Amides are pretty tough to reduce down to their corresponding amines. Typically, you hydrogenate at high temperature and pressure or use LAH, borane, dissolving metals and stuff like that, under – obviously – pretty harsh conditions. Good old March (5th ed., ISBN: 0471585890) says: “The reaction is more difficult than the reduction of most other functional groups, and other groups can be reduced without disturbing an amide function.” In other words, amides are among the last functional groups that surrender to hydrides.

A colleague of mine tipped me about this paper by Beller et al., which turns everything we know about amide reduction upside down. It’s just amazing!

Amide reduction

JACS 2010, 132, 1770-1771. (DOI: 10.1021/ja910083q)

Check it out! Using this protocol, you can selectively reduce amides in the presence of esters, ethers, nitro groups, nitriles, azo functionalities, non-conjugated and conjugated double bonds and – drum roll – even ketones.

As far as I can tell, the limitation seems to be that the amide has to be tertiary. But what about mono- or di-allyl amides then? Would they work? Mono- and di-allyl amines are straightforwardly converted to primary amines under mild conditions, using for instance Pd(PPh3)4 and N,N-dimethylbarbituric acid (JOC 1993, 58, 6109-6113., DOI: 10.1021/jo00074a044).

My two cents.

 

7 Responses to Mild and selective amide reduction (in the presence of pretty much anything else)

  1. Heiko says:

    Hey,
    nice reaction and nice site, too. Keep it rollin’

  2. milkshake says:

    Boranes are fast at reducing amides (and free CO2H, C=C) while reducing esters only very slowly (unless there is a coordinating group nearby). So before this new silane system was discovered, reduction of amides in the presence of esters can be accomplished for example with BH3.Me2S in THF at room temperature.

  3. CTchem says:

    good and interesting info. useful and simple reaction.

  4. CatalysisAlex says:

    Yes, I wonder as well (how well) this would work with secondary or primary amides. Since there is Zn(OAc)2 is in the system, I could imagine there to be a number of side-reactions for the reactant group, not to mention other groups in the molecule, such as ketones….

  5. sandeep says:

    Hey,i want to reduce primary amide to amine in presence of secondary and tertiary amides. Could you pls give me any suggestions on the same.

  6. Having read this I believed it was rather informative.

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