Supported Lewis acids

Supported Lewis acids are an interesting class of catalysts because of their operational simplicity, filterability and reusability. The polymer-bound iron Lewis-acid 53 (Figure 3.8) has been found [52] to be active in the cycloadditions of a, S-unsaturated aldehydes with several dienes. It has been prepared from (ri -vinylcyclopentadienyl)dicarbonylmethyliron which was copolymerized with divinylbenzene and then treated with trimethylsilyltriflate followed by THF. Some results of the Diels-Alder reactions of acrolein and crotonaldehyde with isoprene (2) and 2,3-dimethylbutadiene (4) are summarized in Equation 3.13. 

The use of silica-supported Lewis acids as catalysts for the Diels-Alder reactions of 2,5-dimethylfuran leads to fairly good yields of adducts [28]. Solid supports such as... 

Moreno described the cycloaddition of 2,5-dimethylfuran (42) catalyzed by silica-supported Lewis acids under solvent-free conditions in closed Teflon vessels using a commercial microwave oven (Scheme 9.11) [28, 52]. Under these conditions coordination of the silica-supported catalyst with the oxygen bridge favors ring opening, thus leading to the aromatic compounds in one step. The use of Si (71) gave the best results for aromatic compounds. 

Channel Supported Lewis acid Loading Flow rate Conversion... 

Silica-supported Lewis acids are useful catalysts with microwave irradiation for conjugate additions. The silica-supported catalysts are obtained by treatment of silica with ZnCh [Si(Zn)], Et2AlCl [Si(Al)] or TiCl4 [Si(Ti)] [ 150-152], The Michael addition of methyl a-acetamidoacrylate (196) with indole (2) under Si(M) heterogeneous catalysis assisted by microwave irradiation afforded the alanine derivative 197 within 15 min and/or bis-indolyl 198, depending on the reaction conditions (Scheme 45) [153]. While the bis-indolyl product 198 is only formed when Si(Zn) was used as catalyst, the alanine derivative 197, as a single product is formed under thermal heating in a yield of 12%. The best yields were observed with Si(Al) (Table 5). The product 198 was obtained by elimination of acetamide followed by a-Michael addition between intermediate 199 with a second mole of indole. 

Table 5 Reactions of indole 2 with 196 using silica-supported Lewis acids...

The Michael addition of methyl a-acetamidoacrylate (196) with pyrrole (1) under silica-supported Lewis acid (Si(M) Si(Zn), Si(Al) and Si(Ti)) assisted by microwave irradiation (MW) afforded the alanine derivatives 395 and 396 dependent on the reaction conditions (Scheme 81) [153]. Both MW and thermal activation for pyrrole gave only Michael product 396, whereas alanine derivatives 395, which are the a-Michael addition product, and 396 were observed with A1 and Ti-catalyst. This behavior shows that aluminium and titanium Lewis acids can form a new acceptor in an irreversible way. The Si(M) or p-TsOH catalyzed reactions of N-benzylpyrrolc 397 with the acrylate 196 under MW gave the product 398 as sole product. The reaction yield has been increased by using a catalytic amount of p-TsOH (Scheme 82). 

Itsuno et al. explored the possibility of using polymer-supported chiral Lewis acids in a model Diels-Alder reaction of methacrolein with cyclopentadiene [23a]. By using an insoluble polymer-supported Lewis acid [23], prepared from borane with cross-linked polymers with a chiral moiety such as an A-sulfonylamino acid, the Diels-Alder adduct is obtained in good yield with almost perfect exo selectivity and moderate enantioselectivity (Eq. 23). 

Catalyzed enantioselective Mukaiyama-aldol reactions have been developed extensively [101] and chiral polymer-supported Lewis acids are the catalysts of choice. Polymer-supported chiral A(-sulfonyloxazaborohdinones 86 and 87, prepared by copolymerization of styrene, divinylbenzene, and chiral monomers derived from L-valine and L-glutamic acid, respectively, have been used for aldol reactions [102]. The rates of reaction using the polymeric catalysts were slow and enantioselectivity was lower than was obtained by use of the low-molecular-weight counterpart (88). The best ee obtained by use of the polymeric catalyst was 90 % ee with 28 % isolated yield in the asymmetric aldol reaction of benzaldehyde with 89 (Eq. 27). 

A novel type of polymer-supported Lewis acid, a microencapsulated Lewis acid catalyst was investigated by Kobayashi [117]. Sc(OTf)3 was immobilized on to polystyrene by microencapsulation—Sc(OTf)3 is physically enveloped by polystyrene and stabilized by the interaction between the jr-electrons of benzene rings and vacant orbitals of the Lewis acid. This microencapsulated catalyst was used successfully in several Lewis acid-catalyzed carbon-carbon bond-forming reactions (imino aldol, aza Diels-... 

Kobaysahi, S. Nagayama, S., A Microencapsulated Lewis Acid. A New Type of Polymer-Supported Lewis Acid Catalyst ofWide Utility in Organic Synthesis. / Am. Chem. Soc. 1998, 120,2985. 

To avoid the formation of HCl in the synthesis of supported Lewis acidic ILs, ionic liquids bearing an alkoxylsilyl group on the alkyl chain, which can be covalently bound (grafted) to the surface, were used. In this procedure the aluminium halide was introduced subsequently, giving a highly acidic ionic complex on the surface of the support (Scheme 4.13). 

Polymer-supported Lewis acids represent an important target as they can be applied for the catalysis of a number of different organic reactions of interest for the preparation of fine chemicals. From an applied point of view, those materials have several advantages associated with their easier separation and the potential of their use in continuous processes [1]. Additionally, the presence of the polymeric matrix can modify the activity and selectivity of the reaction under study. 

Activity of these supported Lewis acids was again assayed for the Diels-AIder reaction between methacrolein and cyclopentadiene and results were compared with those obtained for related homogeneous catalysts, such as 16 and 17, prepared from the corresponding N-benzylated aminoalcohols. Results obtained for the catalysts derived from (5)-prolinol are summarized in Table 2. 

Scheme 6.20 The use of polymer-supported Lewis acid catalyst 76 for the enantioselective synthesis of the cyanohydrin 77, using EOF as the pumping mechanism.

Abstract. Three types of polymer-supported rare earth catalysts, Nafion-based rare earth catalysts, polyacrylonitrile-based rare earth catalysts, and microencapsulated Lewis acids, are discussed. Use of polymer-supported catalysts offers several advantages in preparative procedures such as simplification of product work-up, separation, and isolation, as well as the reuse of the catalyst including flow reaction systems leading to economical automation processes. Although the use of immobilized homogeneous catalysts is of continuing interest, few successful examples are known for polymer-supported Lewis acids. The unique characteristics of rare earth Lewis acids have been utilized, and efficient polymer-supported Lewis acids, which combine the advantages of immobilized catalysis and Lewis acid-mediated reactions, have been developed. 

Although the origin of the high activity of MC Sc(OTf)3 is not clear at this stage, it was reported that aldimine-Lewis acid complexes were stabilized by using a polymer-supported Lewis acid. Cf. [24]... 

There are a few other references in the scientific literature (as well as a number in the patent literature) to chemically fixed supported Lewis acids. Iron(III) chloride should be reactive enough to form surface OFeCk bonds, for example, and a stable form of supported FeCl3 has been reported.121 The solid acid has been used to catalyse liquid phase Friedel-Crafts benzoylations, although the surface structure and activity on reuse of the catalyst have not been described. At least one commercial form of supported iron(III) chloride is available." Supported SbFs has also been extensively studied, although mostly for gas-phase reactions such as the skeletal isomerisation of alkanes where it exhibits high activity indicative of its strong acidity (H0 = ca. —14).122... 

Silica-supported Lewis acids (e. g. ZnCl2, Znl2, or TiCl4) were also studied in Diels-Alder reactions of furan [37,38]. Reactions were performed at 25 °C and the best results were obtained in the absence of solvent. The combination of dienophile and supported Lewis acid had a great influence on the outcome of the reactions. Reaction with the chiral dienophile (-)-8-phenylmenthyl acrylate gave the endo adduct in 68 % d. e. and the exo adduct in 70 % d. e. [37]. 

An early example of a Diels-Alder reaction catalyzed by a polymer-supported Lewis acid involves the use of copper-loaded polystyrene-based polymers in the reaction of furan with 2-cyanoacrylonitrile [41]. Nafion-supported scandium... 

Kobayashi, S. and Nagayama, S. 1998. A microencapsulated Lewis acid. A new type of polymer-supported Lewis acid catalyst of wide utility in organic synthesis. /. Am. Chem. Soc. 120 2985-2986. 

Different heterocycles, e.g. furan, pyrrole, N-ben2ylpyrrole, indole, and pyrazole react with methyl a-acetamidoacrylate to give a-amino acid precursors under irradiation with silica-supported Lewis acids as catalysts [135]. Inhomogeneous catalysis, long reaction times were required. The reaction of vmylpyrazoles with imines has also been realized [136]. 

Cativiela et al. [18] reported on the microwave-assisted increased reaction rate and high selectivity in the cycloaddition of normally less reactive methyl and (-)-menthyl 2-acetamidoacrylates 18b with cyclopentadiene 17 using supported Lewis acid catalysts (see Scheme 10). Microwave activation in this case shortened reaction times (0.5 to 1 h) in dry media conditions otherwise requiring long reaction times (24 h). Silica gel modified by treatment with AlEt2Cl or TiCl4 catalysed the cycloaddition with best results in terms of retention of... 

The results in Scheme 24 show that the thermal reaction of selenol ester with isoprene is non-regioselective. Regioselectivity was improved by using a strong Lewis acid at low temperatures. The solid-supported Lewis acid facilitates the reaction but regioselectivity was not improved. The use of thiol esters affords similar results. Selenol and thiol esters are more reactive than the corresponding parent esters. 

Ionic Liquid Catalysts Supported through Covalent Anchoring 5.6.2.3.1 Supported Lewis acidic chlorometalate catalysts... 

Scheme 5.6-1 Preparation of supported Lewis acidic chloroaluminate ionic liquids catalysts by impregnation with [BMIM][(AICl3)jfCl] (top), by grafting of l-(triethoxysilylpropyl)-3-methylimidazolium chloride followed by AICI3 addition (middle), and by sol-gel formation followed byAICis addition (bottom) [73].

In an alternative synthetic approach, the formation of hydrochloric acid was avoided. The supported Lewis acidic ionic liquids were prepared by an... 

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