Nitriles oxidative decyanation

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). 

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. 

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. 

Oxidative decyanation. Selikson and Watt have converted secondary nitriles, for example (1), into ketones (4) by the following sequence. The anion (a) is generated with lithium diisopropylamide in THF at -78° and then oxygen is bubbled into the solution of (a). A lithium a-cyanohydroperoxide (b) is formed. Quenching with aqueous acid or acetyl chloride provides the isolable a-hydroperoxynitrile (2) or the corresponding acetate. Reduction of (2) leads... 

The nitriles obtained by reaction of HPhCN ion with heteroaryl halides can lead to the corresponding ketones in excellent yields (77%) by oxidative decyanation under phase-transfer conditions (PTCs) ... 

The conversion of gardnerine (1) to ochropine (39), a 2-acyl indole alkaloid isolated from the stem bark of Ochrosia poweri 175. was also carried out to establish structure 39 for the latter alkaloid. The reaction sequence is shown in Scheme 10. The nitrile function of 43 was converted to the carbomethoxy grouping by methanolysis. C-D ring cleavage with BrCN gave an epimeric mixture of C-3 hydroxyls which was then subjected to Cornforth oxidation to furnish 46. Decyanation of 46 and... 

Oxidative addition of C-CN bonds to nickel(0) can be followed by transmetalation with various main-group organometaUic reagents, and subsequent reductive elimination can result in the functionalization of C-CN bonds of nitriles (Scheme 5). As the simplest case, C-CN bonds can be transformed to C-H bonds via transmetalation with metal hydrides. Indeed, nickel-catalyzed hydrodecyanation of various aromatic and aliphatic nitriles proceeds with tetramethyldisUoxane as a hydride donor (Scheme 6) [44]. While a wide range of nitriles can be decyanated by this protocol, a relatively high amount of catalyst is required in this process, presumably because of the formation of catalyticaUy inactive (PCy3)2Ni(CN)2. The use of AlMe3 as a Lewis acid is effective in some cases to promote the C-CN bond activation. Under these reaction conditions, the relative reactivity order of different aryl electrophiles is estimated Ar-SMe>Ar-CN>Ar-OAr>Ar-OMe. 

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