Nickel-Based Catalysts for the Selective Monoarylation of Dichloropyridines: Ligand Effects and Mechanistic Insights

This report describes a detailed study of Ni phosphine
catalysts
for the Suzuki–Miyaura coupling of dichloropyridines with halogen-containing
(hetero)aryl boronic acids. With most phosphine ligands, these transformations
afford mixtures of mono- and diarylated cross-coupling products as
well as competing oligomerization of the boronic acid. However, a
ligand screen revealed that PPh2Me and PPh3 afford
high yield and selectivity for monoarylation over diarylation as well
as minimal competing oligomerization of the boronic acid. Several
key observations were made regarding the selectivity of these reactions,
including: (1) phosphine ligands that afford high selectivity for
monoarylation fall within a narrow range of Tolman cone angles (between
136 and 157°); (2) more electron-rich trialkylphosphines afford
predominantly diarylated products, while less electron-rich di- and
triarylphosphines favor monoarylation; (3) diarylation proceeds via
intramolecular oxidative addition; and (4) the solvent (MeCN) plays
a crucial role in achieving high monoarylation selectivity. Experimental
and density functional theory studies suggest that all of these data
can be explained based on the reactivity of a key intermediate: a
Ni0–π complex of the monoarylated product.
With larger, more electron-rich trialkylphosphine ligands, this π
complex undergoes intramolecular oxidative addition faster than ligand
substitution by the MeCN solvent, leading to selective diarylation.
In contrast, with relatively small di- and triarylphosphine ligands,
associative ligand substitution by MeCN is competitive with oxidative
addition, resulting in the selective formation of monoarylated products.
The generality of this method is demonstrated with a variety of dichloropyridines
and chloro-substituted aryl boronic acids. Furthermore, the optimal
ligand (PPh2Me) and solvent (MeCN) are leveraged to achieve
Ni-catalyzed monoarylation of a broader set of dichloroarene substrates.