Azirines ring synthesis

The highly strained and reactive 2iT-azirines have been extensively studied for various synthetic purposes, such as ring expansion reactions, cycloaddition reactions, preparation of functionalized amines and substituted aziridines. The older literature on azirines in synthesis has extensively been reviewed [69]. Concerning azirines with defined chirality only scarce information is available. Practically all reactions of azirines take place at the activated imine bond. Reduction with sodium borohydride leads to cz5-substituted aziridines as is shown in Scheme 48 [26,28]. 

Although the 1-azirine ring system is well known, to date, there are no authentic examples of 2-azirines in spite of several attempts directed toward their synthesis. 

The first synthesis of an isolable fused-ring azirine was reported in 1968 <1968JA2869>. Much of the strain associated with the incorporation of an azirine ring into a fused ring system is lost when larger rings are used. Compound 270 is relatively stable and is prepared in 93% isolated yield. A unique type of reaction that this class of... 

The azirine ring has also been found in several natural products. The first azirine-containing natural product isolated was Azirinomycin (140) <71JAN48>. More recently, the similar azirine-containing antibiotic Dysidazirine (141) was isolated and shown to possess cytotoxic and antibacterial activity <88JOC2103>. The synthesis of an aminoazirine-containing peptide (142) has been reported <93T467l>. 

A one pot, three components synthesis of tetrasubstituted imidazoles has been reported, where an isoxazole gives photochemically an acyla-zirine 7. This intermediate is trapped under basic conditions by an a-(alkylideneamino) nitrile 8 formed in situ from an aldehyde and an a-aminonitrile. The C2-C3 cleavage in the azirine ring is unusual (Scheme 15). ... 

The synthesis of metal-eoordinated 1-azirines and the reaetions of azirines indueed by metals have opened a new area in the ehemistry of this small ring heteroeyele. Many of the reaetions eneountered bear resemblanee to previously diseussed thermally and photo-ehemieally indueed reaetions of 1-azirines. The reaetion of a series of diiron enneaearbonyls in benzene results in eoupling and insertion to give diimine eomplexes and ureadiiron eomplexes as well as pyrroles and ketones (76CC191). A meehanism for the formation of these produets whieh involves initial 1,3-bond eleavage and generation of a nitrene-iron earbonyl eomplex as an intermediate was proposed. 

Azirine, trans-2-methyl-3-phenyl-racemization, 7, 33, 34 1-Azirine, 2-phenyl-reactions, 7, 69 with carbon disulfide, S, 153 1-Azirine, 3-vinyl-rearrangements, 7, 67 Azirines, 7, 47-93 cycloaddition reactions, 7, 26 fused ring derivatives, 7, 47-93 imidazole synthesis from, 5, 487-488 photochemical addition reactions to carbonyl compounds, 7, 56 photolysis, 5, 780, 7, 28 protonated... 

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). 

Reactions related to cyclopropanation can also be carried out with (phosphino) (silyl)carbenes (I). For example, benzaldehyde reacts with la at 0 °C leading to the corresponding epoxide, again as only one diastereomer. Even more striking are the reactions with benzonitrile and tert-butylphosphaalkyne that lead initially to azirine and phosphirene. Both three-membered heterocycles subsequently undergo ring expansion reactions affording azaphosphete and diphosphete, respectively (Scheme 8.18). This reaction is a new route for the synthesis of heterocyclobutadienes, and this demontrates the usefulness of (phosphino)(silyl)carbenes (I) for the synthesis of novel species. 

The Neber reaction generally does not lend itself as a useful method for the synthesis of 1 -azirines. The above reaction is probably successful because of the strong electron-withdrawing substituent which increases the acidity of the a-hydrogens and allows the ring closure to occur under mild conditions. Nevertheless, a few azirines have been prepared by related Neber reactions. 

Ring opening of aziridines and azirines by hydrofluorination 91T5329. Synthesis of JV-arylaziridines based on l-chloroalkyl(aryl)sulfoxides 91YZ205. 

The application of 3-amino-2//-azirines as amino acid equivalents and their use in the synthesis of cyclic dipeptides presumably includes ring enlargement steps [14]. The formation of 12- or 15-membered cyclodepsipeptides from open chain precursors possibly includes ring enlargement steps [3] [15]. 

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

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