A Cyanoketones

The synthesis of this series involved the reaction of disubstituted or benzo fused 6-keto(formyl)-2-cyclohexenones with hydroxylamine (Scheme 176), Base degradation gave a-cyanoketones which can be further degraded to diacids (67AHC(8)277, 80IJC(B)406). 

Cyclic a-cyanoketones, when treated with hydroxylamine, yielded 3-amino-4,5,6,7-tetrahydro-2,1-benzisoxazole. This compound could also be obtained by sodium or potassium cyanide interaction with chlorocyclohexanone oxime (Scheme 187) (67AHC(8)277, 66Bail25>. 

Ketoesters, synthesis of 608, 615 Ketones - see also a-Cyanoketones, Hydroxyketones, Sulphinylketones synthesis of 811-814 y-Ketonitriles, synthesis of 322 /3-Ketosulphones... 

Scheme 6.129 Products prepared from the 121- and 124-catalyzed stereoselective Michael additions of a-chloroacrylonitrile and acrylonitrile to a variety to cyclic a-cyanoketones and acyclic a-substituted cyanoesters.

The first manufacturing route of the GEM side-chain relied on a-cyanoketone 125 however, the number of chemical steps from 125 to the final side-chain was reduced by one step (Noh et ah, 2004a). The sequence began with a selective hydrogenation with Raney nickel followed by double bond migration to enamine 131 (Scheme 4.25). The amino functionality of 131 was then monoprotected, and the double bond was reduced under hydrogenation conditions to afford pyrrolidine-3-one 133. Treatment of 133 with methoxylamine yielded methoxyoxime 129. Deprotection of the carbamate functionality was achieved with methanesulfonic acid to afford the C7-side-chain as the bis-methansulfonate salt. 

Exercise 24-11 Nitriles of the type RCH2CN undergo a self-addition reaction analogous to the aldol addition in the presence of strong bases such as lithium amide. Hydrolysis of the initial reaction product with dilute acid yields a cyanoketone, O CN... 

The organoindium reagent, prepared from indium metal and bromoacetonitrile, reacts with carbonyl compounds in the presence of chlorotrimethylsilane to give /3-hydroxy nitriles (Scheme 93),336 337 Similarly, indium-mediated coupling of bromoacetonitrile or 2-bromopropionitrile with a variety of aromatic acyl cyanides affords the corresponding aromatic a-cyanoketones in moderate to good yields under mild and neutral conditions (Equation (86)).338 Carbonyl compounds are efficiently transformed into 2,2-dichloro-3-hydroxynitriles by the action of trichloroaceto-nitrile and indium(i) bromide (Scheme 94).339 Bromocyanomethylation of carbonyl compounds is also achieved by the reaction of dibromoacetonitrile and indium(i) bromide.340... 

Conversion of the a-cyanoketone 414 to the tosylate 415, and subsequent cyclization using diethyl aminomalonate in the presence of ethoxide, provided the aminopyrrole 416 (Scheme 51). This approach was used for the preparation of a set of related derivatives in moderate yields <2000JOC2603>. 

The key intermediate for synthesis of the diastereoisomers 59 (R = Me) is the tetrahydropyridine 61 obtained by hydrogenation of a cyanoketone a further reduction step using a Pd catalyst gave a separable mixture of isomers 62, which were converted to N-substituted phenolic analogs by standard methods/81 The configurations a c-2-Me, r-3-Ar and /3 f-2-Me, r-3-Ar were... 

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... 

Deng also successfully applied the C6 —OH catalysts 64a,b to the asymmetric tandem conjugate addition-protonation reactions of the a-cyanoketones or... 

Acylation with phosgene occurs under very mild conditions to give enamino-acyl chlorides which undergo solvolysis to esters or amides (Scheme 93). Cyanogen chloride reacts with enamines to give cyanoenamines and a-cyanoketones on hydrolysis. Cyanogen bromide and iodide react differently a 1 1 adduct is formed which, on hydrolysis, leads to 2-haloketone (Scheme 94). 

Enolates are generated from a-cyanoketones. Such species undergo regioselective alkylation. ... 

Cyanoenamines have been prepared from a-cyanoketones and... 

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