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

An enantioselective Michael addition of malonates to alpha,beta-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 alpha,beta-unsaturated esters.

Automated summary

An enantioselective Michael addition of malonates to alpha,beta-unsaturated para-nitrophenyl esters was successfully achieved using the Lewis basic isothiourea HyperBTM as a catalyst.