Palladium(II)‐Catalyzed Nondirected Late‐Stage C(sp2)−H Deuteration of Heteroarenes Enabled Through a Multi‐Substrate Screening Approach

The importance of deuterium labelling in a variety of applications, ranging from mechanistic studies to drug-discovery, has spurred immense interest in the development of new methods for its efficient incorporation in organic, and especially in bioactive molecules. The five-membered heteroarenes at the center of this work are ubiquitous motifs in bioactive molecules and efficient methods for the deuterium labelling of these compounds are therefore highly desirable. However, the profound differences in chemical properties encountered between different heteroarenes hamper the development of a single set of broadly applicable reaction conditions, often necessitating a separate optimization campaign for a given type of heteroarene. In this study we describe the use of a multi-substrate screening approach to identify optimal reaction conditions for different classes of heteroarenes from a minimal number of screening reactions. Using this approach, four sets of complementary reaction conditions derived from our dual ligand-based palladium catalysts for nondirected C(sp