High-Throughput Experimentation for C(sp2)-C(sp3) Cross-Electrophile Coupling

Cross-electrophile coupling (XEC) has become an important tool for introducing sp³-rich functionality into drug candidates, helping medicinal chemists access compounds with improved physicochemical and ADME properties. However, reaction performance is highly dependent on multiple variables including catalysts, reductants, solvents and additives.

In this poster, Sygnature Discovery presents the development and validation of a high-throughput cross-electrophile coupling workflow, enabling rapid screening and optimisation of reaction conditions using minimal material. The study demonstrates successful translation from microscale screening to preparative-scale synthesis, while exploring a broad range of medicinally relevant substrates and coupling partners.

Key Highights

• High-throughput screening of C(sp²)-C(sp³) cross-electrophile coupling reactions
• Evaluation of catalysts, ligands, additives and reductants to optimise reaction performance
• Broad substrate scope with strong functional group tolerance
• Successful scale-up of optimised reactions from screening plates to larger-scale synthesis
• Future application of machine learning and Bayesian optimisation to accelerate compound library generation