Silyl acetate derivatives

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

Various substrates have been successfully used in the present LASC-catalysed aldol reaction. Aromatic as well as aliphatic, a, 3-unsaturated and heterocyclic aldehydes worked well. As for silicon enolates, silyl enol ethers derived from ketones as well as ketene silyl acetals derived from thioesters and esters reacted well to give the corresponding adducts in high yields. It is noted that highly water-sensitive ketene silyl acetals reacted smoothly in water under these conditions. 

The photochemical reaction of ethoxycarbonyl azide with optically active ketene silyl acetals derived from 10-sulfamidoisoborneol were used to prepare a-amino esters 9 with satisfactory yields and diastereoselectivity65. The pure diastereomeric esters were obtained after chromatographic separation. 

Other groups that react with chloromethyleneiminium salts include hydroxylamines, hydrazines, oximes, imines, azines, anhydrides, imides and ketene O-alkyl-O -silyl acetal derivatives however, reactions with these compounds have been relatively infrequent. 

Exquisite diastereochemical control is attained by tuning the relative bulk of the two alkoxy groups in ketene silyl acetals derived from a-alkoxyacetic esters, during aldol reaction with aldehydes. A chiral version is promoted SiCU in the presence of the phos-photriamide 5. The same set of reaction conditions is also applicable to create asymmetric quaternary carbon centers, for example, in the reaction of Al-silyl ketenimines with ArCHO. °... 

Mukaiyama aldol reaction. Reasonably good enantioselection is observed when the catalyzed reaction of ketene silyl acetals derived from thioesters with aldehydes is conducted in supercritical fluoroform. ... 

Next, the application of ketene silyl acetals was tried in the above aqueous reactions of silyl enolates with aldehydes. Ketene silyl acetals are useful ester enolate equivalents that can be isolated [27, 28], and the aldol-type reaction of ketene silyl acetals with aldehydes is among the most important and mildest methods of carbon-carbon bond formation [29]. Disappointingly, no aldol adduct was obtained when the ketene silyl acetal derived from methyl 2-methylpropionate (3) was employed as a representative ketene silyl acetal (structure 3 is shown later in Table 8.10). In aqueous media, hydrolysis of the ketene silyl acetal preceded the desired aldol reaction. 

To a solution of AMjenzylidene-2-hydroxyaniline (31 mg, 0.158 mmol) and 16 (10.0 mg, 16.9 /flnol) in toluene (1.0 mL) at -78 °C is added dropwise a solution of the ketene silyl acetal derived from methyl isobutyrate (41 mg, 0.23 mmol) over 3 min. The reaction mixture is stirred at -78 "C for 13 h, before quenching with a saturated NaHCOs aq. and saturated KF aq. at -78 and filtration through a Celite pad. The pad is washed with ethyl acetate. The combined organic layers are successively washed with a 1-M HCl aq. and then with brine, dried over anhydrous Na2S04, and concentrated in vacuo. The residue is purified by preparative TLC (hexane-ethyl acetate = 3 1) to give the title compound of 89% ee in 98% yield. ... 

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