Nitriles, decyanation

See also Hydrogenolysis Ring opening) of alcohols, 97,113-114, 202-203, 277 of haloalkanes. See Reduction of ketone derivs., 109, 114-115, 155-156 of nitriles (decyanation), 280 of peroxides, 276-277... 

The reaction is an important step in a method for the oxidative decyanation of nitriles containing an a hydrogen. The nitrile is first converted to the a-hydro-peroxy nitrile by treatment with base at — 78°C followed by O2. The hydroperoxy nitrile is then reduced to the cyanohydrin, which is cleaved (the reverse of 16-51) to the corresponding ketone. The method is not successful for the preparation of aldehydes (R =H). 

Though the syn-l,3-diol relationship is ultimately established in the reductive decyanation vide infra), the alkylation is itself highly selective. Selectivities are typically greater than 100 1 in favor of the axial nitrile. This selectivity can be rationalized by a chair-like intermediate 15 (Scheme 3) for which equatorial alkylation is highly favored on steric grounds. Approach of the electrophile from an axial trajectory leads to a syu-pentane-like interaction. 

Aliphatic and aromatic nitriles 19 were decyanated with lithium and a catalytic amount (5%) of DTBB in the presence of different carbonyl compounds as electrophiles... 

Nitriles (Table 11)" The oxidative decyanation of nitriles can be efficient and experimentally convenient. In particular, good yields of ketones are obtained from secondary nitriles the reaction is most efficient with the more acidic compounds. Primary nitriles are converted into the corresponding acids, probably via the aldehydes. In the presence of acetic anhydride the reaction stops at the aldehyde diacetate stage. 

Bisdecarboxylation of malonic acids 9-15 Oxidative decyanation of nitriles 9-16 Oxidation of activated or unactivated methylene groups 9-20 Oxidation of secondary alkyl halides and tosylates... 

Oxidative decyanation (6, 430). This reaction can be conducted under phase-transfer conditions with 50% NaOH in DMSO with catalytic amounts of benzyl-triethylammonium chloride (TEBA). The method fails with purely aliphatic nitriles. The highest yields (85-90%) are obtained with aromatic secondary nitriles. 

Reductive decyanation. K-A1203 reduces alkyl nitriles in hexane at 25° in 70-90% yield. The reaction is rapid for secondary and tertiary nitriles but requires about 1 hour for primary nitriles. Potassium alone is less efficient. The reaction was useful in a synthesis of the sex pheromone 1. 

Marshall has applied the reductive decyanation-elimination of /3, -y-epoxy-nitriles to allylic alcohols212 in a synthesis of cis- and trans-pulegol (Scheme 11) which is converted into ( )-pulegone.213... 

Oxidative decyanation (6,430). Two laboratories have reported regiospedfic syntheses of anthracyclines based on conjugate addition of the enolate of a nitrile to an O, /3-unsaturated ester. For the synthesis of daunomycinone (7), the reaction involved addition of the enolate of 1 to 2 to give 3 in 94% yield. The ester group of 3 was hydrolyzed and the resulting acid was cyclized to 4. Oxygenation of the enolate of 4 by the procedure of Watt results in the quinone 5, which is oxidatively demethylated deketalization of the product led to 6, which had been converted previously into 7. 

Oecyanation. Aliphatic nitriles undergo reductive decyanation in good yield when treated with potassium in HMFF and ether. If the nitrile is tertiary, a protic cosolvcnt (alcohol) is not necessary. Yields are in the range 60-90%. 

Decyanation. Alkyl nitriles can be reductivciy decyanated to hydrocarbons by treatment with iron(lll) acetylacctonatc and sodium sand under argon in dry benzene... 

In conclusion, nitriles may be reduced electrochemically or with dissolving metal to produce amines. Nonetheless, such reactions must be used with caution. In addition to competitive decyanation, aldehyde or 2,4,6-trialkyIhexahydro-l,3,5-triazine formation and reductive dimerization are waiting to overwhelm the unwary. 

Treatment with methanolic ammonia followed by removal of the trifluoroacetyl group resulted in spontaneous cyclization to give the enone (15) without contamination with its diastereomer, presumably owing to the unfavourable steric effects between the C-6 methylene and the amide function in the latter. The amide (15) was transformed into the corresponding nitrile which upon borohydride reduction followed by reductive decyanation, a reaction which appears to have wide applicability, gave (+ )-epimartitine (16). Epimerization of (16) into (-F)-maritine (17) of optical rotation identical with that reported for the natural product was accomplished by treatment with mild acid,... 

The partial synthesis of festuclavine (58) by reduction of agroclavine is unsatisfactory, since it proceeds non-stereospecifically. A much improved partial synthesis has been reported, which simply involves the reductive decyanization of the readily available nitrile (59) by means of potassium in HMPA alternatively, the unsaturated nitrile (59, A ) can be used as starting material. In both reactions the yield is stated to be almost quantitative. 

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