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

An unprecedented direct ortho C-H arylation and chlorination of a-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 a-ketoesters to mon-odent...

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Published inTetrahedron Vol. 123
Main Authors Wang, Jian, Wu, Yongdi, Xu, Wengang, Lu, Xuelian, Wang, Yunfang, Liu, Guangyuan, Sun, Bing, Zhou, Yirong, Zhang, Fang -Lin
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier 24.09.2022
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
FUNCTIONALIZATION
AMINES
Transient directing group
ALKYLATION
ALPHA-KETO ESTERS
ENANTIOSELECTIVE HYDROGENATION
Palladium
ALDEHYDES
Ketoester
C -H activation
ACCESS
BENZALDEHYDES
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Summary:An unprecedented direct ortho C-H arylation and chlorination of a-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 a-ketoesters to mon-odentate, so as to fulfill the ortho C-H activation. Importantly, the key binuclear cyclopalladium inter-mediate 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.(c) 2022 Elsevier Ltd. All rights reserved.
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2022.132980