Tautomeric nitrone/hydroxylamine

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

Oxidation with m-CPBA of monocyclic isoxazolidines (56) without H at a-C gives a tautomeric mixture of acyclic nitrones (57) and six-membered cyclic hydroxylamines (58), with their proportion depending on the substituents... 

Another synthetic approach for generating sugar-containing nitrones is by initial treatment of sugars with unsubstituted hydroxylamine. The resulting cyclic hydroxylamine of the tautomeric mixture (68a) and of the open chain oxime (68b) react with aldehydes to give the corresponding nitrones (69) (Scheme 2.24) (216-220). 

For the alkynyUiydroxylamines 274 smdied by Holmes (309,311), initial intramolecular 1,3-azaprotiocyclotransfer affords the N-oxides 275 via a 5- or a 6-exo-dig process [Baldwin s terminology (312)], which then tautomerize to the cyclic nitrones (276) (Scheme 1.57). The 1-exo-dig cyclization required for the formation of a seven-membered nitrone (277) by this approach from 278 was found to be disfavored with respect to the alternative reaction of hydroxylamine and alkene 5-exo-trig process) to afford a mixture of the alkynylpyiTolidines 279... 

Several examples of ring-chain tautomerism are known where the cyclic tautomer is formed as a result of an intramolecular hydroxy group addition to the C = N bond of nitrones, yielding hydroxylamine derivatives. 

The Grigg group also studied the tautomerization of oximes to N-H nitrones followed by a dipolar cycloaddition reaction. The well-known H-bonding dimeric association of oximes, in both solution and the solid state, allows for a concerted proton transfer to occur and provides nitrone 56 (Scheme 11) (91TL4007). Another possible pathway involves tautomerization of the oxime to an ene-hydroxylamine (i.e. 57) followed by a 1,4-hydride shift to give nitrone 58. To probe the ene-hydro-xylamine mechanism, deuterated oxime 59 was prepared and heated at 140 °C in xylene. The physical characteristics of the isolated product, however, were consistent with compound 60, suggesting that the 1,2-prototropic reactions does not proceed... 

Vasella [58] has shown that the hydroxy-oxime 122 (2,3-0-isopropylidene-5-0-trityl-D-ribose oxime) can be, via its tautomeric form a-alkoxy-hydroxylamine 123, converted by reaction with carbonyl compounds (formaldehyde, acetaldehyde, etc.) to N-(alkoxyalkyl) nitrones 124 which then reacts via 1,3-dipolar cycloaddition with methyl methacrylate to give the protected isoxazolidine ribosides 125, 126 epimeric at C5. This reaction proceeds in high yield (97 %) and with high stereoselectivity (84 16) (Fig. 8.35). 

The stability of ARs is conditioned by tautomeric conversions and depends on the chemical structure of substituents at the N atom, temperature and solvent [5,9]. The general mechanism of AR decay is a disproportionation reaction with formation of nitrones and hydroxylamines. ARs having primary or secondary alkyl groups are short-lived species because they easily undergo disproportionation by the scheme ... 

When 90 was heated in toluene, the hydroxylamine added to the alkyne to afford nitrone 91 (after tautomerization of a presumed intermediate N-hydroxyenamine) which was trapped by styrene in an intermolecular 1,3-dipolar cycloaddition to provide 92. An oxidation state adjustment (with removal of the chiral auxiliary) gave 93. The TBDPS protecting group was removed and the resulting primary alcohol was oxidized with IBX (94) (related to the Dess-Martin periodinane) to give aldehyde 95. Application of the Yamamoto variation of the Peterson olefmation gave 96 with decent control over olefin geometry. 

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