Lewis acid-Lewis acid heterobimetallic cooperative catalysis: mechanistic studies and application in enantioselective aza-Michael reaction.
The full details of a catalytic asymmetric aza-Michael reaction of methoxylamine promoted by rare earth-alkali metal heterobimetallic complexes are described, demonstrating the effectiveness of Lewis acid-Lewis acid cooperative catalysis. First, enones were used as substrates, and the 1,4-adducts were obtained in good yield (57-98%) and high ee (81-96%). Catalyst loading was successfully reduced to 0.3-3 mol % with enones. To broaden the substrate scope of the reaction to carboxylic acid derivatives, alpha,beta-unsaturated N-acylpyrroles were used as monodentate, carboxylic acid derivatives. With beta-alkyl-substituted N-acylpyrroles, the reaction proceeded smoothly and the products were obtained in high yield and good ee. Transformation of the 1,4-adducts from enones and alpha,beta-unsaturated N-acylpyrroles afforded corresponding chiral aziridines and beta-amino acids. Detailed mechanistic studies, including kinetics, NMR analysis, nonlinear effects, and rare earth metal effects, are also described. The Lewis acid-Lewis acid cooperative mechanism, including the substrate coordination mode, is discussed in detail.
Yamagiwa
Noriyuki
N
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Qin
Hongbo
H
Matsunaga
Shigeki
S
Shibasaki
Masakatsu
M
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008674:Metals, Rare Earth / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D012015:Reference Standards; D013237:Stereoisomerism
D001372:Aza Compounds; D007659:Ketones; D008674:Metals, Rare Earth; D009942:Organometallic Compounds; D008094:Lithium