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

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 alpha or beta 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.