Identification of modular chiral bisphosphines effective for Cu(i)-catalyzed asymmetric allylation and propargylation of ketones.
New modular chiral phosphines effective for two distinct Cu(I)-catalyzed asymmetric tetrasubstituted-carbon-forming reactions, namely, allylation and propargylation of ketones, were identified. The optimized phosphine 8 was readily synthesized on a gram scale in high yield via three facile transformations (O-alkylation, bisaminal formation, and phosphination) from commercially available materials. In both reactions, excellent enantioselectivity (up to 98% ee) was produced from a range of substrates, including aromatic and aliphatic ketones, using 0.1-5 mol % catalyst loading. Specifically, catalytic enantioselective propargylation was the first example, affording synthetically useful chiral building blocks that have not been easily accessed to date. In addition to the enantioselectivity, the high catalytic activity of the CuOAc-8 complex is noteworthy. Preliminary studies to elucidate the structure-catalyst activity relationship suggested that the high catalytic activity of the Cu-8 complex is due to the extraordinarily wide bite angle ( angleP-Cu-P = 137.8 degrees ), leading to the stabilization of the active monomeric catalytically active species. Furthermore, mechanistically intriguing nonconventional hydrogen bonds existed between the acetate ligand of Cu and the bisaminal hydrogen atoms, stabilizing the distorted tetrahedral coordination state of the Cu atom.
Shi
Shi-Liang
SL
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Xu
Li-Wen
LW
Oisaki
Kounosuke
K
Kanai
Motomu
M
Shibasaki
Masakatsu
M
D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010720:Phosphines / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D007659:Ketones; D010720:Phosphines; D003300:Copper