Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München “Transition Metal Catalyzed Selective Oxidations of Sugars and Polyols” Matthias Bierenstiel aus Memmingen 2005 Erklärung Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29. Januar 1998 (in der Fassung der vierten Änderungssatzung vom 26. November 2004) außerhalb der Fakultät von Assistant Professor Dr. Marcel Schlaf, University of Guelph, Guelph, Ontario, Kanada betreut. Die Arbeit wird von Univ.-Professor Dr. Peter Klüfers vor der Fakultät vertreten. Ehrenwörtliche Versicherung Diese Dissertation wurde selbständig, ohne unerlaubte Hilfe erarbeitet. Guelph, Ontario, Kanada, den 17. März 2005 (Matthias Bierenstiel) Dissertation eingereicht am 22. März 2005 1. Gutachter Professor Dr. Marcel Schlaf 2. Gutachter Professor Dr. Peter Klüfers Mündliche Prüfung am 29. April 2005 “Chemistry began by saying it would change baser metals into gold; by not doing so it has done much greater things.” Ralph Waldo Emerson Table of Contents Table of Contents Table of Contents .................................................................................................. i Acknowledgements .............................................................................................. v Abstract….............................................................................................................vi Zusammenfassung .............................................................................................viii Abbreviations........................................................................................................xi Chapter 1 The Chemistry of Sugars, Transition Metal Catalysis and Research Motivation......................................................................... 1 1.1 General Significance and Features of Sugars and Their Oxidation Products......................................................................................................... 1 1.1.1 Definitions and Properties of Sugars ...................................................... 1 1.1.2 Equilibria and Mutarotation of Sugars..................................................... 3 1.1.3 Sugar Derivatives and Their Applications ............................................... 4 1.1.4 Oxidation Products of Sugars ................................................................. 6 1.1.4.1 Definition, Occurrence and Applications of Sugar Lactones ............ 8 1.1.4.2 Synthesis of Sugar Lactones ........................................................... 9 1.1.4.3 General Significance and Occurrence of Keto-sugars................... 13 1.1.4.4 Synthesis of Keto-sugars............................................................... 13 1.1.4.5 Synthesis of Usolidulosides ........................................................... 14 1.1.4.6 Application of Keto-sugars in Reactions ........................................ 18 1.1.4.7 Aldehydo-Sugars ........................................................................... 20 1.1.4.8 Other Sugar Oxidation Products.................................................... 20 1.2 Transition Metal Catalyzed Transfer Hydrogenation Reaction as a Strategy for Sugar Transformations ............................................................. 20 1.2.1 Hydrogen Transfer Reactions ............................................................... 20 1.2.2 Other Metal Catalyzed Oxidation Reactions ......................................... 23 1.2.3 Representative Examples of Metal Sugar Complexes.......................... 24 1.2.4 Examples of Transition Metal Complex Catalyzed Transformations of Sugars .............................................................................................. 25 1.3 Motivation, Research Objectives and Potential Applications........................ 28 1.3.1 Motivation ............................................................................................. 28 1.3.2 Research Objectives............................................................................. 29 1.3.3 Potential Applications of Sugar Lactones and Keto-Sugars.................. 30 1.4 References................................................................................................... 31 i Table of Contents Chapter 2 Selective Oxidation of Hemiacetals to Lactones ......................... 36 2.1 Synthesis and Properties of δ- and γ-Sugar Lactones ................................. 36 2.2 Transition Metal Catalysis ............................................................................ 38 2.2.1 RuH2(PPh3)4 and RhH(PPh3)4 in the Synthesis of Sugar Lactones ...... 38 2.2.2 Shvo’s Catalyst ..................................................................................... 41 2.3 Results and Discussion................................................................................ 44 2.3.1 Rationale for the Selection of Catalyst and Reaction Conditions .......... 44 2.3.2 Synthesis and Isolation of δ-Lactones .................................................. 45 2.3.2.1 Variation in Hydrogen Acceptor ..................................................... 45 2.3.2.2 Variation of Co-solvent .................................................................. 48 2.3.2.3 Oxidation Reactions without Co-solvent ........................................ 50 2.3.2.4 Modification of Catalyst.................................................................. 53 2.3.2.5 Optimized Reaction Conditions ..................................................... 54 2.3.3 NMR and Conformational Analysis ....................................................... 57 2.3.4 δ to γ Lactone Rearrangement ............................................................. 62 2.3.4.1 Thermodynamic Considerations .................................................... 62 2.3.4.2 Mechanistic Considerations........................................................... 65 2.4 Conclusions ................................................................................................. 67 2.5 Experimental section.................................................................................... 68 2.6 References................................................................................................... 70 Chapter 3 Oxidation of 2° Alcohols in Unprotected Sugars......................... 73 3.1 General Overview and Research Strategy................................................... 73 3.1.1 Chemical Properties of Keto-Sugars..................................................... 73 3.1.2 Catalyst and Reaction Condition Requirements ................................... 78 3.1.2.1 Reaction Medium........................................................................... 78 3.1.2.2 Solubility ........................................................................................ 79 3.1.2.3 Reaction Temperature ................................................................... 79 3.1.2.4 Transition Metal Catalyst ............................................................... 80 3.1.2.5 Mediator......................................................................................... 80 3.1.2.6 Reaction Time Scale...................................................................... 81 3.1.2.7 Other Factors................................................................................. 81 3.1.3 Research Strategy and Model Systems................................................ 82 3.1.3.1 Vicinal-Diols................................................................................... 83 3.1.3.2 Thermodynamic and Kinetic Parameters....................................... 83 3.1.3.3 Theoretical Calculations of Diol Oxidations ................................... 87 3.1.3.4 Mono-alcohol Model Systems........................................................ 93 3.1.3.5 Diol Model Systems....................................................................... 95 3.1.4 Reaction Monitoring.............................................................................. 96 3.1.4.1 Monitoring of Model Systems ........................................................ 96 3.1.4.2 Monitoring of Sugar Substrate Systems ........................................ 97 ii Table of Contents 3.2 Catalytic Hydrogen Transfer Reactions Investigated ................................... 98 3.2.1 Shvo’s Catalyst ..................................................................................... 98 3.2.1.1 Shvo’s System in the Oxidation of Secondary Alcohols................. 98 3.2.1.2 Experimental Section................................................................... 100 3.2.2 Noyori System .................................................................................... 101 3.2.2.1 Introduction to Metal-Ligand Bifunctional Catalysis and Motivation .................................................................................... 101 3.2.2.2 Results and Discussion ............................................................... 106 3.2.2.3 Conclusions ................................................................................. 141 3.2.2.4 Experimental Section................................................................... 142 3.3 Investigated Transition Metal Catalyzed Peroxide Oxidations ................... 152 3.3.1 Molybdenum/ Tungsten Peroxide Systems......................................... 153 3.3.1.1 Oxidations with (NH4)6Mo7O24 and Na2MoO4............................... 153 3.3.1.2 MoO2(acac)2 System ..................................................................