1 Heavier Group 2 Metals: Application to Intermolecular Hydroamination, C-F Activation and Intramolecular Hydroalkoxylation Christine Brinkmann Imperial College London, Chemistry A Thesis submitted for Doctorate of Philosophy (Imperial College London) 2 3 Statement of copyright The copyright of this thesis rests with the author. No quotation from it should be published without the prior consent of the author and information derived from it should be acknowledged. Declaration The work described in this thesis was carried out in the Department of Chemistry of Imperial College London between January 2008 and April 2011. Between 1 st of July and 30 th of August, work was carried out in the Laboratories of Mike Hill, at the University of Bath. Except where specific reference is made to the contrary, it is original work by the author and neither the whole nor any part had been submitted before for a degree in any other institution. Christine Brinkmann, August 2011. Acknowledgement First of all, I would like to thank my two supervisors Mike Hill and Anthony Barrett for giving me the opportunity to work on an interesting and challenging topic and for their support throughout this work. I would like to thank the past and present members of the Barrett Group for fun Friday nights and giving me a good time during my PhD, especially Marianne who was fun to work and chat with. I thank the Hill group for giving me a very friendly asylum during the summer close-down in 2010. Special thanks belong to Merle Arrowsmith for marathon proof reading and great scientific advice. Without it my excel tables would still be spinning around. For NMR studies, I would like to thank Dick Sheppard and Peter Haycock who were always open for discussion and helping me out on seemingly endless kinetic studies. For technical support, I would like to thank Peter Sulsh and his team, in particular Stefanos Karapanagiotidis who was helping me very patiently with the regularly ailing glovebox. I also would like to thank my family for always being there and believing in me. In particular, I thank Chris for his support, countless encouragements and distractions which made the journey sunnier. 4 5 Abstract This thesis describes the reactivity of different heavier alkaline earth catalysts [M{X(SiMe 3)2}2(THF) n]m (M = Ca, Sr, Ba; X = N, CH; n= 0, 2; m= 1, 2) in the intermolecular hydroamination of styrene derivatives. The scope of these reactions with respect to the substrate was determined and detailed kinetic studies to establish rate law and temperature dependence of the hydroamination reactions reported were conducted. Overall, it ‡ -1 was found that [Ca{N(SiMe 3)2}2]2 is favoured enthalpically (Ca: ∆H = 51 kJ ∙mol , Sr: ∆H‡ = 71 kJ ∙mol -1) however the corresponding strontium bis(amide) proved a significantly better catalyst, likely due to a favourably high entropy of activation value (Ca: ∆S‡ = -168 J/mol -1·K-1, Sr: ∆S‡ = -92 J∙mol -1∙K-1). Large kinetic isotope effects of 4.1 and 7.9 at 55 °C for the intermolecular hydroamination of styrene with piperidine mediated by [Ca{N(SiMe 3)2}2]2 and [Sr{N(SiMe 3)2}2]2, respectively, suggest a rate-determining alkene insertion into the M-N bond with immediate or concerted protonolysis. The methodology used in these hydroamination reactions was extended to simple dienes, diphenylacetylene and an activated enyne. The catalyst initiation of the metal bis(amides) with piperidine was shown to be reversible and the equilibrium constant solvent dependent. Novel calcium and strontium dialkyl complexes [M{CH(SiMe 3)2}2(THF) 2] (M= Ca, Sr) were used to overcome the problem of catalyst initiation and showed a different solvent dependence. An enhanced reactivity was found for the dialkyl complexes compared to the metal bis(amides). This increased reactivity allowed the application in new reactions such as the C-F activation of fluorobenzenes. Furthermore, the use of these catalytic systems was successfully extended to intramolecular hydroalkoxylation reactions of alkynyl alcohols in the formation of five- and six-membered enol ethers. In this case, [Ba{N(SiMe 3)2}2]2 displayed significant reactivity although the “catalyst of choice” for these reactions proved to be strongly dependent on substrate substitution pattern. Through detailed kinetic studies the catalyst, substrate and temperature dependence of the cyclisation reaction were established and an unusual rate law with inverse substrate dependence proposed. 6 7 Contents I. Introduction ..................................................................................................................... 11 1. Characteristics of heavier Group 2 metals (Ca, Sr, Ba) .................................................... 11 2. Heavier Group 2 compounds ............................................................................................ 14 3. Application of heavier Group 2 metals in catalysis .......................................................... 28 II. Results and Discussion .................................................................................................... 43 4. Intermolecular hydroamination of styrene derivatives ..................................................... 45 4.1 Comparison of alkaline earth catalysts for the hydroamination of styrene derivatives ......... 47 4.2 Scope of styrene derivatives and amines ............................................................................... 53 4.3 Kinetic studies ....................................................................................................................... 61 4.4 Solvent variation .................................................................................................................... 78 5. Hydroamination of dienes ................................................................................................. 88 5.1 Hydroamination of isoprene and myrcene............................................................................ 90 5.2 Application of more complex dienes and 1-pentene ............................................................. 94 6. Hydroamination of activated alkynes and enynes............................................................. 99 6.1 Intermolecular hydroamination of activated alkynes ............................................................ 99 6.2 Intermolecular hydroamination of but-3-en-1-ynylbenzene ................................................ 104 7. C-F activation .................................................................................................................. 106 7.1 Stoichiometric C-F activation in hexa- and pentafluorobenzene ........................................ 107 7.2 Attempts towards catalytic C-F activation .......................................................................... 111 8. Intramolecular hydroalkoxylation of alkynyl alcohols ................................................... 117 8.1 Application of heavier alkaline earth complexes and reaction scope .................................. 119 8.2 Kinetic studies ..................................................................................................................... 128 III Conclusions and future work ....................................................................................... 137 9.1 Conclusions ......................................................................................................................... 137 9.2 Future work ......................................................................................................................... 139 IV. Experimental part ......................................................................................................... 142 10. General ............................................................................................................................ 142 11. Experimental procedures................................................................................................. 147 V. Supplement .................................................................................................................... 173 VI References ...................................................................................................................... 179 8 9 Abbreviations Ae Alkaline earth BIAN Bis {2,8-(2,6-di-isopropylphenylimino)}acenaphthalene t Bu tert -Butyl n Bu Normal butyl bp Boiling point boc tert -butyloxycarbonyl BOX Bisoxazoline ligand Car Aromatic carbon COD 1,5-Cyclooctadiene conc. Concentrated Cp Cylcopentadiene Cp* tetra -Methyl cyclopentadiene Cp’’ [1,2,4-(Me 3C) 3C5H2] Cq Quaternary carbon Cy C6H11 dd Doublet of a doublets DME Dimethylether DMF Dimethylformamid EI Electron ionisation ESI Electrospray-ionisation Eq. Equation Equ. Equivalent Et Ethyl GPC Gel permeation chromatography h Hour HRMS High resolution mass spectroscopy k Rate constant KHMDS Potassium hexamethyldisilazane L Ligand Ln Lanthanide M Molar Me Methyl NacNac {(2,6-di-iso-propylphenyl)NC(Me)CH C(Me)N(2,6-di- iso-propylphenyl)} min Minute Ph Phenyl, C 6H5 pip Piperidine iPr Isopropyl RT Room temperature sat. Saturated t time T Temperature To M tris(4,4-dimethyl-2-oxazolinyl)-phenylborate) TOF Turn over frequency THF Tetrahydrofuran TM Transition metal TMEDA tetra -Methylendiamine TMS tri -Methylsilyl 10 Chapter I: Introduction 11 I. Introduction 1. Characteristics of heavier Group 2 metals (Ca, Sr, Ba) 1.1 General Although structural understanding of heavier alkaline earth coordination complexes (Ae = Ca, Sr, Ba) has advanced in recent years, the development of