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MCPBA treatment of fused-ring isoxazolidines furnishes a-(hydroxymethyl)substituted cyclic ketones, which constitute the starting-point for a successive Baeyer-Villiger oxidation allowing the synthesis of novel a-(hydroxymethyl)lactones.Isoxazolidines 1 are becoming popular synthetic intermediates since they (i) can be easily prepared by cycloaddition of nitrones to alkenes and (ii) are prone towards the selective cleavage of the N-O bond under both reductive 2 and oxidative 3-14 conditions. In the latter instance, 3-chloroperbenzoic acid (MCPBA) is the most typical reagent and the usual outcome of the oxidation is again a nitrone derivative (the so-called second generation nitrone), which in certain cases recyclizes spontaneously to 1,3-oxazine 3,7,12,13 but can often be used as a 1,3-dipole for further cycloadditions. 4,5,8,9,11 However, it is apparent from the pioneering work of LeBel 3 as well as from a few successive papers 6-10 that appropriate MCPBA treatment of isoxazolidines can furnish the carbonyl compounds formally corresponding to hydrolysis of the initially formed nitrones. Somehow surprisingly, such a reaction has escaped a systematic study and its synthetic potential has been little exploited. On these grounds, we reasoned that MCPBA treatment of fused-ring isoxazolidines could provide a-(hydroxymethyl)substituted cyclic ketones not easily accessible by other routes. Furthermore, having in mind the known BaeyerVilliger reaction, we planned the further MCPBA oxidation of the so-formed ketones in order to obtain novel a-(hydroxymethyl)lactones.As starting materials, we considered both racemic and enantiopure [1]benzopyrano[4,3-c]isoxazolidines 1a-d and 4a,b as shown in Schemes 1 and 2, respectively. They were treated with MCPBA (2 mol equivalents) in refluxing 90% aqueous THF. In all cases, the resulting mixture contained a major component, which was separated by column chromatography and proven to be a 3-(hydroxymethyl)substituted 4-chromanone of general formula 2 or 5 (see Schemes 1 and 2). Isolation yields of analytically pure products were in the range 31-43% (Tables 1, 2).Control experiments showed that the nitrone species formed by MCPBA oxidation of 1a,b and 4b in CH 2 Cl 2 at room temperature 14 were reluctant to hydrolize and underwent preferably thermolysis rather than hydrolysis reactions when heated in aqueous medium under acid catalysis. This evidence underlines the synthetic usefulness of the procedure now reported, although the intimate step sequence has not been yet understood.As an interesting extention, we submitted the cyclic ketones just obtained to further MCPBA treatment according to the classical Baeyer-Villiger protocol, i.e., in boiling CH 2 Cl 2 . Within the experimental error limits, the observed process was fully regioselective, the products being identified as seven-membered phenol lactones of general formula 3 or 6, which were isolated in 30-58% yield. Alternative structures, namely benzoic acid sevenmembered lactones, 15 were unequivocally discarded in view of spectral...
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