[AlphaScent]

Has anyone ever used lithium hydride as a way to deprotonate a beta-ketoester or any carbonyl for that matter.  I know it is used to make lithium carboxylates.  The pKa of say ethyl acetoacetate is around 11.  Is there a reason lithium hydride is not used besides maybe reactivity?  I am trying to alkylate without getting O-alkylation, and sodium hydride is giving me a bout 20% O-alkylation in DMF and DME.  I have LiH around and am just going to try it but am wondering if anyone has any experience with this.

Any insight is greatly appreciated!

Cheers!

[phth]

it catches fire during weighing. NaH different for that reason

[rolnor]

What electrophile are you using? I have alkylated malonate with a triflate an got 100% O-alkylation, I think a softer electrophile like alkyliodide is better. If you want lithium you can use LDA.

[AlphaScent]

@phth,

It is less reactive than NaH and that is why you find NaH and KH in oil suspensions. I am surprised if it is so pyrophoric that it would not also be in oil.

@rolnor,

I tried to do LDA last night and got terrible conversion.  I made LDA at 0C in DME.  Dropwise added the acetoacetate @ 0 C, and then let warm to RT over 45 min.  Then slipped in some TBAI (2.5 mol %), then added tosylate.

I know that using the iodide works well.  I am trying to use the tosylate and get similar results strictly for industrial applications.  Making the iodide on scale is no fun and am trying to figure out if there are appropriate conditions to get the 95/5 C/O alkylation products I get with the iodide.  There is a bunch in the literature and I have consulted about the hard/soft aspect of the electrophile.  I was able to get 80/20 C/O using KI and 18-crown-6 in DMF using NaH as the base, where previously I was getting 35/65 C/O alkylation without using catalytic KI and 18-Crown-6.  I get 75/25 without the 18-crown-6.  The issue too is that making even the bromide is tough because my alcohol is allylic.  So there is that little wrinkle as well.

Thanks for the thoughts ya'll!

Cheers!

[OrganicDan96]

how about LiHMDS?

[rolnor]

I understand, the tosylate is harder and gives more O-alkylation. On labscale this would be easie problem, in your case its not.