"Naked Nickel"-Catalyzed Heteroaryl-Heteroaryl Suzuki-Miyaura Coupling

Abstract

In this article, we report that the air-stable "naked nickel", [Ni(^4-CF3stb)₃], is a competent catalyst in the catalytic Suzuki-Miyaura cross-coupling reaction (SMC) between heteroaryl bromides and heteroaromatic boron-based nucleophiles. The catalytic system is characterized by its ability to avoid decomposition or deactivation in the presence of multiple Lewis basic sites. The protocol permits the formation of C‒C bonds between two heteroaryl moieties in the absence of complex exogenous ligands, thus minimizing screening procedures and simplifying reaction setups. This method accommodates combinations of distinct 6-membered heteroaryl bromides and 5- and 6-membered heterocyclic B-based nucleophiles.

Keywords: Boron; Cross‐coupling; Heterocycles; Nickel; Synthetic methods.

Figure 1

a) Traditional approaches for Ni‐catalyzed Suzuki‒Miyaura cross‐coupling (SMC) between two heteroaryl units. b) This work: a simple “naked‐nickel”‐catalyzed approach for heteroaryl–heteroaryl SMC coupling.

Figure 2

Scope of the Suzuki–Miyaura cross‐coupling protocol. Reaction conditions: heteroaryl bromide (1.0 equiv.), heteroaryl boronic acid (1.5 equiv.), K₃PO₄ (1.8 equiv.), Ni(^4‐CF3stb)₃ (10 mol%), DMA (0.5 M), 60 °C, 16 h, 0.3 mmol scale. Yields represent isolated yields. ^a)From heteroaryl chloride, 100 °C. ^b)From heteroaryl boronic acid pinacol ester.

Figure 3

a) Practicability and zero‐precaution experiments. b) Scale‐up experiment. Yields determined by ¹H NMR, using 1,3,5‐trimethoxybenzene as internal standard. ^a)Isolated yield.