Stereoselective formation of glycosidic linkages has been the prime focus for contemporary carbohydrate chemistry. Herein, we report cyanomethyl (CNMe) ether as an efficient and effective participating orthogonal protecting group for the stereoselective synthesis of 1,2-trans-β-O-glycosides. The participating group facilitated good to high β-selective glycosylation with a broad range of electron-rich and electron-deficient glycosyl acceptors. Detailed experimental and theoretical studies reveal the involvement of CNMe ether in the formation of a six-membered imine-type cyclic intermediate for the observed stereoselectivity. Rapid incorporation and selective removal of the CNMe ether group in the presence of benzyl ether and isopropylidene acetal protection have also been reported here. The nitrile group provided an opportunity for the glycodiversification through further derivatizations.

Contents:1. General experimental procedure for synthesis of compounds 2-6 and S2their characterization data 2. Copies of 1 H NMR and 13 C NMR spectra S9-S24 3. References S25 S2 2. General Experimental Procedure for Synthesis of Compounds 2-6 and Their Characterization Data General Information Melting points were recorded on a Köfler block. IR spectra were recorded on a Perkin Elmer FT-IR spectrophotometer (Spectrum BX II) in KBr pellets. 1 H and 13 C NMR spectra were recorded in CDCl 3 on a Bruker AV-300 (300 MHz) or a Bruker AVANCE III HD (400 MHz) spectrometer. HRMS data were recorded with a Waters Xevo G2QTof HRMS spectrometer. Analytical samples were routinely dried in vacuo at room temperature. Microanalytical data were recorded on two Perkin-Elmer 2400 Series II C, H, N analyzers. TLC was performed with silica gel G made of SRL Pvt. Ltd. Petroleum ether had the boiling range 60-80 °C. General procedure for preparation of 2-hydroxychalcones (1)The 2-hydroxychalcones used as starting materials in the present work were synthesized by alkali-catalyzed condensation of 2-hydroxybenzaldehydes with acetophenones. Thus, a mixture of 2-hydroxybenzaldehyde (10 mmol) and an acetophenone (10 mmol) was taken in a 50 ml solution of 10% KOH in aqueous ethanol (3:2) and stirred overnight. The resulting mixture was acidified with 3 (N) HCl. The solid thus separated was filtered under suction. It was then collected and crystallized from ethanol. Chromatographic purification was also done in some cases according to requirement.

Inner sphere Tsuji‐Trost reaction has found recent application for β‐selective Ferrier rearrangement of glycal substrates with alcohol nucleophiles. Herein, we report an efficient and stereoselective synthesis of 2,3‐dideoxy‐β‐O‐glycosides from C3‐(o‐cyanobenzoate) ester protected glycal donors via Ferrier rearrangement under Pd(0)‐catalyzed Tsuji‐Trost conditions. The synthesized donors indeed reacted with a variety of acceptors to afford the corresponding glycosides in good yields and excellent β‐stereoselectivity. The stereochemical outcome of the reactions has been found to be independent of the nature of protecting groups or conformational flexibility of the glycal donors. Furthermore, regeneration of ortho‐cyanobenzoic acid post rearrangement makes it a recyclable and reusable stereodirecting group. A preliminary mechanistic study demonstrates the importance of cyano‐group for the observed rearrangement and stereoselectivity. Incorporation of the directing group on the benzoate ester has altered the reactivity of the ester group as a leaving group for Tsuji‐Trost as well as Ferrier Rearrangement pathway.

Logical manipulation of protecting groups is one of the vital strategies involved in the synthesis of complex oligosachharides. As opposed to the robust permanent protecting groups, the chemoselective protection-deprotection operations...

Development of stereoselective synthetic methods for O‐glycosides is of paramount importance in the field of glycochemistry. Therefore, we report herein (1 N/2 N)‐methylated tetrazole methyl (MeTetMe) ethers as a C2‐directing group for the formation of 1,2‐trans‐β‐O‐glycosides. The synthesis of the tetrazole moiety was readily achieved by a 3+2 cycloaddition reaction on nitrile functionality. The tethered thioglycoside donors were found to deliver the β‐O‐glycosides when activated by PIFA‐TfOH reagent system. The reactions were performed with six newly synthesized phenyl and ethyl thioglycosides to obtain the glycosylated adducts in moderate to high yields and excellent to exclusive β‐selectivity. The glycosylation method was easily scalable up to grams without affecting the yield and stereoselectivity. The MeTetMe group was efficiently removed under Birch reduction conditions without affecting the benzyl ethers or isopropylidene acetal protection.