Cycloaddition Route to 4-Iodoisoxazoles

Significance

Reported is a thermal 1,3-dipolar cycloaddition strategy to 4-iodoisoxazoles in a ­reaction between alkynyl iodides and nitrile ­oxides. The nitrile oxides are formed in situ from chlorooximes, by slow addition of base via a syringe pump. The reaction is regioselective, which was proven by NMR studies on the dehalogenated product. The substrate scope in the reaction was well studied, and the yields range from moderate to good. The yields are slightly higher, when a preformed stable nitrile oxide is used rather than the in situ formed ones. Three of the synthesized 4-iodoisoxazoles were subjected to Suzuki cross-couplings with arylboronic acids to afford the corresponding highly substituted isoxazoles.