Cyanoamidation reaction

An intramolecular cyanoamidation reaction was developed, furnishing enan-tioenriched oxindole derivatives, such as 85, in a catalytic asymmetric manner (Eq. (6.20)) [59]. 

An analogous hexahydropyrrolo [2,3- ] indole was also synthesized by a palladium-catalyzed enantioselective intramolecular cyanoamidation reaction of alkenyl cyanoformamides [18]. The nickel-catalyzed carbocyanation reactions of unsaturated carbon-carbon bonds were employed also in the synthesis of (-)-eptazocine [17], plaunotol [19], and pregabalin [20]. 

The scope of conditions of the ketone-nitrile reaction is very broad. For instance, the polyfluorinated ketones 156 and 158 react with nitriles in the presence of concentrated sulfuric acid99 and with cyanoamides 159 by reaction mixtures at room temperature in the absence of acid catalyst100,101 (equations 52 and 53). 

IJ-Thiazine derivatives. The cyanoamide (I)- condenses with an aromatic acid and PPE to form 5-carbamoyl-6-methyllhio-1.3-thiazine-4-oncs (2) in 27 90% yield. The reaction with aliphatic acids gives 5-cyano-6-methylthio-l-keto-l,3-thiazine-4-ones (3) in low yields. ... 

The ready reaction of conjugated azoalkenes with a molar excess of nitriles containing activated methylene groups (e.g. malononitrile, p-cyanoamides, p-phosphononitriles or remotely activated nitriles) has been examined. 

Another example of a microwave-activated three-component reaction is the synthesis of2-anilino-7-amino-l,2,4-triazolo[l,5-d][l,3,5]triazines42 from diaminotriazoles 43, cyanoamide, and triethyl orthoformate (13TL5537). 

A related type b cyanoamidation leading to 3-pyrrohn-2-ones was reported by the Takemoto group (Scheme 19 20060L2711). Treatment of the alkyne 116 with catalytic Pd(PPh3)4 in xylene gives an equal mixture of 3-pyrrolin-2-one 117 and alkyhdene lactam 118. The mechanism presumably involves a 5-cxo-trig oxidative addition of cyanide and the amide carbonyl across the alkyne isomerization of 118 under the reaction conditions then leads to the formation 117. 

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