Isoxazoles vinylogous

Isoxazoles are stable toward many reagents yet undergo alkylation and hydrogenolysis readily. These features make isoxazoles, which may be considered masked diketones, a useful grouping in synthesis (22). Alkylation of 3,5-dimethyllsoxazole, followed by hydrogenolysis and hydrolysis, have been used to prepare a number of diketones (44) and tetraones (4i). Isoxazoles can be opened readily lo the amino ketone, a vinylogous amide (9). 

Although a number of reagents can be used to reduce an isoxazole ring, molybdenum hexacarbonyl31 was selected for use in this synthesis. The action of this reagent on 24 reduces the weak N-0 bond of the isoxazole ring and produces a //-amino-a,//-unsaturated aldehyde (i.e. a vinylogous formamide) (see Scheme 19). Intermediate 87 forms smoothly upon deprotection of the terminal acetylene carbon with basic methanol-THF. 

Isomeric 3,5-disubstituted isoxazoles can be prepared from vinylogous azolides and hydroxylamine hydrochloride. 1391 In this reaction the ratio of the two isomers A and B formed can be controlled by the nature of the base ... 

In Scheme 38 an isoxazole is used to generate the vinylogous urea which ring closes with alcoholic hydrogen chloride (72JHC951). In the same way the isoxazolyl carboxamide (115) is changed, via the substituted enaminone, into (116) (74JHC623). 

Vinylogous a-diazoketones from vinylogous carboxylic acid chlorides— 4-Acyl-5-diazomelhylisoxazoles, condensed isoxazoles s. 17, 854... 

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