Multicomponent Assembly of Complex Oxindoles by Enantioselective Cooperative Catalysis

Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo- and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well-developed. However, the efficient synthesis of chiral 3-substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N-aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5-tricyclic lactone core structure of Speradine A.

Automated summary

Chiral oxindoles are important chemical structures found in many natural products. While there are well-developed methods for constructing C3 quaternary oxindoles with high selectivity, the efficient synthesis of chiral 3-substituted tertiary oxindoles is rarely reported. In this study, a multicomponent assembly method for complex oxindoles through enantioselective cooperative catalysis is presented.