Synthesis of 1-Azirines

Neber and co-workers undoubtedly synthesized the first authentic 1-azirine in 1932 while studying the reaction of oxime y)-toluene-sulfonates with base to give aminoketones. Neber observed that while trying to prepare the -toluenesulfonate derivatives of oximes (21), pyridine was a sufficiently strong base to convert the intermediate p-toluenesulfonates (22) into the aziridines (23). Azirines (24) could then be prepared by treating 23 with sodium carbonate. 

Because of the high degree of instability and reactivity that might be expected for the 1-azirine structure, Cram and Hatch reinvestigated, but confirmed Neber s original assignments.  

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. 

Smith and Most developed a modified Neber reaction for the S5mthesis of aminoketones which was used successfully by Parcell for the synthesis of 3,3-dimethyl-2-phenyl-l-azirine (26).  

Morrow et al. applied this reaction to the synthesis of the steroidal spiroazirine (29) and discovered that higher yields can be achieved if the dimethylsulfinyl carbanion is substituted for sodium isopro-poxide as the base. Unfortunately, this method lacks generality. 

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Smolinsky developed the first general synthesis of 1-azirines by the vapor phase pyrolysis of vinyl azides (41).20,21 In addition to 50-60%... 

Two research groups have independently observed that the pyrolysis of 4,5-dihydro-1,2,6-oxazaphospholes can be a useful synthesis of 1-azirines (99) in some cases.50-53 The oxazaphospholes (98) are readily prepared by the cycloaddition of nitrile oxides (96) to alkyl-idenephosphoranes (97). 

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. 

One of the best known reactions of 1-azirines is the acid/catalyzed hydrolysis to aminoketones. Since the Neber reaction also accomplishes this same synthetic end, this reaction may appear to have little practical value. This is not the situation because with the Neber reaction there is no control over the aminoketone that will be obtained from a given ketone. For example, when oxime (127) derived from benzyl methyl ketone (126) is subjected to the Neber reaction aminoketone 128 is obtained.59 The amino function is substituted for the most acidic a-hydrogen. The isomeric aminoketone (132) that could not be prepared by the Neber reaction can be formed by the hydrolysis of 1-azirine (131). The synthesis of this 1-azirine has been accomplished from allyl benzene (129) through vinyl azide (130) using iodine azide.22... 

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