Regioselectivity-reversed Asymmetric Aldol Reaction Of1,3-Dicarbonyls

1,3-dicarbonyls are versatile bifunctional precursors which havebeen proven to be extremely useful substrates in organic synthesis.Although tremendous achievements were made in catalytic asymmetricconversions involving1,3-dicarbonyls as nucleophiles, all of themexclusively applied C-3position as the nucleophilic site, and no report ofcatalytic asymmetric C-1attack appeared. Since Barbas and List reportedthe proline catalyzed cross-aldol reaction between ketones and aldehydes,significant efforts in organocatalyzed aldol reaction based onenamine-activiation mechanism have been made. Despite the advances,the search for new aldol-type processes with the goal of increasing thesubstrate-diversity, product-utility as well as exploring new catalysismodels continues. Very recently, other groups and our group proved thattertiary amines are optical catalyst to promote the direct aldol reaction.Based on these results, we present the first catalytic asymmetric C-1aldolreaction of1,3-dicarbonyls employing isatins and dihydrofuran-2, 3-dione as electrophiles, regioselectively afforded1-(3-hydroxy-2-oxoindolin-3-yl) pentane-2,4-dione4-dimethyl-dihydrofuran-2(3H)-onederivatives and3-hydroxy-3-(4-hydroxy-2-oxopent-3-enyl)-4,4-dimethyl-dihydrofuran-2(3H)-one with moderate to high opticalpurities. Furthermore, this method provides a facile access toenantio-enriched oxygen-contained spirooxindoles andspirobutyrolactone from simple commercial available starting materials.We also carried out NMR experiments to determine the possible C-1enolintermediate of acetylacetone for the purpose to explain the reactionmechanism.