[Altered State]

Hi, I want to explain the following transformation:



I've been doing some exercises about enol-enolates without much problem, untill I found this one, and I have some doubts.

What I think I should do is, first of all form the enol/enolate and halogenate alpha position to carbonyl. Once I've done that, I need an elimination. What conditions should I use? Using maybe LDA to abstract a H+ from carbon 3 to form double bond?

But where I'm really lost is, In which moment should I run esterification? Before halogenating? After halogenating but before forming the alkene? After forming the alkene? And this said, what are the best conditions for this ester formation? Just Using Methanol? Transforming to acid chloride first?

As you can see I have some questions, hope someone could enlighten me.

[discodermolide]

I would esterify first, this solves the problem of the carboxylate forming with whatever you do. You can make the ester easily using a Fischer esterification method.
Then you make the enolate and react it with an electrophile and eliminate to get the double bond.

[Altered State]

I would esterify first, this solves the problem of the carboxylate forming with whatever you do. You can make the ester easily using a Fischer esterification method.
Then you make the enolate and react it with an electrophile and eliminate to get the double bond.

The halogenation mechanism involves the formation of an acid bromide using PBr3. I think this might not work if we already have an ester and not a carboxylic acid, am I wrong?
If this is true, the only ways left is to esterify after bromination or after elimination.

What are the best elimination agents/conditions to form the alkene? LDA/THF?

[discodermolide]

Sure you can run the Hell-Vollhard-Zelinsky reaction on the acid, then esterify and eliminate bromine, but I'm not sure how you would get the C=C in there. You can oxidise the enolate with sulfonyloxaziridines to get the acyloin.
Then eliminate H₂O.