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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: nox on January 19, 2012, 08:34:58 PM

Title: Reactivity of borane complexes
Post by: nox on January 19, 2012, 08:34:58 PM

I need to reduce a carboxylic acid down to an alcohol, and the single prep I find on Reaxys calls for LAH. While the yield was great, I'm really not a fan of the workup.

Labmate got a 91% yield using borane-DMS (different substrate) and did not even need a column. His only complaint was the lingering smell of DMS. Since we have tons of borane-THF in the lab, I wondered if I could use that instead. Literature is telling me that the THF complex is less stable but more reactive. I just wanted to make sure the two are interchangeable before I do anything stupid.

Title: Re: Reactivity of borane complexes
Post by: Dan on January 20, 2012, 04:10:45 AM

Reduction of carboxylic acids to alcohols with borane-THF is well known. I'd expect it to work, do it cold.

Title: Re: Reactivity of borane complexes
Post by: Oxime on January 20, 2012, 05:18:25 PM

I've done reductions of the carboxylic acid side-chain on appropriately protected amino acids using isobutyl chloroformate, triethylamine, and sodium borohydride in THF. It's always worked very well (~80% yield, easy column).

I've also done the same reaction using BH3-THF. Also successful, but lower yields generally (~60%).

Title: Re: Reactivity of borane complexes
Post by: Honclbrif on January 20, 2012, 11:43:13 PM

got a reference for that?

Title: Re: Reactivity of borane complexes
Post by: Dan on January 21, 2012, 05:48:06 AM

Quote from: Oxime on January 20, 2012, 05:18:25 PM

I've done reductions of the carboxylic acid side-chain on appropriately protected amino acids using isobutyl chloroformate, triethylamine, and sodium borohydride in THF.

Yeah, that is a nice method. I do like reduction methodology that uses relatively stable hydrides. The number of times I've had to quench dodgy old bottles borane, LiBH₄, LAH etc. that were only used a couple of times.

Another alternative is in situ generation of borane from sodium borohydride with iodine:

2NaBH₄ + I₂ :rarrow: 2NaI + H₂ + BH₃

This means you don't have to store borane-THF, which is very handy if you only use it occasionally and wouldn't get through it before it goes off.

Quote

got a reference for that?

An example of borohydride reduction of mixed anhydrides:

http://www.sciencedirect.com/science/article/pii/S0957416607007161

Title: Re: Reactivity of borane complexes
Post by: nox on January 21, 2012, 09:00:34 PM

Thanks for all the help guys, ended up using a prep from Tetrahedron (old boss of a labmate, he vouched for the guy) that used NaBH₄/BF₃^.OEt₂. 98% yield, no purification needed. ;D