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 μ-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 %.