Aldoximes, oxidation with

The reaction of diacetylene with cyanic acid (HCNO) proceeds at room temperature in the presence of sulfuric acid in aqueous methanol to give 3-formyl-5,5 -diisoxazol-3 -aldoxime (85) and 3,3 -diformyl-5,5 -diisoxazoldioxime (86), whose oxidation with potassium permanganate followed by esterification results in 3,3 -dicarbomethoxy-5,5 -diisoxazoles (87) (59G598). 

Nitrile oxides are usually prepared via halogenation and dehydrohalogenation of aldoximes [11] or via dehydration of primary nitro alkanes (Scheme 1) [12]. However, it is important to note that nitrile oxides are relatively unstable and are prone to dimerization or polymerization, especially upon heating. 1,3-Dipolar cycioaddition of a nitrile oxide with a suitable olefin generates an isoxazoline ring which is a versatile synthetic intermediate in that it provides easy access to y-amino alcohols, )5-hydroxy ketones, -hydroxy nitriles, unsaturated oximes, and a host of other multifunctional molecules (Scheme 1) [5a]. Particularly for the formation of )5-hydroxy ketones, nitrile oxide-olefin cycioaddition serve as an alternative to the Aldol reaction. 

Oxidation of aldoximes 327 with sodium hypochlorite or NBS is one of the best-known methods for generation of nitrile oxides (Equation 73) <1999BCJ2277>. 

Nitrile oxides were also readily generated by reaction of aldoximes 172 with icri-butyl hydroperoxide and bis(tributyltin) oxide. The reaction proceeded nnder mild conditions, in which 0-stannylated aldoximes 173 were the key intermediates. This reaction system was applicable to the one-pot synthesis of isoxazoline 174 or isoxazole 175 derivatives... 

The Brown allylboration was used in the enantioselective total synthesis of (-)-calicheamicinone 3318 (Scheme 3.1o). Thus the lactol 34, readily prepared from tetronic acid, was treated with the allylborane d35 to give 36 in a highly stereoselective manner (95% ee, > 98% de). Compound 36 was converted to the aldoxime 37 by standard chemistry. Generation of the nitrile oxide with aqueous sodium hypochlorite was accompanied by spontaneous [3 + 2]-dipolar cycloaddition to afford 38 in 65% yield. 

Lead tetraacetate oxidizes oximes to various products. For exanqrle, the oxime of cyclohexanone gives a-acetoxynitrosocyclohexane in 35% yield.Aldoximes react with lead tetraacetate to give nitrile oxides which then yield acetyl hydroxamates 1 reaction with acetic acid. ... 

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... 

Selective oxidation of polymethylpyrimidines.1 2,4-Di- and 2,4,6-trimethyl-pyrimidines are selectively oxidized to 4-carboxylic acids by a slight excess of Se02 in pyridine. Yields are about 40-65%. This increased reactivity of a 4-methyl group of polymethylpyrimidines is also observed in reaction with ethyl nitrite in liquid ammonia to form 4-aldoximes and with ethyl benzoate in the presence of KOC2H5 to form phenacyl derivatives. 

Aldoximes are easily oxidized with CBT under mild conditions to form nitrile oxides and furoxanes (90SC1373) (Scheme 103). 

Some polyfunctional isoxazolines of generic structure 44 were obtained in 78-91% yields by treatment of aryl aldoximes 42 with Baylis-Hillman adducts 43 in the presence of diacetoxy iodobenzene (DIB). The reaction is completely diastereoselective and involves the formation of nitrile oxides from aldoximes followed by 1,3-DC with the activated alkenes. Under the same conditions, ketoximes afforded only deoximation products <04TL7347>. 

IBX has also been used for the preparation of the 3,5-disubstituted isoxazolines 865. The oxidation of aldoximes 863 with IBX produces the respective nitrile oxides, which then undergo 1,3-dipolar addition with an alkene component 864 to give final products 865 (Scheme 3.345) [1182]. 

Isoxazoles display a range of biological activities, such as anti-inflammatory, antimicrobial, anticancer, and antinociceptive, that justify a constant effort in the development of new synthetic strategies. New syntheses of isoxazoles 1 and isQxazolines 2 via 1,3-dipolar cycloaddition (1,3-DC) of alkynes and alkenes with nitrile oxides were described (130L4010). The 1,3-dipoles were generated by oxidation of aldoximes catalyzed with hypervalent iodine species formed in situ from catalytic iodoarene and oxone as a terminal oxidant, in the presence of hexafluoroisopropanol (HFIP) in aqueous methanol solution. 

Furazan-A-oxides (furoxanes) 104 (Scheme 30) are isolated as a result of the nitrile oxide dimerization when chloro-oximes 101 are treated with bases in the absence of dipolarophiles [21,49, 50]. Oxidation of aldoxime 99 with nitric acid gives furoxan 104 [Rp=H(CF2)8] in 50 % yield [51]. Similarly, furoxane 104 (RF=CgF5)... 

Zhdankin et al. reported the iodine(III) catalyzed oxidative cycloaddition of aldoximes 60 with alkenes and alkynes to prepare isoxazoles and isoxazolines. The active hypervalent iodine(III) species was generated in situ by the oxidation of catalytic 3,5-dimethyliodobenzene using Oxone as an inexpensive and environmentally safe terminal oxidant in aqueous 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). This activated iodine(III) promoted the oxidation of the corresponding aldoximes efficiently affording nitrile oxides 61, which upon cycloaddition reaction with various alk5mes 62 and alkenes 64 resulted in isoxazoles 63 and isoxazolines 65, respectively in moderate-to-excellent yields (up to 92%). In this oxidative conversion, HFIP is believed to increase the electrophilicity of I(III) reagent (Scheme 11) [27]. 

Trifluoromethyl group is one of the important functional groups, which improves liphophilicity and stability of drug molecules. Benoit et al. S5mthesized a series of 3-trifluoromethyl-2-isoxazolines 74 and 3-trifluoromethyl-2-isoxazoles 72 by utilizing DIB-induced oxidation of trifluoromethyl aldoximes 70 followed by 1,3-dipolar cycloaddition of the resulhng nitrile oxides with different dipolarophiles (alk5mes 71 and alkenes 73). This developed a metal-free DIB-mediated 1,3-dipolar cycloaddition protocol to prepare valuable fluorinated bioactive oxazoles and isoxazolines (Scheme 13) [29]. 

The intramolecular cycloaddition of a nitrile oxide (a 1,3-dipole) to an alkene is ideally suited for the regio- and stereocontrolled synthesis of fused polycyclic isoxazolines.16 The simultaneous creation of two new rings and the synthetic versatility of the isoxa-zoline substructure contribute significantly to the popularity of this cycloaddition process in organic synthesis. In spite of its high degree of functionalization, aldoxime 32 was regarded as a viable substrate for an intramolecular 1,3-dipolar cycloaddition reaction. Indeed, treatment of 32 (see Scheme 17) with sodium hypochlorite... 

Aldoximes can be oxidatively dehydrogenated to nitrile oxides using a variety of oxidants such as lead tetraacetate [16a], alkali hypohalites [lla],NBS in DMF followed by base treatment [16b], chloramine-T [11b], 1-chlorobenzotriazole [16c], mercuric acetate [ 16 d], etc. However, we employed either NaOCl or chloramine-T for most of our INOC reactions. For instance, a piperidine ring fused to an isoxazoline as in 14 was constructed using the INOC methodology (Scheme 3) [17]. Monoalkylation of N-tosylallylamine 10 with the bromoacetal... 

The reaction of the a-bromo aldoxime 52e (R = R = Me) with unsaturated alcohols has been extended to the heterocyclic systems furfuryl alcohols and 2-thiophene methanol [29b]. The furanyl and thiophenyl oximes 63a-c were treated with NaOCl and the resulting heterocyclic nitrile oxides were found to undergo spontaneous intramolecular dipolar cycloaddition to produce the unsaturated tricyclic isoxazolines 64a-c in high yield (Eq. 5). In these cases, the heterocyclic ring acts as the dipolarophile with one of the double bonds adding to the nitrile oxide [30]. 

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