Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides

Abstract

The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).

Keywords

• isothiourea
• ammonium enolate
• aryloxide
• quinone methide
• ester functionalization
• 1,6-conjugate addition