2H-Azirine ring

Activation of 3-alkyl and 3-phenyl-2H-aziiines by Lewis acids also promotes their participation in hetero Diels-Alder reactions with a variety of dienes. This methodology circumvents the previous requirement of needing an electron-withdrawing carboxyl moiety at the 3-position of the 2H-azirine ring (01TL9289). Thus, the reaction of 2H-azirine 125 with Danishefsky s diene gave the endo-cycloadduct 126... 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

The addition of methanol or hydrazoic acid to ethenylidenecydopentadiene 3 demonstrates that 3 behaves like an acceptor-substituted allene (Scheme 7.27) [226, 227]. More examples of nudeophilic additions to alkyl-substituted derivatives of 3 were reported by Hafner [228]. Photoelectron spectroscopy of the spirocyclic compound 165b, easily accessible from azide 164b, shows that the lone-pair orbital n(N) of the 2H-azirine nitrogen atom interacts strongly with the Jt1-orbital of the cyclo-pentadiene ring [227]. 

Inspection of the MNDO hypersurface shows the assumed vinyl nitrene to lie in a very shallow minimum with the activation barrier for ring closure to 2H-azirine (Figure 1 a ) calculated to be only a few kJ/mole. Whereas the separating hypersurface "ridge" to ketene imine of AA t 70 kj/mole seems insur-... 

The reactivity of 2H-azirines as 1,3-dipolarophiles towards (5-lactam-based azomethine ylides derived from oxazolidinones has been evaluated <02JCS(P1)2014>, providing cycloadducts 37, which incorporate the novel 2,6-diazatricyclo[4.2.0.02 4]octan-7-one ring system. 

The few examples of ring enlargement reactions of 2H-azirines and aziridines discussed above demonstrate their vast application in the synthesis of hetero-... 

The photochemical addition of 2H-azirines to the carbonyl group of aldehydes, ketones and esters is completely regiospecific (77H143). Besides the formation of the isomeric oxazolines 18 from 3 and ethyl cyanoformate, there is also formed the imidazole 19 from addition to the C = N in the expected regioselective manner. Thioesters lead to thiazolines 20, while isocyanates and ketenes produce heterocycles 21 (Scheme 4). The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphospho-nium salts and p-quinones. 

When the chain between the 2H-aziiine 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 2H-azirine 50 gives zl -pyrroline 52 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 (Scheme 15). 

The 2H-azirines obtained from the vapor phase pyrolysis of 4,5-disubstituted l-phthalimido-l,2,3-triazoles (74) have been found to undergo further thermal reactions (71CC1518). Those 2H-azirines which contain a methyl group in the 2-position of the ring are cleaved to nitriles and phthalimidocarbenes, whereas those 2H-azirines which possess a phenyl substituent in the 2-position rearrange to indoles (Scheme 21). 

The interaction of diazomethane with 2H-azirines (161) was reported in 1964 (64JOC3049) and represents the first example of a 1,3-dipolar cycloaddition with this ring system. 1,3-Dipolar addition produces the triazoline adduct 162. This material can exist in equilibrium with its valence tautomer 163, and allylic azides 164 and 165 are subsequently produced from these triazolines by ring cleavage (Scheme 43). 

Aziridines such as 166 undergo thermal ring opening in a conrotatory manner to generate azomethine ylides. These azomethine ylides are Ttt-components and have also been found to participate in [4+21-cycloadditions with 2H-azirines acting as the 27r-component to give 167 (Scheme 44) (73HCA1351). 

The first synthesis of phosphorylated analogues of pyrazinamides such as substituted pyrazines containing two phosphonate groups (2,5-position) (269) and pyrazines containing one phosphonate group (2-position) (270) has been elaborated. The synthesis is based on thermal ring opening of 2H-azirines (271) followed by dimerization of unstable nitrile ylide intermediates (272) (Scheme... 

Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphon-ates (281), a new class of chiral iminodienophiles, and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts (282). Hydrogenation of (282) results in a ring opening that affords the first examples of optically pure quaternary piperidine phosphonates. Two step synthesis of an enantiomeric pure cyclic phosphite (283) and its application as a chiral phosphorus nucleophile in the asymmetric Michael addition to nitroalkenes (284) provides an efficient... 

Photoisomerization of five-membered heterocycles commonly takes place via ring-contracted intermediates. The 2H-azirine (33)... 

The only example of the ring system of Type I was prepared by Woemer et al. when 3-phenyl-2H-azirine (1) was treated with diphenylketene-/ -tolyli-mine (2) in benzene at 65 °C for 65 h besides benzophenone, a 1 1 isomeric mixture of the azirino[ 1,2-c]quinazoline 3 and the 1,3-benzodiazepine 4 was formed. During heating in trichlorobenzene under a nitrogen atmosphere. 

Photolysis and thermolysis of isoxazoles and oxazoles causes ring-contraction to 2-acyl-2H-azirines, as shown in Scheme 92 . The azirines may be observed in some cases, or may be transformed without observation to other heterocycles. Equation (74) shows an example where the azirine was isolated in good yield <88TL6067>. An isolable azirine was also formed in the photolysis of a 4-acylisoxazole <90JOC40ll>. 

A number of ring expansions of 3- and 4-membered heterocycles have been reported. Among the former is the reaction of 2H-azirines (43) or their salts with nitriles, a reaction first reported by Leonard. The reaction is promoted by perchloric acid ° or boron trifluoride,and is doubtless a... 

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