Polymer-supported Scavengers

Under certain condition, however, reactions are still preferably conducted in solution. This is the case e.g., for heterogeneous reactions and for conversions, which deliver complex product mixtures. In the latter case, further conversion of this mixture on the solid support is not desirable. In these instances, the combination of solution chemistry with polymer-assisted conversions can be an advantageous solution. Polymer-assisted synthesis in solution employs the polymer matrix either as a scavenger or for polymeric reagents. In both cases the virtues of solution phase and solid supported chemistry are ideally combined allowing for the preparation of pure products by filtration of the reactive resin. If several reactive polymers are used sequentially, multi-step syntheses can be conducted in a polymer-supported manner in solution as well. As a further advantage, many reactive polymers can be recycled for multiple use. 

It is worth noting that the use of polymer-supported scavengers offers a perfectly complementary technique to the use of PSRs, and in several cases the two have been successfully employed together [3,9]. 

In this section, we will review the application of the combination of polymer-supported reagents and/or scavengers with microwave irradiation to the syn-... 

Another interesting scavenger is polymer-supported anthracene, developed by Porco for the scavenging of dienophiles [109]. An example of its application to the synthesis of a complex 5,8-dihydro-(l,2,4)triazolo[l,2-a]pyridazine-l,3-diones via hetero-Diels-Alder reaction followed by removal of the excess of triazole-3,5-dione under microwave irradiation is depicted in Scheme 24. For this particular example, moving from thermal heating (toluene, 100 °C) to a microwave-assisted protocol (DCE, 150 °C) reduced scavenging time from 3 h to just 15 min. 

In 2001, Sarko and coworkers disclosed the synthesis of an 800-membered solution-phase library of substituted prolines based on multicomponent chemistry (Scheme 6.187) [349]. The process involved microwave irradiation of an a-amino ester with 1.1 equivalents of an aldehyde in 1,2-dichloroethane or N,N-dimethyl-formamide at 180 °C for 2 min. After cooling, 0.8 equivalents of a maleimide dipo-larophile was added to the solution of the imine, and the mixture was subjected to microwave irradiation at 180 °C for a further 5 min. This produced the desired products in good yields and purities, as determined by HPLC, after scavenging excess aldehyde with polymer-supported sulfonylhydrazide resin. Analysis of each compound by LC-MS verified its purity and identity, thus indicating that a high quality library had been produced. 

Fig. 7.10 Polymer-supported scavengers polystyrene-bound diamine (top left), silica-based diamine (top right), Stratosphere Plugs (bottom left), and Synphase Lanterns (bottom right).

Fig. 7.11 Scavenging efficiencies of polymer-supported scavengers (a) polystyrene, (b) functionalized silica, (c) plugs, (d) lanterns] at room temperature (left) and under microwave heating (right).

Bhattacharyya SJ (2004) New developments in polymer-supported reagents, scavengers and catalysts for organic synthesis. Curr Opin Drug Discov De-vel 7 752-764... 

Ley S V, Baxendale IR, Myers RM (2006) The use of polymer supported reagents and scavengers in the synthesis of natural products. In Boldi AM (ed) Combinatorial synthesis of natural product-based libraries. CRC Press Boca-Raton, pp 131-163... 

Thompson LA (2000) Recent applications of polymer-supported reagents and scavengers in combinatorial, parallel, or multistep synthesis. Curr Opio Chem 4 324-337... 

Support-bound reagents and scavengers have become increasingly popular in the preparation of compound libraries.1111 When polymer-supported... 

Scheme 2.57 Three component condensation reaction using polymer supported scavenger purification alternatively the trisamine resin could be substituted for purification in this step.

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