organic chemistry - Can an ether be selectively hydrolysed in the presence of an ester?

What reaction, or protection/deprotection can be used to transform the ether group of a molecule that also has an ester compound into an alcohol while keeping the ester unchanged? For example:

The usual way of removing ethers, by acid hydrolysis, would also hydrolyse the ester. Could that preserve the ester under certain conditions?

Answer

There are certain ethers which are somewhat easier to remove than others. If you stipulate that the ether must have a CH₂ group immediately adjacent to oxygen, then a couple of possibilities, off the top of my head, would be:

1. 
   

   Benzyl ethers (R' = Ph), or substituted derivatives thereof (e.g. PMB, R' = 4-methoxyphenyl). These are typically removed with catalytic hydrogenation, or under reductive Birch-type conditions. A related choice is the benzyloxymethyl group (R' = OBn), which also comes off with hydrogenation. Electron-rich benzyl ethers can be removed by oxidation (e.g. DDQ, or CAN).

   
   


2. 
   

   Allyl ethers (R' = CH=CH₂) can be deprotected with Pd(0) or Ni(0) in Tsuji–Trost style chemistry.

   
   

If you don't need a CH₂ group next to oxygen, then there are many more choices:

3. 
   
   

   Silyl ethers can be removed with fluoride ion.

   
   


4. 
   

   THP ethers can be cleaved under very mildly acidic conditions (a weak acid such as PPTS is sufficient). Esters usually need slightly more forcing conditions to be hydrolysed.

   
   

However, in general, a random ether (e.g. R = Et) would likely prove difficult to deprotect in a selective fashion. You could try using BBr₃, but it might end up being very messy. Otherwise, ordinary ethers generally require very forcing conditions to be removed. There is a review on methods of effecting ether cleavage here: Tetrahedron 2005, 61 (33), 7833–7863 and a number of ways to cleave simple alkyl ethers are listed, but many of these are very harsh and are probably not very general.