The controlled assembly of complex oligosaccharides and glycoconjugates from monosaccharide precursors, which play a myriad of biological roles in all life processes, 1 is essential to advance the frontiers of glycobiology research. 2, 3 A crucial step in carbohydrate synthesis is the formation of the glycosidic bond. Most chemical approaches rely in the introduction of a latent leaving group at the anomeric position, which can be activated in the presence of a nucleophile acceptor to undergo the coupling step. A less explored strategy for glycosidic bond formation is the dehydrative coupling in which a 1-hydroxy carbohydrate or hemiacetal can be activated directly to generate a highly reactive species to undergoe glycosylation in situ, thus potentially leading to a more efficient process. 5 However, lack of control over the reversibility of the reaction, which in the absence of an excess of nucleophile can lead to incomplete reactions or hemiacetal donor dimerization via self-coupling, 6 has limited its broad utility. 2-deoxy-hexoses are important components of many active natural products. The absence of substituents at C-2 poses significant synthetic challenges in directing the approach of the incoming nucleophile during the glycosylation reaction. This has spurred efforts to devise improved and stereoselective protocols for their assembly. The direct synthesis of deoxyglycosides, which involves the reaction of an activated electrophilic deoxysugar donor with a nucleophile (or acceptor), is the most straightforward strategy and a number of elegant approaches in recent years have been developed, including examples of dehydrative hemiacetal activation. We recently reported a catalytic AuCl3-catalysed dehydrative glycosylation using hemiacetal glycosyl donors and acceptors to access 1,1-⍺,⍺'linked 2-deoxy trehalose analogues with high stereoselectivity (Scheme 1). Although glycosylation with primary OH nucleophiles was also possible, lower yields (10-20%) of the desired 2-deoxy glycoside products were observed with less reactive secondary alcohols due to competitive dimerization of the donor, even when an excess of the alcohol was used. These findings prompted us to investigate more efficient catalysts capable of modulating the activation of the hemiacetal donor and reactivity of the incoming nucleophile to yield 2-deoxyglycosides more efficiently. Organoselenium chemistry has undergone rapid growth in the last few decades due to their increasing applications in organic synthesis. Chalcogen bonding (ChB) is a type of noncovalent interaction in which a covalently bonded chalcogen atom acts as an electrophilic species towards a nucleophilic (negative) region(s) in another or in the same molecule. ChB-catalysis offers several potential advantages, such as high directionality (interaction angle of ca.180°), and easy tunability of the chalcogen bond system Lewis acidity and steric demand by changing the substituents. ChB catalysis has been applied in many intermolecular or intramolecular reactions, including recent elegant examples on carbohydrate chemistry. Unlike divalent chalcogenides, trisubstituted chalcogenonium salts have emerged as a new class of catalysts which are thought to be more Lewis acidic because of the more positive charge at the chalcogen center and have shown excellent performance as Lewis acids in electrophilic halogenations and aldol-type reactions. Despite the growing interest in the catalytic properties of organo-chalcogenonium compounds based on group 16 elements in synthetic applications, no examples in carbohydrate chemistry have been reported to date. We hypothesized that the unique reactivity of hypervalent chalcogenonium salts could help overcome some of the current challenges on the activation of hemiacetal donors in glycosylation reactions. The study began with the evaluation of a series of soft chalcogenonium salts (1a-1h) in a model glycosylation reaction of tri-benzylated 2-deoxy galactosyl hemiacetal 2a and galactoside acceptor 3a in CH2Cl2 at room temperature for 6 h. As summarized in Scheme 1, chalcogenoniums featuring a common chiral Se or S center substituted with two aryl C-Se/S bonds and one Se/S-CH3 (1a-b) were screened. We also explored catalysts with a Se-O rigid ring core structure (1c-1h), which adopt a trigonal bipyramidal geometry with the cyclic selenide occupying the trigonal plane and are generally more reactive. Different counter ions with distinct metal coordination abilities and thus ability to tune catalyst reactivity were also screened. We found that rigid selenonium triflate 1e at 5 mol% catalyst loading at room temperature in CH2Cl2 afforded optimal conversion (83%) to the desired glycoside 4a with complete a-stereocontrol. Changing the reaction temperature to 0 o C slowed the reaction, whilst no significant improvement was observed at 40 o C. Finally running the reaction in solvents such as acetonitrile, ethylacetate, dichloroethane, THF or toluene was detrimental to the overall yield. (See Tables With optimized conditions in hand, we next examined the reaction substrate scope. 1-hydroxy galactoside 2a and glucosides 2b and 2c were reacted with a range of primary and secondary OH nucleophiles 3a-3n under the optimized reaction conditions (Scheme 3). In most cases, reactions proceeded smoothly with high a-selectivity, demonstrating that the catalytic system is tolerant of common alcohol and amine protecting groups such as acetals, ethers, esters and carbamates. Glycosylation of 2a with primary alcohols such as simple alcohols 3b, 3d, 3e and 3l and glycoside acceptors 3a, 3c and amino acid 4f afforded the corresponding glycoside products in 45-89% yield and with a 10:1 a:b to only a ratios. Reactions with secondary nucleophiles such as 3g, 3j and 3k also afforded the desired products in good yields (76-93%) and with complete a-selectivity. Glycosylations with glycosides 3h, 3i, 3m and thiotoluene 3l prove to be more challenging affording lower yields (14-43%) and a-stereocontrol with the exception of 4h (4:1 a:b). Pleasingly, reactions with 2,6 dideoxyglucoside 1c or the less reactive 2-deoxyglucoside 1b or Scheme 3. Substrate scope with donors 2a-c and ROH (3a-n).