Protection of alcohols as silyl ethers

Description: Alcohols can be converted into silyl ethers with trimethylsilyl chloride (TMSCl) or similar silyl groups. This is a useful procedure for the protection of alcohols.

Notes: Silyl ethers are inert to many reagents that react with alcohols, so they serve as protecting groups.

Sometimes a base such as pyridine is added to the reaction to quench excess HCl formed during the reaction.

Silyl ethers are cleaved using strong acids or fluoride ion (such as tetrabutylammonium fluoride, TBAF)

TMSCl is sometimes also written as (CH3)3SiCl.

Examples:

Notes: The last example shows pyridine as a base.

Mechanism: Attack of the oxygen on the silicon leads to displacement of Cl (Step 1, arrows A and B) forming a protonated silyl ether, which is then deprotonated (Step 2, arrows C and D). This reaction actually proceeds much better if a base such as pyridine is used to perform this last step.

Notes: