Oximes configuration

The course of the reaction is dependent on the configuration of the oxime. The (Z)-oxime gave 1,2-benzisoxazoles as the primary product while the (E)-oxime generally produced a Beckmann rearrangement product with or without subsequent cyclization to a benzisoxazole (Scheme 167) (67AHC(8)277). Bunnett conducted a kinetic study on the reaction shown in Scheme 167 and determined that cyclization to intermediate (551) was the rate determining step (61JA3805). 

The importance of the configuration of the oxime is again demonstrated in the oxidative cyclization of o-aminobenzophenone oximes. The (Z)-oxime with nitrous acid produced 3-phenyl-l,2-benzisoxazole, while the (E)-oxime with similar treatment yielded ben-zotriazine N-oxides (27CB1736). 

One of the more important approaches to 1-azirines involves a similar base-induced cycloelimination reaction of a suitably functionalized ketone derivative (route c. Scheme 1). This reaction is analogous to route (b) (Scheme 1) used for the synthesis of aziridines wherein displacement of the leaving group at nitrogen is initiated by a -carbanionic center. An example of this cycloelimination involves the Neber rearrangement of oxime tosylate esters (357 X = OTs) to 1-azirines and subsequently to a-aminoketones (358) (71AHC-(13)45). The reaction has been demonstrated to be configurationally indiscriminate both syn and anti ketoxime tosylate esters afforded the same product mixture of a-aminoketones... 

Evidently, analogously to the mentioned cyclization of similar oximes to ben-zisoxazole derivatives (See Section II.A), reaction can take place only in compounds with suitable configuration. However, in case of hydrazones, due to the tautomeric equilibrium of both possible configurations, the reaction usually achieves complete conversion. The usual setup involves heating with the respective hydroxide if an ester group is present, it is partially or completely hydrolyzed to the corresponding acids, which, in addition, can also undergo decarboxylation. 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

Unlike the Beckmann rearrangement, the outcome of the Neber rearrangement does not depend on the configuration of the starting oxime derivative E- as well as Z-oxime yield the same product. If the starting oxime derivative contains two different a-methylene groups, the reaction pathway is not determined by the configuration of the oxime, but rather by the relative acidity of the a-methylene protons the more acidic proton is abstracted preferentially. ... 

Since diazoates can be considered to be derived from oximes by substitution of nitrogen for the methine group, Hantzsch (1894) put forward the hypothesis that configurational isomerism was also occurring here. He therefore represented the isomeric diazoates by the structures 7.1 and 7.2, assigning the syn structure (7.1) to the labile diazoate and the anti (7.2) to the stable isomer. Nowadays the description recommended by IUPAC (1979) for such configurational isomers, namely (Z) instead of syn and (E) instead of anti, should be used. 

Hantzsch was unable to provide any direct experimental proof for his hypothesis. His grounds for assigning configurations were the analogies to oximes, such as the differences in stability already mentioned. 

Oximes can be alkylated by alkyl halides or sulfates. N-Alkylation is a side reaction, yielding a nitrone. " The relative yield of oxime ether and nitrone depends on the nature of the reagents, including the configuration of the oxime, and on the reaction conditions. For example, anri-benzaldoximes give nitrones, while the syn isomers give oxime ethers. " ... 

In contrast with the Schiff base salen, salicylaldehyde oxime (79) (salox) complexes of Co have received comparatively little attention, but a series of bis-bidentate divalent complexes of the form iraiis-Co(sa 1 ox)2( D M SO)2 have been reported.343 The heterocyclic bidentate oxime violurate (lH,3H-pyrimidine-2,4,5,6-tetrone 5-oximate, Hvi) (80) and its /V-methyl (mvi) and /V,/V -dimethyl (dmvi) derivatives form high-spin divalent [Co(vi)]+ and Co(vi)2 complexes, whereas [Co(vi)3] is low spin.344 The mixed-ligand Co(dmvi)2(phen) complex is also low spin. The crystal structure of m-Co(pxo)2Br2 (pxo = 2-acetylpyridine-l-oxide oxime) is isostructural with the Ni11 relative.345 The dichloro complex also adopts a cis configuration. The tridentate dioximes 2,6-diformyl-4-methylphenol dioxime and 2,6-diacetyl-4-methylphenol dioxime (Hdampo) form binuclear complexes of the type (81a) and (81b) respectively.346 Cobalt oxide nanoparticles were prepared by... 

The stereochemical use of the Beckmann rearrangement in assigning configuration to ketoximes has already been referred to, and it also has a large-scale application in the synthesis of the textile polymer Nylon-6 from cyclohexanone oxime (78) via the cyclic amide (lactam, 79) ... 

Deoxygenation of Cyclic Nitronates Since cyclic nitronates are readily available and are rather stable compounds (see Sections 3.2 and 3.3), simple approaches for their deoxygenation with retention of the configuration of stereocenters can be used for the synthesis of cyclic esters of functionalized oximes. 

The initially formed titanium enolate 80 adds, in a diastereoselective fashion, to the electrophilic center of the activated oxime. The generated adduct 81 cyclizes chemoselectively to afford the desired /f-azetine, which is converted, with retention of configuration, to the corresponding /3-amino carbonyl compounds 82 via 3V-acetylation followed by hydrolysis. 

Solid-state photochemistry of (—)-2-chloro-2-nitrosocamphane 275 was studied145 by irradiation of the blue-crystal with red light to invert the configuration at C(2) (equation 123). This also causes a photochemically initiated Beckmann rearrangement to form chloroxime 276 to give nitroxide radical 278 (equation 124). The intermediate chloro oxime 276 is proposed to arise from the njr excitation and is believed to be the common intermediate for the photo-epimerization and Beckmann rearrangement. Extended... 

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-... 

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