N-0 bond reduction

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Interestingly, both the amino and the hydroxy groups can participate in another reaction with a suitable reacting group present in the molecule as shown with the two examples in Scheme 23 <1998T11581>. Finally, it should be mentioned that this N-0 bond reduction is also efficient starting from quaternary ammonium derivatives of hexahydro-isoxazolo[2,3- ]pyridines <1999JOC1932>. 

Sml2 can reduce N-0 bonds in many other substrates. In 1995, Keck studied the reduction of the N-0 bond in amide 53. Whereas reducing systems including Al(Hg), Na(Hg) and hydrogenolysis proved unsuccessful, treatment of 53 with Sml2 resulted in smooth N-0 bond reduction to give 54 in 91 % yield (Scheme 4.39).42... 

Denmark and coworkers have found that methylaluminum bis (2,6-di-tert-butyl-4-methyl-phenoxide) (MAD) or methylaluminum bis(2,6-diphenylphenoxide) (MAPh) is effective as the Lewis acid promoter for cycloaddition of 2,2-disubstituted 1-nitroalkenes (Eq. 8.100).158 Other Lewis acids such as SnCl4, TiCl4, and TiCl2(Oi-Pr)2 fail to promote the cycloaddition of 2,2-disubstituted 1-nitroalkenes. The products are converted into 3,3-disubstituted pyrrolidines via hydrogenolysis.158 Reductive cleavage of N-0 bonds produces oxime hemiacetals, which are further reduced to amido aldehydes and finally to pyrrolidines. This reaction provides a useful synthetic method for pyrrolidines, which is discussed later. 

Dipolarophiles D3. 1,3-Dipolar cycloadditions of suitably functionalized cyclic nitrones with terminal alkenes, which have potential leaving groups X at the end of the alkane chain -(CHo),- (D3), were successfully used for the synthesis of pyrrolozidine, indolizidine and quinolizidine alkaloids, such as (+ )-and (—)-lentiginosine, a potent amyloglucosidase inhibitor (Scheme 2.243) (742). Reductive cleavage of the N-0 bond in the cycloadduct is important for the subsequent cyclization to pyrrolozidines, indolizidines, and quinolizidines. 

New selected possibilities created by reduction of new types of oxazines (603) in the synthesis of polyfunctional products (473, 554) are presented in Scheme 3.285. Coupling the reduction of the C=N bond with NaBH CN followed by hydrogenation of the N-0 bond or a one-step catalytic hydrogenation, and the double-bond transfer from the C(3) to the C(4) position, enables the synthesis and detection of 14 types of reduction products. In some cases, reduction is stereoselective. 

Finally, the remaining steps were accomplished by methylation of 26a with methyl fluorosulphonate in ether to give the methylammonium salt 25, reductive cleavage of the N-0 bond with LAH and oxidation of the resulting alcohol with Jones reagent. The yields of the last three steps are almost quantitative and the overall yield of the seven steps synthetic sequence leading to optically pure (+)-luciduline (1) is 33%. 

N-nitosoamine Reduction The reduction of N-nitrosoamines can occur across either the N-N bond or the N-0 bond. Both reactions ultimately result in the formation of the parent amine and ammonia. 

At low temperature, the dissociation of adsorbed NO species occmring over reduced perovskite and yielding N2O and N2 was recognized as the rate determining step for catalytie reduction of NO by CO. The dimeric species of NO, such as N2O2, can be an intermediate, the formation of which involves the N-N bond formation and N-0 bond eleavage[40]. Two parallel reaetions for chemisorbed NO dissociation occurring over a redueed surfaee with N2O and N2 as the respective products were assumed ... 

Hydrogenation/Reduction/Reductive Ring Cleavage of the N-0 Bond, 6.2 Hydroxylation of the Ring Carbon-Carbon Double Bond/Oxidation, 6.3 Ozonolysis. 6.4 Epoxidation... 

Hydrogenation/Reduction/Reductive Ring Cleavage of the N-0 Bond... 

Scott Denmark of the University of Illinois reports (J. Org. Chem. 68 8015,2003) a hetero intramolecular Diel-Alder reaction of a nitro alkene 5, followed by intramolecular dipolar cycloaddition of the resulting nitronate 6, to give the tricycle 7. Raney nickel reduction effected cleavage of the N-0 bonds and reductive amination of the liberated aldehyde, to give, after acetylation, the angularly substituted cis-decalin 8. 

Catalytic reduction of 1,2,4-oxadiazoles also breaks the N-0 bond e.g. (349) gives (350). Benzofuroxan can be reduced under various conditions to benzofurazan (351), the dioxime (352) or o-phenylenediamine (353) (69AHC(10)l). Reduction by copper and hydrochloric acid produced o-nitroanilines (Scheme 50) (60AHC(i0)l). 

Catalytic reduction161,162 with various catalysts (Pt02, Pd/C, or Raney Ni) on other oxadiazoles all broke the N—0 bond [Eqs. (47-49)]. The product in one case (52) was acetamidine benzoate, which suggested the reduction pathway shown in Eq. (47). 

The reductive method leads to oximes, which may be hydrolyzed to the corresponding carbonyl compound. Ti(III) serves to reduce the N-0 bond, and titanium s strong affinity towards oxygen facilitates the hydrolysis to complete the conversion ... 

The reduction is straightforward the N-0 bond is weak and is reduced by catalytic hydrogenation but the hydrolysis needs some comments. Early and violent methods included the Nef reaction1—the hydrolysis of the enol form 8 in strong acid, probably via the intermediate 10 with liberation of nitrous oxide N2O. 

The electrocatalytic mechanism of the reduction of 2-nitro- and 4-nitroimidazole [948, 949] and 3-nitro-1,2,4-triazole [950] on gold (Au) potential deposition electrode proceeds through chemisorption of the nitro group and reductive cleavage of one of the two N-0 bonds and gives diffusion-controlled limiting currents. 

The electrochemical behavior of azomethine derivatives, e.g., oximes, of heteroaromatic carbonyl compounds is much like that of the corresponding benzene derivatives.91 Pyridine aldoximes271-274 and ketoximes275 are reduced in acid solution by a four-electron reaction to the amine. The reaction mechanism is probably, as in other oximes,01 a reduction of the protonated compound with cleavage of the N-0 bond, followed by saturation of the C=N double bond. The amine is often further reducible at a more negative potential (Section VI, E). 

Isoxazolines 54, prepared by stereoselective 1,3-DC of nitrile oxides and enantiopure allylic alcohols, were converted into p-amino acids 56 eind 58 by nucleophilic addition to the C=N bond followed by reductive cleavage of the N-0 bond and oxidative cleavage of the diol moiety. The facial selectivity in the nucleophilic addition was dictated by the C-5 substituent in either a directed (hydride addition) or a sterically (Grignard reagents addition) controlled manner <03JA6846>. 

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