Polymer silyl enol ethers

Recently it was found that the aldol reaction of silyl enol ethers with acetals or aldehydes is effectively promoted by a catalytic amount of trityl perchlorate to give the corresponding aldols in good yields (44,45). Polymer-bound trityl perchlorate also successfully catalyzed the aldol reaction (45). 

Silyl group transfer can also be used to functionalize chain ends. For example, allyl silanes, silyl ketene acetals, and silyl enol ethers [301-304] generate polymers with terminal allyl and methacrylate groups [Eq. (103)]. This type of transfer becomes degradative (termination) if reinitiation with silyl halides is not possible. 

When compared with the multifunctional initiators, the corresponding terminators are less available in cationic polymerization [202]. The situation is in sharp contrast to anionic living polymerization, where a variety of multifunctional terminators are developed (e.g., Cl2MeSiCH2CH2Si-MeCl2) [203,204]. However, a series of multifunctional silyl enol ethers were recently found to be effective in multiple termination of living cationic polymers of vinyl ethers [142,147,205,206] and a-methylstyrene [159,207] (Scheme 10). 

Scheme 10 Synthesis of tetraarmed polymers with a tetrafunctional terminating agent (silyl enol ether) [142,205].

On the basis of these studies, a tetrafunctional silyl enol ether (18) carrying four such enolate functions has been prepared the corresponding trifunctional compound is also available [142]. These silyl enolates effectively couple living poly(vinyl ethers) with the chloride counteranion to form tri- and tetraarmed polymers (e.g., 19, Scheme 10) [205]. Similar chemistry also operates with living cationic poly(a-methylstyrene) but specifically needs the additional use of an amine to accelerate the release of the trimethylsilyl groups [159,207]. 

Silyl enol ethers are versatile reagents in organic synthesis [83]. They are used as isol-able enolate equivalents and many useful reactions have been developed using silyl enol ethers [83]. As a new approach to exploit an efficient method for combinatorial synthesis [84], silyl enol ethers were successfully immobilized on to a polymer. Polymer-supported silyl enol ethers (PSSEEs) were prepared according to Sch. 10 [85]. In aldol reactions of PSSEEs with aldehydes, it was again found that Sc(OTf)3 was an efficient catalyst [86]. An example of the preparation of a 1,3-diol library by use of PSSEEs is shown in Sch. 11. In all cases, the reactions proceeded smoothly to afford the corresponding 1,3-diols in good yields. 1,3-Diols are successfully cleaved from the... 

Scheme 10. Synthesis of polymer-supported silyl enol ethers.

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Chiral lithium amide bases have been used successfully in the asymmetric deprotonation of prochiral ketones [55, 56]. WUliard prepared polymer-supported chiral amines from amino acid derivatives and Merrifield resin [57]. The treatment of cis-2,6-dimethylcyclohexanone with the polymer-supported chiral lithium amide base, followed by the reaction with TMSCl, gave the chiral silyl enol ether. By using polymeric base 96, asymmetric deprotonation occurred smoothly in tetrahydrofuran to give the chiral sUyl enol ether (, S )-102 in 94% with 82% ee (Scheme 3.28). 

A library of chiral dihydropyrans (226) [241] was synthesized using asymmetric hetero-Diels-Alder reactions (HAD) on polymer-bound enol ethers (221) and a, 3-unsaturated oxalyl esters (222). A chiral Lewis acidic Cu -bisoxazoline complex was used because of its high efficiency, the high predictability of the reaction outcome, and its broad substrate tolerance [280]. Enol ethers were used as alkene components bearing a hydroxy function for attachment to the resin via a silyl linkage (Scheme 49). The diene components carried allyl-ester groups, which could be readily displaced by amino functions in subsequent steps of the combinatorial synthesis. 

Mannich reaction. This reagent and similar rr-acids on polymer support effect chemoselective condensation between silyl enol ethers and imines in refluxing MeCN aldehydes do not participate in the reaction. 

For these reasons, this variation is not as widely used as the anionic reaction (the aldol condensation). The base catalyzed reaction often leads to dimers, polymers, self-condensation products or a, 5-unsaturated carbonyl derivatives, as described in Section 9.4.A. Mukaiyama and co-workers modified the acid-catalyzed reaction to include silyl enol ethers. He found that they react with carbonyl compounds to produce aldol-like... 

A library of y-amino alcohols has been synthesised using polymer-supported silyl enol ethers. The strategy followed by Kobayashi et al - is outlined in Scheme 3S.2. 

Scandium triflate-catalyzed aldol reactions of silyl enol ethers with aldehyde were successfully carried out in micellar systems and encapsulating systems. While the reactions proceeded sluggishly in water alone, strong enhancement of the reactivity was observed in the presence of a small amount of a surfactant. The effect of surfactant was attributed to the stabiMzation of enol silyl ether by it. Versatile carbon-carbon bondforming reactions proceeded in water without using any organic solvents. Cross-linked Sc-containing dendrimers were also found to be effective and the catalyst can be readily recycled without any appreciable loss of catalytic activity.Aldol reaction of 1-phenyl-l-(trimethylsilyloxy) ethylene and benzaldehyde was also conducted in a gel medium of fluoroalkyl end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer. A nanostmctured, polymer-supported Sc(III) catalyst (NP-Sc) functions in water at ambient temperature and can be efficiently recycled. It also affords stereoselectivities different from isotropic solution and solid-state scandium catalysts in Mukaiyama aldol and Mannich-type reactions. 

CB1981] and the same reaction of the related silyl enol ether (16) using polymer supported mandelic acid leads to (5)-mandelic acid in up to 94% e.e. [94TL2891]. Low temperature protonation of the anion derived from (17) produces mainly the cis product by kinetic control [94CB1495] and hydroboration of (18) gives the cis hydroxymethyl compound with high... 

Polymer-supported silyl enol ethers (PSSEEs) can be employed in Sc(OTf)3-catalyzed reactions with aldehydes and aromatic amines. This process provides a convenient method for the construction of a /8-amino alcohol library. 

For an asymmetric reaction to be really useful enantiomeric excesses typically above 90% are needed and preferably even higher. The recent use of a chiral proton donor attached to polystyrene achieves this and perhaps equally important offers a methodology far superior to the nonsupported analogue [93]. In this work (D)-mandelic acid has been bound to chloromethylated polystyrene via its carboxylic acid. This species was then employed as a proton donor to the silyl enol ether derived from racemic mandelic acid to reform specifically one optical isomer of man-delic acid. Enantiomeric excesses up to 94% have been achieved. The chiral polymer has been recycled satisfactorily and one could speculate that a continuous process could be established converting racemic acid into one pure enantiomer using the corresponding polymer-bound enantiomer as the mediator. 

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