Synthesis and 13C NMR spectroscopy of model compounds for the microstructure analysis of poly(vinyl glycoside)s

Article abstract of DOI:10.1002/ejoc.200800798

A series of glycosylated diol and triol derivatives was synthesized in order to serve as model compounds for the analysis of the stereochemistry, regiochemistry, and defect structures of poly(vinyl glycoside)s. ¹³C NMR spectroscopic analysis of

Full text of DOI:10.1002/ejoc.200800798

FULL PAPER
DOI: 10.1002/ejoc.200800798
13
Synthesis and C NMR Spectroscopy of Model Compounds for the
Microstructure Analysis of Poly(Vinyl Glycoside)s
Jialong Yuan[a] and Holger Frauenrath*[a]
Keywords: Glycosylation / Chiral auxiliaries / Stereochemical effect / Poly(vinyl alcohol) / Microstructure
A series of glycosylated diol and triol derivatives was synthe-
sized in order to serve as model compounds for the analysis
of the stereochemistry, regiochemistry, and defect structures
of poly(vinyl glycoside)s. 13C NMR spectroscopic analysis of
these compounds revealed that the attached chiral carbo-
hydrate substituents induced a strong correlation of the
chemical shifts of both the anomeric C and the α-C atom of
the aglycon with the absolute configuration of the latter. The
influence of the stereoconfiguration of β- and γ-C atoms as
well as the regiochemistry of the aglycon on the chemical
shifts of the α-C and the anomeric C atom was also investi-
gated.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
Synthetic glycopolymers, i.e., hybrid materials of carbo-
hydrates and synthetic polymers, are attracting increasing
interest as potentially biomimetic materials, because carbo-
hydrates play an important role in biomaterials and cell sig-
naling.[1–6] While most of these investigations have dealt
with carbohydrate-functionalized standard monomers such
as styrenes, acrylates, methacrylates, or acrylamides, we
have recently reported the preparation of glycosylated poly-
(vinyl alcohol) via free radical polymerization of 1-O-vinyl
glycosides (Scheme 1).[7,8] The obtained poly(vinyl glyco-
side)s represent the structurally simplest glycosylated poly-
mers with an all-carbon backbone; they may exhibit a de-
fined tacticity and secondary structure formation; and they
may be regarded as interesting candidates for both biocom-
patible and biodegradable materials.
Scheme 1. Synthesis of poly(vinyl glycoside)s via free radical poly-
merization of 1-O-vinyl glycosides; R = OAc, OBz.[7,8]
tail-tail connectivity) would be present in the polymer, (iii)
which kinds of termination or transfer reactions were en-
countered, (iv) and to which extent the polymerization pro-
ceeded in a stereoselective fashion, furnishing polymers
with a controlled tacticity (relative stereochemistry of the
repeating units). Moreover, the analysis of the microstruc-
1
ture by means of H and 13C NMR spectroscopy turned
While the free radical polymerization of the 1-O-vinyl
mannopyranosides has worked acceptably well,[7,8] some de-
tails of the reaction mechanism remained inscrutable be-
cause the vinyl glycosides represent an entirely new class of
radically polymerizable monomers (Scheme 2). Other exam-
ples of simple vinyl acetals had been reported to be non-
polymerizable,[9] and divinyl acetals had been found to pro-
duce complex mixtures of microstructures.[10]
out to be less straightforward than in the case of poly(vinyl
ether)s and poly(vinyl acetate),[11–16] probably due to the
inherent rigidity of the obtained poly(vinyl glycoside)s and
the presence of the chiral carbohydrate substituents.
We report here the preparation of a series of -mannos-
ylated diol and triol derivatives which are to serve as low
molecular weight model compounds for the regiochemical
and stereochemical analysis of poly(vinyl mannopyranos-
ide)s. Furthermore, the 13C NMR spectra of the obtained
derivatives were investigated. The influence of the absolute
and relative stereoconfigurations of the α-, β-, and γ-C
atoms of the aglycon residue on the chemical shifts of both
the anomeric carbon and the α-C atom of the aglycon itself
was analyzed, which may give a useful handle for the in-
terpretation of the microstructural details of poly(vinyl gly-
coside)s.
It was, hence, not obvious (i) that the polymerization
would work regioselectively in the sense of a 1,2-polyaddi-
tion, (ii) what kinds of regiochemical defects (head-head,
[a] ETH Zürich, Department of Materials,
Wolfgang-Pauli-Str. 10, HCI H515, 8093 Zürich, Switzerland
Fax: +41-44-633-1390
E-mail: frauenrath@mat.ethz.ch
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2009, 43–52
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
43

J. Yuan, H. Frauenrath
FULL PAPER
Scheme 2. Synthesis of -mannosylated diol and triol derivatives as model compounds for the regio- and stereochemical analysis of
analogous poly(vinyl mannopyranoside)s. Reagents and reaction conditions, a: phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-α--mannopyranoside
(7), NIS, TfOH, DCM, 0 °C; b: NaOMe/MeOH, room temp.; c: Ac2O/pyridine. Yields see Table 1.
borohydride,[21] as well as stereoselectively in a multi-step
Results and Discussion
synthesis,[22] was straightforwardly prepared in four simple
The diols 1a, 1b, 1c(2R,4R), 1c(2S,4S), and 1d were
commercially available in their diastereomerically and enan-
steps starting from the commercially available 3-hy-
droxyhepta-1,6-diene (4) (Scheme 3).
tiomerically pure forms and were applied in the synthesis
of the corresponding -mannosylated model compounds 2
or 3 without further purification. The meso diastereomer of
alcohol 1c(2R,4S) was obtained by separating it from the
rac diastereomers 1c(2R,4R) and 1c(2S,4S) by means of
silica gel column chromatography.[17] Finally, heptane-2,4,6-
triol (1e),[18,19] which had previously been prepared by high
pressure hydrogenation of diacetylacetone in Et2O at
conditions, a: mCPBA/DCM; b: TMS-Cl, NEt3, THF, 0 °C; c:
100 °C,[20] by reduction of diacetylacetone with sodium DiBAl-H, toluene, 0 °C, silica gel column chromatography.
Scheme 3. Synthesis of heptane-2,4,6-triol. Reagents and reaction
44
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Eur. J. Org. Chem. 2009, 43–52

Models for the Microstructure Analysis of Poly(Vinyl Glycoside)s
Thus, the oxidation of 4 with mCPBA furnished 1,2:6,7- the 2,4,6-triglycosides 2e and 3e) are representative for the
diepoxyheptan-4-ol (5) in quantitative yield. The product typical repeating units of the corresponding polymers re-
was then converted into the corresponding silyl ether 6. Fi- sulting from a 1,2-polyaddition (head–tail connectivity)
nally, the epoxide functions of 6 were regioselectively with different tacticity, i.e., relative and absolute stereocon-
opened by using DiBAl-H, and the TMS-group was quanti- figuration. Likewise, the diglycosides 2b and 3b are models
tatively removed during the purification of the crude prod- for the typical end groups resulting from hydrogen addition
uct using silica gel column chromatography. As none of the to the radical chain end, as is the case for either chain trans-
preceding steps had been performed in a stereoselective fer reactions or termination via disproportionation. Finally,
manner, the desired triol 1e was obtained as an inseparable the 2,3-diglycosides 2a and 3a as well as 2d and 3d mimic
mixture of all different diastereomers which was used in the regiochemical defect structures resulting from 2,1-misinser-
following glycosylation reaction without further purifica- tions with head–head and tail–tail connectivity, respectively.
tion.
In order to be useful as model compounds for the micro-
The different diols 1a–d as well as triol 1e were then gly- structure analysis of poly(vinyl glycoside)s, however, the 13
C
cosylated with phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-α-- NMR spectra of 2a–e and 3a–e must show significant
mannopyranoside (7)[23] as the glycosyl donor and acti- chemical shift changes as a result of the stereo- and regio-
vation with NIS/TfOH (Scheme 2). All benzoylated glyco- chemical differences.
sides were purified by silica gel column chromatography fol-
The 13C NMR spectra of the perbenzoylated model com-
lowed by recrystallization from ethyl acetate/hexane. The pounds 2a–e as well as the peracetylated derivatives 3a–e,
isolated yields of the glycosylation reactions were generally indeed, proved that both their stereoconfiguration and their
good (Table 1), although the glycosylation of the syn diols regiochemistry had a significant effect on the chemical
1a(R,R) and 1a(S,S) was noticeably less efficient than the shifts of the respective α-C atoms of the aglycon (which will
reaction of either its anti diastereomer 1a(S,R) as well as uniformly be referred to as C7 in the following discussion
any of the other diol substrates 1b–d containing either pri- for the sake of simplicity; compare Figure 1) and the anom-
mary hydroxy groups or 1,3-diol functions, indicating that eric carbons of the attached carbohydrate substituent (C1).
steric hindrance may be an issue. Even the threefold glyco- The trends observed in the two different series of perbenzo-
sylation of the triol 1e was accomplished in 70% isolated ylated and peracetylated derivatives were exactly the same;
yield, furnishing a mixture of different stereoisomers.
just the absolute chemical shift values of C7 and C1 were
higher in the perbenzoylated molecules, and the chemical
shift differences tended to be, on average, a little larger, as
Table 1. Isolated yields of the perbenzolyated -mannopyranosides
2a–e synthesized from the corresponding alcohols 1a–e, and iso-
lated yields of the peracetylated -mannopyranosides 3a–e over
two steps starting from 2a–e.
R–OH
% Yield
% Yield
1a(2S,3R)
1a(2R,3R)
1a(2S,3S)
1b(3R)
2a(2S,3R)
2a(2R,3R)
2a(2S,3S)
2b(3R)
84
66
56
85
70
75
86
80
88
70
3a(2S,3R)
3a(2R,3R)
3a(2S,3S)
3b(3R)
75
81
82
76
71
79
82
80
72
75
1b(3S)
2b(3S)
3b(3S)
1c(2S,4R)
1c(2R,4R)
1c(2S,4S)
1d
2c(2S,4R)
2c(2R,4R)
2c(2S,4S)
2d
3c(2S,4R)
3c(2R,4R)
3c(2S,4S)
3d
1e
2e
3e
The attempted analogous glycosylation of the alcohols
1a–e with 7 as the glycosyl donor turned out to be signifi-
cantly less efficient in all cases due to side reactions. The
peracetylated mannopyranosides 3a–e were, instead, pre-
pared by debenzoylation of the corresponding mannopyr-
anosides 2a–e followed by acetylation in situ. As a
recrystallization of the peracetylated compounds failed in
all cases, they were purified by silica gel column chromatog-
raphy and obtained in yields of 71–82% over two steps
(Table 1).
As far as their molecular structure is concerned, the ob-
tained di- and triglycosylated derivatives are appropriate
model compounds for the stereochemical and regiochemical
analysis of the corresponding perbenzoylated and peracety-
lated poly(vinyl mannopyranoside)s via 13C NMR spec-
Figure 1. Preferred conformations of the α--mannopyranosides
with (a) 7R configuration and (b) 7S configuration, i.e., RЈ Ͼ R in
both cases; RЈЈ = OBz; X = CH(ORЈЈ).[34] With a preferred stag-
gered conformation of the C1–O bond (φ ≈ –60°) in both cases and
a staggered conformation of the O–C7 bond with ψ ≈ –60° and
ψ ≈ +60° for the 7S- and the 7R-epimer, respectively, only the latter
would exhibit C–H 1,3-interactions between C1–H1 and C7–H7
responsible for the observed downfield shifts in the 13C NMR
chemical shifts of the anomeric carbon (C1) and the α-C atom of
troscopy. Thus, the 2,4-diglycosides 2c and 3c (as well as the aglycon (C7).
Eur. J. Org. Chem. 2009, 43–52
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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45

J. Yuan, H. Frauenrath
FULL PAPER
well. Most importantly, the chemical shifts of C7 and C1 was attached to a C7 with (R) configuration, were shifted
showed a strong dependence on the absolute stereoconfigu- by 1.8–4.1 ppm downfield as compared to the anomeric
ration of C7 itself (columns ∆α in Tables 2 and 3). Notably, carbons of a carbohydrate residue attached to a C7 with
the chemical shifts of C7 with an (R) configuration were (S) configuration.
always observed to experience a 2.2–4.9 ppm downfield
In contrast to the strong influence of the stereoconfigu-
shift with respect to the C7 with an (S) configuration (given ration of the α-C atom itself, a closer inspection of the
the same constitution). The same trend was observed for NMR spectroscopic data of the different diastereomers of
the anomeric carbons which, when the carbohydrate residue 2a and 3a, respectively, revealed that, in general, the chemi-
cal shifts of the C7 and C1 carbons were only marginally
affected by the stereoconfiguration of the β-C atoms (rows
Table 2. Influence of the stereoconfiguration of the α-, β-, and γ-C
∆β in Table 2 and Table 3). Both the absolute and the rela-
atom of the aglycon on the chemical shifts (in ppm) of the α-C
tive stereoconfiguration of the γ-C atom, on the other hand,
(C7) itself as well as the anomeric C atom (C1) of the attached
had a more pronounced effect in most cases (rows ∆γ in
carbohydrate substituent in the different diastereomers of the per-
Tables 2 and 3). Thus, a detailed comparison of the chemi-
cal shifts of the respective C7 and C1 carbons of the dif-
ferent diastereomers of 2c and 3c showed downfield shifts
of up to 1.9 ppm for γ-C atoms with (R) configuration.
Moreover, the chemical shift differences with respect to the
(R,S) diastereomer were, in all cases, substantially larger for
the (R,R) diastereomers as compared to the (S,S) dia-
stereomers. The significant downfield shifts of C7 and C1
in the (R,R) diastereomers of 3c appear to be even more
relevant taking into account that the diastereomeric mix-
tures of 2e and 3e exhibited C7 and C1 carbons at chemical
shifts of up to 78.3 and 100.6 ppm as well as 78.0 and
98.3 ppm (3e), respectively. In the latter case, these were the
highest values observed for all derivatives 3a–e. Presumably,
the effect of the stereoconfiguration of the two γ-C atoms
on the central C7 and C1 carbons in the (R,r,R) dia-
stereomer present in the mixture is cumulative in this case,
which appears to make the peracetylated compounds the
most suitable model compounds for the microstructure
analysis of, likewise, peracetylated poly(vinyl mannopyr-
anoside)s.
benzoylated compounds 2a–e.
[a]
[b]
[b]
[a]
C7(R)
C7(S)
∆
C17R
C17S
∆
α
α
2a(2R,3R) 79.4
–
98.9
–
+4.9
+4.2
2a(2S,3S)
–
74.5
74.6
–0.1
–
94.7
95.2
–0.5
2a(2S,3R) 79.4
+4.8
99.1
–0.2
+3.9
–
[a]
∆
β
Ϯ0.0
–
2b(3R)
74.7
–
98.2
–
+2.8
+3.3
+2.1
+3.5
2b(3S)
–
71.9
–
96.1
2c(2R,4R) 75.5
–
99.1
–
2c(2S,4S)
–
74.7
+0.8
72.2
71.8
+0.4
–
95.6
95.7
–0.1
2c(2S,4R)
+2.9
97.9
+1.2
+2.2
–
[a]
∆
γ
–
2d
2e
67.1
78.3–72.7
–
–
97.9
100.6–96.3
–
–
[a] Differences in chemical shifts of C7 or C1 depending on the
stereoconfiguration of the α-, β-, and γ-C atom of the aglycon,
respectively. [b] Anomeric carbon C1 of the α--mannopyranosyl
residue attached to C7(R) and C7(S), respectively.
Finally, the regiochemistry constituted another impor-
tant parameter determining the chemical shifts of C7,
whereas the anomeric carbons C1 remained more or less
unaffected. Thus, a comparison of the chemical shifts of the
α-C atoms of the 1,2-diglycosylated derivatives 2a and 3a
with those of the respective 1,3-diglycosylated compounds
2b, 2c, 3b, and 3c as well as the 1,4-diglycosylated molecules
2d and 3d revealed a systematic trend to higher fields, span-
ning a large chemical shift range of more than 12 and
10 ppm in total within the two series. It must be acknowl-
edged, however, that this effect can, apparently, be (over)
compensated by the observed stereochemical effects, since
the highest overall chemical shifts were, presumably, ob-
served for the (R,r,R) diastereomers of 2e and 3e, as already
mentioned above.
In summary, the preceding experimental data proved that
the 13C NMR chemical shifts of the α-C atoms of the agly-
con (C7) and the anomeric carbons (C1) were correlated to
the regiochemistry of the compounds, the absolute stereo-
configuration of C7 itself, as well as the absolute and rela-
tive stereoconfiguration of the γ-C atoms of the aglycon.
While the chemical shift differences as such are, of course,
not surprising because (due to the carbohydrate substitu-
ents’ chirality) a change of the absolute configuration of C7
Table 3. Influence of the stereoconfiguration of the α-, β-, and γ-C
atom of the aglycon on the chemical shifts (in ppm) of the α-carbon
(C7) itself as well as the anomeric carbon (C1) of the attached
carbohydrate substituent in the different diastereomers of the per-
acetylated compounds 3a–e.
[a]
[b]
[b]
[a]
C7(R)
C7(S)
∆
α
C17R
C17S
∆
α
3a(2R,3R) 77.3
–
97.4
–
+4.1
+3.9
3a(2S,3S)
–
73.2
73.0
+0.2
–
97.2
+0.2
93.5
93.1
+0.4
3a(2S,3R) 77.3
+4.3
–
+4.1
–
[a]
∆
β
Ϯ0.0
3b(3R)
72.9
–
96.9
–
+3.1
+3.2
+2.8
+3.3
3b(3S)
–
69.8
–
94.1
3c(2R,4R) 74.4
–
97.9
–
3c(2S,4S)
–
71.2
70.3
+0.9
–
96.2
+1.7
94.6
94.4
+0.2
3c(2S,4R) 72.5
+2.2
–
+1.8
–
[a]
∆
γ
+1.9
3d
3e
67.3
78.0–70.2
–
–
96.7
98.3–95.4
–
–
[a] Differences in chemical shifts of C7 or C1 depending on the
stereoconfiguration of the α-, β-, and γ-C atoms of the aglycon,
respectively. [b] Anomeric carbon C1 of the α--mannopyranosyl
residue attached to C7(R) and C7(S), respectively.
46
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Models for the Microstructure Analysis of Poly(Vinyl Glycoside)s
gives rise to different diastereomers, the large chemical shift prepared. The chemical shifts of the α-C atom of the agly-
range of 10–12 ppm covered deserves a closer inspection.
con and the anomeric carbon were found to be strongly
The conformation at the glycosidic linkage is described dependent on the absolute configuration of the α-C atom
by the dihedral angles φ(H1–C1–O–C7) and ψ(C1–O–C7– itself, the absolute and the relative stereoconfiguration of
H7).[24] As the α-glycosides have been shown to exhibit a the γ-C atom of the aglycon, as well as the regiochemistry.
strong preference for staggered conformation with a dihe- As a result, chemical shift differences of more than 10 ppm
dral angle φ ≈ –60° (Figure 1),[25,26] the stereochemistry of were observed for the α-C atom. These features make the
the aglycon mainly affects the dihedral angle ψ which, in glycosides 2a–e and 3a–e useful as model compounds for
turn, strongly influences the 1H and 13C NMR chemical an investigation of both the mechanism of the novel free
shifts of the anomeric carbon (C1) and the α-C atom of the radical polymerization of vinyl glycosides and a detailed
aglycon (C7), as has been amply demonstrated.[25–31] For 2- analysis of the microstructure and tacticity of the obtained
methylcyclohexyl α--glycosides, for example, dihedral poly(vinyl glycoside)s.
angles of ψՅ0° and ψՆ0° have been observed for the de-
rivatives with 7S and 7R configuration of the α-C atoms,
respectively. The latter exhibited downfield shifts of +6.1
Experimental Section
and +5.1 ppm for the 13C NMR chemical shifts of C1 and
All experiments were carried out in dried Schlenk glassware in an
C7 (i.e., the C1Ј of the 2-methylcyclohexyl substituent).[25,26]
inert N2 atmosphere, unless noted otherwise. All reagents were pur-
Similarly, downfield shifts of +5.0 and +5.4 ppm were, more
chased as reagent grade from commercial sources and used without
recently, observed for the C1 and C7 carbons of enantio-
further purification. Solvents were purchased as reagent grade and
distilled once prior to use. Anhydrous solvents were freshly distilled
and stored over molecular sieves prior to use. DCM was refluxed
and distilled from CaH2. The commercially available derivatives
merically pure menthyl α--mannopyranosides with 7R
configuration (compared to those with 7S configura-
tion).[32]
Interestingly, these downfield shifts for the 13C NMR
1a(2R,3R), 1a(2S,3S), 1a(2S,4R), 1b(3S), 1b(3R), 1c(2R,4R),
1c(2S,4S), and 1d, as well as hepta-1,6-dien-4-ol 4 were used with-
out further purification. Phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-α--
mannopyranoside (7) was prepared according to a published pro-
cedure.[23]
chemical shifts of the anomeric carbon (C1) and the α-C
atom of the aglycon (C7) for derivatives with a 7R-configu-
ration are in absolute agreement with our own observations
and have been attributed[25,26] to the effect of spatial C–H
interactions on the 13C NMR chemical shifts,[33] as they are
also observed for the typical 1,3-interactions in polycyclic
systems.[34] By analogy, it may be expected that α--manno-
pyranosides with two (large) substituents R and RЈ with
different steric demand (RЈ Ͼ R)[35] attached to C7 would
favor a staggered conformation of the O–C7 bond with
ψ ≈ –60° for the 7S-epimer and ψ ≈ +60° for the 7R-epimer,
placing the largest residue RЈ into an antiperiplanar orienta-
tion with respect to the carbohadrate residue in both cases
(Figure 1). These conformations would, consequently, lead
to a strong 1,3-interaction of C7–H7 with C1–H1 only in
the case of the 7R-epimer. This 1,3-interaction, accordingly,
induces a downfield shift in the 13C NMR chemical shifts
of both the anomeric carbon C1 and C7 (α-C atom) simul-
taneously. Likewise, the only marginal influence of the β-C
atoms in the case of the α-mannopyranosides investigated
here is well in line with previous examples.[25,26] This is also
true for the observed stronger effect of the γ-C atoms which
may be explained by C–H 1,5-interactions (γ-gauche ef-
fect).[25,26] It is interesting to note, however, that the latter
effect and its observed cumulative nature also imply the
presence of a preferred backbone conformation which may
lead to defined secondary structures of the corresponding
poly(vinyl glycoside)s.
General Procedure for the Glycosylation Reactions (Procedure A):
The alcohol (typically 0.2 mmol), pyranoside 7 (typically 4 equiv.),
4 Å molecular sieves, and DCM (50 mL/g of 7) were placed in a
dried Schlenk flask under nitrogen. The mixture was cooled to
0 °C, and N-iodosuccinimide (5 equiv.) as well as TfOH (4 equiv.)
were added. After 3 min, the reaction was quenched with triethyl-
amine (large excess). The solution was diluted with Et2O (about
500 mL/g of substrate), washed with 1  HCl, saturated aqueous
NaHCO3 solution, and saturated aqueous NaCl solution, dried
with MgSO4, filtered, and the solvents evaporated to dryness. The
pure products were obtained by flash column chromatography, fol-
lowed by recrystallization in some cases.
General Procedure for the Debenzoylation and Acetylation Reactions
(Procedure B): The benzoylated compound (typically 0.1–
0.2 mmol) and NaOMe (typically 0.37 mmol) were added into a
flask containing MeOH (20 mL), and the reaction mixture was
stirred at room temperature for about 2 h until the conversion was
complete. Amberlite IR-120 (H+; typically 0.37 mmol) was added
into the reaction mixture. After about 3 min, when the pH of the
reaction mixture reached pH 7–8, the Amberlite was filtered off.
The solution was concentrated and dried in high vacuum for 12 h.
The residue was dissolved in pyridine (20 mL), and Ac2O (3 mL,
large excess) was added slowly via a syringe over a time period of
3 h. The reaction mixture was stirred at room temperature for 1 h
and then diluted with Et2O. The organic phase was washed with
1  HCl, saturated aqueous NaHCO3 solution as well as saturated
aqueous NaCl solution, and dried with MgSO4. The pure products
were obtained by flash column chromatography.
Conclusions
(2S,4R)-Pentane-2,4-diol [1c(2S,4R)]: The compound was sepa-
rated from commercially available mixture of pentane-2,4-diols
using silica gel chromatography (ethyl acetate/hexane, 1:2); 1a(S,R)
was obtained as the first fraction. 1H NMR (300 MHz, CDCl3,
In conclusion, a series of perbenzoylated and peracety-
lated glycosides of enantiomerically pure diols as well as
a diastereomeric mixture of one triol derivative have been 25 °C): δ = 4.08 (s, 2 H, OH), 4.00–3.91 (m, 2 H, 2-H, 4-H), 1.51–
Eur. J. Org. Chem. 2009, 43–52
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
47

J. Yuan, H. Frauenrath
FULL PAPER
1.43 (m, 2 H, 3-H), 1.12 (d, JH,H = 6.3 Hz, 6 H, 1-H, 5-H) ppm.
13C NMR (75 MHz, CDCl3, 25 °C): δ = 68.7 (2 C, 2-C, 4-C), 46.3
(3-C), 24.0 (2 C, 1-C, 5-C) ppm.
3
found C 69.08, H 5.05. HRMS (MALDI): m/z calcd. for C72H62O20
([M + Na]+) 1269.3727, found 1269.3706.
(2S,3S)-2,3-Bis(2Ј,3Ј,4Ј6Ј-O-benzoyl-α-D-mannopyranosyloxy)-
Heptane-2,4,6-triol (1e): 1,2:6,7-Diepoxy-4-(trimethylsilyloxy)hep-
tane (6) (100 mg, 0.46 mmol) was added to a flask containing tolu-
ene (30 mL). The solution was cooled to 0 °C, and DiBAl-H
(2.0 mL, 2.4 mmol) was added. After stirring at room temperature
for 12 h, the reaction mixture was evaporated to dryness. After re-
peated purification by flash column chromatography (silica gel,
butane [2a(2S,3S)]: The product was prepared according to pro-
cedure A, using (2S,3S)-butane-2,3-diol [1a(2S,3S)] (0.046 mL,
0.5 mmol), thioglycoside 7 (1.3 g, 1.9 mmol), N-iodosuccinimide
(675 mg, 3.0 mmol), and TfOH (0.18 mL, 2.0 mmol). After flash
column chromatography (silica gel, ethyl acetate/hexane, 1:6) and
recrystallization from ethanol; 2a(2S,3S) (350 mg, 56%) was ob-
ethyl acetate/hexane, 1:2, ethyl acetate/methanol, 5:1, then meth- tained as a white solid, [α]2D5 = –35.46 (c = 0.65, CH3Cl). 1H NMR
anol); 1e (36 mg, 53%, mixture of diastereomers) was obtained as
(500 MHz, CDCl3, 25 °C): δ = 8.19–6.65 (m, 40 H, HAr), 6.31 (t,
3
a colorless syrup. 1H NMR (300 MHz, [D6]DMSO, 25 °C): δ =
3JH,H = 10.0 Hz, 2 H, 4Ј-H), 5.98 (dd, JH,H = 10.0, 3.0 Hz, 2 H,
3
3
4.53 (s, 3 H, OH), 4.00–3.12 (m, 3 H, 2-H, 4-H, 6-H), 2.00–1.23 3Ј-H), 5.76 (dd, JH,H = 3.0, 1.5 Hz, 2 H, 2Ј-H), 5.32 (d, JH,H
=
(m, 4 H, 3-H, 5-H), 1.13–1.05 (m, 6 H, 1-H, 7-H) ppm. 13C NMR
([D6]DMSO, 75 MHz): δ = 68.1, 66.3, 65.2, 65.2, 63.4, 63.2 (2-C,
4-C, 6-C), 47.6, 47.3, 47.0 (3-C, 5-C), 24.8, 24.2, 24.1 (1-C, 7-C)
1.5 Hz, 2 H, 1Ј-H), 4.89 (dd, 3JH,H = 12.5, 2JH,H = 2.0 Hz, 2 H, 6Ј-
H), 4.83–4.79 (m, 2 H, 5Ј-H), 4.72 (dd, JH,H = 12.0, JH,H
3
2
=
=
3
4.0 Hz, 2 H, 6Ј-H), 4.15–4.08 (m, 2 H, 2-H, 3-H), 1.29 (d, JH,H
ppm. MS (EI): m/z calcd. for C7H16O3 ([M – 2C2H5O]+) 58.04, 5.5 Hz, 6 H, 1-H, 4-H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C):
found 58.05.
δ = 166.3–165.7 (8 C, PhCO), 133.6–128.1 (48 C, CAr), 94.7 (2 C,
1Ј-C), 74.5 (2 C, 2-C, 3-C), 71.1 (2 C, 5Ј-C), 70.7 (2 C, 3Ј-C), 70.0
(2 C, 2Ј-C), 66.4 (2 C, 4Ј-C), 63.0 (2 C, 6Ј-C) 14.5 (2 C, 1-C, 4-C)
ppm. HRMS (MALDI): m/z calcd. for C72H62O20 ([M + Na]+)
1269.3727, found 1269.3721.
(2S,3R)-2,3-Bis(2Ј,3Ј,4Ј,6-tetra-O-benzoyl-α-D-mannopyranosyl-
oxy)butane [2a(2S,3R)]: The product was prepared according to
procedure A, using (2S,3R)-butane-2,3-diol [1a(2S,3R)] (0.033 mL,
0.37 mmol), thioglycoside 7 (1 g, 1.5 mmol), N-iodosuccinimide
(405 mg, 1.8 mmol), and TfOH (0.11 mL, 1.2 mmol). After flash (3R)-1,3-Bis(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α-D-mannopyranosyloxy)-
column chromatography (silica gel, ethyl acetate/hexane, 1:6) and
recrystallization from ethanol; 2a(2S,3R) (386 mg, 84%) was ob-
tained as a white solid, [α]2D5 = –43.17 (c = 1.04, CH3Cl). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 8.13–6.99 (m, 40 H, HAr), 6.23 (t,
butane [2b(3R)]: The product was prepared according to procedure
A, using (3R)-butane-1,3-diol [1b(3R)] (18 mg, 0.2 mmol), thiogly-
coside 7 (550 mg, 0.8 mmol), N-iodosuccinimide (247 mg,
1.1 mmol), TfOH (0.055 mL, 0.8 mmol). After flash column
chromatography (silica gel, ethyl acetate/hexane, 1:6) and
recrystallization from ethanol; 2b(3R) (215 mg, 85%) was obtained
as a white solid, [α]2D5 = –63.92 (c = 1.80, CH3Cl). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 8.20–7.22 (m, 40 H, HAr), 6.17 (t,
3
3JH,H = 10.0 Hz, 1 H, 4Ј-H), 6.21 (t, JH,H = 10.0 Hz, 1 H, 4Ј-H),
3
3
6.03 (dd, JH,H = 10.0, 3.0 Hz, 1 H, 3Ј-H), 5.95 (dd, JH,H = 10.0,
3
3.0 Hz, 1 H, 3Ј-H), 5.78–5.75 (m, 2 H, 2Ј-H), 5.44 (d, JH,H
=
3
1.5 Hz, 1 H, 1Ј-H), 5.31 (d, JH,H = 1.5 Hz, 1 H, 1Ј-H), 4.82 (dd,
3JH,H = 13.5, JH,H = 3.5 Hz, 1 H, 6Ј-H), 4.73 (dd, JH,H = 12.0,
3JH,H = 10.0 Hz, 1 H, 4Ј-H), 6.16 (t, JH,H = 10.0 Hz, 1 H, 4Ј-H),
2
3
3
2JH,H = 2.5 Hz, 1 H, 6Ј-H), 4.69–4.63 (m, 3 H, 5Ј-H, 5Ј-H, 6Ј-H), 5.99 (2dd, JH,H = 10.0, 3.0 Hz, 2 H, 3Ј-H), 5.79 (dd, JH,H = 3.0,
3
3
3
3
4.58 (dd, JH,H = 12.0, 4.5 Hz, 1 H, 6Ј-H), 4.17–4.11 (m, 1 H, 2- 1.7 Hz, 1 H, 2Ј-H), 5.67 (dd, JH,H = 3.0, 1.7 Hz, 1 H, 2Ј-H), 5.34
H), 4.09–4.03 (m, 1 H, 3-H), 1.48 (d, JH,H = 6.7 Hz, 3 H), 1.32 (d, 3JH,H = 1.7 Hz, 1 H, 1Ј-H), 5.32 (d, 3JH,H = 1.7 Hz, 1 H, 1Ј-H),
3
(d, JH,H = 6.4 Hz, 3 H, 1-H, 4-H) ppm. 13C NMR (75 MHz,
4.80 (dd, JH,H = 12.1, JH,H = 2.3 Hz, 1 H, 6Ј-H), 4.73 (dd, JH,H
3
3
2
3
2
[D6]acetone, 25 °C): δ = 166.4–165.8 (8 C, PhCO), 134.4–129.1 (48
= 12.1, JH,H = 2.3 Hz, 1 H, 6Ј-H), 4.65–4.48 (m, 4 H, 5Ј-H, 6Ј-
C, CAr), 99.1 (1Ј-C), 95.2 (1Ј-C), 79.4 (3-C), 74.6 (2-C), 71.9 (5Ј- H), 4.20 (m, 1 H), 4.08 (m, 1 H), 3.85 (m, 1 H), (1-H, 3-H), 2.02
3
C), 71.8 (5Ј-C), 71.5 (3Ј-C), 71.4 (3Ј-C), 70.4 (2Ј-C), 70.2 (2Ј-C),
67.5 (4Ј-C), 67.3 (4Ј-C), 63.6 (6Ј-C), 63.5 (6Ј-C), 16.3, 13.8 (1-C, 4-
C) ppm. C72H62O20 (1246.38): calcd. C 69.33, H 5.01; found C
69.14, H 4.99. HRMS (MALDI): m/z calcd. for C72H62O20
([M + Na]+) 1269.3727, found 1269.3716.
(m, 2 H, 2-H), 1.49 (d, JH,H = 6.4 Hz, 3 H, 4-H) ppm. 13C NMR
(50 MHz, CDCl3, 25 °C): δ = 166.3–165.2 (8 C, PhCO), 133.5–
128.3 (48 C, CAr), 98.6 (1Ј-C), 98.2 (1Ј-C), 74.7 (3-C), 71.1 (5Ј-C),
70.4 (5Ј-C), 70.2 (3Ј-C), 70.1 (3Ј-C), 69.1 (2Ј-C), 68.9 (2Ј-C), 67.1
(4Ј-C), 67.0 (4Ј-C), 65.0 (1-C), 63.2 (6Ј-C), 63.0 (6Ј-C), 36.8 (2-C),
22.1 (4-C) ppm. C72H62O20 (1246.38): calcd. C 69.33, H 5.01; found
C 69.06, H 4.96. HRMS (MALDI): m/z calcd. for C72H62O20 ([M
+ Na]+) 1269.3727, found 1269.3721.
(2R,3R)-2,3-Bis(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α-D-mannopyranosyl-
oxy)butane [2a(2R,3R)]: This product was prepared according to
procedure A, using (2R,3R)-butane-2,3-diol [1a (2R,3R)]
(0.083 mL, 0.093 mmol), thioglycoside 7 (0.25 g, 0.38 mmol), N-
iodosuccinimide (101 mg, 0.45 mmol), and TfOH (0.028 mL,
(3S)-1,3-Bis(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α-
butane [2b(3S)]: The product was prepared according to procedure
D-mannopyranosyloxy)-
0.3 mmol). After flash column chromatography (silica gel, ethyl A, using (3S)-butane-1,3-diol [1b(3S)] (18 mg, 0.2 mmol), thiogly-
acetate/hexane, 1:6) and recrystallization from ethanol; 2a(2R,3R)
coside 7 (550 mg, 0.8 mmol), N-iodosuccinimide (247 mg,
1.1 mmol), TfOH (0.055 mL, 0.8 mmol). After flash column
(76 mg, 66%) was obtained as a white solid, [α]2D5 = –53.07 (c =
1.41, CH3Cl). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 8.15–7.19 chromatography (silica gel, ethyl acetate/hexane, 1:6) and
(m, 40 H, HAr), 6.12 (t, 3JH,H = 10.0 Hz, 2 H, 4Ј-H), 6.00 (dd, 3JH,H
recrystallization from ethanol; 2b(3S) (174 mg, 70%) was obtained
as a white solid, [α]2D5 = –43.37 (c = 1.78, CH3Cl). 1H NMR
(300 MHz, [D6]acetone, 25 °C): δ = 8.20–7.25 (m, 40 H, HAr), 6.30
3
= 10.0, 3.5 Hz, 2 H, 3Ј-H), 5.81 (dd, JH,H = 3.0, 1.5 Hz, 2 H, 2Ј-
3
3
H), 5.8 (d, JH,H = 1.5 Hz, 2 H, 1Ј-H), 4.69 (dd, JH,H = 12.0,
3
3
3
2.0 Hz, 2 H, 6Ј-H), 4.60–4.56 (m, 2 H, 5Ј-H), 4.53 (dd, JH,H
=
(t, JH,H = 10.0 Hz, 1 H, 4Ј-H), 6.28 (t, JH,H = 10.0 Hz, 1 H, 4Ј-
12.0, 2JH,H = 4.5 Hz, 2 H, 6Ј-H), 4.00–3.93 (m 2 H, 2-H, 3-H), 1.41 H), 6.04 (dd, JH,H = 10.0, 3.2 Hz, 1 H, 3Ј-H), 6.01 (dd, JH,H
=
3
3
(d, JH,H = 5.5 Hz, 6 H, 1-H, 4-H) ppm. 13C NMR (50 MHz,
CDCl3, 25 °C): δ = 166.3–165.5 (8 C, PhCO), 133.4–128.3 (48 C,
CAr), 98.9 (2 C, 1Ј-C), 79.4 (2 C, 2-C, 3-C), 71.2 (2 C, 5Ј-C), 70.0
10.0, 3.2 Hz, 1 H, 3Ј-H), 5.88 (dd, 3JH,H = 3.2, 1.7 Hz, 1 H, 2Ј-H),
3
3
3
5.83 (dd, JH,H = 3.2, 1.7 Hz, 1 H, 2Ј-H), 5.49 (d, JH,H = 1.7 Hz,
1 H, 1Ј-H), 5.37 (d, 3JH,H = 1.7 Hz, 1 H, 1Ј-H), 4.93–4.64 (m, 6 H,
3
2
(2 C, 3Ј-C), 69.5 (2 C, 2Ј-C), 67.5 (2 C, 4Ј-C), 63.3 (2 C, 6Ј-C), 17.3 5Ј-H, 6Ј-H), 4.35 (m, 1 H, 3-H), 4.26 (dt, JH,H = 10.0, JH,H
(2 C, 1-C, 4-C) ppm. C72H62O20 (1246.38): calcd. C 69.33, H 5.01;
=
3
2
7.0 Hz, 1 H, 1-H), 4.03 (dt, JH,H = 10.0, JH,H = 6.4 Hz, 1 H, 1-
48
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 43–52

Models for the Microstructure Analysis of Poly(Vinyl Glycoside)s
3
H), 2.23 (m, 2 H, 2-H), 1.42 (d, JH,H = 6.2 Hz, 3 H, 4-H) ppm.
2 H, 3Ј-H), 5.64 (dd, 3JH,H = 3.0, 1.7 Hz, 2 H, 2Ј-H), 5.25 (d, 3JH,H
= 1.7 Hz, 2 H, 1Ј-H), 4.72 (dd, JH,H = 12.1, JH,H = 2.3 Hz, 2 H,
13C NMR (75 MHz, [D6]acetone, 25 °C): δ = 166.4–165.8 (8 C,
PhCO), 134.4–129.2 (48 C, CAr), 98.4 (1Ј-C), 96.1 (1Ј-C), 71.90 (3-
3
2
6Ј-H), 4.59–4.53 (m, 4 H, 5Ј-H, 6Ј-H), 4.12–4.04 (m, 2 H, 2-H, 4-
3
C), 71.85 (5Ј-C), 71.64 (5Ј-C), 71.56 (3Ј-C), 71.3 (3Ј-C), 70.2 (2Ј- H), 2.05 (m, 2 H, 3-H), 1.32 (d, JH,H = 6.0 Hz, 6 H, 1-H, 5-H)
C), 69.9 (2Ј-C), 67.55 (4Ј-C), 67.46 (4Ј-C), 66.1 (1-C), 63.6 (6Ј-C), ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 166.2–165.6 (8 C,
63.4 (6Ј-C), 37.3 (2-C), 19.5 (4-C) ppm. C72H62O20 (1246.38): calcd. PhCO), 133.6–128.4 (48 C, CAr), 95.6 (2 C, 1Ј-C), 72.2 (2 C, 2-C,
C 69.33, H 5.01; found C 69.07, H 5.00. HRMS (MALDI): m/z 4-C), 71.5 (2 C, 5Ј-C), 70.3 (2 C, 3Ј-C), 69.6 (2 C, 2Ј-C), 67.0 (2 C,
calcd. for C72H62O20 ([M + Na]+) 1269.3727, found 1269.3703.
4Ј-C), 63.1 (2 C, 6Ј-C), 44.6 (3-C), 19.8 (2 C, 1-C, 5-C) ppm.
C73H64O20 (1260.40): calcd. C 69.52, H 5.11; found C 69.28, H
5.17. HRMS (ESI): m/z calcd. for C73H64O20 ([M + Na]+)
1283.3883, found 1283.3883.
(2S,4R)-2,4-Bis(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α- -mannopyranosyl-
D
oxy)pentane [2c(2S,4R)]: The product was prepared according to
procedure A, using (2S,4R)-pentane-2,4-diol [1c(2S,4R)] (13 mg,
0.12 mmol), thioglycoside 7 (325 mg, 0.47 mmol), N-iodosuccin-
imide (160 mg, 0.71 mmol), TfOH (0.062 mL, 0.71 mmol). After
flash column chromatography (silica gel, ethyl acetate/hexane, 1:6)
and recrystallization from ethanol; 2c(2S,4R) (113 mg, 75%) was
obtained as a white solid, [α]2D5 = –49.59 (c = 2.27, CH3Cl). 1H
1,4-Bis(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α-D-mannopyranosyloxy)butane
(2d): The product was prepared according to general procedure A,
using butane-1,4-diol 1d (34 mg, 0.38 mmol), thioglycoside 7 (1.1 g,
1.6 mmol), N-iodosuccinimide (405 mg, 1.8 mmol), and TfOH
(0.11 mL, 1.2 mmol). After flash column chromatography (silica
NMR (300 MHz, CDCl3, 25 °C): δ = 8.20–7.24 (m, 40 H, HAr), gel, ethyl acetate/hexane, 1:6) and recrystallization from ethanol;
3
3
6.21 (t, JH,H = 10.2 Hz, 1 H, 4Ј-H), 6.18 (t, JH,H = 9.9 Hz, 1 H,
2d (412 mg, 88%) was obtained as a white solid, [α]2D5 = –59.64 (c
4Ј-H), 5.98 (dd, JH,H = 10.2, 3.0 Hz, 2 H, 3Ј-H), 5.71 (dd, JH,H = 0.89, CH3Cl). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 8.18–7.24
= 3.2, 1.7 Hz, 1 H, 2Ј-H), 5.68 (dd, JH,H = 3.2, 1.7 Hz, 1 H, 2Ј-
H), 5.34 (m, 2 H, 1Ј-H), 4.81–4.52 (m, 6 H, 5Ј-H, 6Ј-H), 4.24–4.11 = 10.2, 3.3 Hz, 2 H, 3Ј-H), 5.78 (dd, JH,H = 3.3, 1.5 Hz, 2 H, 2Ј-
(m, 2 H, 2-H, 4-H), 2.34–2.24 (m, 1 H, 3-H), 1.86–1.77 (m, 1 H, H), 5.18 (d, J = 1.5 Hz, 2 H, 1Ј-H), 4.77 (dd, JH,H = 12.1, JH,H
3
3
3
(m, 40 H, HAr), 6.18 (t, 3JH,H = 10.0 Hz, 2 H, 4Ј-H), 5.99 (dd, 3JH,H
3
3
2
3
3
3-H), 1.49 (d, JH,H = 6.2 Hz, 3 H), 1.42 (d, JH,H = 6.2 Hz, 3 H, = 2.3 Hz, 2 H, 6Ј-H), 4.61–4.48 (m, 4 H, 5Ј-H, 6Ј-H), 4.03–3.91
1-H, 5-H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 166.3–
165.6 (8 C, PhCO), 133.5–128.4 (48 C, CAr), 97.9 (1Ј-C), 95.7 (1Ј-
(m, 2 H, 1-H 4-H), 3.74–3.64 (m, 2 H, 1-H 4-H), 1.97–1.85 (m, 4
H, 2-H 3-H) ppm. 13C NMR (50 MHz, CDCl3, 25 °C): δ = 166.3–
C), 74.7 (4-C), 71.8 (2-C), 71.4 (5Ј-C), 71.2 (5Ј-C), 70.3 (3Ј-C), 70.2 165.5 (8 C, PhCO), 133.5–128.4 (48 C, CAr), 97.9 (2 C, 1Ј-C), 70.7
(3Ј-C), 69.6 (2Ј-C), 69.3 (2Ј-C), 67.2 (4Ј-C), 67.1 (4Ј-C), 63.2 (6Ј- (2 C, 5Ј-C), 70.3 (2 C, 3Ј-C), 69.1 (2 C, 2Ј-C), 68.5 (2 C, 4Ј-C), 67.1
C), 63.1 (6Ј-C), 44.0 (3-C), 21.7, 19.5 (1-C, 5-C) ppm. C73H64O20 (2 C, 1-C, 4-C), 63.1 (2 C, 6Ј-C), 26.4 (2 C, 2-C, 3-C) ppm.
(1260.40): calcd. C 69.52, H 5.11; found C 69.24, H 5.08. HRMS
(ESI): m/z calcd. for C73H64O20 ([M + Na]+) 1283.3883, found
1283.3886.
C72H62O20 (1260.40): calcd. C 69.33, H 5.01; found C 69.07, H
5.26. HRMS (ESI): m/z calcd. for C72H62O20 ([M + Na]+)
1269.3727, found 1269.3722.
(2R,4R)-2,4-Bis(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α-
D
-mannopyranosyl-
2,4,6-Tris(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α-D-mannopyranosyloxy)-
oxy)pentane 2c(2R,4R): The product was prepared according to
procedure A, using (2R,4R)-pentane-2,4-diol [1c(2R,4R)] (52 mg,
0.5 mmol), thioglycoside 7 (1.3 g, 1.9 mmol), N-iodosuccinimide
(675 mg, 3.0 mmol), TfOH (0.18 mL, 2.0 mmol). After flash col-
umn chromatography (silica gel, ethyl acetate/hexane, 1:6) and
recrystallization from ethanol; 2c(2R,4R) (540 mg, 86%) was ob-
tained as a white solid, [α]2D5 = –77.32 (c = 0.76, CH3Cl). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 8.07–7.21 (m, 40 H, HAr), 6.06 (t,
heptane (2e): The product was prepared according to procedure A,
using the diastereomeric mixture of heptane-2,4,6-triol (1e) (9 mg,
0.06 mmol, mixture of diastereomers), thioglycoside 7 (324 mg,
0.47 mmol), N-iodosuccinimide (115 mg, 0.51 mmol), TfOH
(0.044 mL, 0.5 mmol). After flash column chromatography (silica
gel, ethyl acetate/hexane, 1:6) and recrystallization from ethanol;
2e (80 mg, 70%, mixture of diastereomers) was obtained as a white
1
solid. H NMR (300 MHz, [D6]acetone, 25 °C): δ = 8.18–7.08 (m,
3
3JH,H = 10.0 Hz, 2 H, 4Ј-H), 5.94 (dd, JH,H = 10.0, 3.0 Hz, 2 H,
HAr), 6.34–5.32 (m), 5.00–3.76 (m, 1Ј-H-6Ј-H, 2-H, 4-H, 6-H),
3
3Ј-H), 5.58 (dd, JH,H = 3.0, 1.7 Hz, 2 H, 2Ј-H), 5.36 (m, 2 H, 1Ј-
2.58–1.98 (m, 3-H, 5-H), 1.68–1.45 (m, 1-H, 7-H) ppm. 13C NMR
3
2
H), 4.65 (dd, JH,H = 12.1, JH,H = 2.4 Hz, 2 H, 6Ј-H), 4.58–4.54 (75 MHz, [D6]acetone, 25 °C): δ = 166.4–165.9 (PhCO), 134.3–
2
(m, 2 H, 5Ј-H), 4.50 (dd, 3JH,H = 12.1, JH,H = 4.9 Hz, 2 H, 6Ј-H),
129.1 (CAr), 100.6–96.3 (1Ј-C), 78.3–75.3, 72.7–69.1, (2-C, 4-C, 6-
C, 2Ј-C, 3Ј-C, 5Ј-C) 68.0–67.6 (4Ј-C), 64.3–63.5 (6Ј-C), 44.3–42.5
4.20–4.12 (m, 2 H, 2-H, 4-H), 1.81–1.76 (m, 2 H, 3-H), 1.45 (d,
3JH,H = 6.0 Hz, 6 H, 1-H, 5-H) ppm. 13C NMR (50 MHz, CDCl3, (3-C, 5-C), 22.8–19.6 (1-C, 7-C) ppm. HRMS (MALDI): m/z calcd.
25 °C): δ = 166.3–165.3 (8 C, PhCO), 133.4–128.3 (48 C, CAr), 99.1
(2 C, 1Ј-C), 75.5 (2 C, 2-C, 4-C), 71.1 (2 C, 5Ј-C), 70.1 (2 C, 3Ј-C),
69.1 (2 C, 2Ј-C), 67.4 (2 C, 4Ј-C), 63.4 (2 C, 6Ј-C), 45.7 (3-C), 22.4
(2 C, 1-C, 5-C) ppm. C73H64O20 (1260.40): calcd. C 69.52, H 5.11;
found C 69.24, H 5.09. HRMS (MALDI): m/z calcd. for C73H64O20
([M + Na]+) 1283.3883, found 1283.3878.
for C109H94O30 ([M + Na]+) 1905.5722, found 1905.5681.
(2S,3R)-2,3-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α- -mannopyranosyloxy)-
D
butane [3a(2S,3R)]: The product was prepared according to pro-
cedure B, using 2a(2S,3R) (250 mg, 0.2 mmol), NaOMe (20 mg,
0.37 mmol), Amberlite IR-120 (H+; 85 mg, 0.37 mmol), and Ac2O
(3 mL, large excess). After flash column chromatography (silica gel,
(2S,4S)-2,4-Bis(2Ј,3Ј,4Ј6Ј-tetra-O-benzoyl-α-D-mannopyranosyl- ethyl acetate/hexane, 1:2); 3a(2S,3R) (113 mg, 75%) was obtained
oxy)pentane [2c(2S,4S)]: The product was prepared according to
procedure A, using (2S,4S)-pentane-2,4-diol [1c(2S,4S)] (13 mg,
0.12 mmol), thioglycoside 7 (325 mg, 0.47 mmol), N-iodosuccin-
imide (160 mg, 0.71 mmol), and TfOH (0.062 mL, 0.71 mmol). Af-
ter flash column chromatography (silica gel, ethyl acetate/hexane,
1:6) and recrystallization from ethanol; 2c(2S,4S) (121 mg, 80%)
was obtained as a white solid, [α]2D5 = –51.10 (c = 1.04, CH3Cl). 1H
as a colorless solid, [α]2D5 = +52.70 (c = 0.74, CH3Cl). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 5.32–5.17 (m, 6 H, 2Ј-H, 3Ј-H, 4Ј-
3
3
H), 4.99 (d, JH,H = 1.5 Hz, 1 H, 1Ј-H), 4.93 (d, JH,H = 1.5 Hz, 1
H, 1Ј-H), 4.31–4.04 (m, 6 H, 5Ј-H, 6Ј-H), 3.82–3.78 (m, 2 H, 2-H,
3-H), 2.13 (s, 3 H, CH3), 2.12 (s, 3 H, CH3), 2.08 (s, 3 H, CH3),
2.07 (s, 3 H, CH3), 2.02 (m, 6 H, CH3), 1.96 (m, 6 H, CH3), 1.24
3
3
(d, JH,H = 6.4 Hz, 3 H), 1.14 (d, JH,H = 6.4 Hz, 3 H, 1-H, 4-H)
NMR (500 MHz, CDCl3, 25 °C): δ = 8.07–7.23 (m, 40 H, HAr), ppm. 13C NMR (75 MHz, [D6]DMSO, 25 °C): δ = 170.0–169.5 (8
6.15 (t, 3JH,H = 10.0 Hz, 2 H, 4Ј-H), 5.93 (dd, 3JH,H = 10.0, 3.0 Hz,
C, CH3CO), 97.2 (1Ј-C), 93.1 (1Ј-C), 77.3 (3-C), 73.0 (2-C), 69.1
Eur. J. Org. Chem. 2009, 43–52
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
49

J. Yuan, H. Frauenrath
FULL PAPER
(5Ј-C), 68.9 (5Ј-C), 68.7 (3Ј-C), 68.6 (3Ј-C), 68.3 (2Ј-C), 68.0 (2Ј-
(ESI): m/z calcd. for C32H46O20 ([M + Na]+) 773.2475, found
C), 65.7 (4Ј-C), 65.3 (4Ј-C), 62.2 (6Ј-C), 62.0 (6Ј-C), 20.6–20.3 (8 773.2480.
C, CH3CO), 15.5, 13.2 (1-C, 4-C) ppm. C32H46O20 (750.26): calcd.
(3S)-1,3-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-mannopyranosyloxy)-
C 51.20, H 6.18; found C 51.16, H 6.20. HRMS (ESI): m/z calcd.
butane [3b(3S)]: The product was prepared according to procedure
B, using 2b(3S) (180 mg, 0.14 mmol), NaOMe (20 mg, 0.37 mmol),
Amberlite IR-120 (H+; 84 mg, 0.37 mmol), and Ac2O (3 mL, large
excess). After flash column chromatography (silica gel, ethyl ace-
tate/hexane, 1:2); 3b(3S) (75 mg, 71%) was obtained as a colorless
syrup, [α]2D5 = +74.06 (c = 2.7, CH3Cl). 1H NMR (500 MHz,
CDCl3, 25 °C): δ = 5.31–5.24 (m, 4 H, 3Ј-H, 4Ј-H), 5.18 (dd, 3JH,H
for C32H46O20 ([M + Na]+) 773.2475, found 773.2479.
(2R,3R)-2,3-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-mannopyranosyloxy)-
butane 3a(2R,3R): The product was prepared according to pro-
cedure B, using 2a(2R,3R) (180 mg, 0.14 mmol), NaOMe (20 mg,
0.37 mmol), Amberlite IR-120 (H+; 85 mg, 0.37 mmol), and Ac2O
(3 mL, large excess). After flash column chromatography (silica gel,
ethyl acetate/hexane, 1:2); 3a(2R,3R) (85 mg, 81%) was obtained
as a colorless syrup, [α]2D5 = +53.30 (c = 0.86, CH3Cl). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 5.32–5.23 (m, 4 H, 3Ј-H, 4Ј-H), 5.20
3
= 3.2, 1.5 Hz, 1 H, 2Ј-H), 5.15 (dd, JH,H = 3.2, 1.5 Hz, 1 H, 2Ј-
3
3
H), 4.93 (d, JH,H = 1.5 Hz, 1 H, 1Ј-H), 4.81 (d, JH,H = 1.5 Hz, 1
3
2
H, 1Ј-H), 4.31 (dd, JH,H = 12.1, JH,H = 5.2 Hz, 1 H, 6Ј-H), 4.28
(dd, J = 12.1, 5.2 Hz, 1 H, 6Ј-H), 4.08 (dd, JH,H = 12.1, JH,H =
3
3
3
2
(dd, JH,H = 3.0, 1.5 Hz, 2 H, 2Ј-H), 4.96 (d, JH,H = 1.5 Hz, 2 H,
1Ј-H), 4.24 (dd, 3JH,H = 12.1, 2JH,H = 5.8 Hz, 2 H, 6Ј-H), 4.12 (dd,
2.6 Hz, 1 H, 6Ј-H), 4.06 (dd, 3JH,H = 12.1, 2JH,H = 2.6 Hz, 1 H, 6Ј-
H), 4.01–3.94 (m, 2 H, 5Ј-H), 3.93–3.88 (m, 1 H), 3.81–3.76 (m, 1
H), 3.59–3.54 (m, 1 H), (1-H, 3-H), 2.14 (m, 6 H, CH3), 2.08 (s, 3
H, CH3), 2.07 (s, 3 H, CH3), 2.03 (s, 3 H, CH3), 2.02 (s, 3 H, CH3),
3JH,H = 12.1, JH,H = 2.6 Hz, 2 H, 6Ј-H), 4.08–4.04 (m, 2 H, 5Ј-
2
H), 3.76–3.71 (m, 2 H, 2-H, 3-H), 2.13 (s, 6 H, CH3), 2.09 (s, 6 H,
3
CH3), 2.04 (s, 6 H, CH3), 1.97 (s, 6 H, CH3), 1.21 (d, JH,H
=
6.0 Hz, 6 H, 1-H, 4-H) ppm. 13C NMR (75 MHz, [D6]DMSO,
1.97 (s, 3 H, CH3), 1.96 (s, 3 H, CH3), 1.93–1.87 (m, 1 H, 2-H),
3
25 °C): δ = 170.0–169.5 (8 C, CH3CO), 97.4 (2 C, 1Ј-C), 77.3 (2 C, 1.84–1.77 (m, 1 H, 2-H), 1.18 (d, JH,H = 6.1 Hz, 3 H, 4-H) ppm.
2-C, 3-C), 69.1 (2 C, 5Ј-C), 68.4 (2 C, 3Ј-C), 68.3 (2 C, 2Ј-C), 65.7
(2 C, 4Ј-C), 62.2 (2 C, 6Ј-C), 20.5–20.3 (8 C, CH3CO), 16.1 (2 C, CH3CO), 96.4 (1Ј-C), 94.1 (1Ј-C), 69.8 (3-C), 69.3 (2 C, 5Ј-C), 68.8
13C NMR (75 MHz, [D6]DMSO, 25 °C): δ = 170.0–169.4 (8 C,
1-C, 4-C) ppm. C32H46O20 (750.26): calcd. C 51.20, H 6.18; found
C 50.99, H 6.12. HRMS (ESI): m/z calcd. for C32H46O20 ([M +
Na]+) 773.2475, found 773.2473.
(3Ј-C), 68.7 (3Ј-C), 68.2 (2Ј-C), 67.9 (2Ј-C), 65.5 (2 C, 4Ј-C), 64.1
(1-C), 62.0 (6Ј-C), 61.96 (6Ј-C), 35.7 (2-C), 20.6–20.3 (8 C,
CH3CO), 18.7 (4-C) ppm. C32H46O20 (750.26): calcd. C 51.20, H
6.18; found C 50.92, H 6.21. HRMS (ESI): m/z calcd. for
C32H46O20 ([M + Na]+) 773.2475, found 773.2473.
(2S,3S)-2,3-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
butane [3a(2S,3S)]: The product was prepared according to pro-
cedure B, using 2a(2S,3S) (160 mg, 0.13 mmol), NaOMe (20 mg, (2S,4R)-2,4-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D-mannopyranosyloxy)-
D
-mannopyranosyloxy)-
0.37 mmol), Amberlite IR-120 (H+; 85 mg, 0.37 mmol), and Ac2O
(3 mL, large excess). After flash column chromatography (silica gel,
ethyl acetate/hexane, 1:2); 3a(2S,3S) (80 mg, 82%) was obtained as
a colorless solid, [α]2D5 = +54.94 (c = 0.46, CH3Cl). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 5.35–5.26 (m, 4 H, 3Ј-H, 4Ј-H), 5.22
pentane [3c(2S,4R)]: The product was prepared according to pro-
cedure B, using 2c(2S,4R) (180 mg, 0.14 mmol), NaOMe (20 mg,
0.37 mmol), Amberlite IR-120 (H+; 84 mg, 0.37 mmol), and Ac2O
(3 mL, large excess). After flash column chromatography (silica gel,
ethyl acetate/hexane, 1:2); 3c(2S,4R) (86 mg, 79%) was obtained as
a colorless syrup, [α]2D5 = +45.53 (c = 1.51, CH3Cl). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 5.32–5.23 (m, 4 H, 3Ј-H, 4Ј-H), 5.13
3
3
(dd, JH,H = 3.2, 1.7 Hz, 2 H, 2Ј-H), 4.97 (d, JH,H = 1.7 Hz, 2 H,
3
2
1Ј-H), 4.36 (dd, JH,H = 12.6, JH,H = 5.3 Hz, 2 H, 6Ј-H), 4.13–
3
3
4.08 (m, 4 H, 5Ј-H, 6Ј-H), 3.90–3.82 (m, 2 H, 2-H, 3-H), 2.16 (s, 6 (dd, JH,H = 3.2, 1.5 Hz, 1 H, 2Ј-H), 5.10 (dd, JH,H = 3.2, 1.5 Hz,
3
3
H, CH3), 2.09 (s, 6 H, CH3), 1.99 (s, 6 H, CH3), 1.97 (s, 6 H, CH3), 1 H, 2Ј-H), 4.92 (d, JH,H = 1.5 Hz, 1 H, 1Ј-H), 4.90 (d, JH,H
=
3
1.16 (d, JH,H = 5.8 Hz, 6 H, 1-H, 4-H) ppm. 13C NMR (50 MHz,
1.5 Hz, 1 H, 1Ј-H), 4.28 (dd, 3JH,H = 12.1, 2JH,H = 5.2 Hz, 1 H, 6Ј-
3
2
[D6]DMSO, 25 °C): δ = 170.0–169.2 (8 C, CH3CO), 93.5 (2 C, 1Ј- H), 4.24 (dd, JH,H = 12.1, JH,H = 5.2 Hz, 1 H, 6Ј-H), 4.10–4.04
C), 73.2 (2 C, 2-C, 3-C), 69.1 (2 C, 5Ј-C), 68.8 (2 C, 3Ј-C), 68.1 (2
C, 2Ј-C), 65.0 (2 C, 4Ј-C), 61.7 (2 C, 6Ј-C), 20.6–20.2 (8 C, CH3CO),
13.8 (2 C, 1-C, 4-C) ppm. C32H46O20 (750.26): calcd. C 51.20, H
6.18; found C 50.92, H 6.32. HRMS (ESI): m/z calcd. for
C32H46O20 ([M + Na]+) 773.2475, found 773.2474.
(m, 3 H, 5Ј-H, 6Ј-H), 3.97–3.93 (m, 1 H, 5Ј-H), 3.91–3.82 (m, 2 H,
2-H, 4-H), 2.13 (s, 3 H, CH3), 2.13 (s, 3 H, CH3), 2.07 (s, 3 H,
CH3), 2.06 (s, 3 H, CH3), 2.03 (s, 3 H, CH3), 2.02 (s, 3 H, CH3),
1.97 (s, 3 H, CH3), 1.97 (s, 3 H, CH3), 1.97–1.93 (m, 1 H, 3-H),
3
1.58–1.53 (m, 1 H, 3-H), 1.29 (d, JH,H = 6.1 Hz, 3 H), 1.18 (d,
3JH,H = 6.1 Hz, 3 H), (1-H, 5-H) ppm. 13C NMR (75 MHz, [D6]-
DMSO, 25 °C): δ = 170.0–169.6 (8 C, CH3CO), 96.2 (1Ј-C), 94.4
(1Ј-C), 72.5 (4-C), 70.3 (2-C), 69.3 (5Ј-C), 69.2 (5Ј-C), 68.7 (3Ј-C),
68.6 (3Ј-C), 68.4 (2Ј-C), 68.1 (2Ј-C), 65.7 (4Ј-C), 65.5 (4Ј-C), 62.2
(2 C, 6Ј-C), 42.7 (3-C), 20.8–20.4 (8 C, CH3CO), 19.0 (2 C, 1-C, 5-
C) ppm. C33H48O20 (764.27): calcd. C 51.83, H 6.33; found C 51.87,
H 6.39. HRMS (ESI): m/z calcd. for C33H48O20 ([M + Na]+)
787.2631, found 787.2630.
(3R)-1,3-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-mannopyranosyloxy)-
butane [3b(3R)]: The product was prepared according to procedure
B, using 2b(3R) (510 mg, 0.41 mmol), NaOMe (50 mg, 0.93 mmol),
Amberlite IR-120 (H+; 215 mg, 0.95 mmol), and Ac2O (3 mL, large
excess). After flash column chromatography (silica gel, ethyl ace-
tate/hexane, 1:2); 3b(3R) (230 mg, 76%) was obtained as a colorless
syrup, [α]2D5 = +32.72 (c = 1.68, CH3Cl). 1H NMR (500 MHz,
[D6]DMSO, 25 °C): δ = 5.12–5.00 (m, 6 H, 2Ј-H, 3Ј-H, 4Ј-H), 4.90
(m, 1 H, 1Ј-H), 4.81 (m, 1 H, 1Ј-H), 4.15–4.10 (m, 2 H, 6Ј-H), 4.03–
(2R,4R)-2,4-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-mannopyranosyloxy)-
3.99 (m, 3 H, 5Ј-H, 6Ј-H), 3.93–3.89 (m, 1 H, 5Ј-H), 3.87–3.82 (m, pentane [3c(2R,4R)]: The product was prepared according to pro-
1 H), 3.72–3.67 (m, 1 H), 3.49–3.44 (m, 1 H), (1-H, 3-H), 2.08–
cedure B, using 2c(2R,4R) (210 mg, 0.17 mmol), NaOMe (20 mg,
3
1.91 (m, 24 H, CH3), 1.79–1.73 (m, 2 H, 2-H), 1.22 (d, JH,H
=
0.37 mmol), Amberlite IR-120 (H+; 84 mg, 0.37 mmol), and Ac2O
6.1 Hz, 3 H, 4-H) ppm. 13C NMR (50 MHz, [D6]DMSO, 25 °C): δ (3 mL, large excess). After flash column chromatography (silica gel,
= 170.0–169.4 (8 C, CH3CO), 96.94 (1Ј-C), 96.90 (1Ј-C), 72.9 (3-
C), 69.2 (5Ј-C), 68.8 (5Ј-C), 68.7 (3Ј-C), 68.5 (3Ј-C), 68.1 (2Ј-C),
67.9 (2Ј-C), 65.7 (4Ј-C), 65.5 (4Ј-C), 64.1 (1-C), 62.2 (6Ј-C), 62.0 (500 MHz, CDCl3, 25 °C): δ = 5.33 (dd, JH,H = 10.1, 3.2 Hz, 2 H,
(6Ј-C), 35.6 (2-C), 21.1–20.4 (9 C, CH3CO, 4-C) ppm. C32H46O20 3Ј-H), 5.23 (t, JH,H = 10.1 Hz, 2 H, 4Ј-H), 5.03 (dd, JH,H = 3.2,
(750.26): calcd. C 51.20, H 6.18; found C 50.95, H 6.19. HRMS
ethyl acetate/hexane, 1:2); 3c(2R,4R) (107 mg, 82%) was obtained
as a colorless solid, [α]2D5 = +10.29 (c = 0.89, CH3Cl). 1H NMR
3
3
3
3
1.7 Hz, 2 H, 2Ј-H), 4.89 (d, JH,H = 1.7 Hz, 2 H, 1Ј-H), 4.23 (dd,
50
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 43–52

Models for the Microstructure Analysis of Poly(Vinyl Glycoside)s
2
3JH,H = 12.1, JH,H = 6.1 Hz, 2 H, 6Ј-H), 4.12–4.07 (m, 4 H, 5Ј-H, flask containing DCM (100 mL). The reaction mixture was stirred
6Ј-H), 3.89–3.85 (m, 2 H, 2-H, 4-H), 2.11 (s, 6 H, CH3), 2.07 (s, 6 overnight at room temperature. The reaction mixture was evapo-
H, CH3), 2.03 (s, 6 H, CH3), 1.99 (s, 6 H, CH3), 1.59–1.56 (m, 2 rated to dryness. After purification by flash column chromatog-
3
H, 3-H), 1.27 (d, JH,H = 6.1 Hz, 6 H, 1-H, 5-H) ppm. 13C NMR raphy (silica gel, ethyl acetate/hexane, 1:3); 5 (660 mg, 100%) was
(75 MHz, [D6]DMSO, 25 °C): δ = 170.0–169.5 (8 C, CH3CO), 97.9
(2 C, 1Ј-C), 74.4 (2 C, 2-C, 4-C), 69.3 (2 C, 5Ј-C), 68.4 (2 C, 3Ј-C),
obtained as a colorless syrup. 1H NMR (300 MHz, CDCl3, 25 °C):
δ = 4.43–4.04 (m, 1 H, 4-H), 3.62–3.55 (m, 1 H, OH), 3.16–3.05
68.2 (2 C, 2Ј-C), 65.8 (2 C, 4Ј-C), 62.2 (2 C, 6Ј-C), 44.4 (3-C), 21.5 (m, 2 H, 2-H, 6-H), 2.81–2.74 (m, 2 H, 1-H, 7-H), 2.58–2.47 (m, 2
(2 C, 1-C, 5-C), 20.6–20.4 (8 C, CH3CO) ppm. C33H48O20 (764.27): H, 1-H, 7-H), 1.96–1.83 (m, 2 H, 3-H, 5-H), 1.62–1.50 (m, 2 H, 3-
calcd. C 51.83, H 6.33; found C 51.90, H 6.40. HRMS (MALDI):
H, 5-H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 68.7, 67.9,
(4-C), 50.3, 50.1, 50.0, (2-C, 6-C), 47.0, 46.6, (1-C, 7-C), 39.9, 39.5,
39.4, (3-C, 5-C) ppm. HRMS (EI): m/z calcd. for C7H12O3 ([M –
C3H5O]+) 87.0441, found 87.0441.
m/z calcd. for C33H48O20 ([M + Na]+) 787.2631, found 787.2636.
(2S,4S)-2,4-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-mannopyranosyloxy)-
pentane [3c(2S,4S)]: The product was prepared according to pro-
cedure B, using 2c(2S,4S) (190 mg, 0.15 mmol), NaOMe (20 mg,
0.37 mmol), Amberlite IR-120 (H+; 84 mg, 0.37 mmol), and Ac2O
(3 mL, large excess). After flash column chromatography (silica gel,
ethyl acetate/hexane, 1:2); 3c(S,S) (90 mg, 80%) was obtained as
colorless solid, [α]2D5 = +73.03 (c = 1.16, CH3Cl). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 5.34–5.24 (m, 4 H, 3Ј-H, 4Ј-H), 5.14
1,2:6,7-Diexpoxy-4-(trimethylsilyloxy)heptane (6): Heptan-1,2:6,7-
diepoxy-4-ol 5 (700 mg, 4.9 mmol), and triethylamine (1.6 g,
15.8 mmol, 3.3 equiv.) were added to a flask containing THF
(50 mL). The solution was cooled to 0 °C, and TMS-Cl (1.3 mL,
10.2 mmol, 2.1 equiv.) was added dropwise. The reaction mixture
was stirred for 6 h, and the reaction was followed by TLC. Then,
the reaction mixture was evaporated to dryness. After purification
by flash column chromatography (silica gel, ethyl acetate/hexane,
3
3
(dd, JH,H = 3.2, 1.5 Hz, 2 H, 2Ј-H), 4.93 (d, JH,H = 1.5 Hz, 2 H,
1Ј-H), 4.29 (dd, 3JH,H = 12.3, 2JH,H = 5.1 Hz, 2 H, 6Ј-H), 4.09 (dd,
J = 12.3, JH,H = 2.1 Hz, 2 H, 6Ј-H), 4.07–4.00 (m, 2 H, 5Ј-H),
2
1
1:5); 6 (890 mg, 85%) was obtained as a colorless syrup. H NMR
3.91–3.81 (m, 2 H, 2-H, 4-H), 2.16 (s, 6 H, CH3), 2.09 (s, 6 H,
CH3), 2.05 (s, 6 H, CH3), 1.99 (s, 6 H, CH3), 1.82 (m, 2 H, 3-H),
(500 MHz, CDCl3, 25 °C): δ = 4.03–3.94 (m, 1 H, 4-H), 2.93–2.82
(m, 2 H, 2-H, 6-H), 2.68–2.57 (m, 2 H, 1-H, 7-H), 2.39–2.27 (m, 2
H, 1-H, 7-H), 1.77–1.36 (m, 4 H, 3-H, 5-H), 0.00 (m, 9 H, SiCH3)
ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 68.3, 68.1, 68.0, (4-
C), 49.4, 49.2, 49.0, 48.9, (2-C, 6-C), 47.3, 47.2, 46.33, 46.27, (1-C,
7-C), 41.0, 40.8, 40.4, 39.9, (3-C, 5-C), 0.1, 0.03, –0.01 (SiCH3)
ppm. HRMS (EI): m/z calcd. for C10H20O2Si ([M – C3H5O]+)
159.0836, found 159.0832.
3
1.21 (d, JH,H = 6.0 Hz, 6 H, 1-H, 5-H) ppm. 13C NMR (75 MHz,
[D6]DMSO, 25 °C): δ = 170.1–169.5 (8 C, CH3CO), 94.6 (2 C, 1Ј-
C), 71.2 (2 C, 2-C, 4-C), 69.4 (2 C, 5Ј-C), 68.6 (2 C, 3Ј-C), 68.2 (2
C, 2Ј-C), 65.5 (2 C, 4Ј-C), 62.1 (2 C, 6Ј-C), 43.6 (3-C), 20.6–20.4 (8
C, CH3CO), 19.4 (2 C, 1-C, 5-C) ppm. C33H48O20 (764.27): calcd.
C 51.83, H 6.33; found C 51.78, H 6.39. HRMS (ESI): m/z calcd.
for C33H48O20 ([M + Na]+) 787.2631, found 787.2635.
Supporting Information (see also the footnote on the first page of
1,4-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-mannopyranosyloxy)butane
1
this article): H and 13C NMR spectra of 1c(2S,4R), 1e, 2a–e, 3a–
(3d): The product was prepared according to procedure B, using 2d
(230 mg, 0.18 mmol), NaOMe (20 mg, 0.37 mmol), Amberlite IR-
120 (H+; 84 mg, 0.37 mmol), and Ac2O (3 mL, large excess). After
flash column chromatography (silica gel, ethyl acetate/hexane, 1:2);
3d (96 mg, 72%) was obtained as white solid, [α]2D5 = +57.56 (c =
e, 5 and 6.
Acknowledgments
1
2.44, CH3Cl). H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 5.10–
The authors would like to thank Dr. Muhua Huang (group of Prof.
A. Vasella, ETH Zürich) for helping us with measuring the optical
rotations and Prof. A. D. Schlüter for his generous support.
5.05 (m, 6 H, 2Ј-H, 3Ј-H, 4Ј-H), 4.85 (m, 2 H, 1Ј-H), 4.15–4.00 (m,
4 H, 6Ј-H), 3.92–3.89 (m, 2 H, 5Ј-H), 3.66–3.62 (m, 2 H, 1-H, 4-
H) 3.50–3.45 (m, 2 H, 1-H, 4-H), 2.08–1.91 (m, 24 H, CH3), 1.64–
1.59 (m, 4 H, 2-H, 3-H) ppm. 13C NMR (125 MHz, [D6]DMSO,
25 °C): δ = 170.1–169.6 (8 C, CH3CO), 96.7 (2 C, 1Ј-C), 68.83 (2
C, 5Ј-C), 68.76 (2 C, 3Ј-C), 67.9 (2 C, 2Ј-C), 67.3 (2 C, 1-C, 4-C),
65.5 (2 C, 4Ј-C), 62.1 (2 C, 6Ј-C), 25.6 (2 C, 2-C, 3-C), 20.6–20.5
(8 C, CH3CO) ppm. C32H46O20 (750.26): calcd. C 51.20, H 6.18;
found C 50.92, H 6.21. HRMS (ESI): m/z calcd. for C32H46O20
([M + Na]+) 773.2475, found 773.2473.
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
51

J. Yuan, H. Frauenrath
FULL PAPER
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Published Online: November 21, 2008
52
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Eur. J. Org. Chem. 2009, 43–52