Ketones, 2-cyano cyclic

It was proposed that the pyridine nitrogen is protonated by the strongest acid sites on SA, while the remaining acid sites and unprotonated pyridine nitrogen act as a highly active acid and base, respectively (Scheme 6.20). This mechanism has been extended to cyano-ethoxycarbonylation [123, 124], 1,4-addition reactions of nitroalkanes and thiols to electron-deficient alkenes such as methyl vinyl ketone and cyclic a,fl-unsaturated ketones [125], Diels-Alder [126], and nitro-aldol reactions [97, 123]. 

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. 

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]. 

On the basis of this pioneering work, Rubenbauer and Bach developed a Bi(OTf)3-catalyzed highly diastereoselective benzylation of silyl enol ethers [65]. Various cyclic and acyclic silyl enol ethers were amenable to this protocol (Scheme 24). Various a-substituted benzyl acetates were tested with terf-butyl-substituted silyl enol ether 31a, and the use of only 1 mol% of Bi(OTf)3 was enough to obtain the desired benzylated ketones 32 in high yields and with excellent diastereoselectivities (up to 95 5). Whereas a-nitro- (30a), ot-cyano- (30b) and a-methylester-substituted (30d) benzyl acetates gave the anti diastereoisomer as the major product, the phosphonate-substituted benzyl acetate (30c) exclusively resulted in the syn isomer (Scheme 24). 

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... 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organ onitriles arises both from die reactivity of the C=N bond, and from die ability of the cyano substituent to activate adjacent bonds, especially C-H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxylic acids and esters, aldehydes, ketones, large-ring cyclic ketones, imines,... 

Enynes (77) can react with arylboronic acids in the presence of a catalytic amount of a rhodium(I) complex under mild conditions to give (Z)-l-(l-arylethyl- (g) idene)-2-vinylcyclopentanes (78).100 In analogy, the rhodium-catalysed cyclization of the cyano-substituted alkynes (79) with arylboronic acids has been reported to produce the cyclic ketone (80) as the first example of a nucleophilic addition of an Rh(I) species to a cyano group.101... 

Moreover, it was demonstrated that not only alkenes may serve as radical acceptors in radical cyclizations. Substrates with polar carbonyl and cyano groups afforded cyclic alcohols and ketones in 30-87% yield [146, 159]. 

Dithiolylium cations (see Chapter 4.31) unsubstituted on the 3- or 5-position react with active methylene compounds, in most cases with simultaneous oxidation, as shown in equation (15). This reaction has been performed with a large variety of ketones, acylic or cyclic, /3-diketones, /3-keto dithioesters and a-cyano ketones (71AHC(13)161,pp. 174,188, 80AHC(27)151,p. 183). 

The total synthesis of galbulimima alkaloid GB 13 was accomplished by L.N. Mander and co-workers. The Birch reduction of a complex intermediate was necessary in order to prepare a cyclic a,p-unsaturated ketone. The treatment of the substrate with lithium metal in liquid ammonia first resulted in a quantitative reductive decyanation of the C6a cyano group. The addition of excess ethanol to the reaction mixture reduced the aromatic ring to the corresponding enol ether that was hydrolyzed in a subsequent step to afford the unsaturated ketone. 

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