Si2 Protection of hydroxy groups as silyl ethers

The trimethylsilyl group has been used extensively for the protection of alcohols. One of the many methods which have been used for protecting a hydroxy group as its trimethylsilyl ether involves adding trimethylsilyl chloride (trimethylchlorosiiane, TMCS) to the alcohol in the presence of a weak base as exemplified in Equation Si2.1. 

Me3Si — NEt2 / N Me3Si — j The order of reactivity of these 

The level of selectivity that can be achieved in the formation of trimethylsilyl ethers is illustrated by the selective protection of the hydroxy group at C-ll in the methyl ester of the prostaglandin 15-methyl PGF20 (Equation Si2.2). Thus the less sterically hindered secondary alcohol at C-ll is selectively protected in the presence of the more sterically hindered secondary alcohol at C-9 and the tertiary alcohol at C-15. 

Tcrt-butyldimethylsilyl ethers have been used extensively for the protection of hydroxy groups. They are more stable to hydrolysis than trimethylsilyl ethers by a rate factor of 104 and they are compatible with a much wider range of reagents used in organic synthesis. 

The steric bulk which accounts for the relative stability of tert-butyldimethylsilyl ethers also hinders their formation and so the reaction between tot-butyldimethylsilyl chloride and hydroxy groups in the presence of pyridine is very slow. In the presence of catalytic amounts of imidazole, however, the reaction proceeds rapidly and in high yield as shown in Equation Si2.3. 

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