Robin Groeters, Niklas Lohmann, Mark S. Taylor, Olga Garcı́a Mancheño
The precise control over the anomeric configuration in glycosylation reactions remains a formidable challenge in synthetic organic chemistry as it is essential for constructing well-defined oligosaccharides. At the same time, the demand for reliable, high-yielding methods is rapidly increasing, driven by the central role of carbohydrate motifs in a wide array of biological processes. In this regard, non-covalent chalcogen-bonding interactions has recently gained rapid attention as a powerful modulation tool in the field of glycosylation. In this work, the activation of glycosyl halides, inter alia, deactivated glycosyl donors, which so far could not efficiently be activated by non-covalent interactions, has been achieved via chalcogen-bonding catalysis. By finetuning the chalcogen-bond donor, challenging disarmed glycosyl donors were effectively activated, while the reaction pathway for activated derivatives was directed towards SN2-type, which furnished glycosides in excellent yields (up to >99%), and selectivities up to α:β = >95:5 and <5:95, respectively.