Synfacts 2021; 17(06): 0669
DOI: 10.1055/s-0040-1720514
Metals in Synthesis

Nagata Hydrocyanation: Synthesis of β-Cyanoketones

Contributor(s):
Paul Knochel
,
Dimitrije Djukanovic
Nagata W, Yoshioka M, Hirai S. * Shionogi Research Laboratory, Osaka, Japan
Eine neue Hydrocyanierungs-Methode.

Tetrahedron Letters 1962;
11: 461-466
DOI: 10.1016/S0040-4039(00)70493-X.
 

Significance

In 1962 Nagata et al. reported a method for the hydrocyanation of demanding α,β-unsaturated ketones for the synthesis of β-cyano­ketones. This reaction employed a mixture of HCN and triethylaluminium in THF at room temperature as a new reagent that performed better than alkali cyanides (commonly used reagents at the time) in terms of yield and diastereoselectivity. This method has become known as Method A for hydrocya­nation of unsaturated ketones.


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Comment

Interesting mechanistic observations were made. It was suggested that polar solvent (THF) leads to a cyanotriethylaluminate, which was deemed to be the active cyanating reagent. Et2Al+ or a simple proton were proposed as Lewis acids. A slow and irreversible addition of cyanide ion gave II as an intermediate, which was quenched with HCN present in situ to give the expected product. Cyano­hydrine III was also observed. The reaction proceeded with gas evolution and formation of ­diethylaluminiumcyanide. This compound in inert solvent would become known as Method B and is the only commercially available reagent for Nagata hydrocyanation.


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Publication History

Publication Date:
18 May 2021 (online)

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