Electrocyclizations nitrile ylides

Detailed mechanistic studies101 indicate that benzazepines arc formed by 1,7-electrocyclization of a nitrile ylidc intermediate followed by a [l,5]-sigmatropic hydrogen shift in the initially formed 9a//-2-benzazepine. Similar products, e.g. 9, have been obtained by generating the nitrile ylide 8 from the imidoylchloride, e.g. 7. with potassium /ert-butoxide in tetrahydro-furan.101... 

An elegant procedure for the synthesis of 5//-dibenz[c,e]azepines 14, which is an extension of the procedure outlined at the beginning of this section, has been developed in which the nitrile ylides, generated by the treatment of iV-(2-arylbenzyl)benzimidoyl chlorides 12 with potassium /er/-butoxide, undergo a 1.7-electrocyclization at the adjacent phenyl ring, followed by a hydrogen shift 13 - 14.102... 

In an attempt to investigate this theory further, the analogous alkoxy-substituted nitrile ylides 171 were investigated. Species of this type were previously unknown but were successfully generated for this work by the thermolysis of the 4-alkoxy substituted l,3-oxazol-5-ones 170 (89). In the absence of a dipolarophile, the nitrile ylides reacted via 1,5-electrocyclization to give the isoindoles 173 [see also... 

Some interesting new chemistry has been produced on the well-known 1,5-electrocyclization reaction of alkene-conjugated nitrile ylides but the greatest... 

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. 

A similar 1,5-electrocyclization involving an aromatic ring was observed for the nitrile ylide 310 (R =Ph, R =Me) (66). This reaction gave 311 as the initial product, which then rearranged via a 1,3-hydrogen shift to give the isoindole 312. 

The intermediacy of the nitrile ylide was demonstrated by a trapping experiment using methyl acrylate in which it was found that the formation of 312 was entirely suppressed. Interestingly and unexpectedly, the nitrile ylide 310 (R =Me, R =Ph) failed to follow a similar path and reacted only via cycloaddition of the nitrile ylide to the double bond of the precursor azirine 313 to give 314. Its failure to undergo 1,5-electrocyclization was attributed to steric destabilization of the required syn isomer. 

Extensive work has been carried out on the 1,7-electrocyclization of diene-conjugated nitrile ylides (324) leading to fused heterocyclic systems containing the azepine ring (325). Reactions of this type for all 1,3-dipoles have been reviewed (197,198). 

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. 

A nitrile ylide intermediate has also been postulated for the thermolysis of the thiapyrans 32 (X = S) [75CR(C)37], The intermediacy of a nitrile ylide 37 and its 1,7-electrocyclization onto a nitro group to give intermediate 38 have been proposed as key steps in the thermolysis of 3-oxazolin-5-ones 36 to 1-acyloxyindazoles 39 (Scheme 14) (73CB2870). 

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). 

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