Short synthetic route to benzaldehyde-functionalized idose and talose derivatives by acetoxonium ion rearrangements

Article abstract of DOI:10.1002/ejoc.201201648

Carbohydrate-carbohydrate interactions (CCI) are mediated by complexation of metal ions. Angyal postulated on the requirements for hydroxy group arrangement in pyranoses to account for metal-ion complexation. These requirements are particularly well fulfilled in α-ido- and α-talopyranosides, whose ring hydroxy groups have all axial and axial-equatorial-axial configurations, respectively. Surface plasmon resonance (SPR) and gold-nanoparticle techniques have proved to be powerful tools to investigate CCIs. Benzaldehyde-functionalized glycans can be used for attachment to both gold nanoparticles and SPR sensor surfaces. Therefore, benzaldehyde-equipped ido- and talopyranosides were synthesized by the almost forgotten Paulsen acetoxonium rearrangement. This approach provides peracetylated idose and talose in only two steps from common glucose and galactose precursors, respectively, in overall yields of up to 41 % and, therefore, avoids long and laborious procedures to obtain these rare carbohydrates. The derivatives are being used in ongoing CCI studies using SPR to test Angyal's postulate about the structural requirements for hydroxy group arrangements. Almost forgotten: The Paulsen acetoxonium rearrangement provides a facile and rapid access to rare carbohydrates. Through a cascade of antimony pentachloride induced acetoxonium rearrangements, ido- and talopyranose derivatives can be synthesized from simple glucose and galactose precursors in a one-pot procedure. Copyright

Full text of DOI:10.1002/ejoc.201201648

FULL PAPER
DOI: 10.1002/ejoc.201201648
Short Synthetic Route to Benzaldehyde-Functionalized Idose and Talose
Derivatives by Acetoxonium Ion Rearrangements
Sebastian Kopitzki[a][‡] and Joachim Thiem*[a]
Dedicated to Professor Hans Paulsen on the occasion of his 90th birthday
Keywords: Rearrangement / Carbohydrates / Metathesis / Idose / Talose / Monosaccharides
Carbohydrate–carbohydrate interactions (CCI) are mediated
by complexation of metal ions. Angyal postulated on the
requirements for hydroxy group arrangement in pyranoses to
account for metal-ion complexation. These requirements are
particularly well fulfilled in α-ido- and α-talopyranosides,
whose ring hydroxy groups have all axial and axial-equato-
rial-axial configurations, respectively. Surface plasmon reso-
nance (SPR) and gold-nanoparticle techniques have proved
to be powerful tools to investigate CCIs. Benzaldehyde-func-
tionalized glycans can be used for attachment to both gold
nanoparticles and SPR sensor surfaces. Therefore, benzalde-
hyde-equipped ido- and talopyranosides were synthesized
by the almost forgotten Paulsen acetoxonium rearrangement.
This approach provides peracetylated idose and talose in
only two steps from common glucose and galactose precur-
sors, respectively, in overall yields of up to 41% and, there-
fore, avoids long and laborious procedures to obtain these
rare carbohydrates. The derivatives are being used in ongo-
ing CCI studies using SPR to test Angyal’s postulate about
the structural requirements for hydroxy group arrangements.
activity relationship study, the catalytic role of an Mn2+ ion
galactose complex was elucidated for a β-galactosidase.[12]
Furthermore, all currently known homo- and hetero-type
CCIs are Ca2+-dependent.[13–15] The trisaccharide Lex
{Galβ(1–4)[Fucα(1–3)]GlcNAc} recognizes itself (homo
type), and GM3 [Neu5Acα(2–3)Galβ(1–4)GlcNAc] inter-
acts with GG3 [GalNAcβ(1–4)Galβ(1–4)Glc, hetero type]
only in the presence of calcium ions. Interactions of calcium
ions with carbohydrates have been invoked in many other
biological processes such as calcium transport,[16] calcifi-
cation,[17] cell–cell adhesion, and the binding of glycopro-
teins to cell surfaces.[18,19] Although many carbohydrate–
metal complexes have been synthesized and characterized
in recent decades, little is known about either the factors
involved in calcium–carbohydrate interactions in biological
systems, or the stereochemistry of the resultant com-
plexes.[20] In the early 1970s, Angyal proposed configura-
tional requirements of the hydroxy groups in carbohydrates
for metal-ion complexation, based on NMR studies.[21–23]
The arrangement of the hydroxy groups in pyranoses
should be either axial-equatorial-axial (ax-eq-ax) or all
axial (all-ax). This leads to a distance of about 295 pm be-
tween three oxygen atoms (Tal: O-2,3,4 or Ido: O-2,4 and
O-5 or O-6), which allows the complexation of metal ions
with radii between 80 and 100 pm (Ca2+ has a radius of ca.
100 pm). These requirements are fulfilled for α-d-talo (ax-
eq-ax) (1) or α-d-ido (all-ax) (2) configured pyranosides, if
the 6-hydroxy groups or the ring oxygen atoms are involved
in the complexation (Scheme 1).
Introduction
All eukaryotic cell surfaces are surrounded by the so-
called “glycocalyx”, a complex layer composed of glycopro-
teins, glycolipids, complex oligosaccharides, proteoglycans,
and other glycoconjugates.[1] Molecular interactions of
these glycoconjugates play a crucial role in many different
cellular processes, including bacterial and viral infection,
cancer metastasis, modulation and activation of the im-
mune system, tissue differentiation and development, and
many other intercellular recognition events.[2–4] Carbo-
hydrate-associated cellular recognition events can be classi-
fied into carbohydrate–protein interactions (CPI), especially
between sugars and lectins[5] such as the selectins,[6] and
carbohydrate–carbohydrate interactions (CCI).[7]
In many cases, the basic mechanism of carbohydrate re-
cognition is associated with metal-ion complexation.[8,9]
Many CPIs occur only in the presence of metal ions. For
example, the lectin concanavalin A requires Mn2+ and Ca2+
ions for its mannose-binding activity.[10,11] In a structure–
[a] Department of Chemistry, Faculty of Sciences, University of
Hamburg,
Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
Fax: +49-40-42383-4325
E-mail: thiem@chemie.uni-hamburg.de
Homepage: http://www.chemie.uni-hamburg.de/oc/thiem/
[‡] Current address: Biofunctional Nanomaterials
CICbiomaGUNE,
Paseo Miramón 182, 20009 San Sebastian, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201648.
4008
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4008–4016

Idose and Talose Derivatives by Acetoxonium Ion Rearrangements
Scheme 1. Benzaldehyde-functionalized d-idose and d-talose derivatives 1 and 2 for assembly on gold surfaces and nanoparticles to
investigate Ca2+-dependent recognition.
Recently, we reported the immobilization of benzalde- synthesis and the use of expensive precursors, the almost
hyde-functionalized glycosides onto amino-SAMs (SAM = forgotten Paulsen acetoxonium rearrangement can be use-
self-assembled monolayer) on surface plasmon resonance ful.
sensors by reduction after imine formation in an overall re-
In 1967, Paulsen et al. found that on treatment of penta-
ductive amination process.[24] Combined with SAM forma- O-acetyl-β-d-glucopyranose (3) with antimony pentachlor-
tion on gold nanoparticles,[25] this approach allows a de- ide in anhydrous dichloromethane, an insoluble salt was
tailed study of the basic mechanisms of Ca2+-dependent formed. This salt was identified as 4,6-O-acetoxonium-
carbohydrate–carbohydrate recognition, in which the com- 1,2,3-tri-O-acetyl-α-d-idopyranosyl
plexation of metal ions, the subject of Angyal’s postulate, antimonate (4).[30] These findings could be used to synthe-
plays a crucial role. size allyl idopyranoside in only six steps from cheap β-
In this paper, a rapid synthesis of benzaldehyde-function- pentaacetylglucopyranose 3 (Scheme 2).
acetoxopentachloro-
alized idose and talose derivatives 1 and 2 by Paulsen’s acet-
Pentaacetate 3 was treated with antimony pentachloride
oxonium rearrangement, and subsequent olefin metathesis in anhydrous dichloromethane at –10 °C to give, after a few
of the corresponding allyl glycopyranosides is presented. By minutes, a white precipitate. After an additional reaction
using the aldehyde functionality, it should be possible to time of 1 h, salt 4 was isolated by filtration in 51% yield
attach the talo- and idopyranosides to amine-functionalized (Scheme 2). In the first step of this rearrangement, the ad-
gold nanoparticles as well as surface plasmon resonance dition of the Lewis acid SbCl5 to the carbonyl oxygen atom
sensors for studies of CCI by SPR to be performed of the anomeric acetate group occurs. This is followed by
(Scheme 1).
nucleophilic attack of the 2-O-acetate group onto the an-
omeric carbon atom (in 3A), resulting in the formation of
acetoxonium
acetylpentachlorideantimony
salt
3B
Results and Discussion
(Scheme 3), which is attacked by the 3-O-acetate group (in
Of the eight d-hexoses, only three occur abundantly in 3C), resulting in inversion of configuration at C-2. Newly
nature: d-glucose, its 2-epimer, d-mannose, and its 4-epi- formed mannose-2,3-acetoxonium ion 3D then continues
mer, d-galactose. Therefore, all the other hexoses are syn- through a cascade of inversive rearrangements via altrose-
thesized from these precursors in multistep approaches. For 3,4-acetoxonium ion 3E until ido-4,6-acetoxonium salt 4
example, the series of l-hexoses (also possible for the d- precipitates from the solution. NMR studies in [D3]-
enantiomers) could be derived from glyceraldehyde or (Z)- nitromethane at –25 °C revealed the equilibrium of the in-
2-buten-1,4-diol by a sequence of Pummerer rearrange- termediates, but the reaction is driven towards the forma-
ment, oxidation, and asymmetric epoxidation.[26,27] Due to tion of salt 4 by its precipitation from solution.[30]
the significant importance of l-idose/l-iduronic acid deriva-
After hydrolysis of salt 4 with aqueous sodium acetate
tives in the assembly of heparin/heparan sulfates and other solution for 20 min and subsequent reacetylation of the free
glycosaminoglycans, numerous syntheses of these carbo- hydroxy groups with acetic anhydride in pyridine, α-penta-
hydrates starting from d-glucose have been described.[28,29] O-acetyl idopyranose
5 was obtained in 80% yield
If these procedures would be used for the synthesis of d- (Scheme 2). Thus, the Paulsen procedure led to d-idose de-
idose, however, it would be necessary to use the expensive l- rivative 5 in only two steps from a cheap precursor in a
glucose as a precursor. To circumvent a laborious multistep good overall yield of 41%. Recently, Ling et al. published
Eur. J. Org. Chem. 2013, 4008–4016
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4009

S. Kopitzki, J. Thiem
FULL PAPER
Scheme 2. Synthesis of peracetylated allyl α-d-idopyranoside 7. Reagents and conditions: (a) SbCl5, CH2Cl2, –10 °C to room temp., 1 h,
51%; (b) NaOAc, H2O, room temp., 20 min; (c) Ac2O, py., room temp., 16 h, 80% over 2 steps; (d) (i) BnNH2, CH2Cl2, room temp., 25 h,
80%; (ii) CCl3CN, DBU, CH2Cl2, 0 °C, 1 h, 65%; (e) allyl alcohol, molecular sieves (4 Å), TMSOTf (TMS = trimethylsilyl), CH2Cl2,
–20 °C to room temp., 4 h, 92%.
Scheme 3. Proposed mechanism of the Paulsen acetoxonium ion rearrangement of β-pentaacetyl-d-glucpyranose 3 and galactopyranose
9 to give α-d-idopyranose acetoxonium salt 4 and α-d-talopyranose acetoxonium salt 10, respectively.
a three-step synthesis of orthogonally protected methyl β- (J) of about 9 Hz. After the Paulsen rearrangement, the
d-idopyranosides starting from methyl β-d-galactopyran- configuration of the ring protons was changed to all-eq,
oside in overall yields of about 45%.[31,32] However, this which led to coupling constants of about 2–3 Hz. The low
procedure includes several time-consuming purification spectral resolution, resulting in pseudo-singlets, is some-
steps and uses expensive and toxic reagents. This makes the times also typical for idose derivatives.
Paulsen approach more suitable. Next, the anomeric acetate
In a subsequent study, Paulsen et al. showed that also
group was removed with benzylamine prior to formation of β-acetochloroglucose and β-acetochlorogalactose could be
idopyranosyl trichloroacetimidate 6 with DBU (1,8-diazabi- subjected to this rearrangement reaction with SbCl5.[33]
cyclo[5.4.0]undec-7-ene) and trichloroacetonitrile. Glycosyl- From β-acetochlorogalactose or β-pentaacetylgalactose 8
ation of allyl alcohol with idopyranosyl trichloroacetimid- the talose-2,3-acetoxonium salt could be formed under suit-
ate 6 led to allyl idopyranoside 7 with a yield of 48% over able conditions, with β-acetochlorogalactose giving slightly
three steps (Scheme 2). The configuration of the idose de- better results. Therefore, penta-O-acetyl-β-d-galactopyr-
rivatives was confirmed by analysis of the 1H NMR spectra anose (8) was transformed in situ with aluminium tri-
of starting material 3 and product 5 (Figure 1A; see also the chloride into β-acetochlorogalactose. Without further puri-
Supporting Information). The all-ax arrangement of ring fication and characterization, the β-acetochlorogalactose
protons 2-H, 3-H, and 4-H gives rise to coupling constants was treated with SbCl5 in CCl4 at 50 °C (Scheme 4). After
4010
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4008–4016

Idose and Talose Derivatives by Acetoxonium Ion Rearrangements
Figure 1. Expanded NMR spectra before and after the Paulsen rearrangement.
a short time, salt 9 precipitated. The attack of the acetyl istic of the talose configuration. The overall yield of 11%
group in intermediate 8C onto the acetoxonium ion can (compared to 27% reported by Paulsen et al.) for com-
only take place when the vicinal acetoxy groups have a trans pound 10 seems to be disappointing in comparison with
relative orientation (Scheme 3). Therefore, opening of the recently published procedures, where 2-O- and 3-O-triflates
dioxolanylium ring in intermediate 8D by neighboring- of methyl β-d-galactopyranosides reacted under Lattrell–
group participation of the acetoxy group at C-4 is not pos- Dax conditions with toxic nitrite salts to yield β-taloside
sible. A rearrangement cascade as observed for glucose is derivatives in four steps and up to 58% overall yield. In
blocked at the stage of talose-2,3-acetoxonium salt 9. In those studies, the corresponding methyl α-d-galactopyran-
solution, a temperature-dependent equilibrium between tal- oside did not react.[34,35] Therefore, the Paulsen method is
ose-2,3-acetoxonium salt 9 and galactose-1,2-acetoxonium more suitable, because it leads to the desired α-configured
salt exists. Therefore, in addition to penta-O-acetyl-α-d-ga- talose anomer. Glycosyl donor 11 could be isolated in 64%
lactopyranose, penta-O-acetyl-α-d-talopyranose (10) was yield over two steps after hemiacetal formation with benz-
isolated in 21% yield after hydrolysis of salt 9 and reacetyl- ylamine followed by treatment with trichloroacetonitrile
ation (Scheme 4). Evidence for the talose configuration of and a catalytic amount of DBU at 0 °C for 1 h. Finally,
1
the rearrangement product came from its H NMR spectra glycosylation of allyl alcohol with talopyranosyl trichloro-
(Figure 1B; see also the Supporting Information). A signifi- acetimidate 11 led to allyl talopyranoside 12 in 70% yield
cant change in signal shift and multiplicity was observed over three steps (Scheme 4).
for the ring protons 2-H, 3-H, and 4-H. For example, the
Application of a previously established procedure real-
3-H appeared as doublet of doublets with similar J values ized the benzaldehyde functionalization of allyl glycopyr-
(ca. 3.8 Hz; in contrast to the values of 3.4 and 10.4 Hz anosides 7 and 12 by olefin cross metathesis with para-all-
from the starting material). After Paulsen rearrangement, yloxybenzaldehyde dimethyl acetal and Grubbs–Hoveyda
the signal of 2-H appears as a ddd, with J values between 2nd generation catalyst.[24] After reaction in anhydrous
1.1 and 3.9 Hz. The 4J2,4 W coupling of 1.1 Hz is character- dichloromethane at 40 °C for 6 h, butenyl derivatives 13 and
Eur. J. Org. Chem. 2013, 4008–4016
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4011

S. Kopitzki, J. Thiem
FULL PAPER
Scheme 4. Synthesis of peracetylated allyl α-d-talopyranoside 12. Reagents and conditions: (a) (i) AlCl3, CH2Cl2, room temp., 2 h;
(ii) SbCl5, CCl4, 50 °C, 15 min, 54% over 2 steps; (b) NaOAc, H2O, room temp., 20 min; (c) Ac2O, pyridine, room temp., 16 h, 21% over
2 steps; (d) (i) BnNH2, CH2Cl2, room temp., 25 h, 82%; (ii) CCl3CN, DBU, CH2Cl2, 0 °C, 1 h, 78%; (e) allyl alcohol, molecular sieves
(4 Å), TMSOTf, CH2Cl2, –20 °C to room temp., 4 h, 70%.
Scheme 5. Synthesis of benzaldehyde-functionalized d-idose and d-talose derivatives 1 and 2 by olefin metathesis. Reagents and condi-
tions: (a) para-allyloxybenzaldehyde dimethyl acetal, Grubbs–Hoveyda 2nd generation catalyst, CH2Cl2, 40 °C, 6 h, 13: 66%, 14: 82%;
(b) (i) THF, TFA (trifluoroacetic acid), H2O, room temp., 1 h; (ii) Pd/C, H2, diphenyl sulfite, EtOAc, room temp., 12 h; (iii) NaOMe,
MeOH, room temp., 6 h, yields over 3 steps, 1: 84%, 2: 79%.
14 were obtained in 66 and 82% yields, respectively
Conclusions
(Scheme 5). Their NMR spectra showed that only the (E)
The rearrangement of peracetates of glucose and galact-
configuration was present for the butenyl moiety. The
ose induced by treatment of antimony pentachloride pro-
carbohydrate derivatives required for surface plasmon reso-
vides a rapid and facile access to the rare carbohydrates
nance studies (i.e., 1 and 2) were obtained by deacetaliza-
idose and talose. Combined with an olefin cross-metathesis
tion of the benzaldehyde dimethyl acetal group, followed by
approach, benzaldehyde-functionalized ido- and talopyr-
hydrogenolysis catalyzed by palladium on charcoal poi-
anosides 1 and 2 were accessible in a few steps. These deriv-
soned with diphenyl sulfite, and subsequent classical
Zemplén deprotection. Thus, the desired target products
atives will be attached to amine-functionalized gold nano-
particles and SPR sensor surfaces, and used in Ca2+-de-
were obtained, purified by column chromatography, and
pendent CCI studies to test Angyal’s postulate about the
characterized by NMR spectroscopy and high-resolution
stereochemical requirements for sugar hydroxy groups in-
volved in metal-ion complexation.
mass spectrometry. To remove the dimethyl acetal, the teth-
ered carbohydrate derivatives were dissolved in aqueous
THF containing 0.1% trifluoroacetic acid.[36] After stirring
for 1 h, the reaction was stopped by dilution with CH2Cl2
and addition of triethylamine, then the mixture was concen-
Experimental Section
trated. To convert the double bond into an alkane motif,
the Pd catalyst was poisoned with diphenyl sulfite, and dry
ethyl acetate was used as solvent. Otherwise, the benzalde-
hyde functionality could be transformed into an undesired
General Remarks: Reagents of commercial quality were purchased
from Aldrich, Sigma, or Merck, and were used without further
purification. Solvents were dried by standard methods. All reac-
methylene group.[37] After filtration and concentration, the tions were carried out under argon with dry solvents under anhy-
drous conditions, unless otherwise noted. Analytical thin-layer
chromatography (TLC) was performed on pre-coated aluminium
plates (Silica Gel 60 F254, Merck 5554), compound spots were vis-
ualized by UV light (254 nm) and by staining with a yellow solution
containing Ce(NH4)2(NO3)6 (0.5 g) and (NH4)6Mo7O24·4 H2O
(24.0 g) in H2SO4 (6%; 500 mL) or with H2SO4 (10% in ethanol)
followed by heat treatment. For column chromatography, Silica Gel
60, 230–400 mesh, 40–63 μm (Merck), was used. 1H and 13C NMR
spectra were recorded with Bruker AMX-400 (400 MHz for 1H,
100.6 MHz for 13C) or Bruker DRX-500 (500 MHz for 1H,
125.8 MHz for 13C) spectrometers at 300 K. Chemical shifts were
acetyl groups were removed by addition of methanolic so-
dium methoxide solution (0.1 m) under Zemplén condi-
tions.[38] Subsequent treatment with Amberlite IR 120 (H+)
and evaporation of the solvents gave syrupy residues. Re-
moval of salts and further purification followed by lyophili-
zation concluded this easy and rapidly worked-up protocol,
and target compounds 1 and 2 were isolated in 84 and 79%
yields, respectively, over the three-step deprotection pro-
cedure, or 55 and 65% yields including the cross-metathesis
step (Scheme 5).
4012
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4008–4016

Idose and Talose Derivatives by Acetoxonium Ion Rearrangements
1
calibrated to solvent residual peaks (CDCl3: δ = 7.24 ppm for H
74.0 (C-5), 72.7 (C-3), 72.1 (C-2), 70.7 (C-4), 68.7 (C-1bu), 68.3 (C-
4bu), 63.5 (C-6), 27.1 (C-3bu), 26.5 (C-2bu) ppm. HRMS (ESI):
calcd. for C17H25O8 [M + H]+ 357.1544; found 357.1677.
1
and δ = 77.0 ppm for 13C; [D4]methanol: δ = 3.35 ppm for H and
δ = 49.30 ppm for 13C). Signals were assigned by using 1H–1H-
COSY, HSQC, HMBC, and, if necessary, NOESY experiments.
Hydrogen and carbon atoms are indexed as follows: The sugar resi-
due is numbered as usual from 1 to 6 with the anomeric position
being number 1, the atoms of the anomeric spacer moiety then
receives numbers with index “bu” for butyl and “ar” for aromatic
by consecutive numbering starting from the glycosidic bond. For
4,6-O-Acetoxonium-1,2,3-tri-O-acetyl-α-D-idopyranose Acetoxopen-
tachloroantimonate (4): Under argon, 1,2,3,4,6-penta-O-acetyl-β-d-
glucopyranose (3; 20.0 g, 51.5 mmol) was dissolved in anhydrous
dichloromethane (120 mL). This solution was stirred and cooled to
–10 °C, and then a solution of antimony pentachloride (8.40 mL,
66.7 mmol) in anhydrous dichloromethane (20 mL) was added. The
reaction mixture was warmed to room temperature. After ad-
ditional stirring at room temperature for 30 min, the resulting sus-
pension was filtered. The residue was washed with anhydrous
dichloromethane (60 mL) and anhydrous diethyl ether (160 mL).
Product 4 (18.1 g, 51%) was obtained as a colorless solid. M.p.
87 °C (ref.[30] 90 °C, decomposition).
1
idose derivatives, signals in the H NMR spectra tended to be less
resolved. In these cases, coupling constants were measured from
shoulder to peak center, and this is indicated in the peak notation
by “p” for “pseudo”. Optical rotations were measured by using a
Krüss Optronic P8000 (589 nm) instrument at 20 °C. MALDI-
TOF-MS was performed with a BrukerBiflex III instrument with
dihydroxybenzoic acid or trihydroxyanthracene as matrices in posi-
tive-reflector mode. FAB-HRMS was performed with a Thermo
Finnigan MAT95 XL mass spectrometer.
1,2,3,4,6-Penta-O-acetyl-α-D-idopyranose (5): Compound 4 (18.1 g,
26.2 mmol) was added to a solution of sodium acetate (30.9 g,
377 mmol) in water (160 mL). This mixture was stirred at room
temperature for 20 min. The aqueous phase was extracted with
dichloromethane (3ϫ 100 mL). The combined organic extracts
were dried with sodium sulfate and concentrated under reduced
pressure. The crude residue (7.69 g) was dissolved in anhydrous
pyridine (50 mL) and cooled to 0 °C. Acetic anhydride (150 mL,
1.59 mol) was added to this solution. After warming to room tem-
perature, the mixture was stirred for 16 h. The solvent was removed
under reduced pressure, and the residue was redissolved in di-
chloromethane (200 mL). The organic phase was washed with HCl
(1 m; 3ϫ 150 mL) and brine (150 mL), dried with sodium sulfate,
and concentrated. The residue was coevaporated with toluene (3ϫ
100 mL) to give compound 5 (8.10 g, 80%) as a colorless solid. Rf
= 0.53 (petroleum ether/EtOAc, 1:2). m.p. 92 °C (ref.[30] 94–95 °C).
[α]2D0 = +69.7 (c = 1 in CHCl3). 1H NMR (400 MHz, CDCl3,
4-(4-Formylphenoxy)butyl α-D-Idopyranoside (1): Compound 13
(200 mg, 352 μmol) was dissolved in a mixture of THF, water, and
TFA (90:9.9:0.1, v/v) to obtain a 0.2 m solution. After stirring for
1 h, the reaction mixture was diluted with CH2Cl2 (20 mL), and
the reaction was stopped by the addition of triethylamine (2 mL),
followed by addition of water (20 mL). The organic phase was sep-
arated and dried with Na2SO4. The solvent was removed under
reduced pressure, and the crude product was used in the next trans-
formation without further purification. For hydrogenolysis, the al-
dehyde was dissolved in anhydrous EtOAc (10 mL) and placed into
a flame-dried flask containing palladium (10% on charcoal) and
diphenyl sulfite (0.01 equiv.). The suspension was degassed, and
after purging with hydrogen, the mixture was stirred for 12 h. Then
the suspension was filtered and thoroughly dried before the residue
was redissolved in methanolic sodium methoxide solution (20 mL,
0.1 m). The solution was stirred at room temperature for 6 h, and
then the mixture was neutralized with Amberite IR 120 (H+) resin.
After filtration and evaporation of the solvent, the crude product
was purified by flash chromatography using silica and dichloro-
methane/methanol (5:1) to give the title compound (105 mg, 84%)
as a colorless syrup. Rf = 0.39 (CH2Cl2/MeOH, 5:1). [α]2D0 = –22.8
3
3
25 °C): δ = 6.06 (ps, J1,2 = 1.3 Hz, 1 H, 1-H), 5.07 (ps, J2,3 = 3.8,
3
3
3J3,4 = 3.8 Hz, 1 H, 3-H), 4.93 (ps, J4,5 = 2.2, J3,4 = 3.8 Hz, 1 H,
3
3
4-H), 4.88 (ps, J1,2 = 1.3 Hz, J2,3 = 3.8 Hz, 1 H, 2-H), 4.47 (ddd,
3J4,5 = 2.2 Hz, 3J5,6b = 6.0 Hz, 3J5,6a = 6.9 Hz, 1 H, 5-H), 4.23 –4.16
(m, 2 H, 6ab-H), 2.12–2.06 (m, 15 H, 5 Ac-H) ppm. 13C NMR
(400 MHz, CDCl3, 25 °C): δ = 170.6, 169.8, 169.2, 168.9, 168.6
(5ϫ CH3CO), 90.8 (C-1), 66.9 (C-3), 66.5 (C-2), 66.4 (C-4), 66.3
(C-5), 61.9 (C-6), 20.9–20.8 (5 CH3CO) ppm.
1
(c = 1.0 in MeOH). H NMR (500 MHz, [D4]methanol, 25 °C): δ
= 9.81 (s, 1 H, ald-H), 7.83 (d, 3JAr = 8.8 Hz, 1 H, 1arom-H), 7.05 (d,
3JAr = 8.8 Hz, 1 H, 2arom-H), 4.45 (ps, 1 H, 1-H), 4.12 (t, 3J3bu,4bu
=
=
2,3,4,6-Tetra-O-acetyl-α-D-idopyranosyl Trichoroacetimidate (6):
3
6.4 Hz, 2 H, 4bu-H), 4.02–3.93 (m, 1 H, 1abu-H), 3.79 (dd, J4,5
Benzylamine (1.26 mL, 11.6 mmol) was added to a solution of
pentaacetate 5 (3.00 g, 7.68 mmol) in anhydrous THF (20 mL). The
mixture was stirred at room temperature for 25 h. The reaction was
quenched by the addition of HCl (1 m; 100 mL), and the resulting
mixture was stirred for 10 min. The solution was diluted with
dichloromethane (150 mL), and the aqueous phase was extracted
with dichloromethane (2ϫ 100 mL). The combined organic ex-
tracts were dried with sodium sulfate and concentrated under re-
duced pressure. Purification by column chromatography using silica
and a petroleum ether/ethyl acetate gradient (2:1 Ǟ 1:1) gave
2,3,4,6-tetra-O-acetyl-d-idopyranose (2.14 g, 80%; α/β mixture,
1:1.1) as a colorless solid. Rf = 0.24 (petroleum ether/EtOAc, 1:1).
α: 1H NMR (400 MHz, CDCl3, 25 °C):[39] δ = 5.25 (dd, 3J2,3 = 3.8,
3
0.8, J3,4 = 1.1 Hz, 1 H, 4-H), 3.74–3.70 (m, 2 H, 6ab-H), 3.62–
3.57 (m, 2 H, 2-H, 1bbu-H), 3.53–3.42 (m, 3 H, 3-H, 5-H), 1.95–
1.86 (m, 2 H, 3bu-H), 1.82–1.74 (m, 2 H, 2bu-H) ppm. 13C NMR
(126 MHz, [D4]methanol, 25 °C): δ = 193.1 (Cald), 133.1 (Carom),
116.2 (Carom), 100.0 (C-1), 78.6 (C-4), 75.0 (C-5), 71.3 (C-3), 70.5
(C-2), 70.1 (C-1bu), 69.1 (C-4bu), 63.5 (C-6), 27.9 (C-3bu), 26.9 (C-
2bu) ppm. HRMS (ESI): calcd. for C17H25O8 [M + H]+ 357.1544;
found 357.2149.
4-(4-Formylphenoxy)butyl α-D-Talopyranoside (2): As for the syn-
thesis of compound 1, benzaldehyde-functionalized glycoside 14
(200 mg, 352 μmol) was treated to obtain title compound 2 (99 mg,
79%) as a colorless syrup. Rf = 0.40 (CH2Cl2/MeOH, 5:1). [α]2D0
=
3
3
–23.4 (c = 1.2 in MeOH). 1H NMR (500 MHz, [D4]methanol,
3J3,4 = 3.8 Hz, 0.9 H, 3-H), 5.15 (dd, J1,2 = 1.2, J1,OH = 8.5 Hz,
3
3
3
3
25 °C): δ = 9.80 (s, 1 H, ald-H), 7.84 (d, JAr = 8.7 Hz, 1 H, 1arom
-
0.9 H, 1-H), 4.86 (ddd, J4,5 = 1.6, J5,6a = 3.5, J5,6b = 4.4 Hz, 0.9
H), 7.10 (d, JAr = 8.7 Hz, 1 H, 2arom-H), 4.77 (d, J1,2 = 1.1 Hz, H, 5-H), 4.85 (dd, J1,2 = 1.2, 3J2,3 = 3.8 Hz, 0.9 H, 2-H), 4.27 (dd,
3
3
3
1 H, 1-H), 4.13 (t, J3bu,4bu = 6.7 Hz, 2 H, 4bu-H), 3.93–3.65 (m, 4 2J6a,6b = 10.7, J5,6a = 3.5 Hz, 0.9 H, 6a-H), 4.26 (dd, J4,5 = 1.6,
3
3
3
3
3
H, 6ab-H, 1bu-H), 3.60 (dd, J4,5 = 0.9, J3,4 = 3.6 Hz, 1 H, 4-H),
3J3,4 = 3.8 Hz, 0.9 H, 4-H), 4.21 (dd, 2J6a,6b = 10.7, 3J5,6b = 4.4 Hz,
3
3.55–3.46 (m, 3 H, 2-H, 3-H, 5-H), 1.90–1.84 (m, 2 H, 3bu-H), 1.82–
0.9 H, 6a-H), 3.50 (d, J1,OH = 8.5 Hz, 1 H, OH), 2.16–2.07 (m,
1.76 (m, 2 H, 2bu-H) ppm. 13C NMR (126 MHz, [D4]methanol, 10.8 H, 4 Ac-H) ppm. β: H NMR (400 MHz, CDCl3, 25 °C) δ =
1
3
3
3
25 °C): δ = 192.9 (Cald), 129.0 (Carom), 115.1 (Carom), 101.1 (C-1),
5.21 (dd, J1,2 = 2.5, J1,OH = 5.6 Hz, 1 H, 1-H), 5.12 (dd, J2,3
=
Eur. J. Org. Chem. 2013, 4008–4016
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4013

S. Kopitzki, J. Thiem
FULL PAPER
3
3
3
4.4, J3,4 = 4.4 Hz, 1 H, 3-H), 4.96 (dd, J4,5 = 2.2, J3,4 = 4.4 Hz, washed with ice-cold water (3ϫ 200 mL). The organic phase was
3
3
1 H, 4-H), 4.85 (dd, J1,2 = 2.5, J2,3 = 4.4 Hz, 1 H, 2-H), 4.59
dried with sodium sulfate and concentrated under reduced pres-
sure. The crude product was recrystallized from diethyl ether to
3
3
3
(ddd, J4,5 = 2.2, J5,6b = 3.5, J5,6a = 6.9 Hz, 1 H, 5-H), 4.26 (dd,
2J6a,6b = 11.7, J5,6a = 6.9 Hz, 1 H, 6a-H), 4.20 (dd, J5,6b = 11.7, give the β-galactopyranosyl chloride (6.73 g, 60%) as colorless
3
2
3J5,6b = 3.5 Hz, 1 H, 6b-H), 3.05(d, J1,OH = 5.6 Hz, 1 H, OH), crystals. Rf = 0.18 (petroleum ether/EtOAc, 1:1). M.p. 94 °C (ref.[30]
3
2.16–2.07 (m, 12 H, 4 Ac-H) ppm. α: 13C NMR (100.6 MHz,
93–94.5 °C). [α]2D0 = +59.6 (c = 1.0 in CHCl3). 1H NMR (400 MHz,
3
3
CDCl3, 25 °C) δ = 170.6, 170.4, 169.9, 169.6 (4 CH3CO), 91.8 (C- CDCl3, 25 °C): δ = 5.41 (dd, J3,4 = 3.4, J4,5 = 2.2 Hz, 1 H, 4-H),
3
3
3
1), 71.5 (C-2), 68.0 (C-3), 67.1 (C-4), 65.6 (C-5), 62.5 (C-6), 20.8–
5.36 (dd, J1,2 = 8.8, J2,3 = 10.1 Hz, 1 H, 2-H), 5.24 (d, J1,2 =
20.6 (4 CH3CO) ppm. β: 13C NMR (100.6 MHz, CDCl3, 25 °C) δ
8.8 Hz, 1 H, 1-H), 4.99 (dd, 3J3,4 = 3.4, J2,3 = 10.1 Hz, 1 H, 3-H),
3
3
3
3
= 170.6, 170.4, 169.9, 169.6 (4 CH3CO), 92.5 (C-1), 68.3 (C-3), 67.4 4.16 (dd, J4,5 = 2.2, J5,6a = 6.0, J5,6b = 6.9 Hz, 1 H, 5-H), 4.16–
(C-4), 67.0 (C-5), 65.1 (C-2), 62.2 (C-6), 20.8–20.6 (4 CH3CO) ppm.
2,3,4,6-Tetra-O-acetyl-d-idopyranose (2.10 g, 6.02 mmol) and tri-
chloroacetonitrile (18.2 mL, 181 mmol) were dissolved in anhy-
4.12 (m, 2 H, 6a-H, 6b-H), 2.16, 2.07, 2.04, 1.97 (s, 12 H, 4 Ac-H)
ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 170.4, 170.1, 169.9,
169.2 (4 CH3CO), 88.2 (C-1), 74.6 (C-3), 70.9 (C-2), 70.7 (C-4),
drous dichloromethane (120 mL) with activated molecular sieves. 66.8 (C-5), 61.3 (C-6), 20.7–20.5 (4 CH3CO) ppm. Under argon,
After stirring for 30 min, the solution was cooled to 0 °C, and DBU
(537 μL, 3.59 mmol) was added. After 1 h, TLC (petroleum ether/
ethyl acetate, 2:1) indicated complete conversion of the starting ma-
terial. The mixture was concentrated under reduced pressure. Puri-
fication by column chromatography on silica (petroleum ether
100% Ǟ hexane/ethyl acetate, 2:1) gave title compound 6 (1.93 g,
65%; only α) as a colorless solid. Rf = 0.57 (petroleum ether/
EtOAc, 2:1). [α]2D0 = +29.5 (c = 0.25 in CHCl3). 1H NMR
(500 MHz, CDCl3, 25 °C) δ = 8.74 (s, 1 H, imidate-H), 6.27 (ps,
2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl
chloride
(6.70 g,
18.3 mmol) was dissolved in CCl4 (180 mL) at 50 °C. A solution of
SbCl5 (2.33 mL, 22.6 mmol) in CCl4 (10 mL) was added dropwise
to the stirred mixture. The resulting suspension was stirred at room
temperature for an additional 15 min. The precipitate was filtered
and washed with CCl4. After drying under high vacuum, com-
pound 9 (11.4 g, 90%) was obtained as a colorless solid. M.p. 46 °C
(ref.[30] 50 °C, decomposition).
1,2,3,4,6-Penta-O-acetyl-α-D-talopyranose (10): As for the synthesis
3
3
3J1,2 = 1.3 Hz, 1 H, 1-H), 5.07 (ps, J3,4 = 2.2, J2,3 = 2.5 Hz, 1 H,
of compound 5, antimony salt 9 (11.3 g, 16.5 mmol) was treated to
obtain title compound 10 as a colorless solid (1.29 g, 20%). Rf =
0.48 (petroleum ether/EtOAc, 1:1). M.p. 103 °C (ref.[30] 104–
105 °C). [α]2D0 = +34.6 (c = 1.0 in CHCl3). 1H NMR (400 MHz,
3
3-H), 5.00 (dd, 3J1,2 = 1.3, J2,3 = 2.5 Hz, 1 H, 2-H), 4.92 (dd, 3J4,5
3
3
= 1.6, J3,4 = 2.2 Hz, 1 H, 4-H), 4.61 (ddd, 3J4,5 = 1.6, J5,6b = 3.8,
3J5,6a = 5.4 Hz, 1 H, 5-H), 4.24 (dd, J6a,6b = 11.7 Hz, J5,6a
=
2
3
2
3
5.4 Hz, 1 H, 6a-H), 4.16 (dd, J6a,6b = 11.7, J5,6b = 3.8 Hz, 1 H,
6b-H), 2.12–2.13 (m, 9 H, 3 Ac-H), 2.02 (s, 3 H, Ac-H) ppm. 13C
NMR (126 MHz, CDCl3, 25 °C): δ = 170.4, 169.9, 168.7, 168.6 (4
CH3CO), 93.9 (C-1), 66.3 (C-3), 65.8 (C-4), 65.6 (C-5), 65.3 (C-2),
62.1 (C-6), 20.8, 20.7, 20.6, 20.4 (4 CH3CO) ppm.
3
CDCl3, 25 °C): δ = 6.15 (d, J1,2 = 1.7 Hz, 1 H, 1-H), 5.37–5.34
3
3
(m, 1 H, 4-H), 5.31 (dd, J3,4 = 3.7 Hz, J2,3 = 3.9, 1 H, 3-H), 5.09
3
3
4
(ddd, J1,2 = 1.7, J2,3 = 3.7, J2,4 = 1.1 Hz, 1 H, 2-H), 4.31 (ddd,
3J4,5 = 1.4, J5,6a = J5,6b = 6.6 Hz, 1 H, 5-H), 4.18–4.13 (m, 2 H,
6a-H, 6b-H), 2.15, 2.14, 2.13, 2.03, 2.00 (s, 15 H, 5 Ac-H) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 170.1, 169.8, 169.4, 168.9,
167.8 (5 CH3CO), 91.3 (C-1), 68.7 (C-3), 66.3 (C-2), 65.2 (C-4),
64.4 (C-5), 61.4 (C-6), 20.5–20.3 (5 CH3CO) ppm.
3
3
Allyl 2,3,4,6-Tetra-O-acetyl-α-D-idopyranoside (7): Idose donor 6
(1.00 g, 2.03 mmol) and allyl alcohol (275 μL, 4.06 mmol) were dis-
solved in dry CH2Cl2 (30 mL) under argon and then cooled to
–20 °C. After the addition of trimethylsilyl triflate (36 μL,
200 μmol), the reaction mixture was warmed slowly to room tem-
perature; after 4 h, it was quenched with triethylamine. The mixture
was diluted with dichloromethane and washed with NaHCO3 (sat-
urated aq.), H2O, and brine. The mixture was concentrated, and
the residue was purified by column chromatography on silica (pe-
troleum ether 100% Ǟ hexane/ethyl acetate, 2:1) to give compound
7 (725 mg, 92%) as a colorless syrup. Rf = 0.49 (petroleum ether/
EtOAc, 2:1). [α]2D0 = +15.7 (c = 1.0 in CHCl3). 1H NMR (500 MHz,
CDCl3, 25 °C) δ = 5.86–5.83 (m, 1 H, 2all-H), 5.25–5.18 (m, 2 H,
3a,ball-H), 5.04 (dd, 3J3,4 = 2.2, 3J2,3 = 2.5 Hz, 1 H, 3-H), 4.98 (dd,
2,3,4,6-Tetra-O-acetyl-α-D-talopyranosyl Trichoroacetimidate (11):
As for the synthesis of compound 6, pentaacetate 10 (1.20 g,
3.07 mmol) was treated with benzylamine (1.25 mL, 11.6 mmol) in
anhydrous THF (20 mL) to obtain 2,3,4,6-tetra-O-acetyl-d-talo-
pyranose (883 mg, 78%) as a colorless syrup. The hemiacetal was
used in the next step without further characterization. As for the
synthesis of compound 6, 2,3,4,6-tetra-O-acetyl-d-talopyranose
(800 mg, 2.30 mmol) was treated with trichloroacetonirile
(6.06 mL, 60.3 mmol) and DBU (171 μL, 1.15 mmol) in anhydrous
dichloromethane (40 mL) to obtain title compound 11 as a color-
less syrup (883 mg, 78%). Rf = 0.52 (petroleum ether/EtOAc, 2:1).
[α]2D0 = +60.1 (c = 0.5 in CHCl3). 1H NMR (400 MHz, CDCl3,
3
3
3
3J1,2 = 1.5, J2,3 = 2.5 Hz, 1 H, 2-H), 4.92 (dd, J4,5 = 1.6, J3,4
=
3
2.2 Hz, 1 H, 4-H), 4.89 (d, J1,2 = 1.5 Hz, 1 H, 1-H), 4.57 (ddd,
3
3
3
3J4,5 = 1.6, J5,6b = 3.8, J5,6a = 5.4 Hz, 1 H, 5-H), 4.24 (dd, 2J6a,6b
25 °C): δ = 8.78 (s, 1 H, imidate-H), 6.30 (d, J1,2 = 2.1 Hz, 1 H,
1-H), 5.40 (pd, 3J3,4 = 3.7 Hz, 1 H, 4-H), 5.25 (dd, 3J2,3 = 3.7, 3J3,4
3
= 11.8 Hz, J5,6a = 5.4 Hz, 1 H, 6a-H), 4.20–4.15 (m, 2 H, 6b-H,
3
3
4
2
3
= 3.7 Hz, 1 H, 3-H), 5.20 (ddd, J1,2 = 2.1, J2,3 = 3.7, J2,4
=
1aall-H), 3.98 (dd, J1aall,1ball = 12.3, J1ball,2all = 4.4 Hz, 1 H, 1ball
-
3
3
H), 2.12–2.13 (m, 9 H, 3 Ac-H), 2.02 (s, 3 H, Ac-H) ppm. 13C
NMR (126 MHz, CDCl3, 25 °C): δ = 170.4, 169.9, 168.7, 168.6 (4
CH3CO), 132.5 (C-2all), 118.1 (C-3all), 98.5 (C-1), 67.7 (C-1all), 66.8
(C-3), 66.0 (C-4), 65.6 (C-5), 65.5 (C-2), 62.1 (C-6), 20.8, 20.7, 20.6,
20.4 (4 CH3CO) ppm. MS (MALDI-TOF): m/z = 411.7 [M +
Na]+.
1.1 Hz, 1 H, 2-H), 4.40 (dd, J5,6a = 5.9, J5,6b = 6.4 Hz, 1 H, 5-
H), 4.29–4.20 (m, 2 H, 6a-H, 6b-H), 2.15, 2.14, 2.13, 2.03, 2.00 (s,
15 H, 5 Ac-H) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
170.1, 169.8, 169.4, 167.8 (4 CH3CO), 95.2 (C-1), 70.3 (C-3), 68.4
(C-2), 66.2 (C-4), 65.1 (C-5), 63.1 (C-6), 20.5–20.3 (4 CH3CO) ppm.
Allyl 2,3,4,6-Tetra-O-acetyl-α-D-talopyranoside (12): As for the syn-
2,3-O-Acetoxonio-1,4,6-tri-O-acetyl-α-
D
-talopyranose Acetoxopen-
thesis of compound 8, talose donor 11 (800 mg, 1.62 mmol) was
treated with allyl alcohol (330 μL, 4.86 mmol) and trimethylsilyl
triflate (29.0 μL, 160 μmol) in anhydrous dichloromethane (10 mL)
to obtain title compound 12 (439 mg, 70%) as a colorless syrup. Rf
= 0.43 (petroleum ether/EtOAc, 2:1). [α]2D0 = +23.6 (c = 1.0 in
CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ = 5.86–5.83 (dddd,
tachloroantimonate (9): Under argon, 1,2,3,4,6-penta-O-acetyl-β-d-
galactopyranose (8; 12.0 g, 30.7 mmol) and aluminium trichloride
(2.60 g, 19.8 mmol) were dissolved in anhydrous dichloromethane
(150 mL). The mixture was stirred at room temperature for 2 h.
Then the solution was diluted with chloroform (120 mL) and
4014
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4008–4016

Idose and Talose Derivatives by Acetoxonium Ion Rearrangements
3
3J2all,3all-cis = 10.0, J2all,3all-trans = 17.2 Hz, 1 H, 2all-H), 5.23–5.19 101.9 (Caectal), 97.1 (C-1), 70.3 (C-3), 68.7 (C-4bu), 68.4 (C-2), 67.5
3
(m, 2 H, H-4, 3aall-H), 5.15 (dd, 3J2,3 = 3.5, J3,4 = 3.8 Hz, 1 H, 3-
(C-1bu), 65.9 (C-4), 65.2 (C-5), 63.0 (C-6), 52.0 (OCH3) 20.5–20.3
(4 CH3CO) ppm. HRMS (FAB): calcd. for C27H37O13 [M + H]+
569.2229; found 569.2185.
3
3
4
H), 4.96 (ddd, J1,2 = 1.5, J2,3 = 3.5, J2,4 = 1.1 Hz, 1 H, 2-H),
4.89 (d, J1,2 = 1.5 Hz, 1 H, 1-H), 4.25 (dd, J5,6a = 5.9, J5,6b
3
3
3
=
6.4 Hz, 1 H, 5-H), 4.20–4.11 (m, 3 H, 6a-H, 6b-H, 1aall-H), 3.94
Supporting Information (see footnote on the first page of this arti-
3
(dd, 2J1aall,1ball = 12.3, J1ball,2all = 4.4 Hz, 1 H, 1ball-H), 2.15, 2.14,
1
cle): Copies of H and 13C NMR spectra of key intermediates and
2.13, 2.03, 2.00 (s, 12 H, 4 Ac-H) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 170.1, 169.8, 169.4, 167.8 (4 CH3CO), 132.2
(C-2all), 117.2 (C-3all), 97.1 (C-1), 70.3 (C-3), 68.4 (C-2), 68.0 (C-
final compounds.
1
all), 65.9 (C-4), 65.1 (C-5), 62.8 (C-6), 20.5–20.3 (4 CH3CO) ppm.
MS (MALDI-TOF): m/z = 411.3 [M + Na]+.
Acknowledgments
(E)-4-[4-(Dimethoxymethyl)phenoxy]but-2-enyl
2,3,4,6-Tetra-O-
acetyl-α-D-idopyranoside (13): Allyl idopyranoside tetraacetate 7
Support of this work by the Deutsche Forschungsgemeinschaft
(SFB 470, A5) is gratefully acknowledged.
(300 mg, 775 μmol) and para-(allyloxy)benzaldehyde dimethyl
acetal (830 mg, 4.00 mmol) were disolved in dry and degassed
dichloromethane (35 mL) and placed into a flame-dried flask con-
taining activated molecular sieves (4 Å) by using standard Schlenk
techniques. Grubbs–Hoveyda 2nd generation catalyst (63 mg,
0.10 mmol), dissolved in dry and degassed dichloromethane
(1 mL), was added by syringe or as a solid to obtain a 0.02 m solu-
tion. The reaction mixture was heated under reflux for 6 h. Conver-
sion of the starting material was monitored by TLC. The solution
was concentrated under reduced pressure, and the crude product
was directly purified by column chromatography using silica and a
petroleum ether/ethyl acetate gradient (4:1 Ǟ 2:1) to give com-
pound 13 (291 mg, 66%) as a colorless syrup. Rf = 0.43 (petroleum
[1] S. Ito, Philos. Trans. B Biol. Sci. 1974, 268, 55–66.
[2] A. Varki, Glycobiology 1993, 3, 97–130.
[3] R. A. Dwek, Chem. Rev. 1996, 96, 683–720.
[4] K. Ohtsubo, J. D. Marth, Cell 2006, 126, 855–867.
[5] H. Lis, N. Sharon, Chem. Rev. 1998, 98, 637–674.
[6] E. E. Simanek, G. J. McGarvey, J. A. Jablonowski, C.-H.
Wong, Chem. Rev. 1998, 98, 833–862.
[7] S. Hakomori, Pure Appl. Chem. 1991, 63, 473–482.
[8] B. Gyurcsik, L. Nagy, Coord. Chem. Rev. 2000, 203, 81–149.
[9] T. Allscher, P. Klüfers, P. Mayer, in Glycoscience: Chemistry and
Chemical Biology, vol. 2, 2nd ed. (Eds.: B. O. Fraser-Reid, K.
Tatsuta, J. Thiem), Springer, Berlin, Heidelberg, New York,
2008, pp. 1077–1140.
ether/EtOAc, 2:1). [α]2D0 = +4.7 (c = 1.0 in CHCl3). 1H NMR
3
(500 MHz, CDCl3, 25 °C) δ = 7.30 (d, JAr = 8.1 Hz, 2 H, 1arom
-
3
H), 6.87 (d, JAr = 8.1 Hz, 2 H, 2arom-H), 5.96–5.80 (m, 2 H, 2bu
-
=
[10] J. N. Sanders, S. A. Chenoweth, F. P. Schwarz, J. Inorg. Bio-
chem. 1988, 70, 71–82.
3
3
H, 3bu-H), 5.29 (s, 1 H, acetal-H), 5.05 (dd, J3,4 = 2.1, J2,3
3
3
2.5 Hz, 1 H, 3-H), 4.99 (dd, J1,2 = 1.5, J2,3 = 2.5 Hz, 1 H, 2-H), [11] J. Bouckaert, F. Poortmans, L. Wyns, R. J. Loris, J. Biol. Chem.
3
3
3
1996, 271, 16144–16151.
[12] R. H. Jacobson, X.-J. Zhang, R. F. DuBose, B. J. Matthews,
Nature 1994, 369, 761–766.
[13] A. Carvalho de Souza, J. P. Kamerling, Methods Enzymol.
2006, 417, 221–243.
[14] M. J. Hernaiz, J. M. de la Fuente, A. G. Barrientos, S. Penades,
Angew. Chem. 2002, 114, 1624–1627; Angew. Chem. Int. Ed.
2002, 41, 1554–1557.
[15] J. M. de la Fuente, S. Penades, Glycoconjugate J. 2004, 21, 149–
163.
[16] P. Charley, P. Saltman, Science 1963, 139, 1205–1210.
[17] C. E. Bugg, J. Am. Chem. Soc. 1973, 95, 908–913.
[18] S.-I. Hakomori, Glycoconjugate J. 2004, 21, 125–137.
[19] S.-I. Hakomori, Glycoconjugate J. 2000, 17, 627–647.
[20] L. Nagy, A. Szorcsik, J. Inorg. Biochem. 2002, 89, 1–12.
4.90 (dd, J4,5 = 1.6, J3,4 = 2.1 Hz, 1 H, 4-H), 4.89 (d, J1,2
1.5 Hz, 1 H, 1-H), 4.57 (ddd, J4,5 = 1.6, J5,6b = 3.8, J5,6a
=
=
3
3
3
5.4 Hz, 1 H, 5-H), 4.53–4.48 (m, 2 H, 4bu-H), 4.38–4.32 (m, 1 H,
2
3
1abu-H), 4.24 (dd, J6a,6b = 11.8 Hz, J5,6a = 5.4 Hz, 1 H, 6a-H),
2
3
4.15 (dd, J6a,6b = 11.8 Hz, J5,6b = 6.4 Hz, 1 H, 6b-H), 4.07–4.03
(m, 1 H, 1bbu-H), 3.27 (s, 6 H, OCH3), 2.12–2.13 (m, 9 H, 3 Ac-
H), 2.08 (s, 3 H, Ac-H) ppm. 13C NMR (126 MHz, CDCl3, 25 °C):
δ = 170.4, 169.9, 168.7, 168.6 (4 CH3CO), 130.4 (Carom), 128.1
(Carom), 127.9 (Carom), 127.5 (Carom), 114.1 (C-2bu), 114.0 (C-3bu),
103.0 (Caectal), 98.2 (C-1), 68.8 (C-4bu), 67.0 (C-1bu) 66.8 (C-3), 66.0
(C-4), 65.6 (C-5), 65.5 (C-2), 62.1 (C-6), 52.3 (OCH3), 20.8, 20.7,
20.6, 20.4 (4 CH3CO) ppm. HRMS (FAB): calcd. for C27H37O13
[M + H]+ 569.2229; found 569.2365.
(E)-4-[4-(Dimethoxymethyl)phenoxy]but-2-enyl
2,3,4,6-Tetra-O- [21] S. J. Angyal, Chem. Soc. Rev. 1980, 9, 415–443.
[22] S. J. Angyal, Adv. Carbohydr. Chem. Biochem. 1989, 47, 1–167.
[23] S. J. Angyal, Tetrahedron 1974, 30, 1695–1701.
[24] S. Kopitzki, K. J. Jensen, J. Thiem, Chem. Eur. J. 2010, 16,
7017–7029.
[25] M. B. Thygesen, K. K. Sørensen, E. Clo, K. J. Jensen, Chem.
Commun. 2009, 6367–6369.
[26] S. Ko, A. Lee, S. Masamune, L. Reed, K. B. Sharpless, F. J.
Walker, Science 1933, 220, 949–951.
[27] S. Ko, A. Lee, S. Masamune, L. Reed, K. B. Sharpless, F. J.
Walker, Tetrahedron 1990, 46, 245–264.
[28] P. Czechura, N. Guedes, S. Kopitzki, N. Vazques, M. Martin-
Lomas, N.-C. Reichardt, Chem. Commun. 2011, 47, 2390–2392.
[29] J. D. C. Codee, B. Stubba, M. Schiattarella, H. S. Overkleeft,
C. A. A. van Boeckel, J. H. van Boom, G. A. van der Marel, J.
Am. Chem. Soc. 2005, 127, 3767–3773.
[30] H. Paulsen, W.-P. Trautwein, F. Garrido Espinosa, K. Heyns,
Chem. Ber. 1967, 100, 2822–2836.
[31] R. Hevey, A. Morland, C.-C. Ling, J. Org. Chem. 2012, 77,
6760–6772.
[32] R. Hevey, C.-C. Ling, Org. Biomol. Chem. 2013, 11, 1887–1895.
acetyl-α- -talopyranoside (14): As for the synthesis of compound
D
13, allyl glycoside 12 (200 mg, 515 μmol) was treated with para-
(allyloxy)benzaldehyde dimethyl acetal (1.04 g, 5.00 mmol) and
Grubbs–Hoveyda 2nd generation catalyst (33 mg, 50 μmol). After
column chromatography, compound 14 (240 mg, 82%) was ob-
tained as a colorless syrup. Rf = 0.36 (petroleum ether/EtOAc, 2:1).
[α]2D0 = –1.3 (c = 0.2 in CHCl3). 1H NMR (400 MHz, CDCl3,
3
3
25 °C): δ = 7.31 (d, JAr = 8.4 Hz, 2 H, 1arom-H), 6.88 (d, JAr
=
8.4 Hz, 2 H, 2arom-H), 5.97–5.81 (m, 2 H, 2bu-H, 3bu-H), 5.28 (s, 1
H, acetal-H), 5.20 (ddd, 3J4,5 = 0.9, 3J3,4 = 3.8, 4J2,4 = 1.1 Hz, 1 H,
3
3
4-H), 5.15 (dd, J2,3 = 3.4, J3,4 = 3.8 Hz, 1 H, 3-H), 4.95 (ddd,
3J1,2 = 1.4, J2,3 = 3.4, J2,4 = 1.1 Hz, 1 H, 2-H), 4.87 (d, J1,2
=
3
4
3
1.4 Hz, 1 H, 1-H), 4.53–4.49 (m, 2 H, 4bu-H), 4.40–4.35 (m, 1 H,
3
3
1abu-H), 4.24 (ddd, 3J4,5 = 0.9, J5,6a = 5.9, J5,6b = 6.4 Hz, 1 H, 5-
H), 4.20–4.13 (m, 2 H, 6ab-H), 4.10–4.07 (m, 1 H, 1bbu-H), 3.28
(s, 6 H, OCH3), 2.15, 2.14, 2.13, 2.03, 2.00 (s, 12 H, 4 Ac-H) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 170.1, 169.8, 169.4, 167.8
(4 CH3CO), 130.4–126.5 (Carom), 114.1 (C-2bu), 114.5 (C-3bu),
Eur. J. Org. Chem. 2013, 4008–4016
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4015

S. Kopitzki, J. Thiem
FULL PAPER
[33] H. Paulsen, F. Garrido Espinosa, W.-P. Trautwein, Chem. Ber.
1968, 101, 186–190.
[34] H. Dong, M. Rahm, T. Brinck, O. Ramström, J. Am. Chem.
Soc. 2008, 130, 15270–15271.
Maegawa, Y. Monguchi, H. Sajiki, Tetrahedron 2006, 62,
11925–11932.
[38] G. Zemplén, E. Pacsu, Ber. Dtsch. Chem. Ges. 1929, 62, 1613–
1614.
[35] H. Xiao, G. Wang, P. Wang, Y. Li, Chin. J. Chem. 2010, 28, [39] NMR characterization of the α and β anomers was achieved
1229–1232.
from the mixture. Therefore, different integrals for the α and β
signals were observed.
[36] T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Syn-
thesis 3rd ed., John Wiley & Sons, New York, 1991.
[37] A. Mori, T. Mizusaki, Y. Miyakawa, E. Ohashi, T. Haga, T.
Received: December 5, 2012
Published Online: May 15, 2013
4016
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 4008–4016