molecules
ISSN 1420-3049
© 2001 by
MDPI
http://www.mdpi.org
Book Received*
Organic
Synthesis on Solid Phase. (Supports, Linkers,
Reactions).
By Zaragoza Dörwald, Florencio. Wiley-VCH, Weinheim , 2000. Pages:
474, Hardcover. Price: 271.86 DM / 139.- EUR / 241.- SFR. ISBN 3-527-29950-5
Received: 1 December 2001
Organic synthesis on solid supports is a rapidly developing methodology, which offers several advantages if compared to traditional synthesis in solution. In recent years the number of substance classes that can be synthesised on solid phase has quickly increased, and solid-phase synthesis is becoming a valuable alternative to traditional synthesis - in particular when large numbers of different compounds in small quantities are needed for screening.
This exhaustive and systematically organised reference work gives an in-depth view on organic syntheses on insoluble polymers from the basic principles to the newest developments. The work quickly guides the reader to any particular type of reaction and to the best method for preparing a given class of compounds on solid support.
Many tables with clear preseantation collect valuable information about the feasibility of a given reaction on solid support, and a wealth of information is opened up to the reader through a thoroughly worked out and comprehensive reference list. This makes the book the first stop when it comes to synthesising your compounds on solid support.
General Techniques and Analytical Tools for Solid-Phase Organic Synthesis
Supports for Solid-Phase Organic Synthesis
Linkers for Solid-Phase Organic Synthesis
Preparation of Organometallic Compounds
Preparation of Hydrocarbons
Preparation of Alkyl and Aryl Halides
Preparation of Alcohols and Ethers
Preparation of Sulfur Compounds
Preparation of Organoselenium Compounds
Preparation of Nitrogen Compounds
Preparation of Phosphorus Compounds
Preparation of Aldehydes and Ketones
Preparation of Carboxylic Acid Derivatives
Preparation of Carbonic Acid Derivatives
Preparation of Heterocycles
Preparation of Oligomeric Compounds
Index
Table of Contens:
Glossary and Abbreviations XIV
Experimental Procedures XX
1 General Techniques and Analytical Tools for Solid-Phase Organic Synthesis 1
1.1 General Techniques for Performing Syntheses on Insoluble Supports 1
1.2 Strategies for Parallel Synthesis 3
1.3 Analytical Methods for Support-bound Intermediates 5
1.3.1 Combustion Analysis 5
1.3.2 Colorimetric Assays 5
1.3.3 Infrared Spectroscopy 7
1.3.4 Mass Spectrometry 7
1.3.5 Nuclear Magnetic Resonance Spectroscopy 7
1.4 Strategies for the Selection of Reactions and Reagents for Parallel Solid-Phase Synthesis 8
2 Supports for Solid-Phase Organic Synthesis 13
2.1 Polystyrene 14
2.1.1 Microporous Styrene--Divinylbenzene Copolymers 14
2.1.1.1 Swelling Behavior 15
2.1.1.2 Chemical Stability 17
2.1.1.3 Functionalization 17
2.1.2 Macroporous Styrene--Divinylbenzene Copolymers 19
2.1.3 Miscellaneous Polystyrenes 20
2.2 Poly(ethylene glycol)--Polystyrene Graft Polymers 21
2.3 Poly(ethylene glycol) 22
2.4 Polyacrylamides 22
2.5 Polyacrylamide--PEG Copolymers 24
2.6 Silica 25
2.7 Polysaccharides 26
2.8 Miscellaneous Supports 27
3 Linkers for Solid-Phase Organic Synthesis 33
3.1 Linkers for Carboxylic Acids 35
3.1.1 Linkers for Acids Cleavable by Acids or Other Electrophiles 35
3.1.1.1 Benzyl Alcohol Linkers 35
3.1.1.2 Diarylmethanol (Benzhydrol) Linkers 37
3.1.1.3 Trityl Alcohol Linkers 37
3.1.1.4 Non-Benzylic Alcohol Linkers 38
3.1.2 Linkers for Acids Cleavable by Bases or Nucleophiles 39
3.1.2.1 Benzyl Alcohol Linkers 40
3.1.2.2 Non-Benzylic Alcohol Linkers 40
3.1.2.3 Miscellaneous Linkers Cleavable by Bases or Nucleophiles 43
3.1.3 Photocleavable Linkers for Carboxylic Acids 45
3.1.4 Linkers for Acids Cleavable by Transition Metal Catalysis 47
3.1.5 Linkers for Acids Cleavable by Enzymes 49
3.2 Linkers for Thiocarboxylic Acids 50
3.3 Linkers for Amides, Sulfonamides, Carbamates, and Ureas 50
3.3.1 Benzylamine Linkers 51
3.3.2 (Diarylmethyl)amine and Tritylamine Linkers 55
3.3.3 Linkers for Amides Cleavable by Nucleophiles 59
3.3.3.1 Nucleophilic Cleavage of Alkyl Esters 59
3.3.3.2 Nucleophilic Cleavage of Aryl Esters 61
3.3.3.3 Nucleophilic Cleavage of Oxime and Related Esters 63
3.3.3.4 Nucleophilic Cleavage of Amides and Carbamates 63
3.4 Linkers for Hydroxamic Acids and Hydrazides 63
3.5 Linkers for Carboxylic Esters 67
3.5.1 Linkers for Esters Cleavable by Nucleophiles 67
3.5.2 Linkers for Lactones Cleavable by Electrophiles or Oxidants 70
3.6 Linkers for Primary and Secondary Aliphatic Amines 71
3.6.1 Benzylamine, (Diarylmethyl)amine, and Tritylamine Linkers 72
3.6.2 Carbamate Attachment 74
3.6.3 Miscellaneous Linkers for Aliphatic Amines 76
3.7 Linkers for Tertiary Amines 77
3.8 Linkers for Aryl- and Heteroarylamines 79
3.9 Linkers for Guanidines and Amidines 81
3.10 Linkers for Pyrroles, Imidazoles, Triazoles, and Tetrazoles 84
3.11 Linkers for Alcohols and Phenols 85
3.11.1 Attachment as Ethers 85
3.11.2 Attachment as Silyl Ethers 89
3.11.3 Attachment as Acetals 91
3.11.4 Attachment as Esters 91
3.11.5 Miscellaneous Linkers for Alcohols and Phenols 94
3.12 Linkers for Thiols 96
3.13 Linkers for Alkyl and Aryl Halides 99
3.14 Linkers for Aldehydes and Ketones 99
3.14.1 Attachment as Enol Ethers, Enamines, and Imines 100
3.14.2 Attachment of Carbonyl Compounds as Acetals 100
3.14.3 Miscellaneous Linkers for Aldehydes and Ketones 103
3.15 Linkers for Olefins 103
3.15.1 Linkers for Olefins Cleavable by b-Elimination 104
3.15.2 Linkers for Olefins Cleavable by Olefin Metathesis 108
3.16 Linkers for Alkanes and Arenes 110
3.16.1 Cleavage followed by Decarboxylation 110
3.16.2 Cleavage of Silanes and related Compounds 111
3.16.3 Reductive Cleavage of Carbon--Oxygen and Carbon--Nitrogen Bonds 114
3.17.1 Ion-Exchange Resins 118
3.17.2 Transition Metal Complexes 118
3.17.3 Miscellaneous Non-Covalent Linkers 119
4 Preparation of Organometallic Compounds 133
4.1 Group I and II Organometallic Compounds 133
4.2 Group III Organometallic Compounds 136
4.3 Group IV Organometallic Compounds 137
4.4 Transition Metal Complexes 138
5 Preparation of Hydrocarbons 143
5.1 Preparation of Alkanes 143
5.1.1 Preparation of Alkanes by Hydrolysis of Organometallic Compounds 143
5.1.2 Preparation of Alkanes by Hydrogenation and Reduction 143
5.1.3 Preparation of Alkanes by Carbon--Carbon Bond Formation 145
5.1.3.1 Coupling Reactions with Group I Organometallic Compounds 145
5.1.3.2 Coupling Reactions with Group II Organometallic Compounds 146
5.1.3.3 Coupling Reactions with Boranes 147
5.1.3.4 Coupling Reactions with Arylpalladium Compounds 148
5.1.3.5 Alkylations with Alkyl Radicals 149
5.1.3.6 Preparation of Cycloalkanes 150
5.2 Preparation of Alkenes 151
5.2.1 Preparation of Alkenes by b-Elimination and Reduction 151
5.2.2 Preparation of Alkenes by Carbonyl Olefination 152
5.2.2.1 By Wittig Reaction 152
5.2.2.2 By Aldol and Related Condensations 155
5.2.2.3 By Other Carbonyl Olefinations 156
5.2.3 Preparation of Alkenes by Olefin Metathesis 156
5.2.4 Preparation of Alkenes by C-Vinylation 159
5.2.5 Preparation of Cycloalkenes by Cycloaddition 163
5.3 Preparation of Alkynes 165
5.4 Preparation of Biaryls 168
6 Preparation of Alkyl and Aryl Halides 177
6.1 Preparation of Alkyl Halides 177
6.2 Preparation of Aryl and Heteroaryl Halides 181
7 Preparation of Alcohols and Ethers 185
7.1 Preparation of Alcohols 186
7.1.1 Reduction of Carbonyl Compounds 186
7.1.2 Addition of Carbon Nucleophiles to C--O Double Bonds 187
7.1.3 Miscellaneous Preparations of Alcohols 191
7.1.4 Protective Groups for Alcohols 193
7.1.4.1 Protective Groups Cleavable by Acids 193
7.1.4.2 Protective Groups Cleavable by Nucleophiles 195
7.2 Preparation of Ethers 197
7.2.1 Preparation of Dialkyl Ethers 197
7.2.2 Preparation of Alkyl Aryl Ethers 200
7.2.3 Preparation of Diaryl Ethers 204
8 Preparation of Sulfur Compounds 209
8.1 Preparation of Thiols 209
8.2 Preparation of Thioethers 211
8.3 Preparation of Sulfoxides and Sulfones 215
8.4 Preparation of Sulfonamides 216
8.5 Preparation of Sulfonic Esters 221
9 Preparation of Organoselenium Compounds 227
10 Preparation of Nitrogen Compounds 229
10.1 Preparation of Amines 229
10.1.1 Preparation of Amines by Aliphatic Nucleophilic Substitution 229
10.1.1.1 With Support-Bound Alkylating Agents 229
10.1.1.2 By Alkylation of Support-Bound Amines 233
10.1.2 Preparation of Amines by Aromatic Nucleophilic Substitution 233
10.1.2.1 With Support-Bound Arylating Agents 233
10.1.2.2 By Arylation of Support-Bound Amines 237
10.1.3 Preparation of Amines by Addition of Amines to C--C Double Bonds 239
10.1.4 Preparation of Amines by Reduction of Imines 239
10.1.5 Preparation of Amines by Reaction of Carbon Nucleophiles with Imines or Aminals 242
10.1.6 Preparation of Amines by Reduction of Amides and Carbamates 245
10.1.7 Preparation of Amines by Reduction of Nitro Compounds 246
10.1.8 Preparation of Amines by Reduction of Azides 247
10.1.9 Miscellaneous Preparations of Amines 248
10.1.10 Protective Groups for Amines 249
10.1.10.1 Carbamates 250
10.1.10.2 Amides 256
10.1.10.3 Cyclic Imides 257
10.1.10.4 Enamines 258
10.1.10.5 Imines 259
10.1.10.6 N-Alkyl and N-Aryl Derivatives 259
10.1.10.7 N-Sulfenyl and N-Sulfonyl Derivatives 260
10.2 Preparation of Quaternary Ammonium Salts 261
10.3 Preparation of Hydrazines and Hydroxylamines 262
10.4 Preparation of Azides 263
10.5 Preparation of Diazo Compounds 264
10.6 Preparation of Nitro Compounds 265
11 Preparation of Phosphorus Compounds 274
11.1 Phosphonic Acid Derivatives 274
12 Preparation of Aldehydes and Ketones 275
12.1 Preparation of Aldehydes and Ketones by C-Acylation 275
12.2 Preparation of Aldehydes and Ketones by Oxidation 277
12.3 Miscellaneous Preparations of Aldehydes and Ketones 278
13 Preparation of Carboxylic Acid Derivatives 285
13.1 Preparation of Amides 285
13.1.1 Preparation of Amides by Acylation of Amines with Isolated Acylating Agents 285
13.1.2 Acylation of Amines with Acylating Reagents Formed In Situ 288
13.1.2.1 Activation of Acids with Carbodiimides 290
13.1.2.2 Activation of Acids with Phosphonium Salts 294
13.1.2.3 Activation of Acids with Uronium Salts 296
13.1.3 Miscellaneous Preparations of Amides 298
13.1.4 Preparation of Amides by C-Alkylation of Other Amides 300
13.1.5 Preparation of Amides by N-Alkylation of Other Amides 301
13.2 Preparation of Hydroxamic Acids and Hydrazides 302
13.3 Preparation of Carboxylic Acids 303
13.4 Preparation of Carboxylic Esters 304
13.4.1 Preparation of Esters from Support-Bound Alcohols 304
13.4.1.1 Esterification of Support-bound Alcohols with N-Protected a-Amino Acids 309
13.4.2 Preparation of Esters from Support-Bound Alkylating Agents 311
13.4.3 Preparation of Esters from Support-Bound Carboxylic Acids 313
13.4.4 Preparation of Esters by Chemical Modification of Other Esters 315
13.5 Preparation of Thiol Esters 315
13.6 Preparation of Amidines and Imino Ethers 315
13.7 Preparation of Nitriles and Isonitriles 318
13.8 Preparation of Imides 319
13.9 Preparation of Thioamides 321
14 Preparation of Carbonic Acid Derivatives 327
14.1 Preparation of Carbodiimides 327
14.2 Preparation of Isocyanates and Isothiocyanates 328
14.3 Preparation of Guanidines 329
14.4 Preparation of Ureas 331
14.5 Preparation of Thioureas and Isothioureas 334
14.6 Preparation of Carbamates 335
14.7 Preparation of Carbonates and Miscellaneous Carbonic Acid Derivatives 338
15 Preparation of Heterocycles 343
15.1 Preparation of Epoxides and Aziridines 343
15.2 Preparation of Azetidines and Thiazetidines 344
15.3 Preparation of Pyrroles and Pyrrolidines 345
15.4 Preparation of Indoles and Indolines 350
15.5 Preparation of Furans and Tetrahydrofurans 354
15.6 Preparation of Benzofurans and Dihydrobenzofurans 356
15.7 Preparation of Thiophenes 358
15.8 Preparation of Imidazoles 361
15.9 Preparation of Hydantoins (2,4-Imidazolidinediones) and Thiohydantoins 363
15.10 Preparation of Benzimidazoles 367
15.11 Preparation of Isoxazoles 369
15.12 Preparation of Oxazoles and Oxazolidines 373
15.13 Preparation of Thiazoles and Thiazolidines 373
15.14 Preparation of Pyrazoles 374
15.15 Preparation of Triazoles, Tetrazoles, Oxadiazoles, and Thiadiazoles 376
15.16 Preparation of Pyridines and Dihydropyridines 378
15.17 Preparation of Tetrahydropyridines and Piperidines 380
15.18 Preparation of Fused Pyridines 382
15.19 Preparation of Pyridazines (1,2-Diazines) 387
15.20 Preparation of Pyrimidines (1,3-Diazines) 389
15.21 Preparation of Quinazolines 391
15.22 Preparation of Pyrazines and Piperazines (1,4-Diazines), and Fused Derivatives thereof 394
15.22.1 Preparation of Diketopiperazines 394
15.22.2 Preparation of Miscellaneous 1,4-Diazines and Quinoxalines 397
15.23 Preparation of Triazines 398
15.24 Preparation of Pyrans and Benzopyrans 399
15.25 Preparation of Oxazines and Thiazines 400
15.26 Preparation of Azepines and Larger Heterocycles with one Nitrogen Atom 402
16.1 Peptides 414
16.1.1 Merrifield\9s Peptide Synthesis 414
16.1.2 The Boc Strategy 415
16.1.3 The Fmoc Strategy 417
16.1.4 Side-Chain Protection 419
16.1.5 Backbone Protection 420
16.1.6 Cyclic Peptides 421
16.2 Oligonucleotides 422
16.2.1 Historical Overview 422
16.2.2 The Phosphotriester Method 424
16.2.3 The Phosphoramidite and H-Phosphonate Methods 425
16.2.4 Oligonucleotide Analogs 428
16.3 Oligosaccharides 428
16.3.1 Glycosylation with Glycosyl Bromides 429
16.3.2 Glycosylation with Glycosyl Sulfoxides 430
16.3.3 Glycosylation with Glycosyl Thioethers 431
16.3.4 Glycosylation with Miscellaneous Glycosyl Donors 431
16.4 Miscellaneous Oligomeric Compounds 433
16.4.1 Oligoamides 433
16.4.1.1 Oligoglycines 434
16.4.1.2 Peptide Nucleic Acids (PNA) 434
16.4.2 Oligoesters 436
16.4.3 Oligoureas and Oligothioureas 436
16.4.4 Oligocarbamates 437
16.4.5 Oligosulfonamides 438
16.4.6 Oligomeric Phosphoric Acid Derivatives 438
16.4.7 Peptide-Derived Oligomeric Compounds 439
16.4.8 Oligomers Prepared by C--C Bond Formation 439
16.4.9 Dendrimers 441
17 Index 449
*Editor's Note: The brief summary and the contents of the books are reported as provided by the author or the publishers. Authors and publishers are encouraged to send review copies of their recent books of potential interest to readers of Molecules to the Editor-in-Chief (Dr. Shu-Kun Lin, MDPI, Saengergasse 25, CH-4054 Basel, Switzerland. Tel. +41 79 322 3379, Fax +41 61 302 8918, E-mail: [email protected]). Some books will be offered to the scholarly community for the purpose of preparing full-length reviews.