Separating polymer-bound products

Polymer beads serve as the solid phase, and synthesis is set up in such a way that eventually every bead carries just one compound (about 100 pmol w 10 molecules). As a consequence the obtained polymer-bound products are spatially separated. In each cycle, one reagent (A-F, e. g. an amino acid) and an encoding tag molecule (M, -M4) are attached to separate samples of resin beads. After this, the beads are thoroughly mixed and split up into equal quantities, and this is followed by the next reaction cycle. Diazoketones (1), which can be selectively incorporated into the excess polymer backbone using the corresponding acylcarbenes, being activated by rhodium catalysis, proved to be good tag molecules. 

Leznoff and Svirskaya achieved the synthesis of nonsymmetric tetraaryl potphyrine 39 (Scheme 1.6.19) on solid support. The polymer-bound product 37 was separated from the soluble symmetric porphyrin byproduct 38 by continuous extraction and 39 was finally released by methanolysis of the ester linkage. 

For the development of an appropriate strategy for cleavage from the novel syringaldehyde resin, the authors adapted a previously elaborated solution-phase model study on intramolecular Diels-Alder reactions for the solid-phase procedure (Scheme 7.60). The resulting pyridines could be easily separated from the polymer-bound by-products by employing a simple filtration step and subsequent evaporation of the solvent. The remaining resins were each washed and dried. After drying,... 

The separation of homogeneous catalysts by means of membrane filtration has been pioneered by Wandrey and Kragl. Based on the enzyme-membrane-reactor (EMR),[3,4] that Wandrey developed and Degussa nowadays applies for the production of amino acids, they started to use polymer-bound ligands for homogeneous catalysis in a chemical membrane reactor (CMR).[5] For large enzymes, concentration polarization is less of an issue, as the dimension of an enzyme is well above the pore-size of a nanofiltration membrane. 

Each microreactor consists of a polymer-bound substrate and a radiofrequency encoded microchip enclosed within a small porous vessel. The radiofrequency tag allows the identity of the substrate contained within each microreactor to be established readily. Using this technology, the polymer-bound substrates 86 were individually elaborated, within separate microreactors, by sequential reactions with acids 87 and alcohols 88 in a similar way to the solution-phase processes [25c]. Each of the microreactors was then subjected to the tandem RCM resin-cleavage conditions employing initiator 3. The products from each microreactor were obtained as a mixture of four compounds (89-92). The library of analogs prepared by this technique was then screened for biological activity [25c]. 

Resins 2 and 3 are treated with dichloromethane containg 3% and 1.5% trifluoroacetic acid (lOmL/g resin), respectively, for 18 h. The resin is filtered off and washed twice with dichloromethane (10 mL / g of resin). The filtrate is washed with saturated NaHCCL (5 mL) and brine (5 mL), and the organic phase is separated and filtered through a short path silica gel column to obtain a colourless solution. In the case of polymer-bound allyl esters giving rise to cleavage products of type 5f, the aqueous workup is omitted. The products obtained after removal of solvent under reduced pressure contain small amounts of silanol by-products (note 5), which is to be accounted for in the calculation of cleavage yields. 

Molecular catalysts, often in the form of metal ions complexed to a suitable ligand, can also be attached to dendrimer surfaces [3,9,10,93,94,96,148,149]. Such materials are generally structurally better defined than catalysts bounded to linear polymers, but like random-polymer catalysts they can be easily separated from reaction products. Note, however, that this approach results in a synthetic dead-end as far as further manipulation of the terminal groups is concerned, and thus some of the advantages of using dendrimers, such as solubility modulation, are lost. 

Relatively few hydroformylations using supported cobalt complexes have been reported. Moffat (78, 79) showed that poly-2-vinylpyridine reversibly reacted with both Co2(CO) and HCo(CO)4, the cobalt carbonyl being displaced by excess carbon monoxide. This enabled the polymer to pick up the cobalt carbonyl at the end of the reaction and, thus, allowed it to be separated from the products by filtration. The polymer acted as a catalyst reservoir by rapidly releasing the cobalt carbonyl into solution in the presence of further carbon monoxide, so that the actual catalysis was a homogeneous process. More recently, cobalt carbonyl has been irreversibly bound to a polystyrene resin... 

An advantage of polymer-based reagents is that both the excess and the spent reagent are easily separated from the product. Bruno Linclau of the University of Southampton has reported J. Org. Client. 2004, 69,5897) the preparation of a polymer-bound carbodiimide. Exposure of the polymer to alcohol gives a family of O-alkylisoureas that smoothly convert carboxylic acids to the corresponding esters. Methyl, benzyl, ally and p-nitrobenzyl transfer smoothly. The polymeric (-butyl reagent could not be prepared. 

In reactions with polymer-bound catalysts, a mass-transfer limitation often results in slowing down the rate of the reaction. To avoid this disadvantage, homogenous organic-soluble polymers have been utilized as catalyst supports. Oxazaborolidine 5, supported on linear polystyrene, was used as a soluble immobilized catalyst for the hydroboration of aromatic ketones in THF to afford chiral alcohols with an ee of up to 99% [40]. The catalyst was separated from the products with a nanofiltration membrane and then was used repeatedly. The total turnover number of the catalyst reached as high as 560. An intramolecularly cross-linked polymer molecule (microgel) was also applicable as a soluble support [41]. 

Thefcphosphine oxide can be reduced back to the phosphine (for example, with Cl- SiH) while still bound to the polymer and the polymer-bound reagent can be used again. Separation of Ph3P=0 from alkene products after a Wittig reaction can be quite a nuisance so the ease of work-up alone makes this an attractive procedure. 

Metal complexes bound to soluble polymers act as homogeneous catalysts they can be selectively precipitated and separated from products, and thus behave as immobilized homogeneous catalysts because of the ease with which they can be separated from reaction products. Alternatively, complexes can be physically trapped within the pores of swellable polymers. In this maimer, they can be effectively immobilized without a direct bond to the support. Polymers may be imprinted to give additional selectivity in the reactions of the supported metal catalysts and reagents. ... 

The byproduct DBF is not an easy compound to handle, as it polymerizes rapidly forming precipitates and gels. Thus adduct formation is a highly favorable side reaction however, the process of adduct formation is an equilibrium reaction between DBF and the deblocking amine, where the product distribution at equilibrium depends on the solvent and identity of the amine.f 1 This fact affects also the use of polymer-bound amines for Fmoc cleavage which would, upon adduct formation, facilitate separation of the DBF for synthesis in solution.t 1 However, with nonquantitative adduct formation, this type of resin scavenger is more or less useless,whereas, as discussed in Section 2.1.1.1.1.3.2, resin-bound thiols are much more efficient scavengers for DBF. 

The semihydrogenation of the carbon-carbon triple bond is a particularly valuable and frequently used application of heterogeneous catalysis to synthetic chemistry, and is the subject of several recent re-views. > Catalysts prepared from palladium and nickel are most commonly used, but the form of the catalyst and the conditions of use affect the results (see Section 3.1.1.2). A polymer-bound palladium catalyst, PdCh with poly-4-diphenylphosphinomethylstyrene, is intended to combine the selective properties of mononuclear transition metal complexes with the ease of separating the product from a solid. Whether catalysts of this type will replace the more traditional heterogeneous catalysts remains to be seen. 

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