Stereodivergent Construction of 3,3′-Disubstituted Oxindoles via One-Pot Sequential Allylation/Alkylation and Its Application to the Total Synthesis of Trigolute B and D

The absolute and relative configurations of bioactive chiral molecules are typically relevant to their biological properties. It is thus highly important and desirable to construct all possible stereoisomers of a lead candidate or a given bioactive natural compound. Synergistic dual catalysis has been recognized as a reliable synthetic strategy for a variety of predictable stereodivergent transformations. Despite the impressive progress made in this field, stereodivergent carbon-carbon bond-formation reactions involving stabilized nucleophiles remain elusive. Herein, we report an iridium- and magnesium-catalyzed one-pot sequential allylic alkylation/nucleophilic alkylation cascade process for the stereodivergent synthesis of all four stereoisomers of 3,3'-disubstituted oxindoles through a three-component reaction. A diverse array of products is readily prepared with high functional group compatibility in good yields with excellent diastereo- and enantioselectivities. Subsequently, the stereodivergent total synthesis of four stereoisomers of the spirooxindole alkaloid trigolutes B and D has been accomplished through a concise and unified synthetic route using the same set of starting materials.