Ketones, 2-cyano

The cyano ketone 89 is converted into the nitrile 90 by heating at 140 C with Pd(Ph3P)4[73,74]. The a-lcetophosphonate 91 is decarbonylated with PdMe2(PMePh2)2 complex to give the phosphonate 92[75]. 

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... 

Activated F (from KF and a crown ether) has been used as the base to cleave an a-cyano ketone. 

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]. 

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. 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

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). 

Cyclization of hydroxy acids 0-24 Cyclization of halo acids 0-89 Intramolecular coupling 2-43 Cleavage of cyclic a-cyano ketones 5-4 Internal addition of alcohols to a ke-tene function... 

Conjugate addition. In the presence of 1 equivalent of triethylaluminum, cyanotrimethylsilane undergoes conjugate addition to a,/ -enones in high yield. The products arc converted into /J-cyano ketones by acid hydrolysis. The addition is kinetically controlled in toluene at room temperature, but thermodynamically controlled in refluxing THF (equation I). 

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