Silyl ketene acetals formation from esters

Aldol Reactions of Ester Derivatives. The Titanium(IV) C/tlor/dc-catalyzed addition of aldehydes to 0-silyl ketene acetals derived from acetate and propionate esters proceeds with high stereoselectivity. Formation of the silyl ketene acetal was found to be essential for high diastereoselectivity. Treatment of the silyl ketene acetal, derived from deprotonation of the acetate ester with LICA in THF and silyl trapping, with a corresponding aldehyde in the presence of TiCU (1.1 equiv) afforded the addition products in 93 7 diastereoselectivity and moderate yield (51-67%). Similarly, the propionate ester provides the anti-aldol product in high antilsyn selectivity (14 1) and facial selectivity (eq 4). 

Silyl ketene acetals from esters.1 Ireland has examined various factors in the enolization and silylation of ethyl propionate (1) as a model system. As expected from previous work (6, 276-277), use of LDA (1 equiv.) in THF at —78 -+ 25° results mainly in (E)-2, formed from the (Z)-enolate. The stereoselectivity is markedly affected by the solvent. Addition of TMEDA results in a 60 40 ratio of (Z)- and (E)-2 and lowers the yield significantly. Use of THF/23% HMPA provides (Z)- and (E)-2 in the ratio of 85 15 with no decrease in yield. This system has been widely used for (E)-selective lithium enolate formation from esters and ketones. Highest stereoselectivity is observed by addition of DMPU, recently introduced as a noncar-... 

A number of factors other than the solvent can affect the stereoselectivity of deprotonation of esters, such as the acid-base ratio and the nature of the base. But selective formation of (E)-silyl ketene acetals from esters remains a problem, particularly since they are more reactive than the (Z)-isomers. 

The addition of propionate-derived enol silanes 140 deUvered 1,2-disubstitut-ed aldol adducts 141 and 142 in useful yields and selectivities (Eq. 17) [90]. As in the acetate-derived additions, the selectivity of the process was dependent on the thioalkyl substituent of the silyl ketene acetal 140. The 1,2-syn adduct was obtained from the addition of E-enolsilane and -butyl glyoxylate (Eq. 17, entry 3). Correspondingly, the formation of 1,2-anti adduct was observed in the addition of a-benzyloxy acetaldehyde and the Z-enol silane derived from the ferf-butyl thio ester. 

Isomerization of silyl ketene acetals. Reaction of these ketone acetals proceed by migration of the silyl group from oxygen to carbon, with the formation of a-silyl-alkanoic esters, is very facile (5 min, room temperature). 

The treatment of an ester (or lactone) with a base and a silyl halide or trillate gives rise to a particular type of sUyl enol ether normally referred to as a silyl ketene acetal. The extent of O- versus C-silylation depends on the structure of the ester and the reaction conditions. The less-bulky methyl or ethyl (or 5-tert-butyl) esters are normally good substrates for O-silylation using LDA as the base. Acyclic esters can give rise to two geometrical isomers of the silyl ketene acetal. Good control of the ratio of these isomers is often possible by careful choice of the conditions. The f-isomer is favoured with LDA in THF, whereas the Z-isomer is formed exclusively by using THF/HMPA (1.24). Methods to effect stereoselective silyl enol ether formation from acyclic ketones are less well documented. ... 

Sol 1. (d) Abstraction of proton from a-methyl group of ester and subsequent treatment with trimethylsilyl chloride (TMSCl) resulted in the formation of cyclohexenyl silyl ketene acetal, which on heating undergoes [3,3] shift, i.e., Ireland—Claisen (silyl ketene acetal) rearrangement. The final step is the removal of the silyl group by acid hydrolysis to get the free acid. 

Although increasing the steric bulk of the nucleophile is necessary to improve selectivity, it has detrimental consequences on reactivity with aliphatic aldehydes (Scheme 7). In reactions with the bulky silyl ketene acetal 28e, aliphatic aldehydes are unreactive. Fortunately, reactivity can be recovered by decreasing the steric bulk of the ester group (from ferf-butyl 28e to ethyl 28b) and by changing the reaction medium. The addition of tetrabutylammonium iodide, which presumably increases the ionic strength of the reaction medium, shifts the equilibrium between the activated aldehyde and the trichlorosilyl chlorohydrin and allows carbon-carbon bond formation to proceed even in the case of aliphatic aldehydes [48]. 

The ability of NHC to activate silylated nucleophiles led to further investigations and useful procedures. Song reported the formation of silyl enol ethers by an NHC-catalyzed silyl exchange reaction that transferred a silyl group from a silyl ketene acetal to a ketone. When aldehydes, rather than ketones, were used as substrates the NHC catalysts promoted a Mukaiyma aldol reaction to give p-hydroxy esters and ketones in good yields. ... 

Sc(DS)3 worked well in aldol reactions of various substrates such as -unsaturated, aliphatic, and heterocyclic aldehydes. As for nucleophiles, silyl enol ethers derived from ketones as well as ketene silyl acetals derived from thioesters and esters also reacted well to give the corresponding products in good yields. A key to the success in this system was assumed to be formation of stable emulsions. The size and the shape of emulsion droplets was examined by transmission electron microscopy. 

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. 

The carbon-carbon bond formation via photoinduced electron transfer has recently attracted considerable attention from both synthetic and mechanistic viewpoints [240-243]. In order to achieve efficient C-C bond formation via photoinduced electron transfer, the choice of an appropriate electron donor is essential. Most importantly, the donor should be sufficiently strong to attain efficient photoinduced electron transfer. Furthermore, the bond cleavage in the donor radical cation produced in the photoinduced electron transfer should occur rapidly in competition with the fast back electron transfer. Organosilanes that have been frequently used as key reagents for many synthetically important transformations [244-247] have been reported to act as good electron donors in photoinduced electron-transfer reactions [248, 249]. The one-electron oxidation potentials of ketene silyl acetals (e.g., E°o relative to the SCE = 0.90 V for Me2C=C(OMe)OSiMe3) [248] are sufficiently low to render the efficient photoinduced electron transfer to Ceo [22], which, after the addition of ketene silyl acetals, yields the fullerene with an ester functionality (Eq. 15) [250, 251]. 

Aldol condensation. The formation of j8-siloxy ester derivatives from ketene silyl acetals and aldehydes may actually be an ene-type reaction involving silyl group migration. 

Lithium diisopropylamide. 13, 163-164 15, 188-189 16, 196-197 17, 165-167 Ester enolates. Procedures for the preparation of ( )- and (Z)-ketene silyl acetals are well developed. Enolates have been generated from conjugate esters by way of Michael addition, and when a remote halide is present, they are quenched by cyclization. Chiral Michael donors such as carbanions of the SAMP/RAMP hydra-zones initiate formation of trani-2-(2 -oxoalkyl)cycloalkanecarboxylic esters with excellent diastereomer excess and enantiomer excess. 

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