ORGANIC
LETTERS
2
007
Vol. 9, No. 17
429-3432
Metal-Free One-Pot Oxidative Amination
of Aldehydes to Amides
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Kekeli Ekoue-Kovi and Christian Wolf*
Department of Chemistry, Georgetown UniVersity, Washington, DC 20057
Received June 20, 2007
ABSTRACT
Metal-free oxidative amination of aromatic aldehydes in the presence of TBHP provides convenient access to amides in 85−99% under mild
reaction conditions within 5 h. This method avoids free carboxylic acid intermediates and integrates aldehyde oxidation and amide bond
formation, which are usually accomplished separately, into a single operation. Proline-derived amides can be prepared in excellent yields
without noticeable racemization.
The formation of amide bonds is one of the most important
organic reactions due to the abundance of this functional
group in natural products, polymers, and pharmaceuticals.
Routine amide synthesis from amines and free carboxylic
acids generally relies on the use of coupling agents such as
Schmidt reaction that forms an amide from a ketone and an
alkyl azide or a hydrazoic acid analogue, for example,
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trimethylsilylazide. Several procedures exploiting hydrative
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amidation of alkynes, transfer of a carbamoyl ligand from
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nickel to alkyl halides, and transition metal-catalyzed
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carbodiimides and 1-hydroxybenzotriazoles. Alternatively,
aminocarbonylation of aryl halides, alkenes, and alkynes
have been reported.
amides are often prepared from activated carboxylic acid
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derivatives. Few methods that utilize other starting materials
Nakagawa and co-workers discovered that aromatic alde-
hydes can be directly converted to amides in the presence
of ammonia and stoichiometric amounts of nickel peroxide.10
An important advantage of this approach is that C-N bond
formation and oxidation are integrated into a single operation
while the generation of a free carboxylic acid intermediate,
have been developed. Among the most prominent examples
are variations of the Staudinger reaction by using thioacids
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or thioesters in the presence of azides, and the acid-promoted
(
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(
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0.1021/ol7014626 CCC: $37.00
© 2007 American Chemical Society
Published on Web 07/27/2007