[azncuzin202]

Lastly I am going to use water/H⁺ to close the ring giving me the final structure.

[spirochete]

Excess water, I believe, will favor the acid/alcohol form. You need to be removing water from the equilibrium or doing something else to favor the ester over the acid.

That is unless there's something specially thermodynamically stable about lactones that causes them to be favored over open chain acids.

[azncuzin202]

If not water, then do you think NaBH4/NaOH would work?

[azncuzin202]

This is what I have so far.

[spirochete]

What is the purpose of the NaBH4 in the last step?

[azncuzin202]

Can't you form the structure via redox-esterification? Or does this not apply in this scenario? Otherwise I would use water/H+ though you mentioned that it may not favor the lactone.

[spirochete]

NaBH4 might work as a basic catalyst but something like acid catalyst plus a non protic polar solvent would work just as well.

There is no redox reaction needed here. We're looking for an intramolecular esterification of a carboxylic acid.

[orgopete]

Excess water, I believe, will favor the acid/alcohol form. You need to be removing water from the equilibrium or doing something else to favor the ester over the acid.

That is unless there's something specially thermodynamically stable about lactones that causes them to be favored over open chain acids.

Although this is not good reasoning, the hydroxyacid is less available than the lactone. The hydroxyacids form lactones readily, see gamma-valerolactone in Wikipedia. I don't have any practical experience with delta-lactones, but as I understand, it is difficult to avoid lactonization upon acidification. I imagine an excess of mineral acid, even in water forms a lactone.

[Dan]

Although this is not good reasoning, the hydroxyacid is less available than the lactone. The hydroxyacids form lactones readily, see gamma-valerolactone in Wikipedia. I don't have any practical experience with delta-lactones, but as I understand, it is difficult to avoid lactonization upon acidification. I imagine an excess of mineral acid, even in water forms a lactone.

This is a very accurate description in my experience. While they do not lactonise as readily as gamma-lactones, it is still very, very difficult to stop a delta-lactone forming in even aqueous acidic media. I spent 4 years working with such compounds (sugar lactones), and they quantitatively lactonise if passed through an acidic ion exchange column in aqueous solution. The only way to reliably keep them open is to convert them to the corresponding carboxylate salt in aqueous base.

[spirochete]

Excess water, I believe, will favor the acid/alcohol form. You need to be removing water from the equilibrium or doing something else to favor the ester over the acid.

That is unless there's something specially thermodynamically stable about lactones that causes them to be favored over open chain acids.

Although this is not good reasoning, the hydroxyacid is less available than the lactone. The hydroxyacids form lactones readily, see gamma-valerolactone in Wikipedia. I don't have any practical experience with delta-lactones, but as I understand, it is difficult to avoid lactonization upon acidification. I imagine an excess of mineral acid, even in water forms a lactone.

How is my reasoning, a simple Le Chatlier argument, not good? Typical esterifications using an alcohol and a carboxylic acid are not run in water because this will definitely make the equilibrium favor the acid form. As you know, esters and alcohols have about the same thermodynamic stability.

I knew there was something different about lactones which I acknowledged from the beginning. I just wasn't sure if it would be enough to make a difference here. Acylic versions of this reaction are not run in water and usually require removing water as the reaction proceeds or some other perturbation of the equilibrium.

Obviously Dan has run this reaction and now I'm remembering the fact that it is common knowledge among synthetic organic chemists that this particular type of esterification (lactonization) is particularly favored. I'm guessing now that it could simply due to entropic considerations.