Pd-Catalyzed Aryl Amination Mediated by Well Defined, N-Heterocyclic Carbene (NHC)-Pd Precatalysts, PEPPSI

Pd–N‐heterocyclic carbene (NHC)‐catalyzed Buchwald–Hartwig amination protocols mediated by Pd–PEPPSI precatalysts is described. These protocols provide access to a range of hindered and functionalized drug‐like aryl amines in high yield with both electron‐deficient and electron‐rich aryl‐ and heteroaryl chlorides and bromides. Variations in solvent polarity, base and temperature are tolerated, enhancing the scope and utility of this protocol. A mechanistic rationalization for base strength (pKb) requirements is also provided. A practical protocol for the amination of aryl chlorides and bromides catalyzed by Pd‐PEPPSI precatalysts affords a range of sterically hindered and functionalized, drug‐like aryl amines in good to excellent yield under strongly (tBuOK) or weakly basic (Cs2CO3) conditions.