Synthesis of pyridines and pyrazines using intramolecular hydroamination

Abstract

Despite recent progress, the scope and efficiency of intramolecular hydroamination has not yet reached its full synthetic potential. In particular, cyclizations to form 6-membered rings and applications in the synthesis of aromatic nitrogen heterocycles remain rare, despite the potential to access a variety of medicinally relevant heterocycles. The intramolecular hydroamination of alkynes presented offers a general approach to such nitrogen heterocycles from appropriately substituted acyclic precursors, in which the oxime functionality allows for a milder cyclization event and allows subsequently for the installation of one additional unsaturation (via loss of H2O). The discovery and optimization of an acid-catalyzed, hydroamination-isomerization-aromatization route for the synthesis of pyridines and pyrazines will be presented and discussed.* *Please refer to dissertation for diagrams.