Organic Reactivity Made Easy and Accurate with Automated Multireference Calculations

Abstract

In organic reactivity studies, quantum chemical calculations play a pivotal role as the foundation of understanding and machine learning model development. While prevalent black-box methods like density functional theory (DFT) and coupled-cluster theory (e.g., CCSD(T)) have significantly advanced our understanding of chemical reactivity, they frequently fall short in describing multiconfigurational transition states and intermediates. Achieving a more accurate description necessitates the use of multireference methods. However, these methods have not been used at scale due to their often-faulty predictions without expert input. Here, we overcome this deficiency with automated multiconfigurational pair-density functional theory (MC-PDFT) calculations. We apply this method to 908 automatically generated organic reactions. We find 68% of these reactions present significant multiconfigurational character in which the automated multiconfigurational approach often provides a more accurate and/or efficient description than DFT and CCSD(T). This work presents the first high-throughput application of automated multiconfigurational methods to reactivity, enabled by automated active space selection algorithms and the computation of electronic correlation with MC-PDFT on-top functionals. This approach can be used in a black-box fashion, avoiding significant active space inconsistency error in both single- and multireference cases and providing accurate multiconfigurational descriptions when needed.

We introduce an approach that automates accurate calculations of hundreds of organic reactions, based on multiconfigurational pair-density functional theory.