Isoxazolines rearrangement

Rahman and Clapp decomposed dinitromethane derivatives in DMF in the presence of alkenes to obtain 2-isoxazolines. Without any alkene present, an acid and KNO2 were obtained. They proposed a mechanism which proceeded via a three-membered ring or a nitrocarbene which rearranged to a nitrile oxide (76JOC122, 75MI41612). 

The rearrangement of fused triazole (493) produced a fused aziridine and a fused 4-isoxazoline (494) (75T831). 

A" -Isoxazolines, which are readily accessible by 1,3-dipolar addition of nitrones and nitronic esters to activated alkynes, undergo facile rearrangement upon warming (<110 °C)... 

Isoxazolin-5-imine, 2,3,4-triphenyl-photolysis, 6, 43 Isoxazolin-5-imines synthesis, 6, 105 2-Isoxazolin-5-ol synthesis, 6, 100 Isoxazolinols synthesis, 6, 100-102 Isoxazolin-3-one, 5-methyl-2-phenyl-rearrangement, 6, 43 Isoxazolin-5-one, 4-acyl-reactions... 

The impulse to the study of these cycloadditions came from the discovery that 5-spirocyclopropane isoxazolidines (or isoxazolines) undergo a thermal rearrangement resulting in the production of selectively substituted tetrahydro-(or dihydro) pyrid-4-ones (Scheme 42) [64], In particular, cyclic nitrones gave ultimately N-bridgehead bicyclic ketones, molecular skeleton of many alkaloid families [65]. 

Halide substituted isoxazolines 371a-f gave bicyclic dihydropyridones 374 after rearrangement. Methoxycarbonyl substituted isoxazolines 371g-k gave the lactams 375, whereas carbonyl substituted isoxazolines 373a-e gave pyrroles 376 (Scheme 51). 

Compound 384 derived from the reaction of two molecules of benzonitrile oxide (341) with one of BCP (3). Its formation can be explained with the cycloaddition of a second molecule of 341 to the isoxazoline Ml to give the isoxazolidine M5, which undergoes a thermal rearrangement to 384 (Scheme 54). 

Dipolar cycloadditions of nitrile oxides 216 onto 1 gave much poorer yields of cycloadducts 217 than those of nitrones 205. The cycloadditions of 216 to 1 require higher temperatures and unfavorably compete with their dimerization to furoxanes. However, stable nitrile oxides 216 with bulky substituents R that hamper dimerization, can be used. The thermal rearrangements of 5-spirocyclopropane-annelated isoxazolines 217 always required higher temperatures than the isoxazolidine counterparts. Under these conditions the second cyclopropane ring was also cleaved to give furopyridines 218 (Scheme 48) [136, 137]. 

Spiro-isoxazoline 57 (Scheme 16) undergoes thermolytic rearrangement followed immediately by cyclization of the intermediate enaminone to bicyclic 58 (89J(P1)1253). Imine 59 when heated gives iminium salt 60, hence providing a new and efficient route to parent substance 2 (03T3099). 

Furazan formation by rearrangement of 2-isoxazoline oximes have also been reported <857727, 91KGS827>. For example, hydroxyiminoacetonitrile oxide reacts with norbornene to afford isox-azoline ( )- and (Z)-oximes (102) and (103) the former is stable in alkali whereas the latter rearranges to furazan (104) (Scheme 20) <85T518l>. 

The [3+2] cycloaddition of terminal alkynes has been investigated with several dipoles. These dipolarophiles are competent in the cycloaddition, however, the corresponding isoxazolines cannot be isolated. Instead, the cycloadduct undergoes spontaneous rearrangement to provide acylaziridine products (Table 2.52) (229). Disubstituted alkynes also undergo this process, however, in lower yield. This rearrangement occurs with all nitronates studied (Chart 2.3) (66,230,231). 

The so-called isoxazoline transposition or Angeli s rearrangement (Scheme 79) involves the conversion of methylfuroxans by treatment with alkoxides or alcoholic alkali hydroxides into the oximes of isoxazolidin-4-ones (531) (81G167). 

T3037). 3-Aroylflavanones (640) offer a choice of sites for attack by hydroxylamine, but the endocyclic carbonyl is preferentially attacked to give the isoxazoline (641) (79IJC(B)5lo). Oximes (642) of flavanones rearrange in acid solution to the isoxazoline (643) (80H(14)1319). 

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