Direct Palladium-Catalysed Cross-Coupling Reactions Between Organolithium or Organozinc Reagents and (Hetero)Aryl Bromides in Nonconventional Solvents

In spite of their enormous synthetic relevance, the use of highly polar organometallic reagents has been to date restricted to anhydrous conditions, inert atmosphere and low temperatures to avoid their fast decomposition and to control their reactivity. One of the most momentous challenge in organic synthesis is the replacement of harsh and volatile organic compounds by more environmentally responsible solvents.[1] Building upon our recent findings on the use of organometallics of in unconventional reaction media [e.g., the so-called deep eutectic solvents (DESs), water],[2–5] in this Communication we report that a wide range of alkyl- and aryllithium or organozinc reagents can undergo fast chemo- and regioselective cross-coupling reactions with (hetero)aryl bromides in the presence of a Pd catalyst, under mild reaction conditions and under air, using bulk water or DES as a privileged reaction medium, to afford the desired adducts in yields up to 98%.[6] The described protocols have been optimised so as to minimize the formation of byproducts mainly arising from a metal-halogen exchange and from a -hydride elimination reaction. This methodology opens up new vistas in the perspective of the development of a sustainable organometallic chemistry in bio-inspired solvents.