Chloromethylated polystyrene crosslinking

Although phase transfer agents have been attached to clays, silica and alumina, the vast majority of studies have used organic polymers, especially polystyrene, as the support. The earliest of these triphase catalysts was prepared from 12% chloromethylated polystyrene crosslinked with 2% divinylbenzene by reaction with a tertiary amine. A wide range of triphase catalysts has since been reported, some examples of which are shown in Figure 5.16. 

Polymers bearing a functional group based on diisobutylphosphine sulfide and containing different spacer arms between the polymeric matrix and the phosphorus functional group were synthesized by Sanchez and co-workers from chloromethylated polystyrene (crosslinked with 4% DVB)... 

A polymer-bound analog of the p-sulfonato-calix[6]arenes is described in a Shinkai patent [31,32], which states that the hexakis(carbetoxymethyl)ether of p-sulfonatocalix[6]arene was partially nitrated, ami-nated, and fixed on crosslinked chloromethylated polystyrene. This resin is stated to absorb 108 ixg of uranium... 

The selected example by Chen and Janda [175] reported the validation of a method for the synthesis of prostanoid libraries on a soluble polymeric support made by non-crosslinked chloromethylated polystyrene (NCPS). The synthesis of supported PGE2 methyl ester is shown in Figure 7.23. 

Owing to this type of reaction, both chloromethylated polystyrene and poly(oc-methylstyrene) show crosslinking properties. 

Besides the classical polymer introduced by Merrifield (1%-crosslinked chloromethylated polystyrene), a broad variety of polymeric supports is available for SPPS and some of the most popular resins are summarized in Table 1. The chemical structures of some selected resins are presented in Figure 1 and electron micrographs of several examples are displayed in Figure 2. In addition to the solid supports listed in Table 1, there are several other carriers used in peptide synthesis such as the gel-type and macroporous poly(meth-acrylates), coated surfaces like polystyrene films on polyethylene (PEt) sheets, polystyrene-coated polyethylene or polytetrafluoroethylene, and modified glass surfaces. (For recent reviews on polymeric carriers see refs . )... 

The asymmetric alkylation of glycine derivatives is one of the most simple methods by which to obtain optically active a-amino acids [31]. The enantioselective alkylation of glycine Schiff base 52 under phase-transfer catalysis (PTC) conditions and catalyzed by a quaternary cinchona alkaloid, as pioneered by O Donnell [32], allowed impressive degrees of enantioselection to be achieved using only a very simple procedure. Some examples of polymer-supported cinchona alkaloids are shown in Scheme 3.14. Polymer-supported chiral quaternary ammonium salts 48 have been easily prepared from crosslinked chloromethylated polystyrene (Merrifield resin) with an excess of cinchona alkaloid in refluxing toluene [33]. The use of these polymer-supported quaternary ammonium salts allowed high enantioselectivities (up to 90% ee) to be obtained. 

Fig. 15.4.60. C NMR spectra of chloromethylated polystyrene resins of 0-6% crosslink ratio swollen in CDCI3 (see Ref. 97).

Amberlite XAD-4 polystyrene was supplied by Rohm Haas (20-50 mesh spheres) and was dried in a rotary evaporator at 50°C for 12 hr before being chloromethylated by the procedure of Pepper etal. [71a], to give a chlorine content of 10-11% (Aldrich also supplies a chloromethylated polystyrene which is a 1 and 2% crosslinked copolymer—called Merrifield s peptide resin and containing 1 meq Cl/gm resin [72]. 

Figure 7.4 Dependence of equilibrium swelling in toluene on the crosslinking degree of networks prepared by crosslinking linear polystyrene with partially chloromethylated polystyrene containing (1) 3 (2) 11.5 and (3) 14.8% chlorine. (After [129]).

In addition to the above-mentioned, rather painstaking, techniques of polypeptide syntheses, a very elegant technique was developed by Merrifield. This solid-phase peptide synthesis automates the reaction sequences. The method makes use of an insoluble crosslinked polymer substrate with pendant reactive groups for attachment of peptide chains. Chloromethylated polystyrene microgels are often used (see Chapter 8 for more discussions on the use of chloromethylated polystyrene for reactions of polymers). The chloromethyl moieties serve as the initiating sites for formation of the polypeptides ... 

The product of a reaction of chloromethylated polystyrene and triphenylphosphine can also convert to nucleophiles. In addition, use of a phase transfer catalyst converts soluble chloromethylated polystyrenes to phosphine oxides. Reactions with dioctylphosphine can serve as an example. Sometimes, phase transfer reactions are easier to carry out than conventional ones. This is the case with a Witting reaction. Both linear and crosslinked chloromethylated polystyrenes react smoothly with triphenylphosphine to give derivatives that react with various aldehydes. Phase transfer catalysts can also be used in carrying out nucleophilic substitutions with the aid of sulfides, like tetrahydrothiophine... 

The first type of polymers was formed by reaction of the phenoxide derived from DPEN with 1% crosslinked chloromethylated polystyrene (Schemes 4 and 5). It has been observed that in the cases of higher content of chloromethyl group or a higher degree of crosslinking, some unreacted chloromethyl groups remain. 

Itsimo has reported interesting work about the effect of the difference of the structure of the polymeric part on the enantioselectivity of the reaction and the stability of the support [117]. They first prepared the chiral aminoalcohols 125 which could react with a crosslinked chloromethylated polystyrene or 126 which could be copolymerised with styrene and some styrene-derived crosslinking compound (Scheme 65). 

---