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.