Durham E-Theses Aromatic transformations facilitated by η6ruthenium complexes PIKE, JACK,ANDREW How to cite: PIKE, JACK,ANDREW (2019) Aromatic transformations facilitated by η6ruthenium complexes, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/13094/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk Aromatic transformations facilitated by η6–ruthenium complexes Jack Andrew Pike A thesis submitted for the degree of Doctor of Philosophy Department of Chemistry December 2018 Abstract The chemistry of η6-arene metal complexes has been explored for over 60 years and the ability to activate arenes through this complexation has been used extensively in organic synthesis. As a result of binding to the metal, the complexed arene becomes more susceptible to nucleophilic attack and deprotonation of the aromatic and benzylic protons is made more facile. Additionally, binding a metal centre to one face of the arene subsequently has a steric effect on the reactivity, wherein the bound face is blocked from reagents and directs attack to the free face. Over the last 15 years, this area of organometallic chemistry has seen a resurgence of interest due to the catalytic capabilities of these complexes. Through an arene exchange mechanism, arenes can participate in reactions when bound to the metal catalyst, and can then exchange for another equivalent of starting material to facilitate catalytic turnover. This thesis will describe a number of projects that have been developed over three years that uses this methodology to perform transformations which are of significant interest to the scientific community. Firstly, a trifluoromethylation protocol is described, which uses a [RuCp]+ binding unit to activate a range of electron-deficient arenes towards the nucleophilic attack of commercially available Me3SiCF3 (Ruppert’s Reagent). A library of complexes exhibit reaction, and a mixture of products are formed via SNAr and ortho-addition mechanisms. Following trifluoromethylation, the unbound arenes can be collected in quantitative yield using photolysis and chemical oxidation. Secondly, a C–H activation and arylation protocol is described, where the same [RuCp]+ binding unit is used to enhance aromatic acidity of a η6-arene complexes. Through a concerted metalation deprotonation mechanism, a library of complexes can be activated by silver, and consequentially arylated using catalytic palladium chemistry. Following arylation, the bi-aryl arene can be liberated from ruthenium by UV irradiation. The largest chapter of this thesis describes the catalytic radical hydrodeiodination of aryl iodides via an arene exchange mechanism. This reaction uses commercially available materials to achieve deiodination for iodoarenes in high yields and with excellent functional group tolerance and chemoselectivity. Lastly, the early findings towards tether assisted arene exchange is described. The rates of arene exchange are studied for a library of tethered Cp ruthenium complexes, which show potential for enhanced arene exchange in catalytic reactions. 2 Declaration The work described in this thesis was undertaken at the Department of Chemistry, Durham University between October 2014 and June 2018. All of the work reported is my own, except where specifically stated otherwise. No part has previously been submitted for a degree at this or any other university. Statement of Copyright The copyright of this thesis rests with the author. No quotations should be published without prior consent and information derived from it must be acknowledged. 3 Acknowledgements Mum and Dad, I cannot begin to explain how grateful I am for everything you have both done for me. The years you went without so Tom, Hettie and I could succeed have carved in me values that have made me the man I am today. You taught me humility, courage, patience and kindness. All I ever wanted was to make you proud, so this thesis is dedicated to you. I also want to thank all members of my family for their love and support over the years, in particular to my Grandmothers (Nan Sheep, Nan Video and Nan Pip) for teaching me that there is no substitute for hard work. I want to thank the friends I have made through Ustinov College, in particular Yan and Jasmine, who have kept me on track through good and bad times. I would also like to thank friends I made in the department of chemistry, including Andrew, Phil, Akkharadet, Brette and Luke. Thanks also to members, past and present, of Ustinov College Spin Doctors for an incredible release of stress and competitive energy. Thank you to Dr Aileen Congreve, Dr Alan Kenwright, Dr Juan Aguilar Malavia, Dr Jackie Mosely, Mr Peter Stokes, Dr David Parker, Dr Emily Unsworth, and Dr Dmitry Yufit for your advice and expertise in analysis. Thanks go to Dr Luke Wilkinson, Archie McNeillis, Niall O’Driscoll and William Helme to their contributions to the Walton group. Thank you to the Department of Chemistry, Durham, for funding and opportunities. Special thanks to Dr James Walton for your guidance and support, and for taking a shot on me. I still remember the first time I walked into your office in the summer of 2015, and I hope you are as proud of our achievements as I am. And lastly, thank you to Jess. You showed me what love is and I could not have done this without you. 4 Abbreviations Ac acetate Ad adamantyl Bu butyl CDCl3 deuterated chloroform CD3OD deuterated methanol CHCl3 chloroform CMD concerted metalation deprotonation COD cyclooctadiene COSY correlation spectroscopy Cp cyclopentadiene Cp* pentamethylcyclopentadiene d doublet DBU 1,8-diazabicyclo[5.4.0]undec-7-ene DBN 1,5-diazabicyclo[4.3.0]non-5-ene DCM dichloromethane DCE dichloroethane dd doublet of doublets ddd doublet of doublets of doublets DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone ddt doublet of doublets of triplets DMAP dimethylaminopyridine DMI 1,3-dimethyl-2-imidazolidinone DMF dimethylformamide DFT density functional theory 5 DPPP 1,3-bis(diphenylphosphino)propane dq doublet of quartets dt doublet of triplets EDG electron donating group ESI electrospray ionisation Equiv equivalent Et ethyl EWG electron withdrawing group FG functional group High Res high resolution HOMO highest occupied molecular orbital HPLC high performance liquid chromatography In situ in the original place LUMO lowest unoccupied molecular orbital m multiplet m meta Mass Spec mass spectrometry Me methyl MW microwave NMR nuclear magnetic resonance NOESY nuclear Overhauser effect spectroscopy o ortho p para PET positron emission tomography Ph phenyl 6 Pr propyl q quartet qdd quartet of doublets of doublets s singlet sept. septet SET single electron transfer SNAr nucleophilic aromatic substitution t triplet TBAF tributylammonium fluoride TEMPO 2,2,6,6-tetramethyl-1-piperidinyloxy Tf triflate TIPS triisopropylsilyl ether tt triplet of triplets td triplet of doublets tdd triplet of doublet of doublets TFA trifluoroacetic acid THF tetrahydrofuran TMS trimethylsilane UV ultraviolet δ delta η eta π pi σ sigma 7 Contents 1. Introduction ......................................................................................................................... 10 1.1 The Chemistry of Benzene .......................................................................................... 10 1.2 Properties of Metal-Arene Complexes ........................................................................ 11 1.3 Synthesis of Arene π-complexes .................................. Error! Bookmark not defined. 1.4 Reactivity of Arene π-Complexes ............................................................................... 13 1.4.1 Reactions Using Chromium and Molybdenum (Group 6) .................................. 13 1.4.2 Reactions Using Manganese, Rhenium and Technetium (Group 7) ................... 17 1.4.3 Reactions Using Iron and Ruthenium (Group 8) ................................................ 19 1.4.4 Reactions Using Cobalt, Rhodium and Iridium (Group 9) ................................. 23 1.5 Arene Exchange .......................................................................................................... 25 1.5.1 Arene Exchange Mechanism .............................................................................. 25 1.5.2 Dependence on Incoming and Outgoing Arene .................................................. 26 1.5.3 Tether Accelerated Arene Exchange ................................................................... 28 1.5.4 Photocatalytic Arene Exchange .......................................................................... 30 1.6 Metal Arene complexes in Catalysis ........................................................................... 31 1.7 Project Aims ................................................................................................................ 39 2. Nucleophilic trifluoromethylation