Origins of Stereospecificity and Divergent Reactivity of Pd-Catalyzed Cross Coupling with α,α-Disubstituted Alkenyl Hydrazones

• Published in: Journal of organic chemistry 2022-11, Vol.87 (22), p.15608-15617
• Main Authors: Liu, Sheng-Nan, Liu, Jian-Biao, Huang, Fang, Wang, Wen-Juan, Wang, Qiong, Yang, Chong, Sun, Qing-Min, Chen, De-Zhan
• Format: Article
• Language: English
• Subjects: Alkenes - chemistry; Catalysis; Hydrazones; Palladium - chemistry; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c02188

This article presents an exploration of stereospecificity and divergent reactivity of Pd-catalyzed α,α-disubstituted alkenyl hydrazones to synthesize 1,4-dienes in the Z configuration and vinylcyclopropane. We calculated the energy profiles of four α,α-disubstituted alkenyl hydrazones. The results show that the energy profiles of the whole catalytic cycle are basically the same before the syn-carbopalladation step. Subsequent syn-β-C elimination yields skipping dienes, or direct β-H elimination yields vinylcyclopropane. Current theoretical calculations reveal that the stereospecificity and the divergent reactivity of reactions result from the competition between syn-β-C elimination and β-H elimination. The C–C bond rotation and subsequent syn-β-C elimination step control the stereospecificity of the reaction by changing the olefin stereostructure from E to Z configuration. The steric factor of α-substituted groups mediates the transformation between syn-β-C elimination and β-H elimination. The results are of great significance for the scientific design of substrates to achieve accurate synthesis of target products.