ABSTRACT
Anomeric Effects, H-Bonding Abilities, Stabilities and Conformations ................. 271
7.1.3 Natural Occurring C-Glycosides............................................................................... 273
7.1.4 C-Glycosides as Stable Pharmacophores.................................................................. 273
7.2 Synthesis of C-Glycosides via Electrophilic Substitutions .................................................. 274
7.2.1 Anomeric Activating Groups and Stereoselectivity ................................................. 275
7.2.2 Cyanation Reactions.................................................................................................. 275
7.2.2.1 Cyanation Reactions on Activated Glycosyl Derivatives ........................ 276
7.2.2.2 Cyanation Reactions on Glycals............................................................... 276
7.2.2.3 Cyanation Reactions on Activated Furanosides....................................... 277
7.2.2.4 Cyanation Reactions with Metallocyanide Reagents ............................... 277
7.2.2.5 Other Cyanation Reactions ....................................................................... 277
7.2.2.6 Cyanoglycoside Transformations ............................................................. 278
7.2.3 Alkylation, Allenylation, Allylation and Alkynation Reactions .............................. 278
7.2.3.1 Use of Activated Glycosyl Derivatives and Anionic
Nucleophiles.............................................................................................. 278
7.2.3.2 Use of Activated Glycosyl Derivatives and Organometallic
Reagents .................................................................................................... 279
7.2.3.3 Use of Modified Sugars and Anionic Nucleophiles................................. 280
7.2.3.4 Lewis Acid-Mediated Couplings with Olefins......................................... 281
7.2.4 Arylation Reactions................................................................................................... 286
7.2.4.1 Reactions with Metallated Aryl Compounds ........................................... 287
7.2.4.2 Electrophilic Aromatic Substitutions........................................................ 287
7.2.4.3 Intramolecular Electrophilic Aromatic Substitutions............................... 290
7.2.4.4 O!C Migrations...................................................................................... 290
7.2.5 Reactions with Enol Ethers, Silylenol Ethers and Enamines................................... 291
7.2.5.1 Reactions with Enolates............................................................................ 292
7.2.5.2 Reactions with Silylenol Ethers................................................................ 293
7.2.5.3 Reactions with Enamines.......................................................................... 293
7.2.6 Nitroalkylation Reactions.......................................................................................... 294
7.2.7 Reactions with Allylic Ethers ................................................................................... 295
7.2.8 Wittig Reactions with Lactols .................................................................................. 297
7.2.8.1 Wittig Reactions........................................................................................ 297
7.2.8.2 Horner-Emmons Reactions ..................................................................... 298
7.2.8.3 Reactions with Sulfur Ylides.................................................................... 298
7.2.9 Nucleophilic Additions to Sugar Lactones Followed by Lactol Reductions........... 299
7.2.9.1 Lewis Acid-Trialkylsilane Reductions ..................................................... 300
7.2.9.2 Other Reductions ...................................................................................... 301
7.2.9.3 Sugar-Sugar Couplings............................................................................ 302
7.2.10 Nucleophilic Additions to Sugars Containing Enones ............................................. 302
7.2.11 Transition Metal-Mediated Carbon Monoxide Insertions........................................ 304
7.2.11.1 Manganese Glycosides.............................................................................. 304
7.2.11.2 Cobalt-Mediated Glycosidations .............................................................. 304
7.2.12 Reactions Involving Anomeric Carbenes ................................................................. 305
7.2.13 Reactions Involving Exoanomeric Methylenes ........................................................ 305
7.3 Synthesis of C-Glycosides via Nucleophilic Sugar Substitutions ....................................... 307
7.3.1 C-1 Lithiated Anomeric Carbanions by Direct Metal Exchange............................. 307
7.3.1.1 Hydrogen-Metal Exchanges .................................................................... 308
7.3.1.2 Metal-Metal Exchanges........................................................................... 309
7.3.1.3 Halogen-Metal Exchanges....................................................................... 310
7.3.2 C-1 Lithiated Anomeric Carbanions by Reduction.................................................. 310
7.3.3 C-1 Carbanions Stabilized by Sulfones, Sulfoxides,
Carboxyl and Nitro Groups....................................................................................... 311
7.3.3.1 Sulfone Stabilized Anions ........................................................................ 311
7.3.3.2 Sulfide and Sulfoxide Stabilized Anions.................................................. 312
7.3.3.3 Carboxy Stabilized Anions ....................................................................... 312
7.3.3.4 Nitro Stabilized Anions ............................................................................ 313
7.4 Synthesis of C-Glycosides via Transition Metal-Based Methodologies ............................. 314
7.4.1 Direct Coupling of Glycals with Aryl Groups ......................................................... 315
7.4.1.1 Arylation Reactions with Unsubstituted Aromatic Rings........................ 315
7.4.1.2 Arylation Reactions with Metallated Aromatic Rings............................. 315
7.4.1.3 Arylation Reactions with Halogenated Aromatic Rings.......................... 316
7.4.2 Coupling of Substituted Glycals with Aryl Groups ................................................. 316
7.4.3 Coupling of p-Allyl Complexes of Glycals ............................................................. 317
7.5 Synthesis of C-Glycosides via Anomeric Radicals.............................................................. 319
7.5.1 Sources of Anomeric Radicals and Stereochemical
Consequences ............................................................................................................ 319
7.5.1.1 Nitroalkyl C-Glycosides as Radical Sources ........................................... 319
7.5.1.2 Radicals from Activated Sugars ............................................................... 320
7.5.2 Anomeric Couplings with Radical Acceptors .......................................................... 320
7.5.2.1 Non-Halogenated Radical Sources ........................................................... 321
7.5.2.2 Glycosyl Halides as Radical Sources ....................................................... 322
7.5.3 Intramolecular Radical Reactions............................................................................. 322
7.6 Synthesis of C-Glycosides via Rearrangements and Cycloadditions .................................. 324
7.6.1 Rearrangements by Substituent Cleavage and Recombination................................ 324
7.6.1.1 Wittig Rearrangements ............................................................................. 325
7.6.1.2 Carbenoid Rearrangements....................................................................... 325
7.6.2 Electrocyclic Rearrangements Involving Glycals .................................................... 326
7.6.3 Rearrangements from the 2-Hydroxyl Group........................................................... 326
7.7 Synthesis of C-Glycosides via Formation of the Sugar Ring .............................................. 327
7.7.1 Wittig Reactions of Lactols Followed by Ring Closures ........................................ 329
7.7.2 Addition of Grignard and Organozinc Reagents to Lactols .................................... 331
7.7.3 Cyclization of Suitably Substituted Polyols ............................................................. 331
7.7.3.1 Cyclizations via Ether Formations ........................................................... 331
7.7.3.2 Cyclizations via Ketal Formations ........................................................... 332
7.7.3.3 Cyclizations via Halide Displacements .................................................... 332
7.7.4 Rearrangements ......................................................................................................... 333
7.7.4.1 Electrocyclic Rearrangements .................................................................. 333
7.7.4.2 Ring Contractions ..................................................................................... 333
The of
7.7.5 Cycloadditions........................................................................................................... 335
7.7.6 Other Methods for the Formation of Sugar Rings ................................................... 336
7.8 Further Reading..................................................................................................................... 336
Acknowledgments ........................................................................................................................ 337
References..................................................................................................................................... 337
Carbohydrates have long been a source of scientific interest because of their abundance in nature,
and to the synthetic challenges posed by their polyhydroxylated structures. However, the
commercial use of carbohydrates has been significantly limited by the hydrolytic lability of the
glycosidic bond. With the advent of C-glycosides, this limitation promises to be overcome, thus
paving the way for a new generation of carbohydrate-based products.
