[someonefromasia]

Can anyone suggest a protecting group for aldehyde that is both acid and base stable?

Standard ones are acetals, but they aren't acid stable. 1,3-Dithaines are acid stable but base would take the aldehyde-H off creating a nucleophile which would mess up my synthesis plan.

Many thanks!

[Dan]

Bear in mind the pKa of 2-alkyl-1,3-dithianes is ~38, so it will be stable in the presence of most bases - it is only the really strong ones that could cause problems (e.g. BuLi, LDA etc.). What is the step in which you think it might cause a problem?

If you need higher base stability as well as acid stability, you will probably have to be a bit more drastic, e.g. "protect" as an alkene (with a Wittig reaction) - the aldehyde can then be revealed later by Lemieux–Johnson oxidation or ozonolysis. Another option is to reduce and protect as a benzyl ether, then debenzylate and reoxidise to the aldehyde later. Not very "elegant" strategies, but solid bread-and-butter chemistry.

You could also use a nitrile or (Weinreb) amide as a latent aldehyde - though if there will be any alpha protons they will be more acidic than the potentially problematic acidic proton of a dithiane.

The choice is obviously going to depend on the rest of the target structure.

[someonefromasia]

Thanks man that's really helpful. The bases in mind are triethyl amine and DBU, so that'd be alright I guess.

The funny thing is I spent loads of time working with the Weinreb amide, but couldn't selectively reduce it. That's why I'm thinking of starting with aldehyde instead.

By the way, any good sites you can recommend on compounds properties such as pka?

Much appreciated!

[Dan]

Yeah I'm pretty sure a dithiane would be OK in the presence of amine bases.

For pKa tables see:

http://www.chem.wisc.edu/areas/reich/pkatable/
http://research.chem.psu.edu/brpgroup/pKa_compilation.pdf
http://evans.harvard.edu/pdf/evans_pka_table.pdf

[someonefromasia]

Thanks a bunch!