Premium
Pd II ‐Catalyzed Asymmetric Addition Reactions of 1,3‐Dicarbonyl Compounds: Mannich‐Type Reactions with N ‐Boc Imines and Three‐Component Aminomethylation
Author(s) -
Hamashima Yoshitaka,
Sasamoto Naoki,
Umebayashi Natsuko,
Sodeoka Mikiko
Publication year - 2008
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200800120
Subject(s) - chemistry , imine , benzylamine , stereoselectivity , steric effects , nucleophile , catalysis , yield (engineering) , mannich reaction , medicinal chemistry , organic chemistry , mannich base , enantioselective synthesis , materials science , metallurgy
This paper describes catalytic asymmetric Mannich‐type reactions of β‐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 %), β‐ketoesters reacted with various N ‐Boc imines (Boc= tert ‐butoxycarbonyl) to afford the desired β‐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 β‐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.