DEVELOPMENT OF NEW SYNTHETIC METHODOLOGIES BASED ON HYPERVALENT IODINE CHEMISTRY A THESIS SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY ALEKSANDRA ZAGULYAEVA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE VIKTOR V. ZHDANKIN July, 2010 © Aleksandra Zagulyaeva 2010 ACKNOWLEDGMENTS I would like to thank the University of Minnesota Duluth, Department of Chemistry and Biochemistry for the opportunity to enter the graduate program and work successfully towards a MS degree. I am very grateful to Prof. Viktor V. Zhdankin for his supervision and professional guidance, as well as for financial support during this project. His invaluable advice helped me to build up confidence for my future career in chemistry. I wish to thank a collaborator in Professor Zhdankin’s research group – Dr. Mekhman Yusubov for his great help and creative ideas. I am also thankful to Evie Tahtinen and Barb Chapin for their help with ordering chemicals and equipment. I also would like to thank Randall Helander and Neil Weberg for their assistance with instrumentation. This work was supported by a research grant from the National Science Foundation (CHE 01726102). To my family in Russia, thank you for your love and support of my educational endeavors. i DEDICATION This thesis is dedicated to my parents, Irina and Alexander Zagulyaevy. ii TABLE OF CONTENTS ACKNOWLEDGEMENTS i DEDICATION ii LIST OF SCHEMES v LIST OF TABLES ix LIST OF FIGURES x LIST OF ABBREVIATIONS xi Chapter 1. Review 1. Hypervalent Iodine in Organic Synthesis 1 1.1 Introduction: Classification and General Structural Features of Organic Iodine(III) and Iodine(V) Compounds 1 1.2 Preparation of Hypervalent Iodine(III) and Iodine(V) Reagents 5 A. [Bis(acyloxy)iodo]arenes, ArI(OCOR) 2 5 B. [Hydroxy(organosulfonoxy)iodo]arenes, ArI(OH)OSO 2R 10 C. Stabilized Alkyl Substituted λ 3-Iodanes: Types C nF2n+1 I(OCOCF 3)2 and C nF2n+1 I(OH)OSO 2R 13 D. Iodylarenes, ArIO 2 16 1.3 Reactions of Hypervalent Iodine(III) and Iodine(V) Reagents 19 A. Oxidative Rearrangements Using Iodine(III) Compounds 19 B. Oxidation of Alcohols and Hydrocarbons Using Iodylbenzene PhIO 2 29 C. Catalytic Oxidation of Alcohols Using Iodylbenzene PhIO 2 31 Chapter 2. Results And Discussion 2. Development of New Approaches to Preparation of Selected Classes of Iodine(III) Compounds and New Synthetic Methodologies 36 2.1 Preparation of [Bis(trifluoroacetoxy)iodo]- perfluoroalkanes and [Bis(trifluoroacetoxy)iodo]arenes 36 A. Introduction 36 iii B. Results and Discussion 37 C. Summary 41 2.2 Oxidative Rearrangement of Amides Using Iodobenzene and Oxone ® 42 A. Introduction 42 B. Results and Discussion 42 C. Summary 50 2.3 PhI/RuCl 3-Cocatalyzed Oxidation of Alcohols and Hydrocarbons 50 A. Introduction 50 B. Results and Discussion 51 C. Summary 59 2.4 Conclusion 60 Chapter 3. Experimental 3. Experimental Section 61 3.1 General Methods 61 3.2 Materials 61 3.3 Synthesis and Characterization of Compounds 61 Bibliography 77 Appendices 87 iv LIST OF SCHEMES Scheme Page 1. Common classes of hypervalent iodine(III) compounds 2 2. Common classes of hypervalent iodine(V) compounds 3 3. Structural types of hypervalent iodine compounds 4 4. Preparation of [bis(trifluoroacetoxy)iodo]arenes by a ligand exchange reaction of the readily available (diacetoxyiodo)arenes with trifluoroacetic acid 6 5. Preparation of [bis(trifluoroacetoxy)iodo]arenes by reaction of arenes with tris(trifluoroacetoxy)iodine 7 6. Direct preparation of [bis(trifluoroacetoxy)iodo]arenes by oxidation of arenes with sodium percarbonate 8 7. Direct preparation of [bis(trifluoroacetoxy)iodo]arenes by oxidation of arenes with HNO 3 in (CF 3CO) 2O 8 8. Direct preparation of [bis(trifluoroacetoxy)iodo]arenes by oxidation of arenes with potassium persulfate 8 9. Direct preparation of [bis(trifluoroacetoxy)iodo]arenes by oxidation of arenes with peroxytrifluoroacetic acid 9 10. Preparation of [hydroxy(tosyloxy)iodo]arenes by a ligand exchange reaction with p-toluenesulfonic acid in CH 3CN 11 11. Preparation of polymer-supported analogues of [hydroxy- (tosyloxy)iodo]benzene 12 12. Preparation of [hydroxy(tosyloxy)iodo]arenes by one-pot reaction of iodoarenes and mCPBA in presence of p-toluenesulfonic acid in CHCl 3 12 13. Preparation of [hydroxy(organosulfonyloxy)iodo]arenes by one-pot reaction of iodoarenes and mCPBA in presence of various sulfonic acids 13 14. Main types of stabilized alkyl substituted λ3-iodanes 14 15. Preparation of [bis(trifluoroacetoxy)iodo]perfluoroalkanes 14 v 16. Preparation of [hydroxy(organosulfonyloxy)iodo]- perfluoroalkanes 15 17. Preparation of iodylbenzene by disproportionation of iodosylbenzene 16 18. Synthesis of iodylarenes by the oxidation of iodoarenes 16 19. Selective preparation of iodylarenes by oxidation of iodoarenes with sodium periodate 17 20. Preparation of iodylarenes by oxidation of iodoarenes with peroxyacetic acid in presence of catalytic amounts of RuCl 3 18 21. Polymer-supported analogs of 2-iodylphenol ethers 18 22. Preparation of methyl carbamates by Hofmann rearrangement of amides using (diacetoxyiodo)benzene (DIB) in methanolic KOH 19 23. Mechanism of Hofmann rearrangement induced by DIB 20 24. DIB-induced Hofmann rearrangement of protected asparagines and glutamines 21 25. Structures of imidazolidin-2-one-4-carboxylates and (tetrahydro)- pyrimidine-2-one-5-carboxylates 21 26. Preparation of alkyl carbamates of 1-protected indole- 3-methylamines from amides via DIB-induced Hofmann rearrangement. Other amino heterocycles 22 27. Various classes of organic compounds obtained via DIB-induced Hofmann rearrangement 22 28. Series of diacetoxy iodoheterocycles used in Hofmann rearrangement 23 29. Synthesis of amines from amides via [bis(trifluoroacetoxy)- iodo]benzene (BTI) induced Hofmann rearrangement 23 30. Mechanism of Hofmann rearrangement induced by BTI 24 31. Preparation of 2-oxazolidinones and 1,3-oxazinan-2-ones via BTI-induced Hofmann rearrangement 25 vi 32. Degradation of carboxyl-terminal amino acid amides via BTI-induced Hofmann rearrangement 26 33. Applications of BTI-induced Hofmann rearrangement 27 34. Mechanism of Hofmann rearrangement induced by [hydroxy(tosyloxy)- iodo]benzene(HTIB)/[methoxy(tosyloxy)iodo]benzene 27 35. Preparation of various amines from amides via HTIB- induced Hofmann rearrangement 28 36. Applications of HTIB-induced Hofmann rearrangement 28 37. Synthesis of amines from amides via Hofmann rearrangement induced by poly([4-hydroxy(tosyloxy)iodo]styrene) 28 38. Preparation of amines from amides via Hofmann rearrangement induced by iodosylbenzene in presence of fromic acid 29 39. Oxidation of alcohols with iodylbenzene 30 40. Application of iodylbenzene to oxidation of activated C-H bonds 31 41. Oxidation of alcohols with iodylbenzene in presence of acetic or trichloroacetic acid as a catalyst 31 42. Catalytic oxidation of alcohols with iodylbenzene in presence of Br 2/NaNO 2 in water 32 43. Application of iodylbenzene/Br 2/NaNO 2 system to oxidation of various alcohols 32 44. Mechanism of oxidation of alcohols in iodylbenzene/Br 2/NaNO 2 33 45. Catalytic oxidation of alcohols with iodylbenzene obtained in situ by disproportionation of DIB in presence of RuCl 3 34 46. Special experiment: catalytic oxidation of alcohols with iodylbenzene in the presence of RuCl 3 34 47. [Bis(trifluoroacetoxy)iodo]arenes and [bis(trifluoroacetoxy)- iodo]perfluoroalkanes 36 48. Preparation of [bis(trifluoroacetoxy)iodo]perfluoroalkanes and [hydroxyl(tosyloxy)iodo]perfluoroalkanes 38 vii 49. Preparation of [bis(trifluoroacetoxy)iodo]arenes using Oxone ® as an oxidant 39 50. Preparation of [hydroxy(tosyloxy)iodo]pentafluorobenzene 41 51. Synthesis of benzylamine hydrochloride from 2-phenylacetamide via Hofmann rearrangement using PhI and Oxone ® 43 ® 52. Oxidation of iodobenzene with Oxone in aq. CH 3CN 43 53. Mechanism of Hofmann rearrangement induced by iodine(III) species generated in situ by oxidation of PhI with Oxone ® 45 54. Preparation of 1,4-benzoquinones from arylamides 45 55. Preparation of 4-hydroxy-2,4,6-trimethylcyclohexa-2,5-dienone 46 56. Preparation of (±)-α-phenylpropylamine 47 57. Preparation of carbamates from amides 48 58. Species inducing Hofmann rearrangement of amides to carbamates 50 ® 59. RuCl 3-catalyzed oxidation of iodobenzene with Oxone 52 60. Hypothetical active monomeric iodine(V) species generated ® from PhI/Oxone mixture in aq. CH 3CN in presence of RuCl 3 52 61. Oxidation of 1-phenylethanol using ArI/Oxone ® mixture in presence of RuCl 3 52 62. Oxidation of alcohols using PhI/Oxone ® mixture in presence of RuCl 3 54 63. Oxidation of ethylbenzene using ArI/Oxone ® mixture in presence of RuCl 3 56 64. Tandem catalytic system for the oxidation of organic substrates with Oxone ® 59 viii LIST OF TABLES Table Page 1. Synthesis of iodylarenes 12 by the oxidation of iodoarenes 17 2. Yields and melting points of [bis(trifluoroacetoxy)iodo]- perfluoroalkanes 136 and tosylates 137 38 3. Yields and melting points of [bis(trifluoroacetoxy)iodo]arenes 139 40 4. Yields and melting points of 1,4-benzoquinones 148 46 5. Yields and melting points of carbamates 155 48 6. Effect of ArI and RuCl 3 on the oxidation of 1-phenylethanol 159 ® to acetophenone 160 with Oxone 53 7. PhI/RuCl 3-cocatalyzed oxidation of alcohols 161 54 8. Effect of ArI and RuCl 3 on the oxidation of ethylbenzene 163 with Oxone ® 56 9. PhI/RuCl 3 co-catalyzed oxidation of hydrocarbons 57 ix LIST OF FIGURES Figure Page 1. ESI mass spectrum of PhI/Oxone ® mixture in aqueous