Nitrogen-oxygen bond, reduction

The reduction of isoxazoles is often rather peculiar and its course depends on the nature both of the isoxazole and of the reducing agent. Together with a normal reduction of groupings in the side chain, cleavage of the nitrogen-oxygen bond of the heterocyclic nucleus often occurs. 

Catalytic cleavage of the nitrogen-oxygen bond occurs very frequently as in reduction of nitro compounds, oximes, and various heterocyclics these reactions are discussed in separate chapters. Considered here are N-oxides, hydroxylamincs, and N- and C-nitroso compounds. 

Amino alcohols are also good substrates for aziridination under Mitsunobu conditions. The rfs-1,4-amino alcohols 48, obtained by reductive cleavage of the nitrogen-oxygen bonds of the hetero Diels-Alder adducts 47, underwent syn-SN2 -type displacement on treatment with PPh3 and DEAD to give cyclic vinylaziridines 49 (Scheme 2.15) [27]. 

Nitrobenzenes with an ortho or a para hydroxyl or amino function form an exceptional group of compounds in which the nitro function can readily be reduced to amino in alkaline solution. Heterolytic cleavage of the nitrogen-oxygen bond in the phenylliydroxylamine intermediate is promoted by any 2- or 4-substituent which can donate a lone pair of electrons. Further reduction steps then lead to the overall... 

Several isoxazolidines or their quaternary salts derived from the 1,3-dipolar cycloaddition of rr/i-hcxcnolidcs (6,7-dihydrooxepin-2(5//)-ones) to cyclic nitrones, were converted into the corresponding piperidyl- and pyrrolidyloxepi-nones by reduction of the nitrogen-oxygen bond (Equation 4). These amino alcohols provide a new access to the l-azabicyclo[5.3.0]decane core of the Stemona alkaloids <2004EJ04215>. 

The reduction of the 0-methyl oximes [94] is probably analogous to the reduction of the oximes in that the nitrogen-oxygen bond is cleaved before the saturation of the carbon-nitrogen double bond. The similarity in the reduction in acid solution of the oxime and its alkylated derivatives is understandable when the close resemblance between the electroactive forms is considered ... 

Oppolzer s camphor-based sultams 92 proved itself as an efficient, robust auxiliary for enolate amination with 1-chloro-l-nitroso cyclohexane 486 as an electrophile. Thus, sultams 92 were first deprotonated with NaHMDS, and to the sodium enolates thus formed was added a solution of the blue nitrosochloride 486. Decolorization occurred immediately, and the mixture was quenched with hydrochloric acid to give hydroxylamines 487, in all cases as essentially pure diastereomers. The reductive cleavage of the nitrogen-oxygen bond was achieved with zinc dust to yield a-aminoacyl sultams 488. By mild hydrolysis with lithium hydroxide, the chiral auxiliary 91 was removed and recovered under concomitant formation of a-amino acids 490. Any racemization was avoided by applying this procedure, even in the case of the labile substrates with R equals a phenyl or / r -methoxyphenyl substituent. On the other hand, the auxiliary could be cleaved at the stage of hydroxylamines 487, so that not only a-amino acids 490 but also a-hydroxyamino acids 489 became available with excellent enantiomeric purity (Scheme 4.103) [232]. 

In this chapter and in Chapters 10-12, we will review and validate some methods for asymmetric (transfer) hydrogenation of carbon-oxygen and carbon-carbon double bonds catalysed by non-metallic systems, homogeneous transition metal catalysts and biocatalysts. Reduction of carbon-nitrogen double bond systems will be reported in another volume of this series. 

From the recent advances the heteroatom-carbon bond formation should be mentioned. As for the other reactions in Chapter 13 the amount of literature produced in less than a decade is overwhelming. Widespread attention has been paid to the formation of carbon-to-nitrogen bonds, carbon-to-oxygen bonds, and carbon-to-sulfur bonds [29], The thermodynamic driving force is smaller in this instance, but excellent conversions have been achieved. Classically, the introduction of amines in aromatics involves nitration, reduction, and alkylation. Nitration can be dangerous and is not environmentally friendly. Phenols are produced via sulfonation and reaction of the sulfonates with alkali hydroxide, or via oxidation of cumene, with acetone as the byproduct. 

The carbon-oxygen bond formation follows the same pathway. For both nitrogen-carbon and oxygen-carbon bond formation, a competing reaction is 13-hydride elimination (if a hydride is present at the heteroatom fragment), which lowers the yield and the reduced arene is obtained after reductive elimination. Reductive elimination of the C-N or C-0 fragments should be faster than 13-hydride elimination in order to avoid reduction of the aryl moiety. The side-reaction is shown at the bottom of Figure 13.25. 

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