Oximes synthesis, sodium borohydride

Pinheiro and coworkers investigated the synthesis and reactions of oxime derivatives of tetramic acids (2009TL2402). Reduction of a tetramic acid oxime with sodium borohydride gives a 4-amino-3-pyrrohn-2-one. 

The same methodology was employed by Tiecco to effect the cyclizations of 0-allyl oximes 164 indicated in Scheme 25. Treatment of the intermediate iminium salt 165 with sodium borohydride affords M-alkyl isoxazolidines 166 [95]. Alternatively, 165 can be treated with water to produce M-unsubstituted isoxazolidines 167 [96]. This synthesis of M-alkyl isoxazolidines represents a valid alternative to that described in Scheme 23. Moreover, the present cyclization reaction is much more stereoselective than the cyclization of 0-allyl hydro-xylamines. In fact, when the methyl derivative 168 was employed, the two isomeric isoxazolidines 153 and 154 were obtained in a ratio of 95 5. The same two products were, in contrast, formed in a 1 1 ratio when the reaction was carried out starting from the corresponding 0-allyl hydroxylamines. Clearly, the steric requirements for the selenium-induced cyclization of the 0-allyl oximes are much greater than those for the corresponding 0-allyl hydroxylamines. 

The synthesis of etoxazoie is shown in Scheme 26.2.3 [19, 26]. Starting from 2-ethoxy-4- butyl acetophenone standard procedures lead to an oxime intermediate, which is reduced to the corresponding amino alcohol. Acylation of this amino alcohol with 2,6-difluorobenzoyl chloride and subsequent base-catalyzed cydization after activation of the hydroxy group leads to etoxazoie (4). An alternative route starts with the amino acid ester, which is first acylated using 2,6-difluorobenzoyl chloride and then reduced with sodium borohydride to the same final intermediate. 

Hydroxylamines and Nitramines.—Oximes are readily reduced to hydroxylamines under various conditions, but when the reduction is carried out using sodium borohydride in the presence of a carboxylic acid alkylation also takes place, affording a useful new synthesis of NiV-dialkylhydroxylamines (Scheme 12). The yields of nitramines obtained from the reduction of nitrimines by sodium borohydride may be improved by carrying out the reactions in the presence of acetic acid. ... 

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