Cycloaddition-reduction-hydrolysis sequence

This cycloaddition-reduction-hydrolysis sequence was also used in an approach to butyrolactones related to ribonolactone (71). These compounds are inducing agents of hunger and satiety in mammalians. Here, a subsequent aldol 1,3-diol reduction was used, and the required carboxy function was established by oxidation of the aromatic ring with ruthenium tetroxide. Cycloaddition of benzonitrile oxide to allyl alcohol afforded an enantiomeric mixture of isoxazolines 55 and 56, which were treated with sodium hydride and methyl iodide to achieve separation by chromatography on cellulose triacetate (71). 0-Demethylation, followed by... 

This was demonstrated by Fukumoto and co-workers in a synthesis of (+)-albicanol (251), a sesquiterpene with potent hsh antifeedant properties (272,273). Oxime 248 [prepared from the (+)-Wieland-Miescher ketone 247] was subjected to cycloaddition using sodium hypochlorite and gave isoxazoline 249 in very good yield (Scheme 6.95). Conversion of 249 into (3-hydroxyketone 250 was again accomplished by the reductive hydrolysis sequence using Raney Ni and trimethyl... 

A related sequence was used by Kozikowski and Park (74) to prepare the ring skeleton of streptazolin (200), a compound that exhibits antibacterial and antifungal effects. In this approach, the tricyclic isoxazoline intermediate 198 was formed in the key cycloaddition step (Scheme 6.86). Thus, the reaction of oxime 197 (obtained from 4-piperidone) with sodium hypochlorite-triethylamine afforded tricyclic isoxazoline 198 in very good yield. This cycloadduct was converted to p-hydroxyketone 199 by reduction/hydrolysis using Raney Ni in the presence of acetic acid. Racemic streptazolin (200) was obtained from 199 in several additional steps (74). 

The sesquiterpene skeleton has also been assembled by the intramolecular nitrile oxide cycloaddition sequence. Oxime 238 (obtained from epoxy silyl ether 237), on treatment with sodium hypochlorite gave isoxazoline 239, which was sequentially hydrolyzed and then subjected to the reductive hydrolysis conditions-cyclization sequence to give the furan derivative 240 (330) (Scheme 6.93). In three additional steps, compound 240 was converted to 241. This structure contains the C11-C21 segment of the furanoterpene ent-242, that could be obtained after several more steps (330). 

Reactions on the three-carbon bridge of oxabicyclo [3.2.1] compounds have been reported but less systematically studied. Because the majority of these compounds are derived from oxyallyl cation cycloadditions, most experiments on the three-carbon bridge involve addition to the bicyclic ketone. The parent oxabicyclo[3.2.1] ketone 90 undergoes reduction with bulky hydride sources such as L-selectride to generate the endo alcohol, Eq. 68 [112]. Presumably, the selectivity is due to equatorial attack of the hydride at the ketone of the pyran-one in a pseudo chair conformation. The exo alcohol is prepared from the endo alcohol by a Mitsunobu inversion-hydrolysis sequence [113]. 

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