Nitriles, reductive decyanation

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. 

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... 

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%. 

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. 

Decyanation.1 Alkyl nitriles can be reductively decyanated to hydrocarbons by treatment with iron(III) acetylacetonate and sodium sand under argon in dry benzene... 

Reduction of tertiary nitriles with lithium in ethylamine or sodium in ammonia often affords reductive decyanation products exclusively. Primary and secondary nitriles give both the expected amine and decyanation products [29, 30]. Doumaux [31] found that calcium in ammonia reduces primary, secondary, and tertiary nitriles to produce modest, synthetically useful amounts of the expected amines. Little decyanation occurs on the basis of the results obtained by use of dodecylcya-nide as the substrate. 

P,Y-unsaturated nitrile- before reductive decyanation with dissolving metals leads to allylic alcohols (Scheme 6.56)... 

Reduction decyanization. Certain biogenetic-type syntheses of some alkaloids from amino acids required elimination of the carboxyl group by conversion to the corresponding nitrile and reductive decyani/alion. Some -amino nitriles... 

Alternative routes to optically active tetrahydroisoquinolines employ reductive decyanation of chiral a-amino nitriles using sodium in liquid ammonia or NaBH4, or the reduction of imines or immonium salts in an asymmetric environment (see Sec. 1.2.2, below). 

The nitrile group of 4-cyanopyridine is replaced quantitatively by hydrogen when treated with titanium trichloride in aqueous acetic acid. Under the same conditions, 2-cyanopyridine undergoes reductive decyanation only in poor yield, and 3-cyanopyridine is inert." Highly dispersed potassium on neutral alumina, easily prepared by melting potassium over alumina in an inert atmosphere, effects reductive cleavage of the cyano-group of alkyl nitriles in hexane at room temperature (e.g. Scheme 2). Alternatively, activated tertiary or secondary... 

Reactions.— Nitriles can be reduced to aldehydes in aqueous media by photochemically generated hydrated electrons. The reduction of nitriles to amines by sodium borohydride is catalysed by Raney nickel. The transition metal promoted reductive decyanation of alkyl nitriles to homologous hydrocarbons with one less carbon atom is reported, and has been shown by van Tamelen to proceed by a different mechanism from that of a similar reduction by alkali metals in ammonia, where a process of stepwise two-electron transfer has been proposed. In the former reaction, where use is made of ferric acetylacetonate and sodium, the proton required for alkane production is derived exclusively from the acetylacetonate ligand, alkane being formed before a proton source is added this suggests a mechanism which involves initial co-ordination of the nitrile to iron, followed by reductive cleavage of the nitrile 1,2-carbon bond and proton transfer to this area, as pictured in Scheme 42. 

Several other reductive-elimination procedures to give olefins have been developed this year. Marshall and Bierenbaum have identified a reductive-decyanation technique to give tetrasubstituted olefins. Hence, alkylation of the readily available mixture of nitriles (25) leads to a mixture of the (j8,y)-double-bond isomers (26) which contains principally the E-isomer. Reduction of the mixture with sodium in liquid ammonia gives the isomerically pure olefin (27) in 92% overall yield (Scheme 15). Generally, the most highly substituted olefin is formed on reduction of the intermediate j8,y-unsaturated nitriles. 

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. 

The procedure developed for the decyanation of secondary nitriles has been extended to a,P-unsaturated nitriles. The reaction of a-unsubstitutcd a,p-unsaturatcd nitriles with LDA in THF/HMPA results in the abstraction of a y-hydrogen from a methylene site to afford a delocalized anion. Trapping this anion at the a-position by dimethylation ° ° followed by reduction-elimination with dissolving metals leads to tetrasubstituted alkenes (Scheme 6.56). ° Epoxidation of the... 

Scheme 4 Compound (45) prepared from a-santonin (41), on reduction afforded alcohol (46), which was converted to derivative (48) by standard organic reaction. Irradiation of (48) in benzene at room temperature followed by reflux in tetrahydrofuran and 2-propanol, produced 15-oxime derivative (49). Its conversion to nitrile (50) was achieved by treatmente with acetic anhydryde in pyridine. Dehydration of (50) followed by decyanation, yielded compound (52). Its acetonide derivative (53), was converted to compound (54), whose convertsion to rishitin (40), was achieved by heating with 0.5% PPA in ethanol...

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... 

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... 

Nitriles can be decyanated by transition metal-promoted reduction e.g. with Na and ferric acetoacetonate... 

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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