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Updated: Jun 22, 2025

Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Published on: June 21, 2017
Selective 1,4-syn-Addition to Cyclic 1,3-Dienes via Hybrid Palladium Catalysis
Yan Liang1, Tiancen Bian2, Komal Yadav2
1Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Materials Science, Zhejiang Normal University, Jinhua 321017, China.
Abstract:
1,4-cis-Disubstituted cyclic compounds play a pivotal role in pharmaceutical development, offering enhanced potency and bioavailability. However, their stereoselective and modular synthesis remains a long-standing challenge. Here, we report an innovative strategy for accessing these structures via mild conditions employing cyclic 1,3-dienes/alkyl(aryl)halides and amines. This procedure exhibits a wide substrate scope that tolerates various functional groups. The utility of this method is demonstrated in the efficient synthesis of a TRPV6 inhibitor, CFTR modulator, and other bioactive molecules. Combined experimental and computational studies suggest that the hybrid palladium-catalyzed radical-polar crossover mechanism is crucial for achieving exceptional 1,4-syn-addition selectivity (dr > 20:1).
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