Nickel-Catalyzed Site-Selective Alkylation of Unactivated C(sp³)–H Bonds

Abstract

The direct alkylation of unactivated sp(3) C-H bonds of aliphatic amides was achieved via nickel catalysis with the assist of a bidentate directing group. The reaction favors the C-H bonds of methyl groups over the methylene C-H bonds and tolerates various functional groups. Moreover, this reaction shows a predominant preference for sp(3) C-H bonds of methyl groups via a five-membered ring intermediate over the sp(2) C-H bonds of arenes in the cyclometalation step.

High-Valent Co(III)- and Ni(II)-Catalyzed C–H Activation

“…This is in agreement with similar Pd-catalyzed reactions where bis-arylation is occasionally observed [93]. Alkyl halides can also serve as electrophiles for these reactions, although a bidentate phosphine ligand is required [95]. Finally, rather than coupling to external electrophiles, Ge found that cyclization can occur to provide b-lactam products when TEMPO is used as an oxidant [96].…”

Nickel Catalysts/N,N′-Bidentate Directing Groups: An Excellent Partnership in Directed C–H Activation Reactions

“…35 Ni(II) complexes were the preferred reagents and the optimized reaction conditions were [Ni(acac) 2 ] (10 mol %) with 1,2-bis(diphenylphosphino)benzene (dppbz) (10 mol %) as the ligand, alkyl halide (5 equiv), Cs 2 CO 3 (5 equiv) in toluene at 150°C for 1224 h (Scheme 13).…”

Nickel-Catalyzed C–H Bond Functionalization Utilizing an N,N′-Bidentate Directing Group

“…As a synthetic application of this alkenylation, a highly functionalized carboxamide 53 was prepared via a sequence involving a Ni(II)-catalyzed arylation step, Ni(II)-alkenylation, hydrogenation under Pd/C, and Ni(II)-catalyzed alkenylation. [52]. In sharp contrast to the arylation of C(sp 3 )-H bonds [47], Ni(cod) 2 was not active as a catalyst.…”