Polystyrene Wang resin

Fig. 5 Microwave-assisted loading protocol of carboxylic acids to chlorinated polystyrene Wang resin...

The earliest published example of microwave-assisted SPOS involved diisopropyl-carbodiimide (DlC)-mediated solid-phase peptide couplings [24], Numerous Fmoc-protected amino acids and peptide fragments were coupled with glycine-preloaded polystyrene Wang resin (PS-Wang) in DMF, using either the symmetric anhydride or preformed N-hydroxybenzotriazole active esters (HOBt) as precursors (Scheme 12.1). 

In a more recent study using dedicated multimode microwave reactors for chemical synthesis, which enable temperature and power control, it was demonstrated that microwave irradiation could be effectively employed to couple aromatic carboxylic acids to polystyrene Wang resin [25], if the symmetrical anhydride procedure was used, and not the three-component O-acylisourea activation method [19]. Almost quantitative loading was achieved in l-methyl-2-pyrrolidone (NMP) at 200 °C within 10 min under... 

Polystyrene stereo structures, 70 180-183 Poly(styrenesulfonic acid) (PSSA) 23 720 preparation of, 20 467-468 synthesis of, 23 535 Polystyrene Wang resin, coupling of aromatic... 

Abbreviations DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DMF, A/fV-dimethylformamide MCPBA, 3-chloroperbenzoic acid NMP, A-methyl-2-pyrrolidinone Pol, undefined polymeric support PS, cross-linked polystyrene Wang resin, 1-2% cross-linked polystyrene with p-benzyloxybenzyl alcohol linker. 

Solid-phase synthesis is of importance in combinatorial chemistry. As already mentioned RuH2(PPh3)4 catalyst can be used as an alternative to the conventional Lewis acid or base catalyst. When one uses polymer-supported cyanoacetate 37, which can be readily obtained from the commercially available polystyrene Wang resin and cyanoacetic acid, the ruthenium-catalyzed Knoevenagel and Michael reactions can be performed successively [27]. The effectiveness of this reaction is demonstrated by the sequential four-component reaction on solid phase as shown in Scheme 11 [27]. The ruthenium-catalyzed condensation of 37 with propanal and subsequent addition of diethyl malonate and methyl vinyl ketone in TH F at 50 °C gave the adduct 40 diastereoselectively in 40 % yield (de= 90 10). 

Iodophenol, immobilized on a polystyrene-Wang resin, has been treated with a series of arylboronic acids dissolved in [C imJfBFJ using Pd(PPh3)4 as the palladium source (Scheme 5).47 The catalytic system was initiated in a similar manner to that previously reported45 and the reactions conducted at 110°C for 2 h. A 1 1 mixture with DMF was required to swell the hydrophobic cross-linked polystyrene resin and when neat [C4mim][BF4] was used no biaryl products were isolated. 

CjCqmHBFJ Pd(PPh3)4 Na2C03 110 °C. Solid-phase reaction coupling of 4-iodophenol immobilised on a polystyrene-Wang resin with arylboronic acids DMF as co-solvent acceleration in the presence of the ionic liquid catalyst recycling not practical. [102]... 

Ganesan and Bonnet [400] have reported a similar N-acyliminium ion-mediated Pictet-Spengler reaction. Again, r-tryptophan linked to a polystyrene-Wang resin through the carboxylic group (557) was first reacted with a number of aldehydes in... 

The synthesis of highly substituted pyrrolidines was performed using commercially available monodisperse polystyrene Wang resin from Rapp Polymere (Tubingen, Germany). The diameter of the beads was 160 pm. 

Polymer types and polymer matrix effects will obviously affect stability of both states. Recently, spiropyran has been attached to polystyrene Wang resin, which serves as a solid support, to minimize thermal back reaction and improve bistability (see Fig. 6.3). The resultant photochromic microbeads suspended in toluene greatly... 

Rapid loading of cross-linked PS Wang resin (4-(benzyloxy)benzyl alcohol PS) with a selection of /3-ketoesters was shown to reach completion within 1-10 min if microwave irradiation at 170 °C was employed. The conventional thermal method for acetoacetylation of hydroxymethyl-functionalized polystyrene resins takes several hours therefore, microwave heating allowed for... 

Polystyrene resin with a hydroxymethylphenoxy linker (Wang resin)1 was originally developed for solid-phase peptide synthesis... 

Fig. 1. Chemical structure of Wang resin, where the resin is 1-2% crosslinked polystyrene and the molecule is the species synthesized and ultimately liberated from the resin.

Tyr Ura UV Val Wang resin XAL linker Z 5-tyrosine uracil ultraviolet 5-valine cross-linked polystyrene with 4-benzyloxybenzyl alcohol linker Sieber linker, 3-alkoxy-9//-9-xanthenylamine Cbz, benzyloxycarbonyl... 

Cleavage conditions for alkyl benzyl ethers prepared from acid-labile benzyl alcohols are similar to those for the corresponding benzyl esters (Table 3.30). Aryl benzyl ethers, however, are generally cleaved more easily by acidolysis than esters or alkyl ethers. Phenols etherified with hydroxymethyl polystyrene, for instance, can even be released by treatment with TFA (Entry 1, Table 3.31). It has also been shown that Wang resin derived phenyl ethers are less stable than Wang resin derived esters towards refluxing acetic acid [29]. Alternatively, boron tribromide may be used to cleave aryl ethers from hydroxymethyl polystyrene [573],... 

Intramolecular Dieckmann cyclization of polystyrene-bound pimelates has been used to prepare (l-keto esters (Entry 4, Table 3.41). Oxidative cleavage reactions leading to the formation of aldehydes include the ozonolysis of resin-bound alkenes, the periodate-mediated cleavage of 1,2-diols, and the oxidation of Wang resin derived ethers (Entries 5-7, Table 3.41). 

Figure 4.2. Halogen-metal exchange on cross-linked polystyrene [1,13,16,18], (PS) Wang resin.

Acrylic acid esterified with cross-linked hydroxymethyl polystyrene or Wang resin reacts smoothly with primary or secondary aliphatic amines at room temperature (Entries 1 and 2, Table 10.6). Only sterically demanding amines or amines of low nucleophilicity (anilines, a-amino acid esters) fail to add to polystyrene-bound acrylate. Support-bound acrylamides are less reactive than acrylic esters, and generally require heating to undergo addition with amines (Entries 4 and 5, Table 10.6). a, 3-Unsaturated esters with substituents in the 3-position (e.g. crotonates, Entry 3, Table 10.6) react significantly more slowly with nucleophiles than do acrylates. The examples in Table 10.6 also show that polystyrene-bound esters are rather stable towards aminolysis, and provide for robust attachment even in the presence of high concentrations of amines. Entry 10 in Table 10.6 is an example of the alkylation of a resin-bound amine with an electron-poor alkene to yield a fluorinated peptide mimetic. 

Standard solid-phase peptide synthesis requires the first (C-terminal) amino acid to be esterified with a polymeric alcohol. Partial racemization can occur during the esterification of N-protected amino acids with Wang resin or hydroxymethyl polystyrene [200,201]. /V-Fmoc amino acids are particularly problematic because the bases required to catalyze the acylation of alcohols can also lead to deprotection. A comparative study of various esterification methods for the attachment of Fmoc amino acids to Wang resin [202] showed that the highest loadings with minimal racemization can be achieved under Mitsunobu conditions or by activation with 2,6-dichloroben-zoyl chloride (Experimental Procedure 13.5). iV-Fmoc amino acid fluorides in the presence of DMAP also proved suitable for the racemization-free esterification of Wang resin (Entry 1, Table 13.13). The most extensive racemization was observed when DMF or THF was used as solvent, whereas little or no racemization occurred in toluene or DCM [203]. 

Trichloroacetimidates are the only type of imino ethers to have found some application in solid-phase synthesis. Trichloroacetimidates can readily be prepared from support-bound alcohols by treatment with trichloroacetonitrile and a base (Entry 6, Table 13.18). Because trichloroacetimidates are good alkylating agents, this reaction offers a convenient alternative for converting support-bound aliphatic alcohols into alkylating agents. Trichloroacetimidates prepared from Wang resin or from hydroxymethyl polystyrene are quite stable and can be stored for several months without decomposition [253],... 

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