Improved Synthesis of Chiral 1,4,7-Triazacyclononane Derivatives and Their Application in Ni-Catalyzed Csp³−Csp³ Kumada Cross-Coupling

Herein, we report four new chiral 1,4,7-triazacyclononane (TACN) derivatives and their corresponding nickel(II) chloride complexes. All TACN ligands are bearing one chiral N-substituent and two alkyl (methyl or tert-butyl) N-substituents, and we have developed a new synthetic method for the dimethyl-substituted TACN derivative, in order to prevent the rotational isomers that hinder the cyclization reaction. The nickel complexes change their coordination geometry significantly depending on the steric bulk of the N-alkyl substituents, from a dinuclear tris(μ-chloro)dinickel complex to mononuclear Ni-dichloride and Ni-chloride complexes. These complexes were then employed in the alkyl-alkyl Kumada cross-coupling reaction and revealed that the more sterically hindered ligands produced more homocoupled product rather than the cross-coupled product, while the mononuclear Ni-dichloride complex exhibited significantly lower catalytic activity. These chiral complexes were also employed in enantioconvergent cross-coupling reactions as well, to afford significant enantioenrichment. Overall, the least sterically hindered Ni complex yields the best yields in the alkyl-alkyl Kumada cross-coupling reaction among the four complexes investigated, as well as the highest enantioselectivity.