Friedel-Crafts reaction, polymer-supported

Rare earth metal triflates are recognized as a very efficient Lewis acid catalysts of several reactions including the aldol reaction, the Michael reaction, allylation, the Diels-Alder reaction, the Friedel-Crafts reaction, and glycosylation [110]. A polymer-sup-ported scandium catalyst has been developed and used for quinoline library synthesis (Sch. 8) [111], because lanthanide triflates were known to be effective in the synthesis of quinolines from A-arylimines [112,113]. This catalyst (103) was readily prepared from poly(acrylonitrile) 100 by chemical modification. A variety of combinations of aldehydes, amines, and olefins are possible in this reaction. Use of the polymer-supported catalyst has several advantages in quinoline library construction. 

It is similarly difficult to prevent the Friedel-Crafts reaction between side chain carboxyl groups and the aromatic nuclei of insoluble polymeric supports used in solid phase peptide synthesis (cf. Chapter X). Here, however, the ketone by-products are firmly anchored to the polymer ... 

In 2008, Chi et al. reported a tandem reaction of indoles, a,P-unsaturated aldehydes, and methyl vinyl ketone (MVK) for the synthesis of chiral indole derivatives with two stereogenic centers [ 19]. To avoid the interference of the two secondary amine catalysts and cocatalyst acid, the soluble star polymer-based site isolatbn method was adopted, whereby the supported imidazolidinone catalyst promoted initial Friedel-Crafts alkylation and the supported pyrrolidine derivative promoted the following Michael addition to MVK (Scheme 9.19). Notably, simple combination of these catalysts in one pot didn t mediate the cascade reaction efficiently despite the fact that the MacMillan imidazolidinone and pyrrolidine catalyst can efficiently promote separate Friedel-Crafts reaction and Michael addition, respectively. Moreover, when the pyrrolidine catalyst was replaced by its enantiomer, a diaste-reomer of the product could be obtained with high enantioselectivity. This smdy presented a novel solution to the efficient combination of incompatible substrates and catalysts. 

Beside borosilicate and fused silica capillaries, PS/DVB monoliths have been fabricated within the confines of steel and PEEK tubings [52]. In order to increase the hydrophobic character of the supports, a Friedel-Crafts alkylation reaction was used for the attachment of Cig-moieties to the polymer surface. The derivatized material was demonstrated to be more retentive and to provide more efficient peptide separations compared with the original, nonderivatized monolith. 

Cross-linked polystyrene can be acylated with aliphatic and aromatic acyl halides in the presence of A1C13 (Friedel-Crafts acylation, Table 12.1). This reaction has mainly been used for the functionalization of polystyrene-based supports, and only rarely for the modification of support-bound substrates. Electron-rich arenes (Entry 3, Table 12.1) or heteroarenes, such as indoles (Entry 5, Table 15.7), undergo smooth Friedel-Crafts acylation without severe deterioration of the support. Suitable solvents for Friedel-Crafts acylations of cross-linked polystyrene are tetrachloroethene [1], DCE [2], CS2 [3,4], nitrobenzene [5,6], and CC14 [7]. As in the bromination of polystyrene, Friedel-Crafts acylations at high temperatures (e.g. DCE, 83 °C, 15 min [2]) can lead to partial dealkylation of phenyl groups and yield a soluble polymer. 

Nafion is another choice of polymer support for Sc-based Lewis acids. Nafion-Sc catalyst is readily prepared by treatment of Nafion with ScCb 6H2O in acetonitrile under reflux [116]. Nafion-Sc catalyst has been found to be effective in several synthetic reactions including allylation of carbonyl compounds with tetraallyltin, Diels-Alder reaction, Friedel-Crafts acylation, and imino Diels-Alder reactions. The use of Nafion-Sc in flow systems has also been tested. 

Alternative catalysts for this reaction are polymer-supported alkyl sulfonic acids [231], even if they show lower performances than the zeolite. Two of the problems in the reactions are the need to vaporize the reactant and the periodic regeneration of the rapidly deactivating zeolite catalysts. It was thus proposed recently that continuous catalytic Friedel-Crafts acylation can be performed in the biphasic medium of an ionic liquid and supercritical carbon dioxide [232]. 

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