A nitrile oxide having a carbamoyl group is readily generated upon the treatment of 2-methyl-4-nitro-3-isoxazolin-5(2H)-one with water under mild reaction conditions, even in the absence of special reagents. The obtained nitrile oxide undergoes cycloaddition with dipolarophiles, alkynes 10 and alkenes, to afford the corresponding isoxazol(in)es, which are useful intermediates in the synthesis of polyfunctionalized compounds. A plausible mechanism underlying the formation of the nitrile oxide is proposed, which involves an anomalous hydration/dehydration sequence. DFT calculations were also performed to support this mechanism.

3-Carbamoyl-2-isoxazolines, prepared by cycloaddition of functionalized nitrile oxide, serve as masked 3-unsubstituted isoxazolines to afford 2-isoxazoline-3-carboxylic acid, b-cyanoalcohol, a,bunsaturated nitrile, and a,b-unsaturated amide upon heating in the alkaline solution. The present reaction is also applicable to synthesis of 3,4-difunctionalized isoxazoles and b-hydroxy-g-lactone.

An Anomalous Hydration/Dehydration Sequence for the Mild Generation of a Nitrile Oxide. -Treatment of isoxazolinones (I) with water under mild conditions generates a nitrile oxide (VI) which smoothly undergoes cycloaddition with various dipolarophiles furnishing isoxazoles (III) and isoxazolines (V). A plausible reaction mechanism is proposed. -(NISHIWAKI*, N.; KOBIRO, K.; KIYOTO, H.; HIRAO, S.; SAWAYAMA, J.; SAIGO, K.; OKAJIMA, Y.; UEHARA, T.; MAKI, A.; ARIGA, M.; Org. Biomol. Chem. 9 (2011) 8, 2832-2839, http://dx.doi.org/10.1039/c0ob01005g ; Sch. Environ. Sci. Eng., Kochi Univ. Technol., Kami, Kochi 782, Japan; Eng.) -Mischke 33-109