Iron-mediated C–H coupling of arylsulfides and simple terminal alkenes A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy (PhD) in the Faculty of Engineering and Physical Sciences 2016 Craig W. Cavanagh School of Chemistry Contents Index of Figures ..................................................................................................................... 6 Index of Schemes ................................................................................................................... 7 Index of Tables ..................................................................................................................... 10 Abstract ................................................................................................................................ 11 Declaration ........................................................................................................................... 12 Copyright Statement ............................................................................................................ 13 Acknowledgements .............................................................................................................. 15 Abbreviations and Definitions ............................................................................................. 16 1. Organoiron Chemistry .................................................................................................. 20 1.1 Introduction ....................................................................................................................... 20 1.2 Cross-Coupling Reactions................................................................................................. 20 1.2.1 Coupling of Alkyl Electrophiles ............................................................................... 22 1.2.2 Couplings of Aryl Electrophiles ............................................................................... 26 1.2.3 Coupling of Heteroaromatic Compounds ................................................................. 29 1.3 C–H Bond Activation ....................................................................................................... 30 1.3.1 Activation of sp2 C–H bonds ..................................................................................... 31 1.3.2 Activation of sp3 C–H bonds..................................................................................... 35 1.4 Cross Dehydrogenative Coupling ..................................................................................... 38 1.4.1 CDC of two sp3 C–H bonds ...................................................................................... 38 1.4.2 CDC between sp2 and sp3 C–H bonds ....................................................................... 40 1.4.3 CDC in Domino Processes ........................................................................................ 42 1.5 Summary ........................................................................................................................... 44 2. Iron-mediated Coupling of Arylsulfides with Silanes .................................................. 45 2.1 Introduction to Pummerer and Pummerer-Type Reactions .............................................. 45 2.1.1 Classical Pummerer Rearrangement ......................................................................... 45 2.1.2 Aromatic Pummerer-Type Reactions ........................................................................ 46 2.2 Results and Discussion ..................................................................................................... 48 3 2.2.1 Proposed Project ....................................................................................................... 48 2.2.2 Preliminary Reaction ................................................................................................ 49 2.2.3 Synthesis of Biarylsulfide Starting Materials ........................................................... 50 2.2.4 Solvent Screen .......................................................................................................... 50 2.2.5 Oxidant Screen ......................................................................................................... 51 2.2.6 Changing The Addition Rate of Allyl Silane ............................................................ 53 2.2.7 Changing Reagent Stoichiometry ............................................................................. 54 2.2.8 Other Biaryl Sulfides ................................................................................................ 55 2.2.9 Reaction with an unfunctionalised alkene ................................................................ 56 3. Metal-catalysed Reactions of Arenes and Alkenes ...................................................... 57 3.1 Oxidative Coupling of Arenes and Alkenes ..................................................................... 57 3.1.1 Examples of Directing Groups ................................................................................. 58 3.1.2 Sulfur Directing Groups in Oxidative Alkenylations ............................................... 61 3.2 Hydroarylation of Alkenes ............................................................................................... 65 3.3 Iron-mediated Functionalisation of Alkenes..................................................................... 68 3.4 Summary ........................................................................................................................... 70 4. Iron-mediated Chloroarylation of Alkenes ................................................................... 71 4.1 This Work ......................................................................................................................... 71 4.2 Optimisation Studies ......................................................................................................... 71 4.2.1 Solvent Screen .......................................................................................................... 71 4.2.2 Oxidant Screen ......................................................................................................... 72 4.2.3 Investigation of Bases and Additives........................................................................ 74 4.2.4 Further Optimisation Studies .................................................................................... 75 4.2.5 Controlled Addition of Reagents .............................................................................. 77 4.3 Substrate Scope ................................................................................................................. 78 4.3.1 Variation of Alkene Coupling Partners .................................................................... 78 4.3.2 Variation of Arene Coupling Partners ...................................................................... 82 4.3.3 Use of Other Aryl Sulfides ....................................................................................... 85 4.4 Mechanistic Studies .......................................................................................................... 87 4 4.4.1 Proposed Mechanism ................................................................................................ 87 4.4.2 Cyclic Voltammetry .................................................................................................. 90 4.4.3 Solvent Investigations ............................................................................................... 91 4.4.4 Use of Other Oxidants ............................................................................................... 91 4.4.5 Electron Paramagnetic Resonance ............................................................................ 93 4.4.6 Alternative Mechanisms ........................................................................................... 94 4.5 Towards a Catalytic Process ............................................................................................. 96 4.5.1 Iron Catalysis ............................................................................................................ 96 4.5.2 Photoredox Catalysis................................................................................................. 97 4.6 Product Manipulation ...................................................................................................... 101 4.6.1 Formation of Dihydrobenzofuran Motifs ................................................................ 104 4.7 Summary ......................................................................................................................... 109 4.8 Future Work .................................................................................................................... 110 4.8.1 Iron-mediated Chloroarylation of Alkenes ............................................................. 110 4.8.2 Manipulation of Allylation Products – The Truce-Smiles Rearrangement ............. 112 5. Experimental ............................................................................................................... 116 5.1 General Experimental ..................................................................................................... 116 5.2 Cyclic Voltammetry ........................................................................................................ 116 5.3 Sulfide Synthesis ............................................................................................................