Double-Activation Catalysis Enables Highly Diastereoselective Cascade Mannich/5-endo-dig Cyclization of 2-(2-Oxoindolin-3-yl)malononitriles with Alkynyl Ketimines
- 13 August 2025
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 90 (33) , 11956-11961
Abstract
Double-activation catalytic systems are potent for making complex molecules in natural products and pharmaceutical fields, yet regulating the synergistic effect between the two catalysts is extremely challenging. Herein, a Cu/Ag double-activation catalysis that enabled the cascade Mannich/5-endo-dig cyclization was developed for the synthesis of a variety of spiro-cyclopentene-oxindole derivatives with three adjacent quaternary centers (up to 88% yield, >19:1 dr). Mechanistic investigations showed that it was not base-catalyzed, a single-metal catalyst showed poor performance, and the bimetallic catalyst was vital for highly efficient conversion.Keywords
Funding Information
- Science and Technology Program of Guizhou Province (ZK[2022]-363, ZK[2023]-288, ZK[2024]-161)
- National Natural Science Foundation of China (22361013, 22401056)
- Hospital Research Foundation of Central Hospital of Guangdong Provincial Nongken (NKYY2023002)
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