Efficient Machine Learning Approach for Yield Prediction in Chemical Reactions

Developing machine learning (ML) models for yield prediction of chemical reactions has emerged as an important use case scenario in very recent years. In this space, reaction datasets present a range of challenges mostly stemming from imbalance and sparsity. Herein, we consider chemical language representations for reactions to tap into the potential of natural language processing models such as the ULMFiT (Universal Language Model Fine Tuning) for yield prediction, which is customized to work across such distribution settings. We contribute a new reaction dataset with more than 860 manually curated reactions collected from literature spanning over a decade, belonging to a family of catalytic meta-C(sp2)-H bond activation reactions of high contemporary importance. Taking cognizance of the dataset size, skewness toward the higher yields, and the sparse distribution characteristics, we developed a new (i) time- and resource-efficient pre-training strategy for downstream transfer learning, and (ii) the CFR (classification followed by regression) model that offers state-of-the-art yield predictions, surpassing conventional direct regression (DR) approaches. Instead of the prevailing pre-training practice of using a large number of unlabeled molecules (1.4 million) from the ChEMBL dataset, we first created a pre-training dataset SSP1 (0.11 million), by using a substructure-based mining from the PubChem database, which is found to be equally effective and more time-efficient in offering enhanced performance. The CFR model with the ULMFiT-SSP1 regressor achieved an impressive RMSE of 8.40 for the CFR-major and 6.48 for the CFR-minor class in yield prediction on the title reaction, with a class boundary of yield at 53 %. Furthermore, the CFR model is highly generalizable as evidenced by the significant improvement over the previous benchmark reaction datasets.

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02is that these HTE datasets also exhibit a relatively more the yield as compared to the m-CHA dataset, where the yield higher end. 44
03Late-Stage Peptide Diversification
04of the corresponding % yield that ranges from 0 to 100. The problem of regression task over a labeled chemical reactiondataset
05yield, ranging from 0 to 53%, are therefore categorized as the CFR-minor class (leading to reactions), and those higher than this threshold form the CFR-major class (711 reactions)

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