Isoxazoline ring opening

A -Pyrazolines and A -isoxazolines (302 Z = NH, O) are cyclic hydrazones and oximes, respectively. 2-Pyrazolines are quaternized at the 2-position (306 307) (64AHC(. ll). 1,3,4-Oxadiazolines (e.g. 308) are very easily ring-opened (66AHCi7 183). 

Base treatment of isoxazolin-5-ones produced the cyano aeids (70JOC3130), while ethoxide treatment of iV-alkyl-A -5-ones gave, after H2O treatment, a malonyl monoamide monoester (69JOC2981) and not an oximoacrylate as was reported earlier (Scheme 61) (23HCA102). The base treatment of a 4-bromoisoxazolin-5-one generated a ring-opened oxime (Scheme 62) (79JOC873). 

In a number of cases the intermediate oxime has been isolated in the reaction of hydroxylamine and /3-keto esters. The reaction of ethyl acetoacetate with hydroxylamine generated an oxime which cyclized on base treatment (Scheme 144) (70MI41600). Likewise, treatment of an analogous amide with hydroxylamine generated a ring opened material which cyclized on treatment with HCl (Scheme 144) (67T831). The presence of a minor contaminant in the standard reaction of ethyl acetoacetate with hydroxylamine was discovered and identified as an isomeric isoxazolin-3-one. The mechanism of product formation has been discussed (70BSF2685). 

For the isoxazolines 284 substituted at position 3, ring-chain tautomerism is depicted by the equilibrium 284 and 285-287 (Scheme 103). In general the cyclic tautomers 284 are strongly preferred. The ring-opened forms exist in equilibrium with 284 in rare cases [95ZOB705 96AHC(66)1, p. 21]. The equilibrium of the oxazolidinones 288 [78MI1, p. 107] is affected by the nature of the solvent. 

Polymeric isoxazolines were prepared by cycloaddition of nitrile oxides to norbomadiene followed by ring-opening metathesis polymerization (ROMP) <06PLM3292 06MM3147>. 

Fullerene isoxazolines are stable compounds. Non-fulleroid alkyl isoxazolines easily undergo a reductive ring opening to yield various synthetically interesting... 

Photolysis of the bicyclic isoxazoline 31 is believed to involve the intermediacy of the (Z)-azirine 33 (R1 = R2 = R3 = R4 = H), which subsequently ring-opens to the corresponding nitrile ylide 34.1,7-Electrocycliza-tion of the nitrile ylide 34 onto the enone system then leads to the 1,3-oxazepine 35 (Scheme 13) [73TL1835 74JCS(CC)373], Thermolysis of the closely related (Z)-azirines 33 (R1 = R3 = R4 = Ph), generated... 

The reaction of 2,2-dialkoxycyclopropane-l-carboxylates and 2-ethoxycyclo-propane-l-carboxylate with NOC1 has provided isoxazoline- and/or isoxazole-3-carboxylates by regioselective ring opening at the C(l)-C(2) bond.170 A mechanistic interpretation has suggested well-stabilized dipolar species as intermediates. 

Nucleophiles usually react with 47/-benzopyran-4-ones at C-2, which results in pyran ring opening. The condensation of dilithiooximes onto 4/7-chroman-4-ones occurs by a 1,2-addition process to afford 47/-chromene 4-spiro-5 -isoxazolines 130 in good yield (Equation 61) <2004TL7351>. 

Isoxazolines are related to 1,2-dioxines in that they are also prone to reductive ring opening. Ishikawa and colleagues found that A-benzylisoxazolines form 2-acylaziridines by SET reduction/ring opening and recyclization of the resulting aminyl radical to the cobalt enolate [430]. 

Hydrogenation of 2-isoxazolines over Raney nickel as catalyst and in the presence of acids often leads first to 1,3-hydroxyimines, and then, through hydrolysis, to 1,3-hydroxycarbonyl compounds. In some cases the stereochemical integrity of the starting material is maintained, but in others hydrolysis of the intermediate imines may cause scrambling of stereochemistry at the a-carbon atom. Rapid protonation of the imine function minimizes this possibility and the use of Lewis acids, such as boron trichloride or aluminum trichloride which release hydrochloric acid on contact with moist methanol, is frequently recommended. Boric acid serves a similar purpose and is effective in, for example, the stereocontrolled reductive ring opening of the 2-isoxazoline (135) en route to crispatic acid (136 Scheme 6). ... 

Isoxazolines have been synthesized by an intramolecular rearrangement of O-propargylic hydroxylamines in yields ranging from 60% to 84% <2006SL463>. To prevent side reactions, derived from base-catalyzed ring opening,... 

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