Nickel‐Catalyzed Reductive Alkylation of Heteroaryl Imines**

Abstract

A Ni-catalyzed reductive cross-coupling of heteroaryl imines with C(sp 3 ) electrophiles for the preparation of heterobenzylic amines is reported. This umpolung-type alkylation proceeds under mild conditions, avoids the pre-generation of organometallic reagents, and exhibits good functional group tolerance. Mechanistic studies are consistent with the imine substrate acting as a redox-active ligand upon coordination to a low-valent nickel center. The resulting Ni-bis(2-imino)heterocycle complexes can engage in alkylation reactions with a variety of C(sp 3 ) electrophiles, giving the heterobenzylic amine products in good yields.

Mannich‐Type Reactions of Alkylzinc Reagents

“…The use of less electrophilic imines bearing a 2‐pyridylsulfonyl electron‐withdrawing group on the nitrogen atom has also been described, but the use of an additional copper catalyst is essential to increase the electrophilicity of the carbon atom [25] . More recently, reductive couplings between alkyl halides and N ‐aryl or N ‐alkyl aldimines have been described, but these transformations also rely on the use of transition metal catalyst in combination with a stoichiometric reductant [26–28] . In continuation with our work on organometallic Mannich reactions using alkylzinc halide reagents, [29] we report, in this comprehensive study, the development of Mannich‐type reactions involving unactivated organozinc reagents and aldimines.…”

“…[25] More recently, reductive couplings between alkyl halides and N-aryl or N-alkyl aldimines have been described, but these transformations also rely on the use of transition metal catalyst in combination with a stoichiometric reductant. [26][27][28] In continuation with our work on organometallic Mannich reactions using alkylzinc halide reagents, [29] we report, in this comprehensive study, the development of Mannich-type reactions involving unactivated organozinc reagents and aldimines.…”

Photoredox‐Catalyzed Synthesis of Homoallylamines from Unactivated Imines and Allyl Bromides

“…Up to date, the 1,2-addition of imines with organometallic reagents (Grignard type [6] or Barbier type [7] ) is a wellestablished method for the synthesis of homoallylamines (Scheme 1B). [8] The different metal-catalyzed approaches to prepare homoallylamines with imines and other allyl compounds (such as allyl trifluoroborates, [9] allyl boron esters, [10] allylic acetates, [11] allyl silicons, [12] enols, [13] etc.) have also been reported (Scheme 1C).…”

Dual-Catalytic Enantioselective Allylation of N-(Heteroaromatic-methyl)imine Derivatives

“…Inspired by the chemistry above, and related work by Hartwig, we postulated whether the use of preformed N -2-(pyridylmethyl)­imine derivatives would allow the development of a practical, enantioselective dual-catalytic allylation reaction of (pyridyl-methyl)­imine derivatives that is complementary to, and addresses some limitations of, prior art. Herein, we report our endeavors in this pursuit …”

“…Herein, we report our endeavors in this pursuit. 9 Initial efforts focused on the coupling of imine 1a and Bocprotected cinnamyl alcohol 2a. Preliminary studies were conducted with Cu(OTf) 2 and Pd(PPh 3 ) 4 as cocatalysts, Cs 2 CO 3 as base, and toluene as solvent (Table 1).…”