The palladium-catalysed Suzuki–Miyaura cross-coupling (SMC) is currently the most commonly used reaction to construct carbon–carbon bonds in the pharmaceutical industry. Typical methods require the use of a base, which limits the substrate scope. To mitigate this shortcoming, substantial effort has been made to develop base-tolerant organoboron reagents, efficient catalysts and reaction conditions that do not require external bases. Still, many boronic acids cannot be used or must be independently protected, and many Lewis-basic functional groups poison the catalyst. Here we report a conceptually different SMC reaction that can proceed even under acidic conditions, with a broad substrate scope. Key to this advance is the formation of an acid-stable, palladium-based ion pair between the reaction partners that does not require base for subsequent productive transmetallation. Boronic acids that cannot be used directly in other SMC reactions, such as 2-pyridylboronic acid and boronic acids with strong Lewis bases, can now be used successfully.
No takes yet. Share an insight, caveat, or question.
Zhang et al. (2024) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: