Cinnamic nitrile

Enamine formation occurs by the thermolysis of diazo compounds (Scheme 150)67 109,278 284 288,304 332 453 454 via a carbene-like intermediate.284 332 When R1 = Ph, it enters into competition with hydrogen migration,284,332 and the electrophilic character of the carbene enhances the migration of the dimethylaminophenyl more than the phenyl.332 When triazoline synthesis is carried out at temperatures higher than that at which thermolysis of diazo compounds occurs, enamines are obtained exclusively, as in the addition of phenyl azide to cinnamic nitriles and ketones, with phenyl migration dominating in the nitrile.284 Enamine is also formed quantitatively in the reaction of ethyl diazoacetate with benzylideneaniline at 110°C.455... 

An example of this class of condensation with elimination of water is the formation of a-phenyl-cinnamic nitrile, from benzaldehyde and benzyl nitrile ... 

In 1989, Isayama and Mukaiyama reported a related Co-catalyzed coupling reaction that employs a,b-unsaturated nitriles, amides, and esters with PhSiLb as a hydrogen source [9]. Cobalt-bis(diketonato) complex, Co(II)(dpm)2 [dpm = bis(dipivaloylmethanato)] (5mol%), exhibited high catalytic activity at 20 °C in the coupling of excess acrylonitrile and ben-zaldehyde to provide b-hydroxy nitrile 4 in 93% yield (syn anti = 50 50) (Scheme 5). N,N-Dimethylacrylamide and methyl cinnamate both reacted... 

Formation of mixtures of the above type, which is common with internal olefins, do not occur with many functionalized alkenes. Thus, tertiary cinnamates and cinnamides undergo cycloadditions with benzonitrile oxides to give the 5-Ph and 4-Ph regioisomers in a 25-30 75-70 ratio. This result is in contrast to that obtained when methyl cinnamate was used as the dipolarophile (177). 1,3-Dipolar cycloaddition of nitrile oxides to ethyl o -hydroxycinnamate proceeds regiose-lectively to afford the corresponding ethyl fra s-3-aryl-4,5-dihydro-5-(2-hydro-xyphenyl)-4-isoxazolecarboxylates 36 (178). Reaction of 4-[( )-(2-ethoxycarbo-nylvinyl)] coumarin with acetonitrile oxide gives 37 (R = Me) and 38 in 73% and 3% yields, respectively, while reaction of the same dipolarophile with 4-methoxy-benzonitrile oxide affords only 37 (R = 4-MeOCr>H4) (85%) (179). 

Baker s yeast catalyzed the regioselective cycloaddition of stable aromatic nitrile oxides ArCNO [Ar = 2,6-C12C6H3, 2,4,6-Me3C6H2, 2,4,6-(MeO)3C6H2] to ethyl cinnamate, ethyl 3-(p-tolyl)acrylate, and tert-butyl cinnamates (218). Reactions of dichloro- and trimethoxybenzonitrile oxides with all three esters proceeded regio- and stereoselectively to form exclusively alkyl tran.v -3,5-diary 1 -... 

Nitrile groups in the substrate may also cause problems. Minnaard, Feringa and de Vries reported the enantioselective hydrogenation of a range of substituted 2-acetamido-cinnamates at 5 bar pressure using Rh/MonoPhos. Whereas most substrates could be hydrogenated with turnover frequencies (TOFs) of between 200 IT1 and 600 h-1, the 4-cyano-substituted substrate was hydrogenated very slowly at this pressure with a TOF of only 4 h 1 [40]. 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

The 1,3-dipolar cycloadditions of benzonitrile oxides with tertiary cinnamides yield the 5-phenyl and 4-phenyl regioisomers in a reversal of the expected regioselectiv-ities shown with methyl cinnamate. Calculations have shown that steric factors are responsible for this reversal of regioselectivity." The 1,3-dipolar cycloadditions of benzonitrile oxide with electron-rich and electron-poor dipolarophiles are accelerated by sodium dodecyl sulfate micelles. Phenyl nitrile ylides react with electron-deficient alkenes to produce five-membered -heterocycles where measured rate constants are between 4 x 10 and 7 x 10 lmoP ... 

On the other hand, reactions of nitrile oxides with 1,2-disubstituted olefins are slower and regioselectivity usually was not so high. For example, benzonitrile oxides, obtained from the corresponding chlorooximes 167, undergo 1,3-dipolar cycloaddition reaction with methyl cinnamate to produce the 5-phenyl 168 and 4-phenyl 169 regioisomers in approximately an 80 20 ratio °. However, use of A,iV-diethylcinnamamide as the dipolarophile... 

In a similar way indole isomerizes to benzyl cyanide, pyridine to cyano-butadiene and quinoline to cinnamic acid nitrile. Aniline and o-phenylenedi-amine also form large amounts of unsaturated nitriles in glow discharges. 

Pr, Bu, Ph etc) to benzonitrile oxide are oxidized to trans-4-hydroxy-2-isoxazolines 10 by t-butyl hydroperoxide (94TL7493). A reversal of regiochemistry was observed in the reaction of aromatic nitrile oxides with derivatives of cinnamic acid the methyl ester gave a mixture of the esters 11 and 12 (R = OMe), in which the former predominated, while in the case of M,N-diethylcinnamide the amide 12 (R = NEt2) was the main product (94TL6473). 

This method is highly selective for unsaturated ketones and aldehydes, whereas reduction of a,p-un-saturated carboxylic acid derivatives, such as esters, amides and nitriles, is very sluggish. Thus, benz-ylideneacetone was selectively and cleanly reduced in the presence of methyl cinnamate, cinnamonitrile or cinnamamide. ... 

A review has highlighted the photocycloaddition reactions of alkenes with aromatic esters and nitriles. Cycloadditions occur by a (3+2)-mode and provides a path to medium size ring systems. When the cinnamic acid derivative (9) is irradiated at 359 nm in ethanol with added Ti02 the product (10) is formed in 30% yield. Analogous products are formed from other straight chain alcohols such as (11) from propan-l-ol. Benzonitrile can be photochemically hydrated in the presence of oxophosphorus porphyrins. " ... 

The other procedure10 illustrates a general method for conversion of carboxylic acids into the corresponding nitriles. Treatment of cinnamic acid (4) with chlorosulfonyl isocyanate gives the carboxylic acid amide N-sulfonyl chloride (5). As above, treatment of (5) with DMF gives cinnamonitrile (6) in 78-87% yield. 

The sodium dianions obtained from acids, treated by NaNH2 in liquid ammonia are easily alkylated (refs. 28-30). These dianions have also been used for Michael addition with benzalacetophenone or ethyl cinnamate. A similar Michael addition (ref. 31) is also observed with the enolate of ethyl phenylacetate (Fig. 4). Nitriles can also be deprotonated with NaNH2 in liquid ammonia. The resulting anion was able to give aldol reaction followed by dehydration (ref. 32) or an alkylation reaction (ref. 33). 

D Auria and Racioppi have reported that the arylacrylonitriles (11) undergo facile (2+2)-cycloaddition when subjected to benzophenone-sensitized irradiation in acetonitrile solution. The products obtained from this treatment and the yields obtained are shown under the appropriate structures in Scheme 3. Again a mixture of addition types is encountered in line with results obtained from the cycloaddition reactions with the cinnamic acids. Dimerization of the nitrile (12) was also studied and yielded the two adducts (13) and (14). Irradiation of 3-(estran-16-yl)acrylates and 2-(estran-16-yl)vinyl ketones brings about the formation of dimers and also isomerization of the unsaturated side chains. ... 

If nitrile imides are generated in the presence of a nucleophilic olefin, the corresponding 1,3-cycloaddition products are isolated, usually in good yield (S3,60-70j example, from diphenylnitrile imide and methyl cinnam-ate a mixture of the isomeric pyrazolines LVI and LVII is obtained in 95 % yield ( ). 

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