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.