Impact of C-H Cross-Coupling Reactions in the One-Step Retrosynthesis of Drug Molecules

Pharmaceutical synthesis requires a diversity of chemical reactions. The discovery of new reactions enable novel retrosynthetic disconnections, potentially expediting access to complex molecules. This Synopsis demonstrates the use of enumerative combinatorics to find impactful underdeveloped reactions for drug synthesis. By mapping pharmaceutical target molecules onto available building blocks using just one retrosynthetic disconnection even if the requisite reaction is not yet known, we highlight the importance of site-selective C-H cross-coupling methods. This cheminformatics-driven retrosynthetic analysis identifies novel reaction methods of value to the synthesis toolbox.