Isothiourea-catalyzed enantioselective Michael addition of malonates to α,β-unsaturated aryl esters

Abstract

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.