Non-cross-linked polystyrene

Non-cross-linked polystyrene is readily prepared from inexpensive materials using standard conditions and the functional group content of the polymer easily controlled by the stoichiometry of each monomer present in the monomer feed. As with PEG, the functional group content can be readily quantified using simple NMR analysis. The polymer has remarkable solubility properties that are extremely useful to organic chemists. It is soluble in THE, dichloromethane, chloro- 

Many different soluble polymers have been used as supports for catalyst immobilization. Since solvation of otherwise insoluble catalysts can frequently be accom-pHshed by attachment to a soluble polymer, these supports have found significant use in the immobihzation of classical solution phase catalysts. Here, we will only survey polyethylene glycol (PEG) as a soluble polymeric support for catalysis. The use of other types of soluble polymers (e.g., polyethylene, non-cross-linked polystyrene) has been reviewed elsewhere [49]. 

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Linear non-cross-linked polystyrene has been used for organic synthesis since it is readily soluble in common organic solvents (i.e., dichloromethane, chloroform, tetrahydrofuran, toluene, ethyl acetate, and pyridine) but precipitates upon addition of water or methanol [123-126]. However, no examples of the use of this polymer in conjunction with microwave chemistry have been reported. 

Soluble polymers that have been used in hquid-phase methodologies are listed in Fig. 5.1 [3, 7, 8, 34, 35]. Polyethylene glycol and non-cross-linked polystyrene are some of the most often used polymeric carriers for organic synthesis and have found frequent use in the preparation of soluble polymer-supported catalysts and reagents consequently, a brief discussion of these polymers is warranted. 

Chen, S. Janda, K. D. Total Synthesis of Naturally Occurring Prostaglandin F2oc on a Non-Cross-Linked Polystyrene Support, Tetrahedron Lett. 1998, 39, 3943. 

In this section the use of polystyrene and copolymers of styrene with various cross-linking agents as supports for solid-phase organic synthesis is discussed. Copolymers of styrene with divinylbenzene are the most common supports for solid-phase synthesis. Depending on the kind of additives used during the polymerization and on the styrene/divinylbenzene ratio, various different types of polystyrene can be prepared. However, non-cross-linked polystyrene has also been used as a support for organic synthesis [10,16-22], Linear, non-cross-linked polystyrene is soluble in organic solvents such as toluene, pyridine, ethyl acetate, THF, chloroform, or DCM, even at low temperatures, but can be selectively precipitated by the addition of methanol or water. 

Polystyrene-bound allylic or benzylic alcohols react smoothly with hydrogen chloride or hydrogen bromide to yield the corresponding halides. The more stable the intermediate carbocation, the more easily the solvolysis will proceed. Alternatively, thionyl chloride can be used to convert benzyl alcohols into chlorides [7,25,26]. A milder alternative for preparing bromides or iodides, which is also suitable for non-benzylic alcohols, is the treatment of alcohols with phosphines and halogens or the preformed adducts thereof (Table 6.2, Experimental Procedure 6.1 [27-31]). Benzhy-dryl and trityl alcohols bound to cross-linked or non-cross-linked polystyrene are particularly prone to solvolysis, and can be converted into the corresponding chlorides by treatment with acetyl chloride in toluene or similar solvents (Table 6.2 [32-35]). 

Figure 16.9. Synthesis of oligonucleotides on non-cross-linked polystyrene using nucleoside 5 -phos-phates [91],...

Lau, K.C.Y. and Chiu, P. (2007) The application of non-cross-linked polystyrene-supported triphenylarsine in Stille coupling reactions. Tetrahedron Letters, 48(10), 1813-16. 

Enholm EJ, Gallagher ME, Jiang S, Batson WA, Free radical allyl transfers utilizing soluble non-cross-linked polystyrene and carbohydrate scaffold supports, Org. Lett., 2 3355-3357, 2000. 

Functional groups attached to solvent-swollen polymer chains exhibit free rotational motion as indicated by electron spin resonance rotational correlation times 132-134) These studies using nitroxide spin labels covalently bound to polystyrene matrices indicated that the mobility of the substituent is a function of the cross-link density and degree of swelling. The rotational correlation time of nitroxide within 2% cross-linked beads was about 100 times shorter in dichloromethane or benzene than in ethanol, and 2-3 times longer than nitroxide bound to non-cross-linked polystyrene. The latter observation shows that the heterogeneous reaction involving 2% cross-linked polystyrene is 2-3 times slower than the same reaction in solution. 

Figure 8.49 S)mthesis of the prostaglandin 8.106 using a non-cross linked polystyrene (NCPS) soluble support.

Enholm [12] has carried out free radical allyl transfer reactions using a non-cross-linked polystyrene, soluble polymer 77. Model reactions of bro-mo ester 78 with allyltin reagents gave products 79 and 80 in excellent yield (Scheme 17). 

In spite of their potential in substitution or in addition reactions, supported allyltins have not been used very often. Examples include radical transfer of an allyl unit to a-bromo ketones or esters, which was described for allyltins grafted on a soluble non-cross-linked polystyrene support. In this case, tin contamination for the initial reaction was 7-54 ppm but increased to 15-80 ppm when recycled polymer was used. 

Chiral ligands can be varied with rhodium catalysts modifications with Diop, Diop-DBP and other variants of Diop, Chiraphos, BPPM, BnCH3PhP, CH3PrPhP, NMDPP, and AMPP type ligands are reported (for abbreviations and literature see Section 1.5.8.2.2.2.). Polymer-supported catalysts are mainly used as non-cross-linked polystyrene with attached phosphane ligands, among others Diop and BPPM9 62,153-155. Aspects of these variations are discussed below under platinum catalysts). 

Several reviews discussing general aspects of this topic are available154- l 55,159. In the first applications the rhodium catalyst was attached to non-cross-linked polystyrene via chiral phosphane ligands such as Diop9. More efficiency is achieved with platinum catalysts attached to cross-linked polystyrene/ Diop systems138. 

A polymer-supported rhodium catalyst modified with Diop attached to non-cross-linked polystyrene, first used in the asymmetric hydroformylation of styrene, gives 95 % branched aldehyde, however with only 2% ee9. Further developments in the preparation and use of cross-linked polymers with attached chiral phosphane ligands (Diop, DIPHOL, BPPM) in rhodium- and platinum-catalyzed asymmetric hydroformylation have led to good to excellent results with respect to the asymmetric induction62-124 157,159 and arc described in Section 1.5.8 2.2.3.2. The results arc integrated in Table 4. 

Generation of dichlorocarbene was also reported when ammonium salts were supported on a non-cross-linked polystyrene matrix [89b], Then the reaction involved mixing of chloroform, polymer-supported PTC catalyst, and styrene in the presence of a sodium hydroxide solution. The product, l,l-dichloro-2-phenylcyclopropane was afforded in a very good yield (94%) after 10 min of MW irradiation at 65 W. 

FIGURE 11.12 Prostaglandins E2 and Fj combinatorial libraries. (From Chen, S. and Janda, K.D., Synthesis of prostaglandin Ej methyl ester on a soluble-polymer support for the construction of prostanoid libraries, J. Am. Chem. Soc., 119, 8724, 1995 Chen, S. and Janda, K.D., Total synthesis of naturally occurring prostaglandin F2on a non-cross-linked polystyrene support. Tetrahedron Lett., 39, 3943, 1998.)... 

Chen, S. and Janda, K.D., Total synthesis of naturally occurring prostaglandin Fj on a non-cross-linked polystyrene support, Tetrahedron Lett., 39, 3943, 1998. 

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