Organocatalytic Asymmetric Conjugate Addition of 3-Monosubstituted Oxindoles to (E)-1,4-Diaryl-2-buten-1,4-diones: A Strategy for the Indirect Enantioselective Furanylation and Pyrrolylation of 3-Alkyloxindoles

An asymmetric conjugate addition of 3-monosubstituted oxindoles to a range of (E)-1,4-diaryl-2-buten-1,4-diones, catalyzed by commercially available cinchonine, is described. This organocatalytic asymmetric reaction affords a broad range of 3,3'-disubstituted oxindoles that contain a 1,4-dicarbonyl moiety and vicinal quaternary and tertiary stereogenic centers in high-to-excellent yields (up to 98?%), with excellent diastereomeric and moderate-to-high enantiomeric ratios (up to 99:1 and 95:5, respectively). Subsequently, cyclization of the 1,4-dicarbonyl moiety in the resultant Michael adducts under different PaalKnorr conditions results in two new kinds of 3,3'-disubstituted oxindoles3-furanyl- and 3-pyrrolyl-3-alkyl-oxindolesin high yields and good enantioselectivities. Notably, the studies presented here sufficiently confirm that this two-step strategy of sequential conjugate addition/PaalKnorr cyclization is not only an attractive method for the indirect enantioselective heteroarylation of 3-alkyloxindoles, but also opens up new avenues toward asymmetric synthesis of structurally diverse 3,3'-disubstituted oxindole derivatives.