Comparison of Monophosphine and Bisphosphine Precatalysts for Ni-Catalyzed Suzuki-Miyaura Cross-Coupling: Understanding the Role of the Ligation State in Catalysis

Practical advances in Ni-catalyzed Suzuki-Miyauracross-coupling(SMC) have been limited by a lack of mechanistic understanding ofphosphine ligand effects. While bisphosphines are commonly used inthese methodologies, we have observed instances where monophosphinescan provide comparable or higher levels of reactivity. Seeking tounderstand the role of ligation state in catalysis, we performed ahead-to-head comparison study of C-(sp(2))-C-(sp(2)) Ni SMCs catalyzed by mono- and bisphosphine precatalystsusing six distinct substrate pairings. Significant variation in optimalprecatalyst was observed, with the monophosphine precatalyst tendingto outperform the bisphosphines with electronically deactivated andsterically hindered substrates. Mechanistic experiments revealed arole for monoligated (P1Ni) species in accelerating thefundamental organometallic steps of the catalytic cycle while highlightingthe need for bisligated (P2Ni) species to avoid off-cyclereactivity and catalyst poisoning by heterocyclic motifs. These findingsprovide guidelines for ligand selection against challenging substratesand future ligand design tailored to the mechanistic demands of Ni-catalyzedSMCs.