hydrolysis of the methyl acetal and oxidation of the hemiacetal results in racisoavenaciolide. As both enantiomers of the “naked sugars” (+)- and (À)-172 are
readily available, the syntheses outlined in Scheme 41 can be applied to prepare
ethisolide and isoavenaciolide in both their enantiomerically pure forms.
As the “naked sugars,” 170–172 can be converted in few steps into
polysubstituted 7-oxabicyclo[2.2.1]heptan-2-ones with high regio- and stereoselectivity, and the fact that these ketones undergo highly regioselective
Baeyer–Villiger oxidations into the corresponding uronolactones makes the
“naked sugar” method [202, 207] quite useful for the preparation of unusual sugars
including long-chain aldoses and alditols [216, 224, 276, 277], iminoalditols [223]
and analogues [278–280], and C-disaccharides [281–284]. As an illustration we
present in Scheme 42 the total asymmetric synthesis of 1,5-dideoxy-1,5-imino- Dlyxitol C-linked to methyl α-D-glucopyranoside, (À)-262 [285]. Benzeneselenyl
chloride adds at 0
C onto the exo face of the alkene moiety of (+)-172 in an anti
fashion. In the absence of external nucleophile, chloride anion is quenched onto the
endo face of C6 exclusively providing adduct (+)-246 [286]. The homoconjugated
carbonyl group acts as an electron-releasing group in this electrophilic reaction as
already discussed above (Scheme 35). When formed at a low temperature, the
potassium enolate of (+)-246 does not undergo 7-oxa ether opening but can be
quenched with the Eschenmoser’s salt giving enone (À)-247. Epoxidation of
“naked sugar” (+)-170 gives an exo-epoxide that is ring-opened under acidic
conditions producing 248 resulting from the migration of the 2-endocamphanoyloxy group to the 6-endo carbon center, forming 7-oxanorbornanone
248 in 71 % yield (considering the recovery of unreacted (+)-170). Protection of
exo-alcohol 248 as a MOM ether and then treatment with MeOH/DBU liberates the
chiral auxiliary (camphanic acid) and an endo-alcohol that is also protected as a
MOM ether. This provides 249 that undergoes Baeyer–Villiger oxidation into
uronolactone 250 as single product. The lithium enolate of 250 (does not undergo
oxa bridge opening at low temperature) adds to enone (À)-247 giving a single
Michael adduct 252 after acidic work-up. Steric factor controls the exo face
selectivity for both the Michael reaction of the uronolactone enolate and the
proton quenching of intermediate oxanorbornanone enolate 251. Reduction of
ketone 252 is also exo face selective. Oxidative removal of the benzeneselenyl
group uses mCPBA and generates the corresponding chloroalkene. Protection
of the endo-alcohol as a MOM ether furnishes 253. BnOLi adds to the lactone
moiety of 253, giving a mixture of furanoses that are silylated. The uronic ester 254
so-obtained is then dihydroxylated on its chloroalkene moiety providing
7-oxanorbornanone 255 after acetylation. Baeyer–Villiger oxidation of 255 leads
to 256. Debenzylation of the uronic ester 256 gives a carboxylic acid that undergoes
in situ Curtius rearrangement. This gives an intermediate isocyanate which reacts
with benzyl alcohol to provide benzyl carbamate 257. After desilylation of 257 and
hydrogenolysis of the benzyl carbamate, the intermediate aminoaldose 258 is
formed. It equilibrates with imine 259 which is reduced into 260 under the conditions of the hydrogenolysis. Final alcohol deprotection into 261 and ester reduction
produces aza-C-disaccharide (À)-262. Enantiomer and stereoisomers of (À)-262
180
A.J. Moreno-Vargas and P. Vogel
readily available, the syntheses outlined in Scheme 41 can be applied to prepare
ethisolide and isoavenaciolide in both their enantiomerically pure forms.
As the “naked sugars,” 170–172 can be converted in few steps into
polysubstituted 7-oxabicyclo[2.2.1]heptan-2-ones with high regio- and stereoselectivity, and the fact that these ketones undergo highly regioselective
Baeyer–Villiger oxidations into the corresponding uronolactones makes the
“naked sugar” method [202, 207] quite useful for the preparation of unusual sugars
including long-chain aldoses and alditols [216, 224, 276, 277], iminoalditols [223]
and analogues [278–280], and C-disaccharides [281–284]. As an illustration we
present in Scheme 42 the total asymmetric synthesis of 1,5-dideoxy-1,5-imino- Dlyxitol C-linked to methyl α-D-glucopyranoside, (À)-262 [285]. Benzeneselenyl
chloride adds at 0
C onto the exo face of the alkene moiety of (+)-172 in an anti
fashion. In the absence of external nucleophile, chloride anion is quenched onto the
endo face of C6 exclusively providing adduct (+)-246 [286]. The homoconjugated
carbonyl group acts as an electron-releasing group in this electrophilic reaction as
already discussed above (Scheme 35). When formed at a low temperature, the
potassium enolate of (+)-246 does not undergo 7-oxa ether opening but can be
quenched with the Eschenmoser’s salt giving enone (À)-247. Epoxidation of
“naked sugar” (+)-170 gives an exo-epoxide that is ring-opened under acidic
conditions producing 248 resulting from the migration of the 2-endocamphanoyloxy group to the 6-endo carbon center, forming 7-oxanorbornanone
248 in 71 % yield (considering the recovery of unreacted (+)-170). Protection of
exo-alcohol 248 as a MOM ether and then treatment with MeOH/DBU liberates the
chiral auxiliary (camphanic acid) and an endo-alcohol that is also protected as a
MOM ether. This provides 249 that undergoes Baeyer–Villiger oxidation into
uronolactone 250 as single product. The lithium enolate of 250 (does not undergo
oxa bridge opening at low temperature) adds to enone (À)-247 giving a single
Michael adduct 252 after acidic work-up. Steric factor controls the exo face
selectivity for both the Michael reaction of the uronolactone enolate and the
proton quenching of intermediate oxanorbornanone enolate 251. Reduction of
ketone 252 is also exo face selective. Oxidative removal of the benzeneselenyl
group uses mCPBA and generates the corresponding chloroalkene. Protection
of the endo-alcohol as a MOM ether furnishes 253. BnOLi adds to the lactone
moiety of 253, giving a mixture of furanoses that are silylated. The uronic ester 254
so-obtained is then dihydroxylated on its chloroalkene moiety providing
7-oxanorbornanone 255 after acetylation. Baeyer–Villiger oxidation of 255 leads
to 256. Debenzylation of the uronic ester 256 gives a carboxylic acid that undergoes
in situ Curtius rearrangement. This gives an intermediate isocyanate which reacts
with benzyl alcohol to provide benzyl carbamate 257. After desilylation of 257 and
hydrogenolysis of the benzyl carbamate, the intermediate aminoaldose 258 is
formed. It equilibrates with imine 259 which is reduced into 260 under the conditions of the hydrogenolysis. Final alcohol deprotection into 261 and ester reduction
produces aza-C-disaccharide (À)-262. Enantiomer and stereoisomers of (À)-262
180
A.J. Moreno-Vargas and P. Vogel