Direct Glycosylation of N,N -Dimethyl Amino Sugars via Halogen/Hydrogen Bonding Interactions

作者：Liming Wang, Meilian Chen, Juan Zou, Shuqin Wu, Kaiyan Guo, D. Liu, Can Liu, Zhen Wang, Thomas Hansen, Qingju Zhang · 发表于：ACS Catalysis · 年份：2025 · DOI：10.1021/acscatal.5c04260 · 被引用次数：7 · 研究领域：Carbohydrate Chemistry and Synthesis、Chemical Synthesis and Analysis、Fluorine in Organic Chemistry

N, N -Dimethyl amino glycosides are widely found in natural products, exhibiting many important biological activities and playing a vital role in human health. However, their synthesis presents challenges due to the basic nitrogen within their structure. Herein, we report a direct glycosylation method for the synthesis of N, N -dimethyl amino glycosides via a halogen/hydrogen bonding interaction. These glycosylation protocols offer several advantages, including mild organocatalytic reaction conditions, the use of catalytic amounts of promoters, a broad substrate scope, controllable stereoselectivity, moderate to high yields, and applicability to the synthesis of natural products. This study demonstrates that noncovalent catalytic activation enabled the tolerance of challenging N, N -dimethyl amino glycosides that are difficult substrates for other types of catalytic/Lewis acidic promoter systems. The reaction mechanism was investigated through 13 C NMR titration, DFT computations, and control experiments.