Transition Metal-Free Cascade Cyclization of Epoxy-Ynamides: To Go for 1,3-Oxazines or 1,4-Oxazines?

An approach to both 1,3- and 1,4-oxazines
is developed by the cascade
cyclization of epoxy ynamides under transition metal-free conditions.
Thus, while 1,3-oxazines are obtained in a regio- and stereoselective
manner by using base, cyclization of epoxy ynamides with sodium azide
as a nucleophile results in 1,4-oxazines. Deuterium-labeling experiment
demonstrates the role of water as a proton source in the formation
of 1,4-oxazines. Epoxy tethered alkyne precursors provide 1,4-oxazines
that undergo click reaction.