Lighting up new pathways: Copper and light unite for selective arene alkylation

In a remarkable leap forward for synthetic chemistry, MacMillan and co-workers have unveiled a clever way to directly forge C(sp2)–H alkyl bonds in arenes using light and copper catalysis. At the heart of their discovery lies the inventive idea of dynamic orbital selection, a concept that allows the catalyst to distinguish between aryl and alkyl radicals generated in situ. This precise control enables the selective union of these two distinct radical species, something long considered a major challenge. What makes the method especially appealing is its practicality: simple alcohols and carboxylic acids serve as alkyl radical sources, making the reaction broadly applicable and ideal for the late-stage functionalization of complex molecules. By elegantly sidestepping the harsh conditions and poor selectivity of classical Friedel–Crafts alkylations, this strategy opens new horizons for sustainable C–H functionalization, paving the way for innovations in drug discovery and molecular design. © Indian Academy of Sciences 2025.