Modified Neber

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... 

An entirely different approach to the synthesis of 2H-azirinecarboxylic esters involves a modified Neber reaction of oxime tosylates derived from -keto esters (Scheme 15) [26]. 

A possible extension of the modified Neber reaction would be the synthesis of sulfonyl-substituted 2ff-azirines following the chemistry shown in Scheme 17 [27]. Unexpectedly, the oxime derived from -keto sulfones could not be converted into the oxime tosylate. Therefore, a different route to these requisite starting materials was designed, viz., via the corresponding sulfides 30 which were then oxidized with peracid to the sulfones 31. 

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. 

Smith and Most13 developed a modified Neber reaction for the synthesis of aminoketones which was used successfully by Parcell for the synthesis of 3,3-dimethyl-2-phenyl-l-azirine (26).14... 

From mechanistic studies on the Neber reaction, the 2//-azirine has been shown to be a distinct intermediate formed by ring closure of a vinyl nitrene. The evidence for the vinyl nitrene has resulted from the reported lack of steieospecificity in converting the ( )- and (Z)-isomers of 0-tosyloximes to the same a-amino ketone. Although a vinyl nitrene has been suggested as a possible intermediate in the thermal and photochemical preparations of the azirine ring, direct evidence for such a species is lacking. In this context, the configurational stereospecificity in a modified Neber reaction has been studied with oxime... 

The synthesis of optically active 3-amino-2/-/-azirines was carried out using a modified Neber rearrangement in the laboratory of I.P. Piskunova. The optically active amidoximes were acylated using mesyl chloride to give 0-mesyl derivatives that upon treatment with sodium methoxide afforded the desired product with high diastereoselectivity. 

The preparation of azirine rings using a modified Neber reaction (an asymmetric deprotonation) was studied by Brown and Jessop (unpublished data, 2002). Asymmetric deprotonations are particularly awkward in SCFs... 

Of all the methods available to generate this 1,3-dipole, the photochemical generation of nitrile ylides from 2tf-azirines offers the greatest opportunity for structural variation. The 2/f-azirine ring can be readily prepared in large quantities using either the vinyl azide route developed by Hassner and coworkers or the modified Neber reaction sequence. 3-Aryl-2 -azirines (15) can also be obtained in good yields by reaction of alkylidene phosphoranes... 

The Neber rearrangement of oxime 0-sulfonates to 2//-azirines (or a-amino ketones, after aqueous acid workup) has been reviewed, together with the modified Neber , involving /V,/V,A-trimethylhydrazonium iodides.With an excess of base, the a-amino acetal can be formed from the 2//-azirine via the unstable 2-alkoxy aziridine. 

The 2//-azirine may be optically active and therefore be regarded as a chiral building block for enatioselective synthesis. This opens a wide field of investigation and recently efforts have been made to produce optically pure azirines. Considering the anionic displacement as the main pathway (and not the nitrene pathway), the Neber reaction may be modified to serve as a synthetic tool for the production of optically active 2//-azirine intermediates. 

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