Diphenylprolinol trimethylsilyl ether catalyst

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... 

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. 

On the other hand, Alexakis et al. have developed a sequential reaction exploiting the compatibility between a cationic iridium catalyst and chiral diphenylprolinol trimethylsilyl ether. The role of the iridium complex was proposed to isomerise the starting allylic primary alcohols into the corresponding aldehydes in the presence of H2, while the chiral amine catalyst promoted the a-functionalisation of these aldehydes through reaction with vinyl sulfone to give the corresponding Michael adducts as a mixture of syn-and (Z h -diastereomers obtained in moderate yields, moderate to excellent... 

Further to this work, the same group published another multicatalytic reaction in aqueous buffer, which involved two aldehydic substrates with similar reactivities but different polarities [11]. The biphasic reaction allowed the differentiation of the two aldehydes, which reacted in a controlled manner to generate the desired cross-product. Two catalysts were used, and each catalyst triggered an individual reaction step in either aqueous or organic phase. L-Proline, soluble in the aqueous phase, catalyzed the addition of nitromethane with the less hydrophobic aldehyde (Scheme 12.6). Diphenylprolinol trimethylsilyl ether 5, which is an efficient catalyst for the conjugated addition of aldehydes to nitroalkenes, catalyzed the reaction of the... 

A one-pot synthesis of 1,3-diamines was described in 2009 by Cordova and coworkers [17]. An asymmetric cascade aza-Michael/Mannich reaction was developed using a combination of diphenylprolinol trimethylsilyl ether 5 and proline as catalysts (Scheme 12.13). The cascade was possible because of the complete difference in reactivity between chiral pyrrolidine 5 and proline in the separate reactions. The conjugate addition of a protected methoxyamine to hex-2-enal was coupled to a three-component Mannich reaction, giving direct access to orthogonally protected chiral diamine derivatives with excellent chemo and enantioselectivities (yield 60-62%, ee 98-99%). The use of l-Pto as a catalyst for the Mannich reaction afforded the 6yn-l,3-diamine 30 (dr > 19/1), while the use of the antipode D-proline gave the anti derivative 31 with similar levels of diastereoselectivity. 

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