Nagata Hydrocyanation: Synthesis of β-Cyanoketones

Key words

hydrocyanation - triethylaluminium - steroids

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.

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.

Publication History

Article published online:
18 May 2021