Of cyano ketones

Macrocyclic 2-pyrones (113) and (114) are prepared from enamine (115) and ketene (75HCA2409). Reduction of cyano ketone (116) with LAH affords an amino ketone which spontaneously cyclizes to generate a tetrahydropyridine (117) dehydrogenation by palladium on charcoal produces the aromatized phane (118) (71TL671). 

In a related study, the enolate of cyano ketone 198 was O-allylated and subjected to Claisen rearrangement (Scheme 31). The allyl group migrated only to the exo face... 

The formation of cyano ketones by this method is illustrated by the conversion of phenacyl halides to the corresponding nitriles. Ring closure to cyclopropane derivatives is a side reaction which has been encountered with y-halo ketones. Benzalacetophenone dibromide is converted by alcoholic potassium cyanide to the fi-cyaao ketone, the a-halogen atom being reduced. Several a-chloro ketones have been found to yield a-cyano epoxides. ... 

The above is an example of the Guareschi reaction. It is applicable to most dialkyl ketones and to alicyclic ketones (e.g., cyclohexanone, cyc/opentanone, etc.). The condensation product (I) is probably formed by a simple Knoe-venagel reaction of the ketone and ethyl cyanoacetate to yield ethyl a-cyano-pp dimethylacrylate (CH3)2C=C(CN)COOCjHj, followed by a Michael ad tion of a second molecule of ethyl cyanoacetate finally, the carbethoxyl groups are converted to the cyclic imide structure by the action of ammonia. 

A convenient preparation of a-cyano ketones via ketone enolates has been recently described149. The yields are consistently high when using p-tolylsulfonyl cyanide (264) in THF at — 78 °C. Thus, the addition of the lithium enolates of 4-t-butylcyclohexanone to 2 equivalents of264 at — 78 °C gives a-cyano ketone 265 in 80% yield (equation 158). Use of... 

Addition of cyano carbonyl compounds to aldehydes or ketones... 

The photodecarbonylation of a series of dibenzyl ketones was studied by Robbins and Eastman/63 The results of this study are presented in Table 4.5. The data in Table 4.5 indicate that the presence of a p-methyl or a p-methoxy group has little effect on the quantum yield for this reaction. p-Cyano groups, on the other hand, essentially totally eliminated the decarbonylation. Since the reaction could also be quenched (inefficiently) by benzonitrile or biphenyl, it was concluded that the decarbonylation occurs from a short-lived triplet state. The effect of the p-cyano groups then could result from internal triplet quenching. 

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... 

A one-pot preparation of pyrrolo[l,2-a]quinazoline libraries with three points of diversification by condensation of a-cyano-ketones and 2-hydrazino-benzoic acids has been developed by Hulme and coworkers (Scheme 6.252) [439]. The protocol simply involved heating a solution of equimolar amounts of the two building blocks in acetic acid at 150 °C for 5 min. In many cases, the final products precipitated directly from the reaction mixture. In such cases, simple washing with diethyl ether yielded the products in >95% purity. A 63-member library was prepared by employing seven a-cyano-ketones and nine 2-hydrazino-benzoic acids. 

A facile synthesis of 5-substituted 3-aminopyrrole-2-carboxylates has been developed wherein condensation of diethyl aminomalonate with a-cyano ketones 46 was facilitated by prior formation of the p-toluenesulfonyl enol ether 47 <00JOC2603>. Addition of the amine component is followed by cyclization and decarboxylation to afford the pyrroles 48. 

The reaction of 2,3-allenenitrile 605 with EtOH in the presence of NaOH afforded the /3-ethoxy-/8,y-unsaturated enenitrile 606, which was isomerized and hydrated to afford a mixture of /8-ethoxy-a,/8-unsaturated enenitrile, enamide carboxylic acid or a-cyano ketone [271]. 

Alkyl-3-cyano-4-hydroxythiophenes 625 were obtained from the reaction of 2,3-allenenitriles 610 with mercaptoacetates 622. The presence of the ester group leads to the formation of cyclic ketones 623, which undergo migration of the C=C and C=0 bonds to form thiophenes 625 [276]. 

Electroreduction of y- and 5-cyano ketones in isoPrOH with a Sn cathode gave a-hydroxyketones with good diastereo-selectivities as cyclization products. The reaction has been used as a key step for the synthesis of, for example, guaiazulene, triquinanes, and dihydrojasmone. Similarly, the corresponding intermolecular couplings were realized [315]. 

For a related example of a reductive alkylation from an a-cyano ketone, see Liu, H.J. Zhu, J.L Shia, K. S. Tetrahedron Lett. 1998, 39, 4183 and pertinent references therein. 

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