Palladium-catalyzed cross-dehydrogenative coupling of (hetero)arenes

Organic compounds based on (hetero)aryl scaffolds are systems with a wide range of application, from pharmaceuticals and agrochemicals to semiconducting materials for optoelectronics. The development of efficient methods for the generation of (hetero)aryl-(hetero)aryl bonds is the key step to synthesize these molecules. In this context, Pd-catalyzed cross-dehydrogenative couplings (CDC) of (hetero)arenes are the most recent and attractive strategy: they can be definitely included among reactions with the lowest economic and environmental impact, since they occur between two different (hetero)arenes without pre-activation of both coupling partners (double C-H activation), allowing for superior atom economy and prevention of waste. The development of efficient CDC protocols is challenging, due to relevant limitations which need to be carefully addressed: in particular, regioselectivity issues on both (hetero)aryl scaffolds and the possible formation of undesired homo-coupling products. However, significant efforts have been recently accomplished to face these aspects. This review offers a general, authoritative and up to date overview on the Pd-catalyzed CDC of (hetero)arenes, emphasizing not only the synthetic aspects but also the most relevant mechanistic features, in order to be useful for the wide community of synthetic organic chemists and to push towards new frontiers of the research on this topic. A general and authoritative literature overview on Pd-catalyzed cross-dehydrogenative coupling reactions of (hetero)arenes from the origins to 2023, where not only the synthetic aspects were described but also the most relevant mechanistic features.