Radical Cross-Electrophile Coupling in Medicinal Chemistry: A New Frontier for C-C Bond Construction

Radical cross-electrophile coupling (XEC) has emerged as a powerful alternative to classical cross-coupling for C–C bond formation in drug discovery. Using single-electron transfer pathways, XEC avoids prefunctionalized reagents and expands functional group tolerance. Key advances include nickel catalysis, dual photoredox/Ni systems, electrochemical methods, and metal-free photocatalysis. These strategies enable late-stage diversification, library synthesis, and bioactive molecule modification. Challenges in scalability, selectivity, and asymmetric control remain, but progress in ligand design, green catalysis, and machine learning points to XEC as a promising frontier in medicinal chemistry.