Isoxazolidines ring opening

Isoxazolidine ring opening under basic conditions... 

The N-substituted isoxazolidine ring is stable under several standard oxidation conditions (for oxidative isoxazolidine ring opening, see Section 4.03.6.3.2). Accordingly, secondary and primary hydroxyl groups on lateral chains can be converted into ketones and aldehydes or carboxylic acid under suitable conditions (Equations 60 and 61) <1997T739, 2005BML1327>. 

Peroxyacetic acid/hydrogen chloride Oxidative isoxazolidine ring opening... 

Oxidative ring opening of isoxazolidines leads to nitrones. Thus, bicyclic isox-azolidines (50) and (51), treated with m-CPBA, afford nitrones (52), (53), (54), and (55) (Scheme 2.19). Conformational analysis has confirmed the key role of the nitrogen lone pair with respect to regioselectivity of the reaction and of the intramolecular kinetic deprotonation of the intermediate oxoammonium derivative (125). 

Similar oxidative ring opening occurs in other bi- and tricyclic isoxazolidines upon treatment with m-CPBA (126, 127). 

The addition of nitrones (647) and (312) to 4-pentenofuranoside (648) derived from D-ribose, followed by reductive opening of the isoxazolidine ring in (649)... 

Further syntheses of tetrahydro-l,3-oxazines are individual processes based on the facile ring opening of isoxazolidines and recyclization to oxa-zines. 

It was proposed that product 167 arises from coordination of the isoxazolidine (164) to AICI3 to generate the dicationic, superelectrophilic intermediate (165), which undergoes ring-opening to give product 167 by a Friedel-Crafts type reaction. 

For some ring systems, open-chain isomers are not detectable but their formation is implicated by inversion of configuration. Upon chromatographic purification on silica gel, the aldehyde 292 slowly epimerizes to the all-trans isoxazolidine 294 via ring opening to the a,(3-unsaturated aldehyde 293 <1997T739>. 

In an alternative two-step transformation of 5-spirocyclopropane isoxazolidines to tetrahydropyridones, for example, 7-amino cyclopropanol 214, prepared by chemoselective N-O reduction of isoxazolidine 213, was converted into 215 by treatment with Cu(OAc)2 and LiOAc in the presence of catalytic amounts of Pd(OAc)2. Interestingly, 7-amino cyclopropanols can also undergo a Pd-catalyzed domino ring-opening/cyclization/oxidation process to afford dihy-dropyridones such as 216 when the reaction is carried out in the presence of air or O2 (Scheme 49) <2005JOC5636>. 

Isoxazolidin-3-ones undergo ring opening by treatment with amines and hydroxylamines to give 3-(aminooxy)pro-panamide and 3-(aminooxy)-A -hydroxypropanamide derivatives, respectively. This process was applied to the... 

Reduction of methyl [5-(bromomethyl)isoxazolidin-3-yl]acetates 324 with trihutyltin hydride in boiling toluene in the presence of AIBN led to opening of the isoxazolidine ring and formation of isoxazolidinones 579. The process is believed to go through the formation of nitroxide radical 577, followed by reduction to hydroxylamine 578 and cyclization to 579 with elimination of methanol (Equation 98) <1999SL79>. 

The photochemical behavior of the isoxazolidine ring is not extensively studied. Depending upon the experimental conditions, 5-nitroxazolidines undergo photolysis to yield either 4-isoxazolines by the elimination of nitrones or to P lactam derivatives, by ring opening followed by reclosure... 

Only strong acidic conditions make the isoxazolidine ring unstable, either leading to ring opening (via N—O cleavage) products or to the formation of isoxazoline ring (via elimination). Isoxazoline... 

Under analogous reaction conditions, tricyclic isoxazolidines 85c afforded the p-homoprolines 87, probably by ring opening and A-acylation of the primary carbapenam intermediates 86c <04EJ02205>. The chemistry of spirocyclopropane isoxazolidines 85 as versatile precursors of different azaheterocycles has been reviewed <04M649>. 

As described later, however, attempted reduction of an isoxazole to an isoxazolidine in most cases causes ring opening. Cyclization of open-chain systems at the 1 5 bond is often a good method (c), but for the isoxazolidine ring this method is not particularly convenient. A few examples of ring enlargement of azetidine /V-oxides are reported (d). Almost all the isoxazolidines so far reported have been prepared by process a. 

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