Isoxazole ring, construction

Giacomelli et al. constructed 3-propylisoxazole-5-yl-methanol via a [3-1-2] cycioaddition (Fig. 15) [158]. Nitrobutane was converted to nitrile oxide in the presence of 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and catalytic 4-dimethylaminopyridine (DMAP). Trityl chloride resin-bound propargyl alcohol was employed as the dipolarophile to trap the nitrile oxide, forming the cyclo adduct isoxazole ring under unusually mild conditions (i.e., microwave irradiation at 80 °C for five times 1 min). Disappearance of the starting material was monitored by FT-IR. 

Construction of Isoxazole, Pyrazole and Pyrimidine Rings from Aminopropenones... 

JME696>. Construction of the five-membered ring is also the key step in the synthesis of the pyrazole- and isoxazole-fused pyridopyrimidines 470 (Equation 198) <2004HC089>. 

In a paper concerned with the synthesis of fused pyridazines, the isoxazole 13 was used as a masked amino alcohol, which was eventually used to construct a fused pyridine ring. A standard hydrazine reaction, followed by hydrogenolysis of the isoxazole of the intermediate... 

The 3-benzyloxyisoxazole system has functioned as a storable /3-keto amide unit in the construction of tetracyclines (78JA3609). Michael addition of the anion of the 3-benzyloxyisoxazole (442) to the dienolone (441) followed by deesterification-decarboxylation gave rise to (443) in 80% yield. Dehydration of this material and sodium hydride-induced cyclization afforded (445). Hydrogenolysis over palladium on carbon produced the desired ( )-dedimethylamino-12a-deoxyanhydrotetracycline (446 Scheme 99). This isoxazole route has also been extended to the preparation of a tetracycline having the usual amino function in the A ring. 

The construction of a heterocyclic ring from two reagents, one of which contains a nitro group, is widely used in the synthesis of the nitro derivatives of pyrazole, isoxazole, and 1,2,3-triazole. Thus, for example, the reaction of sodionitromalonal-dehyde with substituted hydrazines leads to the corresponding derivatives of 4-nitropyrazole [33, 61, 471 173] (Scheme 63). 

Ring aromaticity (and antiaromaticity) presumably influence the selectivity of closure. The construction of certain heterocycles, e.g. pyrazoles, isoxazoles, etc., may be rationalized in this way (equation 70). Indeed, it may be the driving force which... 

Stork and Hagedorn have reported that the highly functionalized A-ring of tetracycline can be readily constructed by Michael addition of the 3-benzyloxy-isoxazole (172) to a suitable enone substrate, followed by Claisen cyclization and hydrogenation to release the protected jS-keto-amide (Scheme 22). °... 

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