A typical strategy for the development of synthetic methodologies consists of several stages (Figure ). Initially, chemists employ random screening based on existing literature to identify potential reaction hits, which serve as starting points. Once an initial hit is discovered, the focus shifts towards optimizing the reaction conditions for a single substrate using a method known as "one-factor-at-atime" (OFAT) . In this approach, various reaction variables, such as ligands, bases, solvents, and temperature, are systematically screened one by one. The best result is retained, and the next variable is subsequently optimized. However, it is crucial to recognize that OFAT optimization fails to capture potential synergistic interactions between multiple variables, which can lead to suboptimal outcomes. Furthermore, it is crucial to acknowledge that following this approach can result in overoptimization for a specific substrate, necessitating subsequent re-optimization of the reaction conditions to discover more general conditions that can be applied across the entire reaction scope. As a result, when these more "general" reaction conditions are uniformly applied to all members of the reaction scope, it may lead to less than optimal reaction yields for a significant portion of the scope.