Macrocyclic NHC Ligands in Hoveyda-Type Ru Alkene Metathesis Catalysts: Only Sterics?

The integration of macrocyclic structures within N-heterocyclic carbene (NHC) ligands in Hoveyda-type catalysts presents a pioneering strategy to enhance selectivity in cross-alkene metathesis. This approach falls within a promising paradigm for avoiding undesired homocouplings between reacting alkenes and introducing site-selectivity into the cross metathesis process. This paper presents a computational study that aims to provide an improved understanding of the impact of these ligand modifications on stability, sterics, and activity, focusing on the precatalyst activation and cross-metathesis. The traditional Hoveyda-type catalyst is compared alongside two recent macrocyclic systems for which experimental data is available. Higher activation barriers in the macrocyclic systems are consistent with the reduced activity observed in these systems. Additionally, a noncovalent interaction component was found to facilitate the selective pathway, in conjunction with the already expected steric descriptors. These results highlight the potential of macrocyclic NHC ligands to enhance catalyst performance, not only offering chemoselectivity based on alkene size, but a potential for stereoselectivity capacity arising from the macrocycle-induced electronic effects.