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Hydrocyanation. VI. Application of the New Hydrocyanation Methods to Conjugate Hydrocyanation of +Unsaturated Ketones, Conjugated Dienones, and Conjugated Enamines and to Preparation of &-Cyanohydrins W. Nagata," M. Yoshioka, and M. Murakami Contribution f r o m the Shionogi Research Laboratory, Shionogi and Company, Limited, Fukushima-ku, Osaka, Japan. Received February 9, 1970 Abstract: The new hydrocyanation methods using a combination of hydrogen cyanide and an alkylaluminum (method A) and diethylaluminum cyanide (method k) have been applied successfully to conjugate hydrocyanation of the following a,P-unsaturated ketones to the corresponding &cyano ketones : mesityl oxide, cyclohexenone, bi-
and tricyclic enones, and steroidal enones. The methods were applied also to conjugate hydrocyanation of a steroidal 4,6-dien-3-oneto the 6a-cyano-4-en-3-one,a 1,4-dien-3-oneto the la- and 5P-cyano-3-ones,and 19-nortestosterone enamines to the 5-cyano-3-ones (after hydrolysis). Application to preparation of a-cyanohydrins from carbonyl compounds of low reactivity is described also.
T
wo new hydrocyanation methods have been developed in our laboratory: la method A uses a combination of hydrogen cyanide (HCN) and an alkylaluminum (AIRB) and method B employs diethylaluminum cyanide (EtzAICN). The most useful application of the new methods will be conjugate hydrocyanation of a,P-unsaturated ketones (for significance of the reaction, see ref la). The choice of the reagent and reaction conditions depends on structures of enones and affects the stereoselectivity in angular cyanation of polycyclic enones. In this paper, we report the conjugate hydrocyanation of various types of a,P-unsaturated ketones, the structure-reactivity relationship, preparation of starting enones, and stereochemical proof for hydrocyanation products. Also are reported conjugate hydrocyanation of conjugated dienones and enamines and preparation of a-cyanohydrins from carbonyl compounds of low reactivity. Results and Discussion Hydrocyanation of a,@-UnsaturatedKetones. Tables I and I1 list the results of hydrocyanation of a,@-unsaturated ketones having a bridgehead P-carbon atom (angular cyanation) in the octalin and hydrindene systems, respectively. Conjugate hydrocyanation of a,Punsaturated ketones having a nonbridgehead P-carbon atom (nonangular cyanation) is shown in Table 111. In these tables, there are listed for comparison the data of hydrocyanation by the earlier method using potassium cyanide and ammonium chlorideza (referred to as method C). Also, the data already published by us are included with indication of references3 to give a better (1) (a) W. Nagata, M. Yoshioka, and S . Hirai, J . Amer. Chem. Soc., 94, 4635 (1972); (b) W. Nagata, M. Yoshioka, and T. Terasawa, ibid., 94,4672 (1972); (c) W. Nagata, M. Yoshioka, and M. Murakami, ibid., 94, 4644 (1972); (d) W. Nagata, M. Yoshioka, T. Okumura, and M. Murakami, J . Chem. Soc. C, 2355 (1970). (2) (a) W. Nagata, S. Hirai, H. Itazaki, and K. Takeda, J . O r g . Chem., 26, 2413 (1961); (b) S. Hirai, Chem. Pharm. Bull., 9, 837 (1961). (3) (a) W. Nagata, I . Kikkawa, and M. Fujimoto, ibid., 11, 226 (1963); (b) W . Nagata, T. Sugasawa, M. Narisada, T. Wakabayashi, and Y. Hayase, J . Amer. Chem. Soc., 85, 2342 (1963); ibid., 89, 1483 (1967); (c) M. Narisada, Ph.D. Dissertation, Kyoto University, 1964; (d) W. Nagata, T. Terasawa, S. Hirai, and I
