Stereoselective Synthesis of α‐Glycosyl Azides by TMSOTf‐Mediated Ring Opening of 1,6‐Anhydro Sugars

Abstract

Access to α‐glycosyl azides in modest to high diastereoselectivity by way of TMSN3 ring‐opening of 1,6‐anhydro sugars mediated by TMSOTf is reported. The reaction tolerates a wide variety of functional groups including alcohol, alkyne, azide and ester groups. The efficient synthesis of a pseudopentasaccharide in five steps from commercially available levoglucosan by way of a “click‐click” approach is presented to highlight the interest of the TMSN3 ring‐opening reaction.

One-Pot, Highly Stereoselective Synthesis of Dithioacetal-α,α-Diglycosides

“…1,6-Anhydro-2,3,4-tri-O-(triisopropylsilylpropargyl)-β-D-glucopyranose ( 2 ). To a solution of 1,6-Anhydro-2,3,4-tri- O -propargyl- β -D-glucopyranose [ 3 ] (1 equiv., 675 mg, 2.44 mmol) in THF (60.9 mL) at −70 °C was added LiHMDS (4 equiv., 1 M, 9.77 mL, 9.77 mmol) dropwise. Then after 20 min TIPSCl (4 equiv., 1.94 g, 2.16 mL, 9.77 mmol) was added dropwise.…”

“…In this context, we have recently reported a molecular Lego approach for the synthesis of functionalized cyclic and acyclic neo-oligosaccharides [ 2 ]. Our strategy was based on the linkage of bifunctional building blocks by Cu(I)-catalyzed azide−alkyne cycloaddition, the reducing end of the sugars being activated as a glycosyl azide and masked as a 1,6-anhydro sugar [ 2 , 3 ]. To explore the interest of thiol-click chemistry for such modular strategies [ 4 , 5 ], we needed to synthesize thioglycoside 1 ( Scheme 1 ).…”

Nucleophilic Ring‐Opening of 1,6‐Anhydrosugars: Recent Advances and Applications in Organic Synthesis

“…[9] In 2013, Compain et al reported the stereocontrolled synthesis of α-glycosyl azides by way of TMSOTf-mediated ring-opening of 1,6-anhydro sugars with a large excess of TMSN 3 (Scheme 1a). [10] According to the absolute configuration and substitution at C-2, moderate to high level of diastereoselectivity could be achieved (up to de > 98 % in the D-gluco series). The αselectivity observed may be explained by assuming a preferential nucleophilic attack along axial trajectories on the most reactive/favored half-chair of the glycosyl cation intermediate (Scheme 1b).…”

“…The αselectivity observed may be explained by assuming a preferential nucleophilic attack along axial trajectories on the most reactive/favored half-chair of the glycosyl cation intermediate (Scheme 1b). [10,11] The α-glycosyl azides were formed with a high level of chemoselectivity and functional group tolerance. Reaction scope studies reported independently by Compain [10] and few years after by Zhu [12] showed that the reaction is compatible with a wide range of functional groups including alcohol, alkyne, and ester groups.…”

AuBr3-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

“…Glycosyl azides can be accessed from the corresponding glycosyl halides [ 37 – 40 ] by nucleophilic displacement with NaN 3 or using trimethylsilyl azide in the presence of a phase transfer catalyst [ 41 – 45 ]. More commonly, glycosyl azides are synthesized from per- O -acetylated sugars using trimethylsilyl azide in the presence of a variety of Lewis acids such as SnCl 4 [ 46 ], TiCl 4 [ 47 – 48 ], BF 3 ·OEt 2 [ 49 ] , TMSOTf [ 50 – 51 ], etc. However, at higher concentration Lewis acids can potentially lead to slow anomerization [ 52 ].…”