Isoxazolidine ring

The isoxazolidine ring exists primarily as an envelope (77AHQ2l)207) and the nitrogen lone pair can occupy an axial or equatorial position. Photoelectronic spectroscopy is a useful tool to determine conformational analysis of molecules possessing vicinal electron lone-pairs. Rademiacher and Frickmann (78TL841) studied isoxazolidine and 2-methyl- and 2-t-butyl-isoxazolidine and found mixtures of equatorial and axial (e/a) compounds. The ratios of H, Me and Bu in the efa position were 1 3, 4 1 and 10 1, respectively. 

Mild base does not effect isoxazolidine ring cleavage by fission of the N—O bond rather, C—O bond cleavage takes place <77AHC(2l)207). The reaction of iV-trimethyl-silylisoxazolidine (185) with KOH produced a /3-hydroxyketone oxime (Scheme 59) (74DOK109). 

The isoxazolidine ring is also readily cleaved by various reducing agents. For example, the degradation 188—>189 proceeds smoothly... 

Isoxazolidines can be converted easily to tetrasubstituted cyclobuty-lamines. This transformation involves a one-pot, two-stage reaction involving hydrogenolysis of the isoxazolidine ring on Pd/C in AcOEt and the N-tert-butoxicarbonylation of the resulting amino group (Scheme 4.144).542... 

The N-O bond in an isoxazolidine ring was hydrogenolyzed on 5% Pd/C in MeOH for 12 hours in a hydrogen atmosphere at room temperature.544... 

As for the regioselectivity of the nitrone cycloaddition to MCP and its alkyl or aryl derivatives, a tendency of the three-membered ring to end up at the 4-position of the final isoxazolidine ring clearly emerges from the experimental findings. This result is particularly noteworthy if compared to regiospecific formation of the 5,5-disubstituted isoxazolidines in the reactions of nitrones, not... 

Also, the effectiveness of 1,3-dipolar cycloadditions to a,p-unsaturated 8-lactones D7a, D7c, D7 d (784) and D7f, (785) in controlling the configuration of the stereogenic centers around the formed isoxazolidine ring, was demonstrated in reactions with nitrones (595). 

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)... 

These studies were carried out for hve-membered monocyclic TV-alkoxy-(406-408) and /V-siloxyisoxazolidines (178) (A), for iV-siloxytetrahydro-4// -oxazines (274), and bicyclic fused derivatives containing the isoxazolidine ring (B) (99, 157, 337). 

These data demonstrate that the nitrogen atom in practically all cyclic nitroso acetals A or B, containing the isoxazolidine ring, deviates from the plane through the other four atoms (envelope). The nitrogen lone pair always pseudo-equatorial. 

Cleavage of the isoxazolidine ring can also be effected directly to give similar products as the isoxazoline. Upon the addition of methoxide to an isoxazolidine bearing a hydrogen at C(3), fragmentation reveals a p-hydroxy oxime, which can be further hydrolyzed to the corresponding ketone (16,20,34,108). The P-hydroxy... 

Enlargement of an isoxazolidine ring is also a method of forming 1,3-oxazin-4-ones.104 A derivative (25) of the antibiotic cycloserine with methyl a-bromoisovalerate yielded two diastereoisomers, namely, 26a and b [Eq. (16)], probably by ring cleavage of 25 as shown, followed by recylization. 

Unequivocal structural proof of l,l,4,4-tetramethyl-l//,4//-thieno[3,4-c]thiophene (see Scheme 19) was obtained by X-ray crystallographic analysis (80TL3617). Methyl iV-vinyl carbamate adds benzonitrile oxide to yield a mono- or bis-adduct, depending upon the experimental conditions. The syn stereochemistry of the bis-adduct (10) has been elucidated by an X-ray structure determination which showed that the carbamate moiety orients its NH above the isoxazolidine ring and toward the oxygen of the syn-oxadiazolinic ring (NH------O is 3.08 A) <80JCR(S)4341>. 

Intramolecular nitrone-alkene cycloaddition. Reaction of cycloalkanones substituted by a 3-(2-propenyl) or a 3-(3-butenyl) side chain with alkylhydroxylamines with azeotropic removal of water results in a bridged bicycloalkane fused to an isoxazolidine ring. The transformation involves formation of a nitrone that undergoes intramolecular cycloaddition with the unsaturated side chain. 

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