2H- Azirines

For isoxazoles the first step is the fission of the weak N—O bond to give the diradical (51) which is in equilibrium with the vinylnitrene (52). Recyclization now gives the substituted 2//-azirine (53) which via the carbonyl-stabilized nitrile ylide (54) can give the oxazole (55). In some cases the 2H-azirine, which is formed both photochemically and thermally, has been isolated in other cases it is transformed quickly into the oxazole (79AHC(2.5)U7). 

PHENYL-2H-AZIRINE-2-CARB0XALDEHTDE [2ff-Azirine-2-cu boxaldeh7de, 3-phenyl-]... 

C. 2-(Dimethoxymethyl)-3-phenyl-2H-azirine. The crude product (71-75 g., 0.32-0.34 mole) obtained from Part B is heated at reflux in 11. of chloroform in a 2-1., round-bottomed flask for 12 hours (Note 9). The solvent is removed with a rotary evaporator and the crude residue... 

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. ... 

In addition to the present method, 2H-azirines can be prepared by using a modified Neber reaction,or by heating 4,5-dihydro-l,2,5-oxazaphospholes. 1... 

Unsaturated oximes are attractive substrates for aziridine synthesis. Treatment of oxime 77 with Red-Al yielded vinylaziridines 78, 79, and 80, in various ratios depending on the E/Z ratio of the starting oxime 77 (Scheme 2.22) [38]. This reaction should proceed through abstraction of HA, Hb, or He in the intermediate 81, followed by hydride reduction of the resulting 2H-azirines 82-84. 

H-Azirine-2-carboxylates such as 57 (Scheme 3.19) are a special class of imines that undergo additions to their C=N double bonds to give aziridine-2-carboxylates... 

Lewis acid-mediated asymmetric Diels-Alder reactions between 2H-azirines 59, bearing chiral auxiliaries, with enophiles such as 60 afforded mixtures of bicyclic aziridine-2-carboxylates 61 (Scheme 3.20) [68]. 8-Phenylmenthol appeared to be the auxiliary of choice in this reaction in terms of yield and diastereoselectivity. 

Treatment of N-sulfmyl-as-aziridine-2-carboxylate 206 (Scheme 3.75) with LDA at -78 °C afforded 2H-azirine-2-carboxylate 207 in 47 % yield. The trans-aziridine 206 gave only a 9% yield of the desired product 207 [95]. Treatment of N-tosyl 2-substi-tuted aziridines 208 (Scheme 3.76) with LDA resulted in the formation of azirines 209 in 61-87% yield [95],... 

Swern oxidation of N-unsubstituted aziridine-2-carboxylate 210 (Scheme 3.77) resulted in the formation of 2H-azirine 211 in >90% yield [95] Similar oxidation of 212 (Scheme 3.78) afforded azirine 213 in 60% yield [66]. 

Swern oxidation of N-unsubstituted aziridine-2-phosphonates resulted in the formation of both 2H-azirine-2-phosphonates and 2H-azirine-3-phosphonates [81, 83]. Treatment of ds-aziridine-2-phosphonate 226 (Scheme 3.84) with DM SO/ (COCl)2/Et3N afforded azirine-phosphonates 227 and 228, with the former predominating [81]. Under similar conditions, however, trans-aziridine-2-phospho-... 

Reactions between organolithium reagents and 3-(2-naphthyl)-2H-azirine in the presence of a range of chiral ligands have been studied. The product aziridines are obtained in at best moderate ees [61]. 

H-azirine-2-carboxylate 80, 102 2H-azirine-2-phosphonate 104 2H-azirine-3-phosphonate 104 azirinomycin 435 azomethine ylide 25, 474... 

This simple procedure resulted in 2H-azirines exclusively in high yields and with retention of chirality at C-2 [24]. Mechanistically, this oxidative synthesis of azirines can be rationalized by invoking the intermediacy of chloro-dimethyl-sulfonium chloride (Me2SCl+- Cl ), which then reacts with the aziridine as indicated in Scheme 12. 

H-azirine no conjugation of the imine function with the ester... 

Palacios et al. utilized the modified Neber reaction for the preparation of 2ff-azirine-2-phosphonates 33 as shown in Scheme 18 [28 a]. The use of quini-dine and dihydroquinidine as the chiral base resulted in moderate chirality transfer (20-52% ee). Similarly, 2-phosphinoyl-2H-azirines could be obtained by the Neber 1,3-elimination reaction [28bj. 

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 pyrazoles from reactions of suitably substituted 2-arylazirines and molybdenum hexacarbonyl has been discussed earlier in this section (see Schemes 89, 90)47 an analogous procedure depicting the transformation of 2-formyl-3-phenyl-2H-azirine into 3-phenylisoxazole is illustrated in Scheme 109.47... 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

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]. 

Example VI Prediction and Detection of 2H-Azirine as Intermediate in the Thermal Decomposition of Vinyl Azide. Predictions concerning the hard-to-prove nonexistence of molecules are less convincing to the lay-colleague than those, which have stimulated successful experiments. Therefore, this last example has not only been selected because of its higher complexity, but rather due to the PE spectroscopic verification of the results anticipated by a preliminary hypersurface study (4,36). 

Figure 6. MNDO heat of formation hypersurface for singlet vinyl nitrene rearrangements to 2H-azirine, ketene imine and the thermodynamically most favorable isomer, acetonitrile.

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-... 

An efficient synthesis of 2Ff-azirines 6 substituted with a phosphate group is described. Its key step is an alkaloid catalyzed Neber reaction of -ketoxime tosylates 5 (equation 3) . Similarly, azirines containing an ester group in position 2 were obtained from tosy-lated oximes . A novel approach to substituted 2Ff-azirines using benzotriazole (Bt) methodology was recently presented. The reaction of benzotriazole oxime tosylates formed from the oxime 7 and TsCl with aqueous KOH yielded 2-(benzotriazol-l-yl)-2H-azirines. 

Photolytic cleavage of 2,3-disubstituted 2H-azirines or monoaryl-2H-azirines provides access to nitrile yiides with the structure 280.1,3-Dipolar cycloaddition of the in situ generated yiides to Cjq affords mono- or disubstituted pyrrolo fullerenes such as 281 (Scheme 4.50) [319, 320]. Aliphatic 2H-azirines are not reactive, as they have shorter excitation wavelengths than the phenylic substituted 2-azirines. 

TABLE 6.12 IMIDAZOLONES PROM 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE AND 2H-AZIRINES, 119... 

Wird die Ringerweiterung statt mit Bortrifluorid mit Meerwein-Reagens durchgefuhrt, so erhalt man mit Benzonitril aus 2-Methyl-3-phenyl-2H-azirin hauptsachlich l-Ethyl-2,5-diphe-nyl-4-methyl-imidazol und aus 3-Methyl-2-phenyl-2H-azirin 1-Ethyl-2,4-diphenyl-5-methyl-imidazol44°. 

Die photochemische Umsetzung von 2,3-Diphenyl-2H-azirin mit Bis-[2-methyl-phenyl]-carbo-diimid fiihrt zu 2,4-Diphenyl-5-(2-methyl-anilino)-l-(2-methyl-phenylj-imidazot441. 

Die Addition von Elektrophilen an 2H-Azirine liefert bei geeigneter Substitution a-Ami-nosaure-Derivate z. B.s ... 

Tab. 89 a-Aminosauren durch Addition von Elektrophilen an 2-Alkoxy- bzw. 2-Amino-2H-azirine... 

H-Azirin Elektrophil Reaktionsbe- dingungen d-Acylamino-carbonsaure-amid Ausbeute [%] Schmp. [ C] Lite- Tatur... 

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