Cyano-ketones., displacement

Active methylene or methine compounds, to which two EWGs such as carbonyl, alko.xycarbonyl, formyl, cyano, nitro, and sulfonyl groups are attached, react with butadiene smoothly and their acidic hydrogens are displaced with the 2,7-octadienyl group to give mono- and disubstituted compounds[59]. 3-Substituted 1,7-octadienes are obtained as minor products. The reaction is earned out with a /3-keto ester, /9-diketone, malonate, Q-formyl ketones, a-cyano and Q-nitro esters, cya noacetamide, and phenylsulfonylacetate. Di(octadienyl)malonate (61) obtained by this reaction is converted into an... 

Subsequent reduction of the prochiral ketone with diborane in THF and chlorination of the resulting secondary alcohol 9 provided a reactive benzylic chloride that underwent subsequent nucleophilic displacement with 4-trifluoromethylphenoxide to give 10. Von Braun degradation of the V,V-dimethyl amine in 10, via the V-cyano intermediate 11, gave racemic fluoxetine (4). 

Hayashi and his co-workers investigated the reactions of 2-substituted quinoxaline 4-oxides with ketones.210-212 2-Phenylquinoxaline 4-oxide (193) yields 2-phenyl-3-phenacylquinoxaline 4-oxide (203) with acetophenone and sodamide. However, 2-cyanoquinoxaline 4-oxide under these conditions yields cu-(3,4-dihydro-3-oxo-2-quinoxalinyl)aceto-phenone (204) by displacement of the cyano group by the ketone carbanion and rearrangement of the N-oxide.212... 

The condensation equilibrium is displaced to the right by removing the unsaturated cyano ester as it is formed by the addition of hydrogen cyanide The effect is analogous to the single-step formation and hydrogenation of a,/S-unsaturated cyanoacetic esters (method 394). The yields are good with most aliphatic ketones and aldehydes (49 75%), but poor results are obtained with aromatic carbonyl compounds and diisopropyl ketone. 

The cyano group in position 4 of quinazolines behaves like a halogen towards nucleophilic reagents and can be displaced by a hydroxide anion, alkoxides, amines, hydrazines, and various carbon nucleophiles, o.g. ketones, a-keto esters, dialkyl malonates, nitroalkanes, Gri-gnard reagents, and enamines, to give 4-substituted quinazolines 1. The cyano group of quin-azoline-2-carbonitriles is less reactive for nucleophilic substitution but its displacement has not been intensively studied. Alkaline or acid hydrolysis of quinazoline-4-carbonitriles affords quinazolin-4(3// )-oncs. ... 

Displacement of a cyano group in a-cyanoketones is possible. Treatment of the a-cyanoketone with Sml2 followed by addition of an excess of allyl bromide gave the a-allyl ketone derivative. a-Cyano amines react with allyl bromide and then zinc metal to give homoallylic amines after treatment with dilute acetic acid in... 

---