Palladium‐Catalysed C(sp3)−H Glycosylation for the Synthesis of C‐Alkyl Glycoamino Acids

• Published in: Angewandte Chemie International Edition Vol. 59; no. 9; pp. 3491 - 3494
• Main Authors: Liu, Yichu, Wang, Yibing, Dai, Wenhao, Huang, Wei, Li, Yingxia, Liu, Hong
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 24.02.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Amino acids; C(sp3)−H activation; C-alkyl glycosides; Chemistry; Chemistry, Multidisciplinary; diastereoselectivity; Glycopeptides; Glycosides; Glycosylation; Palladium; Physical Sciences; Science & Technology; α-amino acids; GLYCOSIDES; DESIGN; OLIGOSACCHARIDES; SGLT2 INHIBITORS; ARYLATION; C-alkyl glycosides; CARBOHYDRATE; diastereoselectivity; STRATEGIES; FUNCTIONALIZATION; COUPLING REACTIONS; C(sp)-H activation; alpha-amino acids; palladium; ARYL; C(sp3)−H activation; α-amino acids
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201914184

We have developed a highly efficient and practical approach for palladium‐catalyzed trifluoroacetate‐promoted N‐quinolylcarboxamide‐directed glycosylation of inert β‐C(sp3)−H bonds of N‐phthaloyl α‐amino acids with glycals under mild conditions. For the first time, C(sp3)−H activation for glycosylation was achieved to build C‐alkyl glycosides. This method facilitates the synthesis of various β‐substituted C‐alkyl glycoamino acids and offers a tool for glycopeptide synthesis. Short and sweet: C(sp3)−H activation was achieved to build C‐alkyl glycosides through palladium‐catalyzed trifluoroacetate‐promoted N‐quinolylcarboxamide‐directed glycosylation of the inert β‐C(sp3)−H bonds of N‐phthaloyl α‐amino acids with glycals under mild conditions. This method facilitates the synthesis of various β‐substituted C‐alkyl glycoamino acids and offers a tool for glycopeptide synthesis.