PhPAd-DalPhos: Ligand-Enabled, Nickel-Catalyzed Cross-Coupling of (Hetero)aryl Electrophiles with Bulky Primary
Joseph P Tassone1, Emma V England1, Preston M MacQueen1
1Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada.
Abstract:
The base metal-catalyzed C-N cross-coupling of bulky α,α,α-trisubstituted primary alkylamines with (hetero)aryl electrophiles represents a challenging and under-developed class of transformations that is of significant potential utility, including in the synthesis of lipophilic active pharmaceutical ingredients. Herein, we report that a new, air-stable Ni(II) pre-catalyst incorporating the optimized ancillary ligand PhPAd-DalPhos enables such transformations of (hetero)aryl chloride, bromide, and tosylate electrophiles to be carried out for the first time with substrate scope rivalling that achieved using state-of-the-art Pd catalysts, including room temperature cross-couplings of (hetero)aryl chlorides that are unprecedented for any catalyst (Pd, Ni, or other).
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