[Qfbale]

Hi

Someone could tell me how is riding his reduction system to carry a carboxylic acid to aldehyde using DIBAL -H

The literature says that the reaction is carried out at -78 ° C

Anyone have any simple method ?

[NiceWeatherSunshine]

dry ice/acetone bath. Even better, use a cold-finger set to -85 C. Be sure to avoid exotherm to prevent over reduction. use a multineck rbf and put a cold temp thermometer in one of the necks. stir rapidly

[Dan]

This paper may be of interest:

http://www.sciencedirect.com/science/article/pii/S0040403997106888

[discodermolide]

DIBAL-H won't reduce acids, you need esters. In my experience over reduction is always achieved (even at T<-85°C) so the yields of aldehyde are low. So let it over reduce, isolate the alcohol. This is easily oxidised back to aldehyde.

[NiceWeatherSunshine]

It does reduce acids. I've done this transformation many times.

Its possible to get 90%+ yields of aldehyde. It just takes a while to add everything.

[discodermolide]

Could you please supply literature for the direct reduction of carboxylic acids to aldehydes with DIBAL-H. Thanks

[Babcock_Hall]

There was a thread on a closely related subject a couple of years ago:  http://www.chemicalforums.com/index.php?topic=67874.0

[kriggy]

Im just wondering, would it be posible to use LAH and trap the aldehyde as acylal using acetic anhydride? I saw this when alcohols were oxidized to aldehydes with CrO3 but I dont recall seeing it with reduction. Is it because it requires acidic condition and the hydrides are rather basic?

[Dan]

Im just wondering, would it be posible to use LAH and trap the aldehyde as acylal using acetic anhydride? I saw this when alcohols were oxidized to aldehydes with CrO3 but I dont recall seeing it with reduction. Is it because it requires acidic condition and the hydrides are rather basic?

The problem with that is competitive reduction of the anhydride reagent and reductive deacetylation of the product. Reductive deacetylation of Ac groups with DIBAL works very well and is useful for systems that will not tolerate standard deacetylation methods (saved my skin on more than one occasion).

The trapping idea is good though - maybe TMSCl or a silyl triflate would work?

[zarhym]

It doesn't work.

For carboxylic acid, it should be reduced to alcohol first using BH3DMS, BH3THF or other reducing agent.
Then, the alcohol can be oxidized to aldehyde with MnO2 or Dess-Martin.

[Babcock_Hall]

One method of making a phenyl carboxylate ester into an aldehyde was published by H C Brown and a colleague many years ago.  IIRC the method used an aluminum hydride derivative that had tertiary butoxy groups.  The details escape me at the moment.  I am not saying that this method has any advantages over or disadvantages to any other, inasmuch as I have only read about it.  Keep meaning to try it...

[BRSM]

First let me agree with the above, DIBAL will not turn your acid into an aldehyde. You'll be doing this in two steps.

A couple of other more "out there" options you might consider, in addition to the above reduction-oxidation sequences:

1. Make the acid into a Weinreb amide. These reduce to aldehydes very neatly under the same principle that makes them great for ketone synthesis. Even LiAlH₄ stops at the aldehyde in Weinreb amide reductions!

2. Make the acid chloride and hydrogenate it. Very underrated way of cleaning making aldehydes, and you often don't need to purify either of the steps.

3. I've personally found that reducing carboxylic acids by making the mixed anhydride with a chloroformate (i-BuOCOCl is popular, for some reason) then using NaBH₄ as the reducing agent is a better way of getting the alcohol than borane. Cheaper, easier workup, more convenient on scale. Your mileage may vary.

[BRSM]

One method of making a phenyl carboxylate ester into an aldehyde was published by H C Brown and a colleague many years ago.  IIRC the method used an aluminum hydride derivative that had tertiary butoxy groups.  The details escape me at the moment.  I am not saying that this method has any advantages over or disadvantages to any other, inasmuch as I have only read about it.  Keep meaning to try it...

You're think of (t-BuO)₃AlH. It's largely been superseded by DIBAL (in the same way that Weinreb amides large beat out thionopyridine esters for ketone synthesis, but it's occasionally useful). I actually did use it last year to reduce a lactone to a lactol, which it surprisingly did much better than DIBAL, but somewhat less well than Red-Al. One good thing about it is that it reliably delivers exactly 1 equivalent hydride per equivalent reagent, where as other aluminum reagents like LiAlH₄ are somewhat more nebulous. It's also down the lower end of the reactivity scale. Occasionally a useful club to have in your bag, even today.

[Babcock_Hall]

It would be interesting to see how slight differences in the leaving group (phenyl vs. substituted phenyl) affected the success of the H-Al(OtBu)₃ reactions.  So much chemistry, so little time.