Directed SN2 Glycosylation Employing an Amide-Functionalized 1‑Naphthoate Platform Featuring a Selectivity-Safeguarding Mechanism

• Published in: Journal of the American Chemical Society Vol. 145; no. 22; pp. 11921 - 11926
• Main Authors: Ma, Xu, Zhang, Yongliang, Zhu, Xijun, Wei, Yongliang, Zhang, Liming
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.05.2023; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; glycosides; glycosylation; hydrogen bonding; oligosaccharides; Physical Sciences; Science & Technology; STEREOSELECTIVE GLYCOSYLATION; BETA-MANNOSYLATION; GLYCOSIDATION REACTIONS
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.3c02792

This work implements a catalytic SN2 glycosylation by employing an amide-functionalized 1-naphthoate platform as a latent glycosyl leaving group. Upon gold-catalyzed activation, the amide group enables the SN2 process by directing the attack of the glycosyl acceptor via H-bonding interaction, which results in stereoinversion at the anomeric center. Unique in this approach is that the amide group also enables a novel safeguarding mechanism by trapping oxocarbenium intermediates and, hence, minimizing stereorandom SN1 processes. The strategy is applicable to the synthesis of a broad range of glycosides with high to excellent levels of stereoinversion from anomerically pure/enriched glycosyl donors. These reactions are generally high-yielding, and their applications in the synthesis of challenging 1,2-cis-linkage-rich oligosaccharides are demonstrated.