Isoxazolidines, conformations

Isoxazolidine-3,3-dicarboxylic acid, 2-methoxy-dimethyl ester reaction with bases, 6, 47 Isoxazolidine-3,5-diones synthesis, 6, 112, 113 Isoxazolidines conformation, 6, 10 3,5-disubstituted synthesis, 6, 109 oxidation, 6, 45-46 PE spectra, 6, 5 photolysis, 6, 46 pyrolysis, 6, 46 reactions, 6, 45-47 with acetone, 6, 47 with bases, 6, 47 reduction, 6, 45 ring fission, S, 80 spectroscopy, 6, 6 synthesis, 6, 3, 108-112 thermochemistry, 6, 10 Isoxazolidin-3-ol synthesis, 6, 111 Isoxazolidin-5-ol synthesis, 6, 111... 

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. 

Isoxazolidine, 3-benzoyl-2-phenyl-reactions with bases, 6, 47 Isoxazolidine, 2-t-butyl-conformation, 6, 10 Isoxazolidine, 2-carbamoyl-3-hydroxy-... 

Absolute configurations of the isoxazolidines obtained in the nitrone cydoaddition reactions described in Schemes 7.21 and 7.22 were determined to be 3S,41 ,5S structure by comparison of the optical rotations as well as retention times in a chiral HPLC analysis with those of the authentic samples. Selection of the si face at C/ position of 3-crotonoyl-2-oxazolidinone in nitrone cydoadditions was the same as that observed in the Diels-Alder reactions of cyclopentadiene with 3-croto-noyl-2-oxazolidinone in the presence of the J ,J -DBF0X/Ph-Ni(C104)2-3H20 complex (Scheme 7.7), and this indicates that the s-cis conformation of the dipolaro-phile has participated in the reaction. 

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). 

Quantum-chemical calculations for model isoxazolidines C and C demonstrated that the conformer C containing the pseudoequatorial nitrogen lone pair is thermodynamically highly favorable, whereas the conformer D with the equatorial... 

If this reaction is assumed to be thermoneutral (neglecting the effects of heteroatoms on conformation and on ring strain), the predicted enthalpy of formation of isoxazolidine is 11.6 kJmoC. Admitting that it may be simplistic, as well as simple, to have assnmed thermoneutrality, we take these two predicted values of 6 and 11.6 kJ moH to be in satisfactory agreement and choose an average value of 9 kJmol for the enthalpy of formation of isoxazolidine. 

Proton NMR (sometimes low temperature NMR or NOE) is the major reliable method for conformational analysis of isoxazolidines which undergo pyramidal inversion at the ring nitrogen atom (82JOC4397, 840MR(22)399>. 

Intramolecular cycloaddition of nitrone (7) led to the diastereomeric fused isoxazolidines (8a) and (8b) in an 82 18 ratio (Scheme 2).7a The authors suggested cyclization through competing conformational isomers A and B as a rationale of the cyclization outcome. Notably, absence of the franj-alkenyl methyl... 

Chmielewski and colleagues reported a Bu3SnH-mediated radical-induced isoxazoli-dine-isoxazolidin-5-one transformation (equation 99)778, while Sulsky and coworkers described conformational switching in the synthesis of a spiro[2H-indol]-3(lH)-ones (e.g. 122) by radical cyclization, an example of which is depicted in equation 100787. In this final example, Takekawa and Shishido described the selective cleavage of substituted cyclopropanes via stannane-induced radical fragmentation, an example of which is illustrated in equation 101791. 

The reactions of the vinyl sulfoximines 281 with C./V-diphenylnitrone 282 are highly regioselective and give only 4-sulfonimidoyl-isoxazolidine cycloadducts 283 and 284.104 These reactions proceed with modest n-facial selectivity with respect to the dipolarophiles 281. The stereochemical outcomes of these reactions are consistent with attack on the ground-state conformation 238 of the sulfoximine through an endo -like transition state. 

It is also shown that the isoxazolidine ring has an envelope conformation (51).173 Ginzburg et al.174 found that the two isoxazolidine rings, each in an envelope conformation, make a dihedral angle of 115° with each other in an isoxazolizidine. X-ray analysis of the compound 52 has also been described.144... 

Condensation of hydroxylamine rac-10 with 1,4-cyclohexanedione monoethylene acetal provided nitrone rac-9, which was treated with ethyl acrylate to give 74% of a 8-9 1 mixture of isoxazolidine rac-8 and its diastereomer. Reduction of this mixture with hydrogen afforded 8-9 1 of a mixture of lactam rac-1 and its diastereomer (Scheme 7). After crystallization, X-ray analysis of the major product confirmed that its stereochemistry is the one required for carrying out the synthesis of FR901483. The excellent stereoselectivity observed in the 1,3-dipolar cycloaddition of nitrone rac-9 was attributed to the substitution pattern in the stereogenic center adjacent to the nitrogen atom. These substituents stabilize one chair conformer relative to the other and thus allow a good... 

The stereofacial differentiation of the diastereotopic sides of nitrones by removable auxiliaries demands the positioning of the chiral group to be within the fV-substituent. In order to exhibit a spatial differentiation, a preferred conformation of this substituent is crucial. Carbohydrates, due to their exo-anomeric effect revealed to be efficient auxiliaries for these transformations. So far the reactivity and efficiency of more than 40 carbohydrate compounds have been examined. When optically active nitrones from inexpensive carbohydrates are applied, generally the optically purities of the N-substituted isoxazolidines are determined after removal of the chiral auxiliary. 

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