Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to -Quinone Methides.

The isothiourea-catalyzed enantioselective 1,6-conjugate addition of -nitrophenyl esters to 2,6-disubstituted -quinone methides is reported. -Nitrophenoxide, generated in situ from initial -acylation of the isothiourea by the -nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of -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).