Regioselective Synthesis of 2,4,5-Trisubstituted Oxazoles and Ketene Aminals via Hydroamidation and Iodo-Imidation of Ynamides

A novel
and straightforward protocol is demonstrated for the synthesis
of highly substituted oxazoles from readily accessible ynamides in
the presence of ytterbium­(III) trifluoromethanesulfonate [Yb­(OTf)3], N-iodosuccinimide (NIS), and acetonitrile.
Multiple oxazole skeletons in the aryl periphery are constructed in
a single operation for the first time. The hydroamidation and iodo-imidation
of ynamides to trisubstituted and tetrasubstituted ketene aminals
is exemplified. An isotope labeling experiment is used to identify
the oxygen source in this transformation. The reactions are scalable
to the gram scale, testifying the robustness of the transformations.