Advancing Base-Metal\nCatalysis: Developing Nickel\nCatalysis for the Direct Telescope of Miyaura Borylation and Suzuki–Miyaura\nCross-Coupling Reactions

The\ndevelopment of an efficient and general telescoped\nnickel-catalyzed\nSuzuki–Miyaura coupling (SMC) process from a nickel-catalyzed\nborylation reaction to form Csp<sup>2</sup>–Csp<sup>2</sup> bonds without isolation of the intermediate aryl boronate has been\na long-standing interest for process chemists. Most scalable borylation/SMC\nsequences currently use palladium catalysts in subsequent catalytic\nsteps, yet the ability to utilize nickel has the potential to greatly\nimprove efficiency and decrease cost while also improving sustainability.\nThis work introduces nickel-catalyzed SMC methodology that operates\nunder homogeneous biphasic conditions to minimize inhibition from\nreaction byproducts of borylation and benefits from the addition of\nmethanol as a cosolvent. These findings enabled the development of\na one-pot, two-reaction method, which is demonstrated with a variety\nof complex heterocyclic coupling partners as both the nucleophilic\naryl boronic acid and the electrophilic aryl halide, including an\narray of bioactive molecules that are representative of pharmaceutical\nsynthetic targets. A comparison of this nickel-catalyzed telescoped\nprocess to the analogous palladium-catalyzed telescoped process is\nincluded to guide future use cases. A decagram scale telescoped process\nutilizing pharmaceutically relevant aryl halides demonstrates its\nscalability.