Suzuki–Miyaura coupling of arylthianthrenium tetrafluoroborate salts under acidic conditions

Abstract

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. Suzuki–Miyaura cross-coupling between (hetero)aryl (pseudo)halides and base-sensitive and Lewis-basic (hetero)arylboronic acids is challenging, owing to potential side reactions and catalyst poisoning. Now, the Suzuki–Miyaura cross-coupling of arylthianthrenium salts with (hetero)arylboronic acids, under acidic conditions, is reported, enabling the efficient coupling of base-sensitive and Lewis-basic (hetero)arylboronic acids.