A mild, operationally simple cross-dehydrogenative coupling between nitrones and terminal alkynes is described by using cheap, readily available 3,3′,5,5′-tetra-tert-butyldipheno-quinone and dioxygen as oxidants. These cross-couplings can be performed on various nitrones and alkynes with good to excellent yields. Product nitrones are readily transformed to pharmaceutically important 3,5-disubstituted isoxazoles. © 2011 American Chemical Society.