From desktop to benchtop with automated computational workflows for computer-aided design in asymmetric catalysis

Abstract

The organic chemist’s toolbox is vast, with technologies to accelerate the synthesis of novel chemical matter. The field of asymmetric catalysis is one approach to accessing new areas of chemical space and computational power is today sufficient to assist in this exploration. Unfortunately, existing techniques generally require computational expertise and are therefore underutilized in synthetic chemistry. Here we present our platform Virtual Chemist, which allows bench chemists to predict outcomes of asymmetric chemical reactions ahead of testing in the laboratory, in just a few clicks. Modular workflows facilitate the simulation of various sets of experiments, including the four realistic scenarios discussed: one-by-one design, library screening, hit optimization and substrate-scope evaluation. Catalyst candidates are screened within hours and the enantioselectivity predictions provide substantial enrichments compared to random testing. The achieved accuracies within ~1 kcal mol–1 provide opportunities for computational chemistry in the field of asymmetric catalyst design, allowing bench chemists to guide the design and discovery of asymmetric catalysts. Computational chemistry has remained largely inaccessible to the experimental chemistry community. Here we report the VIRTUAL CHEMIST, a software suite free for academic use, that enables organic chemists without expertise in computational chemistry to perform virtual screening experiments for asymmetric catalyst discovery and design.