[jiangds05]

help badly needed for one synthesis. as you see from attachment, I do not know whether nBu-Li are strong enough to deprotonate acetal.

if you do not think this pathway cannot work, could you give me some hint in order to synthesis the final product.

Thanks a lot.

[MissPhosgene]

butyl lithium can do that. Can you think of a way to use an umpolung reagent or a way to protect the first formyl group so that it doesn't react when the second is installed?

[jiangds05]

thanks you so much for your reply.

Can i use LDA instead nBuli under very low temperature in order to suppress acyl addition in order to protect formyl group? By performing deprotonation first, i do not see any change formyl group will react simply because of anion anion repulsion?  do I understand you right?

another thing that I worry is that original acetal group will be hydrolyzed under acid workup for formyl group formation, what do you think of this?

butyl lithium can do that. Can you think of a way to use an umpolung reagent or a way to protect the first formyl group so that it doesn't react when the second is installed?

[MissPhosgene]

The anion of the acetal can react with the formyl group.

[jiangds05]

but anion and formyl group are in the same molecule, and all of molecules are deprotonated, so there is no chance for anion to reaction with themseleves.
am I right?

The anion of the acetal can react with the formyl group.

[MissPhosgene]

Yes, they can polymerize.

[jiangds05]

but anion cannot react with anion..
I guess deprotonation is faster than polymerization reaction rate.

Yes, they can polymerize.

[MissPhosgene]

Think about why making a grignard out of methyl 3-bromopropionate and trying to react the resultant grignard with carbon dioxide, for example, will not work out so well.

[jake.n]

Perhaps you could use a less reactive electrophile to indirectly deliver the formyl group?  Immediately the Bodroux reaction comes to mind, though you don't want to have to hydrolyze acetals on workup, so that is a bad example.

I don't know if your enolate will react with CO2, but that could get you to the aldehyde following acid reduction.  If you found a suitable route to the imine, you could hydrolyze that to the aldehyde.