In the Neber rearrangement

Important synthetic paths to azirines and aziridines involve bond reorganization, or internal addition, of vinylnitrenes. Indeed, the vinylnitrene-azirine equilibrium has been demonstrated in the case of trans-2-methyl-3-phenyl-l-azirine, which at 110 °C racemizes 2000 times faster than it rearranges to 2-methylindole (80CC1252). Created in the Neber rearrangement or by decomposition of vinyl azides, the nitrene can cyclize to the p -carbon to give azirines (Scheme 4 Section 5.04.4.1). 

Isolation of an Intermediate. It is sometimes possible to isolate an intermediate from a reaction mixture by stopping the reaction after a short time or by the use of very mild conditions. For example, in the Neber rearrangement (18-12)... 

Asymmetric induction in the Neber rearrangement was also obtained under phase-transfer conditions with chiral quaternary ammonium bromides 544 as catalysts (equation 243). Moderate enantioselectivities (30-70% ee, 60-95% yield) were observed, but there is still an opportunity for extending the full synthetic utility of this classical rearrangement. 

Azirines are prepared by base-catalyzed cycloelimination of imine derivatives, e.g. as isolable intermediates in the Neber rearrangement (87 — 88) (77JA1514). 

An interesting formation of a cyclic imine with a three-membered ring (31) was encountered in the pyrolysis of azidostyrene.188 Compounds of this type are also considered as intermediates in the Neber rearrangement of tosyloxyimino-ketones. 

Ooi, T., Takahashi, M., Doda, K., Maruoka, K. Asymmetric Induction in the Neber Rearrangement of Simple Ketoxime Sulfonates under Phase-Transfer Conditions Experimental Evidence for the Participation of an Anionic Pathway. J. Am. Chem. Soc. 2002, 124, 7640-7641. 

Morrow, D. F., Butler, M. E. Stereoselectivity in the Neber rearrangement-synthesis of a steroidal spiroazirine. J. Heterocycl. Chem. 1964,... 

Oximes which are treated with tosyl chloride can also be used as substrates in the Neber rearrangement to a-amino ketones. The mixture shown in eq 26 was further subjected to reductive amination to 3ueld 14% of the CNS-active cis-lV,A(-dimethylated a-amino alcohol. 

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