Asymmetric 1,4-addition: Highly Reactive α,β-Unsaturated Ester Surrogates

29 November 2004

Japanese workers* have been studying 1,4 additions to α,β-unsaturated acid derivatives, and have found that readily prepared N-acyl pyrroles of general structure

are particularly useful substrates, being as reactive as typical α,β-unsaturated ketones.

They focussed on asymmetric epoxidation (for which the corresponding esters do not perform particularly well), and found that a Sm(OiPr)₃/H₈-BINOL complex was most effective catalyst, giving quantitative yield and >99% ee. Catalyst loading was very low (down to 0.02 mol%, substrate/catalyst ratio 5,000), and good results were consistently obtained, provided the level of water present in the reaction was kept below about 10ppm.

They also report the first direct catalytic asymmetric Michael addition of an unmodified ketone (actually an α-hydroxyketone) to such a system.

* M. Shibasaki et al., J. Amer. Chem. Soc, 2004, 126, 7559-7570.