In the previous post, we saw that amides can be reduced to amines by LiAlH4:

Let’s see how tertiary amides can be reduced to amines and aldehydes using alkyboranes. 

Reduction of Amides by Alkylboranes

The reduction of amides by alkyl boranes such as 9-BBN or Sia₂BH is not common in undergraduate textbooks, however, I thought it is worth mentioning here since we can selectively convert the amide to an amine or an aldehyde.

It is mostly related to tertiary amides but I have not done a thorough research on whether primary or secondary amides can be used as well. In general, one problem with primary and secondary amides is the formation of O-B and N-B esters with boron (J. Am. Chem. Soc. 1970, 92, 24, 7161–7167). There are studies on reducing secondary amides using NIckel catalyst so, feel free to check this article and the references for insight into the topic.

9-BBN: Tertiary Amides to Amines

9-BBN and Sia₂BH are bulky alkyl boranes which we have seen earlier in the hydroboration-oxydation of alkynes. 

The idea behind using alkyl borane or borohydrides in the reactions of alkenes, alkynes, and carbonyl compounds is the fact that boron has an empty p orbital which makes it electrophilic. The electron source can be any pi bond, and when the electrons are added to the boron, it now becomes electron-rich which makes it a donor of a hydride ion. We have seen this in many reduction reactions with NaBH₄, and also with BH₃ (B₂H₆) for the reduction of carboxylic acids. 

Taking into consideration all the patterns we have seen in the reduction reaction, let’s try to put together a plausible mechanism for the reduction of a tertiary amide to an amine:

In the first step, we have an addition to the carbonyl via coordination of the boron forming a boronic ester intermediate. After another coordination, the boronic ester is converted into a good leaving group by the positively charged oxygen and it is kicked out by the second hydride addition. 

Sia₂BH: Tertiary Amides to Aldehydes

Although structurally very similar to 9-BBN, it has been shown that the reduction of tertiary amides can be stopped at aldehydes when Sia₂BH is used. This means the second hydride addition does not occur and the hydrolysis of the boronic ester intermediate gives the corresponding aldehyde as the final product:

Here is the original article for further reading: Tetrahedron Letters, Vol. 38, No. 10, pp. 1717-1720, 1997.

Need some good practice on the reactions of carboxylic acids and their derivatives?

Check this 45-question, Multiple-Choice Quiz with a 50-minute Video Solution covering the reactions of acids, esters, lactones, amides, acid chlorides etc. 

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Carboxylic Acids and Their Derivatives Quiz

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• Reactions of Acid Chlorides (ROCl) with Nucleophiles
• Reaction of Acyl Chlorides with Grignard and Gilman (Organocuprate) Reagents
• Reduction of Acyl Chlorides by LiAlH4, NaBH4, and LiAl(OtBu)3H
• Preparation and Reaction Mechanism of Carboxylic Anhydrides
• Amides – Structure and Reactivity
• Amides Hydrolysis: Acid and Base-Catalyzed Mechanism
• Amide Dehydration Mechanism by SOCl2, POCl3, and P2O5
• Amide Reduction Mechanism by LiAlH4
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