Reactions at Oxygen Atoms
2.1
155
⊡ Scheme 63
Stereoselective anomeric O-alkylation of acyl-protected sugars
⊡ Scheme 64
Anomeric O-alkylation of partially protected pyranoses
tion of 2-O-unprotected tribenzylglucopyranose afforded exclusively the 1-O-alkylated product when the reaction was done with one equivalent of NaH, whereas the undesired 1,2-disubstituted isomer was also obtained when two equivalents of NaH were used [378].
Although ring-chain equilibration permits the formation of many products in fully unprotected
monosaccharides, the regiocontrol in the per-O-benzylation towards uniform glycoside bond
formation is generally very high [379,380] ( > Scheme 65).
The 1-O-alkylation of pyranoses has also been used for glycosidic bond formation [381].
An alternative activation of the anomeric hydroxyl makes use of 1,2-O-dibutylstannylene
acetals [382]. Thus, for instance condensation of the stannylene acetal of 3,4,6-tribenzylmannose with methyl iodide, allyl or benzyl bromide afforded the corresponding β-mannosides in
almost quantitative yields ( > Scheme 66).
On the other hand, carbohydrates carrying an aromatic aglycon are important natural products and therefore methods for the arylation of anomeric hemiacetals have also been developed. Both Mukaiyama [383] and Smith [384] have synthesized aryl glycosides by nucleophilic aromatic substitution for use as glycosyl donors. The method is quite efficient but
requires activation by electron-withdrawing groups in the aromatic counterpart. Thus, direct
reaction of 1-fluoro-2,4-dinitrobenzene with the 1-OH group of the hemiacetal gave 2,4-dinitroglycosides in excellent yields ( > Scheme 67a). In the case of dinitrosalicylic (DISAL) acid
2.1
155
⊡ Scheme 63
Stereoselective anomeric O-alkylation of acyl-protected sugars
⊡ Scheme 64
Anomeric O-alkylation of partially protected pyranoses
tion of 2-O-unprotected tribenzylglucopyranose afforded exclusively the 1-O-alkylated product when the reaction was done with one equivalent of NaH, whereas the undesired 1,2-disubstituted isomer was also obtained when two equivalents of NaH were used [378].
Although ring-chain equilibration permits the formation of many products in fully unprotected
monosaccharides, the regiocontrol in the per-O-benzylation towards uniform glycoside bond
formation is generally very high [379,380] ( > Scheme 65).
The 1-O-alkylation of pyranoses has also been used for glycosidic bond formation [381].
An alternative activation of the anomeric hydroxyl makes use of 1,2-O-dibutylstannylene
acetals [382]. Thus, for instance condensation of the stannylene acetal of 3,4,6-tribenzylmannose with methyl iodide, allyl or benzyl bromide afforded the corresponding β-mannosides in
almost quantitative yields ( > Scheme 66).
On the other hand, carbohydrates carrying an aromatic aglycon are important natural products and therefore methods for the arylation of anomeric hemiacetals have also been developed. Both Mukaiyama [383] and Smith [384] have synthesized aryl glycosides by nucleophilic aromatic substitution for use as glycosyl donors. The method is quite efficient but
requires activation by electron-withdrawing groups in the aromatic counterpart. Thus, direct
reaction of 1-fluoro-2,4-dinitrobenzene with the 1-OH group of the hemiacetal gave 2,4-dinitroglycosides in excellent yields ( > Scheme 67a). In the case of dinitrosalicylic (DISAL) acid