Nitrile ylides cyclizations

Alternatively, initial nucleophilic addition of 384 to 385 gave rise to 386, which underwent internal deprotonation to generate a nitrile ylide 387. Conversion of 387 to 390 could occur via either of two pathways. In the first case, the nitrile ylide cyclized to a 5-(dialkylamino)-2-substimted oxazole 388. Reaction of 388 with a second equivalent of 385 would then afford 390. The authors showed that there was no reaction of an analog of 388 with a second equivalent of 385, thereby discounting this proposal. These results led the authors to conclude that 387... 

Recently, Burger devised an improved method of carrying out mild, regiospecific cyclizations that involve an intermediate that acts as a synthon for a nitrile ylide of HCN [47 (equation 48). With this methodology, cycloadditions with activated alkenes, alkynes, and azo compounds were earned out [47] (equation 49). All such reported reactions were regiospecific and had the same orientational preference... 

The cyclizations of conjugated nitrile ylides forming substituted oxazoles and thiazoles were computed up to the MP4/6-31H-G level [OOJOC47]. Relative to 23, oxazole-4-carboxylic acid24 is stabilized by about -38.1 kcal/mol (Scheme 18). 

Ab initio and density functional calculations have been carried out on the mechanism of the 1,5-electrocyclization reactions of conjugated nitrile ylides (190). The results indicate that vinyl-conjugated systems (306) (X = CH2) cyclize via the classical electrocyclization pathway—a pericyclic, monorotatary process with a relatively early transition state in which there is substantial torsion of the vinyl group as well as pyramidalization at C(5). In contrast, systems with a heteroatom at the cyclization site 306 (X=NH, O) react via a pseudo-pericyclic process that is characterized by the in-plane attack of the lone pair of the heteroatom on the nitrile ylide. Such reactions have a lower activation energy. 

The nitrile ylides were generated from amides via the imidoyl chloride-base method and hence the reaction is, overall, the electrocyclic equivalent of a Bischler-Napieralski type of process. However, it has the advantage that it is effective for cyclization on to both electron-rich and electron-poor aromatic rings, unlike the Bischler-Napieralski reaction itself, which is an electrophihc process and only works well for electron-rich rings. 

On heating, 4-(isopropoxy)-2-phenyl-2-(trifluoromethyl)-5(2/i/)-oxazolone 65 underwent decarboxylation to the alkoxy-substituted nitrile ylide 66 that was trapped in a 1,3-dipolar cycloaddition by trifluoroacetophenone to generate 68." Other dipolarophiles reacted similarly. In the absence of a dipolarophile, cyclization of 66 yielded the isoindole 67 (Scheme 7.16 Table 7.11, Fig. 7.12). 

Substituent Directive Effects in the Cyclization of Nitrile Ylides 18... 

Diene systems of the type 158 have been studied by O Shea and Sharp [96JCS(Pl)515].The oxiranes 157 were subjected to flash vacuum pyrolysis at 625°C, to yield some new hetero-fused dihydrobenzoxepines 159. This 1,7-electrocyclization of carbonyl ylides 158, irrespective of whether the heterocyclic ring under attack is electron rich or electron poor, parallels the cyclization of the analogous nitrile ylides (Scheme 48). 

Cyclization of the nitrile ylide generated from amide (150a) via an imidoyl chloride led to an 18% yield of a fused tricyclic pyrrole (Scheme 46).77 Similarly, the nitrile ylide derived from (150b) cyclized in 6% yield. 

Intramolecular cyclization of nitrile ylides produces the cyclopropyl-fused quinolines (Equation 43) <1998J(P1)807>. 

Oxazoles of various substitution patterns are well known heterocycles for which a number of methods of synthesis have been reported.129 Acyl carbenes or functionally equivalent species have been found to undergo cyclization with nitriles to give oxazoles in high yield via nitrile ylide intermediates.130,131 This reaction can be induced to occur under thermal, photolytic, or catalytic conditions.129,132,133 Huisgen and coworkers were the first to study this process in some detail.132 Thermolysis (or copper catalysis) of a mixture of ethyl diazoacetate and benzonitrile resulted in the formation of oxazole 254. The isolation of this product is... 

Oxazoles are the products of the rearrangement of isoxazoles and of C-acylazirines, these processes being intimately related (81MI41800, 76ACR37I, 77H(6)143). Photolysis of 3-acylazirines gives nitrile ylides which cyclize thermally to oxazoles (equation 131). Flash vacuum pyrolysis of 3,5-diphenylisoxazole yields as major products 2,5-diphenyloxazole, 1,2-diphenylazirine, 2-phenylindole and benzamide. 13C labelling experiments indicate that the first two compounds are formed as shown in Scheme 31. 

Rhodiumcatalyzed decomposition of 10a in the presence of benzaldehyde and methyl cyanoformate does not afford the dihydrooxazole derived fi om carbonyl ylide 21, but rather the interestingly functionalized 1,3-oxazole [19]. This product is likely to arise from cyclization of the nitrile ylide intermediate 26 [20]. 

Photochemical cyclization of nitrile ylides (29) derived from suitably substituted 2ff-azirines gives imidazoles (Scheme 2.1.13) [75, 76]. 

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