Merrifield resin polymer-supported

One-shot crosslinking of multifunctional monomers and copolymerization therefore is limited to the radical induced copolymerization of styrene and some derivatives with divinylbenzene or of methacrylates with ethyleneglycol dimethacrylate as crosslinker in suspension polymerization to form densely crosslinked polymer beads for applications such as ion exchange resins, Merrifield resins, polymer supports for chemical reagents especially with the aspect of combinatorial syntheses. 

In cases where Noyori s reagent (see p. 102f.) and other enantioselective reducing agents are not successful, (+)- or (—)-chlorodiisopinocampheylborane (Ipc BCl) may help. This reagent reduces prochiral aryl and tert-alkyl ketones with exceptionally high enantiomeric excesses (J. Chandrasekharan, 1985 H.C. Brown, 1986). The initially formed boron moiety is usually removed hy precipitation with diethanolamine. Ipc2BCl has, for example, been applied to synthesize polymer-supported chiral epoxides with 90% e.e. from Merrifield resins (T. Antonsson, 1989). 

Metal ion complexes. These classic CSPs were developed independently by Davankov and Bernauer in the late 1960s. In a typical implementation, copper (II) is complexed with L-proline moieties bound to the surface of a porous polymer support such as a Merrifield resin [28-30]. They only separate well a limited number of racemates such as amino acids, amino alcohols, and hydroxy acids. 

Devaky and Rajasree have reported the production of a polymer-bound ethylenediamine-borane reagent (63) (Fig. 41) for use as a reducing agent for the reduction of aldehydes.87 The polymeric reagent was derived from a Merrifield resin and a 1,6-hexanediol diacrylate-cross-linked polystyrene resin (HDODA-PS). The borane reagent was incorporated in the polymer support by complexation with sodium borohydride. When this reducing agent was used in the competitive reduction of a 1 1 molar mixture of benzaldehyde and acetophenone, benzaldehyde was found to be selectively reduced to benzyl alcohol. 

A large variety of polymers has been considered. In the beginning, polystyrene and styrene/ divinylbenzene copolymers (Merrifield resins) were by far the most used.73 Then others were tested such as polyvinyls,47-50,61-64 polyacrylates,72 4,75 and cellulose.76,77 Most commonly, diphenylphos-phane groups were grafted on the polymeric support, either directly or via one CH2 group. 

The Dupont method to prepare polymer-supported bidentate phosphorus-containing ligands makes use of Merrifield s resin (Scheme 10).69... 

As far as polymer supports for microwave-assisted SPOS are concerned, the use of cross-linked macroporous or microporous polystyrene (PS) resins has been most prevalent. In contrast to common belief, which states that the use of polystyrene resins limits reaction conditions to temperatures below 130 °C [14], it has been shown that these resins can withstand microwave irradiation for short periods of time, such as 20-30 min, even at 200 °C in solvents such as l-methyl-2-pyrrolidone or 1,2-dichlorobenzene [15]. Standard polystyrene Merrifield resin shows thermal stability up to 220 °C without any degradation of the macromolecular structure of the polymer backbone, which allows reactions to be performed even at significantly elevated temperatures. 

As a suitable model reaction, the coupling of various substituted carboxylic acids to polymer resins has been investigated by Stadler and Kappe (Scheme 7.8) [28]. The resulting polymer-bound esters served as useful building blocks in a variety of further solid-phase transformations. In a preliminary experiment, benzoic acid was attached to Merrifield resin under microwave conditions within 5 min (Scheme 7.8 a). This functionalization was additionally used to determine the effect of micro-wave irradiation on the cleavage of substrates from polymer supports (see Section 7.1.10). The benzoic acid was quantitatively coupled within 5 min via its cesium salt utilizing standard glassware under atmospheric reflux conditions at 200 °C. 

Scheme 7.8 Resin functionalization with carboxylic acids using (a) Merrifield resin and (b) chlorinated Wang resin as the polymer support.

In a more recent study, Westman and Lundin have described solid-phase syntheses of aminopropenones and aminopropenoates en route to heterocycles [32], Two different three-step methods for the preparation of these heterocycles were developed. The first method involved the formation of the respective ester from N-pro-tected glycine derivatives and Merrifield resin (Scheme 7.12 a), while the second method involved the use of aqueous methylamine solution for functionalization of the solid support (Scheme 7.12 b). The desired heterocycles were obtained by treatment of the generated polymer-bound benzylamine with the requisite acetophenones under similar conditions to those shown in Scheme 7.12 a, utilizing 5 equivalents of N,N-dimethylformamide diethyl acetal (DMFDEA) as reagent. The final... 

The group of Botta demonstrated the feasibility of their microwave-assisted iodi-nation protocol (see Scheme 6.143 d) toward a polymer-supported substrate [68], An appropriate pyrimidinone attached to conventional Merrifield polystyrene resin was suspended in N,N-dimethylformamide, treated with 2 equivalents of N-iodosuccini-mide (NIS), and subjected to microwave irradiation for 3 min. Treatment of the polymer-bound intermediate with OXONE released the desired 5-iodouracil in almost quantitative yield (Scheme 7.57). 

In a more recent study, Wang and coworkers have discussed microwave-assisted Suzuki couplings employing a reusable polymer-supported palladium complex [141]. The supported catalyst was prepared from commercial Merrifield polystyrene resin under ultrasound Bonification. In a typical procedure for biaryl synthesis, 1 mmol of the requisite aryl bromide together with 1.1 equivalents of the phenyl-boronic acid, 2.5 equivalents of potassium carbonate, and 10 mg of the polystyrene-... 

In addition to the aforementioned microwave-assisted reactions on solid supports, several publications also describe microwave-assisted resin cleavage. In this context it has been demonstrated that carboxylic acids could be cleaved from conventional Merrifield resin, using the standard TFA-DCM 1 1 mixture, by exposure of the polymer-bound ester and the cleavage reagent to microwave irradiation in a dedicated Teflon autoclave (multimode instrument). After 30 min at 120 °C, complete recovery of the carboxylic acid was achieved (Scheme 12.9) [26]. At room temperature, however, virtually no cleavage was detected after 2 h in 1 1 TFA-DCM. 

In our first attempt to bind linker-modified bis(pyrazol-l-yl)acetic acids to a solid phase we used Merrifield resin, which is one of the most popular solid phase supports. Since Merrifield polymer was designed to bind carboxylic acids, we used the ester methyl 2,2-bis(3,5-dimethylpyrazol-l-yl)-3-hydroxypropionate (52) instead of the 2,2-bis(3,5-dimethylpyrazol-l-yl)-3-hydroxypropionic acid (49). 

Another traditional method used for polymer support characterization is elemental analysis. Its use as an accurate quantitative technique for monitoring solid-phase reactions has also been demonstrated [146]. Microanalysis can be extremely valuable if a solid-phase reaction results in the loss or introduction of a heteroatom (usually N, S, P or halogen). In addition, this method can be used for determination of the loading level of a functional group (e. g. usually calculated directly from the observed microanalytical data). For example, in many cases, the displacement of chloride from Merrifield resin has been used as a guide to determine the yield of the solid-phase reaction. 

Buchwald has shown that, in combination with palladium(II) acetate or Pd2(dba)3 [tris(dibenzylideneacetone)dipalladium], the Merrifield resin-bound electron-rich dialkylphosphinobiphenyl ligand (45) (Scheme 4.29) forms the active polymer-supported catalysts for amination and Suzuki reactions [121]. Inactivated aryl iodides, bromides, or even chlorides can be employed as substrates in these reactions. The catalyst derived from ligand (45) and a palladium source can be recycled for both amination and Suzuki reactions without addition of palladium. 

Soluble polymer-bound catalysts for epoxidation reactions have also been explored, with a complete study into the nature of the polymeric backbone performed by Janda [70]. Chiral (salen)-Mn complexes were appended to MeO-PEG, NCPS, Jan-daJeF and Merrifield resin via a glutarate spacer. It was found that for the Jacobsen epoxidation of ds-/ -mefhylstyrene, the enantioselectivities for each polymer-supported catalyst were comparable (86-90%) to commercially available Jacobsen catalyst (88%). Both soluble polymer-supported catalysts could be used twice before a decline in yield and enantioselectivity was observed. However, neither soluble polymer support proved as suitable as the insoluble JandaJel-supported (salen)-Mn complex for the epoxidation because residual impurities during precipitation and leaching of Mn from the complex, resulted in lowered yields. 

A variety of SCS and PCP Pd (II) pincer complexes were prepared and immobilized on polymer or silica supports. (Figure 2 shows supported PCP complexes on poly(norbornene) and silica). Insoluble supports such as mesoporous silica and Merrifield resins along with soluble supports such as poly(norbornene) allowed for generalization of our observations, as all immobilized catalysts behaved similarly. The application of poisoning tests, kinetics studies, filtration tests, and... 

The alternative strategy for heterogenization has been pursued by Blechert and co-workers, for a polymer-supported olefin metathesis catalyst. A polymer-anchored carbene precursor was prepared by coupling an alkoxide to a cross-linked polystyrene Merrifield-type resin. Subsequently, the desired polymer-bound carbene complex was formed by thermolytically induced elimination of ferf-butanol while heating the precursor resin in the presence of the desired transition metal fragment (Scheme 8.30). 

Polystyrene has been used most often as the support for phase transfer catalysts mainly because of the availability of Merrifield resins and quaternary ammonium ion exchange resins. Although other polymers have attrative features, most future applications of polymer-supported phase transfer catalysts will use polystyrene for several reasons It is readily available, inexpensive, easy to functionalize, chemically inert in all but strongly acidic media, and physically stable enough for most uses. Silica gel and alumina offer most of these same advantages. We expect that large scale applications of triphase catalysis will use polystyrene, silica gel, or alumina. 

An optically active, supported chelating diphosphine has been prepared from the Merrifield resin using reaction (15) to give a polymer-supported analog of the homogeneous diop catalysts (28, 94). 

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