I am not seing tBu listed as alcohol protection group in all of these places:

On the other hand it seems to be quite common in peptide synthesis to protect the alcohol of serine, threonine and tyrosine with tBu.

It is listed on the German Wikipedia page: https://de.wikipedia.org/wiki/Schutzgruppe#Alkohole

Can I conclude from this that tBu is very rarely used in non-peptide syntheses? Or is it just plain missing from the English Wikipedia article?


1 Answer 1


Protecting group selection is a balancing act of ease of preparation and deprotection. In common practice, use of a protecting group adds two steps to a synthetic route. Installation and removing a tert-butyl group requires stronger (acidic) conditions. Of course, it's a rock while in place and inert to nearly all conditions short of strong acid.

Peptide synthesis is particularly amenable to use of tert-butyl protection of hydroxyl groups because (1) all of the suitably protected residues are commercially available and (2) the protecting groups have been designed to be globally deprotected with trifluoroacetic acid. These factors minimize the inherent inefficiency to protecting groups.

The workhorse protecting groups for alcohols are silyl ethers (e.g.trimethylsilyl, triethylsilyl, tertbutyldimethylsilyl, triisopropylsilyl, tertbutyldiphenylsilyl). The silyl ethers are easier to form and cleave than standard ethers and have excellent compatibility with reactions that require alcohol protection.

Specialized (carbon) ethers can be useful as well, including unsubstituted or substituted benzyl ether (removed by oxidative or reductive conditions) and acetals (removed by mild acid treatment).

For a more complete description of protecting groups (including tert-butyl), see the books by Greene and Wuts or Kocienski.


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.

Not the answer you're looking for? Browse other questions tagged or ask your own question.