Chemistry of 4,6-O-Benzylidene-d-glycopyranosyl Triflates:  Contrasting Behavior between the Gluco and Manno Series

Abstract

Activation of either anomer of S-phenyl 2,3-di-O-benzyl-4,6-O-benzylidene-1-deoxy-1-thia-D-glucopyranoside with triflic anhydride in dichloromethane at -78 degrees C in the presence of 2,6-di-tert-butyl-4-methylpyridine affords a highly active glycosylating species which, on addition of alcohols, provides alpha-glucosides with high selectivity. This selectivity stands in stark contrast to the analogous mannopyranoside series, which affords the beta-mannosides with excellent selectivity under the same conditions. Low-temperature NMR experiments support the notion that a glucosyl triflate is formed in the initial activation step. Possible reasons for the diverging stereoselectivity in the gluco and manno series are discussed.

4,6-O-[1-Cyano-2-(2-iodophenyl)ethylidene] Acetals. Improved Second-Generation Acetals for the Stereoselective Formation of β-d-Mannopyranosides and Regioselective Reductive Radical Fragmentation to β-d-Rhamnopyranosides. Scope and Limitations

“…We tentatively assign this signal to glycal 90 (H1) on the basis of the previous isolation of such 2-alkoxyglycals from this type of experiment. 25 Exactly analogous results were observed with the 2,3-di-O-benzyl protected glucosyl donor 31 (See supporting information for VT-spectra). Thus, on addition of Tf 2 O to a CD 2 Cl 2 mixture of 31, and Ph 2 SO at −78 °C the substrate was consumed and two new anomeric signals were formed at δ 6.02 (d, J = 3.3 Hz) and δ 5.63 (d, J = 9.6 Hz), representing an α-and a β-derivative, respectively.…”

“…In line with the precedent for coupling to 2,3-di-O-benzyl-4,6-O-benzylidene protected glucosyl donors, the reactions were α-selective. 25 As discussed below, VT-NMR experiments were again conducted in an attempt to understand the problematic couplings.…”

New Principles for Glycoside‐Bond Formation

“…For example, glycosidation of the 4,6-O-benzylidenated thioglucoside donor 164 with a range of acceptors gave a-glucosides with excellent selectivities (Scheme 24 a). [243] These results seem to stand in sharp contrast to the b-selective mannosylation reactions described above. However, in these reactions and most glycosidation reactions, a continuum of intermediates with different stabilities and lifetimes are likely to exist, each of which has its own reactivity and selectivity.…”

On the Influence of the C2−O2 and C3−O3 Bonds in 4,6-O-Benzylidene-Directed β-Mannopyranosylation and α-Glucopyranosylation

“…4,[6][7][8][9] This contrast in selectivity, originally seen with donors 1 and 2 ,7 on activation with trifluoromethanesulfonic anhydride in the presence of a hindered non-nucleophilic base such as 2,4,6-tri-tert-butylpyrimidine (TTBP), 10 and subsequently observed with donors 3 and 4, on activation with 1-benzenesulfinyl piperidine (BSP) and triflic anhydride, 4 is reflected in the reduced β-selectivity seen on going from the 3,4-O-carbonate protected 6-deoxymanno (rhamno) donor 5 to the corresponding gluco donor 6. 11…”

“…21 While we can not exclude this mechanism conclusively, we consider it unlikely on the grounds that our NMR experiments provided no evidence for the existence of a β-glucosyl triflate. 7 We considered that the shift toward the SSIP 9 implied by the change from β-to α-selectivity observed on going from the manno to the gluco series might be due to greater repulsion between the O-2 substituent and the triflate counter ion in the CIP 8 in the gluco series, which would have the effect of facilitating SSIP formation (Figure 1). …”