Silylations with Monofunctional Silylating Reagents

ScHMEissER, P. Sartori, B. Lippsmeyer, Chem. Ber. 1970, 303, 868 H. Emde, D. Domsch, H. Feger, U. Frick, A. Gotz, H.H. Hergott, K. Hofmann, W. Kobee, K. Krageloh, T. Oesterle, W. Steppan, W. West, G. Simchen, Synthesis 1982, 1 

Hofmann, G. Simchen, Liebigs Ann. Chem. 1981, 1657 T. Bach, H. Brummerhop, J. Prakt. Chem. 1999, 343, 410 

The mono-silylated or free acetamides, which are liberated during silylation with 22 a, can, furthermore, interfere with any subsequent reaction, e.g. with electrophiles. Thus in the one-pot/one-step silylation, Friedel-Crafts catalyzed, nucleoside synthesis starting from protected sugar derivatives and pyrimidine or purine bases, the mono- or bis-silylated amides such as 22 a can compete with less reactive silylated heterocycHc bases for the intermediate electrophilic sugar cation to form protected 1-acetylamino sugars in up to 49% yield [42, 47]. On silylation with trimethylsilylated urea 23 a the Hberated free urea is nearly insoluble in most solvents, for example CH2CI2, and thus rapidly precipitated [43]. 

Provencio, M.L Jimeno, J. Balzarini, E. De Clercq, Nucleos. Nucleot. 1998, 17, 901 

Because steric factors strongly influence the rate of silylations, primary alcohols are normally silylated much more rapidly than secondary alcohols whereas tertiary alcohols are silylated much more slowly. The same is true for phenols - ortho-substituted phenols such as o-cresol are silylated much more slowly than unsubstituted phenols. Obviously, the same applies to cleavage of silylated alcohols or phenols on transsilylation, e.g. with excess boiling methanol (Section 2.3). 

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Polar functional groups such as alcohols or phenols 11 or trimethylsilanol 4 are transformed by monofunctional silylating reagents Me3SiX 12 into their hpophilic and often volatile trimethylsilyl ethers 13 whereas water is converted into persilyl-ated water (=Me3SiOSiMe3, hexamethyldisiloxane, HMDSO, 7, b.p. 100 °C). The persilylation of phenols and, in particular, catechol (or hydroquinone) systems (Scheme 2.1) protects them efficiently against air oxidation even at temperatures of up to 180 °C. (cf, e.g., the silylation-amination of purine nucleosides with dopamine hydrochloride in Section 4.2.4)... 

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