Azirines reactions with enamines

The exploration of the chemistry of azirines has led to the discovery of several pyrrole syntheses. From a mechanistic viewpoint the simplest is based upon their ability to behave as a-amino ketone equivalents in reactions analogous to the Knorr pyrrole synthesis cf. Section 3.03.3.2.2), as illustrated in Schemes 91a and 91b for reactions with carbanions. Parallel reactions with enamines or a-keto phosphorus ylides can be effected with electron-deficient 2//-azirines (Scheme 91c). Conversely, electron-rich azirines react with electron deficient alkynes (Scheme 91d). 

Aziiines with electron-withdrawing substituents at the imine function can be used in ring-transformation reactions with enamines to give pyrrole mono- or di-carbox-ylates". L abbe and coworkers proposed a mechanism involving cycloaddilion of the enamine 232 to the C=N bond of the azirine 233, to give the zwitterion 234, which cyclizes to 235. Ring expansion of 235 and elimination of the amine residue give a pyrrole 239, whereas Katritzky and coworkershave proposed that the bicycle 235 is converted into a mixture of 2,3-dihydropyrrole 237 and a 3,4-dihydropyrrole 238, before elimination of amine (equation 49). 

Catalyt c hydrogenation (palladium or Raney nickel catalyst) surprisingly results in reduction of the carbon-nitrogen single bond rather than the double bond.4,12,40 The imines, or possibly enamines, are usually not isolated and their existence has only been inferred in most instances. Harvey and Ratts have shown that this reaction with azirine (165) does not proceed first to the aziridine which is then reduced to 166, since aziridine (167) is inert to hydrogen and palladium on carbon.40... 

Because of their predictable behavior and reactivity, thioacyl isocyanates comprise the bulk of this work, and extensive studies of their [4 + 2] reactions with olefins,83 enamines,84 enol ethers,843 thioacyl isocyanates,85 imines,85 1 86 carbodiimides,84387 isocyanates,843 azirines,88 /3-enaminoke-tones,89 dianils,86d azines,90 hydrazones,91 imidazoline-4,5-diones,92 aryl cyanates,93 disubstituted cyanamides,93 aldehydes,94 ketones,94 ketenes,94 alkyl or aryl iminodithiocarbonates,95 and the carbon-carbon double bond of ketenimines96 have been detailed. In an extensive comparative study of the [4 + 2] cycloaddition reactions of thioacyl isocyanates, the heterocu-mulenes bearing strong electron-withdrawing substituents were found to be more stable and less prone to participate in cycloaddition reactions.84 Representative examples are summarized in Scheme 9-IV. 

The conversion of enaminones and enamine carboxylic esters to trifluoroethoxylated 2//-azirines through reactions with PhIO in trifluoroethanol is postulated to proceed via a PhlO-mediated oxidative trifluoroethoxylation and a subsequent azirination of the a-trifluoroethoxylated enamine intermediates. " ... 

Enamines are also prepared from azirines by thermolysis/ and from iminium salts by dehydrobromination/" Enaminones are prepared from ketones by reaction with hexamethydisilazane " and from vinamidinium salts by reaction with enolates/ and thioenaminones are now conveniently prepared directly from enaminones/" ... 

Again, the main reactions correspond to formal insertion of the ring-opened cyclopropen-one (or -thione) into the C—N bond rather than into the C—C bond of the unsaturated nitrogen compounds. The comparable reactions of (431) with l-azirines and of enamines and ynamines with substituted methylenecyclopropenes have recently been reported. 

The reaction of azirines with Grignard reagents is an anomalous reaction of imines. Normally an a-hydrogen is abstracted to give the enamine anion which is unreactive toward further attack of the Grignard reagent.64 The enamine derived from a 1-azirine is a 2-azirine (146) it is an unknown and probably unstable compound (Section I,A). 

Aromatic and aliphatic acyl isocyanates participate in a similar range of [4 + 2] cycloadditions although [2 + 2] and simple addition reactions often are observed. The acyl isocyanate substituents may determine or alter the observed course of the reaction, and the substituent effects have been detailed in extensive reviews.7,71 Observed [4 + 2] cycloadditions of acyl isocyanates with selected olefins, p-quinones, allenes, the carbon-carbon double bond of ketenes, electron-rich acetylenes, imines, dianils, ethy-lenediimines, enamines, enol ethers, ketene acetals, carbodiimides, azirines, and vinyl sulfides have been described.7 0 The reaction of aromatic acyl isocyanates with carbodiimides is not a simple, direct [4 + 2] cycloaddition but proceeds by a kinetic [2 + 2] cycloaddition followed by a subsequent rearrangement to provide the observed [4 + 2] cycloadduct [Eq. (40)].97... 

The 3 -I- 2-cycloaddition reactions of A-alkylsufonylimines with alkenes, enamines, ynamines, diazo compounds, azirines, silyloxydienes, and azadienes have been extensively reviewed. Rhodium(III)-catalysed cycloaddition of cyclic sulfonylketimines with internal alkynes afforded multifunctional spirocyclic sultam products in high... 

The products of reactions of two methyl 2-aryl-2 f-azirine-3-carboxylates (21 aryl = 2,6-Cl2C6H3 or 4-MeC6H4) with a range of nucleophiles are reported. Although a wide range of compounds have been added (thiols, propargyl alcohol, amines, enamines, enones and -diketones), all appear to involve initial addition to the C=N bond. 

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