Diels polymer-supported catalysts

Figure 39 The enantioselective polymer-supported catalysts (61) of chiral oxazaborolidinone with cross-linking structures for use in the Diels-Alder reaction of methacrolein with cyclopentadiene. (Adapted from ref. 85.)...

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

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. 

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]. 

Other polymer-supported catalysts for the asymmetric Diels-Alder reaction include aluminum and titanium complexes of chiral amino alcohols [74],... 

Most recent research has been focused on the application of polymers as chiral auxiliaries in enantioselective Lewis-acid-catalyzed reactions. Studies of Itsuno and co-workers [44] culminated in the development of a polymer-supported catalyst containing a chiral oxazaborolidinone with oxyethylene crosslinkages which gave the Diels-Alder adduct of cyclopentadiene and methacrolein in 88 % isolated yield with an exotendo ratio of 96 4 and 95 % e. e. for the exo adduct. A variety of polymer-supported chiral Lewis acids was also investigated by Mayoral et al. [45]. Some supported catalysts were more active than their homogeneous analogs, but enantioselectivity was always lower. 

The enantioselective Diels-Alder reaction is another main motif in chiral Lewis acid catalysis. In 1996, Itsuno and coworkers reported an asymmetric Diels-Alder reaction using polymer-supported catalysts under flow conditions. Immobilized chiral oxazoboloridune (34) was prepared from a copolymer of N-sulfonylvabne and borane having styrene moiety, affording the Diels-Alder adduct in an enantioselective manner (up to 71% yield) [126], The authors used a gravity-fed-type column for the flow reaction. Ti-TADDOL-functionalized monolithic resins (35) were developed by Altava and Luis for the asymmetric Diels-Alder reaction (Scheme 7.30). 

Kami996 Kamahori, K., Ito, K. and Itsuno, S., Asymmetric Diels-Alder Reaction of Methacrolein with Cyclopentadiene Using Polymer-Supported Catalysts Design of Highly Enantioselective Polymeric Catalysts, J. Org. Chem., 61 (1996) 8321-8324. 

The polymer-supported chiral oxazaborolidinone catalyst 5 prepared from valine was found by Ituno and coworkers to be a practical catalyst of the asymmetric Diels-Alder reaction [7] (Scheme 1.12). Of the several cross-linked polymers with a... 

A -sulfinylacetamide 297 in greater than 90% yield when a catalytic amount of methyltrioxorhenium is employed. Futhermore, the hetero-Diels-Alder adduct is highly soluble in both chlorinated and ethereal solvents. A detailed investigation of the retro-Diels-Alder reaction of 298 by thermogravimetric analysis revealed an onset temperature of 120 °C and complete conversion of bicycle 298 to pentacene 296 at 160 °C, which are temperatures compatible with the polymer supports typically used in electronics applications. The electronic properties of these newly prepared OTFTs are similar to those prepared by traditional methods. Later improvements to this chemistry included the use of A -sulfinyl-/< r/-butylcarbamate 299 as the dienophile <2004JA12740>. The retro-Diels-Alder reaction of substrate 300 proceeds at much lower temperatures (130 °C, 5 min with FlTcatalyst 150 °C, Ih with no catalyst). 

Several researchers have reported synthetic approaches based on asymmetric Diels-Alder reactions catalyzed by TADDOL-Ti complexes [117-120]. Dendritic [121] and polymer-supported TADDOL-Ti complexes [122] have also been employed as recoverable and reusable catalysts to give comparatively high enantioselectivity. Transition-state models have been proposed independently by several groups for TADDOL-type titanium catalysis [121,123]. 

Other important titanium alkoxide-based Lewis acids are Ti-TADDOLate (a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol)ates, among the most effective chiral catalysts for several important asymmetric reactions. These will be discussed in the sections on polymer-supported Diels-Alder reactions (Section 21.10) and alkylations (Section 21.9). 

The Diels-Alder reaction of a diene and a dienophile has become one of the most powerful carbon-carbon bond-forming processes [81]. In normal Diels-Alder reactions of an electron-poor dienophile with an electron-rich diene, the main interaction is between the HOMO of the diene and the LUMO of the dienophile. Coordination of a Lewis acid to the dienophile reduces its frontier orbital energies, and this increases the rate of the reaction. Regio- and stereoselectivity are also markedly affected by the Lewis acid. Recent extensive studies on the design of chiral Lewis acids have led to fruitful results in the control of the stereochemistry of a variety of pericyclic reactions. Several chirally modified Lewis acids have been developed for the asymmetric Diels-Alder reaction [82,83] and spectacular advances have recently been achieved in this area. Various kinds of polymer-supported chiral Lewis acid have also been developed. Polymer-supported A1 Lewis acids such as 62 have been used in the Diels-Alder reaction of cyclopentadiene and methacrolein (Eq. 20) [84] as has polymer-supported Ti alkoxide 63 [84]. These Ti catalysts are readily prepared and have high activity in the Diels-Alder reaction. 

The same reaction has also been catalyzed by chiral oxazaborolidinones derived from amino acids and boranes. They proved to be efficient catalysts for enantioselec-tive Diels-Alder reaction [91,92]. The polymer-supported chiral oxazaborolidinones 75 were reported to be efficient catalysts [93]. These polymer-supported chiral oxaza-borolidinone ligands were prepared both by chemical modification and by the copolymerization shown in Sch. 5 [94]. The polymer-supported chiral ligands were then reacted with borane to give the oxazaborolidines which were used as catalysts in Diels-Alder reaction of cyclopentadiene with methacrolein. 

Polymer-supported TADDOL-Ti catalyst 79 prepared by chemical modification was poorly active in the Diels-Alder reaction of 3-crotonoyloxazolidinone with cyclo-pentadiene (Eq. 24) whereas polymeric TADDOL-Ti 81 prepared by copolymerization of TADDOL monomer 80 with styrene and divinylbenzene had high activity similar to that of the soluble catalyst. In the presence of 0.2 equiv. 81 (R = H, Aryl = 2-naphthyl) the Diels-Alder adduct was obtained in 92 % yield with an endolexo ratio of 87 13. The enantioseleetivity of the endo product was 56 % ee. The stability and recyclability of the catalyst were tested in a batch system. The degree of conversion, the endolexo selectivity, and the enantioseleetivity hardly changed even after nine runs. Similar polymer-supported Ti-TADDOLate 82 was prepared by the chemical modification method [99]. Although this polymer efficiently catalyzed the same reaction to give the (2R,2S) adduct as a main product, asymmetric induction was less than that obtained by use of a with similar homogeneous species. 

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. 

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-... 

Chiral cationic Pd-complexes with phosphinooxazolidine (POZ) represent another choice of catalyst for asymmetric Diels-Alder reaction [59]. Polymer-supported cationic POZ catalyst 107 effectively catalyzed the Diels-Alder reaction of cyclopentadiene 104 and acryloyl-1,3-oxazolidin-2-one 108 (Scheme 3.30). 

Itsuno et al. have reported the use of polymer-supported oxazaborolidinone 102 as a chiral catalyst for asymmetric Diels-Alder reactions (Scheme 17)... 

Seebach s TADDOL auxiliaries, derived from tartrate (chapter 23), combine well with Ti(IV) to make an effective Lewis acid catalyst 130 for Diels-Alder reactions. The reaction of isoprene with the doubly activated amide dienophile 128 gives one adduct 129 in good yield.29 Polymer supported versions of this catalyst are available. 

Polymer-supported A1 and Ti species as catalysts for Diels-Alder reactions ... 

Catalytic activity of these polymer-supported Ti and A1 species was assayed for the Diels-Alder reaction between cyclopentadiene and methacrolein [6]. As polymerization of cyclopentadiene competes with the cycloaddition process, all reactions were carried out using an excess (1.5 times) of the diene. Catalysts to dienophile ratios of ca. 0.05-0.2 were used for the different experiments. 

The polymer-supported Zr catalyst (12) is useful for asymmetric aza-Diels-Alder cycloaddition of benzaldehyde imine to Danishefsky diene [9]. The 6-substituted BINOL-Zr(IV) catalyst is useful for the enantioselective anft -preferred aldol reaction of benzaldehyde with ketene silyl thioacetal (15) (Scheme 5.5) [ 10]. The calculated charge densities on the oxygen atoms of the BINOL derivatives revealed that there is a good correlation between the charge density and the reactivity of 6-substituted BINOL [ 10]. 

A variety of solid Lewis and Br0nsted acids has been shown to catalyze Diels-Alder reactions. In several instances the results obtained with heterogeneous catalysts were better than those with homogeneous Lewis acid catalysts. Most of the reported reactions of interest in the synthesis of fine chemicals were catalyzed by (modified) zeolites, clays, alumina, or silica. Catalysts with interesting properties were obtained when support materials such as zeolites, alumina, or silica were treated with Lewis acids. These catalysts were moderately selective in diastereo-selective Diels-Alder reactions with chiral dienophiles and induced enantioselec-tivity (up to 31 % e. e.) in the reaction of cyclopentadiene with methacrolein after treatment with chiral derivatives. Excellent enantioselectivity in this reaction (up to 95 % e. e.) was observed with a polymer-supported chiral oxazaborolidinone. Because of their facile recovery and recycling, we expect that solid-acid catalysts will find increasing use in Diels-Alder reactions in the future. 

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