Chemical Forums

Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: asa029 on April 16, 2012, 02:09:28 AM

Title: Deprotonation of a terminal alkyne
Post by: asa029 on April 16, 2012, 02:09:28 AM
Hi everyone!

I want to deprotonate a terminal alkyne and react it with an aldehyde to give the Favorskii adduct. I am therefore looking for suitable bases to do this reaction. Everyone always talks about sodium amide (NaNH2) or LDA. I have worked with LDA before and it's not my best friend, so I was wondering if anyone had any experience with sodium amide in this type of reaction (especially concerning handling).
Title: Re: Deprotonation of a terminal alkyne
Post by: g-bones on April 16, 2012, 02:39:42 AM
Unless you have other sensitive functionality on your alkyne, you can just butyl lithium directly, then quench with your aldehyde to get your 1,2-addition adduct.
Title: Re: Deprotonation of a terminal alkyne
Post by: superg on April 16, 2012, 05:39:07 AM
n-BuLi works well, at 0°C in THF. i'll on consider using LDA if there is possibility of addition on another part of your molecule.

just wondering: by adding a lithio acetylide on an aldehyde, won't you get the corresponding propargylic alcohol?
Title: Re: Deprotonation of a terminal alkyne
Post by: OC pro on April 16, 2012, 05:56:58 AM
just wondering: by adding a lithio acetylide on an aldehyde, won't you get the corresponding propargylic alcohol?

Of course.
Title: Re: Deprotonation of a terminal alkyne
Post by: asa029 on April 16, 2012, 06:22:30 AM
just wondering: by adding a lithio acetylide on an aldehyde, won't you get the corresponding propargylic alcohol?

Of course.

But it will likely enolize into the alfa, beta-unsaturated ketone after quenching with weak acid.
Title: Re: Deprotonation of a terminal alkyne
Post by: asa029 on April 16, 2012, 06:23:26 AM
Unless you have other sensitive functionality on your alkyne, you can just butyl lithium directly, then quench with your aldehyde to get your 1,2-addition adduct.

I have a tosylate which doesn't love base. One of the professors here said buli would be a "dead end", but he didn't explain why!
Title: Re: Deprotonation of a terminal alkyne
Post by: fledarmus on April 16, 2012, 07:21:53 AM
Unfortunately, the n-butyl anion is also a good nucleophile. If there are available leaving groups, you will get substitution reactions.

Deprotonated amines are not particularly good nucleophiles and don't typically have this problem.

If you really need a base stronger than metal amides, you can use phenyllithium or in the worst case, t-butyllithium, but t-butyllithium is almost too reactive to handle.