Glycal Derivatives
3.6
719
Subsequently, it has been demonstrated that, under aprotic reaction conditions, various metal
chlorides can catalyze not only double bond migration but also C-3 epimerization [189].
Some caution is required in predicting regioselectivity in analyzing Ferrier type rearrangements that are not catalyzed by Lewis acid or that occur under conditions that favor kinetically
controlled products. For example, nucleophilic agents can sometimes react with glycals in the
absence of Lewis catalysts to produce 2,3-unsaturated products [2]. Thus, as observed in one
study, condensation of 3,4-bis-O-(4-nitrobenzoyl)-D-xylal with purines and pyrimidines without an acid catalyst led to anomeric mixtures of 2 ,3 -unsaturated nucleosides [190]. Moreover,
4 can react with thiophenol to give kinetically favored phenyl 4,6-di-O-acetyl-2,3-dideoxy1-thio-D-erythro-hex-2-enopyranoside 92 [191] and only a minor admixture of the expected
3-regioisomer. The tendency of this unsaturated thioglycoside to undergo rearrangement was
exploited in order to synthesize 1-C-substituted glycals and related bicyclic spiroketals [192].
Also, oxidation of the phenyl thioglycoside 92 with m-CPBA to 93, followed by treatment
with piperidine, led to the allal derivative 95, apparently via sulfenate 94 as intermediate
( > Scheme 32) [193]. However, because m-CPBA can give rise to complex mixtures upon
oxidation of unsaturated thioglycosides, use of 3,3-dimethyldioxirane, which cleanly affords
the desired sulfoxides, is recommended [194].
The same synthetic approach was applied in obtaining a unique thiosugar and constituent of
ene-diyne antitumor antibiotics; in contrast, unsaturated glycosides 96 were treated with [195]
phenylselenol at −90 °C in the presence of BF 3 ·Et 2 O to give mainly unsaturated glycoside
97 [196,197], which in turn was rearranged into glycal 98 after oxidation with m-CPBA
( > Scheme 33). An analogous sequence of reactions employing a dinitrophenyl thiol protective
group has been used to obtain 2,3-unsaturated thiophenyl glycosides [198].
⊡ Scheme 32
⊡ Scheme 33
3.6
719
Subsequently, it has been demonstrated that, under aprotic reaction conditions, various metal
chlorides can catalyze not only double bond migration but also C-3 epimerization [189].
Some caution is required in predicting regioselectivity in analyzing Ferrier type rearrangements that are not catalyzed by Lewis acid or that occur under conditions that favor kinetically
controlled products. For example, nucleophilic agents can sometimes react with glycals in the
absence of Lewis catalysts to produce 2,3-unsaturated products [2]. Thus, as observed in one
study, condensation of 3,4-bis-O-(4-nitrobenzoyl)-D-xylal with purines and pyrimidines without an acid catalyst led to anomeric mixtures of 2 ,3 -unsaturated nucleosides [190]. Moreover,
4 can react with thiophenol to give kinetically favored phenyl 4,6-di-O-acetyl-2,3-dideoxy1-thio-D-erythro-hex-2-enopyranoside 92 [191] and only a minor admixture of the expected
3-regioisomer. The tendency of this unsaturated thioglycoside to undergo rearrangement was
exploited in order to synthesize 1-C-substituted glycals and related bicyclic spiroketals [192].
Also, oxidation of the phenyl thioglycoside 92 with m-CPBA to 93, followed by treatment
with piperidine, led to the allal derivative 95, apparently via sulfenate 94 as intermediate
( > Scheme 32) [193]. However, because m-CPBA can give rise to complex mixtures upon
oxidation of unsaturated thioglycosides, use of 3,3-dimethyldioxirane, which cleanly affords
the desired sulfoxides, is recommended [194].
The same synthetic approach was applied in obtaining a unique thiosugar and constituent of
ene-diyne antitumor antibiotics; in contrast, unsaturated glycosides 96 were treated with [195]
phenylselenol at −90 °C in the presence of BF 3 ·Et 2 O to give mainly unsaturated glycoside
97 [196,197], which in turn was rearranged into glycal 98 after oxidation with m-CPBA
( > Scheme 33). An analogous sequence of reactions employing a dinitrophenyl thiol protective
group has been used to obtain 2,3-unsaturated thiophenyl glycosides [198].
⊡ Scheme 32
⊡ Scheme 33