Comparative Screening of DalPhos/Ni Catalysts in C‐N Cross‐couplings of (Hetero)aryl Chlorides Enables Development of Aminopyrazole Cross‐couplings with Amine Base

Abstract

Abstract A systematic competitive evaluation of the DalPhos ligand family in nickel‐catalyzed N ‐arylation chemistry is reported, involving primary (linear and branched) and secondary alkylamines, as well as a primary five‐membered heteroarylamine (aminopyrazole), in combination with a diverse set of test electrophiles and bases (NaO t Bu, K 2 CO 3 , DBU/NaTFA). In addition to providing optimal ligand/catalyst identification, and bringing to light methodology limitations (e. g., unwanted C−O cross‐coupling with NaO t Bu), our survey enabled the development of the first efficient catalyst system for heteroatom‐dense C−N cross‐coupling of aminopyrazoles and related nucleophiles with (hetero)aryl chlorides by use of an amine ‘dual‐base’ system.