Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling Facilitated by a Weak Amine Base with Water as a Cosolvent

The development of a Ni-catalyzed Suzuki-Miyaura cross-coupling that utilizes a weak amine base and performs optimally with water as a cosolvent is reported. The aqueous amine base facilitates an equilibrium between the Ni oxidative addition complex and Ni mu-hydroxo dimers, enabling productive catalysis at low metal loadings (typically 1 mol %). A practical catalytic system is enabled by use of a commercially available Ni oxidative addition complex as a precatalyst. The mild conditions allow high functional group tolerance and application to complex pharmaceutical substrates, one of which was demonstrated on a 50 g scale with a catalyst loading of 0.5 mol %.

Automated summary

This study reports the development of a Ni-catalyzed Suzuki-Miyaura cross-coupling reaction using an aqueous amine base as a catalyst. The reaction exhibits high catalytic activity and low metal loadings, while tolerating various functional groups. Additionally, the method is applicable to complex pharmaceutical substrates.