Cyano ketones, from nitriles

The second cycloaddition substrate took to form of 91 (Scheme 1.9b), incorporating a vinyl sulfone dipolarophile. Beginning with cyano ketone 84, which was readily prepared from 1,5-dicyanopentane via a previously reported three-step sequence [45], condensation with thiophenol produced vinyl sulfide 85 in 84 % yield. Vinyl sulfide 85 underwent bromination in acetonitrile to afford bromo-vinyl sulfide 86 (86 %), which was then treated with isopropylmagnesium chloride [46] to effect metal-halogen exchange affording an intermediate vinyl magnesium bromide species. Subsequent alkylation with Mel in the presence of catalytic CuCN provided the alkylated vinyl sulfide 87 in 93 % yield. The nitrile within vinyl... 

Ketones from / -ketocarboxylic acid esters s. 13, 131 nitriles from a-cyano-carboxylic acid esters s. Am. Soc. 81, 5397 (1959)... 

Szantay and coworkers were able to improve the efficiency of the yohimbine synthetic sequence by utilizing the nitrile 265, derived from the ketone 260 (Scheme 3.42) (48,49). Dieckmann cyclization of 265 afforded regioselec-tively the a-cyano ketone 267 which on treatment with sodium borohydride provided the epimeric j5-cyano alcohols 268, 269, and 270. Nitriles 268 and 269 were then independently converted to yohimbine (4) and ) -yohimbine (5), respectively. 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

Most solid-phase syntheses of pyrazoles are based on the cyclocondensation of hydrazines with suitable 1,3-dielectrophiles. The reported examples include the reaction of hydrazines with support-bound a,(3-unsaturated ketones, 1,3-diketones, 3-keto esters, a-(cyano)carbonyl compounds, and a, 3-unsaturated nitriles (Table 15.19). Pyrazoles have also been prepared from polystyrene-bound 3-(hydrazino)esters, which are generated by the addition of ester enolates to hydrazones (Entry 7, Table 15.19 see also Section 10.3). Benzopyrazoles can be prepared from support-bound hydra-zones using the reaction sequence outlined in Figure 15.11. Oxidation of a polystyrene-bound benzophenone hydrazone yields an a-(acyloxy)azo compound. Upon treatment with a Lewis acid, this intermediate is converted into a 1,2-diazaallyl cation,... 

The indium hydride compound, generated in situ from sodium borohydride and a catalytic amount of indium(m) chloride, selectively reduces carbon-carbon double bonds in conjugated alkenes such as a,a-dicyano olefins, a,/3-unsaturated nitriles, cyano esters, cyanophosphonates, diesters, and ketones (Scheme 107).372 This combined reagent system in acetonitrile reduces exclusively the a,/3-carbon-carbon double bond in a,/3,7,<5-unsaturated diaryl ketones, dicarboxylic esters, cyano esters, and dicyano compounds (Scheme 108).373... 

The factors affecting the competition between transesterification and olefination in reactions of phosphonoalkylcarboxylates (111) with aldehydes and potassium carbonate in alcohols under heterogeneous conditions have been investigated.57 The reaction of the carbanion of I-cyano-1-fluoromethanephosphonate, prepared in situ from diethyl cyanomethane-phosphonate (112) and N-fluorobis(trifluoromethanesulphonyl)imide, with aldehydes and ketones provides a synthesis of a-fluoro-a,3-unsaturated nitriles (113) in moderate yield (Scheme 8).5 Wadsworth-Emmons... 

Treatment of the 7-oxo-32-nitrile (607) with potassium t-butoxide eliminated the cyano-group to give the unsaturated ketone (608) Wolff-Kishner reduction then removed the 7-oxo-function but gave a mixture of isomeric olefinic derivatives. When the 7,ll-dioxo-32-nitrile was used, the elimination product was the 14 -8-ene-7.11-dione (609), the ds-junction of rings c and d being preferred. The l4a-isomer of (609) was synthesized independently from cholesterol, and shown to epimerize readily at C-14. ... 

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