Carboxylic acids trialkylsilylation

Nafion-H has been shown to be effective in a variety of protection-deprotection reactions including (9-trialkylsilylation of alcohols, phenols, and carboxylic acids, as well as the preparation and methanolysis of tetrahydropyranyl (THP) ethers.672 However, when compared, for example, with HBF4-silica or Nafion nanocomposites,... 

Trialkylsilyl protection of carboxylic acids and amines is rare owing to hydrolytic lability. Nevertheless, synthetically useful silicon protecting groups have been developed for these functional groups in which the requisite stability is achieved by incorporating the silicon atom into a 2-(trimethylsilyl)ethyl substituent. The principle is illustrated [Scheme 1.9] by the reaction of 2-(trimethylsilyl)ethyl esters with tetrabutylammonium fluoride the pentavalent siliconate intermediate fragments with loss of ethylene and fluorotrimethylsilane14-15 to liberate a carboxylic arid as its tetrabutylammonium salt. 

BINOL-Me, and stoichiometric amounts of 2,6-dimethylphenol as an achiral proton source, protonation of the ketene bisftrime-thylsilyl)acetal derived from 2-phenylpropanoic acid proceeds at —80°C to give the (5)-carboxylic acid with 94% ee. (/ )-BINOL-Me is far superior to (/ )-BINOL as a chiral proton source during the catalytic protonation, and 2,6-dimethylphenol is the most effective achiral proton source. In addition, it is very important that the molar quantity of SnCU should be less than that of (/ )-BINOL-Me to achieve a high enantioselectivity. For the reaction of 2-phenylcyclohexanone, however, the use of tin tetrachloride in molar quantities lower than BINOL-Me remarkably lowers the reactivity of the chiral LBA (eq 3). Excess SnCLt per chiral proton source, in contrast, promotes this protonation. In the protonation of silyl enol ethers less reactive than ketene bis(trialkylsilyl) acetals, chelation between excess tin tetrachloride and 2,6-dimethylphenol prevents the deactivation of the chiral LBA. 

Hydrozirconation of alkenes as a route to rr-alkylzirconiums is limited by other reactive functional groups e.g., alkynes react more readily than alkenes with (/j -Cp)2ZrHCl, and other reactive functional groups with ( / -Cp)2ZrHCl include alcohols, aldehydes, ketones, carboxylic acids, carboxylic acid esters, nitriles and thiocarbonyls . Alcohols may be protected either as alkyl ethers or as trialkylsilyl ethers. 

Enol phosphates phosphonates were also obtained by the reaction of perfluoroalkanoyl chlorides with triethyl phosphite. In this case, it was not possible to isolate the putative intermediate perfluoroacylphosphonates. This result is in contrast with the facile formation of bis (trialkylsilyl) trifluoroacetylphosphonates (see previous section), and it indicates that acylphosphonates derived from carboxylic acids with strongly electron-withdrawing groups can be prepared using tris(trialkylsilyl) phosphites. Such silyl phosphites seem to be uniquely suitable for this purpose, by virtue of their high reactivity in the first step and their steric hindrance, which presumably retards the second step. 

Protection and Deprotection.—Carboxylic acids and amides can be silylated rapidly and in very high yield by exchange reactions with keten methyl trialkylsilyl acetals obtained from methyl propionate." Known procedures have been modified to allow the preparation of keten bis(phenylthio) acetals from adds or esters using aluminium thiophenoxide yields are generally very good."... 

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