Reduction carbon-nitrogen double bonds

Selective hydrogenation of carbon-nitrogen double bonds Reduction at controlled potential... 

Acetylide addition in the racemic version Originally, 4equiv of lithium 2-pyridylacetylide (6) in THF/hexane was added to a mixture of 5 and 4equiv of Mg(OTf)2 in Et20 at room temperature. Precoordination with Mg(OTf)2 and 5 was reported to be essential to prevent reduction of the carbon-nitrogen double bond in 5 [2]. However, it turned out that precoordination was unnecessary for this reaction, as shown in Scheme 1.4, and racemic adduct 7 was obtained in 86% yield by treatment with 1.3 equiv of 6 at -15 °C in THF without Mg(OTf)2. 

Fry and Newberg 1,2> examined the electrochemical reduction of nor-camphor oxime (109) and camphor oxime (110) to the corresponding amines. The results of this study are shown in Table 3. It is clear from a comparison of these data with those in Table 2 that the electrochemical reduction of oximes 109 and 110 takes a very different stereochemical course from reduction of the corresponding anils 103 and 104. Reduction of oximes apparently proceeds under kinetic control, affords products corresponding to protonation at carbon from the less hindered side of the carbon-nitrogen double bond, and affords the less stable epimeric amine in each case. It is not evident why the stereochemistry of reduction of anils and oximes should differ, however. 

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. 

N 1 C2 N II c Reduction of carbon-nitrogen double bond 1 Must belong to a primary or secondary amine group 2 Cannot be a terminal atom 2 sp Carbon... 

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

The carbon-nitrogen double bond in imines is reduced at less negative potentials than the corresponding carbonyl function. Also imine radical-anions are more basic than carbonyl radical-anions. Imines with at least one phenyl substituent on the carbon-nitrogen double bond are sufficiently stable for examination in aprotic solvents and reversible one-electron reduction of benzaldehyde anil [179] or benzophenone anil [ISO] can be demonstrated with rigorous exclusion of moisture. 

Under ordinary conditions, reduction of these imines in dimethylformamide is a two-electron process involving saturation of the carbon-nitrogen double bond [181] because the radical from protonation of the radical-anion is more easily reduced than the starting imine. Immonium salts with two or more phenyl substituents are reduced reversibly in acetonitrile to the radical-zwitterion such as 42. Other immo-niura salts, e.g. 43, are reduced irreversibly to the dimer [182]. Radical-zwitterion intermediates generated from immonium salts exhibit nucleophilic character on carbon. Intramolecular interaction between the reduced immonium function and a... 

The carbon-nitrogen double bond of A1-piperideines is susceptible to reduction. This can be useful for the stereospecific introduction of ring substituents. An illustration is the preparation of ds-2,6-disubstituted piperidines (211) by catalytic hydrogenation of the corresponding A1-piperideine (210) (77T1569). 

Reduction of the Carbon-Nitrogen Double Bond C.AADihydro-addition... 

The carbon-nitrogen double bond of phenanthridine can be reduced selectively by hydrogenation over Raney nickel, and attempted reductive dechlorination of 6-chloro derivatives in the presence of this catalyst normally results in the formation of the corresponding 5,6-dihydro compounds.106 Hydrogenations over palladium catalysts are more successful.203 325 Desulfurization of phenanthridinthione... 

Treatment of an ethereal solution of 4-oxo-dihydro-l,3-diaza-anthracene (108) with lithium aluminum hydride reportedly resulted in the reduction of only the 1,2-carbon-nitrogen double bond with 4-oxo-l,2,3,4-tetrahydro-l,3-diazaanthracene (109) being the only product isolated.134 Apparently conditions were not sufficiently vigorous for the further reduction of the tautomeric form of 109, or possibly the formation of a complex with the aluminohydride pre-... 

Oximes, hydrazones, semicarbazones, diazines and carbodiimides all undergo reactions involving addition to a carbon-nitrogen double bond (A, D], but these reactions are of limited value, with the exception of the reaction with ketoximes. This last reaction, with an excess of Grignard at elevated temperatures, is a useful route to aziridines, (4), although yields are rarely high. In some cases, reduction of the intermediate azirine (2) leads to an alternative aziridine (5). 

Alper has used this same system for reduction of the carbon -nitrogen double bond. Thus treatment of phthalazinc (I) with Fe3(CX)),2 in refluxing methanol-benzene for... 

The mechanism of the cathodic reduction of carbon-nitrogen double bonds is not very different from that of a carbonyl group. As shown in Scheme 3, an initial one-electron reduction leads to a radical anion... 

In this chapter the reduction of compounds with a carbon-nitrogen double bond is discussed besides the classic carbonyl derivatives, such as Schiff bases, hydrazones, and oximes, diazoalkanes are also treated. 

In alkaline solution, a two-electron reduction is found that results primarily in a saturation of the carbon-nitrogen double bond the reducible species is probably the azomethine compound C6H5CH=N-C(S )C6H5. 

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 ... 

Many aldehydes (RCHO) and ketones (R2CO) are converted into amines by reductive amination reduction in the presence of ammonia. Reduction can be accomplished catalytically or by use of sodium cyanohydridoboratc, NaBHjCN. Reaction involves reduction of an intermediate compound (an imine RCH NH or R2C NH) that contains a carbon-nitrogen double bond. 

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