Routes to organogold compounds and gold catalysed A3-coupling reactions A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy in the Faculty of Engineering and Physical Sciences. 2013 Gregory Arthur Price School of Chemistry Contents Abbreviations ...................................................................................................................................... 7 Abstract ............................................................................................................................................. 11 Declaration ........................................................................................................................................ 12 Copyright .......................................................................................................................................... 13 Acknowledgments ............................................................................................................................. 14 1 The Chemistry of Gold ............................................................................................................. 15 1.1 Introduction ....................................................................................................................... 15 1.2 Oxidation states of gold .................................................................................................... 16 1.2.1 Gold(I) complexes..................................................................................................... 16 1.2.2 Gold(III) complexes .................................................................................................. 16 1.2.3 Other oxidation states................................................................................................ 17 1.3 Uses of gold complexes .................................................................................................... 17 1.3.1 Medicinal applications .............................................................................................. 17 1.3.2 Catalysis using gold complexes ................................................................................ 19 2 Gold Organometallics ............................................................................................................... 24 2.1 Introduction ....................................................................................................................... 24 2.2 Organolithium reagents ..................................................................................................... 32 2.3 Attempted Oxidation of gold(I) compounds ..................................................................... 33 2.3.1 Preparation of Organolithium reagents ..................................................................... 33 2.3.2 Preparation of gold(I) complexes .............................................................................. 34 2.3.3 Attempted Oxidation of gold(I) complexes .............................................................. 35 2.4 New Transmetallation routes to gold complexes .............................................................. 38 3 The preparation of gold(III) organometallics via transmetallation from boroxines .................. 42 3.1 The synthesis of amines .................................................................................................... 42 3.2 Synthesis and isolation of organolithium reagents ............................................................ 43 3.3 Synthesis of boroxines ...................................................................................................... 44 3.4 Gold(III) complexes prepared via transmetallation with boroxines .................................. 46 4 The Preparation of novel di-tin(IV) organometallics and their application to the synthesis of a di-gold(III) complex .................................................................................................................. 51 4.1 Dinuclear organogold complexes ...................................................................................... 51 4.2 Preparation of amine ligand and established transmetallation reagents ............................ 52 4.3 Organotin(IV) Chemistry .................................................................................................. 54 4.4 The preparation of organo-ditin(IV) compounds .............................................................. 56 4.5 Discussion of lithium chemistry and preparation of phosphines ...................................... 63 4.6 Synthesis of 1,4-(AuCl2)2-2,5-(Me2NCH2)2-C6H2 (71) and substitution reactions ........... 68 2 4.7 Ligand substitution in gold(III) complexes ....................................................................... 69 4.7.1 Substitution resulting in neutral complexes .............................................................. 70 4.7.2 Substitution resulting in mono-cationic gold(III) compounds .................................. 72 4.7.3 Substitution resulting in di-cationic gold(III) compounds ........................................ 73 4.7.4 Dithiocarbamate ligands ........................................................................................... 74 4.8 Ligand substitution on 1,4-(AuCl2)2-2,5-(Me2NCH2)2-C6H2 (71) ..................................... 76 3 5 Propargylamines and the A -coupling reaction ......................................................................... 78 5.1 Propargylamines ............................................................................................................... 78 3 5.2 The A -coupling reaction .................................................................................................. 80 3 5.3 Tentative mechanism for the A -coupling reaction........................................................... 82 3 5.4 Transition and Main Group Metals as homogeneous catalysts in the A -reaction ........... 82 3 5.5 Group 11 metal complexes as homogeneous catalysts in the A -reaction ........................ 86 5.5.1 Copper Catalysts ....................................................................................................... 86 3 3 5.5.2 Copper catalysed asymmetric A -(AA ) coupling reactions ..................................... 91 5.5.3 Silver catalysts .......................................................................................................... 98 5.5.4 Gold catalysts ............................................................................................................ 99 5.6 Summary ......................................................................................................................... 127 3 6 A -screening with N,N-dimethylbenzylamine catalyst ........................................................... 129 6.1 Introduction to chiral gold catalysts ................................................................................ 137 6.2 Preparation of chiral gold complexes .............................................................................. 139 6.3 Introduction to N-heterocyclic carbenes ......................................................................... 144 3 6.3.1 Gold NHCs as catalysts for A -coupling ................................................................ 150 6.4 Preparation of 1,3-bis-(1(S)-1-phenyl-ethyl)-imidazolin-2-ylidene gold(I) chloride (138) .. ........................................................................................................................................ 157 3 6.5 Screening of chiral gold complexes in A -coupling reactions ........................................ 162 1 6.6 Reactions in Acetonitrile and H-NMR Experiments ..................................................... 165 6.7 Catalyst and Solvent screening studies ........................................................................... 168 31 1 19 1 6.8 Monitoring reaction by P{ H} and F{ H} NMR spectroscopy ................................. 174 7 Conclusion .............................................................................................................................. 181 8 Experimental ........................................................................................................................... 185 8.1 General Considerations ................................................................................................... 185 8.1.1 Crystallography ....................................................................................................... 185 8.2 Preparation of Organolithium reagents for oxidation experiments ................................. 186 8.2.1 Synthesis of [1-Li-2-OMe-C6H4] .n TMEDA (21) ................................................. 186 8.2.2 Synthesis of [Li-C6H5] .n TMEDA (22).................................................................. 186 8.2.3 Synthesis of [1-Li-4-OMe-C6H4] .n TMEDA (23) ................................................. 186 3 8.3 Preparation of gold(I) compounds .................................................................................. 187 376 8.3.1 Preparation of ClAuPPh3 (25) ............................................................................. 187 142 8.3.2 Preparation of [Ph3PAu(1-OMe-C6H4)] (26) ....................................................... 187 143 8.3.3 Preparation of [Ph3PAu(4-OMe-C6H4)] (27) ....................................................... 188 390 8.3.4 Preparation of [Ph3PAu-C6H5] (28) ....................................................................