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Solid-phase organik syntheses - Burdges K.

Burdges K. Solid-phase organik syntheses - John Wiley & Sons, 2000. - 283 p.
ISBN 0-471-22824-9
Download (direct link): phaseorganicsynthesis2000.pdf
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Tags
chemical, 150, 151 radiofrequency, 150, 211 Tamoxifen, 52 Taxol, 253, 256 TentaGel resin, 29, 198 Tests
for conversion of resin-bound secondary amines to triazenes, 127 Tethers, 126
Tetrabutylammonium chloride, 29, 34 Tetrafluorophthalic anhydride, 158, 186
Tetrahydroquinones, 172
INDEX 277
Tetramethylguanidine, 30 Tetramic acids, 179, 180 Tetrazole, 67 Thiazepinones, 111 Thiazinones, 84, 97 Thiiranes, 168 Thiocarbonyl, 16 Thiocarbonyldiimidazole, 16
1,1'-, 106
Thiocyanate ions, polymer-supported,
168
Thiolactic acid, 97
Thiophene, nitro-substituted, 111
Thioureas, 4, 6, 10, 11, 12, 16, 157
Thiouronium salt, 12
Three component strategy, 248
Tin
containing-polymers, 255 fluorous-tagged reagents, 175 tetraallyl, 172 triphenylmethyl, 46 TNF, 263 TOCSY, 42, 138 TPAP, 239
Traceless linkers, 39, 47, 62, 109 silicon-based, 55 silyl-based, 47, 59 Transesterification, 29 as a resin cleavage method, 49 TransStems, 211 Triazenes, 122, 123 as traceless linker, 39 diethyl, 38, 39 linkers, 126
preparation of, as linkers, 144 Triazines, 175 Triflates aryl, 29 vinyl, 31, 64 Triflic acid, 18 Trifluoroacetamides, 30 Triflylguanidines, 7
Trimethylorthoformate in reductive alkylations, 84 Trimethylsilanolate potassium, 35 Trimethylsilyl deprotection, 122, 140 TROC, 16 Tropanes, 55
Tubulin inhibitors, 253, 258 Tweezer receptor, 18 Tyrosine, 261
Tyrosine kinase inhibitors, 258
Ugi reactions, 176 Universal library, 25 Ureas, 88, 154, 164 dehydration of, 7 N-acyl, 88
Veber, 59 Verapamil, 84 Verruculogens, 260 Vibrational spectroscopy, 219 Vinyl boronates, 53, 54 Vinyl triflates, 31, 64
Wang linker, 105
Wang resin, 27, 40, 42, 45, 104, 224, 261
Wittig reactions, 253 Yields
determination in solid phase syntheses of polymers, 139 determination of, spectroscopically, 239
Zearalenone, 253 Zinc organometallics, 70
CHAPTER 1
Solid-Phase Organic Synthesis. Edited by Kevin Burgess Copyright 2000 John Wiley & Sons, Inc. ISBNs: 0-471-31825-6 (Hardback); 0-471-22824-9 (Electronic)
SOLID-PHASE SYNTHESES OF GUANIDINES
intermediate
KEVIN BURGESS and JIONG CHEN Texas A & M University
1.1. INTRODUCTION
Guanidines are basic molecules (pKa of guanidine = 12.5) with a capacity to form intermolecular contacts mediated by H-bonding interactions. Consequently, they are potentially useful pharmacophores in medicinal chemistry,1 have proven applications as artificial sweeteners,2,3 and are useful as probes in academic studies of intermolecular associations, including su-pramolecular complexes. Expedited access to these molecules via solid-phase synthesis is therefore a worthy goal. This chapter outlines various
1
2 SOLID-PHASE SYNTHESES OF GUANIDINES
solution-phase syntheses of guanidines, then gives a more detailed description of work that has been done to adapt these methods to supported syntheses.
1.2. OUTLINE OF SOME SOLUTION-PHASE APPROACHES TO GUANIDINES
It is difficult to formulate retrosynthetic analyses of guanidines because their substitution patterns determine the most efficient routes to these materials. Some generalities are outlined in Scheme 1. These syntheses are discussed more fully in the following subsections, although the coverage is intended to be an outline of the approaches most relevant to solid-phase syntheses, not a comprehensive summary.
1.2.1. From Electrophiles Containing One Nitrogen Atom
Imidocarbonyl dichlorides that are functionalized with an electron-withdrawing group (e.g., 1) react with amines at room temperature or below, affording symmetrical guanidines.4 It was originally suggested that guanidines with less symmetrical substitution patterns could not be formed
r1n=nr2
Scheme 1.
1.2. OUTLINE OF SOME SOLUTION-PHASE APPROACHES TO GUANIDINES 3
Scheme 2.
by stepwise displacement of leaving groups from imidocarbonyl dichlorides,4 but that suggestion has been shown to be incorrect, as illustrated in Scheme 2.5
Stepwise displacement of phenoxide from diphenyl carbonimidates (e.g., 2) is also possible, as in Scheme 3.6
Scheme 3.
Imidoyl dichlorides are formed by chlorination of the corresponding 5,5-dialkylimidodithiocarbonimidates, but the latter compounds can also be used as starting materials for syntheses of guanidines. In this type of synthesis, an amine is generally heated with the 5,5-dialkylimidodithiocar-
4 SOLID-PHASE SYNTHESES OF GUANIDINES
N-Ts cbznk^nh N"Ts
. .. 1
AgNOb
-------------> CBZNH
NH3, MeCN, 0
Scheme 4.
bonimidate (e.g., 3) to cause the first displacement; then the product is treated with the second amine and a metal salt with high affinity for sulfur to give the guanidine (Scheme 4).7,8
1.2.2. From Electrophiles Containing Two or More Nitrogen Atoms
Cyanamides like 4 (from amines and cyanogen bromide) provide access to guanidines. This approach allows for introduction of different substituents, and alkylating intermediates can further increase the diversity of products produced. However, high temperatures are required, especially with aromatic amines, for the final addition to give the guanidine products (Scheme 5).9
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