Ketoxime carboxylates

A copper-catalyzed homocoupling of ketoxime carboxylates 19 was invented to afford symmetrical pyrroles 20. Treatment of ketoxime with CuBr in the presence of NaHSOs as an additive in dimethyl sulfoxide (DMSO) at elevated temperatures led to the synthesis of pyrroles 20 in good yield (14GC112). 

Recently, Guan et al. developed a novel Cu(OAc)2-promoted oxidative coupling of enamides with electron-deficient alkynes for the synthesis of multisubstituted NH pyrroles. This reaction tolerates a wide range of functional groups and is a reliable procedure for the rapid elaboration of readily available enamides into a variety of diester-substituted NH pyrroles. The reaction proceeded through C-H and N-H bond functionalization of enamides CU/O2 system [22]. They also developed an efficient CuBr-catalyzed homocoupling of ketoxime carboxylates for the synthesis of symmetrical pyrroles [23] (Scheme 8.10). 

The rearrangement of oximes 1 under the influence of acidic reagents to yield A -substituted carboxylic amides 2, is called the Beckmann rearrangement. The reaction is usually applied to ketoximes aldoximes often are less reactive. 

Azirines can be prepared in optically enriched form by the asymmetric Neber reaction mediated by Cinchona alkaloids. Thus, ketoxime tosylates 173, derived from 3-oxocarhoxylic esters, are converted to the azirine carboxylic esters 174 in the presence of a large excess of potassium carbonate and a catalytic amount of quinidine. The asymmetric bias is believed to be conferred on the substrate by strong hydrogen bonding via the catalyst hydroxyl group <96JA8491>. 

The reaction of ketoximes with monoactivated allenes is either slow or complicated. However, the reaction with allene-l,3-carboxylate 476 afforded addition product ( )-527 highly stereoselectively [238]. 

Yields are frequently moderate for Scholl reactions. Aldoximes are not usually compatible with these harsh reaction conditions and are very sensitive to factors such as temperature and reaction time. Consequently, oxidation to the corresponding carboxylic acid is a major side-reaction. However, both the ketoxime (51) and the aldoxime (53) are reported to give good yields of the corresponding m-dinitro compounds, (52) and (54) respectively, on treatment with absolute nitric acid in methylene chloride followed by hydrogen peroxide. 

Under these reaction conditions, nitriles can readily transform to the salts of the corresponding carboxylic acids. This may account for the loss of ketoxime without visible signs of resinification occasionally observed in the synthesis of pyrroles from ketoximes and acetylene or its equivalents, i.e., vinyl halides and dihaloethanes (see Section V.B). 

Such condensation reactions are also promoted by certain trTvalent phosphorus compounds, e.g. triphenyl phosphite (2) or diphenyl ethylphosphonite (3), or to a lesser extent by pFosphonate esters, e.g. diphenyl n-butylphosphonate (3). "Bates reagent," p-oxobi s[tri s(cTi methyl ami no)phosphoni urn] bi s-tetra-f1uoroborate (2) may also be used to activate the carboxyl function towards amide bond formation during peptide synthesis (4) and to bring about the Beckmann rearrangement of ketoximes (F). 

A new synthesis of isoxazoles is by successive treatment of a ketoxime with butyllithi-um, the ester of a carboxylic acid and sulfuric acid, e.g. 1 -> 2 (94S989). Hitrovinyl oximes 3 (R1, R3 = alkyl or aryl) undergo oxidative cyclization to isoxazoles 4 by the action of DDQ or iodine/potassium iodide (94JHC861). Flash-vacuum pyrolysis of the 1,3-dipolar cycloadduct 5 of acrylonitrile oxide to norbornadiene results in a retro-Diels-Alder reaction to give cyclopentadiene and 3-vinylisoxazole 6 (94CC2661). 

Ketoximes containing a CH2 group adjacent to the oxime group are also capable of entering into the Pfitzinger reaction. Thus in the reaction of the isatin 7 with the ketoxime 199 3-cyano-2-methylquinoline-4-carboxylic acid 200 is formed with a 50% yield [177],... 

Good to excellent yields of jfc/M-difluoridcs are obtained from the reaction of ketoximes with NO BF4, (HF) /pyridine. The reactions are carried out under very mild conditions (rt, Nj atmosphere. 5 h) and the method is applicable to alkyl aryl (entry 7). diaryl (entry 8), and dialkyl ketoximes (entries 1 -6). In the ca.se of aldoximes. oxidation occurs and carboxylic acids are obtained. The concentration of the hydrogen fluoride in pyridine has an important effect on the yield of the reaction. The best results are obtained in the case of pyridinium poly(hydrogcn fluoride) with 60 wt % hydrogen fluoride. With lower concentrations, the major... 

Heating of secondary carboxylic acid amides with HMPA gives rise to formation of A(-substituted V JV -dimethylamidines (310 Scheme 48). - In this procedure the secondary amide can be replaced by a ketoxime in which at least one substituent has to be an aromatic one. Similar methods were de-... 

Cyclobutanone-3-carboxylic acid, 357 Cyclobutanones, 357 Cyclobutylamine, 376 Cyclobutyl chloride, 463 Cyclobutyl phenyl ketoxime, 289 cis,cis-, 6-Cyclodecadiene, 275 Cyclodecane, 246... 

Reaction with ketoximes. Ketoximes and an aromatic carboxylic acid react with this system at 0° to form diacylated aromatic amines (equation I). 

Chloronitro compounds are prepared by treating nitronate anions with NCS in aqueous dioxane, or alternatively by reaction of ketoximes with NCS (eq 14). Oxidative decarboxylation of carboxylic acids with Lead(IV) Acetate and NCS has been used effectively for the synthesis of tertiary alkyl chlorides (eq 15). ... 

In addition to tin and silicon, carbon-nitrogen double bonds as hydrazones, oximes, and nitrones can be treated with ozone to form carbonyl compounds (eq 53)7 While the transformation can be accomplished on several types of substrates, ketone-derived starting materials (e.g., ketoximes) perform better in the reaction, as the aldehyde-derived starting materials have the potential for overoxidation to the corresponding carboxylic acid product. 

Oximes can be converted to their corresponding nitro compounds with Oxone and refluxing acetonitrile (eq 58). They can also be cleaved to their parent carbonyl compounds by Oxone in conjunction with glacial acetic acid, or silica gel/alumina and microwave irradiation (eq 58). Ketoximes and aldoximes are both converted to carbonyl compounds in high yields using the microwave and alumina procedure. Several of the above transformations are highlighted in the oxidative decarboxylation of a-amino acids to form ketones and carboxylic acids. ... 

Liebeskind reported a copper-catalyzed Chan-Lam C-N crosscoupling methodology for JV-imination of boronic acids by using oxime O-carboxylates 291 as iminating agents and either Cu(I)-thiophene-2-carboxylate (CuTC) or Cu(OAc)2 as the catalyst under nonbasic and nonoxidizing conditions.Subsequently, the A-alkenylated a,3-unsaturated ketoxime 0-pentafluorobenzoates 293, were preeursors in a cascade reaction for the one-pot synthesis of tri-, tetra-, and penta-substituted pyridines 295 in moderate to excellent isolated yields. 

A new, eco-friendly o-iodoxy benzoic acid-mediated synthesis of 3,5-dia-rylisoxazoles and 5-arylisoxazole-3-carboxylic acids from a,p-unsaturated ketoximes has been reported (14SC1453). 

Scheme 4.26 shows the development of two general reactions based on copper(I) thiophene-2-carboxylate (CuTC) or Cu(OAc)2 for the formal arylation of imtnes with arylboronic acids [62]. The O-acetyl or O-pentafluorophenyl oximes react with a wide range of electron-rich, electron-poor and electron-neutral boronic acids, and even ortho-substituted substrates react well. The mechanism is proposed to proceed, as shown in Scheme 4.27, via an initial oxidative addition of the copper(I) species, either CuTC or through reduction of Cu(OAc)2 by the boronic acid, to the ketoxime O-carboxylate. This is followed by transmetallation and reductive elimination to generate the final product and regenerate the catalytically active copper(I) species. 

The pentachloride is most used. It will convert snlphonic acids to snlphonyl halides (12.276), alcohols to halides (12.277) and carboxylic acids to halides (12.278). Af-alkyl-substituted amides (12.279) and ketoximes (12.280) can be converted to nitriles and the Beckmann rearrangement promoted (12.281). 

More recently, the same group reported another novel procedure for the synthesis of pyridines by cyclization of ketoxime acetates with ruthenium as the catalyst (Scheme 3.46) [95]. Here, a methyl carbon on DMF performed as a source of a one carbon synthon. For different propiophenone oxime carboxylates tested, such as propionate, tert-butyrate, and benzoate, showed similar reactivity as the corresponding acetate derivative. Only a trace of product was observed with pentafluorobenzoate. 

Complex M(AAOPD), (18) (M = Co or Cu), catalyses the oxidation of aldoximes, ketoximes and carboxylic acids by dioxy iodobenzene (oxidant) in the presence of imidazole to corresponding carbonyl products in high yields. The rate of oxidation of oximes in the presence of Cu(AAOPD) is higher than that with Co(AAOPD) no such effect is observed in the oxidation of carboxylic acids. " ... 

For the next two retrosynthetic steps, we need new knowledge related to the Hofmann rearrangement of amides to amines with the loss of one C atom, discussed in Sect. 8.3. This rearrangement enables the introduction of an amino group in TM 7.3b starting from the corresponding carboxylic amide. The high value of this retrosynthetic approach becomes obvious on the next disconnection steps, refro-cyclization to p-ketoxime and its interconversion to easily available diketo-carboxylic acid. 

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