Sequential Dy(OTf)₃‐Catalyzed Solvent‐Free Per‐O‐Acetylation and Regioselective Anomeric De‐O‐Acetylation of Carbohydrates

Abstract

Dysprosium(III) trifluoromethanesulfonate-catalyzed per-O-acetylation and regioselective anomeric de-O-acetylation of carbohydrates can be tuned by adjusting the reaction medium. In this study, the per-O-acetylation of unprotected sugars by using a near-stoichiometric amount of acetic anhydride under solvent-free conditions resulted in the exclusive formation of acetylated saccharides as anomeric mixtures, whereas anomeric de-O-acetylation in methanol resulted in a moderate-to-excellent yield. Reactions with various unprotected monosaccharides or disaccharides followed by a semi-one-pot sequential conversion into the corresponding acetylated glycosyl hemiacetal also resulted in high yields. Furthermore, the obtained hemiacetals could be successfully transformed into trichloroimidates after Dy(OTf) -catalyzed glycosylation.

Selective S‐Deacetylation of Functionalized Thioacetates Catalyzed by Dy(OTf)3

“…Moreover,D y(OTf) 3 minimizes reagent use and can be recycled. Therefore, in combination with our recently developed catalytic per-O-acetylation and anomeric de-O-acetylationr eactions, [17] we believe that this new catalytic S-deacetylationm ethodc an be broadly applied to the synthesis of thiol-containing natural products, as well as S-linkedg lycoconjugates.…”

“…To suppress byproduct formation, we also used our optimized conditions for selective S-deacetylation (Table 2), but we observed no apparent improvement in the reaction yield (Table 4, entry 2). Based on as imilars tudy, [17] we assumed that Dy(OTf) 3 in MeOH wass till too active for carbohydrate molecules and readily afforded multihydrationb yproducts. To confirm this assumption,c ompound 8 was reacted in ac o-solvent system that has previously been reported to offer mild conditions for the S-deacetylation reaction.…”

“…To improvet he selective S-deacetylation reaction, furthero ptimizationo ft he reaction conditions was performed for compound 3 with equimolar amountso fD y(OTf) 3 and NaHCO 3 ,b ased on our previ-ous study on the anomeric deacetylation of carbohydrates. [17] With 1mol %D y(OTf) 3 andN aHCO 3 at room temperature, selective S-deacetylation proceeded smoothly,a nd the yield of the desired product (3a)i mproved to 60-64 %( Ta ble 2, entries 3a nd 4) within 3-5 h. However,t he yield of compound 3a decreased, and the fully deacetylated compound (3b)w as obtained when the reaction time exceeded 5h (Table 2, entry 5). Based on previous studies, [17,19] we assumed that dysprosium(III) was linked throughac oordinated bicarbonate anion, thereby resulting in low initial catalytic activity.T herefore, the combination of Dy(OTf) 3 and an equimolar amount of NaHCO 3 was likely to be less reactive than that of Dy(OTf) 3 alone,a nd therefore impede the interactions between the Oacetate group and the Dy III catalyst.…”

“…[17] With 1mol %D y(OTf) 3 andN aHCO 3 at room temperature, selective S-deacetylation proceeded smoothly,a nd the yield of the desired product (3a)i mproved to 60-64 %( Ta ble 2, entries 3a nd 4) within 3-5 h. However,t he yield of compound 3a decreased, and the fully deacetylated compound (3b)w as obtained when the reaction time exceeded 5h (Table 2, entry 5). Based on previous studies, [17,19] we assumed that dysprosium(III) was linked throughac oordinated bicarbonate anion, thereby resulting in low initial catalytic activity.T herefore, the combination of Dy(OTf) 3 and an equimolar amount of NaHCO 3 was likely to be less reactive than that of Dy(OTf) 3 alone,a nd therefore impede the interactions between the Oacetate group and the Dy III catalyst. Hence, this selectives trategy was expanded to bifunctional structures with thioacetate groups and other functional groups that could be deprotected under acidic conditions (e.g.,B oc, PMB,B z, and TBDMS; Ta ble 3a nd the Supporting Information).…”

“…We recently performed the acetylation and regioselective anomeric deacetylationo fc arbohydrates by using dysprosium(III) as ac atalyst. [17] To comprehensively analyze the catalytic applicationso ft his lanthanide(III) catalysti nv arious organic transformations, based on our experience of catalytic transesterification reactions, we investigated the feasibility of our catalytic system for the selective S-deacetylation of functionalized thioester derivatives (Scheme 1e).…”