Organocatalysts immobilization

Asymmetric organocatalysis From proHne to highly efficient immobilized organocatalysts 12IZV1299. 

Y. Qiao, A.D. Headley, Ionic liquid immobilized organocatalysts for asymmetric reactions in aqueous media. Catalysts 3 (2013) 709-725. 

The use of Merrifield resin-bound alkaloid-based organocatalysts has also been reported [66-67]. The best results were obtained when attachment to the Merrifield resin was made via the hydroxy moiety of a (cinchonidine) alkaloid derivative [67]. The immobilization of alkaloid-derived catalysts on poly(ethylenglycol) (and modifications thereof) was also developed [68a, b]. Furthermore, asymmetric catalytic alkylations under micellar conditions were reported [68c],... 

Several investigations addressing these issues were performed in process-optimization experiments [71]. With regard to efficient recovery and re-use of the catalyst, use of chloroform is suitable, because of the insolubility of L-proline. Although the ee obtained was somewhat lower (61% ee for (R)-38b in CHCI3 compared with 76% ee in DMSO), the organocatalyst was quantitatively recovered by simple filtration and re-use of the catalyst indicated there was no loss of activity. As an alternative method, immobilization of L-proline on a silica gel column was studied but resulted in less satisfactory results [71]. 

The preparation of immobilized catalysts related to the imidazolidinone-type organocatalyst 13 and their application in the asymmetric Diels-Alder reaction was reported by Pihko and co-workers [9]. The reactivity of the immobilized catalysts depended on the type of solid support. The silica-supported imidazolidinone 24, which was prepared starting from N-Fmoc-protected L-phenylalanine, was found to be a highly active organocatalyst. Several dienes and a,/i-un saturated aldehydes have been successfully used in the presence of only 3.3 to 20 mol% 24, usually... 

Recovery of organocatalysts for re-use after downstream-processing has already been reported for some processes (see also the discussion below on immobilization). For example, recovery and re-use has been investigated for L-proline catalysis [10]-... 

Immobilization is a popular means of simplifying separation of a catalyst from the reaction mixture. In contrast with immobilized metal complexes (via a solid-support-bound ligand) leaching problems are a less critical issue when using organocatalysts immobilized by covalent bonding to the solid support. 

Several organocatalysts have been recycled efficiently (selected examples are shown in Scheme 14.2). For example, the Jacobsen group has reported results from an impressive study of the recycling of the immobilized urea derivative 6, a highly efficient organocatalyst for asymmetric hydrocyanation of imines (Scheme 14.2) [11]. It was discovered that the catalyst can be recycled and re-used very efficiently - over ten reaction cycles the product was obtained with similar yield and enantioselectivity (96-98% yield, 92-93% ee). 

In addition, immobilized catalysts related to the MacMillan imidazolidinone-type organocatalyst 5 have been used for the asymmetric Diels-Alder reaction (Section... 

Several other organocatalysts have also been immobilized (these applications are described in the appropriate chapters of this book). Thus, immobilization of organocatalysts has already been achieved successfully and found to be a suitable tool for simple catalyst recovery and re-use. 

In addition, minor variation of the catalyst in combination with immobilization on a resin support gave an analogous recyclable solid-supported organocatalyst. Varying the derivatization method by trapping the a-amino nitrile intermediate with formic acid and acetic anhydride gives the crystalline formamides 19 in excellent yield and with high enantioselectivity. These features of this catalytic process have been demonstrated by results from the synthesis of r-tert-leucine (Scheme 14.8) [49]. 

In this chapter, an overview of the different modes of action of NHC carbenes and their impact on the catalytic availability of certain classes of reactive intermediates will be provided, prefaced by a short discussion of the current state of the art concerning the preparation of (chiral) heterazolium catalysts including methods for the immobilization of this versatile class of organocatalyst. 

L-Proline catalyzes the aldol reaction. This approach has been applied to the synthesis of carbohydrate derivatives as illustrated by the glucose derivative 7 (Fig. 11) (237). The three-component Mannich reaction can be used to prepare p-amino and p-amino a-hydroxy carbonyl compounds in a single step (Fig. 12) (233). As with other types of catalysts, organocatalysts can be immobilized to aid recovery (253). 

Chiral secondary amines such as nonracemic imidazolidin-4-ones have been found to be effective asymmetric organocatalysts in the Diels-Alder cyclization of cyclopentadiene and a,p-unsaturated aldehydes [60]. A tyrosine-derived imidazoli-din-4-one was immobilized on PEG to provide a soluble, polymer-supported catalyst 110. In the presence of 110, Diels-Alder cycloaddition of acrolein 112 to 1,3-cyclohexadiene 111 proceeded smoothly to afford the corresponding cycloadduct 113 with high endo selectivity and enantioselectivity up to 92% ee (Scheme 3.31) [61]. 

By using of a modified proline, L-prolinamide 47 (which is known to be a more reactive catalyst than L-proline in cross-aldol reactions [80]), the enantioselectivity of the direct aldol reactions in ionic liquid [bmim][BF4] was remarkably increased as compared with the reaction carried out in acetone (69% ee) (Scheme 7.26) [81]. However, the reusability of the recovered 47 when immobilized in the ionic liquid layer was somewhat inferior to that of the L-proline catalyst this effect could be ascribed to the increased solubility of the organocatalyst 47 in the extracting organic solvents (not provided in the literature), leading to an increased leaching of the catalyst. 

Interest in proline as an organocatalyst is reflected in the variety of inorganic and organic supports on which the immobilization has been assayed very recently. 

---