Azirines irradiation

Cycloaddition of azirines. Irradiation of the azirinc 2 in the presence of DCN (1) forms a radical cation (3), which is trapped by imincs to form imidazoles (4). 

Whereas the cycloaddition of arylazirines to electron-deficient olefins produces J -pyrrolines, a rearranged isomer is formed when the alkene and the azirine moieties are suitably arranged in the same molecule. This intramolecular electrocyclization reaction was first observed by Padwa and Smolanoff using 2-vinyl-substituted 2/f-azirines. Irradiation of 2i/-azirine 107 afforded a 2,3-disubstituted pyrrole (108), while thermolysis gave a 2,5-disubstituted pyrrole (109). Photolysis of azirine 110 proceeded similarly and gave 1,2-diphenylimidazole (111) as the exclusive photoproduct. This stands in marked contrast to the thermal reaction of 110 which afforded l,3-diphenylp3nrazole... 

Photolysis of 2,3-diphenyl-A -azirine (442) generates benzonitrile ylide (443). Irradiation in the presence of ethyl cyanoformate resulted in a mixture of the oxazoline (444) and the imidazole (445) by 1,3-dlpolar cycloaddition to the carbonyl and nitrile group, respectively (72HCA919). 

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). 

When the chain between the azirine ring and the alkene end is extended to three carbon atoms, the normal mode of 1,3-intramolecular dipolar cycloaddition occurs. For example, irradiation of azirine (73) gives A -pyrroline (74) in quantitative yield 77JA1871). In this case the methylene chain is sufficiently long to allow the dipole and alkenic portions to approach each other in parallel planes. 

A variety of 1-azirines, including the first fused derivatives, have been prepared by the selective irradiation at 350 nm of the appropriate vinyl azide precursors (68JA2869). 

The irradiation of 3,5-diphenylisoxazole in the presence of propylamine gave a mixture of 2,5-diphenyloxazole (20%) and A-propyl-2,5-diphenylimidazole (1%). The same distribution of the products was obtained starting from the azirine 46 (75T785). 

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]. 

The irradiation of 3-carbomethoxyisoxazole (47) gave the corresponding oxazole (48) in very low yields (5-8%) without the isolation of the corresponding azirine (Scheme 22) [71JCS(C)1196]. Also in this case calculations show that the energy of the triplet state allows the formation of the biradical intermediate and then of the azirine. However, the low yields of the conversion can be explained considering that the transformation of the biradical intermediate into the azirine is an endothermic reaction (Fig. 10) [99H(50)1115]. 

Photolysis of (Z)-3-phenyl-2-(2-phenylvinyl)-2//-azirine (1) in benzene solution yields 1-phenyl-3//-2-benzazepine (2) in excellent yield.39 However, the stereochemistry of the alkenyl side chain and the solvent used are important in determining the outcome of the reaction. For example, the E-isomer of the 2//-azirine 1 on photolysis in benzene solution yields 2,3-diphenyl-pyrrole as the major product (85 %) the pyrrole is also obtained on heating the Z- or E-isomer in benzene solution. In contrast, irradiation of the Z-isomer in methanol yields only acyclic products. 

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... 

Another photochemical ring enlargement leading to a 1,3-oxazepine is the formation of 2-phenyl-l,3-oxazepine (13) by irradiation of 4-phenyl-2-oxa-3-azabicyclo[3.2.0]hepta-3,6-diene (11).12 It is proposed that the process involves the azirine 12 as an intermediate. 

Although 2-acyl-2//-azirines are known to give oxazoles upon irradiation, the reaction is wavelength dependent, and isoxazoles are formed at some wavelengths, as they are in the thermal rearrangement of 2-acyl-2//-azirines.<74TL29,75JA4682> Since the thermal reaction of diazocarbonyl compounds with nitriles leads to oxazole formation, it would seem that mechanistic path C is unlikely in these reactions. 

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 first example of a [ 6 + 4] cycloaddition of a nitrile ylid has recently been reported104 irradiation of 3-phenyl-2,2-dimethyl-2i/-azirine (129) in the presence of 6,6-dimethylfulvene (130) in cyclohexane gave the [n6 + 4] adduct 131 together with the [ 4 + 2] adduct 132. 

Nitrile ylids generated in this way can be trapped with methanol108 Thus, on irradiation in methanol, the azirine 137 was converted to the methoxy-imine (138). The intramolecular equivalent reaction leading to the oxazoline 139 has also been observed on irradiation of the 2//-azirine (140 R = OH),... 

The reverse process has also been examined. 2-Phenyloxazole is converted in a similar fashion to 3-phenyl-2//-azirine-2-carbaldehyde on irradiation in benzene or cyclohexane.128 Further rearrangement to the corresponding isoxazole can be effected thermally but not photochemically. A competing pathway leading to the formation of 4-phenyloxazole has also been observed and is thought to involve a bicyclic intermediate arising by 2,5-bonding. 

The irradiation of 2//-aryl azirines yields nitrile ylides which can be trapped by various dipolarophiles to form five-membered ring heterocycles116,140-142 (equations 80-82). 

Much work has been done since the early 1980s on the detailed investigation of the azirine-nitrile ylide interconversion using pulsed-laser photolysis. Thus the azirines 103 (R =R =Ph, R =H R =Me, R = R =Ph R = p-napthyl, R = Me, R = H), on irradiation in isooctane, gave intense long-hved absorptions (250-400 nm) attributed to the nitrile ylides 104 (44). Quenching studies with electon-deficient alkenes led to the determination of absolute rate constants that were similar to those reported earlier for steady-state trapping experiments. The nitrile ylide-olefin reactions are discussed in more detail in Section 7.3.1. 

In contrast, photolysis followed by y-irradiation of 3-(4-biphenylyl)-2//-azirine 105 resulted in the formation of the nitrile ylide radical anion 111 (57). Two mechanisms were suggested, either the one shown in the scheme, or via the photochemical opening of the azirine radical anion. 

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