Nagata hydrocyanation

R = alkyl, aryl, 0-alkyl, O-aryl, (NR2) R = H, alkyl, aryl R = Me, Et, -Bu APCj = EtAICl2, MesAI, EtsAI, EtsAICI 

Reversible 1,4-addition using dialkylaluminum cyanide (S = solvent)  

Termite soldiers produce a large number of different chemical defense agents. Several of these molecules are unusual bioactive terpenoids such as the secotrinervitanes that have been isolated and their structure elucidated. In the laboratory of T. Kato, the total synthesis of (+)-3a-acetoxy-7,16-secotrinervita-7,11-dien-15P-ol was accomplished. The Nagata hydrocyanation was used to introduce a carbon at the P-position of a macrocyclic enone intermediate. The substrate was treated with excess diethylaluminum cyanide in dry toluene and the addition resulted in the formation of a 1 1 mixture of diastereomers, which could be readily separated by column chromatography. The cyano group was later converted to the corresponding methyl ester. 

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The second and ultimately most practical sequence involved the introduction of the C-4a angular methyl group via the Nagata hydrocyanation reaction on the enone (85) (Scheme 11). Robinson annelation between the enone (84) and... 

Nagata, W. Voshioka, M. "Hydrocyanation of Conjugated Carbonyl Compounds in Organic Reactions" Wiley New York, N.Y., 1977, 25, 255. 

W. Nagata, M. Yoshioka, Hydrocyanation of Conjugated Carbonyl Compounds, Org. React. 1977, 25, 255-476. 

The problem of the hydrocyanation of conjugated carbonyl compounds has been reviewed in detail by Nagata and Yoshioka [281. The reactions proceed smootltly and base or acid catalysts are sometime useful with HCN. Cyanides (KCN. NaCN. etc.) arc recommended reagents in some cases, particularly in nonaqueous Solvents (28], and even cyanohydrins (e.g., acetone cyanohydrin) have been used as cyanation reagents. 

Hydrocyaaation. Nagata ei have published in detail their results on hydro-cyanation with diethylaluminum cyanide (method B) and with a trialkylaluminum and hydrogen cyanide (R,A1-HCN, method A). The main difference between the two methods is that method A hydrocyanation is irreversible and thus controlled kinetically, whereas method B is reversible and therefore can be controlled both kinetically and thermodynamically that is, the product is kinetically controlled in the early stages. 

Nagata, W., Yoshioka, M., Hirai, S. Angular substituted poiycyciic compounds. IX. A new hydrocyanation method. Tetrahedron Lett. 1962, 461 66. 

Nagata, W., Yoshioka, M. Hydrocyanation and its application to steroid syntheses. Proc. Int. Congr. Horm. Steroids, 2nd 1967, 327-335. Nagata, W., Okumura, T., Yoshioka, M. Hydrocyanation. VIII. Conjugate hydrocyanation of steroidal a,P-unsaturated carboxylic acid derivatives. J, Chem. Soc. C. 1970, 2347-2355. 

Hydrocyanation of Conjugated Carbonyl Compounds Wataru Nagata and Mitsuru Yoshioka... 

Cyanation of carbon-carbon multiple bonds can be regarded as an area of increasing importance and one in which metal-catalysed methods predominate. The well known Nagata conditions for olefin hydrocyanation were employed in the conversion of (54) to (55) during the early stages of a ( )-cycloeudesmol (56) synthesis. 

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