Machine-Assisted Preparation of a Chiral Diamine Ligand Library and In Silico Screening Using Ab Initio Structural Parameters for Heterogeneous Chiral Catalysts

A ligand library containing 31 chiral diamines was synthesized using a flow-based semiautomatic reductive amination system. These ligands were evaluated in a continuous-flow asymmetric 1,4-addition reaction with a heterogeneous Ni catalyst. Based on the experimental results of ab initio DFT calculations, a prediction model for enantioselectivities was successfully constructed. Furthermore, virtual screening of possible ligands was conducted to identify promising structures, which showed good enantioselectivities in experiments.