Ketone oximes derivatives, reduction with

The conversion of nitroalkanes to ketoximes can be achieved by the reduction with Zn in acetic acid,112 or Fe in acetic acid.113 Nitroalkenes are direcdy reduced into saturated ketoximes by these reagents, which are precursors for ketones (see Section 6.1.4 Nef reaction). Reduction of 3-O-ace-ty lated sugar 1 -nitro-1 -alkenes with Zn in acetic acid gives the corresponding 2,3-unsaturated sugar oximes in high yield, which is a versatile route to 2,3-unsaturated sugar derivatives (Eq. 6.58).114... 

The 36d-LAH complex was applied to the reduction of ketone oximes and their O-tetrahydropyranyl and O-methyl derivatives to optically active amines (69). Results for a variety of phenyl alkyl and dialkyl ketones are shown in Table 4. The predominant amines formed all were of the S absolute configuration with optical purities up to 56%. The oxime hydroxy group presumably reacts with the less hindered H2 in the 36d-LAH complex (cf. Scheme 6) to form an oxime complex (45), which probably undergoes infermolecular hydride transfert of H2 from a second molecule of the 36d-LAH complex (Scheme 8). Asymmetric reduction with the ethanol-modified 36d-LAH reagent gave amines of R con-... 

Reduction of Ketone Oximes and O-Tetrahydropyranyl and O-Methyl Derivatives with... 

Primary and secondary nitroso compounds tautomerize to isonitroso compounds - oximes of aldehydes and ketones, respectively. Their reductions are dealt with in the sections on derivatives of carbonyl compounds (pp. 106,132). 

An alternative synthesis of ( )-a- and ( )--y-lycoranes (57 and 93) commenced with the 2-oxocyclohexyl acetic acid derivative 114 obtained by the alkylation of the enamine derived from 113 (Scheme 10) (116). Refluxing the oxime of 114 with zinc dust in glacial acetic acid afforded a mixture of the lactams 115, 116, and 117 in an approximate ratio of 4 6 3. The structure of 115 was verified by catalytic hydrogenation to give the lactam 118, which had previously been converted to ( )-a-lycorane (57). When the lactam 116 was subjected to sequential catalytic hydrogenation, hydride reduction, and Pictet-Spengler cyclization, ( )-y-lycorane (93) was obtained. A more efficient route to ( )-a-lycorane (57) involved refluxing the ketone 114 first with benzylamine in xylene and then with 87% formic acid to furnish the unsaturated lactam 119. 

Trifluoropropcnc itself reacts regioselectively with various nitrile oxides, even nonaromatic nitrile oxides. The latter arc prepared in one step from oximes and A -chlorosuccin-imide, or in a two-step sequence with isolation of the hydroximoyl chlorides. Cycloadducts, obtained at room temperature in the presence of triethylamine, are then converted into trilluoro- 8-hydroxy ketones 9 by reductive cleavage. The reaction with a dipole substituted by a group derived from L-phcnylalanine allows the preparation of chiral ketones. ... 

Hydroxylamine converts a 16a-bromoandrostan-17-one (216) cleanly into the 17-oxime (217) of the 16a-hydroxy-ketone,""" closely paralleling the action of hydrazine."" Reduction of the oxime-acetate (218) with diborane gave the 17/8-acetamido- 16a -acetoxy-derivative (219)."""... 

Several structural modifications of the C-9 ketone of erythromycin have been explored oximes and hydrazones are less prone to intramolecular cydization, but they often have less antibiotic activity than erythromycin (140). Synthesis of more complex oxime derivatives resulted in the development of roxithromycin, the 9-[0-(2-methoxyethoxy)methyl]oxime (33) (141). Reduction of the oximes and hydrazones produced 9(S)-erythromycylamine (34) as the principal product, with minor amounts of the 9(R)-isomer (140) however, clinical studies showed that 9(5)-erythromycyclamine and its N-benzylidene derivative were poody absorbed in humans (142). Evaluation of more complex oxazine derivatives of erythromycylamine led to dirithromycin, the 2-(2-methoxyethoxy)ethylidene oxazine derivative (35) (143). A third route to modification of the ketone utilized a Beckmann rearrangement of the 9-oxime to expand the 14-membered ring to a 15-membered intermediate, which was subsequently reduced and AT-methylated to yield azithromycin (36) (144,145). The term azalide was proposed to denote these 15-membered azalactones (10,145). 

Reduction of oxime ethers. The O-methyl derivatives of conjugated ketone oximes are reduced to unsaturated amines together with smaller amounts of aziri-dines and saturated amines. 

In an analogous sequence of reactions, 16,23-diisosolanocapsine (160) was synthesized from soladulddine (161). Catalytic hydrogenation of ketone 162 furnished the piperidinols 163 and 164 in yields of 46% and 17%, respectively, whereas reduction with sodium borohydride gave 163 exclusively. The benzyloxycarbonyl derivatives of 163 and 164 yidded the same 23-ketone, 165. Cyclization to ketal 166 was effected by hydrogen chloride in aqueous methanol. Compound 166 was oxidized to the 3-ketone, and its oxime 167 was treated with sodiiun in liquid ammonia and catalytically hydrogenated to furnish 16,23-diisosolanocapsine (160) (792). 

Amino-Alditols.- Anti-selective reduction of acyclic or-alkoxy and of, -dialkoxy ketone oximes occurs with aluminium hydride reagents, L-threo-ketotetrose derivatives (24) giving L-xylitol... 

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

The imides, primaiy and secondary nitro compounds, oximes and sulphon amides of Solubility Group III are weakly acidic nitrogen compounds they cannot be titrated satisfactorily with a standard alkaU nor do they exhibit the reactions characteristic of phenols. The neutral nitrogen compounds of Solubility Group VII include tertiary nitro compounds amides (simple and substituted) derivatives of aldehydes and ketones (hydrazones, semlcarb-azones, ete.) nitriles nitroso, azo, hydrazo and other Intermediate reduction products of aromatic nitro compounds. All the above nitrogen compounds, and also the sulphonamides of Solubility Group VII, respond, with few exceptions, to the same classification reactions (reduction and hydrolysis) and hence will be considered together. 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

The ready accessibility of 1,2-dioximes (glyoximes) and the ease with which they are dehydrated has ensured that this is the most common route to furazans. The starting materials are usually prepared by oximation of the appropriately substituted 1,2-diketone or, more often, by a-nitrosation of an alkyl ketone followed by oximation of the resulting 1,2-dione monooxime (Scheme 16). 1,2-Dioximes can also be prepared by reduction of furoxans (Section 4.05.5.2.4) and, in cases where the furoxan is more readily available than the furazan, for example, by nitrile oxide dimerization, this furoxan-> glyoxime-> furazan sequence represents a viable synthetic strategy for symmetrically substituted derivatives. 

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