Nitrile oxides, reactions

Zinc-tartrate complexes were applied for reactions of both nitrones and nitrile oxides with allyl alcohol and for both reaction types selectivities of more than 90% ee were obtained. Whereas the reactions of nitrones required a stoichiometric amount of the catalyst the nitrile oxide reactions could be performed in the presence of 20 mol% of the catalyst. This is the only example on a metal-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrile oxides. It should however be no-... 

Natural products, synthesis of 829, 835, 837, 840-842, 948, 958 Nitrile oxides, reactions of 807 Nitriles - see also y-Ketonitriles reactions of 277 synthesis of 815 Nitrilimines, reactions of 277 Nitritosulphonium intermediates 206 Nitrogen compounds, as oxidizing agents 970-972... 

Cycloalkene Derivatives Cyclopropenes readily interact with nitrile oxides. Reactions of a broad series of 3,3-disubstituted cyclopropenes with 4-substituted benzonitrile, methoxycarbonyl- and cyanoformonitrile oxides (229) as well as with di(isopropoxy)phosphorylformonitrile oxide (230) give 2-oxa-3-azabicyclo[3.1.0]hexene derivatives 62. Stereoselectivity of the cycloaddition is governed by both steric and polar factors. In particular, steric factors are supposed to prevail for 3-methyl-3-phenylcyclopropene affording 62 [R1 =... 

The above dramatic dependence of regio- and stereoselectivity on the nature of the metal can be explained by the reaction mechanism shown in Scheme 11.49 (167). The nitrone cycloadditions of allylic alcohols are again magnesium-specific just like the nitrile oxide reactions described in Section 11.2.2. Magnesium ions accelerate the reaction through a metal ion-bound intramolecular cycloaddition path. On the other hand, zinc ions afford no such rate acceleration, but these ions catalyze the acetalization at the benzoyl carbonyl moiety of the nitrone to provide a hemiacetal intermediate. The subsequent intramolecular regio- and stereoselective cycloaddition reaction gives the observed products. 

Nitrile oxide reactions D. P. Curran, Advances in Dipolar Cycloaddition Chemistry, Vol. 1, p 129, JAI, Greenwich 1988. 

MBH adducts and their derivatives derived from methyl acrylate and aldehydes undergo stereoselective cycloadditions with diazomethane and benzonitrile oxide to give the corresponding cycloadducts in good yields (Scheme 3.214). The stereochemical outcome can be explained by the so-called inside alkoxy elfect theory.However, in the case of diazomethane cycloadditions, electrostatic factors play a reduced role compared to the corresponding nitrile oxide reactions, while steric elfects are of major importance in governing the stereoselectivity. This dilferent behavior of the two 1,3-dipoles has been rationalized by analysis of the atomic charges, as calculated at the RHF/3-21G level of theory, for the transition structure of these reactions. 

Weak to moderate chemiluminescence has been reported from a large number of other Hquid-phase oxidation reactions (1,128,136). The Hst includes reactions of carbenes with oxygen (137), phenanthrene quinone with oxygen in alkaline ethanol (138), coumarin derivatives with hydrogen peroxide in acetic acid (139), nitriles with alkaline hydrogen peroxide (140), and reactions that produce electron-accepting radicals such as HO in the presence of carbonate ions (141). In the latter, exemplified by the reaction of h on(II) with H2O2 and KHCO, the carbonate radical anion is probably a key intermediate and may account for many observations of weak chemiluminescence in oxidation reactions. 

Dipolar cycloaddition reactions with azides, imines, and nitrile oxides afford synthetic routes to nitrogen-containing heterocycles (25—30). 

Hi) Preparation of isoxazoles from nitrile N-oxides The reaction between a nitrile //-oxide and an alkyne is so facile that it is usually sufficient to leave an ether solution of the reactants at room temperature to obtain the desired isoxazole in good yield. The reaction is in general sensitive to the size of the substituent on the alkyne but not on the nitrile -oxide. In the case of poorly reactive alkynes, the difficulty may be overcome by generating the nitrile -oxide in situ and keeping its concentration low. 

A -Isoxazolines are readily available from the 1,3-dipolar cycloaddition of nitrile -oxides with alkenes and from the condensation reaction of ehones with hydroxylamine. Therefore, methods of conversion of -isoxazolines into isoxazoles are of particular interest and of synthetic importance. 

The two major methods of preparation are the cycloaddition of nitrile oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamines. Additional methods include reaction of /3-haloketones and hydroxylamine, the reaction of ylides with nitrile oxides by activation of alkyl nitro compounds from isoxazoline AT-oxides (methoxides, etc.) and miscellaneous syntheses (62HC(i7)i). 

Nitrile oxides react with a wide variety of alkenic compounds and this reaction may be complicated by dimerization of the nitrile oxide to furoxan in the presence of unreactive double bonds (Scheme 98). 

The reaction of alkyl nitro compounds with acetyl chloride in the presence of an alkenic compound produced a 2-isoxazoline. The mechanism is believed to proceed via a nitrile oxide and is illustrated in Scheme 112 (B-79MI41613). 

Generalized methods of preparation include the reaction of /3-keto esters (or amides) with hydroxylamine, a-alkynic and a,/3-unsaturated esters (or amides) with hydroxylamine (real or generated in situ), hydroxylamine and nitrile oxides, and /3-keto and a-alkynic nitriles with hydroxylamine (62HC(l7)l, pp. 3,7). 

Alkynic esters react with nitrile oxides in a pH dependent reaction to product isoxazolin-5-ones (Scheme 145) (71JCS(C)86). Alkynic ethers also react with benzonitrile oxide to produce an isoxazole-ether which on treatment with HCl or HBr gave an isoxazolinone (Scheme 145) (63CB1088,58MI41600). The reaction of benzonitrile oxide with dimethoxyketene yielded a dimethyl acetal which was split with acid into the isoxazolinone (Scheme 145) (59G15H). 

Isoxazolin-5-imines were produced by nitrile oxide addition to cyanoacetates (62HC(17)l,p.7), by the reaction of nitrones with phenylacetonitrile (74CB13), and by base addition of nitrosobenzene to nitriles (Scheme 148) (72LA(762)154). 

The reaction of vinylogous amides, or ketoaldehydes, with hydroxylamine produced 4,5,6,7-tetrahydro-l,2-benzisoxazole. A side product is the 2,1-benzisoxazole (Scheme 173) (67AHC(8)277). The ring system can also be prepared by the reaction of cyclohexanone enamines with nitrile oxides (Scheme 173) (78S43, 74KGS901). Base treatment produced ring fission products and photolysis resulted in isomerization to benzoxazoles (76JOC13). 

A variety of 1-azirines are available (40-90%) from the thermally induced extrusion (>100 °C) of triphenylphosphine oxide from oxazaphospholines (388) (or their acyclic betaine equivalents), which are accessible through 1,3-dipolar cycloaddition of nitrile oxides (389) to alkylidenephosphoranes (390) (66AG(E)1039). Frequently, the isomeric ketenimines (391) are isolated as by-products. The presence of electron withdrawing functionality in either or both of the addition components can influence the course of the reaction. For example, addition of benzonitrile oxide to the phosphorane ester (390 = C02Et) at... 

It IS likely that the syn selectivity exhibited in cycloadditions of fluoroallene IS due to electrostatic interactions [23 25] As in the case of difluoroallene the reactions of fluoroallene with diazoalkanes and nitrile oxides are facile, but such reactions, other than that shown in equation 18, are neither regio nor stereospeutic [23, 25] Indeed, the addition of phenylnitrile oxide to fluoroallene occurs with preferential anti addition for both regioisomenc products (equation 20)... 

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