Aliphatic nitrile oxides

A wide range of aliphatic nitrile oxides 370a-k and 372a-e, variously functionalized on the side chain, were added to MCP and its derivatives, on the route for the synthesis of functionalized dihydropyridones (Tables 29 and 30) [92]. 

The 1,3-dipolar cycloaddition of a variety of aromatic and aliphatic nitrile oxides to 2.5-/ra//.v-2.5-diphenylpyrrolidine-derived acrylamide and cinnamamide 399, efficiently affords the corresponding 4,5-dihydroisoxazole-5-carboxamides 400 in highly regio- and stereoselectivity (Scheme 1.47). Acid hydrolysis of these products affords enantiopure 4,5-dihydroisoxazole-5-carboxylic acids 401 (443). 

The cycloaddition of aliphatic nitrile oxides to the analogous methacrylamide also proceeds smoothly to afford the expected cycloadducts in moderate yields... 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

Carreira and co-workers (138) successfully applied the Mg(II) ion-mediated nitrile oxide cycloaddition method to the total synthesis of epothilones A and B (Scheme 11.36). The key step in the synthesis was a hydroxyl-directed syn-selective nitrile oxide cycloaddition using a phosphorus-functionalized aliphatic nitrile oxide. This cycloaddition step served not only to introduce a heterocycle-substituted appendage into the skeleton of the epothilones, but also to assemble two... 

Aliphatic nitrile oxides are too unstable to be isolated. They immediately dimerize unless a 1,3 dipolar addition of the nitrile oxide immediately occurs on the active double bond of a suitable reagent (C=C, C=0, C=N). The following paragraphs describe the preparation of oxa-diazoles from those starting materials. 

It has been recently described [55d) that aliphatic nitrile oxides can be formed in solution by treating an aliphatic a-nitro-hydrocarbon with phenylisocyanate in the presence of a catalytic amount of tri-ethylamine. Dehydration of the nitro compounds occurs with the con-committant formation of benzoylurea. From nitroethane, the reaction is formulated as follows ... 

Nitrile oxides have the structure R—C=N —(/ > or Ar—C=N —(/ >. Aliphatic nitrile oxides usually can be prepared only in situ, while the analogous aromatic compounds, which are resonance-stabilized, generally can be isolated. The most common preparation of nitrile oxides is the dehydration of aliphatic nitro compounds. Figure 15.43 shows in detail how this... 

Magnesium ion-mediated nitrile oxide 1,3-DC reactions to allylic alcohols have been reviewed <02SL1371>. New examples have been recently reported, in particular, cycloadditions of aromatic and aliphatic nitrile oxides with optically active a-silylallyl alcohols in the presence of magnesium cations. The substituted isoxazolines, which were obtained with high diastereo- and enantioselectivity, were smoothly converted to [1,2]-oxazine derivatives by treatment with TBAF. For example, oxazin-3-one (S)-58 was obtained in 81% ee starting from dipolarophile (S)-55 <02T9613>. 

Aliphatic nitrile oxides can also be prepared by the dehydration of primary nitro compounds with phenylisocyanate in the presence of a catalytic amount of a tertiary base such as triethylamine. Phenylcarbamate generated in situ on reaction with phenylisocyanate is subsequently converted into urea derivative (Scheme 5.37). 

Cycloadditions involving nitrile oxides have received only scant attention in the literature yet this year has seen exploration of the generalized reaction leading to isoxazolines, and its use during the synthesis of a natural product. The method affords high yields under mild conditions and is stereospecific (Scheme 51). A serious limitation to the use of simple aliphatic nitrile-oxides would appear to be their facile dimerization to l,2,5-oxadiazole-2-oxides. 

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