Ethers diphenylprolinol trimethylsilyl

The mechanism proposed by the authors is depicted in this scheme. A first equivalent of a,fS-unsaturated aldehyde was activated as its corresponding iminium ion by chiral diphenylprolinol trimethylsilyl ether and then underwent the first nitromethane Michael addition to afford a nitroalkane enamine intermediate. Subsequent hydrolysis generated a nitroaldehyde intermediate and the catalyst, which could promote a second Michael addition with a second equivalent of iminium, furnishing an enamine intermediate. This enamine reacted via an intramolecular aldol cyclization to give a novel iminium intermediate. After hydrolysis, the catalyst was regenerated, and the intermediate alcohol could be dehydrated to afford the final products. 

Polymer-supported organocatalysts are valuable materials for conducting catalytic asymmetric transformations under simple and environmentally begnin conditions [275]. A novel polymer-supported diphenylprolinol trimethylsilyl ether was synthesized by Hansen et oi. [276], and further applied as catalyst to induce a diastereo- and enantioselective three-component domino Michael/Michael/aldol... 

FIGURE 2.14. Transition state model for the diphenylprolinol trimethylsilyl ether-catalyzed a-oxyamination of aldehydes. 

L-Prohne catalyzes the direct hydroxymethylation of aldehydes and ketones, though with low yields [116]. Higher yields and enantioselectivities are generated by a,a-diphenylprolinol trimethylsilyl ether [117]. The desired a-substituted P-hydroxymethylated products are not stable and have to be converted to more readily isolable derivatives. This method should be the first choice for synthesis of a-hydroxymethylated aldehydes since it is suitable for large scales (75.8 g of aldol). 

Friedel-Crafts-type vinylogous conjugate addition of 2-vinyl pyrroles to enals was achieved site-selectively with the use of diphenylprolinol trimethylsilyl ether 14 as an iminium-enaniine activation catalyst (Scheme 41) [71]. Stepwise, formal [2-1-2] cycloaddition would be a plausible outcome of the reaction for constructing stereochemically enriched cyclobutanes. The polarity of the solvent had a critical impact on the catalytic efficiency. Trace amounts or none of the desired product was formed when less polar toluene or dichloromethane was used. Increasing the polarity of the solvent led to enhancement of the turnover frequency of 14 the polar protic solvent, ethanol, was optimal. 

The organocatalysed asymmetric cycloaddition reaction of a,p-unsaturated ketones and aldehydes is scarcely studied, especially for fluorine-containing substrates. In this area, Liu et al. have reported unusual inverse-electron-demand oxa-Diels-Alder reactions of a,p-unsaturated trifluoromethyl ketones with aldehydes catalysed by chiral a,a-diphenylprolinol trimethylsilyl ether. It was shown that the addition of pura-fluorophenol and silica gel along with this catalyst was necessary, otherwise the reaction was very slow and a poor yield was obtained. Under these optimal conditions, the expected cyclic adducts were obtained in good yields and high fl n-diastereo- and enantioselectivities, as shown in Scheme 6.11. 

Scheme 2.17 Domino Michael-benzoin reaction catalysed by a combination of chiral diphenylprolinol trimethylsilyl ether and a chiral N-hetero-cyclic carbene.

In 2012, Wang et al. reported a pseudo-three-component highly enantioselective domino Michael-Michael-Henty reaction catalysed by a combination of chiral diphenylprolinol trimethylsilyl ether and a chiral quinine-derived thiourea. The reaction occurred between aliphatic aldehydes and two equivalents of nitroalkenes, providing the corresponding hexasubstituted chiral cyclohexanols in moderate to good yields and dia-stereoselectivities of up to 60% de, combined with generally excellent enantioselectivities ranging from 96 to >99% ee (Scheme 2.23). The authors... 

The same year, Lin et al. employed a combination of r-proline with chiral diphenylprolinol trimethylsilyl ether to catalyse a remarkable highly dia-stereo- and enantioselective domino a-aminoig lation-aza-Michael-aldol reaction of aliphatic aldehydes, a,p-unsaturated aldehydes and nitroso compounds. The reaction afforded the corresponding almost enantiopure 1,2-oxazine derivatives in moderate to good yields, as shown in Scheme 2.24. A plausible mechanism of the reaction is depicted in Scheme 2.24, beginning with a a-ojg amination of the aldehyde with the... 

In another context, Frechet et al. have described a polarity-directed three-component domino Henry-Michael reaction of two aliphatic aldehydes with different polarities and nitromethane catalysed by a combination of chiral diphenylprolinol trimethylsilyl ether and L-proline. In this original process. 

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