[AlphaScent]

of an ester.

The reaction is run with the ester being dissolved in a 3:1 w/w solution of THF/ethanol and added dropwise to 10% w/w solution of lithium borohydride in THF.

Is this the mechanism?  Does the ethanol protonate the alkoxide?

[baum0372]

From my experience, the alkoxide you mentioned is usually coordinated with the boron from sodium borohydride.  Elimination of the ethoxide anion from your molecule displaces the boron to form NaNH₃OEt.  This can still donate hydride ions to further reduce other molecules.  Your mechanism is essentially correct though as far as my knowledge goes.

[AlphaScent]

Thanks baum,

It is Lithium Borohydride, not sodium borohydride.  I have read that the greater lewis acid nature of lithium makes the lithium borohydride a stronger reducing agent than sodium borohydride.  Under standard condtions NaBH4 will not reduce esters, but LiBH4 will.

But, what you mentioned about the coordination makes sense. The LiBH3OEt would then be able to reaction again.  The process would then proceed until all the hydrides are replaced by -OEt.

[Dan]

But, what you mentioned about the coordination makes sense. The LiBH3OEt would then be able to reaction again.  The process would then proceed until all the hydrides are replaced by -OEt.

Yes, but LiBH₄ will react with EtOH as well (you probably noticed fizzing), so you will need more than 0.5 equiv LiBH₄ to fully reduce an ester in the presence of an alcohol.

LiBH₄ + nEtOH  LiBH_(4-n)(OEt)_n + 0.5nH₂

The active reducing species is probably ^-BH_(4-n)(OEt)_n where n = 1 or 2 (I'm not 100% sure), not ^-BH₄.

[AlphaScent]

Does that species effect the reactivity?  Like sodium cyanoborohydride and sodium borohydride?

I just dont know exactly why the ethanol is beneficial to the reaction. 

[Dan]

I think so yes - I was always taught that the donating alkoxy groups increase the reactivity of the hydride - but I don't have a specific source to back this up right now.

[kriggy]

Does that species effect the reactivity?  Like sodium cyanoborohydride and sodium borohydride?

I just dont know exactly why the ethanol is beneficial to the reaction.

It formes methoxyborohydride which is more reactive.
I have only this article but it doesnt discuss the mechanism of reduction (its just the procedure):

Simple reduction of ethyl, isopropyl and benzyl aromatic esters to
alcohols using sodium borohydride-methanol system
Jorge C. S. da Costa, Karla C. Pais et al.
ARKIVOC 2006 (i) 128-133

I had one which discuss the mechanism but cant find it

[orgopete]

I think so yes - I was always taught that the donating alkoxy groups increase the reactivity of the hydride - but I don't have a specific source to back this up right now.

I am not inclined to think this. By implication, trialkoxy would be the most reactive. If borohydride reacted with ethanol, and each product was more reactive, the decomposition should accelerate. I am more inclined to think the last hydride would be more tightly held by boron as oxygen pulls electrons away. I think boric acid acts as a Lewis acid with water. I don't think the lone pairs make it less acidic, though they are a factor.

[Dan]

By implication, trialkoxy would be the most reactive. If borohydride reacted with ethanol, and each product was more reactive, the decomposition should accelerate.

Yes, this has always bothered me. The decomposition should accelerate if each successive species is more basic - this does not always tie well with nucleophilic reactivity though. Despite the inductively withdrawing character of O, there might be overlap between the lone pair and a B-H σ* that encourages hydride donation (but I can't offer a reason as to why this might increase nucleophilicity but not basicity).

It is of course true that trialkoxyaluminium hydrides are less nucleophilically reactive than LAH, which would imply by analogy that (as you propose) reactivity of LiBH₄ decreases with successive reactions with ethanol. Your proposal makes more sense to me.

The question then is why add EtOH to a LiBH₄ reduction?

I have heard of people advocating a "few drops" of alcohol to (they claim) catalyse or activate LiBH₄ reductions - I personally find the reagent capricious at best and avoid it if at all possible.

[orgopete]

The question then is why add EtOH to a LiBH₄ reduction?

I have heard of people advocating a "few drops" of alcohol to (they claim) catalyse or activate LiBH₄ reductions - I personally find the reagent capricious at best and avoid it if at all possible.

I have no experience with LiBH4. I looked up one paper of H.C. Brown and from the first page (I don't have access) I note the reaction in ether was slow. Obviously, I don't have any details, but coupled with the 'capricious' comment, I begin to sense some of the details are missing. Slow, in and of itself can mean anything. However, I wonder about solubility in ether. How soluble is it? I can imagine adding ethanol can improve solubility. It can limit the bulk around boron by exchange with ethanol. I can also imagine ethanol changing the coordination of lithium compared with ether or THF.

As I look at the reaction of borohydride, the difference in reactivity could be due to the solvent and counter ion. However, as I think about this, I could be completely wrong. I think the electron donor is a tetravalent boron. The product of a reduction would be a trivalent boron. Replacing a hydrogen with an alkoxide group in that case would arguably increase the Lewis acidity. If that is rate limiting, then replacing hydrogens with alkoxide groups could increase the net reaction rate. That is, the reaction may be analogous to borane reduction of an acid. I write that mechanism with a tetravalent boron to a neighboring carbocation and I use a similar reaction in hydroboration reactions. I do not write a 2+2 reaction.

[AlphaScent]

Pete,

Can you link the paper??

I have access.

Cheers!!