Isocyanates, addition from nitrile oxide

Another route involving 1,3-dipoIar addition was next attempted (54). The key feature of this route is a cycloaddition of nitrile oxide (55) 88 with citraconate 87 (Scheme 16). Treatment of 89 prepared from 3-bromopropanol with phenyl isocyanate produced the nitrile oxide 88 which was then subjected to cycloaddition with dimethyl citraconate 87 to afford the adducts 86a and 86b as a 1 1 mixture. In this reaction, as expected, 86a, in which the less hindered oxygen is substituted at the quaternary carbon, was the major product (56). Conveniently, however, the undesired adduct 86b could be separated in the following dehydration step. These adducts were next subjected to various reduction conditions (57) in order to obtain intermediate 85 (eq.9). Unfortunately, we could not obtain any of the desired compound even under Curran s conditions (Raney-Ni (W-2), boric acid) which are mild enough to suppress undesired side reactions. All compounds produced in this reduction were retro-aldol products 90-93 probably derived from 85 or its imine form. This... 

Some routes of chemical transformations of nitrile oxides connected with the problem of their stability were briefly discussed in Section 1.2. Here only two types of such reactions, proceeding in the absence of other reagents, viz., dimerization to furoxans and isomerization to isocyanates, will be considered. All other reactions of nitrile oxides demand a second reagent (in some cases the component is present in the same molecule, and the reaction takes place intramolecularly) namely, deoxygenation, addition of nucleophiles, and 1,3-dipolar cycloaddition reactions. Also, some other reactions are presented, which differ from those mentioned above. 

Isoxazoline derivatives of Cgo such as 250 (Scheme 4.40) are accessible by 1,3-dipolar cycloadditions of nitrile oxides to [6,6] double bonds of the fullerene [2, 278, 291-305]. The nitrile oxides 249 with R = methyl, ethyl, ethoxycarbonyl and anthryl are generated in situ from the corresponding nitroalkane, phenyl isocyanate and triethylamine. The isoxazoline derivative of Cgo 250 (with R = anthryl) crystallizes in black prisms out of a solvent mixture of CS2 and acetone (3 2) [292]. X-ray crystal structure analysis shows that addition of the nitrile oxide occurs on a [6,6] double bond of the fullerene framework. 

Dihydrooxadiazoles 106 have been syntheised in moderate to high diastereomeric excess by the addition of aromatic nitrile oxides across the C=N bond of the hydrazones 105. The N-N bond can subsequently be cleaved with formic acid, and the chiral auxiliary recycled <99H(50)995>. The oxadiazolone 108 was produced (56%) from the oxime 107 by heating it with phenyl isocyanate <99SC3889>. ... 

Nitrile oxide J -I- 2 cycloaddition.1 A key step in a recent stereospecific synthesis of biotin (6) from cycloheptene (1) is an intramolecular [3 + 2]cyclo-addition of a nitrile oxide (a), obtained by dehydration of a primary nitro compound (3), preferably with phenyl isocyanate. This cycloaddilion is more efficient than the well-known olefinic nitrone cycloaddition. The carbon atoms in 6 derived from cycloheptene are marked with asterisks. 

A number of alkyl- and arylnitrile oxides have been reacted with methylenecyclopropane to give 4-oxa-5-azaspiro[2.4]hept-5-enes 1 (4,5-dihydrospiro[isoxazole-5-cyclopropane]). The nitrile oxides were usually generated in situ from the appropriate primary nitro compound with phenyl isocyanate and triethylamine. The addition is usually regioselective in such a way that the oxygen atom forms a bond with Cl of the three-membered ring. 

Simple addition, in which both fragments of the NH molecule enter the new compound as in the preparation of alkanolamines from alkylene oxides, aminonitriles from unsaturated nitriles, and ureas and thioureas from isocyanates and isothiocyanates. 

From 3-picoline A -oxide and phenyl isocyanate the cycloadduct can be isolated Also, nitrile oxides, generated from arylhydroxamoyl chloride and triethylamine, react with phenyl isocyanate to give 2,4-diaryl-l,2,5-oxadiazol-3-ones and nitrile oxide dimers". Mesitonitrile oxide reacts with a l-oxa-3-azonia-butatriene salt 419 (R = 2,4,6-MesPh) by addition across the C=0 bond of the isocyanate to give a 1,2,5-oxadiazole derivative 420" ". ... 

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