NMR Shift

Reagents

Author

Thomas J. Wenzel, Ph.D. Assistant Professor of Chemistry

Bates College Lewiston, Maine

CRC Press, Inc. Boca Raton, Florida

TABLE OF CONTENTS

Chapter 1 Introduction I. Structural Studies 2 II. Future Prospects 3

Chapter 2 Achiral Lanthanide Chelates I. Shift Reagent Selection 5

A. Metal 5 B. Ligand 7

II. Experimental Techniques 9 A. Solvent 9 B. Shift Reagent Preparation and Purification 10 C. Scavengers 11 D. Procedures for Use of LSR 12 E. Recovery of the Substrate 13 F. High Field NMR 13

III. Applications 14 A. Monofunctional Substrates 14

1. Alcohols and Phenols 14 2. Ketones 23 3. Esters 31 4. Lactones 35 5. Aldehydes 36 6. Carboxylic Acids 37 7. Anhydrides 38 8. Ethers 38 9. Peroxides 41

10. Amines 41 11. Nitrogen Heterocycles 44 12. Nitriles 46 13. Amides 47 14. Lactams and Imides 49 15. Carbamates 50 16. Nitrogen Oxides 50 17. Nitrosos 51 18. Azoxys 52 19. Nitros 52 20. Isocyanates 52 21. Oximes 53 22. Azos and Azides 53 23. Imines 54 24. Substrates with a Sulfur Atom 54

a. Sulfoxides 55 b. Sulfones and Sulfanate Esters 56 c. Sulfites, Sultones, and Sulfate Diesters 56 d. Sulfines 57 e. Thiolsulfinates, Sulfinamates, and Thiacarbamates 58 f. Sulfides and Thiols 58

g. Thiocyanates and Isothiocyanates 59 h. Thioamides, Thioketones, Thioacetates, and

Thiocarbamates 59 25. Substrates with a Phosphorus Atom 60

a. Phosphates 60 b. Phosphonates, Phosphorinanes, and

Oxazophospholines 60 c. Phosphine Oxides 61 d. Phosphoranes 63 e. Phosphites 63 f. Phosphines 64 g. Phosphoramides 64

26. Organohalides 64 B. Organic Salts 64 C. Metal Complexes and Substrates with a Silicon Atom 66

1. Metal ß-Diketonates 66 2. Organometallics 68 3. Silicon and Germanium-Containing Compounds 70

D. Polyfunctional Substrates 71 1. Alcohols 72 2. Ketones 79 3. Esters 87 4. Lactones 92 5. Aldehydes 94 6. Acid Chlorides 95 7. Ethers 95 8. Peroxides 99 9. Amines 99

a. Primary 99 b. Secondary 100 c. Tertiary 101

10. Nitrogen Heterocycles 102 11. Nitriles 108 12. Amides 109 13. Lactams and Imides 112 14. Nitrogen Oxides, Nitrones, and Azoxys 115 15. Nitros 116 16. Oximes 116 17. Azos, Azines, and Azides 117 18. Imines 118 19. Substrates with a Sulfur Atom 118 20. Substrates with a Phosphorus Atom 120

E. Polymers 121 IV. Influences of LSR on Coupling Constants 123 V. Separation of Diastereotopic Protons 124 VI. Secondary Deuterium Isotope Effects 124 VII. Chemically Induced Dynamic Nuclear Polarization 125

Chapter 3 Studies of Chiral Substrates with Lanthanide Tris Chelates I. Shift Reagent Selection 127

A. Metal 127

B. Ligands 127 II. Experimental Techniques 129

A. Solvent 129 B. Preparation and Purification 129 C. Procedures for Using Chiral LSR 130

III. Assignment of Absolute Configuration 131 A. Circular Dichroism Spectra 131 B. MTPA Esters 131 C. Camphanate Esters 133 D. Preparation of Amides 134 E. Other Derivatives 134

IV. Determination of Optical Purity 135 A. Enantiomeric Resolution with Achiral LSR 135 B. Application of Chiral LSR 136

1. Alcohols 136 2. Ketones 140 3. Esters 142 4. Lactones 145 5. Aldehydes 145 6. Carboxylic Acids 145 7. Ethers 146 8. Amines 147 9. Nitrogen Heterocycles 148

10. Amides 149 11. Lactams 149 12. Nitrosoamines 150 13. Organoborons 150 14. Substrates with a Sulfur Atom 150 15. Substrates with a Phosphorus Atom 152 16. Metal Complexes 153 17. Organic Salts 154

Chapter 4 Binuclear Lanthanide(III)-Silver(I) Shift Reagents I. Shift Reagent Selection 155

A. Metal 155 B. Ligand 156

II. Experimental Techniques 157 A. Solvent 157 B. Shift Reagent Preparation and Purification 157 C. Use of Binuclear Reagents 158

III. Structure and Theory 158 IV. Applications 159

A. Olefins 159 B. Alkynes 160 C. Aromatics 160 D. Halogenated Compounds 161 E. Phosphines 162 F. Polyfunctional Substrates 162 G. Multifunctional Substrates 163 H. Organic Salts 165 I. Chiral Binuclear Reagents 167

Chapter 5 Theory of Lanthanide Shift Reagents I. Shift Mechanism , 169

A. Pseudocontact and Contact Shifts 169 B. Pseudocontact Shift Equation 169

II. Separation of Dipolar and Contact Shifts 171 III. Stoichiometry and Symmetry 172

A. X-Ray Crystallography 173 B. Low-Temperature NMR Studies 174 C. Vapor Phase Osmometry 174 D. Infrared Spectroscopy 174 E. Optical Spectroscopy 175 F. Luminescence Spectroscopy 175 G. Circular Dichroism 175 H. Mass Spectrometry 175 I. Graphical or Iterative Procedures 176 J. Conclusions and "Effective Axial Symmetry" 176

IV. Application of the Pseudocontact Shift Equation 177 A. Complexation Shifts 178 B. Bound Shifts 178 C. Location of the Principal Magnetic Axis 180 D. Atomic Coordinates and L-S Bond Length 180 E. Significance Testing 181 F. Limitations of Configurational and Conformational Assignment 181

V. Relaxation Phenomena with LSR 183

Chapter 6 Water-Soluble Lanthanide Shift Reagents I. Shift Reagent Selection 185 II. Applications to Biological Systems 186

A. Amino Acids, Peptides, and Proteins 186 B. Nucleotides and Nucleic Acids 190 C. Carbohydrates 191 D. Membranes 193 E. Cations 194

III. Other Applications 197 A. Carboxylates 197 B. Phenols 200 C. Oxides 200 D. Amines 201 E. Nitrogen Heterocycles 201 F. Substrates with a Sulfur Atom 202 G. Organometallics 202

IV. Chiral Shift Reagents 202

References 205

Index 269