The Influence of Anomeric Configuration and Aglycone Structure on the Outcome of Acid‐Promoted Ring Contraction in 2,3‐Di‐O‐Silylated S‐Galactopyranosides

Abstract

Acid-promoted rearrangement of a series of 1-thio-α/β-dgalactopyranosides with bulky triisopropylsilyl (TIPS) or tertbutyldiphenylsilyl (TBDPS) groups at both O-2 and O-3 and bearing various substituents at the S atom in anomeric position leading to ring contraction has been studied. The reaction rates of pyranose ring contraction in S-galactopyranosides were found to be strongly influenced by anomeric configuration and aglycone structure. Ethyl 1-thio-β-d-galactopyranosides underwent ring contraction faster than ethyl 1-thio-α-d-thiogalacto-pyranosides. 1-Thio-β-d-galactopyranosides with TIPS groups bearing electron-donating 5-tert-butyl-2-methylphenyl group in aglycone could be involved into rearrangement to furanosides under milder acidic conditions (aq TFA in CH 2 Cl 2 ) than the corresponding 1-thio-β-d-galactopyranosides with phenyl or 4chlorophenyl groups in aglycone (anhydrous TFA in CH 2 Cl 2 ). On the contrary, 1-thio-β-d-thiogalactopyranoside bearing electron-withdrawing 4-nitrophenyl group in aglycone did not undergo ring contraction under identical conditions.

Stereocontrolling Effect of a Single Triisopropylsilyl Group in 1,2‐cis‐Glucosylation

“…Since reactivity of primary hydroxy groups at C-6 in alcohols 15 and 16 is higher than that of secondary hydroxy groups in O-benzylated (17) and O-benzoylated (18)(19)(20) glycosyl acceptors we expected deterioration of 1,2-cis-stereoselectivity in glycosylation of primary glycosyl acceptors due to higher S N 2 character of glycosylation reaction.…”

“…[27] However, a poor stability of TIPS groups during trifluoroacetic acid promoted ring contraction in 2,3-di-O-silylated S-and Ogalactopyranosides was observed in some cases. [18] Besides, a putative cleavage of silyl (TBS, TIPS) groups in the brominepromoted glycosidation of conformationally superarmed thioglycosides [26] was suggested as the reason for diminished glycosylation yields, although the authors did not provide experimental evidence to support this hypothesis.…”

“…[17] We found that conformational changes induced by bulky 2,3-di-O-TIPS (or TBDPS) substituents in both S-and O-galactopyranosides favor the reaction of ring contraction with the formation of derivatives of the corresponding furanosides. [18] Herein, we compare the results of α-d-glucosylation of with a wide range of glycosyl acceptors with different nucleophilicity using various TIPS-substituted thioglucosides.…”