Bis-silyl ketene acetals

The original assignment of the absolute configuration (3S) for products 12 based on a comparison of the optical rotation value with a reported one for the phenyl derivative [27] must be considered uncertain. It would contradict the preferred attack of the nucleophile from the unshielded back side and the stereoselectivity observed in the reaction of A -galactosyl imines 7 with prochiral bis-silyl ketene acetals [28]. N-Galactosyl P-amino acids 13 are produced from bis-silylketene acetals in high yields and excellent diastereoselectivity (Scheme 10). The configuration at the P-position is R. 

Bis-silyl ketene acetals devoid of -protons undergo a clean silatropic ene reaction with singlet oxygen (see Sections 2.3.2.1,3.ii and 2.3.2.4.3.H) to generate the a-silylperoxy silyl ester quantitatively. Treatment with methanol affords the a-hydroperoxy acid, also quantitatively (Scheme 23). Hytkogenation over platinum reveals the a-hydroxy acid, once again, quantitatively. Despite diis encouragement the substrate limitation is severe. 

Bis(silyl)ketene acetals undergo silatropic ene reaction with nitrosobenzene to give N-hydroxyamino acid derivatives. When allylmagnesium chloride is reacted with nitroarenes, unstable adducts result. Reduction of these adducts with LAH in the presence of palladium on charcoal leads to A -allyl-W -aryl-hydroxylamines (73 Scheme 15). With alkyl Grignard reagents this reaction is negligible. ... 

Dumas et al. noted the good yields and syn diastereoselectivities obtained in a high-pressure aldol reaction of bis-silyl ketene acetals 154 with benzaldehyde (155) (Scheme 7.39). The syn aldol 156 was obtained with a diastereoselectivity that was significantly correlated with the steric bulkiness of the R-substituent in the acetals 154. The preference for syn bis-silyl aldols 156 has been attributed to the reaction pathway that involves compact transition states in which steric interactions between the R substituent of 154 and the phenyl group of benzaldehyde are minimized. The authors also studied the condensation of unsaturated bis-silyl ketene acetal as a model for the synthesis of retinoid compounds. ... 

An optically active polymer has been prepared by repetitive Mukaiyama aldol reaction, using a bis(silyl ketene acetal) and a dialdehyde, plus a chiral oxazaborolidinone catalyst,and the role of Lewis basicity of aldehydes in oxazaborolidinone-catalysed Mukaiyama aldols has been examined." ... 

In the presence of Znl2 in acetonitrile the saturated sulfoxide 1262 is converted by the O-trimefhylsilylketene acetal 663 into the sulfide 1263 in 55% yield and HMDSO 7 [54] whereas the unsaturated sulfoxide 1264 affords with excess O-silyl-ketene acetal 663 the bis-addition product 1265 in 45% yield [55, 56] (Scheme 8.22). 

Functionalized silacyclobutanes 16 result from photochemical decomposition of [azido-, isocya-nato- and isothiocyanato-bis(tert-butyl)silyl]diazoacetates 15. They undergo a remarkably facile ring-expansion reaction to cyclic O-silyl ketene acetals 17 even at 60°C. 

The isomerization of an O-silyl ketene acetal to a C-silyl ester is catalyzed by a cationic zirconocene—alkoxide complex [92], This catalysis was observed as a side reaction in the zirconocene-catalyzed Mukaiyama aldol reactions and has not yet found synthetic use. The solvent-free bis(triflate) [Cp2Zr(OTf)2] also catalyzes the reaction in nitromethane (no reaction in dichloromethane), but in this case there may be competitive catalysis by TMSOTf (cf. the above discussion of the catalysis of the Mukaiyama aldol reaction) [91] (Scheme 8.51). 

Further investigation with various silyl ketene acetals is summarized in Table 6. Silyl ketene acetals derived from various esters were reacted with /V-benzyloxy-carbonylamino sulfones 1 in the presence of 0.5-1 mol% Bi(0Tf)3-4H20. The corresponding (3-amino esters 24 were obtained in moderate to good yields (Table 6). Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. The /V - be n z v I o x v c ar bo n v I a m i n o sulfone derived from n-butvraldehyde lp led to moderate yields of (3-amino esters when reacted with (thio)acetate-derived silyl ketene acetals (Table 6, entries 1 and 2). A very good yield was obtained when the same sulfone was subjected to a tetrasubstituted silyl ketene acetal (Table 6, entry 3). The latter afforded moderate to good yields of (3-amino esters 24 with phenylacetaldehyde, / -tolu aldehyde, and o-tolualdehyde-derived sulfones (Table 6, entries 4-6). 

Table 6 Bi(0Tf)3-4H20-catalyzed Mannich-type reactions with various iV-benzyloxycarbonyl-amino sulfones and silyl ketene acetals...

Conditions iV-benzyloxycarbonylamino sulfone (1.0 equiv.), silyl ketene acetal (1.3 equiv.), Bi(0Tf)3-4H20 (0.5-1.0 mol%) in CH2C12 at 22 °C Isolated yield... 

A stereoselective Mukaiyama-type aldol reaction of bis(trimethylsilyl)ketene acetals produces silyl aldols with syn stereoselectivity, predominantly due to steric effects.23... 

Aldol reactions of aldehydes with cycloakanones were performed in ionic liquids and catalyzed by FeCl3-6H20 [32]. Mukaiyama aldol reactions of silylenol ethers with aldehydes can be carried out in aqueous media however, among several Lewis acidic catalysts investigated, iron compounds were not the optimal ones [33], If silyl ketene acetals are applied as carbon nucleophiles in Mukaiyama aldol reactions, cationic Fe(II) complexes give good results. As catalysts, CpFe(CO)2Cl [34] and [CpFe(dppe) (acetone)] BF4 [35] [dppe = l,2-bis(diphenylphosphano)ethane] were applied (Scheme 8.8). No diastereomeric ratio was reported for product 26a. 

Jorgensen and co-workers reported the asymmetric additions of a silyl ketene acetal to aldehydes (40) using the chiral bis-sulfonamide catalyst 27 [109]. Among the limited number of aldehydes examined, adducts were obtained in moderate to high yields (41-90%) and modest levels of ee (30-56% Table 6.44). The corresponding mono-sulfonamide catalyst was inactive under the reported conditions. 

For catalytic asymmetric aldol-type reactions, the transformation of the methylene compounds to a silyl enolate or a silyl ketene acetal was at one time necessary. Recently, the aldol reaction of aldehydes with non-modified ketones was realized by use of the lanthanum-Li3-trisf(/ )-bi-naphthoxidej catalyst 22 [18]. According to the proposed catalytic cycle, after abstraction of an a-proton from the ketone, the reaction between the lithium-enolate complex and the aldehyde... 

Evans et al. recently reported the use of structurally well-defined Sn(II) Lewis acids for the enantioselective aldol addition reactions of a-heterosubstituted substrates [47]. These complexes are readily assembled from Sn(OTf)2 and C2-symmetric bis(oxazoline) ligands. The facile synthesis of these ligands commences with optically active 1,2-diamino alcohols, which are themselves readily available from the corresponding a-amino acids. The Sn(II)-bis(oxazoline) complexes were shown to function optimally as catalysts for enantioselective aldol addition reactions with aldehydes and ketone substrates that are suited to putatively chelate the Lewis acid. For example, use of 10 mol % Sn(II) catalyst, thioacetate, and thiopropionate derived silyl ketene acetals added at -78 °C in dichloromethane to glyoxaldehyde to give hydroxy diesters in superb yields, enantioselectivity, and diastereoselectivity (Eq. 27). The process represents an unusual example wherein 2,3-ant/-aldol adducts are obtained stereoselec-tively. 

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