Potassium permanganate reductive amination

Since many aliphatic primary amines are usually prepared by methods not involving the reduction of a nitroalkane (cf. aromatic amines), their oxidation may provide a useful route to this class of compound. For amines which lead to tertiary nitroalkanes, potassium permanganate appears to be the most satisfactory reagent198 (the preparation of 2-nitro-2-methylpropane, Expt 5.191). In the case of amines which lead to primary or secondary nitroalkanes the oxidant of choice is m-chloroperbenzoic acid, and Expt 5.191 includes a general procedure for this reaction.199... 

The presence of a tertiary methyl group and an exocyclic double bond in spiradine G was demonstrated by H-NMR analysis. Mild reduction of spiradine G with sodium borohydride afforded the triol 173, which indicated that the remaining two oxygen atoms exist as a part of two carbinol-amine ether (N—C—O—C) linkages in spiradine G. The presence of an exocyclic double bond in the six-membered ring was confirmed by catalytic hydrogenation of spiradine G to compound 174 and oxidation of 172 with potassium permanganate to compound 175. 

The popularity of the Nef reaction is due in part to the ready availability of nitro compounds. Primary and secondary halides react with sodium nitrite in dimeAyl sulfoxide (DMSO) or dimethylform-amide (DMF) to give useful yields of nitro compounds. Primary amines can be oxidized to nitro compounds with potassium permanganate, m-chloroperbenzoic acitP or ozone. Chlorination of oximes with hypochlorous acid and reduction with magnesium, zinc or hydrogen/lpalladium gives secondary nitro compounds. Stabilized carbanions can be nitrated by treauitent with a nitrate ester, and enol acetates are nitrated by acetyl nitrate to give nitro ketones. ... 

Extension of the scope of the methodology to a full stereocontrol in the addition sequence A in order to obtain either, Z-anti- or l,2-ry -diol units was hampered by the inherent //-selectivity of the addition of 2-TST to a,/3-dialkoxy aldehydes. Control of the selectivity by the use of Lewis acids acting as chelating agents was also foiled by substantial decomposition of 2-TST. This limitation was overcome by conversion of the 7 //-adduct into the syn-isomer via an oxidation-reduction sequence <1989JOC702>. The secondary (Rj-alcohol 457 was oxidized to ketone 461 with potassium permanganate partly solubilized with TDA-1 (tris[2-(2-methoxyethoxy)ethyl]amine). It was proved that under these neutral nonaqueous oxidation conditions no appreciable racemization occurred via exchange... 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

An example of this reaction is the synthesis of 4,6-dimethylpteridin-2-amine (1) from 2,4-dichloro-6-methyl-5-nitropyrimidine and aminoacetone. Initially 4-acetonylamino-2-chloro-6-methyl-5-nitropyrimidine is formed which, by reaction with ammonia, gives the corresponding pyrimidin-2-amine.132 This undergoes reductive cyclization to 4,6-dimethyl-7,8-dihydropteridin-2-amine, which may be subsequently oxidized (potassium permanganate) to l.133... 

Compounds of formula 63 are readily cyclized by reduction of the nitro group with Raney nickel and hydrogen. The amine thus formed condenses intramolecularly, with the carbonyl function providing the 3,4-dihydro system 64. This may be smoothly oxidized with iodine or an acetone solution of potassium permanganate. " " This route has been used for the unambiguous synthesis of compounds 65, 66, 67, and 68 48.49 Qf particular interest are compounds 66 and 67, which have been used to confirm the orientation of products from the reaction of polyaminopyridines with pyruvaldehyde and p-chlorophenylglyoxal. ... 

On treatment of acomonine with potassium permanganate in aqueous acetone, an anhydro-oxy-derivative resulted. This internal carbinol amine ether was converted into the original base by sodium borohydride reduction. Permanganate oxidation of desoxyacomonine gave an oxo-derivative containing a y-lactam. On the basis of this chemical and additional spectral data, the secondary hydroxy-group was located at C-3. 

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