616
3
Chemical Glycosylation Reactions
( > Scheme 47) [168]. The reaction of 292, as an anomeric mixture, with various acceptors
was examined in acetonitrile at −40 °C in the presence of TMSOTf as catalyst. Reaction of
2 with 6-OH and 4-OH methyl glucosides as acceptors gave the corresponding disaccharides
in 61 and 67% yield and as 85:15 and 75:25 β/α mixtures, respectively. Similar results were
obtained for tetra-O-benzyl galactose.
3.2 Isopropenyl Glycosides
Sinaÿ and co-workers described the synthesis of isopropenyl glycosides [169] by reaction of
the corresponding anomeric acetates with the Tebbe reagent [170]. Reaction of 1-O-acetyl2,3,4,6-tetra-O-benzyl-D-glucopyranose (294) with a solution of Tebbe reagent in toluene
gave the isopropenyl glycosides 295, in 87–90% yields ( > Scheme 48a). Likewise, isopropenyl galactoside 297 (α:β ≈ 1:1) was prepared from the corresponding acetate 296 by
Tebbe methylenation in 88% yield ( > Scheme 48b). Treatment of 295 (α:β = 4:1) in MeCN at
−25 °C with the primary hydroxyl acceptor 298, in the presence of TMSOTf gave the disaccharides 299 (68%) with an excellent β-selectivity (20:1) ( > Scheme 48c). The condensation
of 295 with the secondary alcohol 300 in MeCN at −25 °C in the presence of BF 3 ·Et 2 O
afforded the disaccharide 301 in good yield, albeit with reduced stereoselectivity (β:α = 5:1)
( > Scheme 48d). When the same glycosylation was carried out in CH 2 Cl 2 instead of MeCN
the disaccharide 301 was obtained in limited yield ( > Scheme 48e). The successful glycosylation of phenyl 1-thio-glycoside 302 with 295 in the presence of TMSOTf illustrates the
usefulness of isopropenyl glycosides in the synthesis of thiophenyl disaccharides (e. g. 303,
> Scheme 48f ). The authors found no significant variations on yield or stereoselectivity by the
use of either mainly α or mainly β isopropenyl derivatives. The best results for galactosylation
were achieved in CH 2 Cl 2 with TMSOTf as promoter ( > Scheme 48g).
Chenault and co-workers reported the use of O-isopropenyl glycosides bearing ester protecting
groups [171,172]. These compounds are stable at room temperature and can be readily purified
by column chromatography on silicagel, moreover their glycosylation would proceed to give
β-glycosides via neighboring group participation. The reaction of bis(acetonyl)mercury [173]
with glycopyranosyl halides proved to be a good method for the preparation of isopropenyl
β-glycopyranosides (e. g. 305, > Scheme 49a). The authors described routes to O-isopropenyl
2,3,4,6-tetra-O-pivaloyl-α, and β-D-glucopyranosides α-307 and β-307, respectively. Reaction of 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide (306) with diacetonyl mercury
led to β-307 ( > Scheme 49b), whereas regioselective methylidenation [174] of 309 (prepared
stereoselectively by acid-catalyzed exchange of the anomeric pivaloyloxy group of pentaO-pivaloyl-β-D-glucopyranose, 308) generated α-307 as the only product ( > Scheme 49c).
The β-isomer, however, exhibited greater shelf life than the latter.
On the basis of the reaction of NPGs with electrophiles, Chenault et al. considered the possible activation of isopropenyl glycosides with electrophiles. The mechanism of activation was
expected to involve initial capture of the electrophile (E + ) by the vinyl ether double bond of
310 leading to the formation of cation 311 or 312 ( > Scheme 50). Collapse of 311 or 312 to
form glycosyl oxocarbenium ion 313 and acetone derivative 314 would be followed by nucleophilic attack on 313 to generate glycoside 315. An alternative reaction would involve direct
nucleophilic attack on 311 or 312 to generate the addition product 316.
3
Chemical Glycosylation Reactions
( > Scheme 47) [168]. The reaction of 292, as an anomeric mixture, with various acceptors
was examined in acetonitrile at −40 °C in the presence of TMSOTf as catalyst. Reaction of
2 with 6-OH and 4-OH methyl glucosides as acceptors gave the corresponding disaccharides
in 61 and 67% yield and as 85:15 and 75:25 β/α mixtures, respectively. Similar results were
obtained for tetra-O-benzyl galactose.
3.2 Isopropenyl Glycosides
Sinaÿ and co-workers described the synthesis of isopropenyl glycosides [169] by reaction of
the corresponding anomeric acetates with the Tebbe reagent [170]. Reaction of 1-O-acetyl2,3,4,6-tetra-O-benzyl-D-glucopyranose (294) with a solution of Tebbe reagent in toluene
gave the isopropenyl glycosides 295, in 87–90% yields ( > Scheme 48a). Likewise, isopropenyl galactoside 297 (α:β ≈ 1:1) was prepared from the corresponding acetate 296 by
Tebbe methylenation in 88% yield ( > Scheme 48b). Treatment of 295 (α:β = 4:1) in MeCN at
−25 °C with the primary hydroxyl acceptor 298, in the presence of TMSOTf gave the disaccharides 299 (68%) with an excellent β-selectivity (20:1) ( > Scheme 48c). The condensation
of 295 with the secondary alcohol 300 in MeCN at −25 °C in the presence of BF 3 ·Et 2 O
afforded the disaccharide 301 in good yield, albeit with reduced stereoselectivity (β:α = 5:1)
( > Scheme 48d). When the same glycosylation was carried out in CH 2 Cl 2 instead of MeCN
the disaccharide 301 was obtained in limited yield ( > Scheme 48e). The successful glycosylation of phenyl 1-thio-glycoside 302 with 295 in the presence of TMSOTf illustrates the
usefulness of isopropenyl glycosides in the synthesis of thiophenyl disaccharides (e. g. 303,
> Scheme 48f ). The authors found no significant variations on yield or stereoselectivity by the
use of either mainly α or mainly β isopropenyl derivatives. The best results for galactosylation
were achieved in CH 2 Cl 2 with TMSOTf as promoter ( > Scheme 48g).
Chenault and co-workers reported the use of O-isopropenyl glycosides bearing ester protecting
groups [171,172]. These compounds are stable at room temperature and can be readily purified
by column chromatography on silicagel, moreover their glycosylation would proceed to give
β-glycosides via neighboring group participation. The reaction of bis(acetonyl)mercury [173]
with glycopyranosyl halides proved to be a good method for the preparation of isopropenyl
β-glycopyranosides (e. g. 305, > Scheme 49a). The authors described routes to O-isopropenyl
2,3,4,6-tetra-O-pivaloyl-α, and β-D-glucopyranosides α-307 and β-307, respectively. Reaction of 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide (306) with diacetonyl mercury
led to β-307 ( > Scheme 49b), whereas regioselective methylidenation [174] of 309 (prepared
stereoselectively by acid-catalyzed exchange of the anomeric pivaloyloxy group of pentaO-pivaloyl-β-D-glucopyranose, 308) generated α-307 as the only product ( > Scheme 49c).
The β-isomer, however, exhibited greater shelf life than the latter.
On the basis of the reaction of NPGs with electrophiles, Chenault et al. considered the possible activation of isopropenyl glycosides with electrophiles. The mechanism of activation was
expected to involve initial capture of the electrophile (E + ) by the vinyl ether double bond of
310 leading to the formation of cation 311 or 312 ( > Scheme 50). Collapse of 311 or 312 to
form glycosyl oxocarbenium ion 313 and acetone derivative 314 would be followed by nucleophilic attack on 313 to generate glycoside 315. An alternative reaction would involve direct
nucleophilic attack on 311 or 312 to generate the addition product 316.