Azirines isomerism

In 1980 Dunkin and Thomson [84] studied the photochemistry of these azides by infrared spectroscopy. These workers photolyzed 1- and 2-naphthyl azides in argon at 10 K and observed the formation of several new IR bands between 1708 and 1736 cm 1 attributed to azirine type of species. Prolonged photolysis of the matrix isolated azirines isomerized these primary photoproducts to dehydroazepines which were observed by IR spectroscopy between 1911 and 1926 cm 1. 

The course of the photochemically mediated isomerization of vinylazirines is dependent on the stereochemistry of the vinyl group, as is illustrated in Scheme 94a (75JA4682). Under thermal conditions the isomerization proceeds through formation of the butadienylnitrene and subsequent pyrrole formation. Analogous conversions of azirines to indoles have also been effected (Scheme 94b). It is possible that some of the vinyl azide cyclizations discussed in Section 3.03.2.1 proceed via the azirine indeed, such an intermediate has been observed... 

Isoxazoles largely undergo photochemical isomerization to azirines, which sometimes undergo a further thermal or photochemical reaction. 3,4,5-Triarylisoxazole (529) formed the 2,3-diphenyl-3-benzoylazirine (530) which underwent further reaction to the oxazole (531) 72JA1199). A small amount of the corresponding benzoyl ketenimine was also obtained. 

The conversion of small rings to smaller ones, without loss, is not common. 3-Chloroazetidine isomerizes reversibly to 2-chloromethylaziridine (Section 5.09.2.2.5). Flash vacuum pyrolysis can convert isoxazoles to azirines (Section 5.04.4.3). More common is the isomerization of medium-sized, i.e. five- or six-membered rings, e.g. certain succinimides (Scheme 23) (81JOC27) to azetidinediones, or bicyclic 1,2-dioxetanes to bis-oxiranes (Section 5.05.4.3.2). 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

Nitrile ylides derived from the photolysis of 1-azirines have also been found to undergo a novel intramolecular 1,1-cycloaddition reaction (75JA3862). Irradiation of (65) gave a 1 1 mixture of azabicyclohexenes (67) and (68). On further irradiation (67) was quantitatively isomerized to (68). Photolysis of (65) in the presence of excess dimethyl acetylenedicar-boxylate resulted in the 1,3-dipolar trapping of the normal nitrile ylide. Under these conditions, the formation of azabicyclohexenes (67) and (68) was entirely suppressed. The photoreaction of the closely related methyl-substituted azirine (65b) gave azabicyclohexene (68b) as the primary photoproduct. The formation of the thermodynamically less favored endo isomer, i.e. (68b), corresponds to a complete inversion of stereochemistry about the TT-system in the cycloaddition process. 

The photochemical behavior of the isomeric 3-methyl-2-phenyl-2-allyl-l-azirine (66) system was also studied. Irradiation of (66) in cyclohexane gave a quantitative yield of azabicyclohexenes (67) and (68). Control experiments showed that (65) and (66) were not interconverted by a Cope reaction under the photolytic conditions. Photocycloaddition of (66) with an added dipolarophile afforded a different 1,3-dipolar cycloadduct from that obtained from (65). The thermodynamically less favored endo isomer (68b) was also formed as the exclusive product from the irradiation of azirine (66b). 

A variety of 1-azirines are available (40-90%) from the thermally induced extrusion (>100 °C) of triphenylphosphine oxide from oxazaphospholines (388) (or their acyclic betaine equivalents), which are accessible through 1,3-dipolar cycloaddition of nitrile oxides (389) to alkylidenephosphoranes (390) (66AG(E)1039). Frequently, the isomeric ketenimines (391) are isolated as by-products. The presence of electron withdrawing functionality in either or both of the addition components can influence the course of the reaction. For example, addition of benzonitrile oxide to the phosphorane ester (390 = C02Et) at... 

In the photochemical isomerization of isoxazoles, we have evidence for the presence of the azirine as the intermediate of this reaction. The azirine is stable and it is the actual first photoproduct of the reaction, as in the reaction of r-butylfuran derivatives. The fact that it is able to interconvert both photochemically and thermally into the oxazole could be an accident. In the case of 3,5-diphenylisoxazole, the cleavage of the O—N bond should be nearly concerted with N—C4 bond formation (8IBCJ1293) nevertheless, the formation of the biradical intermediate cannot be excluded. The results of calculations are in agreement with the formation of the azirine [9911(50)1115]. The excited singlet state can convert into a Dewar isomer or into the triplet state. The conversion into the triplet state is favored, allowing the formation of the biradical intermediate. The same results [99H(50)1115] were obtained using as substrate 3-phenyl-5-methylisoxazole (68ACR353) and... 

Some data were obtained from the photochemical isomerization of amino-isoxazoles. 5-Aminoisoxazoles gave the corresponding azirine (Scheme 21) [70JCS(C)1825] when a4-carboethoxy-substituted derivative was used, no azirine was isolated and the oxazole was the only product obtained (Scheme 21) (72CB748). The azirine intermediate was not observed upon irradiating 3-amino derivatives [91H(32)1765]. 

In agreement with the previously reported theoretical study, the results of semi-empirical calculations showed that the formation of the Dewar isomer is favored [99H(50)1115]. Probably, the observed formation of the azirine derives from a thermal isomerization of the first photoproduct, in line with that described in the case of furan and thiophene derivatives (Fig. 11). 

The first reported example31,117 involved the diethyltetraphenyl-3//-azepines 18 and 19 which were obtained in 85% overall yield by the reaction of2,3-diethyl-2//-azirine with 2,3,4,5-tetraphenylcyclopentadienone (see Section 3.1.1.1.2.). The two isomeric azepines are separable by column chromatography (alumina or silica gel), and each isomer, on warming in xylene for three days, equilibrates to a 3 8 mixture of the 3//-azepines 18 and 19. 

Azcpincs under acid conditions reportedly117-225 yield aniline derivatives although ring contraction to pyridines is more usual. Thus, highly substituted 3//-azepines, e.g. 28, with a vacant 7-position, formed by cycloaddition of 2//-azirines with cyclopentadienones, on heating in acetic acid isomerize rapidly to the correspondingly substituted anilines 29.117... 

Attempts to induce valence isomerization of 5W-dibcnz[c,e,]azepine (3) to dihydrophenanthro-[9,10-6]azirine under thermal conditions have failed.85 However, the aziridine 5 is formed, albeit in low yield (3 %), by irradiating the dibenzazepinc 3 in dichloromethane solution. Isomerization can also be achieved by deprotonation of SH-dibenzIr.eJazepine with lithium diiso-propylamide at — 78 "C, and then allowing the resulting anion 4 to reprotonate by heating the reaction mixture at 50°C.85... 

Desilylation of a,P-aziridinylsilanes is a route to nonstabilized metalated aziridines. Treatment of 254 with CsF in the presence of PhCHO furnished substituted aziridine 255 in good yield (Scheme 5.65). Interestingly, the isomeric aziridine 256 gave azirine 257 on treatment with CsF, presumably via a phenyl-stabilized metalated aziridine [91]. 

Independent work by Schmid93 and by Padwa94 on the photochemistry of 2H-azirines has shown that irradiation of such systems leads in the first instance to the formation of nitrile ylids (nitrilium betaines). Subsequent 1,3-addition to a variety of dipolarophiles affords five-membered heterocycles. These additions take place in a stereospecific and regioselective manner thus, irradiation of the diphenyl-2f/-azirine 117 in the presence of dimethyl maleate leads to the formation of the two isomeric 1-pyrrolines... 

The formation of 2H-pyrroles (21) and a pyrrole derivative (22) from the reaction of 3-phenyl-2//-azirines and acetylenic esters in the presence of molybdenum hexacarbonyl is intriguing mechanistically (Schemes 24, 25).53 Carbon-nitrogen bond cleavage must occur perhaps via a molybdenum complex (cf. 23 in Scheme 26) but intermediate organometallic species have not yet been isolated.53 Despite the relatively poor yields of 2H-pyrrole products, the process is synthetically valuable since the equivalent uncatalyzed photochemical process produces isomeric 2H-pyrroles from a primary reaction of azirine C—C cleavage54 (Scheme 24). 

The ring cleavage of 3-aryl-2-substituted-2//-azirines by molybdenum hexacarbonyl has been described earlier in regard to the synthesis of pyrroles, pyrazoles and isoxazoles. In contrast to this behavior, analogous reactions of 2-unsubstituted derivatives lead to the formation of mixtures of 2,5-diarylpyrazines (139) and isomeric 3,6- and 1,6-dihydropyrazine derivatives (140,141) (Scheme 163).47,53 It is possible that the pyrazine products are formed by an intermolecular nitrene mechanism akin to the intramolecular processes described earlier (see Scheme 22 in Section IV,A,1). 

Strong acid hydrolysis of 1,2,6-thiadiazine 1,1-dioxides 239 or 240 results in ring contraction to afford the 1,2,5-thiadiazolinone 1,1-dioxides 241 in low yield <1996J(P2)293>. 3-Dialkylamino-2/7-azirines 242 suffer ring expansion with in situ-prepared iV-sulfonylamides 243 and carbamates to give both the 1,2,3-oxathiazoline 244 and the thiadiazoline 1,1-dioxide 245 (Equation 56). The oxathiazole 244 isomerizes quantitatively to the thermodynamically favored thiadiazoline 245 <1996J(P1)1629>. 

It was found that the azirine-nitrile ylide isomerization was a completely reversible process. The unlabeled nitrile ylide showed a prominent band at 1926 cm that underwent a 66-cm shift with N substitution. This shift was interpreted as being consistent with an allene-like skeleton (8) rather than the alternative pwpargyl-like stmcture (9). This conclusion was supported by the spectra from the C- and H-labeled variants. Warming the nitrile ylide in a xenon matrix from 12 to 82 K provided no new absorptions suggesting that the allene-like structure may also be adopted in solution. Some absorption spectra for benzonitriho benzylide (DPNY) and some substituted benzonitrilio methylides obtained via pulsed-laser photolysis of azirines are given in Table 7.1 (5). 

Extensive work has been done to determine and understand the factors controlling diastereoselectivity in the cycloaddition of nitrile oxides to alkenes but very little is known about nitrile ylides in this regard. Work on their reactions with alkenes that are geminally disubstituted with electron-withdrawing groups (e.g., 187) has illustrated some of the difficulties in such studies. When the imidoyl chloride-base route was used to generate the nitrile ylides it was found that the products 188 epimerized under the reaction conditions. When the azirine route was used, the reaction was complicated by the photochemical isomerization of the dipolarophiles (96,97). Thus, in both cases, it proved impossible to determine the kinetic product ratio. 

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