Protection of alcohols as silyl ethers

by James

Description: Alcohols can be converted into silyl ethers with trimethylsilyl chloride (TMSCl) or similar silly groups such as t-butyldimethylsilyl chloride (TBDMSCl).  This is a useful procedure for the protection of alcohols.
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Notes: Silyl ethers are inert to many reagents that react with alcohols, so they serve as excellent 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). Silicon forms very strong bonds to fluorine.

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

Examples:

Notes: The last example shows pyridine as a base. Another common base is “imidazole”.

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: Sometimes a base such as pyridine is added that will react with the H-Cl that is formed; this helps the reaction proceed forward.

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{ 3 comments… read them below or add one }

Adam Moyer

Might want to mention that the mechanism of silyl ether removal is caused by the very strong F-Si bond

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James Ashenhurst

Thank you, very good suggestion.

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Stacey Kelm

When a base is used as a catalyst in this reaction, does it first react with the protecting agent via SN2 mechanism or is it added during step 2 to cause deprotonation of the alcohol.

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