Scheme 13. Synthesis of 1,2-trans-Glycosides Using 2,3-Protected Glucosyl Donors Scheme 14. Roush's Synthesis of 2-Deoxy-2-iodo-βgalactosides Using a 3,4-O-Carbonate-Protected Donor

We demonstrate that tuning the reactivity of Cu by the choice of oxidation state and counterion leads to the activation of both "armed" and "disarmed" type glycals towards direct glycosylation leading to the α-stereoselective synthesis of deoxyglycosides in good to excellent yields. Mechanistic studies show that Cu I is essential for effective catalysis and stereocontrol and that the reaction proceeds through dual activation of both the enol ether as well as the OH nucleophile. Carbohydrates play significant roles in a wide range of biological events 1 and efficient catalytic and asymmetric methods to access this class of chiral molecules are needed to further our understanding of their various roles and functions in health and disease. 2, 3 First row transition metals have recently attracted attention as alternatives to precious metals in catalysis. 4 Among those, copper is a cost-effective, earth-abundant and sustainable metal and Cu-complexes can display unique and versatile reactivity and good functional group tolerance. 4 The chemistry exhibited by Cu can be very diverse depending on its oxidation state, as this metal can efficiently catalyse reactions involving one or twoelectron mechanisms. 4-7 In the context of O-linked glycosylation reactions, a few examples of Cu(II) as a mild oxophilic Lewis acid catalyst for the activation of oxygen-containing leaving groups have been reported. 8-11 More recently, the use of Cu II (OTf)2 as an in situ oxidant in the photoinduced-activation of thioglycosides was also exemplified. 12 However, despite copper catalysts being relatively cheap and widely available, we were surprised by the overall under exploration of this metal in glycosylation chemistry 13-17. Our group is interested in the development of sustainable and catalytic methods for the synthesis of oligosaccharides. 18-21 2deoxy-hexoses are prominent components of natural products which due to the lack of substituents at C-2 to direct the nucleophile approach present significant synthetic challenges and their improved and stereoselective protocols for their assembly has been of great intetest. 5, 18, 22-37 Previous work from our group and others has shown that activation of glycals to yield glycosides can be achieved using transition metals such as Pd(II) 38, 39 , Au(I) 40 or Re(V) 41 catalysts, however activation of sensitive enol ethers bearing electronwithdrawing groups at the C-3 position of the glycal was not possible under those conditions (Scheme 1) and in general harsher conditions used to activate such glycals often lead to donor hydrolysis and/or Ferrier type products. 26 Scheme 1: Cu I-catalysed direct synthesis of deoxyglycosides from glycals

Heparan sulfate (HS) and dermatan sulfate (DS) are l-iduronic acid containing glycosaminoglycans (GAGs) which are implicated in a number of biological processes and conditions including cancer and viral infection. Chemical synthesis of HS and DS is required to generate structurally defined oligosaccharides for a biological study. Herein, we present a new synthetic approach to HS and DS oligosaccharides using chemoselective glycosylation which relies on a disarmed [2.2.2] l-ido lactone motif. The strategy provides a general approach for iterative-reducing end chain extension, using only shelf-stable thioglycoside building blocks, exploiting a conformational switch to control reactivity, and thus requires no anomeric manipulation steps between glycosylations.

<p><a></a>We demonstrate that tuning the reactivity of Cu by the choice of oxidation state and counterion leads to the activation of both “armed” and “disarmed” type glycals towards direct glycosylation leading to the a-stereoselective synthesis of deoxyglycosides in good to excellent yields. Mechanistic studies show that CuI is essential for effective catalysis and stereocontrol and that the reaction proceeds through dual activation of both the enol ether as well as the OH nucleophile.</p>

A new practical, catalytic, and highly stereoselective method for directly accessing 1,1-α,α′-linked 2-deoxy trehalose analogues via AuCl 3 -catalyzed dehydrative glycosylation using hemiacetal glycosyl donors and acceptors is described. The method relies on the chemoselective Brønsted acid-type activation of tribenzylated 2-deoxy hemiacetals in the presence of other less reactive hemiacetals.