An Initiation Kinetics Prediction Model Enables Rational Design of Ruthenium Olefin Metathesis Catalysts Bearing Modified Chelating Benzylidenes

Rational design of second-generation ruthenium olefin metathesis
catalysts with desired initiation rates can be enabled by a computational
model that is dependent on a single thermodynamic parameter. Using
a computational model with no assumption about the specific initiation
mechanism, the initiation kinetics of a spectrum of second-generation
ruthenium olefin metathesis catalysts bearing modified chelating ortho-alkoxy benzylidenes were predicted in this work. Experimental
tests of the validity of the computational model were achieved by
the synthesis of a series of ruthenium olefin metathesis catalysts
and investigation of initiation rates by ultraviolet–visible
light (UV-vis) kinetics, nuclear magnetic resonance (NMR) spectroscopy,
and structural characterization by X-ray crystallography. Included
in this series of catalysts were 13 catalysts bearing alkoxy groups
with varied steric bulk on the chelating benzylidene, ranging from
ethoxy to dicyclohexylmethoxy groups. The experimentally observed
initiation kinetics of the synthesized catalysts were in good accordance
with computational predictions. Notably, the fast initiation rate
of the dicyclohexylmethoxy catalyst was successfully predicted by
the model, and this complex is believed to be among the fastest initiating
Hoveyda–Grubbs-type catalysts reported to date. The compatibility
of the predictive model with other catalyst families, including those
bearing alternative N-heterocyclic carbene (NHC)
ligands or disubstituted alkoxy benzylidenes, was also examined.