Monodentate transient directing group promoted Pd-catalyzed direct ortho-C‒H arylation and chlorination of α-ketoesters for three-step synthesis of Cloidogrel racemate

An unprecedented direct ortho C–H arylation and chlorination of α-ketoesters were successfully accomplished by using a combination of monodentate transient directing group strategy and palladium catalysis. The in situ formed imine changed the bidentate coordination model of α-ketoesters to monodenta...

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Bibliographic Details
Published in:Tetrahedron 2022-09, Vol.123, p.132980, Article 132980
Main Authors: Wang, Jian, Wu, Yongdi, Xu, Wengang, Lu, Xuelian, Wang, Yunfang, Liu, Guangyuan, Sun, Bing, Zhou, Yirong, Zhang, Fang-Lin
Format: Article
Language:English
Subjects:
C–H activation
Palladium
Transient directing group
α-Ketoester
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Summary:An unprecedented direct ortho C–H arylation and chlorination of α-ketoesters were successfully accomplished by using a combination of monodentate transient directing group strategy and palladium catalysis. The in situ formed imine changed the bidentate coordination model of α-ketoesters to monodentate, so as to fulfill the ortho C–H activation. Importantly, the key binuclear cyclopalladium intermediate bridged by acetate anion was unambiguously characterized by X-ray diffraction, which solidly supports the proposed mechanism. The practical utility was further depicted as facile access to oral antiplatelet agent Clopidogrel racemate via subsequent two-step derivatization. [Display omitted]
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2022.132980