Virtual Ligand Strategy in Transition Metal Catalysis Toward Highly Efficient Elucidation of Reaction Mechanisms and Computational Catalyst Design

Wataru Matsuoka, Yu Harabuchi, and Satoshi Maeda (2023)
Highlighted by Jan Jensen

This perspective shows how an old computational tool can be adapted to serve a new purpose. When I started in compchem changing, say, a few F atoms to and H atoms in a molecule often made the difference between waiting a few days and a few weeks for the calculations to finish. People therefore developed pseudo H atoms that could mimic the electronic effect of larger atoms or even entire functional groups. Some of these methods were later adapted to serve as boundary atoms in QM/MM calculations and now they have found a new use in screening for ligands in organometallic catalysts.

The use of pseudoatoms to model such ligands not only speeds up the individual calculations but also maps the chemical space on to just two dimensions, electronic and steric, that allows the space to be searched more efficiently. Once the desired combination of electronics and sterics is found corresponding real ligands are found by another, much faster, screen if commercially available or synthetically accessible ligands.

The authors use this approach to identify two phosphine ligands for a chemoselective Suzuki–Miyaura cross-coupling catalyst, complete with experimental verification.

The downside is that the parameterisation of these "virtual ligands" are a bit involved and very ligand-dependent. But an interesting approach non-the-less.

This work is licensed under a Creative Commons Attribution 4.0 International License.