Hidden in Plain Sight: Commonly Used Copper N-Heterocyclic Carbene Catalysts Gain Stabilization from Anagostic Cu···H–C Interactions

Abstract

The ubiquity in organic chemistry of copper catalysts supported by N-heterocyclic carbene (NHC) ligands is often attributed to the ability of sterically bulky and electronically donating NHCs to stabilize low-coordinate intermediates. Here, we show using meta-analysis of 893 solid-state Cu-NHC structures that nearly all Cu-NHC complexes contain at least one short Cu···H-C contact within the range expected for anagostic interactions, implying that Cu···H-C stabilization is prevalent in commonly used Cu-NHC catalysts. A quantum crystallography study of one example, ItBuCuCl (1), provided evidence for four Cu···H-C anagostic interactions in the solid state. Based on experimental solid-state NMR spectroscopy and QTAIM analysis of theoretical charge density, evidence for four Cu···H-C anagostic interactions was also obtained for the solid-state structure of IPrCuCl (2), a ubiquitous complex in homogeneous Cu catalysis. The effect of these anagostic interactions on the solution-phase chemistry of 1 was probed by comparing catalytic activity of ItBuCuCl with its deuterated analogue, d18-ItBuCuCl, revealing a secondary kinetic isotope effect (KIE) of kH/kD = 1.09 ± 0.01 for the hydrosilylation of a ketone at 315 K. Since these anagostic interactions were not previously assigned apart from selected supramolecular systems, knowledge of anagostic stabilization of Cu-NHC complexes is expected to guide future catalyst designs.