Water and Sodium Chloride: Essential Ingredients for Robust and Fast Pd-catalysed Cross-Coupling Reactions between Organolithiums and (Hetero)aryl halides.

Direct palladium-catalysed cross-couplings between organolithiums and (hetero)aryl halides (Br, Cl) proceed fast, cleanly and selectively at room temperature in air, with water as the only reaction medium and in the presence of NaCl as a cheap additive. Under optimised reaction conditions, a water-accelerated catalysis is responsible for furnishing Csp3-Csp2, Csp2-Csp2, and Csp-Csp2 cross-coupled products, competitively with protonolysis, within a 20 s reaction time, in yields of up to 99%, and in the absence of undesired dehalogenated/homocoupling side-products even if it starts from challenging secondary organolithiums. It is worth noting that the proposed protocol is scalable and the catalyst and water can easily and successfully be recycled up to 10 times, with an E-factor as low as 7.35.