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).
The base metal-catalyzed C-N cross-coupling of bulky α,α,α-trisubstituted primary n class="Chemical">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).
Authors: Yu Kawamata; Julien C Vantourout; David P Hickey; Peng Bai; Longrui Chen; Qinglong Hou; Wenhua Qiao; Koushik Barman; Martin A Edwards; Alberto F Garrido-Castro; Justine N deGruyter; Hugh Nakamura; Kyle Knouse; Chuanguang Qin; Khalyd J Clay; Denghui Bao; Chao Li; Jeremy T Starr; Carmen Garcia-Irizarry; Neal Sach; Henry S White; Matthew Neurock; Shelley D Minteer; Phil S Baran Journal: J Am Chem Soc Date: 2019-04-02 Impact factor: 15.419