Alcohols reaction with azirines

Irradiation of a benzene solution of 8 with 253-7 nm light produced 9,10-dicyanophenanthrene (97) in about 20% yield . When the photolysis was carried out in methanol, small amounts of methyl benzoate were also found. It has been suggested that the dihalo-azirine 95 is formed, then undergoes reaction with the alcohol to give first benzoyl cyanide and then the observed ester (equation 14). 

Interestingly, certain chiral tertiary bases, viz., the Cinchona alkaloids, result in an asymmetric 1,3-elimination to give enantiomerically enriched azirine esters 29 (Scheme 15). The best results were obtained with quinidine in toluene as the solvent at a rather high dilution (2 mg mL ) at 0 °C. In an alcoholic solvent no asymmetric conversion was observed. It is of importance to note that the pseudoenantiomers of the alkaloid bases gave opposite antipodes of the azirine ester, whereby quinidine leads to the predominant formation of the (k)-enan-tiomer (ee = -80%). To explain this asymmetric Neber reaction, it is suggested... 

FIGURE 25. The heterogeneous gas-phase dehydrochlorination of /1-chloroethyazide on solid potassium rm-butoxide yielding vinyl azide, and the subsequent thermal decomposition of the latter to 27/-azirine. The double-oven apparatus is equipped with cold traps for the by-product tert-butyl alcohol and the end product 2/7-azirine. The PES ionization patterns of the pure compounds were used for optimization of the reaction conditions. Reproduced by permission of Verlag der Zeitschrift der Naturforschung from Reference 215... 

Photo-triggered ring opening of 2//-azirines is a well-known reaction to produce pyrrolines [8, 71]. Padwa and co-workers showed that photoirradiation of azirines with a mercury arc lamp (450 W) equipped with Vycor filter generated the reactive nitrile ylide intermediate (72), which can be stabilized by the phenyl substituents. The nitrile ylide (72) then reacts with the electron-deficient olefins (73) such as acrylate and acrylonitrile in a cycloaddition reaction to form A -pyrrolines (74) (Scheme 10) [8]. Steenken and co-workers studied reaction kinetics of azirines with dipolarophiles as well as nucleophiles such as alcohols [72]. They showed that the reaction rate depends on the azirine substituents, the nucleophilicity of the reactant and the acidity of the alcohol. 

The absolute reaction rate of methyl acrylate and the nitrile ylide derived from 2,3-diphenyl-2/f-azirine at 25°C has been estimated as 7.6 X 10 AT sec. Inductive effects exerted by substituents on the nitrile ylide also have an important effect on the regioselectivity of the cycloaddition. Benzonitrilio-hexafluoro-2-propanide (44) and methyl acrylate yield products with inverse regioselectivity as compared with the reactions of the related benzonitrilo-2-propanide 47. The difference in regioselectivity has been attributed to the larger coefficient at the trisubstituted carbon atom of the gem-trifluoromethyl substituted nitrile ylide 44. This result parallels the different mode of addition of alcohols to nitrile ylides 44 and 47. 

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. 

Reaction of l-azirine-3-methacrylates (42) with imidazoles or pyrazoles under mild conditions leads to the formation of 2-aza-1,3-dienes (43)." Simple alcohols also act as nucleophiles in the presence of sodium carbonate. The proportions of Z and E isomers formed depend considerably on R and Nu. 

Stable AT-alkyl-azirino-arenes have been reported.Thus a general route to 1-butyl-, 1-cyclohexyl-, and l-benzyl-la,9b-dihydrophenanthra[9,10-ft]azirines (389) utilises the reaction of phenanthrene 9,10-oxide with the appropriate amine followed by cyclodehydration of the amino-alcohol with PPhs and CCI4. 

The distal arrangement of the substituents in 24 prevents cyclization to a benzoxazole-type intermediate. While stable in alcohols, this intermediate can undergo hydrolysis (in water) to give hydroxyformanilide (25). Further analysis of the reaction revealed that 24 is a secondary photoproduct of the first-formed azirine 26, in contrast with the thermally induced azirine conversion to isonitrile that is observed for 18. Triplet quenchers such as oxygen and methyl acrylate quench the reaction efficiently. The authors propose a mechanism for conversion of 23 to 26 that involves a deprotonation-reprotonation sequence preceded by intramolecular electron transfer from the triplet-excited state of 23. 

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