Underexplored Catalysts as General Structures: Application of Machine Learning Techniques for Reaction‐Specific Datasets

General catalysts are usually identified through broad experimental screening to find structures that perform reliably across many substrates and reaction classes. In secondary amine organocatalysis, historical reporting is strongly skewed toward a small set of standard catalysts, leaving many plausible scaffolds underexplored and difficult to evaluate objectively. Here, we apply a bias-aware machine learning workflow designed for small, uneven datasets to prioritize candidate general catalysts from limited historical data. Within the iminium-based reaction space used to construct the curated and virtually balanced dataset, this analysis surfaced several high-performing candidates, including a rarely studied imidazolidinone bearing a benzyl-protected indole substituent. Despite minimal precedent, this scaffold performed competitively in experimental benchmarking and external transferability tests. In a retrospective analysis restricted to pre-2005 examples, the same workflow prioritized catalyst families that later became widely adopted (e.g., diarylprolinol silyl ethers and imidazolidinones) among its top candidates, consistent with earlier prioritization from the literature available at the time. Together, these results show how bias-aware modeling can highlight overlooked scaffolds and reduce the experimental burden required to identify broadly useful catalysts. Pairing targeted experiments with data-driven prioritization provides a practical route to expanding the set of reliable secondary-amine catalysts beyond the structures that dominate current practice.