbital to coordinate to Lewis acids. When NHCs coordinate to a transition metal, metal carbene complexes are formed. The transition- metal NHC complexes formally contain both a π-bond and a σ-bond between the carbene and the metal atom.39 In terms of the electron multiplicity, Metal-NHC compounds can be classifed into two categories, the Fischer-type carbenes and the Schrock-type carbenes.40 Generally, the Fischer carbenes are considered as singlet state and are formed by carbenes when they coordinate to late transition metals of groups 6-8 in low oxidation states.41 Schrock carbenes, on the other hand, exist as a triplet state, and are formed when NHC’s bind to early transition metals of group 4-6 with high oxidation states.42,43

Figure 2.5 Schematic representation of (a) donor-acceptor bonding in Fischer-type carbene and (b) normal covalent bonding in Schrock-type carbene complexes39

Gold-NHC’s are Fischer-type carbene complexes. Like other Au(I) organometallic compounds, the Au(I)-NHC complexes predominantly have linear, bi-coordinated geometries, while Au(III)-NHC complexes prefer a tetra-coordinated planar structure. Catalysis by Au(I)-NHC complexes has become a ‘hot’ research area in recent years. As the NHCs ligand are better than phosphine ligands at increasing the stability of gold catalysts, Au(I)-NHC catalysts have many advantages in terms of stability, turnover number, and tunability.44,45,46 Au(I)-mono(NHC) complexes, especially the halogen atom-bonded NHC complex (NHC-Au-Cl), are generally used as catalyst precursor, and are activated by a silver salt. Recently, the Nolan group reported a new silver free protocol for Au(I)-NHC catalysts in which Au(I)-mono(NHC) complexes are bridged by oxygen or nitrogen in structures that show moderate to high catalytic activities without addition of silver. 47 , 48 , 49 Au(I)-bis(NHC) complexes generally are latent in most cases. Besides their use as catalyst, Au(I)-NHC complexes have also been found to be luminescent,50,51 and have biological activity as antitumor agents.52

17

There are four main types of synthetic routes to the Au(I)-NHC complex shown in Figure 2.6. As a general method to synthesize the transition metal-NHC complexes, gold-NHC can be synthesized using free carbene route by treating the precursor imidazolium salts with followed by coordination with gold (Figure 2.6 a). However, the reaction usually results in a mixture of an Au(I)- monoNHC complex and an Au(I)-bis(NHC) complex. The product ratio largely depends on the type and strength of base. A strong base such as Potassium bis(trimethylsilyl)amide (KHMDS) may result in Au(I)-bis(NHC) complex,53 while the fine powder of potassium carbonate prefer to force a Au(I)- monoNHC complex generation.54,55 Another general method for the synthesis of gold-NHC complexes is via transmetallation. (Figure 2.6 b) In this method, a silver-NHC complex is synthesized first, which can subsequently undergo a transmetallation reaction with a Au(I) salt to form a new Au-carbene bond.56 An can be used by directly cleavage of electron-rich alkenes with Au(I) cation has also be used to prepare Au(I)-bis(NHC) complexes, (Figure 2.6 c).57 Finally, the treatment of group 6 transition metal carbonyl-NHC complexes with Au(I) salt also gives Au(I)-NHC complexes.58

R NN R (a) Au X Base R NN R NN R R + Au(SMe2)Cl X Base R NN R Au (b) X

R NN R R NN R Au(SMe2)Cl Ag X Au X

R NN R R NN R

(c) N N Au(phosphine)Cl N N Au N N N N

(d) R R R N N N Au(SMe2)Cl W(CO)5 Au N N Cl N R R R

Figure 2.6 Different methods to synthesize Au(I)-NHC complexes

18

2.3 Results and discussion: the synthesis of Gold-NHC complexes

2.31 The synthesis of model Au(I)-bis(NHC) molecule

In this project, the final target mechanophore contains a Au(I)-bis(NHC) complex functionalized with long poly(tetrahydrofuran) (pTHF) chains . In order to find an efficient way to synthesize the Au(I)- bis(NHC) structure and to find a proper molecule for characterization comparison, a low molecular weight NHC gold complex 5 with short substituents was selected as the model molecule. In this molecule, the ethyl group attached to the NHC is identical with the ethyl group in the polymer mechanophore. The butyl group in 5 replaces the polyTHF chain in the mechanophore. The introduction of the non-nucleophilic PF6 as counterion aims to strengthen the Au(I)-carbene bond and is in line with the anion used in the silver(I)-bis(NHC) mechanophore reported in our group earlier.59 To synthesize the molecule 5, a free carbene route was designed. Carbene precursor 3 was synthesized starting from ethyl 1, via a SN2 reaction, by co-reflexing with iodobutane in THF. The anion of the resulting imidazolium salt was exchanged to chloride over ion exchange resin. The free carbene method using KHMDS as base to deprotonate the imidazolium followed by coordination with Au(I) in situ was used following literature report.53 chloride ion exchange n-BuI resin N N N N N N THF reflux I MeOH Cl 1 2 3

1. KHMDS N N N N NH PF 2. Au(SMe2)Cl 4 6 3 Au Au Cl PF6 DMF rt. H2O N N N N

4 5

Scheme 2.1 The synthetic route of model molecule 5

The structure of complex 5 was confirmed by 1H, 13C NMR spectroscopy and MALDI-TOF analysis. In the 13C NMR spectrum, the carbene carbon resonates at 183.77 ppm; above 180 ppm indicating the Au(I) complex has a bis-NHC coordinated structure rather than a mono-NHC coordination.60 The MALDI-TOF mass spectrum established the molecular mass of the Au(I)-bis(NHC) cation moiety (Figure 2.7).

19

Figure 2.7 MALDI-TOF MS spectrum of complex 5

Considering that steric hindrance may result in a faster mechanoscission, a ligand with a mesityl group instead of an ethyl group as N-substituent was also synthesized. Au(I) complex 11, as another model molecule, was prepared using a transmetallation approach (Scheme 2.2).

NH2 CHO Chloride ion CHO I exchange resin N N N N N N HCHO Toluene I Methanol Cl NH Cl reflux 4 6 7 8

NH4PF6 H2O

N N N N

AuSMe2Cl Ag2O PF6 Au PF6 Ag N N DCM NaOH/H2O DCM N N N N PF6

11 10 9

Scheme 2.2 The synthetic route of model molecule 11

Imidazole 6 was first prepared by a three-component condensation reaction following the procedure in 61 literature. The lower nucleophilicity of 6 compared to ethyl imidazole may cause a slow SN2 type substitution reaction. The synthesis of imidazolium chloride salt 8 was initially attempted by heating the mixture of 6 with excess 1-chlorobutane without solvent under microwave irradiation. The result of a small scale trial with 10-20 mg loading of imidazole 6 gave a quantitative yield of 8. However, when loading of 6 was scaled up to 500 mg, conversion was incomplete even after extending the irradiation time. The incomplete conversion is possibly due to the high polarity of the product imidazolium salt, which has stronger microwave absorption than the less polar starting material, resulting in limitation of heat transfer. Increasing the temperature above 120 °C did not promote a higher yield of 8, but on the contrary caused decomposition of the product via a β-elimination reaction to 1-butene. Therefore, iodobutane was re-selected to first obtain iodine salt 7. After sequential ion 20

exchange to the hexafluorophosphate salt, the silver-bis(NHC) PF6 complex 10 was easily obtained under basic bi-phase condition in the dark. The final transmetallation reaction was carried out in a dry dichloromethane solution by treating 10 with AuSMe2Cl, with very fast precipitation of silver chloride. The structures of the complex 10 and 11 were confirmed by 1H, 13C NMR spectroscopy and MALDI- TOF analysis (Figure 2.8).

N N

Ag

N N

N N

Au

N N

Figure 2.8 MALDI-TOF MS spectra of complex 10 (above) and 11 (below)

2.32 The synthesis of Au(I) mono-NHC complex.

The Au(I)-mono-(NHC) complexes, commonly described with the formula NHC-Au-Cl, are generally used as gold catalyst, showing catalytic property after activation by adding silver salt. Synthesizing the Au(I) mono-NHC complex also has important significance. On one hand, it can be used as model catalyst to test and to compare the catalytic properties of the mechanocatalysts, on the other hand the characterization results can be used to compare the results from sonication experiments to identify the 21

products with Au(I) mono-NHC structure. To synthesize the Au(I)-mono-NHC complex, based on literature in most of the Au(I)-mono-NHC catalyst the NHC ligands have a plane symmetry structure, such as IMes (1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene). The application of symmetric ligands not only can efficiently protect the coordinated transition metal by steric hindrance, but is also more straightforward because they are more easily synthesized than unsymmetrical ligands. The unsymmetrical ligands may induce an unsymmetrical electronic distribution on NHC ring, further influencing the stability of the coordination bond (metal-carbene bond).

To compare the catalytic properties of a chemically activated gold-NHC catalyst and a mechano- activated gold-NHC catalyst, a small gold-NHC molecule that has a similar structure as the polymer gold complex was synthesized. Since the un-symmetric NHC gold complexes are more difficult to synthesize, a symmetric compound, based on 1,3-Bis(2,4,6-trimethylphenyl)imidazolium chloride, was synthesized first. The imidazolium ligand and Au(DMS)Cl were reacted with one equivalent 55 K2CO3 at 60°C in acetone in a one-pot reaction, according to a reported procedure. However, significant amounts of pink-purple color precipitate was formed, indicating the formation of gold nanoparticles during the reaction, and a low yield of the target molecule was obtained, as based on 1H NMR spectroscopy. We therefore focused on a two-step procedure. In the first step, 12 was obtained as white solid after precipitation in ether (Scheme 2.3 b). A high yield (89% from imidazolium chloride ligand) of compound 13 was then obtained by treating 12 with an excess of K2CO3 in DCM at room temperature, followed by filtration through celite and precipitation in ether.

(a) Au(SMe2)Cl N N N N N N K2CO3 DCM Cl 60°C Cl Au Cl Au

Cl

(b)

Au(SMe2)Cl K2CO3 N N N N N N DCM DCM Cl Cl Au Cl Au

Cl 12 13

Scheme 2.3 (a) The reported one-pot synthetic method (b) The two-step synthetic route

The two-step synthetic method was used for the synthesis of model molecule 15 in 78% yield. Alternatively, the transmetallation method was also success to synthesize the asymmetric ligand 15 in a somewhat lower yield of 60% from imidazolium chloride ligand.

Au(SMe2)Cl K2CO3 N N N N N N DCM DCM Cl Cl Au Cl Au

Cl 14 15

Scheme 2.4 The two-step synthetic route of 15

22

Ag2O AuSMe2Cl N N N N N N DCM DCM Cl Ag Au

Cl Cl 16 15 Scheme 2.5 The transmetallation synthetic route of 15

2.32 The synthesis of Au(I)-bis(NHC) mechanophore

To synthesize the Au(I)-bis(NHC) mechanophore, the imidazolium end functionalized polymer ligand (17 kDa, PDI:1.05) was first synthesized by the cationic Ring-opening polymerization reaction of THF, which was end capped by quenching with imidazole. The same free carbene method that was developed for synthesizing 5 was first used to synthesize the Au(I)-bis(NHC) mechanophore. The results indicated that Au(I)-bis(NHC) was generated, but usually with incomplete conversion and subject to easy formation of gold nanoparticles (more detail in Chapter 3).

Alternatively, the Au(I)-bis(NHC) mechanophore 19 was synthesized using the transmetallation route (Scheme 2.6). A silver bis-NHC polymer complex 18 was synthesized and subsequently the silver was replaced by gold by using Au(SMe2)Cl in DCM. The transmetallation route gives a higher yield (60- 80%) and purity as compared to the free carbene route.

Chloride ion O exchange resin CF SO Et 1) 3 3 N N O nN N pTHF 2) N N Cl CF3SO3 3) H2O, ether 16

NH4PF6 MeOH

N N N N pTHF pTHF pTHF N N Au(SMe2)Cl Ag2O Au Ag PF6 PF6 PF DCM DCM NaOH 6 overnight 5d pTHF N N pTHF N N Transmetallation Route

19 18 17

Scheme 2.6 The synthetic route of mechanophore 19

2.4 Results and discussion: mechanoscission of Gold(I)-bis(NHC) mechanophore

23

The Au(NHC)2 mechanophore with 17 kDa polyTHF functionalized ethyl NHC ligands was sonicated under methane in toluene without adding trapping agent. After one hour sonication, the 1H NMR spectroscopy results indicated that no significant bond scission happened (Figure 2.9). In another sonication experiment, by adding trapping agents, acetic acid and acetonitrile, the gold mechanophore still no significant mechanoscission after one hour sonication.

N N O n Sonication almost no scission Au PF6 Toluene O N N n Acetonitrile

Figure 2.9 The sonication experiments for ethyl imidazolium ended gold mechanophore show alomost no scission under sonication

In order to decrease the gold-carbene bond strength and improve the mechanoscission rate by introducing steric-hindrance and electronic effects, a new polymer ligand with mesityl linked imidazolium salt was synthesized as well as the corresponding gold-bisNHC polymer complex 19 (2Χ17kDa polyTHF). The mechanoscission for the new gold polymer complex was tested in the presence of acetonitrile and acetic acid as trapping agent in toluene under methane (Figure 2.10).

CH N N pTHF 2 CH N N Sonication pTHF 2 pTHF CH2 N N + Au PF6 5 mL Toluene Au PF6 0.5mL Acetonitrile O pTHF CH2 N N 0.5mL Acetic acid O Bubbling with methane 30mg

Figure 2.10: Mechanochemical chain scission of NHC-gold complex 19

The MALDI results indicated that mechanochemical scission occurs. Abundant new polymers with half molecular weight (17kDa) were observed (Figure 2.11). 1H NMR spectroscopy results indicated that after sonication two species were generated: monocoordinated Au-NHC and an imidazolium salt (Figure 2.12). Further integration analysis revealed that after one hour sonication about 63% of Au mechanophores were torn into two pieces.

24

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2.43 Mechanochemical activation of Au(I)-NHC catalyst

It is known that Au(I) catalyst can activate π-bonds. To test whether the latent Au(I)-NHC mechanophore can be activated to show catalytic activity under sonication, a couple of substrates reported in literature were selected for testing. The experiments were carried out by sonicating the mixture of Au(I)-NHC mechanophore 19 with selected substances in toluene and acetonitrile under bubbling with methane, while keeping the internal temperature at 2 ºC. The results show that no hydroamination reaction and propargyl ester rearrangement reaction takes place. (Figure 2.13 a. b.). A possible reason is that without adding acidic trapping agent to deactivate the NHC moiety, which is formed by breaking the gold-carbene bond during mechanoscission, the mechanoscission of Au(I)- NHC mechanophore 19 is reversible. If adding acetic acid, scission can happen under the same conditions as used for the mechanoscission test described above, however the acetic acid will be also involved in the catalytic reaction, yielding multiple products due to the nucleophilicity of the acetate anion. Combining the need to deactivate the activity of NHC, with need to prevent the trapping agent from interfering with the catalytic reaction, 4-Pentynoic acid 20 was selected as substance to test as this compound not only can be used as trapping agent for its acidity but can be used as substrate, while the terminal alkyne structure is more reactive than internal alkynes.

NH2 sonication a. + + 19 no conversion

O O sonication + no conversion b. 19

sonication COOH + 19 c. O O 20 21

Figure 2.13 Mechanochemical tests for different substances

The mechanocatalytic tests of gold mechanocatalyst 19 with 20 were carried out on of 19 (130 mg, 2×15.6KDa, 0.004 mmol) in a solvent mixture of toluene (2.5 mL) and acetonitrile (1 mL) with a concentration of 5.2 mg mL–1. A sample of 0.03 mL solution was withdrawn to a GC vial as control experiment. The rest of the solution was cooled to 2°C (external cooling water temperature), and then saturated with methane. Subsequently, the solution was sonicated for 120 mins at 30% of the maximum amplitude (corresponding to a total power input of 14–20 W). During the sonication the temperature of the solution inside the vessel was maintained around 10°C. A small amount of sample (0.03 mL solution) was regularly withdrawn from the sonication vessel (after each 20 mins) to submit GC-MS and GC-FID to test the conversion. 26

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internal standard. The multiplicity of the signal is indicated as: br – broad, s – singlet, d – doublet, t – triplet, q – quartet and m – multiplet, dd – doublet of doublets, dt – doublet of triplets, etc. Coupling constants (J) were measured to the nearest 0.1 Hz.

13C NMR spectra were recorded on a 400 Varian Mercury NMR spectrometer with broadband decoupling using the deuterated solvent as internal lock. Chemical shift data are given in units δ relative to residual protic solvent.

GC-MS was performed on a Shimadzu GC-2010 equipped with a GCMS-QP2010plus detector, using a Phenomenex Zebron ZB-5MS column (30 m, 0.25 mm, 0.25 µm). GC-FID was performed on a Shimadzu GC-2010 using a Chrompack CP-sil 5CB-MS column (25 m, 0.32 mm, 0.25 µm).

Sonication experiments were carried out using a Sonics VC 750 Watt Ultrasonic processor from Sonics and Materials, Inc., with a 13 mm probe operating at a frequency of 20 kHz and 30% maximum amplitude using continuous sonication method. The external temperature was controlled by cooling water (2°C) leading to an internal temperature of approximately 10 °C during sonication.

1-Butyl-3-ethyl-1H-imidazol-3-ium iodide (2): To a 25 mL round bottle flask, 1-ethyl-1H-imidazole (1) (500 mg, 5.2 mmol) NN was added into a solution of 1-iodobutane (1.24 g, 6.76 mmol) in dry THF (5 I mL, 1.04M). The mixture was heated to reflux overnight. After cooling down to room temperature, the upper layer of biphasic mixture was decanted off. Fresh THF was added to wash the imidazolium product for several times. The residue solvent was removed in vacuo giving the title compound as colorless viscous liquid (1.12g, 77% yield).

1H NMR (400 MHz, -d) δ 10.15 (s, 1H), 7.60 (t, J = 1.8 Hz, 1H), 7.52 (t, J = 1.8 Hz, 1H), 4.46 (q, J = 7.4 Hz, 2H), 4.38 (t, J = 7.4 Hz, 2H), 1.94 (p, J = 7.5 Hz, 2H), 1.63 (t, J = 7.4 Hz, 3H), 1.41 (dq, J = 14.8, 7.4 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H).

1-Butyl-3-ethyl-1H-imidazol-3-ium chloride (3): The Dowex® 1X8 chloride form ion exchange resin (3 g) was added to a NN solution of 3-Butyl-1-ethyl-1H-imidazol-3-ium iodide (1) (1.12 g, 4 mmol) in Cl methanol (10 mL). The mixture was stirred at room temperature for 5 - 6 hours. After that, the exchange resin was removed by filtration under argon atmosphere and the solvent was removed in vacuo giving the title compound as pale yellow viscous liquid. (Quantitative yield)

1H NMR (400 MHz, Chloroform-d) δ 10.54 (s, 1H), 7.56 (d, J = 3.6 Hz, 1H), 7.46 (t, J = 1.8 Hz, 1H), 4.45 (q, J = 7.4 Hz, 2H), 4.36 (t, J = 7.4 Hz, 2H), 1.97 – 1.83 (m, 2H), 1.61 (t, J = 7.4 Hz, 3H), 1.39 (dq, J = 14.8, 7.4 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H). 1 H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 7.82 (t, J = 1.8 Hz, 1H), 7.81 (d, J = 1.8 Hz, 1H), 4.24 – 4.17 (m, 2H), 4.15 (t, J = 7.1 Hz, 2H), 1.82 – 1.69 (m, 2H), 1.40 (td, J = 7.3, 0.7 Hz, 3H), 1.23 (dt, J = 14.7, 7.4 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H).

28

Bis(1-butyl-3-ethylimidazol-2-ylidene)gold(I) hexafluorophosphates (5): To a 10 mL Schlenk tube, placed under inert argon atmosphere, a toluene N N solution (0.5 M) of Potassium bis(trimethylsilyl)amide (KHMDS) (1.1 mL, 0.55 mmol) was added to a solution of 1-Butyl-3-ethyl-1H-imidazol-3-ium Au PF6 chloride (91.7 mg, 0.48 mmol) in DMF (2 mL). The resulting solution was N N stirred for 30 min. A suspension of (Me2S)AuCl (66.83 mg, 0.23 mmol) in DMF (0.5 mL) was added to the stirred mixture dropwise. The mixture was stirred for another 4 h. After the period, the solvent was removed in vacuo, and the resulting black color viscous solid was washed with diethyl ether. The resulting hygroscopic solid, Bis(1-butyl-3- ethylimidazol-2-ylidene) gold(I) chloride, was collected and dissolved in water (2 mL). A clear solution was collected after centrifugation of the suspension. To the clear solution, a saturated aqueous potassium hexafluorophosphate (KPF6) (0.2 mL) was added drop by drop until no significant precipitation observed. The resultant precipitate was collected and washed with water and dried in vacuo giving the title compound as white solid. (175mg, 56% yield)

1 H NMR (399 MHz, Methylene Chloride-d2) δ 7.10 (d, J = 1.9 Hz, 1H), 7.07 (d, J = 1.9 Hz, 1H), 4.23 (q, J = 7.3 Hz, 2H), 4.18 (t, J = 7.2 Hz, 2H), 1.88 (p, J = 7.4 Hz, 2H), 1.52 (t, J = 7.3 Hz, 3H), 1.37 (dt, J = 14.8, 7.5 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 183.77, 121.95, 121.49, 51.85, 47.06, 34.03, 20.34, 17.28, 13.96.

1-mesityl-1H-imidazole (6) In a 100 mL two-neck round bottle flask, a mixture of acetic acid (20 mL), 37% N N (wt%) aqueous solution of formaldehyde (6 mL) and 37% (wt%) aqueous solution of glyoxal (9.2 mL) was heated to 70 °C. A mixture of 2,4,6- trimethylaniline (10.78g, 80.0 mmol), ammonium acetate (6.16 g, 80.0 mmol) in 4 mL water and acetic acid (20 mL) was added into the flask dropwise. The mixture was heated for 20h at 70 °C (external temperature). After cooling down to room temperature, the mixture was slowly added to a stirred aqueous solution of 30g NaHCO3 in 300 mL DI water. The resulting brownish solid was separated and dried. The crude product was purified under a sublimation and recrystallization giving the title compound as colourless crystal. (7.8g, the collected chunk crystal give a yield of 53%)

+ GC/MS (ESI) calculated for C12H15N2 [M+H] 187.12, found 187.3 Fragments peaks (above 10% intensity): 41.15, 51.15, 64.9, 71.65, 77, 78.05, 91.1, 115.05, 131.15, 143.15, 144.15, 145.15, 146.15, 158.1, 159.2, 186.2, 187.3) 1 H NMR (200 MHz, Acetone-d6) δ 7.48 (t, J = 1.1 Hz, 1H), 7.12 (t, J = 1.1 Hz, 1H), 7.05 (t, J = 1.2 Hz, 1H), 7.02 (dt, J = 1.3, 0.6 Hz, 2H), 2.32 (s, 3H), 1.96 (s, 6H). 1H NMR (399 MHz, Chloroform-d) δ 7.43 (d, J = 1.1 Hz, 1H), 7.23 (d, J = 1.1 Hz, 1H), 6.97 (s, 2H), 6.89 (d, J = 1.3 Hz, 1H), 2.34 (s, 3H), 1.99 (s, 6H).

(1-butyl-3-mesityl-1,3-dihydro-2H-imidazol-2-ylidene)silver(I) chloride (14)

To a 10 mL round bottom flask, the imidazolium chloride 8 (103 mg, N N 0.369 mmol, 1eq) and silver(I) oxide (80 mg, 0.345 mmol, 0.93eq) were Ag suspended in dry dichloromethane (3 mL) with 4Å molecular sieves in Cl 29

dark. The reaction mixture was stirred for 16 h at room temperature. The mixture was then filtered through a celite pad and concentrated. A small amount of pentane was added dropwise, allowing the product to precipitate. The product was collected. The residual solvent was removed in vacuo giving the title complex as a colorless crystalline solid.(133 mg, 93.3% yield)

1H NMR (399 MHz, Chloroform-d) δ 6.95 (d, J = 4.0 Hz, 3H), 4.22 (t, J = 7.2 Hz, 2H), 2.33 (s, 3H), 1.97 (s, 6H), 1.88 (q, J = 7.4 Hz, 2H), 1.37 (p, J = 7.4 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H).

13C NMR (100 MHz, Chloroform-d) δ 139.52, 135.37, 134.68, 129.42, 122.68, 120.71, 51.91, 33.48, 21.06, 19.66, 17.65, 13.70.

(1-butyl-3-mesityl-1,3-dihydro-2H-imidazol-2-ylidene)gold(I) chloride (15)

To a 5 mL pear-shaped single neck flask, The silver(I)-NHC complex 14 N N (20.5 mg, 0.053 mmol, 1eq) was dissolved in dry DCM (1.5 mL). A

Au solution Chloro(dimethyl sulfide)gold(I) (Au(SMe2)Cl) (19.04 mg, 0.064

Cl mmol, 1.2 eq) in dry DCM (0.5 mL) was added to the stirred solution drop by drop under argon atmosphere. The mixture was stirred for 2h in a dark. The resulting mixture was filtered over Celite and concentrated. A small amount of diethyl ether was added dropwise, allowing the product to precipitate. The product was collected and washed with pentane. The residual solvent was removed in vacuo giving the title complex as a colorless crystalline solid.(28.6 mg, 92% yield).

1H NMR (399 MHz, Chloroform-d) δ 7.16 (d, J = 1.9 Hz, 1H), 6.95 (d, J = 1.2 Hz, 2H), 6.88 (d, J = 1.9 Hz, 1H), 4.30 (t, J = 7.2 Hz, 2H), 2.32 (s, 3H), 2.00 (s, 6H), 1.97 – 1.85 (m, 2H), 1.47 – 1.33 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H).

13C NMR (100 MHz, Chloroform-d) δ 171.87, 139.71, 134.92, 134.89, 129.49, 122.21, 120.47, 51.36, 33.21, 21.23, 19.74, 17.90, 13.84.

α-(N- mesitylimidazolium)-ω-methoxy poly(tetrahydrofuran) (17KDa) (16):62

To an oven dried 250 mL Schlenk round-bottom flask, dry THF * O nNN (150 mL) and 2,6-Di-tert-butylpyridine (DTBP) (0.1 mL, 0.46 mmol) was placed and stirred for 15 minutes. methyl Cl trifluoromethanesulfonate (0.1 mL, 0.91 mmol) was added and stirred at room temperature for 2 hours. After that, 1-ethyl-1H- imidazole (0.2 mL, ca. 2.1 mmol) was added to the flask and stirred for 15 minutes, followed by quenching the reaction with 2 mL methanol and stirred for another 5 minutes. The solvent was partly removed under reduced pressure to about 80 mL left. The highly viscosity solution was poured into water and stay overnight. After decant the water, the chunk polymer solid was dissolved in diethyl ether and dried with magnesium sulfate, followed by filtration and precipitated overnight at -30 °C yielding the polymer ligand as white powder. The ion exchange to chloride anion was carried out by treating the polymer ligand with the Dowex®

30

1X8 chloride form ion exchange resin in methanol for 2 - 3 hours. After filtration and solvent removal, the polymer was re-dissolved in diethyl ether and precipitated in -30 °C overnight. The white solid was filtered and dry under vacuum giving the title polymer ligand as white powder.

1 H NMR (399 MHz, Acetone-d6) δ 10.25(t, J = 1.74 Hz, 1H, NCHN), 8.16 (t, J = 1.74 Hz, 1H,

CH=CH), 7.84 (t, J = 1.74 Hz, 1H, CH=CH), 7.14 (s, 2H, ArH), 4.66 (t, J = 7.61 Hz, 2H, NCH2), 3.4-

3.6 (br, n×4H, CH2OCH2), 3.26 (s, 3H, OCH3), 2.36 (s, 3H, ArCH3), 2.13 (s, 6H, Ar(CH3)2), 1.4-1.8

(br, n×4H, CH2CH2).

α-(N-mesitylimidazolium)-ω-methoxy poly(tetrahydrofuran) hexafluorophosphate (17):

* To a 100 mL round bottle flask, α-(N-ethylimidazolium)-ω- O nNN methoxy poly(tetrahydrofuran) chloride (17KDa) (100mg, 1eq) was dissolved in methanol (50 mL). A solution of ammonium PF6 hexafluorophosphate or potassium hexafluorophosphate (10eq) was added to the flask. The mixture was stirred at room temperature for 4 hours. After evaporate the solvent under reduced pressure, DCM (20 mL) was added to dissolve the polymer. The white precipitate was filtered out through filter paper and the filtrate was concentrated and dried in vacuo overnight giving the title polymer as colorless film.(>90% yield)

1 H NMR (399 MHz, Acetone-d6) δ 9.31(t, J = 1.61 Hz, 1H, NCHN), 8.16 (t, J = 1.79 Hz, 1H,

CH=CH), 7.91 (t, J = 1.81 Hz, 1H, CH=CH), 7.17 (s, 2H, ArH), 4.61 (t, J = 7.61 Hz, 2H, NCH2), 3.4-

3.6 (br, n×4H, CH2OCH2), 3.26 (s, 3H, OCH3), 2.37 (s, 3H, ArCH3), 2.11 (s, 6H, Ar(CH3)2), 1.4-1.8 (br, n×4H, CH2CH2).

α-(Bis(3- mesitylimidazol-2-ylidene)silver(I))-ω-methoxy poly(tetrahydrofuran) hexafluorophosphate (18):

* To a 10 mL pear-shaped single neck flask, the O nNN poly(tetrahydrofuran) hexafluorophosphate ligand (17KDa) (100mg, 1eq) was dissolved in 4 mL DCM. A Ag PF6 solution (2 mL, 1M) and silver oxide (30mg, 0.13mmol) were * O N N added sequentially to the flask. The bi-phasic mixture was under n vigorously stir in dark for 2 – 5 days. After the period, the separated organic layer was diluted with 5 mL DCM and dried with magnesium sulfate followed by passing over Celite. The filtrate was concentrated at room temperature and dried under vacuum in dark giving the title polymer complex as a transparent white (colorless) film in a pure form.

1 H NMR (399 MHz, Acetone-d6) δ 7.65 (t, J = 1.7 Hz, 2×1H, CH=CH), 7.38 (d, J = 1.7 Hz, 2×1H,

CH=CH), 7.09 (s, 2×2H, ArH), 4.16 (t, J = 7.1 Hz, 2×2H, NCH2), 3.4-3.6 (br, n×4H, CH2OCH2), 3.26

(s, 2×3H, OCH3), 2.42 (s, 2×3H, ArCH3), 1.88 (s, 2×6H, Ar(CH3)2), 1.4-1.8 (br, n×4H, CH2CH2).

31

α-(Bis(3- mesitylimidazol-2-ylidene)gold(I))-ω-methoxy poly(tetrahydrofuran) hexafluorophosphate (19):

* To a 25 mL pear-shaped single neck flask, The silver(I)-NHC NN O n polymer complex (2×17KDa) (126mg, 0.0037mmol) was dissolved in 10 mL dry DCM. A solution Chloro(dimethyl PF6 Au * sulfide)gold(I) (Au(SMe2)Cl) (1.08 mg, 0.0037mmol) in dry DCM O nN N (0.5-1 mL) was added to the stirred solution drop by drop under argon atmosphere. The mixture was stirred overnight in a dark. The resulting mixture was filtered through syringe filter and filter over Celite. The solvent was removed in vacuo giving the desired polymer complex as a transparent white (colorless) film in a pure form.(60-80% yield from 16)

1 H NMR (399 MHz, Acetone-d6) δ 7.70 (d, J = 1.9 Hz, 2×1H, CH=CH), 7.39 (d, J = 1.9 Hz, 2×1H,

CH=CH), 7.09 (s, 2×2H, ArH), 4.17 (t, J = 7.1 Hz, 2×2H, NCH2), 3.4-3.6 (br, n×4H, CH2OCH2), 3.26

(s, 2×3H, OCH3), 2.43 (s, 2×3H, ArCH3), 1.90 (s, 2×6H, Ar(CH3)2), 1.4-1.8 (br, n×4H, CH2CH2).

32

2.7 References

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36 Surry, D. S.; Buchwald, S. L. Angewandte Chemie International Edition 2008, 47 (34), 6338–6361. 37 Werner, H. Angewandte Chemie International Edition 2004, 43 (8), 938–954. 38 Crabtree, R. H. Journal of Organometallic Chemistry 2005, 690 (24–25), 5451–5457. 39 Giesbrecht, G. R.; Gordon, J. C. Dalton Trans. 2004, No. 16, 2387–2393. 40 Díez-González, S.; Nolan, S. P. Coordination Chemistry Reviews 2007, 251 (5–6), 874–883. 41 Baba, E.; Cundari, T. R.; Firkin, I. Inorganica Chimica Acta 2005, 358 (10), 2867–2875. 42 Buchmeiser, M. R.; Sen, S.; Unold, J.; Frey, W. Angew. Chem. Int. Ed. 2014, 53 (35), 9384–9388. 43 Blacquiere, J. M.; McDonald, R.; Fogg, D. E. Angewandte Chemie International Edition 2010, 49 (22), 3807–3810. 44 Lin, I. J.; Vasam, C. S. Can. J. Chem. 2005, 83 (6-7), 812–825. 45 Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008, 37 (9), 1776–1782. 46 Wurm, T.; Mohamed Asiri, A.; Hashmi, A. S. K. In N-Heterocyclic Carbenes; Nolan, S. P., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA, 2014; pp 243–270. 47 Patrick, S. R.; Gómez-Suárez, A.; Slawin, A. M. Z.; Nolan, S. P. Organometallics 2014, 33 (1), 421–424. 48 Gómez-Suárez, A.; Ramón, R. S.; Slawin, A. M. Z.; Nolan, S. P. Dalton Trans. 2012, 41 (18), 5461–5463. 49 Nahra, F.; Patrick, S. R.; Collado, A.; Nolan, S. P. Polyhedron 2014, 84, 59–62. 50 Visbal, R.; Ospino, I.; López-de-Luzuriaga, J. M.; Laguna, A.; Gimeno, M. C. J. Am. Chem. Soc. 2013, 135 (12), 4712–4715. 51 Gómez-Suárez, A.; Nelson, D. J.; Thompson, D. G.; Cordes, D. B.; Graham, D.; Slawin, A. M. Z.; Nolan, S. P. Beilstein Journal of Organic Chemistry 2013, 9, 2216–2223. 52 Zou, T.; Lum, C. T.; Lok, C.-N.; Zhang, J.-J.; Che, C.-M. Chem. Soc. Rev. 2015. 53 Baker, M. V.; Barnard, P. J.; Berners-Price, S. J.; Brayshaw, S. K.; Hickey, J. L.; Skelton, B. W.; White, A. H. Dalton Trans. 2006, No. 30, 3708–3715. 54 Visbal, R.; Laguna, A.; Gimeno, M. C. Chem. Commun. 2013, 49 (50), 5642–5644. 55 Collado, A.; Gómez-Suárez, A.; Martin, A. R.; Slawin, A. M. Z.; Nolan, S. P. Chem. Commun. 2013, 49 (49), 5541–5543. 56 Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17 (5), 972–975. 57 Lee, K. M.; Lee, C. K.; Lin, I. J. B. Angew. Chem. Int. Ed. Engl. 1997, 36 (17), 1850–1852. 58 Liu, S.-T.; Reddy, K. R. Chem. Soc. Rev. 1999, 28 (5), 315–322. 59 Groote, R.; Szyja, B. M.; Pidko, E. A.; Hensen, E. J. M.; Sijbesma, R. P. Macromolecules 2011, 44 (23), 9187–9195. 60 Rit, A.; Pape, T.; Hahn, F. E. Journal of the American Chemical Society 2010, 132 (13), 4572– 4573. 61 Zhao, Y.; Gilbertson, S. R. Org. Lett. 2014, 16 (4), 1033–1035. 62 Rooze, J.; Groote, R.; Jakobs, R. T. M.; Sijbesma, R. P.; van Iersel, M. M.; Rebrov, E. V.; Schouten, J. C.; Keurentjes, J. T. F. J. Phys. Chem. B 2011, 115 (38), 11038–11043.

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Chapter 3 Colloidal gold nanoparticles and a potential gold cluster

3.1 Introduction

On the road to the synthesis of Au(NHC)2 with polymer chains attached to the ligands two other unexpected products were formed, for which the synthesis has been worked out and the characterization is reported. The current describes these products,, a simple method for the synthesis of gold nanoparticle (AuNPs) and a gold cluster which is most probably a hexamer.

3.2 Results and discussion

3.21 Colloidal gold nanoparticles

In chapter 2, the synthetic route for the Au(I)-NHC2 mechanophore embedded in a polyTHF chain

(2×17 kDa) was reported by using transmetallation from the corresponding Ag(I)-NHC2 complex. The reason for using this method is that free-carbene methods (Figure 3.1) always gave incomplete conversion resulting in a product mixture containing imidazolium ligand, Au(I)-monoNHC and Au(I)- bisNHC complex. The best results with the free-carbene route were obtained using DMF as solvent and KHMDS as base. GPC of the product mixture obtained under these conditions show a peak with double molecular weight of polymer chain coexisting with a peak representing the single polymer chain (Figure 3.2).

Remarkably, when the reaction of free carbene route was carried out in the dark and with an aluminum boat in the Schlenk tube using THF as solvent, a homogeneous reddish-purple solution was obtained (Figure 3.3). The UV-Vis spectrum of the resultant solution indicates a strong absorption at 530 nm. These interesting results drive a further characterization. DLS (dynamic light scattering) shows that nanoparticles exist in this solution with an average radial size of about 76.89 nm and a narrow size distribution (Figure 3.4). TEM of samples deposited on copper further confirms the presence of nanoparticles with an average diameter of 12-20 nm red-purple color solution (Figure 3.5). By referring with literatures,1,2 the UV-Vis absorption and the TEM results indicate gold nanoparticle (AuNPs) formed. Since the optical of AuNPs strongly depend on their size, size distribution and shape, the specific color of AuNPs can reflect the diameter of the nanoparticle.3,4 In this case, by referring with literature reports, 5,6 the purple color of AuNPs reflect a size around 15 nm diameter, which matches with the results from TEM.

Combined with the results from DLS, the proposed nanoparticle size suggests that they are surrounded by a large number of polyTHF chains. According to literature, the syntheses of AuNPs requires adding reducing agents such as sodium borohydride or citrate to reduce the gold cation to metallic gold. In this case, the KHMDS possibly plays a role of reducing agent. A further experiments by stirring a simple mixture of imidazolium end capped polyTHF with Au(SMe2)Cl in the dark also can form purple color AuNPs. We conclude that polyTHF probably acts as a stabilizer during the process of seeding and nucleation to inhibit a fast growth of the NP’s due to the ‘metallophilic property’ of π-π interact between gold atoms.

pTHF N N Et KHMDS pTHF N N Et Au Cl Cl Au(SMe2)Cl Solvent pTHF NN Et

Figure 3.1 The free35 carbene route



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With these results and literature information for gold cluster,7,8,9,10,11 we speculate that a gold cluster formed having a ‘hexamer’ structure as the central core, to which six polymer chains are attached. However, limitation in further characterization, such as the inability of X-ray in XPS to penetrate polyTHF chain to reach the core metal, hampers identification of this complex. To shed more light on the structure of the purported hexamer, a small butyl group linked imidazolium ligand was used under the same condition for the ‘hexamer’ synthesis. However, in several attempts, the reaction only yielded Au(I)-mono-NHC complex and Au(I)-bis-NHC complex. This means the polymer chain possibly plays a role in the formation of the ‘hexamer’.

3.4 Conclusion

Compared with literature reports, as far as we know, the discovered simple synthetic method of AuNPs by just stirring the polyTHF with Au(I) salt without adding any other reducing agents is the most convenient method to obtain AuNPs.

A new stable gold-polyTHF complex, the so called ‘hexamer’, with six times molecular weight of polyTHF chain determined by THF-GPC, was accidentally synthesized. Further investigation and characterizations to determine the structure are still needed.

3.3 Experiment Section

The simplest method of synthesis of AuNPs:

To a 10 mL round bottle flask, the imidazolium ended polyTHF (100 mg) was dissolved in toluene (5 mL). A solid of Au(SMe2)Cl (1 mg) was added to this solution. After stirring in dark at room temperature, a red-purple color solution containing AuNPs was formed.

The synthesis of ‘Hexamer’ complex

To a Schlenk tube, the imidazolium chloride end-functionalized polyTHF (300mg, 18KDa, 0.0166 mmol, 2.24 eq) was dissolved in dry THF (5 mL). To this solution, KHMDS (0.05 mL, 0.5mol/L in toluene, 3.36eq) was added under argon. After stir for 20mins, a solid of Au(SMe2)Cl (2.19mg, 0.0074 mmol,1eq) was added to this solution in one portion. After stirring at room temperature exposed to light for 2h, another portion of KHMDS (0.2 mL, 0.5mol/L in toluene, 13.4eq) was added to the solution and stirred for another 1h.

The resulting solution was diluted with DCM (15 mL), and sequentially washed with DI water (10 mL), diluted hydrochloride acid (0.1M, 10mL), and DI water (10 mL). The orgnic layer was dried with magnesium sulfate, and then filtered through celite. After solvent removal under vacuum, the polymer complex obtained as a dry film. (THF-GPC results indicate after workup, the ‘hexamer’ peak still firmly exist without significant decompose to single polymer chain)

39

3.5 References

1 Daniel, M.-C.; Astruc, D. Chem. Rev. 2004, 104 (1), 293–346. 2 Schmid, G. Chem. Rev. 1992, 92 (8), 1709–1727. 3 Gole, A.; Murphy, C. J. Chem. Mater. 2004, 16 (19), 3633–3640. 4 Whetten, R. L.; Gelbart, W. M. J. Phys. Chem. 1994, 98 (13), 3544–3549. 5 Leff, D. V.; Ohara, P. C.; Heath, J. R.; Gelbart, W. M. J. Phys. Chem. 1995, 99 (18), 7036–7041. 6 Alshammari, A.; Köckritz, A.; Narayana Kalevaru, V.; Bagabas, A.; Martin, A. Open Journal of Physical Chemistry 2012, 02 (04), 252–261. 7 Oliver-Meseguer, J.; Cabrero-Antonino, J. R.; Domínguez, I.; Leyva-Pérez, A.; Corma, A. Science 2012, 338 (6113), 1452–1455. 8 Gramage-Doria, R.; Reek, J. N. H. Angew. Chem. Int. Ed. 2013, 52 (50), 13146–13148. 9 Jin, L.; Weinberger, D. S.; Melaimi, M.; Moore, C. E.; Rheingold, A. L.; Bertrand, G. Angew. Chem. Int. Ed. 2014, 53 (34), 9059–9063. 10 Bosch-Navarro, C.; Laker, Z. P. L.; Thomas, H. R.; Marsden, A. J.; Sloan, J.; Wilson, N. R.; Rourke, J. P. Angew. Chem. Int. Ed. 2015, 54 (33), 9560–9563. 11 Wan, X.-K.; Xu, W. W.; Yuan, S.-F.; Gao, Y.; Zeng, X.-C.; Wang, Q.-M. Angew. Chem. Int. Ed. 2015, 54 (33), 9683–9686.

40

Chapter 4 Mechanochemical scission of Pd(II)-NHC complex

4.1 Introduction

In our group, a series of mechanophores with a similar metal-bisNHC structure have been studied. The sonication experiments for Ag(I)-bisNHC mechanophore indicate that the Ag-NHC bond is labile. The Ag(I)-NHC mechanophore polymer is unstable at room temperature and light sensitive. When the metal was changed to palladium(II), however, the Pd(II)-bisNHC mechanophore is fairly stable under sonication. In line with our group research, the Au(I)-NHC mechanophore was designed as described in chapter 2. We originally expected that the Au(I)-NHC bond is stronger than Ag(I)-NHC bond but weaker than Pd(II)-NHC bond. However, quantitatively understanding of the bond strength sequence between Au(I)-NHC mechanophore and Pd(II)-NHC mechanophore cannot only rely on a simple bond energy comparison, as there are multiple factors that determine the bond strength under force. For example, introducing different functional groups attached to the NHC ring may cause variable steric hindrance which further influences the metal-NHC bond strength. A metal coordinated by nucleophilic ligands, such as chloride, or a non-nucleophilic ligand, such as hexafluorophosphate, may result in weakening or strengthening of the metal-NHC bond. A transition metal with higher valence may cause a stronger metal-NHC bond than that with low valence. On one hand, the nature of transition metal with strong relativistic effects may strengthen the metal-NHC bond, but on the other hand, the more diffusive orbital of the late transition metal may cause a smaller orbital overlap and weaken the metal- NHC bond. Therefore, to compare the metal-NHC bond strength, a series of comprehensive factors need to be taken into account case by case. Experimental studies are necessary to compare the bond strength between Au(I)-NHC and Pd(II)-NHC. In this chapter, the synthesis and mechanochemical scission of Pd(II)-NHC mechanophore are described

* * O nNN R O nNN R

PF6 Au Cl Pd Cl * * R R O nN N O nN N

Figure 4.1 Structural comparison of Au(I)-bis(NHC) mechanophore (left) and Palladium(II)-bis(NHC) mechaonophore (right)

4.2 Results and discussion

4.21 Synthesis of Pd(II)-NHC model complex

A short butyl chain linked NHC palladium complex 22 was first selected as the target module molecule. It was successfully synthesized in two ways: 1) via a free carbene route according to the literature method1 and 2) by a transmetallation reaction2 from silver -monoNHC complex (Figure 4.2).

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For developing a transmetallation method for synthesis of 23, a two-step method by separating the 22, followed by transmetallation was first investigated. The mechanophore 23 was successfully obtained. However, it was found that the yield of 23 is largely determined by the purity of 22, which is not stable at room temperature. Therefore, an idea of using one-pot condition to synthesize 23 without separate 22 was tested. The first experiment by mixing silver(I) oxide with palladium dichloride acetonitrile complex indicated that no reaction happens by mixing the two agents. Considering the small amount of water generated during the step of silver-NHC synthesis will influence on the next transmetallation step which is sensitive to water, the 4Å molecular sieves was added during the reaction. This one-pot method gives a fully conversion of polymer ligand.

4.23 Mechanochemical scission of Pd(II)-NHC complex

Mechanochemical scission tests of palladium mechanophore 23 were carried out on solutions of 23 (31.2 mg, 2×15.6KDa, 0.001 mmol) in a solvent mixture of toluene (5 mL), acetonitrile (0.5 mL) and acetic acid (0.5 mL) with a concentration of 5.2 mg mL–1. A sample of 0.5 mL solution was withdrawn to a vial as control experiment. The rest of the solution was cooled to 2°C (external cooling water temperature), and then saturated with methane. Subsequently, the solution was sonicated for 120 mins at 30% of the maximum amplitude (corresponding to a total power input of 14–20 W). During the sonication the temperature of the solution inside the vessel was maintained around 10°C. A small amount of sample (0.4 mL solution) was regularly withdrawn from the sonication vessel (after each 20 mins). The solvent in the sample was evaporated in vacuo. The residual polymer was dissolved in chloroform (0.3 mL) submitted to GPC to determine the amount of scission.

The GPC result of the control experiment indicates that no scission takes place without sonication, meaning that the palladium mechanophore in toluene in the presence of trapping agents is stable at room temperature. The kinetic study on the GPC results of sonication indicate that the mechanophore 23 give a fast mechanoscission (Figure 4.6).

The scission rate is under investigation by applying Gaussian function:

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MALDI-TOF MS analyses were recorded on PerSeptive Biosystems Voyager‐DE Pro in reflector mode using DCTB matrix, 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]manolnitrile.

GPC was measured on a Shimadzu LC-10DVP system with a Shimadzu RID-10A detector and a PLgel 5-μm mixed-D column with THF as the eluent (flow rate: 1 mL/min) and poly(styrene) standards for the calibration.

Sonication experiments were carried out using a Sonics VC 750 Watt Ultrasonic processor from Sonics and Materials, Inc., with a 13 mm probe operating at a frequency of 20 kHz and 30% maximum amplitude using continuous sonication method. The external temperature was controlled by cooling water (2°C) leading to an internal temperature of approximately 10 °C during sonication.

The synthesis of bis(1-butyl-3-mesityl-2,3-dihydro-1H-imidazol-2-yl)palladium(II) chloride 22:

N N N N

Cl Pd Cl + Cl Pd Cl

N N N N

trans-anti trans-syn

To a 5 mL pear-shape single neck flask, the silver(I)NHC 16 (5.36 mg, 0.0139 mmol, 1eq) was dissolved in dry DCM (0.5 mL). Bis(acetonitrile)dichloropalladium(II) (1.802 mg, 0.0069 mmol, 0.5eq) was added to this solution. After stirring for 2h at room temperature, the reaction mixture was then filtered of a pad of celite and concentrated. It is then layered with pentane, allowing the product to precipitate. After decanting the solution, the product is washed with pentane and dried in vacuo giving the title compound as pale yellow powder. (4.28 mg, 92% yield)

1H NMR (500 MHz, Chloroform-d) δ 6.97 (s, 1H), 6.93 (d, J = 1.8 Hz, 0H), 6.88 (d, J = 1.8 Hz, 1H), 6.85 (s, 1H), 6.70 (d, J = 1.8 Hz, 0H), 6.65 (d, J = 1.8 Hz, 0H), 4.63 (dd, J = 8.6, 6.7 Hz, 1H), 4.23 (t, J = 7.6 Hz, 1H), 2.46 (s, 1H), 2.34 (s, 2H), 2.21 (s, 3H), 2.18 – 2.09 (m, 1H), 1.90 (s, 2H), 1.78 (tt, J = 9.3, 6.8 Hz, 1H), 1.49 (dt, J = 14.9, 7.4 Hz, 1H), 1.22 (h, J = 7.4 Hz, 1H), 1.03 (t, J = 7.4 Hz, 1H), 0.90 (t, J = 7.3 Hz, 2H).

13C NMR (100 MHz, Chloroform-d) δ 170.42, 170.12, 138.17, 137.36, 136.64, 136.14, 135.93, 135.64, 128.72, 128.65, 122.38, 122.15, 120.54, 120.32, 50.72, 50.67, 33.14, 32.88, 21.27, 21.11, 20.14, 19.88, 18.89, 18.53, 13.92.

46

The synthesis of Palladium(II)-bisNHC mechanophore 24:

O NN O NN * n * n Cl Pd Cl + Cl Pd Cl

N N NN O * O n n *

To a Schlenck tube, 100mg imidazolium chloride ended 15.6kDa polyTHF (1eq.) was dissolved in 2-4 mL dry DCM. To this solution, 2-4 eq of silver oxide and 4Å molecular sieves were added. The mixture was keep stirring under argon in dark for at least 48h. After this period, A solution of (0.831 mg, 0.0032 mmol, 0.5 eq.) Bis(acetonitrile)- dichloropalladium(II) in dry DCM (1 mL) was added to this flask drop by drop under argon. The mixture was allowed to keep stirring for another 18h in dark condition.

Work up: The resulting mixture was filtered through filter paper. The DCM solvent was pumped out under vacuum. Dry toluene (5 mL) was added to dissolve the residue polymer complex. The toluene solution was sequentially filtered over anhydrous magnesium sulfate, dry neutral alumina, and dry Celite and flushed with toluene. The resulting solution was filtered through syringe filter (0.22 µm pore size). The palladium polymer complex was finally obtained after solvent removal under vacuum. (60- 80% yield)

1H NMR (500 MHz, Chloroform-d) δ 6.97 (d, J = 1.3 Hz, 1H), 6.91 (d, J = 1.9 Hz, 0.40H), 6.85 (s, 0.39H), 6.70 (d, J = 1.8 Hz, 0.39H), 6.65 (d, J = 1.9 Hz, 0.18H), 4.65 (t, J = 7.5 Hz, 0.40H), 4.24 (t, J

= 7.5 Hz, 0.85H), 3.65 – 3.21 (m, nH, CH2OCH2), 3.33 (s, 3H), 2.47 (s, 0.54H), 2.35 (s, 1.13H), 2.20

(s, 2.18H), 1.90 (s, 1.27H), 1.68 (s), 1.80 – 1.41 (m, nH, CH2CH2).

4.5 References

1 Lebel, H.; Janes, M. K.; Charette, A. B.; Nolan, S. P. J. Am. Chem. Soc. 2004, 126 (16), 5046–5047. 2 Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17 (5), 972–975. 3 Tyrrell, E.; Whiteman, L.; Williams, N. Journal of Organometallic Chemistry 2011, 696 (22), 3465–3472. 4 Huynh, H. V.; Wu, J. Journal of Organometallic Chemistry 2009, 694 (3), 323–331.

47

Conclusions and Outlook

The Au(I)-NHC mechanocatalyst was successfully synthesized. The mechanoscission experiments indicate it has a scission in the Au-NHC bond. The latent catalyst can be activated and catalyse a alkyne isomerization reaction.

A Pd(II)-NHC mechanophore was synthesized by a transmetallation reaction. The mechanoscission experiments indicate it has a fast scission.

For the research of Au(I)-NHC mechanocatalyst, one control experiment that sonicating the mixture of the latent Au(I)-bisNHC model compound, which has a short butane chain linked NHC ligand, with 4- Pentynoic acid is need to be test.

Synthesize and test the catalytic property of Au(I)-NHC mechanocatalyst with different MW of the polymer ligand are necessary in order to prove that the different scission rates may lead to different catalytic activity under sonication.

The solvent effect need to be furtherly investigated that how much the using of acetonitrile can influence on the catalytic property of the mechanocatalyst.

Some other ideas for trapping agent selection that using chiral phosphoric acid to deactivate the NHC catalytic property and using tetra-alkyl ammonium chloride (Phase Transfer Catalysts) to deactivate the Au(I) catalytic property are worth to try.

The mechanoscission rate of Pd(II)-NHC mechanophore with different molecular weights of polyTHF ligand are going to test. The integration methods for using ‘origin’ software are going to be furtherly analysed.

The potential mechanochemical activation of Pd(II)-NHC mechanocatalyst with substrates with π- donor will be selected to test.

48

Acknowledgements

First, I would like to express my deepest gratitude to my research advisor, Prof. Rint Sijbesma, for giving me this opportunity to work on the interesting research projects in your group. I greatly appreciate your encouragement, guidance and giving me a free space for doing research. Your continuous supports for students, face to face weekly meeting and your organized time management leave me a deep impression. I would like to especially, sincerely thank you to revise my thesis. Working in Rint group for doing research and learning knowledge is my happiness.

I sincerely hope our group have continuous growing in TU/e and have more success in science.

I would like to thank Dr. Erik Schwartz for your guidance, helps and your friendliness. Your supports leave me a deep impression. I cannot forget it.

I would like to thank Abidin Balan, I like to discuss science with you. And the most important thing is your presence in office/lab in weekends can allow me as a student to work in lab during weekends. Thanks for it!

I express my sincerely thanks to Dr. Lech Milroy. I cannot forget your sincere help and our interesting discussion on organic chemistry. I respect your passion for research and appreciate your truly motivation to support me on my road of doing academic research.

I would like to thank my thesis committee members, Dr. Anja Palma and Dr. Tim Noel. I like Anja’s advanced stereochemistry course. After took your course, it changed my reading habit that when I regularly look through academic publication websites, I find I also become interested in reading paper in chiral supramolecular polymer area.

I thank Dr. Tim Noel to continually send me many ‘VIP’ (Very Interesting Paper) to read in organic flow chemistry area. You are the first person let me know what does the ‘VIP’ mean in academia.

I would like to thank Dr. Lou and Ralf for your helps and your professional dedication spirit.

Finally, I want to express my appreciation to family members for their love, support, understanding and encouragement.

Yong Niu

49

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