Ruthenium Olefin Metathesis Catalysts: Tuning of the Ligand Environment Ruthenium olefine metathese katalysatoren: Optimalisatie van de ligandsfeer Nele Ledoux Promotor: Prof. Dr. F. Verpoort Proefschrift ingediend tot het behalen van de graad van Doctor in de Wetenschappen: Scheikunde Vakgroep Anorganische en Fysische Chemie Vakgroepvoorzitter: Prof. Dr. S. Hoste Faculteit Wetenschappen 2007 ii Members of the Dissertation Committee: Prof. Dr. F. Verpoort Prof. Dr. Ir. C. Stevens Dr. V. Dragutan Dr. R. Drozdzak Dr. R. Winde Prof. Dr. Ir. D. Devos Prof. Dr. J. Van der Eycken Prof. Dr. P. Van Der Voort Prof. Dr. K. Strubbe This research was funded by the Fund for Scien- tific Research - Flanders (F.W.O.-Vlaanderen). Acknowledgments This dissertation is the final product of an educative and fascinating journey, which involved many contributors. First of all, I wish to express my gratitude to the people with whom I learned how to do research. There is my promotor Prof. Dr. Francis Verpoort who gave me the opportunity to join his ’Catalysis group’ and ensured the necessary funding. I’m especially grateful for his confidence and indulgence. In addition, I have been extremely lucky to work with several nice colleagues. Thank you, Thank you (= double thank you ♥) to Bart who helped me conquer many small and big difficulties, and by doing so, contributed a lot to the results reported here. Special thanks to Hans for many funny moments and support over the years. Of course, my acknowledgments also go to the other boys: Carl, Stijn, David, Jeroen, Prof. Dr. Pascal Van Der Voort and not to forget Siegfried, Steven, and Mike for the pleasant working atmosphere and supportive chats. I owe thanks to Dr. Renata Drozdzak for the introduction of Schlenk equipment, helping us to make blue THF, and for friendly words. I’d like to thank Fu and Oana for their friendship, and never-ending kindness. I’ve enjoyed the presence of many thesis students and foreign visitors in our group and I will remember them with pleasure. Many more S3 members deserve to be mentioned here, which is not only for good-humored coffee breaks and innocent gossip. I’m indebted to Dr. Anthony Linden of Institute of Organic Chemistry, University of Z¨urich, for several single crystal analyses, and a very pleasant cooperation. More thanks go out to Jacques P´ecaut of CEA-Grenoble for crystal structure analysis, and to Olivier Grenelle and Dr. Marc Proot of Chevron Technology, Ghent, for elemental analyses. I would like to thank the members of the dissertation committee for their valuable feedback. My parents, brother, sister, family, and friends are gratefully acknowledged for providing unconditional, warm-hearted support. ii Preface The basic subject of interest throughout this thesis is the olefin metathesis trans- formation. The formation of carbon-carbon double bonds is one of the most fundamental chemical processes. In this context, metathesis makes a significant contribution, since this transition metal catalyzed reaction is a C-C bond breaking and bond making process in which an overall exchange of groups around the double bonds results in several outcomes. As were many catalytic reactions, olefin metathesis was discovered by accident. Researchers at DuPont were trying to expand the scope of the addition poly- merization reactions but obtained a highly unsaturated polymer. 1 In those early days olefin metathesis was rather cumbersome, but it has been upgraded to a very practical, efficient and flexible synthetic methodology. The amount of synthetic transformations that can be accomplished is staggering, since the same catalytic systems can promote different types of metathesis reactions, depending on the substrates and reaction conditions employed. Olefin metathesis now allows cleaner, more efficient, and less expensive industrial production of polymers, fine chemicals, pesticides, and pharmaceutical intermediates. The recent Nobel Prize awarding of Y. Chauvin for groundbreaking contributions to the discovery of the olefin metathesis mechanism, and to R. R. Schrock and R. H. Grubbs, who introduced a large number of catalytic metathesis initiators, has put emphasis on this increasing industrial interest. 2–4 Despite the recent advances, the search for commercially relevant catalyst systems remains challenging. When thinking of commercial applications, even a small increase in catalyst efficiency becomes of major importance. Today’s catalysts are well defined and the mechanisms well understood. This allows for further growth of this fascinating field of research by the design of new catalysts or the improvement of existing catalytic systems, as the work presented in the next chapters will hopefully help to demonstrate. Since specifically designed ligands are key in optimizing the efficiency of olefin metathesis mediators, we mainly focused on the effects of ligand modification. A first type of ligand which caught our attention, is a bidentate Schiff base. Schiff bases are known to strongly enhance the thermal and moisture stability of the corresponding complexes. These features were employed in the development of latent catalysts, which are chemically activated upon the addition of acids. A iv second type of ligands playing an important role in the carried out research, are N -heterocyclic carbenes (NHCs). NHC ligands have recently gained popularity due to a large number of attractive properties. Through distinct variations in the amino side groups of the NHC ligands, we aimed at catalyst fine tuning. A range of different catalysts was synthesized, fully characterized and subjected to representative test reactions, which allowed comparison with benchmark olefin metathesis catalysts. v Outline Chapters 3, 4, 5, and 6 have been published as peer review articles. Chapter 3 is adapted from references 5,6, chapter 4 from 7,8, chapter 5 from 9,10, and chapter 6 from 11. All chapters contain their own abstract introducing the subject matter. Chapter 1 was devoted to a general introduction on the olefin metathesis reac- tions, mechanism, catalysts, and applications. Chapter 2 comprises a second introductory part. Since the catalyts developed during this project all contain an N -heterocyclic carbene (NHC) ligand, some general properties of these ligands in organometallic complexes were described. Furthermore, the beneficial properties of NHC ligands in ruthe- nium based olefin metathesis catalysts were explained through profound consideration of the reaction mechanism. Chapter 3 addresses the synthesis and catalytic performance of a ruthenium benzylidene catalyst bearing a Schiff base ligand. The bidentate Schiff base ligand exerts, due to its ”dangling” character, a pronounced effect on both the activity and stability of the resulting complex. This complex shows negligible metathesis activity at room temperature, while the addition of an acid was found to induce a substantial activity enhancement. The catalyst latency is of particular interest for industrial applications such as reaction injection molding (RIM) processes, since catalyst and monomer can be stored without concomitant polymerization. Chapter 4 deals with the search for alternative synthetic pathways. When aiming at the development of new catalysts, one should not only focus on catalyst activity or stability, as highly sophisticated and well-defined initiators are sometimes too expensive for applications on an industrial scale. Other important aspects deserving consideration are the cost to make the catalyst, availability of the starting materials, and the complexity of the preparative routes. In addition, it is often relevant to search for patent-free synthetic strategies. In this context, chapter 4 encloses a contribution to the search for new synthetic routes, which lead to alternatives for the classic ruthenium ben- zylidene complexes. The air and moisture stable, easy to synthesize, Ru dimer [(p-cymene)RuCl2]2 was chosen as a catalyst precursor. Chapter 5 examines the effect of new N -heterocyclic carbenes in Grubbs cata- lysts. Various symmetrical and asymmetrical NHCs bearing aliphatic amino side groups were synthesized. In our attempts to isolate the corresponding Grubbs 2nd generation catalysts, we were unsuccessful for the symmetrical aliphatic NHCs. For the asymmetrical ligands bearing an aliphatic moiety vi on one side and an aromatic mesityl group on the other side, substitution of a phosphine ligand was achieved. Replacement of the NHC mesityl ring with a 2,6-diisopropylphenyl moiety was found to have a substantial effect. Facile bis-coordination of the NHC ligands was observed, which was assigned to an enhanced phosphine dissociation rate of the corresponding mono(NHC) complexes. Chapter 6 describes how new NHC ligands were successfully coordinated to the Hoveyda-Grubbs catalyst. In various olefin metathesis test reactions, subtle steric differences in the NHC amino side groups were found to exert a critical influence on the activity of the corresponding catalysts. Chapter 7 briefly summarizes the conclusions made throughout the thesis, and a short future outlook is given. Chapter 8 summarizes this thesis in Dutch. Table of Contents Acknowledgments i Preface ii 1 Olefin Metathesis 1 1.1 Metathesis transformations . 1 1.2 Mechanism ............................... 1 1.3 Catalystsystems ............................ 3 1.4 Industrial applications . 7 1.4.1 Production of petrochemicals . 7 1.4.2 Polymer synthesis . 8 1.4.3 Finechemistry ......................... 9 2 N -Heterocyclic Carbenes 13 2.1 General properties . 13 2.2 Stability of N -heterocyclic