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PhPAd‐DalPhos: Ligand‐Enabled, Nickel‐Catalyzed Cross‐Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines
Author(s) -
Tassone Joseph P.,
England Emma V.,
MacQueen Preston M.,
Ferguson Michael J.,
Stradiotto Mark
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201812862
Subject(s) - electrophile , aryl , catalysis , ligand (biochemistry) , combinatorial chemistry , chemistry , bromide , nickel , substrate (aquarium) , base (topology) , organic chemistry , biochemistry , alkyl , receptor , oceanography , geology , mathematical analysis , mathematics
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).