Comprehensive Evaluation of Oxidation Resistance for Tertiary Phosphines Using Universal Machine Learning Interatomic Potential-Aided Molecular Dynamics Simulation

Abstract

Tertiary phosphines play important roles in a wide range of chemical reactions, but they suffer from oxidation in air. Here, we propose a computational workflow for the comprehensive prediction of oxidation resistance in tertiary phosphines based on molecular dynamics (MD) simulations using Matlantis PFP, a universal machine learning interatomic potential (uMLIP). MD simulations were conducted for 51 different tertiary phosphines and analyzed to estimate mean survival time by survival analysis (τ). The resulting τ reproduced experimentally and theoretically recognized trends in oxidation resistance across chemically diverse phosphines. In particular, it captured electronic, steric, and aromatic effects on oxidation resistance, even in systems where these factors are intertwined. Comparisons with reported oxidation behaviors further showed that τ correctly identifies both highly air-sensitive and highly air-stable phosphines. These results demonstrate that the present workflow provides a practical, generalizable tool for pre-experimental assessment of phosphine oxidation resistance and for more rational ligand design.