Buttressing Effect as a Key Design Principle towards Highly Efficient Palladium/N‐Heterocyclic Carbene Buchwald–Hartwig Amination Catalysts

Abstract The backbone substitution of the standard 1,3‐bis(2,6‐diisopropylphenyl)‐2 H ‐imidazol‐2‐ylidene (IPr) ligand by dimethylamino groups was previously shown to induce a dramatic improvement in the catalytic efficiency of the corresponding Pd–PEPPSI (pyridine‐enhanced pre‐catalyst preparation, stabilization, and initiation) pre‐catalysts in N‐arylation reactions. Herein, a thorough structure/activity study towards rationalizing this beneficial effect has been described. In addition to the previously reported IPr and IPr ligands, the new IPr and IPr ligands, which bear one bulkier diisopropylamino group and a combination of dimethylamino and chloro substituents, respectively, have been designed and analyzed in the study. The influence of the backbone substitution was found to be steric in origin and is related to the well‐known buttressing effect encountered in arene chemistry. The usefulness and versatility of this approach was demonstrated through the development of a highly efficient catalytic system for the challenging arylation of bulky α,α,α‐trisubstituted primary amines. The optimized system based on the [PdCl(η 3 ‐cinnamyl)(IPr )] or [PdCl(η 3 ‐cinnamyl)(IPr )] pre‐catalysts operates under unprecedented mild conditions (catalyst loadings: 0.5–2 mol %, reaction temperatures: 40–60 °C) with a wide substrate scope.