Silyl acyloin reaction

Acyl imidazoles take part in a silyl acyloin reaction to give the corresponding silyl enol ethers in moderate yields. A possible mechanism is outlined in Scheme 2092. The silyl enol ethers could be hydrolysed to acyl silanes by treatment with acid. 

Lithium alkoxides of bis(trimethylsilyl) carbinols react with benzophenone to produce silyl enol ethers of acyl silanes in good yields93. The alcohols were prepared in reasonable yields by hydrolysis of the bis(trimethylsilyl) carbinol silyl ethers94,95, which in turn were produced from the corresponding esters using another silyl acyloin reaction, which itself, ironically, proceeds through an acyl silane intermediate (Scheme 21)94. 

A much more general synthesis of these silyl enol ethers, however, is based on the reductive cleavage of the carbon-sulphur bond of the silyl enol ether of a thiolester using sodium metal and chlorotrimethylsilane, once again in a silyl acyloin reaction (Scheme 22)97,98. 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

The solution to these problems is to add trimethylsilyl chloride to the reaction mixture. The silyl chloride silylates the enediolate as it is formed, and the product of the acyloin reaction becomes a bis-silyl ether. 

Acyloin condensations of esters conducted with TMS-Cl and sodium in toluene give 1,2-bis(trimethyl-silyloxy)alkenes. In general, the silylacyloin reaction provides higher yields than the conventional acyloin reaction and is particularly useful for the preparation of cyclic enol silyl ethers. " The synthesis of compound (47) serves as an illustration. 

The acyloin reaction is still particularly useful for large rings but it is now available for other ring sizes and for open chain compounds by the addition of MejSiCI which traps dianion (30) and removes the EtO" byproduct, preventing side reactions.The silylated product (32) is easily hydrolysed to the acyloin (33). 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

Yields in the acyloin condensation can be improved by running the reaction in the presence of chlorotrimethylsilane MesSiCl, in which case the dianion 36 is converted to the bis silyl enol ether 38, which can be isolated and subsequent )... 

Based on bis-silylated dienes another approach to quinoxaline derivatives such as 80 (Scheme 4.10) was found [97]. Fast [4+2] cycloaddition takes place by treatment of Cgo with 2,3-bis(trimethylsilyloxy)butadiene 98, yielding the acyloin-fused fullerene derivative 100 in good yields (Scheme 4.16). The silylated diene is formed in situ by treatment of 98 at 180 °C in o-dichlorobenzene. Controlled bromination of the intermediate 99 leads to the transient diketone 101, which reacts readily in a one-pot reaction with various o-diaminoarenes to yield the quinoxaline-fused fullerenes 102. 

Acyloin-type reactions of esters provide the simplest route to 1-siloxy-l-alkoxycyclopropane [21,22] Eq. (6). The reaction of commercial 3-halopropionate with sodium (or lithium) in refluxing ether in the presence of Me3SiCl can easily be carried out on a one mole scale [21]. Cyclization of optically pure methyl 3-bromo-2-methylpropionate [23], available in both R and S form, gives a cyclopropane, which is enantiomerically pure at C-2, yet is a 1 1 diastereo-meric mixture with respect to its relative configuration at C-l Eq. (7). Reductive silylation of allyl 3-iodopropionate with zinc/copper couple provides a milder alternative to the alkali metal reduction [24] Eq. (8). 

However, the presence of an alkene exo to the chain 40 stops the reaction, presumably because the 120° angle holds the ends too far apart. The solution is conjugate addition of an amine 41 the acyloin then works well 42 and the synthesis of the flavouring compound corylone 43 is completed simply by a silica column.7 Hydrolysis of the silyl enol ethers leads to elimination of Me2NH under the slightly acidic conditions. 

In the presence of TMS-Cl the enediolate dianion and, importantly, the alkoxide ions, are trapped as their neutral silyl ethers (Scheme 5). This leads to much improved yields of the coupled product the acyloin is isolated in the form of its silyl enediol ether (3). Work-up is much easier. It is only necessary to filter the solution, evaporate the solvent, and isolate the product by distillation or chromatography. The TMS-Cl should be purified by distillation from calcium hydride, under a nitrogen or argon atmosphere, before use. A convenient procedure when using an organic solvent is to add the ester and the TMS-Cl together, dropwise, to the alkali metal finely dispersed in the solvent, at a rate sufficient to maintain the reaction. An explosion has been reported where this procedure was not followed. For a reaction conducted in liquid ammonia the TMS-Cl is added at the end of the reaction and after all the ammonia has been allowed to evaporate. Particularly in cases where sodium-potassium alloy has been used, a pyrophoric residue may have formed, so that the filtration must be carried out under an inert atmosphere. 

The introduction of the trimethylsilyl chloride trapping technique" led to improved yields in the case of simple aliphatic esters. The initial silylated products are easily isolated and can be converted into the acyloins simply and in high yield. For simple aliphatic esters the yields are in the range 56-92%. Use of trimethylsilyl esters, rather than simple alkyl esters, leads to faster reactions, but lower yields.Substituted esters which have been successfully used in the newer procedure include ethyl 2-ethylhexanoate (83%), ethyl trimethylsilylacetate (90%)," ethyl 3-trimethylsilylpropionate (65%)," ethyl phenylacetate (48%)," ethyl 3-phenylpropionate (79%)" and 2-(2-methoxycarbonylethyl)-2-methyl-l,3-dioxolane derived from levulinic acid (65%)." In the case of ethyl adamantane-l-carboxylate the yield using the newer procedure is reported to be inferior to that using the earlier procedure. 

Hydroxycyclopropanecarbaldehyde (2) has not been isolated as the free acyloin, only the silylated or tetrahydropyranyl ether derivatives have been prepared. Attempts to effect the contraction of 2-hydroxycyclobutanone (1), by heating it in a sealed tube either alone (210°C) or with water (230°C) failed to bring about any reaction at all. The conclusion drawn was that while contraction almost certainly occurs, the equilibrium lies heavily on the side of the four-membered ring. ... 

Ester homoenolates can be made from 3-chloroesters 20 with sodium in the presence of Me3SiCl which traps them as the cyclopropyl silyl ethers4 21, analogues of silyl enol ethers, in a step reminiscent of the acyloin condensation.5 Reaction with aldehydes and ketones again gives y-lactones 19 and Kuwajima has shown that the titanium homoenolate 22 is a true intermediate in this reaction.6... 

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