C-Glycosylation
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771
⊡ Scheme 19
⊡ Scheme 20
Since the stereoelectronic effect determines the stereochemical outcomes in the above-mentioned C-glycosidation of pyranose derivatives, application of the same method for the synthesis of β-C-glycosylation seems to be difficult. However, when the conformation of the
substrate can be inverted, axial attack of a nucleophile from the β face would be predominant for stereoelectronic reasons, yielding β-C-glycoside. On the basis of the above outlined
hypothesis, Shuto and co-workers demonstrated β-C-allylation of pentoxylose protected with
TIPS (tri-isopropylsilyl) ( > Scheme 19) [34]. Installation of the sterically hindered protecting
group fixed the inverted conformation ( 1 C 4 ) to avoid the gauche repulsion, thereby axial attack
of allylsilane from the β face resulted in the β-C-glycoside, while allylation of 1-fluoroxylose
protected with butane 2,3-diacetal (BDA) gave α-C-glycoside exclusively.
The stereochemical outcome of the similar C-allylation of pentofuranose does not depend on
the substituent at the C-4 position of the carbohydrate, but rather depends on the type of substituent at the C-3 position as shown in > Scheme 20. Woerpel explained the stereochemical
outcome by stereoelectronically controlled attack of allylsilane to the lower energy envelope
conformer as shown below [35]. The reaction of 7 gave α-C-products through the transition
state shown for intermediate 9, while the reaction of 8 afforded β-allyl product 12 through
a different transition state 11, in which the methyl substituent occupied the equatorial position.
2.3.3 Aryl-C-Glycosylation with Aromatic Nucleophiles
Stereoselective formation of the aryl-C-glycosidic linkage has been developed for synthesis of biologically important antibiotics and plant constituents. The most direct and widely
used synthetic method is the Friedel–Crafts type reaction between electrophilic carbohydrate
3.8
771
⊡ Scheme 19
⊡ Scheme 20
Since the stereoelectronic effect determines the stereochemical outcomes in the above-mentioned C-glycosidation of pyranose derivatives, application of the same method for the synthesis of β-C-glycosylation seems to be difficult. However, when the conformation of the
substrate can be inverted, axial attack of a nucleophile from the β face would be predominant for stereoelectronic reasons, yielding β-C-glycoside. On the basis of the above outlined
hypothesis, Shuto and co-workers demonstrated β-C-allylation of pentoxylose protected with
TIPS (tri-isopropylsilyl) ( > Scheme 19) [34]. Installation of the sterically hindered protecting
group fixed the inverted conformation ( 1 C 4 ) to avoid the gauche repulsion, thereby axial attack
of allylsilane from the β face resulted in the β-C-glycoside, while allylation of 1-fluoroxylose
protected with butane 2,3-diacetal (BDA) gave α-C-glycoside exclusively.
The stereochemical outcome of the similar C-allylation of pentofuranose does not depend on
the substituent at the C-4 position of the carbohydrate, but rather depends on the type of substituent at the C-3 position as shown in > Scheme 20. Woerpel explained the stereochemical
outcome by stereoelectronically controlled attack of allylsilane to the lower energy envelope
conformer as shown below [35]. The reaction of 7 gave α-C-products through the transition
state shown for intermediate 9, while the reaction of 8 afforded β-allyl product 12 through
a different transition state 11, in which the methyl substituent occupied the equatorial position.
2.3.3 Aryl-C-Glycosylation with Aromatic Nucleophiles
Stereoselective formation of the aryl-C-glycosidic linkage has been developed for synthesis of biologically important antibiotics and plant constituents. The most direct and widely
used synthetic method is the Friedel–Crafts type reaction between electrophilic carbohydrate