Ketones oxime synthesis

Suginome, H., Kaji, M., and Yamada, S., Photo Induced Molecular Transformations. 87. Regiospecihc Photo Beckmann Rearrangement of Steroidal a,P Unsaturated Ketone Oximes Synthesis of Some Steroidal Enamino Lactams, J. Chem. Soc., Perkin Trans. 1, 1988, 321 326. 

Ichikawa, J., Nadano, R. and Ito, N. (2006) 5-endo Heck-type cyclization of 2-(trifluoromethyl)allyl ketone oximes synthesis of 4-difluoromethylene-substituted... 

Synthesis of quinolines by nucleophilic substitution of nitrogen atom in oxime derivatives was described by Narasaka and coworkers. /3-Aryl ketone oximes 297 in the presence of trifluoroacetic anhydride and 4-chloranil afforded quinolines 298 in 72-82% yield (equation 128). However, interaction of oxime 299 with 48% HBr at 105 °C proceeded with elimination of hydroxyimino group and gave 2,3-dimethoxynaphtho[l,2-fc]quinolizinium bromide (300) in 45% yield (equation 129). ... 

The synthesis of furoxans has been discussed in a recent review (81AHC(29)25l), and the material summarized in the following sections is cited therein unless otherwise stated. The principal routes comprise oxidative ring closure of a-dioximes dehydration of a-nitro ketone oximes and dimerization of nitrile oxides. In choosing the method the possibility of equilibration between the 2- and 5-oxides of asymmetrically substituted furoxans, which was described in Section 4.22.3.2.1, must be taken into account. There has been no case of direct oxidation of a furazan to a furoxan. 

Table 4. Synthesis of Aminocyclopropane Lactams by the Beckmann Rearrangement of Cyclopropyl Ketone Oximes...

Ring Synthesis of IR-Indazoles, 1,2-Benzisothiazoles and 1,2-Benzisoxazoles The earliest syntheses of 1,2-benzisoxazoles depended on the cycUsation of an ortfto-haloary 1-ketone oxime, typical conditions are shown below and involve an intramolecnlar nncleophilic substitution of the halide. Only one geometrical isomer of the oxime will ring close. Applying this approach to amidoximes is easier, because the two imine geometrical isomers in such compounds are easily interconvertible. Comparable reaction with hydrazones produces indazoles. ... 

This ozonolysis method has also been applied to 0-methyl ketone oximes 204, in the absence of carbonyl compounds or protic solvents, also affording tetroxanes (Scheme 36). The method has been extended to the synthesis of dispirotetroxanes devoid of the usual hexaoxonane by-products often seen in acidic peroxidation reactions (see Section 9.14.8.3) <2002RMC113>. 

Jiang and coworkers developed a highly efficient synthesis of imidazo[l,2-a]pyridine derivatives from pyridine with ketone oxime esters using Cul catalyst (Scheme 8.64). The C(sp )-H bond of ketone oxime esters and C(sp )-H bond pyridinium were activated in this transformation. Air is used as the sole oxidant and HOAc and H2O are the only green by-products [109]. 

Scheme 8.64 Synthesis of imidazo[l,2-a]pyridine derivatives from pyridine with ketone oxime esters.

A version of the pyrrole synthesis involving one-pot transformation of ketones into NH- and N-vinylpyrroles has been worked out. Preliminary isolation of oximes is always associated with consumption of reactants, solvents, and time. In some cases (e.g., for ketoximes having high solubility in water), this procedure presents certain preparative difficulties. To exclude the stage of ketoximes isolation, a possibility of ketone oximation in situ in DMSO and the subsequent application of the oxime solutions in the reaction with acetylene has been studied [181]. 

All of the reactions shown are fairly standard in type. The first is a Strecker synthesis the first formed product is the a-aminonitrile, which is then hydrolyzed to an amino acid. The second reaction is a standard oxime synthesis as the ketone is symmetric, there is no stereochemistry to worry about. In (c), an imine is formed the stereochemistry about the carbon-nitrogen double bond is determined by steric hindrance. Since the SM is racemic, two diastereoisomers will be formed, hence the wavy bond to the methyl group. In the final example, a hydrazine is prepared while it s not possible to be certain of the stereochemistry about the C=N double bond, it s logical to assume that the less sterically hindered isomer will predominate ... 

Synthesis from Aldehydes and Ketones. Treatment of aldehydes and ketones with potassium cyanide and ammonium carbonate gives hydantoias ia a oae-pot procedure (Bucherer-Bergs reactioa) that proceeds through a complex mechanism (69). Some derivatives, like oximes, semicarbazones, thiosemicarbazones, and others, are also suitable startiag materials. The Bucherer-Bergs and Read hydantoia syntheses give epimeric products when appHed to cycloalkanones, which is of importance ia the stereoselective syathesis of amino acids (69,70). 

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... 

Craig s synthesis of nicotine (V to VII, p. 42) proceeds via nomicotine. Nicotinic acid nitrile reacts with the Grignard reagent derived from ethyl y-bromopropyl ether to give 3-pyridyl-y-ethoxypropyl ketone (V). This yields an oily oxime (VI) reducible to a-(3-pyridyl)-a-amino-8-ethoxy-w-butane (VII), which with 48 per cent, hydrobromic acid at 130-3° gives womicotine, and this on methylation yields dZ-nicotine. 

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

The regiochemical course reacting saturated ketones depended on the substitution pattern of the a-positions. In most cases, the intermediate oxime had an anti N-OH function with respect to the chain branched a-position. Consequently, the more substituted alkyl group preferentially migrates. This advantage was utilized for synthesizing the spiro a-amino-e-caprolactam (202 203, Scheme 38) [12c], the Mexican bean beetle azamacrolide allomone (205 206, Scheme 39) [44 a], in a key step of the chiral synthesis of benzomorphanes... 

Although harmine 52 is frequently obtained by isolation (or purchase order), a synthesis of this compound as well as a number of analogs has recently appeared [47,48]. The key step to this synthesis was the thermal electrocyclization of oxime intermediate 55, which was prepared by acylation of vinylindole derivative 54 followed by treatment with hydroxylamine hydrochloride. Neither oxime 55 nor its ketone precursor were isolated— instead, the crude reaction mixture was heated at reflux in o-dichlorobenzene to ultimately yield harmine in 56% yield overall starting from 54 (Fig. 18). 

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