Synfacts 2020; 16(03): 0291
DOI: 10.1055/s-0039-1690382
Metals in Synthesis
© Georg Thieme Verlag Stuttgart · New York

Synthesis of C-Alkyl Glycoamino Acids via Palladium-Catalyzed C(sp3)–H Glycosylation

Paul Knochel
Simon Graßl
Liu Y, Wang Y, Dai W, Huang W. Li Y. * Liu H. * Fudan University, Shanghai and Shanghai Institute of Materia Medica, P. R. of China
Palladium-Catalysed C(sp3)–H Glycosylation for Synthesis of C-Alkyl Glycoamino Acids.

Angew. Chem. Int. Ed. 2020;
59: 3491-3494
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18. Februar 2020 (online)



The authors report a highly efficient, regio- and diastereoselective palladium-catalyzed glycosylation of inert β-C(sp3)–H bonds of N-phthaloyl α-amino acids under mild conditions. The method utilizes a combination of silver carbonate and trifluoroacetic acid in a polar solvent (THF), which enabled the activation cycle of this C–H bond. The reaction has a high tolerance towards functional groups and a broad scope, providing over 30 β-substituted C-alkyl glycoamino acids with up to 88% yield.



This method allows for the first time to activate C(sp3)–H bonds for glycosylation reactions, thus advancing the state-of-the-art techniques in carbohydrate chemistry. Liu and co-workers propose a mechanistic cycle for the C–H activation, based on experimental studies. Therein, the formation of a palladacycle via cyclometallation plays a key role in the activation and the resulting diastereoselectivity.