Silyl ether

Common silyl ethers are: trimethylsilyl (TMS), tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBS/TBDMS) and triisopropylsilyl (TIPS).

One reliable and rapid procedure is the Corey protocol in which the alcohol is reacted with a silyl chloride and imidazole at high concentration in DMF.

When using a silyl chloride, no special precautions are usually required, except for the exclusion of large amounts of water.

Water quenches remaining silyl reagent and protonates amine bases prior to their removal from the reaction mixture.

Larger substituents increase resistance to hydrolysis, but also make introduction of the silyl group more difficult.

If the reaction were controlled solely by thermodynamics, and if the dianion is of similar reactivity to the monoanion, then a corresponding statistical mixture of 1:2:1 disilylated:monosilylated:unsilylated diol would be expected.

However, the reaction in THF is made selective by two factors: 1. kinetic deprotonation of the first anion and 2. the insolubility of the monoanion.

This small portion reacts and shifts the equilibrium of the monoanion to draw more into solution, thereby allowing for high yields of the mono-TBS compound to be obtained.