SCALABLE PALLADIUM-CATALYSED NEGISHI CROSS-COUPLING REACTIONS BETWEEN ORGANOZINC REAGENTS AND (HETERO)ARYL BROMIDES IN NONCONVENTIONAL SOLVENTS

In spite of their enormous synthetic relevance, the use of polar organometallic reagents has been to date restricted to anhydrous conditions, inert atmospheres 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 in unconventional reaction media [e.g., the so-called deep eutectic solvents (DESs), water],[2 7] in this Communication we report that a wide range of alkyl- and arylzinc reagents can undergo fast chemo- and regioselective cross-coupling reactions with functionalized (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 and over 98% (Figure 1).[8] The described protocol is scalable (up to 5g), and proceed in the absence of additional ligands, and with an easy recycling of both the DES or water and the catalyst. This methodology opens up new vistas in the perspective of the development of a sustainable organometallic chemistry in bio-inspired solvents.