Chapter 10 - Looking behind the scenes of Grubbs catalysis with the Unified Reaction Valley Approach

Abstract

In this study we analyzed the mechanism of [2+2] cycloaddition and cycloreversion reactions between trichlorovinylsilane and one first-generation Grubbs model catalyst M1 with a ▪ ligand and two second-generation Grubbs model catalysts M2 with an N-heterocyclic carbene (NHC) ligand and M3 with a 2,5-di-methyl-NHC ligand. As a mechanistic tool, we applied the Unified Reaction Valley Approach (URVA), based on reaction path calculations performed at the B3LYP/6–31G(d,p)/SDD(Ru) level of theory. In addition, for all stationary points of these reactions, we performed a Local Mode Analysis (LMA) and QTAIM analysis of the electron density at the B3LYP/6–31G(d,p)/NESC/Jorge–TZP(Ru) and DLPNO–CCSD(T)/def2–TZVP/ECP(Ru) levels of theory. In all reactions investigated in this work, four target bonds play a key role, either being formed and/or broken or changing from double to single bonds, and vice versa during the catalytic process. As revealed by the URVA analysis in the cycloaddition reactions, the bond forming events leading to the intermediate metallacyclobutane occur in a concerted fashion after the transition state (TS), i.e., this process does not contribute to the energy barrier. The bond breaking events of the following cycloreversion reactions transforming the intermediate into to final product are also concerted, however, they occur before the TS, i.e., this process contributes to the barrier height. In this way URVA rationalizes why all cycloaddition reactions have a lower activation energies than their cycloreversion counterparts. According to our results, M3 is the most effective model catalyst. Its activity is related to a strong stabilization of the metallacyclobutane intermediate and specific interactions between the reacting species and the methyl hydrogen atoms of the 2,5-di-methyl-NHC ligand of the catalyst. Based on LMA, we could also quantify the important role of a 4-center–2-electron α,β-(CCC) agostic interaction in the metallacyclobutane intermediate donating electron density to the Ru coordination center and facilitating the CC bond cleavage of the ring-opening cycloreversion step, lowering in this way the energy barrier. Overall, the new mechanistic details obtained with the URVA and LMA analysis can serve as a roadmap for the optimization of current and the future design of the next generations of Grubbs catalysts and beyond.