Reduction, of oximes

Oximes can be reductively converted into the Boc-protected primary amines in good yields with the combination of PMHS/(Boc)20/Pd/C (Eq. 327).548 O-Benzyloxyimines549 are reported to be reduced in good to excellent yields by this method. 

O -Benzoyloximcs are nicely reduced to 9-benzoyl hydroxy lamincs with EtsSiH/TFA (Eq. 328) 550,551 9-Acetyl oximes arc reduced with Et3SiH/TMSOTf in moderate to high yields.552 The diethylphosphatoimine 88 is reduced to the hydroxylamine derivative.553 

The treatment of ketoximes with lithium aluminum hydride is usually a facile method for the conversion of ketones into primary amines, although in certain cases secondary amine side products are also obtained. Application of this reaction to steroidal ketoximes, by using lithium aluminum deuteride and anhydrous ether as solvent, leads to epimeric mixtures of monodeuterated primary amines the ratio of the epimers depends on the position of the oxime function. An illustrative example is the preparation of the 3(x-dj- and 3j5-di-aminoandrostane epimers (113 and 114, R = H) in isotopic purities equal to that of the reagent. 

Deuteration at C-3 by Reduction of 5a.-Androstan-3-one Oxime with Lithium Aluminum Deuteride 

A solution of 5a-androstan-3-one oxime (112 0.6 g) in dry ether (40 ml) is added dropwise to a boiling suspension of lithium aluminum deuteride (1.6 g) in dry ether (80 ml). The reaction mixture is heated under reflux for 

30 min, cooled, then saturated aqueous sodium sulfate solution is added dropwise with caution. Ether extraction, washing of the ether phase with water and drying over anhydrous magnesium sulfate, followed by evaporation of the solvent, yield a semi-solid mixture of 3a- and 3)5-aminoandrostanes, which are acetylated directly with acetic anhydride (1 ml). After storing the reaction mixture at room temperature for 10 min, water and then dilute sodium carbonate solution are added. Ether extraction and the usual workup (see above) give a crystalline mixture of the 3a-dj-3)5- and 3j5-di-3a-acetamino-5a-androstanes (113 and 114, R COCHs) in 83% yield. The epimers (113) and (114) can be separated by fractional crystallization from ethyl acetate, both epimers exhibiting virtually 100% isotopic purity.  

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By the reduction of oximes with sodium and absolute ethyl alcohol, for example ... 

The reduction of oxime derivatives (section IV-C) is useful for the preparation of steroidal amines labeled with a deuterium on the nitrogen-bearing carbon atom... 

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. 

Derivatives of Aziridines Prepared by Reduction of Oximes with Lithium Aluminum Hydride... 

Aziridines from reduction of oximes with lithium aluminum hydride, 48,23... 

Asymmetric reduction of oxime ethers,2 The complex (1) of (- )-norephedrine with BH3 (2 equiv.) reduces prochiral oxime ethers to optically active amines the... 

Stannous chloride is used most frequently for the reduction of nitro compounds [177, 178, 179] and of quinones [180, 181], It is also suitable for conversion of imidoyl chlorides [182] and of nitriles [183] to aldehydes, for transformations of diazonium salts to hydrazines [184], for reduction of oximes [f[Pg.30]

Preparative scale reduction of oximes at a mercury or lead cathode in acid solution has been used in the conversion of the carbonyl function to amine. Originally, 30-50% sulphuric acid was used as solvent [195] but ethanol with dilute hydrochloric acid is usually satisfactory. Aliphatic and aromatic oximes give amines in 64-86% yields [196]. Aromatic ketoximes are also reducible in alkaline solution and acetophenone oxime has been converted to 1-phenylethylamine in a tri-potassium orthophosphate solution [197], The reduction of oximes in acid solution is tolerant of many other substituents as indicated by a number of examples [198, 199, 200. Phenylglyoxa monoxime in acid solution is however reduced at both the carbonyl and the oxime centres by sodium amalgam to yield 2-amino-1-phenylethanol [201]... 

The synthesis of amines from oximes is exemplified by the reduction of oxime 332 to 333 (99W032453) and of bicyclic oximes (derived from ketones 3 and 23a), for instance, of oxime 387 (Scheme 87) to amine 388 that is acylated to yield potential pharmaceutical agent 390 (92BML1147). Nucleophilic substitution of chloropyridine 384 generates morpholino derivative 385 (76IJB400). 

C. Hydroxylamines through Reduction of Oximes, Oxime Ethers... 

Reduction of oximes and nitrones with complex hydrides. 136... 

Complex hydrides are reagents of choice for reduction of oximes, oxime ethers and nitrones. Hydrogenation is rarely used for reduction of these compounds although several examples are known. Other methods, especially reduction with silanes in the presence of acid, can also be useful for providing alternative stereochemical outcomes. 

Sodium cyanoborohydride is the most commonly used reagent for reduction of oximes and oxime ethers. Although this reaction is highly versatile, and does not interfere with a majority of functional groups, careful control of reaction conditions is necessary. A considerable problem in the reduction, especially for aldoximes 80 (equation 57), is the reaction of initially formed A-alkylhydroxylamine 81 with the starting oxime 80. The obtained nitrone 82 is subsequently reduced to A,A-dialkylhydroxylamine 83, which was found to be a major reaction product at pH = 4 and above. This side reaction can be avoided by adjusting the pH of the reaction mixture to 3 or below. 

Lithium cyanoborohydride reduces oximes to hydroxylamines in good yield. Careful pH control is not necessary in this case and reduction can be done efficiently in the presence of acetic acid at pH 5 . Lithium borohydride reduces oximes as well. Sodium borohydride in acetic acid or on silica gel has been used for reduction of oximes, but reported yields were low to moderate only. Lithium aluminum hydride " and DIBAL are capable of reducing oximes, but are sufficiently chemoselective for reduction of polyfunctional oximes. 

Stereoselectivity in reductions of acyclic oximes depends on the configuration of C=N bond. ( )-Isomer of oxime 89 produced syn-hydroxylamine 90 in excellent stereoselectivity in reaction with phenyldimethylsilane-trifluroacetic acid while giving anti-product in the reaction with lithium aluminium hydride. Stereoselectivity in reductions of (Z)-isomers of 89 was substantially lower in both cases (equation 62) . It can be assumed that the rules of stereoselectivity established in diastereoselective reduction of ketones can be applied to reduction of oximes as well. 

Enantioselective reduction of ketoxime ethers with chiral boron hydrides produces chiral 0-alkylhydroxylamines with variable ee. Reduction of oxime ethers of type 94 (equation 65) with norephedrine-derived oxazoborolidine 95 proceeds with very high ee. However, an analogous reduction of acyclic aromatic oximes with chiral oxab-orazolidines produced a mixture of amine and hydroxylamine . 

Reduction of oxime 90 with NaBH4 leads to a mixture of three products 91-93. At low temperatures (—10 °C) pyrroloindole 91 was isolated as the main product (equation 39) ". ... 

The electrochemical reduction of phenylglyoxylate oxime in the presence of strychnine afforded the corresponding optically active amines (equation 4). Also, the electrochemical reduction of oximes by utihzing poly-L-vahne-coated graphite electrode afforded optically active amine. However, in both cases the enantioselectivities were very low. 

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