Azirines as Substrates

This type of synthesis has been investigated extensively. It can occur by several general routes that are illustrated in the following examples  

6- tetramethyl-3,6-dihydropyrazine (7) [PhCH(N02)C02Me, MeCN, reflux, 6 h 85% it is not clear whether the nitroester plays any role].948 

Methyl 3,3-diethoxycarbonyl-l-methyl-2-azididinecarboxylate gave dimethyl 

2-Dimethyl-3-phcnyl-2//- tzirinc (9) and ammonia gave 3,3,6,6-tetramethyl- 

5- diphenyl-l,2,3,6-tetrahydro-2-pyrazinamine (11, R = NH2) [NH3, MeOH, 20°C, 30 min 73% the mechanism appears to involve condensation of the NH3 adduct (10) with original substrate (9)] 408 the same substrate (9) and 2-chloroethanethiol likewise gave 2- (2-chloroethylthio)-3,3,6,6-tetramethyl- 

N /VMe Me Me MeCN, reflux Me MejN CC N NMej Me Me EtO2C N COjMe EtOjC T T COaEt MeOjC N CO,Et H 

---

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... 

Imines are much less reactive than carbonyl compounds toward TMSCF3, and the process proceeded mostly in the case of highly activated C=N bonds, using azirines, polyfluorinated imines and iV-sulfonyl- or iV-sulfinylimines as substrates. In the latter case, highly diastereoselective trifluoromethyl-ations were achieved from chiral iV-sulfinylimines (eq 13). Nitrones are another source of activated C=N bonds, suitable for the introduction of CF3 groups with TMSCF3. ... 

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

Cyclic imines 8 and 9 are intermediates or models of biologically active compounds and can be reduced with ee-values of 88 to 96% using Ti-ebthi, Ir-bcpm or Ir-binap in the presence of additives (entries 5.7, 5.9), as well as with the transfer hydrogenation catalyst Ru-dpenTs (entries 5.8, 5.10-5.12). As pointed out earlier, Ru-diphosphine-diamine complexes are also effective for imines, and the best results for 7 and 8a were 88% and 79% ee, respectively [36]. Azirines 10 are unusual substrates which could be transfer-hydrogenated with a catalyst prepared in situ from [RuCl2(p-cymene)]2 and amino alcohol L12, with ee-values of 44 to 78% and respectable TOFs of up to 3000 (entry 5.13). 

Reaction of l-azirine-3-methylaciylates (155) with imidazoles and pyrazoles under mild conditions results in the formation of 2-aza-1,3-dienes (156), which are useful as dienes in hetero Diels-Alder reactions with electron-deficient dienophiles <99JOC49>. When the related methyl 2-aryl-2ff-azirine-3-carboxylate (157) was used as fee substrate, reaction with an amine induced a ting opening by addition of the amino group onto fee C=N bond followed by cleavage to provide enediamine 158 <99JCS(P1)1305>. 

An exciting cycloaddition which is not pericyclic in nature has been developed on the basis of PET opening of azirines to 2-azaallenyl radical cations [373] these add readily to substrates such as imines and acetylenes. This paves the way for the synthesis of imidazoles [373a, e], heterophanes [373b, e], and even porphyrins (cf. the preparation of 34) [373c, e]. 

---