Computational, Data Science, and Experimental Evaluation and Design of Homogeneous Transfer Hydroformylation Catalysts

The computational
design of transition-metal catalysts
remains
a grand challenge in chemistry. Here, we used density functional theory
(DFT) calculations, data science, and experiments to tackle the analysis
and design of new catalysts for transfer hydroformylation because
only a single known bisphosphine ligand combined with Rh has been
reported to provide high reactivity. We first used experiments to
screen commercially available and common bisphosphines, and this data
was then combined with DFT calculations and data science to screen
>600 bisphosphine ligands from our ReaLigands library and develop
interpretable chemical space mapping. Following another round of DFT
calculations, we identified several promising bisphosphine ligands
that were subsequently synthesized and validated experimentally.