Silicon as a Strategic Element in Carbohydrate Chemistry: Glycomimetic Design, Reductive Migration, and Ring Editing

Silicon offers a powerful yet underexplored handle for re-engineering carbohydrate structure and function. This Synpacts highlights recent advances in the synthesis and reactivity of Si-linked glycomimetics. First, a reductive intramolecular O → C silyl migration from C2 silyl ethers to C1 delivers 1,2-cis C–Si glycosides across diverse mono- and disaccharides with high anomeric control. A systematic variation of the reagent, counterion, solvent, and temperature delineates conditions that favor migration over competing elimination. Second, complementary anionic opening of glycal epoxides with aryl-substituted silicon nucleophiles furnishes 1,2-trans C–Si linkages cleanly while suppressing Peterson-type olefination. We further show that saccharide chirality can be relayed to silicon: monohydrosilanes undergo kinetic resolution under the transfer conditions, enabling access to configurationally defined silicon stereocenters. Beyond linkage construction, an oxidative ring contraction of anomeric metal/metalloid glycosides converts hexoses to pentose-derived γ-lactones under mild, stereospecific conditions, whereas β-anomers diverge to C2 ketones, revealing a stereoelectronic switch. Computations map the competition between (1,3)-retro-Brook transfer and Peterson elimination, identify a low-barrier Berry pseudorotation within a pentacoordinate oxasiletanide manifold that renders the transfer stereoretentive at silicon, and rationalize temperature-dependent pathways. Together, these results provide design rules and practical transformations for constructing Si-linked glycomimetics, installing silicon stereocenters, and editing carbohydrate ring size.