Merrifield polymer resins

Merrifield polymer resins are often used as substrates for polymer brush synthesis using NMP. To achieve this, TEMPO is reduced with sodium ascorbate. 

Difficulties due to side reactions (cyclization) and a broad molecular weight distribution accompanying the polycondensation of active esters led to the application of methods wherein the polymers are built up stepwise. In 1968, Sakakibara et al.31) introduced the solid-phase technique using Merrifield s resin. By stepwise addition of tert-pentyloxycar-bonyl tripeptides, they have synthesized (Pro-Pro-Gly)n with n = 5, 10, 15 and 20. 

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

One of the key technologies used in combinatorial chemistry is solid-phase organic synthesis (SPOS) [2], originally developed by Merrifield in 1963 for the synthesis of peptides [3]. In SPOS, a molecule (scaffold) is attached to a solid support, for example a polymer resin (Fig. 7.1). In general, resins are insoluble base polymers with a linker molecule attached. Often, spacers are included to reduce steric hindrance by the bulk of the resin. Linkers, on the other hand, are functional moieties, which allow the attachment and cleavage of scaffolds under controlled conditions. Subsequent chemistry is then carried out on the molecule attached to the support until, at the end of the often multistep synthesis, the desired molecule is released from the support. 

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. 

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 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). 

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). 

A frequently investigated approach is based on Merrifield s resin, which is a polystyrene polymer [6]. 

Polymer-supported bis(diphenylphosphino)methane (DPPM) has been prepared by treatment of Merrifield s resin with... 

Tricarbonyliron diene complexes have found many uses in synthetic chemistry but their synthesis is often not easy. Knolker has developed a range of tricarbonyl(7] -l-aza-l,3-butadiene) iron complexes that are excellent transfer agents for the Fe(CO)3 complexation of 1,3-dienes, and showed their versatility. As an extension to this work, Knolker and Gonser have prepared a polymer-supported l-aza-l,3-butadiene 321 by reaction of Merrifield s resin with phenolic l-aza-l,3-butadiene 320, formed from cinnamaldehyde and /> ra-hydroxyaniline (Scheme 105). The corresponding tricarbonyl iron complex 322 was formed by treatment of 321 with an excess of Fe2(CO)9 in THF using ultrasound. The iron complex was subsequently used efficiently as a transfer agent for the tricarbonyliron complexation of 1,3-dienes. 

The diaryliodonium carboxylate route to benzynes (Type B2) has been adapted to the polymer-bound precursor 58, prepared from Merrifield s resin by standard methods". (An earlier example of a polymer-bound h nzyne has been described. ) The polymer afforded benzyne 59 when heated above 200 °C, as demonstrated by trapping with 2-furoic acid the initial cycloadduct decarboxylates spontaneously at that temperature, affording naphthols 60 in about 20% yield. The three-phase test involving transfer of aryne from 58 to a... 

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