Regioselective synthesis of isoxazole and 1,2,4-oxadiazole-derived phosphonates via [3 + 2] cycloaddition?

Organic & Biomolecular Chemistry Pub Date: 2018-10-01 DOI: 10.1039/C8OB02257G

Abstract

The results of the study on reactions of halogenoximes bearing (protected) functional groups or fluorinated substituents with various phosphorus-containing dipolarophiles are described. To control the regioselectivity of the reaction, vinylphosphonates bearing a leaving group (i.e. bromine or dialkylamino group) in the α or β position were used; 3,5- and 3,4-disubstituted isoxazoles were obtained in 47–80% and 63–75% yields, respectively. The reaction was also effective for the parent vinyl phosphonate and cyanophosphonate; in this case, the corresponding isoxazoline- and 1,2,4-oxadiazole-derived phosphonates were isolated in 55–69% and 34–73% yields, respectively. The utility of the products obtained was demonstrated by the preparation of direct conformationally restricted analogues of phosphohistidine.

Graphical abstract: Regioselective synthesis of isoxazole and 1,2,4-oxadiazole-derived phosphonates via [3 + 2] cycloaddition
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