Making ketones from esters

When attacking esters with carbanions, the product ketone is more reactive than the starting ester, so another alcohol attacks to produce a secondary alcohol. There are two solutions to this:

1. Making the starting materials more reactive

This can be done by converting to ester to an acid chloride using HCl. The acid chloride can then be attacked by the carbanion, example:

This can be helped by transmetallating a grignard reagent with a copper salt, making the carbanion less reactive too, hence the reaction is more likely to only go halfway.

2. Making the product less reactive

One example is a carboxylate salt. These are bad electrophiles, but an organolithium is just about sufficiently nucleophillic to attack one:

Obviously the dianion has no good leaving group, so it sits stable until the acid workup.

The water/acid quench also destroys any remaining organolithium, preventing further attack.

Another way of stabilizing the tetrahedral intermediate is to use a Weinreb amide, which is a N-methoxy-N-methyl amide:

The stabilization is from chelation from the methoxy group:

Quenching mechanism:

Overall reaction: