Trimethylchlorosilane reaction with carboxylic acid

Kuhlmann has reviewed the reactions of carboxylic acid esters with sodium in the presenee of trimethylchlorosilane. 

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). 

P-Keto acids. A new synthesis of /i-keto acids involves the reaction of dianions of carboxylic acids with esters.6 The intermediates are trapped with trimethylchlorosilane and isolated as the trimethylsilyl esters. For example, isobutyric acid is converted into the dianion (1) by treatment with 2 eq. of lithium diisopropylamide in THF at 0°. Addition of I eq. of methyl pivalate (2) and an excess of trimethylchlorosilane yields the... 

Bis(trimethylsilyl)acetamide (1). Mol. wt. 203.44, b.p. 71-73735 mm. Prepared in 80% yield by reaction of acetamide with trimethylchlorosilane with triethylamine as catalyst, the reagent effects trimethylsilyUuion of amides, ureas, amino acids, phenols, carboxylic acids, enols. ... 

An alternative reagent, trimethylsilyldiazomethane in hexane, is commercially available and appears useful for preparation of bile acid methyl esters [62], Like carboxylic acid groups, hydroxyl groups also require protection prior to GC-MS analysis. A common and mild method to prepare trimethylsilyl (TMS) ethers is to react the sample with a mixture of dry pyridine, hexamethyldisilazane (HMDS), and trimethylchlorosilane (TMCS), 3 2 1 or 9 3 1 (by volume) with, or without heating [32], However, if 0X0 groups are present in the bile acid, this reaction can yield enol-TMS ethers and multiple products. This artifact can be avoided by converting the 0X0 group into an oxime, usually a methyloxime (MO). To do this, the sample is dissolved in 50 pL pyridine with 5 mg methoxyammonium chloride and heated for 30 min at 60°C [32]. 

The s)mthesis of e /iro-L-j -hydroxyglutamic acid (844) makes use of the furan heterocycle as a carboxyl equivalent (Scheme 122) [185]. After reduction of 793a to 839 and acetylation (840), the aminal acetate and furan are coupled in the presence of zinc bromide and a catalytic amount of trimethylchlorosilane to give a 67 33 mixture of 841 and 842. In the absence of silane the reaction requires 12 h at room temperature for completion, but with silane present the reaction time is reduced to2hat —15°C. 

---