The cost and environmental impact of precious metal catalysts has led to increased demand for nonprecious alternatives for widely practiced reactions such as the Suzuki-Miyaura coupling. Ni-catalyzed versions of this reaction do not tolerate many important heteroaryl boron nucleophiles, especially those that are Lewis bases. To address this significant limitation, we investigated a bespoke collection of ligands for Ni using high-throughput experimentation. These experiments led to the identification of the highly active ligands PPh2Me, DCPP, and PBn3, and ultimately the application of (PPh2Me)2NiCl2 as an air-stable and inexpensive precatalyst for the Suzuki-Miyaura coupling of heterocyclic aryl pinacol boronates and heterocyclic aryl halides. The reaction is generally catalyzed by 1–3 mol % (PPh2Me)2NiCl2 with in situ activation by n-BuMgCl and PPh2Me. Using this method, biheteroaryl compounds of industrial relevance can be prepared with a nonprecious metal catalyst, including examples with multiple Lewis-basic functional groups. The origin of the unprecedented activity afforded by relatively simple PPh2Me in these reactions was also investigated. We demonstrated that coordination of Lewis-basic substrates is the primary cause of low activity with several other commonly employed ligands for Ni. The PPh2Me-Ni catalyst showed kinetics consistent with a rate-determining preequilibrium between a Ni-substrate complex and PPh2Me-Ni when Lewis-basic substrates were employed. Thus, while Lewis bases such as pyridine can displace PPh2Me from Ni, the process is reversible and allows the Suzuki-Miyaura coupling to proceed.

Suzuki-Miyaura coupling of biheteroaryls: A nonprecious metal catalyst with broad scope and Lewis base tolerance

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.