Using mechanistic insight, a new ligand (EPhos) for the Pd-catalyzed C-N cross-coupling between primary amines and aryl halides has been developed. Employing an isopropoxy group at the C3-position favors the C-bound isomer of ligand-supported Pd(II) complexes and leads to significantly improved reactivity. The use of a catalyst system based on EPhos with NaOPh as a mild homogeneous base proved to be very effective in the formation of 4-arylaminothiazoles and highly functionalized 2-arylaminooxazoles. Previously, these were not readily accessible using Pd-catalyzed methodology.
“Mechanistic Insight Leads to a Ligand That Facilitates the Pd-Catalyzed Formation of 2-(Hetero)Arylaminooxazoles and 4-(Hetero)Arylaminothiazoles”, Angew. Chem. Int. Ed., 2017, 56, 10569-10572.