Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters

An enantioselective
Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic
isothiourea HyperBTM, giving excellent levels of product enantioselectivity
(up to >99:1 enantiomeric ratio) in good yields and with complete
regioselectivity (>20:1 regioselectivity ratio) in the presence
of
alternative (phenyl ketone and ethyl ester) Michael acceptors. Density
functional theory calculations indicate that N-acylation is rate-limiting.
This constitutes a rare example of a highly enantioselective addition
of simple, readily available malonates to α,β-unsaturated
esters.