Tartramide Ligands for Copper-Catalyzed N-Arylation at Room Temperature

Abstract

Readily accessible tartramide ligands have been demonstrated to promote copper-catalysed N-arylation under mild conditions. In addition, the coupling protocol employs cheap and readily available pre-catalyst, ligand, and base (NaOH), and overcomes many current limitations often associated with Ullmann coupling: it can be run with low catalyst loadings, does not require the use of excess amine, operates at room temperature, is fully homogeneous, and displays improved tolerance to air and moisture. Detailed kinetic studies using reaction progress kinetic analysis (RPKA) methods have provided insight into the factors influencing the reaction rate in terms of impact of ligand structure, reactant/catalyst dependence and catalyst (in)stability. These kinetic insights have been used in a quality-by-design approach for further optimization of the reaction protocol. The reaction scope was extended to 22 examples, showing broad applicability for a wide range of substituted aryl iodides with both primary and secondary amines. (Figure presented.).