Integrating Machine Learning and Large Language Models to Advance Exploration of Electrochemical Reactions

Abstract Electrochemical C−H oxidation reactions offer a sustainable route to functionalize hydrocarbons, yet identifying suitable substrates and optimizing synthesis remain challenging. Here, we report an integrated approach combining machine learning and large language models to streamline the exploration of electrochemical C−H oxidation reactions. Utilizing a batch rapid screening electrochemical platform, we evaluated a wide range of reactions, initially classifying substrates by their reactivity, while LLMs text‐mined literature data to augment the training set. The resulting ML models for reactivity prediction achieved high accuracy (>90 %) and enabled virtual screening of a large set of commercially available molecules. To optimize reaction conditions for selected substrates, LLMs were prompted to generate code that iteratively improved yields. This human‐AI collaboration proved effective, efficiently identifying high‐yield conditions for 8 drug‐like substances or intermediates. Notably, we benchmarked the accuracy and reliability of 12 different LLMs–including LLaMA series, Claude series, OpenAI o1, and GPT‐4‐on code generation and function calling related to ML based on natural language prompts given by chemists to showcase potentials for accelerating research across four diverse tasks. In addition, we collected an experimental benchmark dataset comprising 1071 reaction conditions and yields for electrochemical C−H oxidation reactions.