Silyl polymer-supported

A novel and versatile method for preparing polymer-supported reactive dienes was recently developed by Smith [26]. PS-DES (polystyrene diethyl-silane) resin 28 treated with trifluoromethanesulfonic acid was converted to a polymer-supported silyl triflate 29 and then functionalized with enolizable a,jS-unsaturated aldehydes and ketones to form silyloxydienes 30 and 31 (Scheme 4.4). These reactive dienes were then trapped with dienophiles and the Diels Alder adducts were electrophilically cleaved with a solution of TFA. 

A polymer-supported silyl triflate and subsequent functionalization synthesis and solid-phase Diels-Alder reactions of silyloxydienes [25]... 

Many other linkers besides those listed above have been developed for two-phase synthesis of oligosaccharides on insoluble supports, and it can be expected that at least some of them will be tested on soluble supports. It should be kept in mind that MPEG-supported syntheses can be easily scaled up therefore, any relationship between both types of polymer supports will be cooperative rather than mutually exclusive. Such linkers will most probably include dialkyl- or diaryl-silyl linkers,10,41 3 and linkers cleavable by photolysis such as the o-nitrobenzyl group and its modifications.44 16... 

A class of photolabile linkers has been developed to circumvent the use of silyl ethers as linkers and allow for the use of temporary silyl protecting groups.34,35 Photolabile linkers, such as 2, often involve the use of o-nitrobenzyl ether groups. This functional group is stable to a variety of conditions however, cleavage from the polymer support is often slow and... 

Monolith Column—Porous silica column prepared in situ to completely fill the column tube with a fully porous silica foam skelton. After the organic polymer support is heated off, the silica surface is silylated in place to product bonded-phase surface. Column is high resolution and can be used at high flow rates with relatively low back-pressure (see Chapter 16). 

The silylated polymer was reacted with a solution of partially protected galactal in dichloromethane and Hiinig s base to give the corresponding saccharide-linked polymer construct. The loading of the solid support... 

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.

Kobayashi et al. reported the first synthesis of polymer-supported silyl enolates (thioketene silyl acetals) and their reactions with aldehydes for the preparation of 1,3-diol, / -hydroxy carboxylic acid, and /i-hydroxy aldehyde libraries (Scheme 10.37) [104]. In the presence of 20 mol% Sc(OTf)3, polymer-supported silyl enolate 42 derived from chloromethyl copoly(styrene-l% divinylbenzene) resin via 41 reacts smoothly with a variety of aldehydes. The resulting adducts can be easily purified by acid treatment and subsequent washing with water and organic solvents. The purified adducts are converted into 1,3-diols with LiBH4, -hydroxy carboxylic acids with NaOH, and -hydroxy aldehydes with DIBALH. This strategy has been used for efficient synfhesis of diverse monosaccharide derivatives [105]. 

It is well recognized fhat aldimines are less reactive than aldehydes toward nucleophilic addition. In the presence of a catalytic amount of Yb(OTf)3, however, silyl enolates react with aldimines exclusively to afford / -aminocarbonyl compounds in high yield, even when aldehydes are present (Scheme 10.74) [209]. Selective formation of aldimine-Yb(OTf)3 complexes rather than aldehyde-Yb(OTf)3 complexes is attributable to fhe inverted reactivity. Polyallylscandium trifylamide ditriflate (PA-Sc-TAD), a polymer-supported Sc catalyst, also has high aldimine-selectivity. 

Suginome and Ito have developed a reliable method for the synthesis of highly enantioenriched allyl- and allenylsilanes. The synthetic process involves 1,3-chirality transfer from homochiral allyl and propargyl alcohols through Pd-catalyzed intramolecular bis-silylation and subsequent Peterson-type elimination (Scheme 10.142) [395]. This method provides an efficient route to enantioenriched allylsilanes bearing a hydroxyalkyl group, which are very valuable as synthetic intermediates for diastereo- and enantioselective synthesis of heterocycies and carbocycles [396]. Polymer-supported highly enantioenriched allylsilanes have been prepared from enantioenriched allyl alcohols and a polymer-supported disilanyl chloride [397]. 

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). 

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]. 

---