Figure lists the transformations that give the lowest percentage of characterized products for each starting heterocycle type for the Enamine database. In this table, each of the analyzed starting heteroaromatic substrates are represented exactly once. Figure lists the ten transformations in the dataset with the lowest percentages of characterized products regardless of the starting heterocycle type. In the tables, the transformations are listed in the order of increasing percentage of products that are characterized. The high potential impact of a pyrazole-to-furan transformation is evidenced by the lowest percentage (0.60%) of characterized compounds. In Figure , some starting heterocycle types are listed more than once. Transformations involving ring contractions of the pyrimidine heterocycle (to give imidazoles, pyrroles, and pyrazoles) emerge as highly impactful. Three other heterocycle types -thiazoles, imidazoles, and pyrroles -appear more than once in the top ten transformations. However, pyrimidine is the only starting substructure that appears three times in the top ten transformations of the single-atom edits, highlighting the potential for single-atom skeletal edits of pyrimidines to greatly expand accessible heteroaromatic chemical space. Accordingly, McNally and coworkers recently reported a powerful strategy for the diversification of the pyrimidine scaffold into several types of other heterocyclic substructures using skeletal editing approaches. In this representation of the data, the potential value of methods to convert a single starting heteroaromatic into several different heterocycles is clear. However, our analysis suggests an orthogonal direction that could be equally valuable would be to focus on accessing previously inaccessible products, such as pyrroles, from a broader range of heterocycles rather than accessing a wide range of heterocycles from one starting substructure. For example, conversion of different types of starting substructures into pyrroles generally leads to the lowest percentages of known compounds, positioning pyrroles as an attractive target for continued development in skeletal editing. In fact, Park and coworkers recently reported a strategy for the skeletal editing of furans to pyrroles, an important development with this analysis in mind. Finally, the five single-atom transformations with the lowest percentage of characterized products (i.e., of high value) from the Enamine 350/3 database are graphically represented in Figure .