Catalyst-free regioselective acetylation of primary hydroxy groups in partially protected and unprotected thioglycosides with acetic acid

Abstract

Highly regioselective acetylation of primary hydroxy groups in thioglycoside derivatives was achieved by treatment with aqueous or anhydrous acetic acid (60–100%) at elevated temperatures (80–118 °C), avoiding manipulations with protective groups.

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

“…A similar situation was observed in case of ethyl 6‐ O ‐acetyl‐1‐thio‐α‐ d ‐galactopyranoside ( 10 ) with electron withdrawing acetyl substituent at O‐6, which was obtained recently by us by regioselective acetylation of diol 9 using aqueous acetic acid [13] . After the treatment of compound 10 with anhydrous TFA in CH 2 Cl 2 at 0 °C (method B ), a mixture of furanosides 12 along with unreacted starting material 10 was detected by NMR (Table 3, entry 6).…”

“…Earlier we reported that the cleavage of 4,6‐ O ‐benzylidene group in ethyl 1‐thio‐β‐ d ‐galactopyranoside with TIPS groups at O‐2 and O‐3 (compound 1 , Figure 1) with aq TFA in CH 2 Cl 2 (method A ) gave the corresponding 1‐thio‐β‐ d ‐galactofuranoside 5 in 76 % yield (Table 2, entry 1) [12] . During the reaction of isomeric ethyl 4,6‐ O ‐benzylidene 2,3‐di‐ O ‐TIPS‐1‐thio‐α‐ d ‐galactofuranoside ( 2 ) [13] with α‐configuration under identical conditions (method A ) the formation of 1‐thio‐α‐ d ‐galactofuranoside 6 with TIPS groups at O‐2 and O‐3 and α‐configured diol 4 in pyranose form (Table 2, entry 2) was observed.…”

“…Heating 4,6‐ O ‐benzylidene derivative 17 bearing electron‐donating 5‐ tert ‐butyl‐2‐methylphenyl aglycone containing TIPS groups at O‐2 and O‐3 with 80 % aq AcOH at 100 °C for 2 h (method D ) gave the normally expected diol 18 in pyranose form (39 % yield) accompanied by formation of thiopyranoside 29 (9 % yield according to NMR data) with acetyl group [13] at O‐6 (Scheme 2, Table 4, entry 6). Treatment of diol 18 in pyranose form with anhydrous TFA in CH 2 Cl 2 (method B ) gave the corresponding thiofuranoside 30 in 60 % yield (Scheme 2, Table 4, entry 7).…”

“…Earlier we reported that the cleavage of 4,6-O-benzylidene group in ethyl 1-thio-β-d-galactopyranoside with TIPS groups at O-2 and O-3 (compound 1, Figure 1) with aq TFA in CH 2 Cl 2 (method A) gave the corresponding 1-thio-β-d-galactofuranoside 5 in 76 % yield (Table 2, entry 1). [12] During the reaction of isomeric ethyl 4,6-O-benzylidene 2,3-di-O-TIPS-1-thio-α-d-galactofuranoside (2) [13] with α-configuration under identical conditions (method A) the formation of 1-thio-α-d-galactofuranoside 6 with TIPS groups at O-2 and O-3 and α-configured diol 4 in pyranose form (Table 2, entry 2) was observed. At the same time, the treatment of α-configured diol 4 with anhydrous TFA in CH 2 Cl 2 (method B) (Table 2, entry 5) resulted in complete conversion of diol 4 and formation of an anomeric mixture of the corresponding furanosides 5 + 6 (α : β = 3 : 1) in 80 % yield.…”

“…A similar situation was observed in case of ethyl 6-O-acetyl-1-thio-α-d-galactopyranoside (10) with electron withdrawing acetyl substituent at O-6, which was obtained recently by us by regioselective acetylation of diol 9 using aqueous acetic acid. [13] After the treatment of compound 10 with anhydrous TFA in CH 2 Cl 2 at 0°C (method B), a mixture of furanosides 12 along with unreacted starting material 10 was detected by NMR (Table 3, entry 6). This mixture was subjected to an additional treatment with TFA at slightly elevated temperature (method B) to complete the transformation to furanosides 12, which were isolated in 45 % yield as an α/β mixture after silica gel chromatography (Table 3, entry 7).…”