Salt to Taste: The Critical Roles Played by Inorganic Salts in Organozinc Formation and in the Negishi Reaction.

The first cross-coupling of organozinc nucleophiles with aryl halides was reported in 1977 by Negishi. Unknown to all at the time was the importance of salt additives that were often present as a byproduct from the organozinc preparation. For decades, these salt additives were overlooked until 2006 when it was discovered that two different, yet effective methods for preparing organozinc solutions (i.e. one with salt and one without) provided drastically different results. Since this finding, the exact role of salt additives in cross-coupling has been debated in the catalysis community. In this Review we highlight all the major discoveries regarding the influence of salt additives on the formation of organozinc reagents and their use in the Negishi reaction. These effects include solubilizing key intermediates, the formation of higher-order zincates, product inhibition, catalyst protection, and solvent effects.