Dissecting Tin-Based Activation and Anomerization Pathways in Carbohydrate Chemistry

Tin-based Lewis acids are widely used in glycosylation chemistry, but their precise mechanistic role is still not fully understood. In this study, we combine ¹¹⁹Sn NMR spectroscopy and density functional theory (DFT) calculations to investigate how Sn-(IV) promoters interact with glycosyl donors and influence anomerization. Our results indicate that glycosyl oxocarbenium ions can form stable ion pairs with tin-based counterions, underscoring the relevance of these species in glycosylation processes. The agreement between experimental and computed ¹¹⁹Sn chemical shifts provides structural insights into the coordination environment of the tin species. For anomerization, DFT energy profiles support a mechanism involving endocyclic C-O bond cleavage, rotation, and subsequent ring closure. These findings refine our understanding of tin-mediated transformations and offer a framework for rational design of Lewis acid promoters in glycochemistry.