Neber oxime tosylate-amino

Neber oxime tosylate-amino ketone rearrangement... 

An a-amino ketone, obtained by the Neber rearrangement, can be further converted into an oxime tosylate, and then subjected to the Neber conditions a ,a -diamino ketones can be prepared by this route. 

N-Chlorocyclohexylideneimine is of theoretical interest, being isoelectronic with the oxime tosylate. On treatment with 1 mole of base the imine undergoes a Neber-type rearrangement to the a-amino ketone and has been shown to be an intermediate in the rearrangement of N,N-dichloroc> clohexylamine to 2-2imino-cyclohexanone. ... 

The Neber rearrangement involves the base-catalyzed conversion of oxime tosylates, quaternary salts of hydrazones or /V-chloroimines to a-amino ketones via isolable azirine intermediates (equation... 

In the synthesis of various heterocycles from a-amino ketones, pyrazine formation can be a complicating side reaction due to the tendency of the a-amino ketone to dimerize. One way of avoiding this problem would be to generate the a-amino ketone in a protected form, specifically, as an a-amino acetal. Such derivatives allow the manipulation of the amino moiety as desired. Accordingly, the azirine intermediates derived from oxime tosylates by the Neber rearrangement are subsequently treated with acidic ethanol to furnish the corresponding a-amino acetals (equation 65). ° ... 

Fewer mechanistic details are available for the Neber rearrangement than for the closely related Favorskii and Ramberg-Backlund reactions. Oxime tosylates, when treated initially with base and then with water, yield a-amino-ketones, viz-... 

This reaction, like all Neber rearrangements, is limited by availability of the appropriate oxime tosylate. Substrates in which the aryl group contain an electron-donating function are unstable, since they have a propensity to undergo Beckmann rearrangement. However, this difficulty can be resolved by subsequent conversion of the a-amino acetals. For example, catalytic hydrogenation of 2,2-diethoxy-2-(p-bromophenyl)ethylaraine yields the known parent compound, 2,2-diethoxy-2-phenylethylamine These two a-amino acetals readily undergo hydrolysis and should be protected from moisture. 

The Neber route has been noted to be mildly influenced by the introduction of chiral auxiliaries. Thus, rearrangement of the tosyl oxime 860 (formed in situ from the oxime 859) in the presence of catalytic amounts of the chiral quaternary ammonium bromide 858 led to the formation of enantiomerically enriched amino ketone 863, which is presumed to arise from the preferential formation of the intermediate 2//-azirine 862. Association of the cationic chiral auxiliary with an anionic intermediate (i.e, 861) has been invoked to rationalize the stereochemical outcome (Scheme 215) <2002JA7640>. 

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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