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

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 (NaOtBu, K2CO3, DBU/NaTFA). In addition to providing optimal ligand/catalyst identification, and bringing to light methodology limitations (e. g., unwanted C-O cross-coupling with NaOtBu), 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.