Pd(II)-Catalyzed asymmetric addition reactions of 1,3-dicarbonyl compounds: Mannich-type reactions with N-Boc imines and three-component aminomethylation.
This paper describes catalytic asymmetric Mannich-type reactions of beta-ketoesters and malonates using chiral palladium complexes. Although readily enolizable, carbonyl compounds are attractive substrates, the use of such compounds as nucleophiles in Mannich-type reactions has not been extensively investigated. In the presence of chiral Pd aqua complexes (2.5 mol %), beta-ketoesters reacted with various N-Boc imines (Boc=tert-butoxycarbonyl) to afford the desired beta-aminocarbonyl compounds in good yield with high to excellent stereoselectivity (up to 96:4 d.r., 95-99 % ee in most cases). In these reactions, construction of highly crowded vicinal quaternary and tertiary carbon centers was achieved in one step. A chiral Pd enolate is considered to be the key intermediate. To elucidate the stereoselectivity observed in the reaction, possible transition-state models are discussed, taking into account steric and stereoelectronic effects. Furthermore, this catalytic system was applied to the Mannich-type reaction of malonates with N-Boc imine as well as one-pot classical aminomethylation of beta-ketoesters using benzylamine salt and formalin. The reactions proceeded smoothly, and the corresponding Mannich products were obtained in high yield with moderate to good enantioselectivity.
Hamashima
Yoshitaka
Y
Synthetic Organic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Sasamoto
Naoki
N
Umebayashi
Natsuko
N
Sodeoka
Mikiko
M