Arylation of Diethyl Acetamidomalonate with Diaryliodonium Salts En Route to α‑Arylglycines

Diethyl acetamidomalonate (DEAM) has been widely used for the synthesis of α-amino acids via C-alkylation under basic conditions followed by hydrolysis/decarboxylation. In contrast, the C-arylation of this reagent remains undeveloped. Herein, we report a novel strategy for the synthesis of racemic α...

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Bibliographic Details
Published in:Journal of organic chemistry 2024-07, Vol.89 (14), p.9923-9928
Main Authors: Bugaenko, Dmitry I., Tikhanova, Olga A., Andreychev, Valeriy V., Karchava, Alexander V.
Format: Article
Language:English
Subjects:
alkylation
aromatic hydrocarbons
arylation
chemoselectivity
decarboxylation
hydrolysis
organic chemistry
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Summary:Diethyl acetamidomalonate (DEAM) has been widely used for the synthesis of α-amino acids via C-alkylation under basic conditions followed by hydrolysis/decarboxylation. In contrast, the C-arylation of this reagent remains undeveloped. Herein, we report a novel strategy for the synthesis of racemic α-arylglycines based on the selective arylation of DEAM with diaryliodonium salts under mild, transition metal-free conditions. The reaction features good functional group tolerance and easy scalability and is applicable to the chemoselective C–H-modification of arenes including approved drugs, thus enabling a straightforward approach to complex α-arylglycines that would be challenging to make otherwise.
ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/acs.joc.4c00768