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

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 through¹³C NMR titration, DFT computations, and control experiments.