Catalytic Asymmetric Direct-Type 1,4-Addition Reactions of Simple Amides

The development of
catalytic asymmetric direct-type reactions of less acidic carbonyl
compounds such as amides and esters has been a challenging theme in
organic chemistry for decades. Here we describe the asymmetric direct
1,4-addition reactions of simple amides with α,β-unsaturated
carbonyl compounds using a catalytic amount of a novel chiral catalyst
consisting of a potassium base and a macrocyclic chiral crown ether.
The desired 1,5-dicarbonyl compounds were obtained in high yields
with excellent diastereo- and enantioselectivities. This is the first
example of a highly enantioselective catalytic direct-type reaction
of simple amides. In addition, the structure of the chiral potassium
catalyst has been investigated by X-ray crystallographic, dynamic 1H NMR, and MALDI-TOF MS analyses.