Nitrogen transformation, hydroxylamines

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

Alkenyl nitrones, having the alkene connected to the nitrone nitrogen atom, have been used in another approach to intramolecular reactions (231-235). Holmes and co-workers have this method for the synthesis of the alkaloid (—)-indolizidine 209B 137 (210,231). The alkenyl nitrone 134, was obtained from the chiral hydroxylamine 133 and an aldehyde. In the intramolecular 1,3-dipolar cycloaddition, 135 was formed as the only isomer (Scheme 12.45). The diastereofacial selectivity was controlled by the favored conformation of the cyclohexane-like transition state in which the pentyl group was in a pseudoequatorial position, as indicated by 134. Further transformation of 135 led to the desired product 137. 

E. C. Szarvasky found that the electrolysis of hydroxylamine was accompanied by the spontaneous transformation of hydroxylamine into ammonia. Secondary reactions always occur—the base being reduced to ammonia at the cathode and at the anode oxidized to nitrogen oxides. F. Balia found that with various electrodes the percentage current yield of NaN02 NaN03 in the electrolytic oxidation of hydroxylamine with anodes of different metals was as follows ... 

Interestingly, the stereochemistry of the hydroxyl group on the imino nitrogen in oxime 10 affects the stereochemistry of hydroxylamine 11 (see Scheme 9.4). Thus, hydride reduction of either (Z)- or (E)-oximes 10 with hydroborane in the presence of chiral amino alcohols produces (S)- and (R)-A-benzyl oximes 11, respectively, as shown in the table in Scheme 9.4, which were subsequently transformed to (R)-and (S)-trifluoroalanine 12 [14]. 

Cyclopropyl ketone oximes 35 were converted to 5,6-dihydro-l,2-oxazines 36 on refluxing in ethanol with acid. Alternatively, the original ketones 34 sustained the same transformation on prolonged heating with hydroxylamine hydrochloride in ethanol. A plausible mechanism involves protonation of the nitrogen atom followed by endo-tet ring closure. 

Formation of diaziridinimine 134 had been postulated shortly before to account for a labeling experiment Ohme and Preuschhof had found that in the transformation of hydroxyguanidine-O-sulfonic acid to semi-carbazide there is equilibration of the N-content between hydroxylamine nitrogen and one other nitrogen. 

Oxidation of nitrogen and sulfur compounds. These oxidations serve to complete transformation of amines to hydroxylamines, hydrazones to nitriles, and p-amino esters to conjugated esters.- ... 

Tethering the alkene to the carbon atom of the nitrone allows the preparation of cw-l,2-disubstituted cycloalkanes such as 212. Examples in which the alkene is tethered to the nitrogen atom of the nitrone are also common. Thus, addition of formaldehyde to the hydroxylamine 213 promoted formation of the intermediate nitrone and hence the cycloadduct 214 (3.140). " Subsequent transformations led to the alkaloid luciduline. This synthesis illustrates a useful feature of the 1,3-dipolar cycloaddition reaction of nitrones, in that it provides an alternative to the Mannich reaction as a route to (3-amino-ketones, via reductive cleavage of the N-0 bond in the isoxazolidine and oxidation of the 1,3-amino-alcohol product. In another example of such an intramolecular cycloaddition reaction, the bridged bicyclic product 217, used in a synthesis of indolizidine 209B, was formed by addition of an aldehyde to the hydroxylamine 215, followed by heating the intermediate nitrone 216 (3.141).142... 

Reactions at the Hydroxylamine Nitrogen. These reagents have been used as 0-protected forms of hydroxylamine for synthetic transformations involving the unprotected nitrogen. Thus O-silylhydroxylamines have been used to prepare iV-hydroxy- 8-lactams and substituted dihydro-3-hydroxy-l,2,3-benzotria-zines, as weU as N-alkylated hydroxylamines for use as leuko-triene biosynthesis inhibitors. ... 

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