[Fluoro]

Hi All,

I'm trying to make an aliphatic carboxylic acid with a trifluro group at the alpha position. So far I have used trifluoromethyl pyruvate and reacted that with an ylide. I can form the unsaturated ester and reduce it. When it comes to hydrolysis of the ester using a mild base, I get elimination of the fluorine. The hydrolysis doesn't work with an acid, nor can I hydrolyse the unsaturated methyl ester first and then reduce the double bond.

I have found a way round this by reducing the ester to the alcohol and then to oxidise this back up but this seems like a long winded process of something that should be quite simple. Any suggestions will be very gratefully received!

Thanks

[Dan]

Could you start with a different ester? Methyl esters are really rather stable, perhaps a t-Bu ester would suit you better, they are more acid labile than Me esters.

[Shaun]

Reducing an ester to the alcohol and later oxidizing that back to the carboxylic acid is a very common way of doing what you want to do.  Even the most legendary natural products chemists do it.  Both steps are simple to perform and give nearly quantitative yield. 

Sometimes it is better to do two easy high-yielding steps than to do a single inefficient step.

Another added benefit is that you already know how to do this.  Who knows how long it will take you to optimize a single step procedure.

Onward and upward I always say.

[Fluoro]

Thanks for your suggestions.  I will try to trans esterify the methyl ester and then remove this when I reduce the double bond.