580
3
Chemical Glycosylation Reactions
2.4 Conversion of NPGs to Other Glycosyl Donors
NPGs have been converted into different glycosyl donors.
2.4.1 Conversion to Glycosyl Bromides
Konradsson and Fraser-Reid [44] reported the conversion of NPGs into glycosyl bromides,
e. g. 76, by treatment of the corresponding pentenyl glycoside with a dilute dichloromethane
solution of bromine, conditions that favor unimolecular reaction. The reaction was shown to be
compatible with acetals, benzyl, silyl, and allyl protecting groups in the NPG ( > Scheme 11a).
2.4.2 Conversion to Glycosyl Phosphates
Pale and Whitesides [45] described the synthesis of glycosyl phosphates 77 [46,47], by reaction of dibenzyl phosphate with NPG 12, with the use of either IDCP or NBS as promoters.
The authors noted the influence of the solvent (MeCN, Et 2 O, CH 2 Cl 2 ) and the promoter in the
α/β selectivity of the glycosyl phosphates formed ( > Scheme 11b).
2.4.3 Conversion to Glycosyl Fluorides
Clausen and Madsen [48] reported the transformation of NPG 78 into glycosyl fluoride 79 by
treatment with NBS and (diethylamino)-sulfur trifluoride (DAST) ( > Scheme 11c).
López et al. [49] described the preparation of glycosyl fluorides 80, by reaction of NPGs with
bis(pyridinium) iodonium (I) tetrafluoroborate (IPy 2 BF 4 ) in the presence of tetrafluoroboric
acid ( > Scheme 11d). The process was compatible with the presence of silyl and benzyl groups
in the NPG.
2.4.4 Chemoselective Liberation Followed by Anomeric Activation
The ability to chemoselectively deprotect pent-4-enyl glycosides opens an avenue for a twostep transformation of NPGs into different glycosyl donors. In this context, NPGs can be
transformed [50] into thioglycosides 81 [51,52,53], glycosyl trichloroacetimidates 82 [54],
and glycosyl chlorides 83 [55] ( > Scheme 11e).
2.5 NPGs in the Stereocontrolled Assembly of α- and β- Glycoproteins
2.5.1 Pyranosylacetonitrilium Ions from NPGs
Ratcliffe and Fraser-Reid found that acetonitrile was able to trap glycosyl oxocarbenium ions
(e. g. 46), arising from NPGs, to give acetonitrilium ions, e. g. 84 ( > Scheme 12a) [56]. The
latter reacted with water to produce intermediate 85 that evolves to α-amide 86, in a Ritter-type
reaction [57] ( > Scheme 12a).
This transformation was significant from a mechanistic standpoint. The formation of the α-acetonitrilium ion was not expected on the basis of the reverse anomeric effect (originally defined
as the tendency of positively charged substituents at C-1 of a pyranose ring to adopt the equatorial orientation [58]). The authors, however, unambiguously established the α-orientation of
3
Chemical Glycosylation Reactions
2.4 Conversion of NPGs to Other Glycosyl Donors
NPGs have been converted into different glycosyl donors.
2.4.1 Conversion to Glycosyl Bromides
Konradsson and Fraser-Reid [44] reported the conversion of NPGs into glycosyl bromides,
e. g. 76, by treatment of the corresponding pentenyl glycoside with a dilute dichloromethane
solution of bromine, conditions that favor unimolecular reaction. The reaction was shown to be
compatible with acetals, benzyl, silyl, and allyl protecting groups in the NPG ( > Scheme 11a).
2.4.2 Conversion to Glycosyl Phosphates
Pale and Whitesides [45] described the synthesis of glycosyl phosphates 77 [46,47], by reaction of dibenzyl phosphate with NPG 12, with the use of either IDCP or NBS as promoters.
The authors noted the influence of the solvent (MeCN, Et 2 O, CH 2 Cl 2 ) and the promoter in the
α/β selectivity of the glycosyl phosphates formed ( > Scheme 11b).
2.4.3 Conversion to Glycosyl Fluorides
Clausen and Madsen [48] reported the transformation of NPG 78 into glycosyl fluoride 79 by
treatment with NBS and (diethylamino)-sulfur trifluoride (DAST) ( > Scheme 11c).
López et al. [49] described the preparation of glycosyl fluorides 80, by reaction of NPGs with
bis(pyridinium) iodonium (I) tetrafluoroborate (IPy 2 BF 4 ) in the presence of tetrafluoroboric
acid ( > Scheme 11d). The process was compatible with the presence of silyl and benzyl groups
in the NPG.
2.4.4 Chemoselective Liberation Followed by Anomeric Activation
The ability to chemoselectively deprotect pent-4-enyl glycosides opens an avenue for a twostep transformation of NPGs into different glycosyl donors. In this context, NPGs can be
transformed [50] into thioglycosides 81 [51,52,53], glycosyl trichloroacetimidates 82 [54],
and glycosyl chlorides 83 [55] ( > Scheme 11e).
2.5 NPGs in the Stereocontrolled Assembly of α- and β- Glycoproteins
2.5.1 Pyranosylacetonitrilium Ions from NPGs
Ratcliffe and Fraser-Reid found that acetonitrile was able to trap glycosyl oxocarbenium ions
(e. g. 46), arising from NPGs, to give acetonitrilium ions, e. g. 84 ( > Scheme 12a) [56]. The
latter reacted with water to produce intermediate 85 that evolves to α-amide 86, in a Ritter-type
reaction [57] ( > Scheme 12a).
This transformation was significant from a mechanistic standpoint. The formation of the α-acetonitrilium ion was not expected on the basis of the reverse anomeric effect (originally defined
as the tendency of positively charged substituents at C-1 of a pyranose ring to adopt the equatorial orientation [58]). The authors, however, unambiguously established the α-orientation of