Reduction aldoximes

A nitrile oxide generated from a sugar derived aldoxime 30 underwent INOC reaction to the chiral pyranoisoxazoline 31 (Eq. 4) [20]. Reductive cleavage of isoxazoline 31 followed by acetylation provided the tetrasubstituted pyran 32. 

In an alternative approach, the isomeric unsaturated pyrrolidine or piperidine aldoximes 245 a and 245b were prepared and subjected to lOOC reaction affording 246a and 246b, respectively (Eq. 28). Esterification of 240 followed by N-tert-BOC protection and DIBALH reduction provided aldehyde 244 (X = 0) which was subjected to Wittig olefination. Introduction of a two carbon aldoxime chain on N in 244 (X = CH2) was carried out by alkylation with Et a-bromoacetate after deprotection of the N atom in 244. Reduction and oxima-tion led to 245. 

The 10 OC route was followed for the synthesis of tetrahydrofurans possessing a y-amino alcohol moiety 247 (Eq. 29) 118]. Aldoximes 21a-f (see also Eq. 3 and Table 2), when heated in benzene in a sealed tube at 110 -120 °C for 6 h, underwent smooth intramolecular cycloaddition to the tetrahydrofuranoisoxazo-lidines 246a-f in 70-83% yield (Eq. 29). This ring closure proceeded stereo-specifically to generate three adjacent stereogenic centers. LAH reduction of 246 b resulted in isolation of stereospecifically functionalized tetrahydrofuran derivative 247b in 75% yield. 

The present preparation illustrates the general method for the synthesis of aziridines by reduction of ketoximes 4 having an aromatic ring attached to carbon a or /3 to the oximino function and of aldoximes 4 having the aromatic ring attached to the carbon atom j3 to the oximino group. It has also been applied... 

Similarly the reduction of both aldoxime and ketoxime gives again primary amines. 

Generally primary nitro compounds are reduced to aldoximes and secondary to ketoximes by metal salts. On reduction with stannous chloride 1,5-... 

Aldoximes yielded primary amines by catalytic hydrogenation benzaldehyde gave benzylamine in 77% yield over nickel at 100° and 100 atm [803, with lithium aluminum hydride (yields 47-79%) [809, with sodium in refluxing ethanol (yields 60-73%) [810] and with other reagents. Hydrazones of aldehydes are intermediates in the Wolff-Kizhner reduction of the aldehyde group to a methyl group (p. 97) but are hardly ever reduced to amines. 

Sodium cyanoborohydride is the most commonly used reagent for reduction of oximes and oxime ethers. Although this reaction is highly versatile, and does not interfere with a majority of functional groups, careful control of reaction conditions is necessary. A considerable problem in the reduction, especially for aldoximes 80 (equation 57), is the reaction of initially formed A-alkylhydroxylamine 81 with the starting oxime 80. The obtained nitrone 82 is subsequently reduced to A,A-dialkylhydroxylamine 83, which was found to be a major reaction product at pH = 4 and above. This side reaction can be avoided by adjusting the pH of the reaction mixture to 3 or below. 

Sera and coworkers, during their investigation on electroreduction of nitroalkenes, found that plates of powder or metalhc lead can reduce nitroalkene 20 to give oxime 21 in acetic acid-DMF solution without electricity (Scheme 18). The reduction of 1-nitro-1-alkenes afforded the corresponding aldoximes or ketoximes in excellent yield. 

The reduction of conjugated nitroalkenes such as S-nitrostyrenes to oximes provides easy access to a large number of versatile organic intermediates. However, despite their potential utility, many of these methods suffer from the use of strongly acidic or basic conditions, requirement of anhydrous conditions, and incompatibility with halogenated arenes. Eurther, some of the methods are inefficient for the preparation of aldoximes due... 

Electrochemical oxidation of aldoximes using halide ions as mediators afforded the corresponding nitrile oxides in the anode compartment, which were simultaneously reduced to nitriles by cathodic reduction (equation 15). Sodium chloride affords the best result among the supporting electrolytes (Cl > Br > 1 > C104 > TsO ). Accordingly, the electrochemical reaction of oximes carried out in the presence of dipolephiles yielded isooxazolines (equation 16). 

Reduction of ketoximes.1 Ketoximes are reduced by LiAlH4 to a mixture of primary and secondary amines. In contrast, reduction with LiAlH4-HMPT in the molar ratio 1 10 in refluxing THF (130°, 3 hours) results in ketones. HMPT is believed to prevent further reduction of the imine intermediate and to facilitate hydrolysis. This method is not useful for reversion of aldoximes to aldehydes because of dehydration to nitriles. 

Compounds containing the C=N functional group derivatives undergo anodic oxidation when the nitrogen atom bears an electron-rich heteroatom. Perhaps the simplest such species are aldoximes, which are anodically oxidized to nitrile oxides (34)38. The reaction was carried out in an undivided cell3 , hence the species 34 underwent immediate reduction to a nitrile (equation 19). However, since nitrile oxides are 1,3-dipolar species, one could in principle carry out the oxidation in a divided cell in the presence of a good 1,3-dipolarophile40 to effect the synthesis of substituted heterocycles. 

An alternative to solid-supported catalysts are catalysts that are insoluble themselves [136]. A pyridine-aldoxime ligand was presented and evaluated in the Suzuki-Miyaura reaction using water as a solvent. Using an Irori kan to contain the polymeric catalyst, the reaction could be repeated 14 times without any noticeable reduction in efficiency. The optimized reaction conditions were then used to create a small library of approximately 30 biaryl compounds using aryl iodides, bromides, triflates as well as an activated chloride (Scheme 56) [136]. 

Isopropylamine is formed in the reduction of aeetoxime in sulphuric-acid solution at a lead cathode (Tafcl and Pfeffer-mann1). This process is a general one. The electrolytic reduction of ketoximes leads, like that of the aldoximes and phenylhydrazones, to the final formation of amines. About 66% of the theoretically possible quantity of isopropylamine is formed from aeetoxime acetonphenylhydrazone gives about the same yield. 

Selective reductions. Borch et af. have recenlly reported a study of the reduction of various organic functional groups with sodium cyanoborohydride. Under neutral conditions, carbonyl groups are reduced to a negligible extent, but reduction is rapid at pH 3 4. Ketoximes are reduced smoothly at pH 4 to the corresponding alkyl-hydroxylamines. Reduction of aldoximes results mainly in the dialkylhydroxylaminc. 

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