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Synthesis of C-Alkyl Glycoamino Acids via Palladium-Catalyzed C(sp3)–H Glycosylation
Palladium-Catalysed C(sp3)–H Glycosylation for Synthesis of C-Alkyl Glycoamino Acids.
Angew. Chem. Int. Ed. 2020;
18 February 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.