Silyl carboxylates

A, A -Bistrimethylsilylurea, CH2Cl2. The reagent readily silylates carboxylic acids and alcohols. The byproduct urea is easily removed by filtration. 

Isopropenyloxytrimethylsilane. In the presence of an acid catalyst the reagent silylates alcohols and phenols. It also silylates carboxylic acids without added catalyst. 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

Conversion of Free or Silylated Carboxylic Acids into Esters, Thioesters, Lactones, or Ketenes. Transesterification of Esters with Alcohols... 

Carboxylic acids such as acetic acid react with alcohols such as methanol or with methoxytrimethylsilane 13 a in the presence of trimethylchlorosilane (TCS) 14 in THF or 2-methyl-THF to give esters such as methyl acetate in 97% yield and hex-amethyldisiloxane 7. Even methyl pivalate can be readily prepared in 91% yield [111]. Reaction of a variety of carboxylic acids, for example N-benzoylglycine 329, with two equivalents of yS-trimethylsilylethanol 330 and with 14 has been shown to afford esters such as 331 in 98% yield [112, 112 a]. Likewise, silylated carboxylic acids react with silylated alcohols or thiophenols in the presence of 4-trifluoro-methylbenzoic anhydride and TiCl4/AgCl04 to furnish esters or thioesters in high yields [113, 114] (Scheme 4.43). 

Similar reactivity is realized with 2-acetylthiophene using triethylsilane with aluminum chloride.259 Treatment of the ethylene glycol acetal of 2-thiophenecar-baldehyde with Et3SiH/TFA results in reduction of the ring and oxidation of the side chain to the silylated carboxylic acid (Eq. 119),260 whereas similar treatment of 2-thiophenecarbaldehyde gives 2-methyltetrahydrothiophene and 2-... 

The fragmentation of the latter, after elimination of silyl carboxylate, affords silyl derivatives of conjugated enoximes (379) in moderate yields. 

Reductions. Silicon hydrides such as 1, which can achieve intramolecular pentacoordination, show enhanced reducing properties. Thus they can reduce aldehydes or ketones to alcohols,1 and reduce carboxylic acids to aldehydes via thermal decomposition of a silyl carboxylate (equation I).2 Reaction of acid chlo-... 

The analytical control of this step is of special importance the alcaline saponification is performed at a relatively low pH in order to prevent cleavage of the silicon-carbon bond. The closer the electron-with-drawing carboxyl group is located to the Si-C-bond, the larger is the danger of scission. Therefore, for the B-silyl carboxylic acid derivatives the pH during saponification should not surpass 10.5 however, at this pH saponification of the methyl ester requires about 1 day, even at 60°C. For the -silyl derivatives, the pH of the reaction mixture is not critical. We therefore now exclusively utilize the latter. 

Silylation of carboxylic acids.1 The reagent converts carboxylic acids into silyl carboxylates within 15-20 minutes in CC14 at 65-77° in the absence of a catalyst. The by-product is 2-oxazolidinone (insoluble in CC14). It is particularly useful for silylation of gem- or 1,2-dicarboxylic acids, which are easily decarboxylated when heated or in the presence of bases. 

Besides the methods already described for synthesizing silylated heterocycles via cyclisation reactions another possible alternative is the direct silylation of heterocyclic substances. Very early investigations219 showed that the use of silylated amines219 and silylated carboxylic acid amides220 is a very appropriate choice221 when the direct silylation222 223 by means of a chlorosilane fails. 

In this series, a relatively clean condensation process was demonstrated124-263 by reactions of the silylated carboxylic acids with acetylated phenol moieties. This procedure avoids the presence of acidic protons as well as reduces the effects of acid-catalyzed side reactions.1266 ... 

Stannyl- (and -silyl-) carboxylic acids undergo oxidative decarboxylation with LTA under mild conditions to provide the corresponding alkenes. This represents an improvement on the well-known alkene-forming decarboxylation of acids with LTA, which requires thermtd or photochemical conditions, for example. The directing metal effect leads to improved yields and regioselectivity. However, stereo-specific alkene formation did not occur and this could imply free radical involvement or transmetallation (Pb for Sn) (stereochemistry ) followed by cation formation, see for example Scheme 27. 

The anodic oxidation of yS-silyl carboxylic acids is fascinating. The reaction results in the elimination of the carboxylate group and the silyl group to form olefinic products [Eq. (43)] [157,158]. A plausible mechanism involves the initial electrochemical oxidation to eliminate CO, followed by facile S-elimination of the silyl group from the generated carbocation to form the carbon-carbon double bond. 

Mesocyclic lactones. Cyclization of w-hydroxycarboxylic acids via the 0,0 -disilyl intermediates is applicable to medium-sized rings (7-membered, 35% 8- to 13-membered, 79-88%). An initial silyl carboxylate formation step is catalyzed by (Ph3P)3RhCl at room temperature which is followed by an intramolecular 0-silylation at 80°. Elimination of l,l,3,3-tetramethylbenzo-2,l,3-oxadisilazole occurs when the cyclic silylether/esters are exposed to MejSiiOTf). ... 

Silyladon of carboxylic acids. This reagent in the presence of sulfuric acid silylates carboxylic acids in 75-95% isolated yield. The actual reagent may be bis(trimethylsilyl) sulfate, [(CH Si SO. Several other acids are less effective as catalysts. 

Acylsulfenyl halides are formed by the reaction of N-bromosuccinimide or tert-butyl hypochlorite with thiocarboxylic acid O-trimethylsilyl esters164 (equation 172). Treatment of silyl carboxylates with triphenylphosphine dibromide gives the corresponding acyl bromide along with the silyl bromide165 (equation 173). It is also possible to convert silyl ethers to the alkyl bromide with this reagent165 or with a mixture of carbon tetrabromide and triphenylphosphine166. The mild nature and selectivity of the reaction is underscored by the conversion of the trimethylsiloxy /Mactam 83 to the bromide 84165 (equation 174). 

Carboxyl protection. Highly hindered silyl carboxylates are formed by the AgOTf-mediated esterification. The silyl esters are stable to aq HOAc, aq NaOH, and LiAlH4, but they are cleaved by l-BuOK-DMSO, or HF-pyridine in THE at 50°, and reduced by (-Bu2AlH to alcohols. 

The advantages of using MTBSTFA rather than TBDMSIM and TBDMCS include (i) enhanced reactivity, including its ability to silylate carboxyls, hydroxyls, thiols and primary and secondary amines (ii) short reaction times, often at room temperature, and (iii) simplified work-up owing to derivatization by-products being neutral and largely volatile, so providing the possibility for direct injection of the reaction mixture for GC analysis. 

Me3SiO>2S02 is used with Si02 in thioacetalisation of R2C=0, silyl carboxylates promote Friedel-Crafts acylation of aryl anhydrides and give carboxanilides with anilines, while silyl... 

Pentacoordinated hydrosilanes react with excess aryl isocyanates to give isocyanurates. Carboxylic acids are directly reduced to aldehydes in a one-pot process through the thermal decomposition of pentacoordinated silyl carboxylates (eq 4). The aldehydes are extracted from the crude product mixture by distillation, or separated from the trisiloxane by column chromatography over FlorisU. The reaction is selective, since fluoro, nitro, cyano, methoxy and heteroaryl substituents do not react with the silane. The present method also permits the reduction of Q , -unsaturated acids. The efficiency follows the order (2) > (1) > (3). 

---