Amines from reductive amination

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. 

Amine synthesis from reductive amination of a ketone and an amine in the presence of excess formic acid, which serves as the reducing reagent by delivering a hydride. When the ketone is replaced by formaldehyde, it becomes Eschweiler-Clarke reductive alkylation of amines. 

If the addition of hydrogen takes place in a 1,2-mode the products are oximes, hydroxylamines, amines, and carbonyl compounds resulting from the hydrolysis of the oximes [567], Oximes and carbonyl compounds also result from reductions of a,/3-unsaturated compounds with iron [569, 570] and an oxime was prepared by catalytic hydrogenation of a )S-nitrostyrene derivative over palladium in pyridine (yield 89%) [571]. 

The secondary amine and nitrous oxide are the only isolated products from reduction of nitrosamines in alkaline solution [117]. 

An example that demonstrates the possibilities inherent in the Hg cathode —(C4H9)4N + electrolyte method, for the preparation of products which are inaccessible by other methods, is found in the reduction of diphenyl ether 12). The only products of 12 from reduction with alkali metals in liquid NH3, amine solvent or HMPA 43b-e) were phenol and benzene, presumably arising from cleavage at the radical anion stage. Similarly phenol and benzene were formed by cathodic reduction... 

Tie first product from reduction of the N-O bond is an unstable imino-enol. The enol tautomerizes the ketone and the imine maybe reduced further to the amine. We used this sort of chemistry on products of 1,3-dipolar cycloadditions in Chapter 35 and isoxazoles are usually formed by such ons. 

This transient intermediate decarboxylates under reaction conditions to afford the bis(enone) 154. Hydrogenation over platinum proceeds to give the saturated ketone (155). Treatment of 155 with benzylamine in the presence of cyanoborohydride leads to the product from reductive amination (156). Acylation with hydrocinnamoyl chloride affords the amide 157. ... 

Dimethylamine and trimethylamine (commercially available), 1,3,5-tri-N-methyl hexahydro-5-triazine (from reaction of formaldehyde and methylamine), tetramethylhydiazine (gift of B. J. Aylett), tetramethylmethylenediamine (from reaction of formaldehyde with dimethylamine), dimethyl- and diethylnitrosamine (from reaction of nitrous acid with the appropriate dialkylamine), diethylmethyl-amine (from reductive methylation of diethylamine), ethylethylideneamine (from reaction of ethylamine and acetaldehyde), and TMT and TET (from oxidation of the appropriate wnst/m-dialkylhydrazine). 

Scheme 6-35 Mechanisms for forming Pd(PPh3)2 from reduction of a Pd(II) salt with amines or phosphines.

Acyloxaziridines are easily obtained from compounds unsubstituted at nitrogen by reaction with acid chlorides or isocyanates. Acylation proceeds so smoothly that, in the amination of carbonyl compounds, oxaziridine compounds are obtained in better yields on addition of acid chlorides than in the absence of the acylating agent. With aliphatic aldehydes, amination does not succeed at all except in the presence of benzoyl chloride. Proof of structure comes from reduction by iodide to give the acid amide and carbonyl compound. 

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