TY - JOUR
T1 - Improved Synthesis of Chiral 1,4,7-Triazacyclononane Derivatives and Their Application in Ni-Catalyzed Csp3−Csp3 Kumada Cross-Coupling
AU - Hu, Chi Herng
AU - Byeong Chae, Ju
AU - Mirica, Liviu M.
N1 - Publisher Copyright:
© 2023 The Authors. Helvetica Chimica Acta published by Wiley-VHCA AG, Zurich, Switzerland.
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - 1,4,7-triazacyclononane
KW - Kumada cross-coupling reaction
KW - chiral ligands
KW - cross-coupling
KW - nickel
KW - nickel complexes
UR - http://www.scopus.com/inward/record.url?scp=85178924190&partnerID=8YFLogxK
U2 - 10.1002/hlca.202300170
DO - 10.1002/hlca.202300170
M3 - Article
AN - SCOPUS:85178924190
SN - 0018-019X
VL - 107
JO - Helvetica Chimica Acta
JF - Helvetica Chimica Acta
IS - 1
M1 - e202300170
ER -