Convenient syntheses and transformations of 2-C-malonyl carbohydrates

Article abstract of DOI:10.1002/chem.200701151

2-C-malonyl carbohydrates were synthesized in only few steps and high yields by radical additions of malonates to glycals. For the first time, the undesired formation of nitrates was completely suppressed with anhydrous cerium ammonium nitrate (CAN) as ox

Full text of DOI:10.1002/chem.200701151

DOI: 10.1002/chem.200701151
Convenient Syntheses and Transformations of 2-C-Malonyl Carbohydrates
Jian Yin, Thomas Sommermann, and Torsten Linker*[a]
Abstract: 2-C-malonyl carbohydrates
were synthesized in only few steps and
high yields by radical additions of mal-
onates to glycals. For the first time, the
undesired formation of nitrates was
completely suppressed with anhydrous
cerium ammonium nitrate (CAN) as
oxidizing agent. A coherent explana-
tion for the high stereoselectivities of
the additions to gluco-configured gly-
cals was provided by variation of the
substituents in the 3-position. We es-
tablished steric effects for the face se-
lectivity, and electronic effects strongly
influence the reactivity of the double
bonds. The scope and limitation of
transition-metal-mediated radical reac-
tions in the synthesis of 2-C-branched
carbohydrates was thoroughly investi-
gated. Thus, unsaturated disaccharides
and benzyl-protected glycals were used
as substrates for the first time. Finally,
the 2-C-malonyl carbohydrates were
transformed into various products by
decarboxylation, saponification and re-
duction, which afforded interesting pre-
cursors for C-disaccharides. In this
paper we describe the syntheses of
more than 40 new 2-C-analogues of
carbohydrates, which were isolated in
high yields in analytically pure form.
Therefore, the transition-metal-mediat-
ed radical addition of malonates to gly-
cals offers a simple and convenient
entry to such important carbohydrate
derivatives.
Keywords:
carbohydrates
·
C-glycosides · radicals · synthetic
methods · transformations
Introduction
Radical reactions have become an important and versatile
ꢀ
tool for the selective formation of carbon carbon bonds in
C-Glycosides are of current interest in chemistry, biology,
and medicine.[1] They are characterized by the substitution
of the interglycosidic oxygen by a carbon atom, resulting in
higher stabilities towards enzymatic and chemical hydroly-
ses. Although many synthetic strategies for simple C-glyco-
sides were developed over the years,[2] the preparation of C-
oligosaccharides is more laborious and depends on a con-
venient access to the corresponding C-branched monosac-
charides.[3] For this purpose, carbon substituents can be
easily introduced at the anomeric center, whereas C-func-
tionalizations at other positions of the carbohydrate require
many steps. Especially carboxylic acid side chains are of cur-
rent interest, since they offer an elegant entry to C-oligosac-
charides by ring-closing metathesis.[4] Herein, we describe
general and convenient syntheses of such C-branched carbo-
hydrates in only few steps and high selectivities from easily
available precursors.
highly functionalized molecules and have found many appli-
cations in natural product chemistry.[5] In context with our
studies on transition-metal-mediated radical reactions,[6] we
became interested in the synthesis of 2-C-branched carbohy-
drates by this methodology.[7] The introduction of carbon
chains at the 2-position of carbohydrates was previously re-
alized by epoxide opening[8] or by rearrangements,[9] howev-
er the synthesis of the precursors required many reactions
steps. More recently, the cyclopropanation of glycals and
subsequent ring opening offered a simpler access,[10] but rad-
ical reactions are still a very convenient way for the stereo-
selective synthesis of 2-C-branched carbohydrates. The two
different radical strategies are summarized in Scheme 1.
Starting from precursor 1, the carbohydrate radicals 2 can
be generated and added to alkenes to afford the 2-C-
branched carbohydrates 3 (Scheme 1, pathway A). Although
many inter- and intramolecular applications of such reac-
tions have been described,[4d,e,11] the tedious synthesis of the
precursors 1, the high toxicity of the reagents, and the often
moderate stereoselectivities are disadvantageous. Therefore,
we developed a simple procedure to introduce malonyl sub-
stituents at the 2-position of carbohydrates in only one step
from commercially available starting materials (Scheme 1,
[a] J. Yin, Dr. T. Sommermann, Prof. Dr. T. Linker
Department of Chemistry, University of Potsdam
Karl-Liebknecht-Strasse 24–25, 14476 Potsdam (Germany)
Fax : (+49)331-977-5056
E-mail: linker@chem.uni-potsdam.de
pathway B).[7] The reaction of malonates 4 with Mn
ACHTREUNG(OAc)3
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FULL PAPER
yl malonate (4b) to the glycals 6a–c under various condi-
tions (Scheme 2).
Scheme 1. Radical strategies for the syntheses of 2-C-branched carbohy-
drates. R=protecting group; X=I, HgOAc, PhOC(S)O; Y=acceptor,
CH2SnBu3; Mn+ =Mn3+, Ce4+
.
or cerium ammonium nitrate (CAN) generates the electro-
philic radicals 5, which add to glycals 6 to afford 2-C-malon-
yl carbohydrates via the radicals 7 in high yields, regio- and
stereoselectivities.
We were able to extend our methodology to 1-substituted
glycals,[12] to other CH acidic precursors,[13] and applied tran-
sition-metal-mediated radical reactions as the key step in
the synthesis of 3-deoxy-d-oct-2-ulosonic acids (KDO).[14]
Very recently, we described the decarboxylation of the mal-
onate addition products to carboxylic acids.[15] However, our
previous studies were limited to acetylated monosaccharides
and no disaccharides were investigated. Furthermore, base
stable protecting groups would allow various further trans-
formations of the malonyl sided chain.
Scheme 2. Addition of malonates 4 to glycals 6. Method A: 4 equiv
CAN; method B: 4 equivCAN, 0.5 equivwater; method C: 4 equivanhy-
drous CAN. Yields of isolated products after column chromatography are
indicated in parentheses.
Herein we examine the scope and limitations of transi-
tion-metal-mediated radical reactions in the synthesis of 2-
C-branched carbohydrates. The formation of nitrates could
be suppressed and a coherent explanation for the high ste-
reoselectivities of the additions by variation of the substitu-
ents in the 3-position is provided. Unsaturated disaccharides
and benzyl-protected glycals, which are stable under basic
reaction conditions, are used as substrates for transition-
The generation of malonyl radicals from commercially
available CAN affords the nitrates 9 as by-products in 8–
17% yield (method A). Such nitrates are often observed in
transition-metal-mediated radical reactions.[16] In our previ-
ous studies we discussed the direct attack of the adduct radi-
cals 7 to the nitrate ligand of CAN as a mechanistic ration-
al.[7] However, an ionic trapping of the anomeric carbenium
ion by nitric acid, which is always present in wet CAN,
might explain the formation of the nitrates 9 as well. To
prove this hypothesis, we added 0.5 equiv of water to the
commercially available CAN (method B) and conducted the
radical additions under otherwise identical conditions.
Indeed, the yields of the nitrates 9 increased to 34–38%
(Scheme 2), which is in accordance to an ionic mechanism.
For synthetic applications and further transformations of
the 2-C-malonyl carbohydrates 8, it was important to sup-
press the undesired formation of the nitrates 9. This was
achieved employing anhydrous CAN, derived from drying of
the commercially available material in a desiccator under
high vacuum. Under such conditions no nitrate 9 was ob-
tained and the methyl glycosides 8 could be isolated in high
yields in analytically pure form (method C, Scheme 2). Ad-
ditionally, separation of the products by column chromatog-
raphy was much easier. Therefore, the new method C with
anhydrous cerium ammonium nitrate represents an im-
provement for transition-metal-mediated radical reactions in
carbohydrate chemistry and was employed for all subse-
quent malonate additions in this paper.
ꢀ
metal-mediated C C-bond formations for the first time. Fi-
nally, selective transformations of the addition products pro-
vide an easy access to a variety of 2-C-branched carbohy-
drates, which can serve as precursors for the synthesis of C-
glycosides.
Results and Discussion
Optimization and stereoselectivities of the radical additions:
The reaction of malonates 4 with glycals 6 and oxidative
trapping of the radicals 7 could lead to eight different regio-
and stereoisomers (Scheme 1, pathway B). However, our
previous studies have shown that the radicals add selectively
to the 2-position under orbital control to afford only one re-
gioisomer.[7] Furthermore, the reactions are highly 1,2-trans
selective, since the methyl glycosides 8 are formed by a
neighboring group participation of the malonyl substituents.
On the other hand, nitrates 9 were isolated as by-products,
which reduced the yields of the desired 2-C-analogues 8. To
optimize the reactions and to study the stereoselectivities,
we investigated the addition of dimethyl (4a) and diisoprop-
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T. Linker et al.
Table 1. Addition of dimethyl malonate (4a) to various 3-substituted gly-
cals 6.
The attack of the radicals to the double bonds of the gly-
cals 6 proceeds with good to excellent stereoselectivities. Es-
pecially tri-O-acetyl-d-galactal (6b) and di-O-acetyl-d-arabi-
nal (6c) afford exclusively one diastereomer 8 in high yields
(Scheme 2). This can be rationalized by unfavorable interac-
tions of the incoming radicals with a pseudo-axial O-acetyl
group (Figure 1), which is in accordance to our previous
studies.[7]
Glycal
R
gluco/
gluco-8 [%][c] manno-8 [%][c]
6[a]
manno[b]
6a
OAc
84:16
gluco-8a
(80)
manno-8a
(15)
6e
O2CPh
83:17
gluco-8e
(78)
manno-8e
(16)
6 f
6g
O2CPhpOMe 79:21
O2CPhpNO2 81:19
gluco-8 f (74) manno-8 f (20)
Figure 1. Preferred side of attack for radicals 5 to glycals 6a–c.
gluco-8g
(73)
manno-8g
(17)
6h
6d
6i
O2C
OH
H
A
82:18
94:6
gluco-8h
(75)
gluco-8d
(45)
manno-8h
(16)
manno-8d (3)
On the other hand, only a moderate influence of the
steric demand of dimethyl malonate (4a) versus diisopropyl
malonate (4b) on the stereoselectivities was observed, since
the ester groups are too far away from the reaction center.
Finally, tri-O-acetyl-d-glucal (6a) represents an interesting
example for the addition of malonates 4. Although both O-
acetyl groups are oriented pseudo-equatorial (Figure 1), the
gluco/manno ratio of the methyl glycosides 8 was rather
high with values ranging from 84:16 to 91:9.
54:46
gluco-8i (47) manno-8i (40)
[a] All reactions were performed on a 2 mmol scale with method C
(4 equivanhydr. CAN, MeOH, 0 8C). [b] gluco/manno ratios determined
by H NMR analysis of the crude product (600 MHz). [c] Yields of isolat-
ed products after column chromatography.
1
In order to explain the good selectivities in favor of the
gluco isomers, we synthesized various 3-substituted glycals
6e–h from 4,6-di-O-acetyl-d-glucal (6d)[17] by esterification.
High yields were obtained with the acid chlorides 10 and
triethylamine as base, only the sterically hindered pivaloyl
chloride (10h) reacted less efficiently (Scheme 3). All gly-
cals were isolated in analytically pure form by column chro-
matography.
with tri-O-acetyl-d-glucal (6a) and with the unsubstituted
4,6-di-O-acetyl-3-deoxy-d-glucal (6i)[18] (Table 1).
Interestingly, the different ester groups in the 3-position
have no influence on the facial selectivity of the radical
attack. Thus, for all glycals 6a and 6e–f the ratio of gluco/
manno is approximately 5:1. Even the sterically most de-
manding pivaloyl derivative 6h did not change the diaste-
reoselectivity and the methyl glycoside gluco-8h was isolat-
ed in 75% yield. This can be rationalized by a conformation
of the ester groups, where the substituents R are too far
away from the reacting double bond (see Scheme 3).
On the other hand, the unprotected 4,6-di-O-acetyl-d-
glucal (6d) exhibits the highest selectivity in favor of the
gluco isomer (Table 1). An explanation might be the com-
plexation of CAN or the polar solvent to the free OH
group, which shields the upper side of the glycal closer to
the double bond and hinders the manno attack of radicals
more efficiently. The fact that the steric influence of the sub-
stituents in the 3-position is indeed responsible for the high
gluco selectivity was finally demonstrated with 4,6-di-O-
acetyl-3-deoxy-d-glucal (6i).[18] Now both faces are not
shielded (R=H) and the addition of dimethyl malonate
(4a) afforded the methyl glycosides 8i in a gluco/manno
ratio of almost 1:1 (Table 1).
Scheme 3. Synthesis of the glycals 6e–h.
The radical addition of dimethyl malonate (4a) to the
gluco-configured glycals 6d–h was performed with anhy-
drous CAN to suppress the formation of nitrates (method
C). Indeed, the methyl glycosides 8 were obtained regiose-
lectively in high yields as sole 1,2-trans isomers (Table 1).
Only the unprotected glycal 6d afforded oxidative by-prod-
ucts, due to the labile allylic alcohol. The diastereoselectivi-
ties of the additions (gluco/manno ratios) were compared
Besides the stereoselectivities, an interesting influence of
the benzoate groups on the reactivity of the glycals 6e–g
was established. Thus, the p-methoxy substituted derivative
6 f gave complete conversion after 3 h, whereas the reaction
of benzoyl glucal 6e took 6 h and the p-nitro substituted
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Malonyl Carbohydrates
FULL PAPER
system 6g even 12 h. These differences in reaction times
nicely correlate with the electronic properties of the func-
tional groups. The electrophilic malonyl radicals 5 interact
preferentially with the HOMO of the double bond,[5] and
therefore electron donors should accelerate the additions.
However, the fact that the electronic effects of the p-sub-
stituents influence the HOMO energies of the glycals 6e–g
through many bonds is a remarkable finding.
In summary, the application of anhydrous CAN (method
C) suppressed completely the formation of nitrates 9 and in-
creased the yields of the desired methyl glycosides 8 consid-
erably. A coherent explanation for the high stereoselectivi-
ties of the additions to glucals was provided by unfavorable
steric interactions of the incoming radicals with the substitu-
ents in the 3-position. Although benzoates do not alter the
stereochemical course of the reactions, a remarkable influ-
ence of the p-substituents on the reactivity was established.
Commercially available cerium ammonium nitrate afforded
the nitrates 9 as by-products and therefore anhydrous CAN
(method C) gave again the best results. Thus, the methyl gly-
cosides malto-8 and lacto-8 were obtained as sole products
in high yields (Scheme 4). All products were isolated by
column chromatography or even simple recrystallization in
analytically pure form. The exclusive formation of one ste-
reoisomer can be rationalized by the second sugar ring,
which efficiently shields the upper face of the double bond.
Therefore, the malonyl radicals 5 can only attack from one
side, independent of the steric demand of the ester groups
(Me vs iPr). To summarize, we realized the first syntheses of
2-C-malonyl disaccharides in only few steps, which clearly
ꢀ
extends the scope of transition-metal-mediated C C-bond
formations in carbohydrate chemistry.
For synthetic applications and further transformations of
the 2-C-malonyl carbohydrates 8 it was necessary to change
the O-acetyl groups at the sugar ring, since acetates and
malonates undergo similar reactions. Especially base stable
protective groups, like O-benzyl, would allow saponifica-
tions and reductions without cleavage. Additionally, the
benzyl ethers could be removed selectively by hydrogenoly-
sis.[20] We decided to introduce the protective groups directly
into the starting materials, since O-benzylated glycals 11 are
available from the O-acetylated precursors 6 on a large
scale by a one-step procedure.[21] However, the stability of
benzyl ethers under the oxidative and Lewis-acidic condi-
tions of the radical reactions had to be examined. Indeed,
the addition of dimethyl malonate (4a) to the glycals 11 in
Addition of malonates to unsaturated disaccharides and
benzyl-protected glycals: After the successful addition of
malonates 4 to the glycals 6a–i we became interested in the
conversion of unsaturated disaccharides 6j–k, to extend the
scope of transition-metal-mediated radical reactions in car-
bohydrate chemistry. Especially the stability of the glycosi-
dic linkage under the oxidative and acidic conditions in the
presence of MnACHTREUNG(OAc)3 or CAN was problematic. We chose
hexa-O-acetyl-d-maltal (6j) and hexa-O-acetyl-d-lactal (6k)
as representative examples, since they are components of
many naturally occurring oligosaccharides and can be easily
synthesized on a large scale.[19] The addition of dimethyl
malonate (4a) and diisopropyl malonate (4b) was investi-
gated with respect to the stereoeselectivities and yields
(Scheme 4).
We conducted the first experiments with MnCAHTRE(UGN OAc)3 to
generate the malonyl radicals 5, but the acidic reaction con-
ditions led to the partial cleavage of the glycosidic linkages.
the presence of MnACHTRE(UNG OAc)3 or commercially available CAN
failed. Even anhydrous CAN (method C) led to partial
cleavage of the protective groups and an undesired Ferrier-
rearrangement.[22] Therefore, we added four equivalents of
NaHCO3 to the reaction mixture (method D) to suppress
the formation of such by-products. Under these conditions
the addition of dimethyl malonate (4a) to the glycals 11 pro-
ceeded smoothly and the methyl glycosides 12 were isolated
in high yields (Scheme 5). The reactions were applicable for
unsaturated hexoses, pentoses, and disaccharides and again
the 1,2-trans isomers were obtained as the sole products.
The stereoselectivities are in accordance to the radical addi-
tions to O-acetylated glycals 6 and only the gluco- and xylo-
Scheme 4. Addition of malonates 4 to glycals 6j and 6k. Method C:
4 equivanhydrous CAN, MeOH, 0 8C. Yields of isolated products after
column chromatography are indicated in parentheses.
Scheme 5. Addition of dimethyl malonate (4a) to glycals 11. Method D:
4 equivanhydrous CAN, 4 equivNaHCO 3, MeOH, 08C. Yields of isolat-
ed products after column chromatography are indicated in parentheses.
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T. Linker et al.
configured glycals 11a and 11d afforded diastereomeric
mixtures. All products were isolated in analytically pure
form after column chromatography and the O-benzylated
methyl glycosides 12 can be used for further transformations
under basic reaction conditions. In summary, in this paper
we synthesized more than 20 new 2-C-malonyl carbohy-
drates, which demonstrates the broad applicability of transi-
tion-metal-mediated radical reactions in carbohydrate
chemistry.
experimental procedure, the diisopropyl malonates 8b were
treated under thermal conditions as well. Indeed, the 2-C-
branched carbohydrates 13b were isolated in analytically
pure form in similar yields (Scheme 6). This is a remarkable
result, since the iodide has to attack the sterically more hin-
dered isopropyl ester by a SN2 mechanism. To the best of
our knowledge, this is the first example for a cleavage of a
diisopropyl malonate under such conditions.
The reaction of the 2-C-malonyl carbohydrates 12 at
1808C (method E) proceeded less efficiently, due to the la-
bility of the benzyl protective groups. Therefore, microwave
irradiation (method F) was applied, which afforded the
products 14 in high yields under milder conditions
(Scheme 6). In summary, 18 different 2-C-branched glyco-
acetic esters 13 and 14 were synthesized in only two steps
from glycals. The products were isolated in high yields as
sole diastereomers, which demonstrates the broad applica-
bility of malonate addition and decarboxylation in carbohy-
drate chemistry.
To investigate the potential of further transformations, we
selected the gluco and galacto isomers, which represent
common configurations of hexoses in nature. Especially the
saponification should provide an easy entry point to malonic
and acetic acids. Best conditions were found with 10 equiva-
lents of lithium hydroxide in mixtures of methanol and
water, where the products 15–18 could be isolated in quanti-
tative yields (Scheme 7). In contrast to the benzylated deriv-
Transformations of the 2-C-malonyl carbohydrates: Many
transformations of carboxylic acid derivatives are known in
literature,[23] and the decarboxylation of malonates is a well
established reaction.[24] However, only one example of a 1-
C-malonyl carbohydrate has been described, which afforded
the corresponding methyl acetate in low yield.[25] In a very
recent communication, we succeeded in a more efficient de-
methoxcarbonylation in the presence of lithium iodide for
selected methyl glycosides 8a.[15] Herein we investigate the
scope and limitations of this reaction for various 2-C-malon-
yl carbohydrates with methyl 8a and isopropyl 8b ester
groups as well as O-benzyl protected derivatives 12 for the
general synthesis of the corresponding acetic esters 13a,
13b, and 14 (Scheme 6). First experiments were conducted
with the dimethyl malonates 8a in the presence of lithium
iodide at 1808C (method E). Although carbohydrates are
quite labile under thermal conditions, the 2-C-branched
acetic esters 13a were isolated in high yields, only the disac-
charides malto-8a and lacto-8a afforded some decomposi-
tion products. We were able to increase the yields slightly by
microwave irradiation (method F),[26] but due to the simple
Scheme 7. Syntheses of the malonic acids 15 and 16 and acetic acids 17
and 18.
atives, the acetylated starting materials 8a and 13a gave
access to the completely free methyl glycosides 15 and 17.
Interestingly, the partly protected glyco-acetic acids 18 are
suitable precursors for the synthesis of C-disaccharides.[4]
Finally, we investigated reductions of the gluco and galac-
to isomers 12 and 14, for the synthesis of further functional-
ized carbohydrate 2-C-analogues. Due to their stability
under the basic reaction conditions, the benzyl protective
groups were advantageous. Thus, the malonates 12 were re-
duced with lithium aluminium hydride in good yields to the
diols 19 (Scheme 8), which might be used to build up den-
dritic structures. The same reductions with the acetic esters
14 gave an easy access to the 2-C-ethanol carbohydrates 20.
Similar compounds were previously synthesized in literature
Scheme 6. Syntheses of the acetic esters 13 and 14 by dealkoxcarbonyla-
tion of the 2-C-malonyl carbohydrates 8 and 12. Method E: 1.5 equivLiI,
DMSO, 1808C, 5–7 h; method F: 1.5 equivLiI, DMSO, microwave, 200
W, 10 bar, 1008C, 10–20 min. Yields of isolated products after column
chromatography are indicated in parentheses.
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Malonyl Carbohydrates
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ExperimentalSection
Generalmethods : All reactions were carried out under argon by using
standard Schlenk techniques. Solvents and commercially available chemi-
cals were purified by standard methods or used as purchased. Excess of
malonate was removed by a Kugelrohrofen (GKR-50, Büchi). TLC was
performed on aluminium sheets silica gel 60F254 (Merck, Darmstadt).
Silica gel (63–200 mm, Woelm, Erlangen (Germany)) was used for
column chromatography. Optical rotations were measured on a JASCO
P-1020 polarimeter, melting points on a Büchi SMP 20 apparatus (uncor-
rected). IR spectra were recorded on a Perkin–Elmer 1600 FT-IR spec-
trometer. NMR spectra were recorded either on a Bruker AM 250, AC
300, Avance 500 or DMX 600 with CDCl3 as the solvent and internal
standard. Elemental analyses were performed on an ELEMENTAR
vario EL analysator.
Scheme 8. Reductions of the methyl esters 12 and 14. Method G: 3 equiv
LiAlH4, 1,4-dioxane, 1008C, 3 h; method H: 1.2 equiv iBu2AlH, CH2Cl2,
ꢀ788C, 3 h. Yields of isolated products after column chromatography are
indicated in parentheses.
Synthesis of the glycals 6 and 11: The O-acetylated glycals 6a–c,j,k were
prepared by the method of Helferich[19a] or Korreda,[19b] 4,6-di-O-acetyl-
d-glucal (6d) by the procedure from Holla[17] and the 3-deoxy-glycal (6i)
by the method of Fraser-Reid.[18] The benzylated glycals 11a–f were ob-
tained from the O-acetylated precursors 6a–f by an one-step proce-
dure.[21] The 3-substituted glycals 6e–h were synthesized by the following
procedure: 4,6-di-O-acetyl-d-glucal (6d) (2.30 g, 10.0 mmol) and triethyl-
amine (1.52 g, 15.0 mmol, 1.5 equiv) were dissolved in dichloromethane
(20 mL) at 08C. At this temperature the acid chlorides 10e–h (15 mmol,
1.5 equiv) were added over a period of 1 h and the mixture was stirred at
room temperature for 14 h. After dilution with dichloromethane
(50 mL), the solution was washed with water (30 mL), diluted aqueous
sodium hydrogen carbonate (30 mL) and again water (30 mL), and the
organic phase was dried (Na2SO4) and concentrated under reduced pres-
sure. Purification by column chromatography (pentane/ethyl acetate 7:3)
afforded the glycals 6e–h as colorless oils.
by multi-step sequences in only moderate yields,[9a,27] and
thus our strategy by radical addition and further transforma-
tion is more convenient. Selective syntheses of aldehydes 21,
which again represent suitable precursors for C-disacchar-
ides,[28] were finally realized in the presence of diisobutylalu-
minium hydride (Scheme 8). All reduction products were
isolated by column chromatography in high yields in analyti-
cally pure form.
Conclusion
3-O-Benzoyl-4,6-di-O-acetyl-d-glucal (6e): 2.91 g (87%); Rf =0.62 (pen-
tane/ethyl acetate 1:1); [a]2D0 =ꢀ134.9 (c=1.02 in CHCl3); 1H NMR
(250 MHz, CDCl3): d=2.04, 2.07 (2s, 3H each, OAc), 4.23 (dd, J=11.9,
3.1 Hz, 1H, 6-H), 4.33 (ddd, J=7.6, 5.5, 3.1 Hz, 1H, 5-H), 4.48 (dd, J=
11.9, 5.5 Hz, 1H, 6’-H), 4.97 (dd, J=6.1, 3.4 Hz, 1H, 2-H), 5.41 (dd, J=
7.6, 5.9 Hz, 1H, 4-H), 5.53 (ddd, J=5.9, 3.4, 1.2 Hz, 1H, 3-H), 6.49 (dd,
J=6.1, 1.2 Hz, 1H, 1-H), 7.36–7.58 (m, 3H, arom. H), 7.94–8.02 ppm (m,
2H, arom. H); 13C NMR (63 MHz, CDCl3): d=21.1, 21.2 (2q, OAc), 61.8
(t, C-6), 67.4, 68.5, 74.3 (3d, C-3, C-4, C-5), 99.4 (d, C-1), 128.7, 128.8,
129.3, 129.9, 130.0 (5d, C-arom.), 133.7 (s, C-arom.), 146.2 (d, C-2), 166.3,
169.9, 171.0 ppm (3s, OAc, COOR); IR (KBr): n˜ =2975, 1732, 1651,
We presented a general and convenient entry to carbohy-
drate 2-C-analogues in high yields. The key step is the radi-
cal addition of malonates to glycals, which proceeds with
high regio- and stereoeselectivity. For the first time, the un-
desired formation of nitrates was completely suppressed by
employing anhydrous CAN. A coherent explanation for the
high stereoselectivities of the reactions was provided by var-
iation of the steric demand of substituents in the 3-position
of glucals. Additionally, these substituents exhibit a remark-
able electronic influence on the reactivity of the double
bond.
1542, 1372, 1231 cmꢀ1
; elemental analysis calcd (%) for C17H18O7
(334.32): C 61.07, H 5.43; found: C 60.84, H 5.52.
3-O-(4-Methoxybenzoyl)-4,6-di-O-acetyl-d-glucal (6 f): 3.06 g (84%);
Rf =0.79 (pentane/ethyl acetate 1:1); [a]2D0 = ꢀ124.2 (c=1.35 in CHCl3);
1H NMR (500 MHz, CDCl3): d=2.05, 2.10 (2s, 3H each, OAc), 3.85 (s,
3H, OMe), 4.23 (dd, J=12.0, 3.1 Hz, 1H, 6-H), 4.34 (ddd, J=7.4, 5.8,
3.1 Hz, 1H, 5-H), 4.51 (dd, J=12.0, 5.8 Hz, 1H, 6’-H), 5.00 (dd, J=6.2,
3.2 Hz, 1H, 2-H), 5.42 (dd, J=7.4, 5.7 Hz, 1H, 4-H), 5.51 (ddd, J=5.7,
3.2, 1.2 Hz, 1H, 3-H), 6.51 (dd, J=6.2, 1.2 Hz, 1H, 1-H), 6.91 (dt, J=
11.8, 2.8 Hz, 2H, arom. H), 7.95 ppm (dt, J=11.8, 2.8 Hz, 2H, arom. H);
13C NMR (63 MHz, CDCl3): d=21.1, 21.2 (2q, OAc), 55.9 (q, OMe), 61.9
(t, C-6), 67.5, 68.0, 74.3 (3d, C-3, C-4, C-5), 99.6 (d, C-1), 114.2, 114.5,
132.2, 133.2 (4d, C-arom.), 122.3 (s, C-arom.), 146.0 (d, C-2), 164.0, 164.9,
169.9, 170.0 ppm (4s, OAc, COOR, C-arom.); IR (film): n˜ =2964, 1782,
1746, 1606, 1512, 1259, 1160 cmꢀ1; elemental analysis calcd (%) for
C18H20O8 (364.35): C 59.34, H 5.53; found: C 59.79, H 5.70.
ꢀ
The applicability of transition-metal-mediated C C-bond
formations was extended to unsaturated disaccharides and
benzyl-protected glycals, which allowed further transforma-
tions of the 2-C-malonyl carbohydrates. For instance the de-
carboxylation proceeded smoothly under thermal or micro-
wave conditions and afforded acetic esters in high yields.
The saponification of the esters opened an easy entry to 2-
C-branched glyco-malonic and -acetic acids, which represent
suitable precursors for the synthesis of C-disaccharides. Fi-
nally, other functional groups were introduced by reduction
to alcohols and aldehydes in high yields.
3-O-(4-Nitrobenzoyl)-4,6-di-O-acetyl-d-glucal (6g): 3.37 g (89%); Rf =
In summary, the radical addition of malonates to glycals
in combination with further transformations offers a general
method in carbohydrate chemistry. More than 40 new 2-C-
analogues were synthesized in only few steps, high yields
and with high regio- and stereoselectivities. Due to the im-
portance of the products as precursors for C-disaccharides,
the herein described syntheses open interesting prospects
for future applications in carbohydrate chemistry.
0.77 (pentane/ethyl acetate 1:1); [a]D20
=
ꢀ141.8 (c=1.02 in CHCl3);
1H NMR (500 MHz, CDCl3): d=2.06, 2.10 (2s, 3H each, OAc), 4.25 (dd,
J=12.2, 3.0 Hz, 1H, 6-H), 4.34 (ddd, J=8.2, 5.5, 3.0 Hz, 1H, 5-H), 4.49
(dd, J=12.2, 5.5 Hz, 1H, 6’-H), 4.97 (dd, J=6.2, 3.2 Hz, 1H, 2-H), 5.44
(dd, J=8.2, 6.0 Hz, 1H, 4-H), 5.60 (ddd, J=6.0, 3.2, 1.1 Hz, 1H, 3-H),
6.53 (dd, J=6.2, 1.1 Hz, 1H, 1-H), 8.16 (dt, J=8.9, 2.1 Hz, 2H, arom. H),
8.28 ppm (dt, J=8.9, 2.1 Hz, 2H, arom. H); 13C NMR (63 MHz, CDCl3):
d=21.1, 21.2 (2q, OAc), 61.7 (t, C-6), 67.2, 70.1, 74.4 (3d, C-3, C-4, C-5),
98.9 (d, C-1), 124.0, 131.3 (4d, C-arom.), 135.4 (s, C-arom.), 146.7 (d, C-
Chem. Eur. J. 2007, 13, 10152 – 10167
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10157

T. Linker et al.
2), 151.1 (s, C-arom.), 164.5 (s, COOR), 169.9, 171.0 ppm (2s, OAc); IR
(film): n˜ =3277, 2928, 1655, 1628, 1541, 1266, 1049 cmꢀ1; elemental analy-
sis calcd (%) for C17H17NO9 (379.32): C 53.83, H 4.52, N 3.69; found: C
53.68, H 4.67 N 3.61.
4.85 (d, J=8.8 Hz, 1H, 1-H), 5.12 (dd, J=12.3, 3.2 Hz, 1H, 3-H),
5.27 ppm (dd, J=3.2, 1.0 Hz, 1H, 4-H); 13C NMR (63 MHz, CDCl3): d=
22.1, 22.3, 22.4 (3q, OAc), 43.5, 49.2 (2d, C-2, C-7), 54.0, 54.1 (2q,
COOMe), 59.1 (q, OMe), 63.1 (t, C-6), 67.6, 71.2, 72.1 (3d, C-3, C-4, C-
5), 103.5 (d, C-1), 170.0, 170.3, 171.3, 171.9, 172.0 ppm (5s, OAc,
COOMe); IR (CCl4): n˜ =3038, 2955, 1748, 1437, 1244 cmꢀ1; elemental
analysis calcd (%) for C18H26O12 (434.39): C 49.77, H 6.03; found: C
49.50, H 6.04.
3-O-Pivaloyl-4,6-di-O-acetyl-d-glucal (6h): 1.97 g (63%); Rf =0.29 (pen-
tane/ethyl acetate 85:15); [a]2D0 = ꢀ44.6 (c=1.02 in CHCl3); 1H NMR
(250 MHz, CDCl3): d=1.14 (s, 9H, CACTHRE(UNG CH3)3), 2.03, 2.07 (2s, 3H each,
OAc), 4.14 (dd, J=12.0, 2.9 Hz, 1H, 6-H), 4.26 (ddd, J=8.2, 5.9, 2.9 Hz,
1H, 5-H), 4.41 (dd, J=12.0, 5.9 Hz, 1H, 6’-H), 4.82 (dd, J=6.1, 3.0 Hz,
1H, 2-H), 5.24 (dd, J=8.2, 5.9 Hz, 1H, 4-H), 5.27 (ddd, J=5.9, 3.0,
0.9 Hz, 1H, 3-H), 6.43 ppm (dd, J=6.1, 0.9 Hz, 1H, 1-H); 13C NMR
Methyl3,4-di- O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)methyl]-a-d-
arabinopyranoside (arabino-8a): 1.61 g (89%); Rf =0.50 (pentane/ethyl
acetate 1:1); m.p. 99–1008C; [a]2D0 =ꢀ1.5 (c=1.03 in CHCl3); 1H NMR
(250 MHz, CDCl3): d=1.97, 2.12 (2s, 3H each, OAc), 2.84 (ddd, J=11.9,
8.6, 3.9 Hz, 1H, 2-H), 3.45 (s, 3H, OMe), 3.64 (dd, J=13.3, 1.1 Hz, 5-H),
3.68 (d, J=3.9 Hz, 6-H), 3.71, 3.72 (2s, 3H each, COOMe), 4.01 (dd, J=
13.2, 2.0 Hz, 1H, 5’-H), 4.73 (d, J=8.6 Hz, 1H, 1-H), 5.13 (dd, J=11.9,
3.3 Hz, 1H, 3-H), 5.17 ppm (ddd, J=13.3, 2.0, 1.1 Hz, 1H, 4-H);
13C NMR (63 MHz, CDCl3): d=20.9, 21.4 (2q, OAc), 42.7, 48.2 (2d, C-2,
C-6), 52.8, 52.9 (2q, COOMe), 57.8 (q, OMe), 64.7 (t, C-5), 67.5, 69.8
(2d, C-3, C-4), 102.5 (d, C-1), 168.9, 169.2, 170.1, 170.8 ppm (4s, OAc,
COOMe); IR (CHCl3): n˜ =3012, 2965, 2848, 1750, 1439, 1374, 1298, 1236,
1132, 1093 cmꢀ1; elemental analysis calcd (%) for C15H22O10 (362.33): C
49.72, H 6.12; found: C 49.48, H 6.02.
(63 MHz, CDCl3): d=20.7, 20.8 (2q, OAc), 27.0 (3q, C
ACHTRE(UGN CH3)3), 38.7 (s,
CACHTREUNG(CH3)3), 61.5 (t, C-6), 67.1, 67.2, 73.9 (3d, C-3, C-4, C-5), 99.1 (d, C-1),
145.5 (d, C-2), 169.5, 170.7 (2s, OAc), 177.8 ppm (s, COOR); IR (film):
n˜ =2975, 1746, 1650, 1482, 1369, 1231 cmꢀ1; elemental analysis calcd (%)
for C15H22O7 (314.33): C 57.32, H 7.05; found: C 57.51, H 7.07.
Addition of dimethyl malonate (4a) or diisopropyl malonate (4b) to
acetyl protected glycals 6 with anhydrous CAN (method C): A solution
of the acetylated glycal 6 (5.0 mmol) and dimethyl malonate (4a) (6.61 g,
50 mmol, 10 equiv) or diisopropyl malonate (4b) (9.41 g, 50 mmol,
10 equiv) in dry methanol (20 mL) was cooled to 08C under an argon at-
mosphere. At this temperature, a solution of CAN (11.0 g, 20 mmol,
4 equiv), which was dried in a desiccator under high vacuum overnight,
in methanol (30 mL) was added dropwise over a period of 6 h until TLC
showed complete conversion of the starting material. After stirring for
30 min at 08C, an ice-cold diluted solution of sodium thiosulfate
(200 mL) was added, and the mixture was extracted with dichlorome-
thane (4”80 mL). The combined organic phases were dried (Na2SO4),
concentrated, and the excess of malonate was removed at 0.01 mbar in a
Kugelrohrofen. The crude product was purified by column chromatogra-
phy or medium pressure liquid chromatography (MPLC) and the 2-C-
malonyl carbohydrates 8 were isolated as colorless oils or solids.
Methyl3,6,8,9,10,12-hexa- O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)-
methyl]-b-d-maltopyranoside (malto-8a): 3.0 g (83%); Rf =0.23 (pen-
tane/ethyl acetate 1:1); m.p. 163–1648C; [a]2D0 =+49.1 (c=0.80 in
CHCl3); 1H NMR (600 MHz, CDCl3): d=1.98, 2.01, 2.03, 2.04, 2.09, 2.13
(6s, 3H each, OAc), 2.41 (ddd, J=11.3, 8.6, 3.7 Hz, 1H, 2-H), 3.35 (d,
J=3.7 Hz, 1H, 13-H), 3.43 (s, 3H, OMe), 3.64–3.71 (m, 1H, 5-H), 3.69,
3.74 (2s, 3H each, COOMe), 3.87 (dd, J=9.4, 8.7 Hz, 1H, 4-H), 3.97
(ddd, J=10.2, 4.1, 2.3 Hz, 1H, 11-H), 4.04 (dd, J=12.4, 2.3 Hz, 12-H),
4.23 (dd, J=12.4, 4.1 Hz, 12’-H), 4.26 (dd, J=12.1, 4.3 Hz, 1H, 6-H), 4.46
(dd, J=12.1, 2.8 Hz, 1H, 6’-H), 4.86 (dd, J=10.5, 4.0 Hz, 1H, 8-H), 5.04
(dd, J=10.2, 9.6 Hz, 1H, 10-H), 5.12 (d, J=8.6 Hz, 1H, 1-H), 5.29 (dd,
J=11.3, 8.7, 1H, 3-H), 5.32 (d, J=4.0 Hz, 1H, 7-H), 5.33 ppm (dd, J=
10.5, 9.6 Hz, 1H, 9-H); 13C NMR (63 MHz, CDCl3): d=20.4, 20.5, 20.6,
20.7, 20.8, 20.9 (6q, OAc), 47.2, 48.1 (2d, C-2, C-13), 52.4, 52.5 (2q,
COOMe), 57.5 (q, OMe), 61.5, 63.2 (2t, C-6, C-12), 68.0, 68.4, 69.4, 70.0,
72.0, 73.7, 74.3 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11), 95.5, 101.3 (2d,
C-1, C-7), 168.1, 168.4, 168.7, 169.1, 169.4, 170.1, 170.5, 170.8 ppm (8s,
OAc, COOMe); IR (KBr): n˜ =2984, 1744, 1371, 1241, 1042 cmꢀ1; elemen-
tal analysis calcd (%) for C30H42O20 (722.64): C 49.86, H 5.86; found: C
49.65, H 5.87.
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-[(bis-methoxycarbonyl)methyl]-b-d-
glucopyranoside (gluco-8a): 1.73 g (80%); Rf =0.45 (pentane/ethyl ace-
tate 1:1); m.p. 100–1018C; [a]2D0 =ꢀ6.9 (c=1.08 in CHCl3); 1H NMR
(250 MHz, CDCl3): d=1.98, 1.99, 2.06 (3s, 3H each, OAc), 2.57 (ddd, J=
11.6, 8.6, 3.6 Hz, 1H, 2-H), 3.45 (s, 3H, OMe), 3.57 (d, J=3.6 Hz, 1H, 7-
H), 3.69 (ddd, J=10.0, 4.6, 2.4 Hz, 1H, 5-H), 3.70, 3.73 (2s, 3H each,
COOMe), 4.10 (dd, J=12.2, 2.4 Hz, 1H, 6-H), 4.28 (dd, J=12.2, 4.6 Hz,
1H, 6’-H), 4.95 (d, J=8.6 Hz, 1H, 1-H), 4.98 (dd, J=10.0, 9.0 Hz, 1H, 4-
H), 5.27 ppm (dd, J=11.6, 9.0 Hz, 1H, 3-H); 13C NMR (63 MHz, CDCl3):
d=20.5, 20.6, 20.7 (3q, OAc), 46.3, 48.0 (2d, C-2, C-7), 52.4, 52.5 (2q,
COOMe), 57.5 (q, OMe), 62.2 (t, C-6), 69.8, 71.3, 71.6 (3d, C-3, C-4, C-
5), 101.6 (d, C-1), 168.2, 168.3, 169.7, 170.0, 170.7 ppm (5s, OAc,
COOMe); IR (KBr): n˜ =3005, 2951, 1750, 1366, 1227 cmꢀ1; elemental
analysis calcd (%) for C18H26O12 (434.39): C 49.77, H 6.03; found: C
49.51, H 5.92.
Methyl3,6,8,9,10,12-hexa- O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)-
methyl]-b-d-lactopyranoside (lacto-8a): 2.92 g (81%); Rf =0.28 (cyclo-
hexane/ethyl acetate 1:1); [a]2D0 =ꢀ1.4 (c=1.05 in CHCl3); 1H NMR
(300 MHz, CDCl3): d=1.96, 2.04, 2.06, 2.07, 2.12, 2.14 (6s, 3H each,
OAc), 2.47 (ddd, J=12.0, 7.8, 3.9 Hz, 1H, 2-H), 3.44 (s, 3H, OMe), 3.51
(d, J=3.9 Hz, 1H, 13-H), 3.61 (ddd, J=9.3, 4.5, 1.8 Hz, 1H, 5-H), 3.70
(dd, J=9.3, 6.3 Hz, 1H, 4-H), 3.71, 3.75 (2s, 3H each, COOMe), 3.87 (t,
J=6.8 Hz, 1H, 11-H), 4.04–4.20 (m, 2H, 12-H, 12’-H), 4.17 (dd, J=12.0,
4.5 Hz, 1H, 6-H), 4.46 (d, J=7.8 Hz, 1H, 1-H), 4.48 (dd, J=12.0, 1.8 Hz,
1H, 6’-H), 4.95 (dd, J=10.2, 3.3 Hz, 1H, 8-H), 5.04 (dd, J=9.0, 8.4 Hz,
1H, 10-H), 5.09 (d, J=7.8 Hz, 1H, 7-H), 5.18 (dd, J=11.4, 8.4 Hz, 1H, 9-
H), 5.35 ppm (d, J=3.0, 1H, 3-H); 13C NMR (75 MHz, CDCl3): d=20.4,
20.5, 20.6, 20.7, 20.8, 20.9 (6q, OAc), 46.7 (d, C-13), 48.3 (d, C-2), 52.3,
52.4 (2q, COOMe), 57.4 (q, OMe), 60.8, 62.2 (2t, C-6, C-12), 66.6, 69.1,
69.3, 70.6, 71.0, 71.6, 72.4 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11), 100.0,
101.4 (2d, C-1, C-7), 168.0, 168.6, 168.8, 169.6, 169.9, 170.0, 170.2,
170.3 ppm (8s, OAc, COOMe); IR (film): n˜ =2957, 1752, 1371, 1228,
1052 cmꢀ1; elemental analysis calcd (%) for C30H42O20 (722.64): C 49.86,
H 5.86; found: C 49.76, H 5.87.
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)methyl]-a-
d-mannopyranoside (manno-8a): 325 mg (15%); Rf =0.43 (pentane/ethyl
acetate 1:1); [a]2D0 =ꢀ8.4 (c=1.04 in CHCl3); 1H NMR (600 MHz,
CDCl3): d=2.02, 2.08, 2.11 (3s, 3H each, OAc), 3.02 (ddd, J=10.1, 4.6,
2.1 Hz, 1H, 2-H), 3.39 (s, 3H, OMe), 3.67 (d, J=10.1 Hz, 1H, 7-H), 3.72,
3.76 (2s, 3H each, COOMe), 3.92 (ddd, J=9.8, 5.6, 2.1 Hz, 1H, 5-H),
4.11 (dd, J=12.1, 2.1 Hz, 1H, 6-H), 4.37 (dd, J=12.1, 5.6 Hz, 1H, 6’-H),
4.68 (d, J=2.1 Hz, 1H, 1-H), 5.26 (dd, J=9.8, 9.2 Hz, 1H, 4-H), 5.46 ppm
(dd, J=9.2, 4.6 Hz, 1H, 3-H); 13C NMR (63 MHz, CDCl3): d=20.3, 20.5,
20.6 (3q, OAc), 40.9, 48.9 (2d, C-2, C-7), 52.3, 52.4 (2q, COOMe), 55.3
(q, OMe), 62.4 (t, C-6), 68.7, 69.6, 71.1 (3d, C-3, C-4, C-5), 99.3 (d, C-1),
168.1, 168.3, 169.6, 169.9, 170.3 ppm (5s, OAc, COOMe); IR (film): n˜ =
3008, 1748, 1354, 1214 cmꢀ1; elemental analysis calcd (%) for C18H26O12
(434.39): C 49.77, H 6.03; found: C 49.83, H 5.82.
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[bis-methylethoxycarbonyl)meth-
yl]-b-d-glucopyranoside (gluco-8b): 2.10 g (86%); Rf =0.46 (pentane/
ethyl acetate 6:4); m.p. 86–878C; [a]2D0 =ꢀ7.4 (c=0.99 in CHCl3);
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)methyl]-b-
d-galactopyranoside (galacto-8a): 1.89 g (87%); Rf =0.46 (pentane/ethyl
acetate 1:1); [a]2D0 =ꢀ4.4 (c=1.17 in CHCl3); 1H NMR (250 MHz,
CDCl3): d=1.98, 2.02, 2.11 (3s, 3H each, OAc), 2.80 (ddd, J=12.3, 8.8,
3.7 Hz, 1H, 2-H), 3.47 (s, 3H, OMe), 3.66 (d, J=3.7 Hz, 1H, 7-H), 3.71,
3.72 (2s, 3H each, COOMe), 3.87 (ddd, J=7.3, 6.6, 1.0 Hz, 1H, 5-H),
4.12 (dd, J=11.2, 7.3 Hz, 1H, 6-H), 4.17 (dd, J=11.2, 6.6 Hz, 1H, 6’-H),
1H NMR (600 MHz, CDCl3): d=1.19–1.29 (m, 12H, 2COOCH
ACHTREUNG(CH3)2),
1.97, 2.00, 2.05 (3s, 3H each, OAc), 2.52 (ddd, J=11.6, 8.6, 3.4 Hz, 1H,
2-H), 3.45 (d, J=3.4 Hz, 1H, 7-H), 3.47 (s, 3H, OMe), 3.64 (ddd, J=10.0,
4.7, 2.4 Hz, 1H, 5-H), 4.05 (dd, J=12.2, 2.4 Hz, 1H, 6-H), 4.25 (dd, J=
10158
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 10152 – 10167

Malonyl Carbohydrates
FULL PAPER
12.2, 4.7 Hz, 1H, 6’-H), 5.05 (d, J=8.6 Hz, 1H, 1-H), 4.94–5.11 (m, 3H,
21.9, 22.0, 22.1 (10q, OAc, COOCH
57.5 (q, OMe), 62.0, 63.7 (2t, C-6, C-12), 68.4, 68.8, 69.2, 69.8, 69.9, 70.4,
72.5, 74.0, 75.0 (9d, C-3, C-4, C-5, C-8, C-9, C-10, C-11, COOCH(CH3)2),
95.9, 102.0 (2d, C-1, C-7), 167.6, 168.3, 169.9, 170.1, 170.2, 170.4, 170.6,
171.0 ppm (8s, OAc, COOiPr); IR (KBr): n˜ =2980, 2958, 1742, 1362,
1212, 1089 cmꢀ1; elemental analysis calcd (%) for C34H50O20 (778.75): C
52.44, H 6.47; found: C 52.39, H 6.45.
ACHTRENU(G CH3)2), 47.4, 49.9 (2d, C-2, C-13),
4-H,
13C NMR (150 MHz, CDCl3): d=22.2, 22.3, 22.4, 22.5, 23.0, 23.2, 23.4
(7q, 3OAc, 4COOCH(CH3)2), 47.7, 50.4 (2d, C-2, C-7), 63.9 (t, C-6),
69.8, 69.9, 70.7, 71.1, 71.6 (5d, C-3, C-4, C-5, 2COOCH(CH3)2), 103.6 (d,
(CH3)2); IR
2 COOCHACHTREUNG(CH3)2), 5.18 ppm (dd, J=11.6, 9.0 Hz, 1H, 3-H);
ACHTREUNG
G
AHCTREUNG
C-1), 168.9, 169.3, 171.4, 171.5, 172.4 ppm (5s, OAc, COOCHACHTREUNG
(CCl4): n˜ =2982, 2938, 1755, 1374, 1228 cmꢀ1; elemental analysis calcd
(%) for C22H34O12 (490.50): C 53.87, H 6.99; found: C 53.88, H, 6.68.
Methyl3,6,8,9,10,12-hexa-
O-acetyl-2-deoxy-2-C-[(bis-methylethoxycar-
AHCTREbUNG onyl)methyl]-b-d-lactopyranoside (lacto-8b): 3.35 g (86%); Rf =0.30
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[bis-methylethoxycarbonyl)meth-
yl]-a-d-mannopyranoside (manno-8b): 220 mg (9%); Rf =0.48 (pentane/
ethyl acetate 6:4); [a]2D0 =+21.4 (c=1.02 in CHCl3); 1H NMR (600 MHz,
(cyclohexane/ethyl acetate 1:1); [a]2D0 =ꢀ1.5 (c=1.09 in CHCl3); 1H NMR
(300 MHz, CDCl3): d=1.20–1.32 (m, 12H, 2COOCHACHTER(UNG CH3)2), 1.96, 2.04,
2.06, 2.09, 2.12, 2.14 (6s, 3H each, OAc), 2.46 (dddd, J=11.4, 8.7, 3.6 Hz,
1H, 2-H), 3.38 (d, J=3.6 Hz, 1H, 13-H), 3.43 (s, 3H, OMe), 3.61 (ddd,
J=9.3, 5.4, 1.5 Hz, 1H, 5-H), 3.71 (ddd, J=9.6, 6.6, 3.0 Hz, 1H, 11-H),
3.87 (t, J=6.9 Hz, 1H, 4-H), 4.06–4.13 (m, 2H, 12-H 12’-H), 4.17 (dd, J=
11.7, 5.4 Hz, 1H, 6-H), 4.45 (d, J=8.7 Hz, 1H, 1-H), 4.47 (dd, J=11.7,
1.5 Hz, 1H, 6’-H), 4.94 (dd, J=10.5, 3.3 Hz, 1H, 8-H), 5.00–5.10 (m, 2H,
CDCl3): d=1.19–1.29 (m, 12H, 2COOCHACHTRE(UNG CH3)2), 1.97, 2.02, 2.03 (3s,
3H each, OAc), 3.08 (ddd, J=10.2, 4.8, 2.3 Hz, 1H, 2-H), 3.36 (s, 3H,
OMe), 3.46 (d, J=10.2 Hz, 1H, 7-H), 4.04 (ddd, J=10.4, 5.6, 3.1 Hz, 1H,
5-H), 4.12 (dd, J=12.0, 5.6 Hz, 1H, 6’-H), 4.26 (dd, J=12.0, 3.1 Hz, 1H,
6-H), 4.72 (d, J=2.3 Hz, 1H, 1-H), 4.94–5.11 (m, 3H, 4-H, 2COOCH-
ACHTREUNG
(CH3)2), 5.45 ppm (dd, J=8.7, 4.8 Hz, 1H, 3-H); 13C NMR (150 MHz,
COOCHCAHTREU(NG CH3)2), 5.09 (d, J=7.8 Hz, 1H, 7-H), 5.11 (dd, J=10.5, 3.0 Hz,
CDCl3): d=20.7, 20.8, 20.9, 21.0, 21.3, 21.4, 21.5 (7q, 3OAc, 4COOCH-
(CH3)2), 40.0, 50.0 (2d, C-2, C-7), 61.4 (t, C-6), 67.2, 67.3, 69.7, 69.8, 70.4
(5d, C-3, C-4, C-5, 2 COOCH(CH3)2), 99.5 (d, C-1), 166.3, 166.5, 169.4,
169.6, 170.5 (5s, OAc, COOCHAHCRTE(UGN CH3)2); IR (CCl4): n˜ =2981, 2927, 1752,
1H, 10-H), 5.16 (dd, J=11.4, 8.4 Hz, 1H, 9-H), 5.35 ppm (d, J=3.0, 1H,
ACHTREUNG
3-H); 13C NMR (75 MHz, CDCl3): d=20.4, 20.5, 20.7, 20.8, 20.9, 21.0,
AHCTREUNG
21.2, 21.3, 21.5, 21.6 (10q, OAc, COOCHACHTRE(UNG CH3)2), 46.5 (d, C-13), 49.0 (d,
C-2), 57.0 (q, OMe), 60.3, 60.8 (2t, C-6, C-12), 62.3, 66.6, 68.8, 69.1, 69.2,
70.6, 70.9, 71.0, 72.5 (9d, C-3, C-4, C-5, C-8, C-9, C-10, C-11, COOCH-
1369, 1224 cmꢀ1; elemental analysis calcd (%) for C22H34O12 (490.50): C
53.87, H 6.99; found: C 53.72, H, 6.78.
AHCTRE(UNG CH3)2), 100.9, 101.7 (2d, C-1, C-7), 167.1, 167.8, 168.8, 169.3, 169.9,
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[(bis-methylethoxycarbonyl)meth-
yl]-b-d-galactopyranoside (galacto-8b): 2.16 g (88%); Rf =0.30 (pentane/
ethyl acetate 1:1); m.p. 109–1108C; [a]2D0 =ꢀ17.3 (c=1.24 in CHCl3);
170.0, 170.2, 170.3 ppm (8s, OAc, COOiPr); IR (film): n˜ =2984, 2939,
1752, 1373, 1227, 1051 cmꢀ1; elemental analysis calcd (%) for C34H50O20
(778.75): C 52.44, H 6.47; found: C 52.22, H 6.56.
1H NMR (600 MHz, CDCl3): d=1.20–1.31 (m, 12H, 2COOCH
ACHTRE(UNG CH3)2),
Addition of dimethyl malonate (4a) to the 3-substituted glycals 6d–i with
anhydrous CAN (method C): A solution of the 3-substituted glycal 6
(2.0 mmol) and dimethyl malonate (4a) (2.64 g, 20 mmol, 10 equiv) in
dry methanol (10 mL) was cooled to 08C under an argon atmosphere. At
this temperature, a solution of CAN (4.4 g, 8.0 mmol, 4 equiv), which was
dried in a desiccator under high vacuum overnight, in methanol (12 mL)
was added dropwise over a period of 3–12 h until TLC showed complete
conversion of the starting material. After stirring for 30 min at 08C, an
ice-cold diluted solution of sodium thiosulfate (100 mL) was added, and
the mixture was extracted with dichloromethane (4”30 mL). The com-
bined organic extracts were dried (Na2SO4) and concentrated, and the
excess of malonate was removed at 0.01 mbar in a Kugelrohrofen. The
gluco/manno ratios were determined by 1H NMR (600 MHz). The crude
product was purified by column chromatography or medium pressure
liquid chromatography (MPLC) and the 2-C-malonyl carbohydrates 8
were isolated as colorless oils or solids.
1.96, 2.04, 2.13 (3s, 3H each, OAc), 2.82 (ddd, J=12.3, 8.8, 3.5 Hz, 1H,
2-H), 3.48 (s, 3H, OMe), 3.60 (d, J=3.5 Hz, 1H, 7-H), 3.87 (ddd, J=7.0,
6.5, 1.0 Hz, 1H, 5-H), 4.13 (dd, J=11.2, 7.0 Hz, 1H, 6-H), 4.18 (dd, J=
11.2, 6.5 Hz, 1H, 6’-H), 4.83 (d, J=8.8 Hz, 1H, 1-H), 5.05 (dddd, J=18.9,
12.6, 6.4, 2.2 Hz, 2H, 2COOCH
H), 5.31 ppm (dd, J=3.1, 1.0 Hz, 1H, 4-H); 13C NMR (63 MHz, CDCl3):
d=20.8, 21.1, 21.8, 21.9, 22.0, 22.0, 22.1 (7q, OAc, COOCH(CH3)2), 42.0,
48.7 (2d, C-2, C-7), 57.8 (q, OMe), 62.0 (t, C-6), 66.6, 69.3, 69.7 (3d, C-3,
C-4, C-5), 70.2, 71.0 (2d, COOCH(CH3)2), 102.6 (d, C-1), 168.0, 168.1,
(CH3)2); IR (KBr): n˜ =2985,
ACHTRE(UNG CH3)2), 5.17 (dd, J=12.3, 3.1 Hz, 1H, 3-
AHCTREUNG
AHCTREUNG
170.0, 170.7, 170.9 ppm (5s, OAc, COOCHACHTREUNG
2938, 1732, 1664, 1467, 1376 cmꢀ1; elemental analysis calcd (%) for
C22H34O12 (490.50): C 53.87, H 6.99; found: C 53.88, H, 7.09.
Methyl3,4-di- O-acetyl-2-deoxy-2-C-[(bis-methylethoxycarbonyl)methyl]-
a-d-arabinopyranoside (arabino-8b): 1.82 g (87%); Rf =0.68 (pentane/
ethyl acetate 1:1); [a]2D0 =ꢀ11.1 (c=0.98 in CHCl3); 1H NMR (600 MHz,
CDCl3): d=1.20–1.27 (m, 12H, 2COOCHACHTRE(UNG CH3)2), 1.97, 2.12 (2s, 3H
Methyl4,6-di-
O-acetyl-2-deoxy-2-[(bis-methoxycarbonyl)methyl]-b-d-
each, OAc), 2.85 (ddd, J=11.9, 8.6, 3.7 Hz, 1H, 2-H), 3.46 (s, 3H, OMe),
3.59 (d, J=3.7 Hz, 1H, 6-H), 3.64 (dd, J=13.4, 1.0 Hz, 1H, 5-H), 4.01
(dd, J=13.4, 1.8 Hz, 1H, 5’-H), 4.71 (d, J=8.6, 1H, 1-H), 5.00–5.08 (m,
glucopyranoside (gluco-8d): 350 mg (45%); m.p. 137–1388C; Rf =0.30
(pentane/ethyl acetate 1:1); [a]2D0 =ꢀ34.0 (c=1.21 in CHCl3); 1H NMR
(600 MHz, CDCl3): d=2.05, 2.09 (2s, 3H each, OAc), 2.43 (ddd, J=11.3,
8.5, 3.7 Hz, 1H, 2-H), 2.91 (brs, 1H, OH), 3.44 (s, 3H, OMe), 3.60 (ddd,
J=9.2, 4.7, 2.3 Hz, 1H, 5-H), 3.72, 3.74 (2s, 3H each, COOMe), 3.84 (dd,
J=11.3, 9.8 Hz, 1H, 3-H), 3.95 (d, J=3.7 Hz, 1H, 7-H), 4.11 (dd, J=12.2,
2.3 Hz, 1H, 6-H), 4.27 (dd, J=12.2, 4.7 Hz, 1H, 6’-H), 4.72 (d, J=8.5 Hz,
1H, 1-H), 4.81 ppm (dd, J=9.8, 9.2 Hz, 1H, 4-H); 13C NMR (63 MHz,
CDCl3): d=21.2, 21.3 (2q, OAc), 48.7, 49.0 (2d, C-2, C-7), 52.9, 53.0 (2q,
COOMe), 57.8 (q, OMe), 62.3 (t, C-6), 71.8, 72.1, 73.1 (3d, C-3, C-4, C-
5), 102.3 (d, C-1), 169.6, 169.8, 171.3, 171.6 ppm (4s, OAc, COOMe); IR
(film): n˜ =2960, 1744, 1443, 1371, 1040 cmꢀ1; elemental analysis calcd
(%) for C16H24O11 (392.35): C 48.98, H 6.17; found: C 48.59, H 6.29.
2H, 2COOCH
(ddd, J=3.3, 1.8, 1.0 Hz, 1H, 4-H); 13C NMR (63 MHz, CDCl3): d=20.8,
21.3, 21.6, 21.8, 21.9, 22.0 (6q, OAc, COOCH(CH3)2), 42.4, 48.9 (2d, C-2,
C-6), 57.4 (q, OMe), 64.7 (t, C-5), 67.6, 69.2, 69.5, 69.9 (4d, C-3, C-4,
2COOCH(CH3)2), 102.7 (d, C-1), 168.0, 168.1, 170.0, 170.8 ppm (4s,
OAc, COOCH
ACHTREUNG(CH3)2), 5.14 (dd, J=11.9, 3.3 Hz, 1H, 3-H), 5.18 ppm
AHCTREUNG
ACHTREUNG
ACHTREUNG(CH3)2); IR (CHCl3): n˜ =3031, 2984, 2938, 1746, 1459,
1376, 1234, 1181, 1103, 1023 cmꢀ1; elemental analysis calcd (%) for
C19H30O10 (418.44): C 54.54, H 7.23; found: C 54.78, H 7.39.
Methyl3,6,8,9,10,12-hexa-
O-acetyl-2-deoxy-2-C-[(bis-methylethoxycar-
ACHTREUNGbonyl)methyl]-b-d-maltopyranoside (malto-8b): 3.23 g (83%); Rf =0.34
(pentane/ethyl acetate 6:4); m.p. 151–1528C; [a]2D0 =+49.8 (c=1.02 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=1.20–1.27 (m, 12H, 2COOCH-
Methyl4,6-di- O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)methyl]-a-d-
mannopyranoside (manno-8d): 25 mg (3%); Rf =0.32 (pentane/ethyl ace-
tate 1:1); NMR signals are overlapped with gluco isomer.
ACHTREUNG(CH3)2), 1.96, 1.99, 2.03, 2.04, 2.07, 2.11 (6s, 3H each, OAc), 2.38 (dddd,
J=11.4, 8.6, 3.4 Hz, 1H, 2-H), 3.21 (d, J=3.4 Hz, 1H, 13-H), 3.41 (s, 3H,
OMe), 3.67 (ddd, J=9.2, 4.4, 2.7 Hz, 1H, 5-H), 3.86 (dd, J=9.2, 8.7 Hz,
1H, 4-H), 3.96 (ddd, J=10.3, 3.9, 2.4 Hz, 1H, 11-H), 4.01 (dd, J=12.5,
2.4 Hz, 12-H), 4.24 (dd, J=12.5, 3.9 Hz, 12’-H), 4.25 (dd, J=12.1, 4.4 Hz,
1H, 6-H), 4.43 (dd, J=12.1, 2.7 Hz, 1H, 6’-H), 4.87 (dd, J=10.3, 3.7 Hz,
Methyl3- O-benzoyl-4,6-di-O-acetyl-2-deoxy-2-[(bis-methoxycarbonyl)-
methyl]-b-d-glucopyranoside (gluco-8e): 775 mg (78%); Rf =0.33 (pen-
tane/ethyl acetate 6:4); [a]2D0 =ꢀ17.8 (c=1.02 in CHCl3); 1H NMR
(600 MHz, CDCl3): d=1.96, 2.09 (2s, 3H each, OAc), 2.72 (ddd, J=11.7,
8.6, 3.7 Hz, 1H, 2-H), 3.48 (s, 3H, OMe), 3.58 (d, J=3.7 Hz, 1H, 7-H),
3.66, 3.68 (2s, 3H each, COOMe), 3.78 (ddd, J=9.9, 4.6, 2.3 Hz, 1H, 5-
H), 4.14 (dd, J=12.3, 2.3 Hz, 1H, 6-H), 4.33 (dd, J=12.3, 4.6 Hz, 1H, 6’-
H), 5.09 (d, J=8.6 Hz, 1H, 1-H), 5.21 (dd, J=9.9, 9.2 Hz, 1H, 4-H), 5.53
1H, 8-H), 4.95–5.09 (m, 2H, COOCHCATHRE(UNG CH3)2), 5.03 (dd, J=10.3, 9.7 Hz,
1H, 10-H), 5.16 (d, J=8.6 Hz, 1H, 1-H), 5.27 (dd, J=11.4, 8.7 Hz, 1H, 3-
H), 5.29 (d, J=3.7, 1H, 7-H), 5.31 ppm (dd, J=10.3, 9.7 Hz, 1H, 9-H);
13C NMR (125 MHz, CDCl3): d=20.9, 21.0, 21.1, 21.2, 21.3, 21.7, 21.8,
Chem. Eur. J. 2007, 13, 10152 – 10167
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10159

T. Linker et al.
(dd, J=11.7, 9.2 Hz, 1H, 3-H), 7.40–7.60 (m, 3H, arom. H), 7.95–
8.00 ppm (m, 2H, arom. H); 13C NMR (63 MHz, CDCl3): d=21.0, 21.3
(2q, OAc), 47.2, 48.7 (2d, C-2, C-7), 53.3, 53.4 (2q, COOMe), 58.2 (q,
OMe), 62.7 (t, C-6), 70.1, 72.1, 72.5 (3d, C-3, C-4, C-5), 102.3 (d, C-1),
129.0, 129.3, 130.3, 130.4, 134.0 (5d, C-arom.), 130.2 (s, C-arom.), 166.2,
168.6, 168.7, 170.1, 171.3 ppm (5s, OAc, COOMe); IR (film): n˜ =3048,
2987, 1722, 1602, 1439, 1370, 1094 cmꢀ1; elemental analysis calcd (%) for
C23H28O12 (496.46): C 55.64, H 5.68; found: C 55.97, H 5.84.
(63 MHz, CDCl3): d=20.9, 21.2 (2q, OAc), 46.8, 48.6 (2d, C-2, C-7),
52.9, 53.0 (2q, COOMe), 58.1 (q, OMe), 62.5 (t, C-6), 69.9, 71.9, 73.5 (3d,
C-3, C-4, C-5), 102.0 (d, C-1), 124.1, 131.5 (4d, C-arom.), 134.7, 151.3 (2s,
C-arom.), 164.4, 168.6, 168.7, 170.1, 171.1 ppm (5s, OAc, C-arom.
COOMe); IR (film): n˜ =2957, 1743, 1726, 1527, 1346, 1276, 1116 cmꢀ1; el-
emental analysis calcd (%) for C23H27NO14 (541.46): C 51.02, H 5.03, N
2.59; found: C 50.80, H 5.05, N 2.58.
Methyl3- O-(4-nitrobenzoyl)-4,6-di-O-acetyl-2-deoxy-2-C-[(bis-methoxy-
carbonyl)methyl]-a-d-mannopyranoside (manno-8g): 185 mg (17%);
Rf =0.63 (pentane/ethyl acetate 1:1); [a]2D0 =+34.5 (c=1.03 in CHCl3);
1H NMR (600 MHz, CDCl3): d=1.98, 2.13 (2s, 3H each, OAc), 3.36
(ddd, J=10.0, 4.9, 2.2 Hz, 1H, 2-H), 3.43, 3.46, 3.74 (3s, 3H each, OMe,
COOMe), 3.73 (d, J=10.0 Hz, 1H, 7-H), 4.02 (ddd, J=9.7, 5.1, 2.3 Hz,
1H, 5-H), 4.18 (dd, J=12.2, 2.3 Hz, 1H, 6-H), 4.26 (dd, J=12.2, 5.1 Hz,
1H, 6’-H), 4.80 (d, J=2.1 Hz, 1H, 1-H), 5.44 (dd, J=9.5, 9.4 Hz, 1H, 4-
H), 5.67 (dd, J=9.0, 4.9 Hz, 1H, 3-H), 8.12 (dt, J=9.0, 2.2, 2H, arom.
H), 8.28 ppm (dt, J=9.0, 2.2, 2H, arom. H); 13C NMR (63 MHz, CDCl3):
d=21.1, 21.4 (2q, OAc), 43.2, 50.0 (2d, C-2, C-7), 53.2, 53.4 (2q,
COOMe), 55.8 (q, OMe), 62.6 (t, C-6), 68.9, 70.4, 71.7 (3d, C-3, C-4, C-
5), 100.9 (d, C-1), 124.0, 124.1, 131.1, 131.2 (4d, C-arom.), 133.1, 152.2
(2s, C-arom.), 164.3, 167.5, 167.7, 170.2, 170.4 ppm (5s, OAc, C-arom.,
COOMe); IR (film): n˜ =2945, 1746, 1734, 1534, 1343, 1103 cmꢀ1; elemen-
tal analysis calcd (%) for C23H27NO14 (541.46): C 51.02, H 5.03, N 2.59;
found: C 51.23, H 5.14, N 2.74.
Methyl3- O-benzoyl-4,6-di-O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)-
methyl]-a-d-mannopyranoside (manno-8e): 160 mg (16%); Rf =0.35
(pentane/ethyl acetate 6:4); [a]2D0 =+21.4 (c=1.02 in CHCl3); 1H NMR
(600 MHz, CDCl3): d=2.01, 2.11 (2s, 3H each, OAc), 3.33 (ddd, J=9.5,
5.0, 2.0 Hz, 1H, 2-H), 3.40, 3.41, 3.73 (3s, 3H each, OMe, COOMe), 3.76
(d, J=9.5 Hz, 1H, 7-H), 4.01 (ddd, J=9.4, 5.2, 2.3 Hz, 1H, 5-H), 4.17
(dd, J=12.1, 2.3 Hz, 1H, 6-H), 4.24 (dd, J=12.1, 5.2 Hz, 1H, 6’-H), 4.80
(d, J=2.0 Hz, 1H, 1-H), 5.42 (dd, J=9.4, 9.1 Hz, 1H, 4-H), 5.66 (dd, J=
9.1, 5.0 Hz, 1H, 3-H), 7.40–7.60 (m, 3H, arom. H), 7.95–8.00 ppm (m,
2H, arom. H); 13C NMR (63 MHz, CDCl3): d=21.3, 21.4 (2q, OAc),
42.9, 49.9 (2d, C-2, C-7), 53.0, 53.4 (2q, COOMe), 56.0 (q, OMe), 62.8 (t,
C-6), 68.9, 70.1, 72.1 (3d, C-3, C-4, C-5), 100.0 (d, C-1), 129.0, 129.5,
129.8, 130.4, 134.0 (5d, C-arom.), 130.3 (s, C-arom.), 166.0, 168.6, 168.8,
169.0, 171.4 ppm (5s, OAc, COOMe); IR (film): n˜ =3052, 2986, 1725,
1602, 1374, 1098 cmꢀ1
; elemental analysis calcd (%) for C23H28O12
(496.46): C 55.64, H 5.68; found: C 55.87, H 5.79.
Methyl3- O-(4-methoxybenzoyl)-4,6-di-O-acetyl-2-deoxy-2-[(bis-methoxy-
carbonyl)methyl]-b-d-glucopyranoside (gluco-8 f): 780 mg (74%); Rf =
0.55 (pentane/ethyl acetate 1:1); [a]2D0 =ꢀ9.0 (c=2.37 in CHCl3);
1H NMR (500 MHz, CDCl3): d=1.85, 2.09 (2s, 3H each, OAc), 2.75
(ddd, J=11.6, 8.5, 3.8 Hz, 1H, 2-H), 3.48 (s, 3H, OMe), 3.62 (d, J=
3.8 Hz, 1H, 7-H), 3.65, 3.68 (2s, 3H each, COOMe), 3.77 (ddd, J=9.8,
4.6, 2.4 Hz, 1H, 5-H), 3.84 (s, 3H, arom. OMe), 4.13 (dd, J=12.3, 2.4 Hz,
1H, 6-H), 4.13 (dd, J=12.3, 4.6 Hz, 1H, 6’-H), 5.09 (d, J=8.5 Hz, 1H, 1-
H), 5.22 (dd, J=9.8, 9.3 Hz, 1H, 4-H), 5.61 (dd, J=11.6, 9.3 Hz, 1H, 3-
H), 6.91 (dt, J=8.9, 1.9, 2H, arom. H), 7.93 ppm (dt, J=8.9, 1.9, 2H,
arom. H); 13C NMR (63 MHz, CDCl3): d=20.6, 20.9 (2q, OAc), 46.8,
48.4 (2d, C-2, C-7), 52.5, 52.9 (2q, COOMe), 55.5, 57.7 (2q, OMe, arom.
OMe), 62.3 (t, C-6), 66.1, 69.7, 71.7 (3d, C-3, C-4, C-5), 101.9 (d, C-1),
113.9, 114.0, 131.9, 132.1 (4d, C-arom.), 121.2 (s, C-arom.), 163.9, 165.5,
168.8, 169.7, 169.8, 170.9 ppm (6s, OAc, C-arom., COOMe); IR (film):
n˜ =2939, 1749, 1732, 1598, 1438, 1358, 1081 cmꢀ1; elemental analysis calcd
(%) for C24H30O13 (526.49): C 54.75, H 5.74; found: C 54.58, H 5.72.
Methyl3-
O-pivaoyl-4,6-di-O-acetyl-2-deoxy-2-[(bis-methoxycarbonyl)-
methyl]-b-d-glucopyranoside (gluco-8h): 715 mg (75%); Rf =0.35 (pen-
tane/ethyl acetate 7:3); [a]2D0 =ꢀ11.3 (c=1.12 in CHCl3); 1H NMR
(600 MHz, CDCl3): d=1.14 (s, 9H, CACTHRE(UNG CH3)3), 1.97, 2.08 (2s, 3H each,
OAc), 2.60 (ddd, J=11.2, 8.7, 3.6 Hz, 1H, 2-H), 3.45 (d, J=3.6 Hz, 1H,
7-H), 3.47 (s, 3H, OMe), 3.70 (ddd, J=10.5, 4.5, 2.2 Hz, 1H, 5-H), 3.71,
3.74 (2s, 3H each, COOMe), 4.10 (dd, J=12.3, 2.2 Hz, 1H, 6-H), 4.27
(dd, J=12.3, 4.5 Hz, 1H, 6’-H), 5.05 (d, J=8.7 Hz, 1H, 1-H), 5.08 (dd,
J=10.5, 9.2 Hz, 1H, 4-H), 5.15 ppm (dd, J=11.2, 9.2 Hz, 1H, 3-H);
13C NMR (63 MHz, CDCl3): d=21.0, 21.4 (2q, OAc), 27.3, 27.4, 27.5 (3q,
CACTHER(NGU CH3)3), 39.2 (s, CACHRTEU(GN CH3)3), 46.9, 48.5 (2d, C-2, C-7), 52.7, 52.8 (2q,
COOMe), 58.1 (q, OMe), 62.6 (t, C-6), 69.8, 71.2, 72.1 (3d, C-3, C-4, C-
5), 102.2 (d, C-1), 168.4, 169.1, 169.8, 171.1 ppm (4s, OAc, COOMe); IR
(film): n˜ =2959, 1732, 1436, 1366, 1236, 916 cmꢀ1; elemental analysis calcd
(%) for C21H32O12 (476.47): C 52.94, H 6.77; found: C 53.06, H 6.90.
Methyl3-O-pivaoy-l4,6-di- O-acetyl-2-deoxy-2-C-[(bis-methoxycarbonyl)-
methyl]-a-d-mannopyranoside (manno-8h): 150 mg (16%); Rf =0.33
(pentane/ethyl acetate 7:3); [a]2D0 =+13.7 (c=1.06 in CHCl3); 1H NMR
Methyl3-
O-(4-methoxybenzoyl)-4,6-di-O-acetyl-2-deoxy-2-C-[(bis-me-
(manno-8 f): 210 mg
thoxycarbonyl)methyl]-a-d-mannopyranoside
(600 MHz, CDCl3): d=1.14 (s, 9H, CACTHRE(UNG CH3)3), 2.02, 2.11 (2s, 3H each,
(20%); Rf =0.58 (pentane/ethyl acetate 1:1); [a]2D0 =+12.3 (c=1.13 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=1.95, 2.11 (2s, 3H each, OAc),
3.31 (ddd, J=9.6, 5.0, 2.1 Hz, 1H, 2-H), 3.41, 3.43, 3.73 (3s, 3H each,
OMe, COOMe), 3.72 (d, J=9.6 Hz, 1H, 7-H), 3.85 (s, 3H, arom. OMe),
4.00 (ddd, J=9.5, 5.4, 2.4 Hz, 1H, 5-H), 4.16 (dd, J=12.2, 2.4 Hz, 1H, 6-
H), 4.24 (dd, J=12.2, 5.4 Hz, 1H, 6’-H), 4.80 (d, J=2.1 Hz, 1H, 1-H),
5.41 (dd, J=9.5, 9.3 Hz, 1H, 4-H), 5.62 (dd, J=9.3, 5.0 Hz, 1H, 3-H),
6.93 (dt, J=8.9, 2.7, 2H, arom. H), 7.89 ppm (dt, J=8.9, 2.7, 2H, arom.
H); 13C NMR (63 MHz, CDCl3): d=20.6, 20.8 (2q, OAc), 42.5, 49.6 (2d,
C-2, C-7), 52.9, 53.0 (2q, COOMe), 55.5, 57.7 (2q, OMe, arom. OMe),
62.7 (t, C-6), 66.1, 68.5, 70.3 (3d, C-3, C-4, C-5), 99.6 (d, C-1), 113.9,
114.1, 131.9, 132.2 (4d, C-arom.), 121.6 (s, C-arom.), 163.8, 164.9, 167.9,
168.3, 169.7, 170.8 ppm (6s, OAc, C-arom., COOMe); IR (film): n˜ =2948,
1764, 1734, 1600, 1442, 1356, 1098 cmꢀ1; elemental analysis calcd (%) for
C24H30O13 (526.49): C 54.75, H 5.74; found: C 54.52, H 5.62.
OAc), 3.09 (ddd, J=7.3, 4.6, 3.0 Hz, 1H, 2-H), 3.36 (s, 3H, OMe), 3.64
(d, J=7.3 Hz, 1H, 7-H), 3.75, 3.76 (3s, 3H each, COOMe), 3.95 (ddd, J=
8.5, 5.5, 2.4 Hz, 1H, 5-H), 4.11 (dd, J=12.2, 2.4 Hz, 1H, 6-H), 4.19 (dd,
J=12.2, 5.5 Hz, 1H, 6’-H), 4.79 (d, J=3.0 Hz, 1H, 1-H), 5.21 (dd, J=9.0,
8.5 Hz, 1H, 4-H), 5.40 ppm (dd, J=9.0, 4.6 Hz, 1H, 3-H); 13C NMR
(63 MHz, CDCl3): d=21.0, 21.1 (2q, OAc), 27.3, 27.4, 27.5 (3q, C
39.9 (s, C(CH3)3), 42.5, 49.2 (2d, C-2, C-7), 52.8, 53.3 (2q, COOMe), 55.8
(q, OMe), 63.1 (t, C-6), 67.1, 68.8, 72.0 (3d, C-3, C-4, C-5), 99.5 (d, C-1),
ACHTREUNG(CH3)3),
AHCTREUNG
168.6, 169.2, 169.8, 171.0 ppm (4s, OAc, COOMe); IR (film): n˜ =2964,
1734, 1433, 1362, 1244, 923 cmꢀ1
; elemental analysis calcd (%) for
C21H32O12 (476.47): C 52.94, H 6.77; found: C 53.08, H 6.81.
Methyl4,6-di- O-acetyl-2,3-dideoxy-2-[(bis-methoxycarbonyl)methyl]-b-d-
xylohexanoside (gluco-8i): 355 mg (47%); Rf =0.64 (pentane/ethyl ace-
tate 1:1); [a]2D0 =+16.2 (c=1.33 in CHCl3); 1H NMR (600 MHz, CDCl3):
d=1.59 (ddd, J=13.0, 12.5, 10.8 Hz, 1H, 3-Hax), 2.02, 2.07 (2s, 3H each,
OAc), 2.28 (ddd, J=12.5, 5.0, 4.0 Hz, 1H, 3-Heq), 2.39 (dddd, J=13.0,
8.5, 5.4, 4.0 Hz, 1H, 2-H), 3.45 (s, 3H, OMe), 3.61 (d, J=5.4 Hz, 1H, 7-
H), 3.65 (ddd, J=9.8, 5.2, 2.5 Hz, 1H, 5-H), 3.71, 3.73 (2s, 3H each,
COOMe), 4.15 (dd, J=12.0, 2.5 Hz, 1H, 6-H), 4.23 (dd, J=12.0, 5.2 Hz,
1H, 6’-H), 4.48 (d, J=8.5 Hz, 1H, 1-H), 4.78 ppm (ddd, J=10.8, 9.8,
5.0 Hz, 1H, 4-H); 13C NMR (63 MHz, CDCl3): d=20.7, 20.9 (2q, OAc),
30.4 (t, C-3), 39.9 (d, C-2), 51.4 (d, C-7), 52.4, 52.5 (2q, COOMe), 57.0
(q, OMe), 62.8 (t, C-6), 67.0 (d, C-4), 75.0 (d, C-5), 103.6 (d, C-1), 168.2,
168.4, 169.7, 170.8 ppm (4s, OAc, COOMe); IR (CHCl3): n˜ =2956, 1747,
Methyl3- O-(4-nitrobenzoyl)-4,6-di-O-acetyl-2-deoxy-2-[(bis-methoxycar-
bonyl)methyl]-b-d-glucopyranoside (gluco-8g): 790 mg (73%); Rf =0.62
(pentane/ethyl acetate 1:1); m.p. 130–1318C; [a]2D0 =ꢀ23.6 (c=1.04 in
CHCl3); 1H NMR (600 MHz, CDCl3): d=1.87, 2.08 (2s, 3H each, OAc),
2.75 (ddd, J=11.6, 8.6, 3.6 Hz, 1H, 2-H), 3.48 (s, 3H, OMe), 3.62 (d, J=
3.6 Hz, 1H, 7-H), 3.66, 3.68 (2s, 3H each, COOMe), 3.81 (ddd, J=10.0,
4.4, 2.3 Hz, 1H, 5-H), 4.14 (dd, J=12.3, 2.3 Hz, 1H, 6-H), 4.35 (dd, J=
12.3, 4.4 Hz, 1H, 6’-H), 5.03 (d, J=8.6 Hz, 1H, 1-H), 5.22 (dd, J=10.0,
9.0 Hz, 1H, 4-H), 5.61 (dd, J=11.6, 9.0 Hz, 1H, 3-H), 8.15 (dt, J=9.0,
2.0, 2H, arom. H), 8.29 ppm (dt, J=9.0, 2.0, 2H, arom. H); 13C NMR
10160
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 10152 – 10167

Malonyl Carbohydrates
FULL PAPER
1436, 1372, 1244, 1039 cmꢀ1; elemental analysis calcd (%) for C16H24O10
(376.36): C 51.06, H 6.43; found: C 50.96, H 6.49.
(15d, arom, C-H), 138.0, 138.3 (3s, arom. C-CH2O), 168.9, 169.1 ppm (2s,
COOMe); IR (film): n˜ =3060, 3028, 2951, 2864, 1733, 1435, 1267 cmꢀ1; el-
emental analysis calcd (%) for C33H38O9 (578.65): C 68.50, H 6.62; found:
C 68.75, H 6.90.
Methyl4,6-di- O-acetyl-2,3-dideoxy-2-[(bis-methoxycarbonyl)methyl]-a-
d-lyxohexanoside (manno-8i): 300 mg (40%); Rf =0.74 (pentane/ethyl
acetate 1:1); [a]2D0 =+93.7 (c=1.11 in CHCl3); 1H NMR (600 MHz,
CDCl3): d=1.79 (ddd, J=13.5, 4.8, 4.4 Hz, 1H, 3-Heq), 1.99 (ddd, J=
13.5, 10.1, 4.2 Hz, 1H, 3-Hax), 2.02, 2.09 (2s, 3H each, OAc), 2.67 (dddd,
J=11.1, 4.4, 4.2, 2.0 Hz, 1H, 2-H), 3.38 (s, 3H, OMe), 3.67 (d, J=
11.1 Hz, 1H, 7-H), 3.73, 3.80 (2s, 3H each, COOMe), 3.92 (ddd, J=10.0,
5.6, 2.7 Hz, 1H, 5-H), 4.16 (dd, J=12.0, 2.7 Hz, 1H, 6-H), 4.20 (dd, J=
12.0, 5.6 Hz, 1H, 6’-H), 4.56 (d, J=2.0 Hz, 1H, 1-H), 4.86 ppm (ddd, J=
10.1, 10.0, 4.8 Hz, 1H, 4-H); 13C NMR (63 MHz, CDCl3): d=20.8, 21.0
(2q, OAc), 26.5 (t, C-3), 38.1 (d, C-2), 51.8 (d, C-7), 52.7, 52.8 (2q,
COOMe), 55.1 (q, OMe), 63.1 (t, C-6), 64.8 (d, C-4), 68.5 (d, C-5), 99.0
(d, C-1), 168.4, 168.8, 170.5, 170.8 ppm (4s, OAc, COOMe); IR (CHCl3):
n˜ =2956, 1741, 1435, 1372, 1242, 1040 cmꢀ1; elemental analysis calcd (%)
for C16H24O10 (376.36): C 51.06, H 6.43; found: C 50.84, H 6.22.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)methyl]-b-
d-galactopyranoside (galacto-12): Flash chromatography (cyclohexane/
ethyl acetate 10:1!8:1) gave the carbohydrate 2-C-analogue galacto-12
as a colorless syrup (2.40 g, 83%); Rf =0.44 (cyclohexane/ethyl acetate
4:1); [a]2D0 =+38.3 (c=1.01 in CHCl3); 1H NMR (500 MHz, CDCl3): d=
2.91 (ddd, J=12.5, 9.0, 4.0 Hz, 1H, 2-H), 3.34 (s, 3H, OMe), 3.46 (s, 3H,
COOMe), 3.53 (ddd, J=11.5, 4.0, 2.5 Hz, 1H, 5-H), 3.57 (dd, J=11.5,
4.0 Hz, 1H, 6-H), 3.60 (s, 3H, COOMe), 3.61 (dd, J=12.5, 6.5 Hz, 1H, 3-
H), 3.71 (dd, J=11.5, 2.5 Hz, 1H, 6’-H), 3.88 (dd, J=11.5, 6.5 Hz, 1H, 4-
H), 3.88 (d, J=4.0 Hz, 1H, 7-H), 4.28 (d, J=11.0 Hz, 1H, CH2-Ph), 4.38
(d, J=11.5 Hz, 1H, CH2-Ph), 4.42 (d, J=12.0 Hz, 1H, CH2-Ph), 4.50 (d,
J=11.5 Hz, 1H, CH2-Ph), 4.56 (d, J=11.0 Hz, 1H, CH2-Ph), 4.61 (d, J=
9.0 Hz, 1H, 1-H), 4.80 (d, J=12.0 Hz, 1H, CH2-Ph), 7.15–7.29 ppm (m,
15H, arom. H); 13C NMR (125 MHz, CDCl3): d=43.3, 47.8 (2d, C-2, C-
7), 51.8, 51.9 (2q, COOMe), 56.9 (q, OMe), 68.8 (t, C-6), 70.9, 71.4, 73.3
(3t, CH2-Ph), 73.4, 74.2, 78.7 (3d, C-3, C-4, C-5), 102.0 (d, C-1), 127.3,
127.6, 127.7, 127.9, 128.0 128.2, 128.3 (15d, arom, C-H), 137.4, 137.9,
138.6 (3s, arom. C-CH2O), 169.2, 169.8 ppm (2s, COOMe); IR (film): n˜ =
3030, 2951, 1956, 1735, 1436, 1286 cmꢀ1; elemental analysis calcd (%) for
C33H38O9 (578.65): C 68.50, H 6.62; found: C 68.65, H 6.60.
Addition of dimethylmaolnate (4a) to the
O-benzylated glycals 11
(method D): A solution of the benzyl-protected glycal 11 (5.0 mmol), di-
methyl malonate (4a) (6.61 g, 50 mmol, 10 equiv) and sodium hydrogen
carbonate (1.68 g, 20 mmol, 4 equiv) in dry methanol (20 mL) was cooled
to 08C under an argon atmosphere. At this temperature, a solution of
CAN (11.0 g, 20 mmol, 4 equiv), which was dried in a desiccator under
high vacuum overnight, in methanol (30 mL) was added dropwise over a
period of 4–6 h until TLC showed complete conversion of the starting
material. After stirring for 30 min at 08C, an ice-cold diluted solution of
sodium thiosulfate (200 mL) was added, and the mixture was extracted
with dichloromethane (4”80 mL). The combined organic extracts were
dried (Na2SO4) and concentrated, and the excess of malonate was re-
moved at 0.01 mbar in a Kugelrohrofen. The crude product was purified
by column chromatography (cyclohexane/ethyl acetate) and the 2-C-ma-
lonyl carbohydrates 12 were isolated in analytically pure form.
Methyl3,4-di- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)methyl]-a-d-
arabinopyranoside (arabino-12): Flash chromatography (cyclohexane/
ethyl acetate 8:1!6:1) afforded the carbohydrate 2-C-analogue arabino-
12 as a colorless syrup (1.88 g, 82%); Rf =0.42 (cyclohexane/ethyl acetate
3:1); [a]2D0 =ꢀ76.4 (c=0.82 in CHCl3); 1H NMR (500 MHz, CDCl3): d=
2.97 (ddd, J=13.0, 9.0, 4.5 Hz, 1H, 2-H), 3.32 (d, J=13.0 Hz, 1H, 5-H),
3.42 (s, 3H, OMe), 3.58 (s, 3H, COOMe), 3.67 (s, 3H, COOMe), 3.69 (s,
2H, 4H, 5’-H), 3.98 (d, J=4.5 Hz, 1H, 6-H), 4.13 (dd, J=13.0, 1.5 Hz,
1H, 3-H), 4.26 (d, J=11.5 Hz, 1H, CH2-Ph), 4.50 (d, J=11.5 Hz, 1H,
CH2-Ph), 4.64 (d, J=12.5 Hz, 1H, CH2-Ph), 4.66 (d, J=9.0 Hz, 1H, 1-H),
4.75 (d, J=12.5 Hz, 1H, CH2-Ph), 7.24–7.39 ppm (m, 10H, arom. H);
13C NMR (125 MHz, CDCl3): d=43.4, 48.1 (2d, C-2, C-6), 52.0 (2q,
COOMe), 57.0 (q, OMe), 63.3 (t, C-5), 70.8, 71.0 (2t, CH2-Ph), 69.8, 76.7
(2d, C-3, C-4), 102.5 (d, C-1), 127.6, 127.7, 127.9, 128.0, 128.3 (10d, arom,
C-H), 137.5, 138.3 (2s, arom. C-CH2O), 169.2, 169.9 ppm (2s, COOMe);
IR (film): n˜ =2951, 1731, 1435, 1238 cmꢀ1; elemental analysis calcd (%)
for C25H30O8 (458.50): C 65.49, H 6.60; found: C 65.67, H 6.70.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)methyl]-b-
d-glucopyranoside (gluco-12): Flash chromatography (cyclohexane/ethyl
acetate 10:1!8:1) gave the carbohydrate 2-C-analogue gluco-12 as a col-
orless syrup (2.25 g, 78%); Rf =0.42 (cyclohexane/ethyl acetate 4:1);
[a]2D0 =+5.0 (c=1.10 in CHCl3); 1H NMR (500 MHz, CDCl3): d=2.43
(ddd, J=12.5, 9.0, 4.0 Hz, 1H, 2-H), 3.38 (s, 3H, OMe), 3.43 (ddd, J=
11.5, 4.0, 3.0 Hz, 1H, 5-H), 3.50 (s, 3H, COOMe), 3.58 (dd, J=12.5,
8.5 Hz, 1H, 3-H), 3.62 (s, 3H, COOMe), 3.68 (d, J=3.0 Hz, 2H, 6-H),
3.73 (dd, J=11.5, 8.5 Hz, 1H, 4-H), 3.85 (d, J=4.0 Hz, 1H, 7-H), 4.46 (d,
J=11.0 Hz, 1H, CH2-Ph), 4.49 (d, J=12.0 Hz, 1H, CH2-Ph), 4.52 (d, J=
10.5 Hz, 1H, CH2-Ph), 4.59 (d, J=12.0 Hz, 1H, CH2-Ph), 4.66 (d, J=
9.0 Hz, 1H, 1-H), 4.69 (d, J=11.0 Hz, 1H, CH2-Ph), 4.82 (d, J=10.5 Hz,
1H, CH2-Ph), 7.06–7.30 ppm (m, 15H, arom. H); 13C NMR (125 MHz,
CDCl3): d=48.0, 48.2 (2d, C-2, C-7), 52.1, 52.2 (2q, COOMe), 57.2 (q,
OMe), 68.9 (t, C-6), 73.5, 74.6, 74.7 (3t, CH2-Ph), 75.0, 80.0, 80.4 (3d, C-
3, C-4, C-5), 101.9 (d, C-1), 127.6, 127.7, 127.8, 128.3, 128.4 (15d, arom,
C-H), 137.9, 138.1, 138.2 (3s, arom. C-CH2O), 169.0, 169.5 ppm (2s,
COOMe); IR (film): n˜ =3025, 2947, 2860, 1729, 1435, 1237 cmꢀ1; elemen-
tal analysis calcd (%) for C33H38O9 (578.65): C 68.50, H 6.62; found: C
68.75, H 6.58.
Methyl3,4-di- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)methyl]-b-d-
xylopyranoside (xylo-12): Flash chromatography (cyclohexane/ethyl ace-
tate 8:1!6:1) gave the carbohydrate 2-C-analogue xylo-12 as a colorless
syrup (1.72 g, 75%); Rf =0.40 (cyclohexane/ethyl acetate 3:1); [a]D20
=
ꢀ2.6 (c=0.89 in CHCl3); 1H NMR (500 MHz, CDCl3): d=2.33 (ddd, J=
12.0, 8.5, 4.0 Hz, 1H, 2-H), 3.20 (dd, J=10.0, 2.0 Hz, 1H, 5-H), 3.34 (s,
3H, OMe), 3.50 (s, 3H, COOMe), 3.57 (ddd, J=5.5, 2.5, 2.0 Hz, 1H, 4-
H), 3.61 (s, 3H, COOMe), 3.65 (dd, J=10.0, 2.5 Hz, 1H, 5’-H), 3.85 (d,
J=4.0 Hz, 1H, 6-H), 3.93 (dd, J=12.0, 5.5 Hz, 1H, 3-H), 4.46 (d, J=
11.0 Hz, 1H, CH2-Ph), 4.54 (d, J=11.0 Hz, 1H, CH2-Ph), 4.58 (d, J=
11.0 Hz, 1H, CH2-Ph), 4.60 (d, J=8.5 Hz, 1H, 1-H), 4.85 (d, J=11.0 Hz,
1H, CH2-Ph), 7.19–7.27 ppm (m, 10H, arom. H); 13C NMR (125 MHz,
CDCl3): d=47.1, 48.4 (2d, C-2, C-6), 52.2 (2q, COOMe), 57.0 (q, OMe),
63.4 (t, C-5), 72.7, 74.6 (2t, CH2-Ph), 78.4, 80.2 (2d, C-3, C-4), 102.2 (d,
C-1), 127.6, 127.8, 127.9, 128.2, 128.3, 128.5 (10d, arom, C-H), 138.0,
138.2 (2s, arom. C-CH2O), 169.0, 169.5 ppm (2s, COOMe); IR (film): n˜ =
3030, 2952, 1735, 1454, 1262 cmꢀ1; elemental analysis calcd (%) for
C25H30O8 (458.50): C 65.49, H 6.60; found: C 65.51, H 6.57.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)methyl]-a-
d-mannopyranoside (manno-12): Flash chromatography (cyclohexane/
ethyl acetate 10:1!8:1) afforded the carbohydrate 2-C-analogue manno-
12 as a colorless syrup (375 mg, 13%); Rf =0.42 (cyclohexane/ethyl ace-
tate 4:1); [a]2D0 =+3.4 (c=0.92 in CHCl3); 1H NMR (500 MHz, CDCl3):
d=3.14 (ddd, J=10.5, 5.0, 1.5 Hz, 1H, 2-H), 3.27 (s, 3H, OMe), 3.36 (s,
3H, COOMe), 3.58 (ddd, J=9.5, 6.0, 3.5 Hz, 1H, 5-H), 3.64 (s, 3H,
COOMe), 3.65–3.70 (m, 2H, 6-H, 6’-H), 3.67 (d, J=5.0 Hz, 1H, 7-H),
3.77 (dd, J=9.5, 4.5 Hz, 1H, 4-H), 4.08 (dd, J=10.5, 4.5 Hz, 1H, 3-H),
4.35 (d, J=11.0 Hz, 1H, CH2-Ph), 4.38 (d, J=11.0 Hz, 1H, CH2-Ph), 4.42
(d, J=12.5 Hz, 1H, CH2-Ph), 4.50 (d, J=11.0 Hz, 1H, CH2-Ph), 4.54 (d,
J=12.5 Hz, 1H, CH2-Ph), 4.65 (d, J=1.5 Hz, 1H, 1-H), 4.73 (d, J=
11.0 Hz, 1H, CH2-Ph), 7.06–7.31 ppm (m, 15H, arom. H); 13C NMR
(125 MHz, CDCl3): d=42.2, 49.4 (2d, C-2, C-7), 52.4, 52.7 (2q, COOMe),
55.1 (q, OMe), 69.1 (t, C-6), 72.2, 73.3, 74.6 (3t, CH2-Ph), 71.4, 73.3, 78.7
(3d, C-3, C-4, C-5), 99.8 (d, C-1), 127.5, 127.6, 127.7, 128.0, 128.2, 128.3
Methyl3,4-di- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)methyl]-a-d-
lyxopyranoside (lyxo-12): Flash chromatography (cyclohexane/ethyl ace-
tate 8:1!6:1) gave the carbohydrate 2-C-analogue lyxo-12 as a colorless
syrup (275 mg, 12%); Rf =0.40 (cyclohexane/ethyl acetate 3:1); [a]D20
=
+59.7 (c=1.02 in CHCl3); 1H NMR (500 MHz, CDCl3): d=2.49 (ddd,
J=11.0, 6.0, 3.0 Hz, 1H, 2-H), 3.19 (s, 3H, OMe), 3.44 (s, 3H, COOMe),
3.48 (dd, J=10.5, 3.5 Hz, 1H, 5-H), 3.57 (s, 3H, COOMe), 3.57 (ddd, J=
9.0, 5.0, 3.5 Hz, 1H, 4-H), 3.63 (d, J=6.0 Hz, 1H, 6-H), 3.65 (dd, J=10.5,
5.0 Hz, 1H, 5’-H), 3.88 (dd, J=11.0, 9.0 Hz, 1H, 3-H), 4.54 (d, J=
Chem. Eur. J. 2007, 13, 10152 – 10167
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10161

T. Linker et al.
11.5 Hz, 1H, CH2-Ph), 4.59 (d, J=11.5 Hz, 1H, CH2-Ph), 4.61 (d, J=
11.0 Hz, 1H, CH2-Ph), 4.84 (d, J=3.0 Hz, 1H, 1-H), 4.95 (d, J=11.0 Hz,
1H, CH2-Ph), 7.18–7.25 ppm (m, 10H, arom. H); 13C NMR (125 MHz,
CDCl3): d=45.8, 49.9 (2d, C-2, C-6), 52.2, 52.3 (2q, COOMe), 55.2 (q,
OMe), 60.2 (t, C-5), 72.8, 74.9 (2t, CH2-Ph), 77.6, 80.2 (2d, C-3, C-4),
99.2 (d, C-1), 127.4, 127.7, 127.8, 128.2, 128.4 (10d, arom, C-H), 138.1,
138.6 (2s, arom. C-CH2O), 168.8, 168.9 ppm (2s, COOMe); IR (film): n˜ =
2950, 1732, 1454, 1126 cmꢀ1; elemental analysis calcd (%) for C25H30O8
(458.50): C 65.49, H 6.60; found: C 65.55, H 6.56.
hexane/ethyl acetate) and the glyco-acetic esters 13 were isolated in ana-
lytically pure form.
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-b-d-
glucopyranoside (gluco-13a): Flash chromatography (cyclohexane/ethyl
acetate 4:1!3:1) gave the methyl ester gluco-13a as a white solid
(345 mg, 92%); Rf =0.43 (cyclohexane/ethyl acetate 1:1); m.p. 75–778C;
[a]2D0 =+20.3 (c=1.20 in CHCl3); 1H NMR (300 MHz, CDCl3): d=2.01,
2.02, 2.08 (3s, 3H each, OAc), 2.27 (dddd, J=11.1, 8.7, 5.7, 2.4 Hz, 1H,
2-H), 2.39–2.43 (m, 2H, 7-H, 7’-H), 3.51 (s, 3H, OMe), 3.67 (s, 3H,
COOMe), 3.70 (ddd, J=9.6, 4.5, 2.4 Hz, 1H, 5-H), 4.13 (dd, J=12.3,
2.4 Hz, 1H, 6-H), 4.30 (dd, J=12.3, 4.5 Hz, 1H, 6’-H), 4.47 (d, J=8.7 Hz,
1H, 1-H), 4.99 (dd, J=9.6, 9.3 Hz, 1H, 4-H), 5.12 ppm (dd, J=11.1,
9.3 Hz, 1H, 3-H); 13C NMR (75 MHz, CDCl3): d=20.5, 20.6 (3q, OAc),
31.5 (t, C-7), 43.2 (d, C-2), 51.6 (q, COOMe), 57.1 (q, OMe), 62.2 (t, C-
6), 69.6, 71.6, 72.9 (3d, C-3, C-4, C-5), 103.0 (d, C-1), 169.7, 170.3, 170.6,
171.6 ppm (4s, OAc, COOMe); IR (film): n˜ =3002, 2972, 1751, 1372,
1237 cmꢀ1; elemental analysis calcd (%) for C16H24O10 (376.36): C 51.06,
H 6.43; found: C 51.03, H 6.57.
Methyl3,6,8,9,10,12-hexa- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)-
methyl]-b-d-maltopyranoside (malto-12): Flash chromatography (cyclo-
hexane/ethyl acetate 10:1!8:1) gave the carbohydrate 2-C-analogue
malto-12 as a colorless syrup (4.09 g, 81%); Rf =0.38 (cyclohexane/ethyl
acetate 4:1); [a]2D0 =+18.7 (c=1.00 in CHCl3); 1H NMR (500 MHz,
CDCl3): d=2.62 (ddd, J=12.5, 8.5, 4.0 Hz, 1H, 2-H), 3.44 (s, 3H, OMe),
3.46 (ddd, J=6.5, 3.0, 2.5 1H, 5-H), 3.49 (dd, J=7.5, 1.5 Hz, 2H, 12-H,
12’-H), 3.55–3.58 (m, 1H, 11-H), 3.60 (dd, J=11.0, 3.0 Hz, 1H, 6-H), 3.63
(dd, J=11.0, 6.5 Hz, 1H, 4-H), 3.63, 3.65 (2s, 3H each, COOMe), 3.64–
3.68 (m, 1H, 8-H), 3.76 (dd, J=11.0, 2.5 Hz, 1H, 6’-H), 3.85 (dd, J=10.5,
8.0 Hz, 1H, 10-H), 3.90 (d, J=4.0 Hz, 1H, 13-H), 3.94 (dd, J=12.5,
6.5 Hz, 1H, 3-H), 4.07 (t, J=8.3 Hz, 1H, 9-H), 4.37 (d, J=12.5 Hz, 1H,
CH2-Ph), 4.45 (d, J=11.0 Hz, 1H, CH2-Ph), 4.47 (d, J=11.0 Hz, 1H,
CH2-Ph), 4.53 (d, J=6.5 Hz, 2H, CH2-Ph), 4.55 (s, 4H, CH2-Ph), 4.74 (d,
J=11.0 Hz, 1H, CH2-Ph), 4.81 (d, J=8.5 Hz, 1H, 1-H), 4.83 (d, J=
12.5 Hz, 1H, CH2-Ph), 5.08 (d, J=11.0 Hz, 1H, CH2-Ph), 5.30 (d, J=3.5,
1H, 7-H), 7.12–7.32 ppm (m, 30H, arom. H); 13C NMR (125 MHz,
CDCl3): d=46.8 (d, C-13), 48.5 (d, C-2), 52.2 (2q, COOMe), 57.0 (q,
OMe), 68.5, 69.5 (2t, C-6, C-12), 73.2, 73.4, 75.0, 75.3, 75.5 (6t, CH2-Ph),
71.1, 72.2, 77.7, 79.6, 80.0, 81.9 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11),
97.3, 101.6 (2d, C-1, C-7), 127.3, 127.5, 127.6, 127.8, 127.9, 128.2, 128.3
(30d, arom, C-H), 137.9, 138.0, 138.2, 138.3, 138.4, 138.7 (6s, arom. C-
CH2O), 168.8, 169.5 ppm (2s, COOMe); IR (film): n˜ =2863, 1734, 1496,
1142, 1027 cmꢀ1; elemental analysis calcd (%) for C60H66O14 (1011.17): C
71.27, H 6.58; found: C 71.37, H 6.49.
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-b-d-
galactopyranoside (galacto-13a): Flash chromatography (cyclohexane/
ethyl acetate 4:1!3:1) gave the methyl ester galacto-13a as a colorless
syrup (305 mg, 81%); Rf =0.45 (cyclohexane/ethyl acetate 1:1); [a]D20
=
ꢀ0.84 (c=1.02 in CHCl3); 1H NMR (300 MHz, CDCl3): d=1.99, 2.05,
2.14 (3s, 3H each, OAc), 2.42 (dddd, J=11.1, 8.4, 4.8, 3.0 Hz, 1H, 2-H),
2.36–2.49 (m, 2H, 7-H, 7’-H), 3.52 (s, 3H, OMe), 3.67 (s, 3H, COOMe),
3.87 (ddd, J=6.9, 6.6, 0.9 Hz, 1H, 5-H), 4.12 (dd, J=11.1, 6.9 Hz, 1H, 6-
H), 4.20 (dd, J=11.1, 6.6 Hz, 1H, 6’-H), 4.40 (d, J=8.4 Hz, 1H, 1-H),
4.92 (dd, J=11.4, 3.3 Hz, 1H, 3-H), 5.29 ppm (dd, J=3.3, 0.9 Hz, 1H, 4-
H); 13C NMR (75 MHz, CDCl3): d=20.5, 20.6 (3q, OAc), 31.4 (t, C-7),
38.6 (d, C-2), 51.6 (q, COOMe), 57.2 (q, OMe), 61.6 (t, C-6), 65.8, 70.6,
71.3 (3d, C-3, C-4, C-5), 103.6 (d, C-1), 170.0, 170.3, 170.4, 171.9 ppm (4s,
OAc, COOMe); IR (film): n˜ =2956, 2849, 1747, 1372, 1244 cmꢀ1; elemen-
tal analysis calcd (%) for C16H24O10 (376.36): C 51.06, H 6.43; found: C
51.54, H 6.53.
Methyl3,4-di- O-acetyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-b-d-xy-
lopyranoside (xylo-13a): Flash chromatography (cyclohexane/ethyl ace-
Methyl3,6,8,9,10,12-hexa- O-benzyl-2-deoxy-2-C-[bis-(methoxycarbonyl)-
methyl]-b-d-lactopyranoside (lacto-12): Flash chromatography (cyclohex-
ane/ethyl acetate 10:1!8:1) gave the carbohydrate 2-C-analogue lacto-12
as a colorless syrup (4.14 g, 82%); Rf =0.39 (cyclohexane/ethyl acetate
4:1); [a]2D0 =+14.9 (c=0.86 in CHCl3); 1H NMR (500 MHz, CDCl3): d=
2.41 (ddd, J=12.0, 9.0, 4.0 Hz, 1H, 2-H), 3.21 (d, J=2.0 Hz, 1H, 11-H),
3.27 (dd, J=9.0, 3.5 Hz, 1H, 12-H), 3.30 (dd, J=9.0, 4.0 Hz, 1H, 12’-H),
3.36 (s, 3H, OMe), 3.39 (dd, J=11.0, 8.5 Hz, 1H, 4-H), 3.42 (ddd, J=8.5,
2.5, 2.0 1H, 5-H), 3.54 (dd, J=11.0, 2.5 Hz, 1H, 6-H), 3.56, 3.59 (2s, 3H
each, COOMe), 3.62 (m, J=11.0, 2.0 Hz, 1H, 6’-H), 3.67 (dd, J=9.5,
8.0 Hz, 1H, 1H, 8-H), 3.79 (dd, J=11.0, 4.0 Hz, 1H, 10-H), 3.82 (d, J=
2.5 Hz, 1H, 9-H), 3.93 (dd, J=12.5, 8.5 Hz, 1H, 3-H), 3.95 (d, J=4.0 Hz,
1H, 13-H), 4.16 (d, J=12.0 Hz, 1H, CH2-Ph), 4.27 (d, J=12.0 Hz, 1H,
CH2-Ph), 4.28 (d, J=10.5 Hz, 1H, CH2-Ph), 4.31 (d, J=12.0 Hz, 1H,
CH2-Ph), 4.34 (d, J=8.0, 1H, 7-H), 4.45 (d, J=11.5 Hz, 1H, CH2-Ph),
4.52 (d, J=12.0 Hz, 1H, CH2-Ph), 4.63 (s, 2H, CH2-Ph), 4.73 (d, J=
4.5 Hz, 2H, CH2-Ph), 4.75 (d, J=9.0 Hz, 1H, 1-H), 4.88 (d, J=11.5 Hz,
1H, CH2-Ph), 5.08 (d, J=10.5 Hz, 1H, CH2-Ph), 7.04–7.28 ppm (m, 30H,
arom. H); 13C NMR (125 MHz, CDCl3): d=47.7 (d, C-13), 48.4 (d, C-2),
52.1 (2q, COOMe), 57.3 (q, OMe), 68.0, 68.1 (2t, C-6, C-12), 72.6, 73.1,
73.4, 74.6, 74.7, 75.3 (6t, CH2-Ph), 73.0, 73.7, 75.2, 77.6, 78.4, 80.1, 82.3
(7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11), 101.9, 102.7 (2d, C-1, C-7),
127.2, 127.4, 127.5, 127.6, 127.7, 127.8, 127.9, 128.1, 128.2, 128.3, 128.4
(30d, arom, C-H), 138.1, 138.4, 138.5, 138.6, 138.7, 139.0 (6s, arom. C-
CH2O), 169.2, 169.8 ppm (2s, COOMe); IR (film): n˜ =3029, 2864, 1734,
1453, 1027 cmꢀ1; elemental analysis calcd (%) for C60H66O14 (1011.17): C
71.27, H 6.58; found: C 71.31, H 6.49.
tate 4:1!3:1) gave the methyl ester xylo-13a as
a colorless syrup
(245 mg, 81%); Rf =0.47 (cyclohexane/ethyl acetate 1:1); [a]2D0 =+26.82
(c=1.08 in CHCl3); 1H NMR (300 MHz, CDCl3): d=2.03, 2.05 (2s, 3H
each, OAc), 2.25 (dddd, J=10.2, 7.8, 4.2, 1.2 Hz, 1H, 2-H), 2.43 (d, J=
6.0, 2H, 6-H), 3.36 (dd, J=11.7, 8.7 Hz, 1H, 5-H), 3.46 (s, 3H, OMe),
3.67 (s, 3H, COOMe), 4.11 (dd, J=11.7, 5.4 Hz, 1H, 5’-H), 4.39 (d, J=
7.8 Hz, 1H, 1-H), 4.89 (ddd, J=8.7, 8.4, 5.4 Hz, 1H, 4-H), 5.05 ppm (dd,
J=10.2, 8.4 Hz, 1H, 3-H); 13C NMR (75 MHz, CDCl3): d=20.7, 20.8 (2q,
OAc), 32.2 (t, C-6), 42.2 (d, C-2), 51.7 (q, COOMe), 56.8 (q, OMe), 62.3
(t, C-5), 70.2, 72.1 (2d, C-3, C-4), 103.2 (d, C-1), 170.0, 170.2, 171.8 ppm
(3s, OAc, COOMe); IR (film): n˜ =2955, 2849, 1747, 1372, 1244 cmꢀ1; ele-
mental analysis calcd (%) for C13H20O8 (304.29): C 51.31, H 6.62; found:
C 51.72, H 6.73.
Methyl3,4-di- O-acetyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-b-d-ara-
binopyranoside (arabino-13a): Flash chromatography (cyclohexane/ethyl
acetate 4:1!3:1) gave the methyl ester arabino-13a as a colorless syrup
(240 mg, 79%); Rf =0.48 (cyclohexane/ethyl acetate 1:1); [a]2D0 =ꢀ26.85
(c=1.22 in CHCl3); 1H NMR (300 MHz, CDCl3): d=2.02, 2.14 (2s, 3H
each, OAc), 2.42 (t, J=5.7, 2H, 6-H), 2.52 (dddd, J=11.4, 8.4, 3.6,
1.5 Hz, 1H, 2-H), 3.50 (s, 3H, OMe), 3.65 (dd, J=13.2, 1.2 Hz, 1H, 5-H),
3.67 (s, 3H, COOMe), 4.05 (dd, J=13.2, 2.4 Hz, 1H, 5’-H), 4.30 (d, J=
8.4 Hz, 1H, 1-H), 4.91 (dd, J=11.4, 3.3 Hz, 1H, 3-H), 5.17 ppm (ddd, J=
3.3, 2.4, 1.2 Hz, 1H, 4-H); 13C NMR (75 MHz, CDCl3): d=20.6, 20.9 (2q,
OAc), 31.7 (t, C-6), 39.0 (d, C-2), 51.6 (q, COOMe), 57.0 (q, OMe), 64.2
(t, C-5), 66.8, 71.0 (2d, C-3, C-4), 103.8 (d, C-1), 170.1, 170.4, 172.0 ppm
(3s, OAc, COOMe); IR (film): n˜ =2955, 2847, 1742, 1373, 1249 cmꢀ1; ele-
mental analysis calcd (%) for C13H20O8 (304.29): C 51.31, H 6.62; found:
C 51.40, H 6.60.
Decarboxylation of the acetyl-protected 2-C-malonyl carbohydrates 8
(method E): A solution of the 2-C-malonyl carbohydrate 8 (1.0 mmol)
and lithium iodide (200 mg, 1.5 mmol) in DMSO (12 mL) was heated to
1808C in a Kugelrohrofen and kept under rotation at this temperature
for 5.5–6.5 h. DMSO was removed at 0.01 mbar directly in the Kugelroh-
rofen. The crude product was purified by column chromatography (cyclo-
Methyl3,6,8,9,10,12-hexa-
O-acetyl-2-deoxy-2-C-[(methoxycarbonyl)-
methyl]-b-d-maltopyranoside (malto-13a): Flash chromatography (cyclo-
hexane/ethyl acetate 3:1!2:1) gave the methyl ester malto-13a as a
white solid (485 mg, 73%). Rf =0.26 (cyclohexane/ethyl acetate 1:1); m.p.
10162
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 10152 – 10167

Malonyl Carbohydrates
FULL PAPER
144–1468C; [a]2D0 =+72.8 (c=1.07 in CHCl3); 1H NMR (300 MHz,
CDCl3): d=2.00, 2.03, 2.06, 2.10, 2.14 (6s, 3H each, OAc), 2.07 (dddd,
J=11.1, 8.7, 5.7, 5.4 Hz, 1H, 2-H), 2.31 (dd, J=16.4, 5.7 Hz, 1H, 13-H),
2.41 (dd, J=16.4, 5.4 Hz, 1H, 13’-H), 3.48 (s, 3H, OMe), 3.66 (s, 3H,
COOMe), 3.68 (ddd, J=9.3, 4.5, 2.7 Hz, 1H, 5-H), 3.90 (dd, J=9.3,
8.7 Hz, 1H, 4-H), 3.98 (ddd, J=10.2, 3.6, 2.4 Hz, 1H, 11-H), 4.05 (dd, J=
12.3, 2.1 Hz, 1H, 12-H), 4.26 (dd, J=12.3, 4.5 Hz, 1H, 12’-H), 4.26 (dd,
J=12.0, 4.5 Hz, 1H, 6-H), 4.47 (dd, J=12.0, 2.7 Hz, 1H, 6’-H), 4.49 (d,
J=8.7 Hz, 1H, 1-H), 4.89 (dd, J=10.5, 3.9 Hz, 1H, 8-H), 5.05 (dd, J=
10.5, 9.3 Hz, 1H, 10-H), 5.20 (dd, J=11.1, 8.7 Hz, 1H, 3-H), 5.35 (d, J=
3.9 Hz, 1H, 7-H), 5.35 ppm (dd, J=10.5, 9.3 Hz, 1H, 9-H); 13C NMR
(75 MHz, CDCl3): d=20.6, 20.8, 20.9 (6q, OAc), 31.4 (t, C-13), 43.9 (d,
C-2), 51.6 (q, COOMe), 57.1 (q, OMe), 61.6, 63.2 (2t, C-6, C-12), 68.1,
68.4, 69.4, 70.0, 72.2, 74.0, 75.3 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11),
95.5, 102.7 (2d, C-1, C-7), 169.4, 169.8, 169.9, 170.4, 170.5, 171.0,
171.7 ppm (7s, OAc, COOMe); IR (film): n˜ =2960, 1746, 1371, 1230,
1042 cmꢀ1; elemental analysis calcd (%) for C28H40O18 (664.61): C 50.60,
H 6.07; found: C 50.34, H 6.08.
(3q, OAc), 21.7 (2q, COOCH
OMe), 61.6 (t, C-6), 65.8 (d, COOCH
C-4, C-5), 103.7 (d, C-1), 170.0, 170.3, 170.4, 170.9 ppm (4s, OAc,
COOCH
(CH3)2); IR (film): n˜ =2982, 2939, 1749, 1374, 1245 cmꢀ1; ele-
mental analysis calcd (%) for C18H28O10 (404.41): C 53.46, H 6.98; found:
C 53.29, H 7.11.
ACHTREUNG
AHCTREUNG
AHCTREUNG
Methyl3,4-di- O-acetyl-2-deoxy-2-C-[(methylethoxycarbonyl)methyl]-b-
d-xylopyranoside (xylo-13b): Flash chromatography (cyclohexane/ethyl
acetate 4:1!3:1) gave the isopropyl ester xylo-13b as a colorless syrup
(273 mg, 82%); Rf =0.51 (cyclohexane/ethyl acetate 1:1); [a]2D0 =ꢀ19.4
(c=1.05 in CHCl3); 1H NMR (300 MHz, CDCl3): d=1.20–1.26 (m, 6H,
COOCHCAHTREU(GN CH3)2), 2.03, 2.05 (2s, 3H each, OAc), 2.24 (dddd, J=10.2, 7.5,
5.9, 3.8 Hz, 1H, 2-H), 2.38 (dd, J=5.9, 3.8 Hz, 2H, 6-H), 3.36 (dd, J=
12.0, 8.7 Hz, 1H, 5-H), 3.46 (s, 3H, OMe), 4.10 (dd, J=12.0, 5.1 Hz, 1H,
5’-H), 4.40 (d, J=7.5 Hz, 1H, 1-H), 4.89 (ddd, J=8.7, 8.3, 5.1 Hz, 1H, 4-
H), 4.95–5.03 (m, 1H, COOCH
1H, 3-H); 13C NMR (75 MHz, CDCl3): d=20.7 (2q, OAc), 21.7 (2q,
COOCH(CH3)2), 32.7 (t, C-6), 42.1 (d, C-2), 56.8 (q, OMe), 62.2 (t, C-5),
68.0 (d, COOCH(CH3)2), 70.2, 71.9 (2d, C-3, C-4), 103.3 (d, C-1), 170.0,
170.1, 170.8 ppm (3s, OAc, COOCH(CH3)2); IR (film): n˜ =2982, 2937,
1749, 1373, 1242 cmꢀ1
elemental analysis calcd (%) for C15H24O8
ACHTREU(NG CH3)2), 5.06 ppm (dd, J=10.2, 8.3 Hz,
AHCTREUNG
AHCTREUNG
Methyl3,6,8,9,10,12-hexa-
O-acetyl-2-deoxy-2-C-[(methoxycarbonyl)-
AHCTREUNG
methyl]-b-d-lactopyranoside (lacto-13a): Flash chromatography (cyclo-
hexane/ethyl acetate 3:1!2:1) gave the methyl ester lacto-13a as a color-
less syrup (480 mg, 72%); Rf =0.29 (cyclohexane/ethyl acetate 1:1);
[a]2D0 =+13.7 (c=1.03 in CHCl3); 1H NMR (300 MHz, CDCl3): d=1.96,
2.05, 2.06, 2.07, 2.12, 2.15 (6s, 3H each, OAc), 2.22 (dddd, J=10.8, 8.7,
5.7, 2.4 Hz, 1H, 2-H), 2.38 (dd, J=5.7, 3.0 Hz, 2H, 13-H), 3.34 (dd, J=
10.8, 0.9 Hz, 1H, 4-H), 3.47 (s, 3H, OMe), 3.57 (ddd, J=9.9, 5.1, 2.1 Hz,
1H, 5-H), 3.66 (s, 3H, COOMe), 3.67–3.73 (m, 1H, 11-H), 3.84–3.91 (m,
1H, 12-H), 4.04–4.20 (m, 2H, 6-H, 12’-H), 4.38 (d, J=8.7 Hz, 1H, 1-H),
4.44–4.52 (m, 1H, 6’-H), 4.45 (dd, J=7.8, 2.4 Hz, 1H, 8-H), 4.95 (dd, J=
10.5, 3.3 Hz, 1H, 10-H), 5.07 (d, J=7.8 Hz, 1H, 7-H), 5.07 (dd, J=2.4,
1.2 Hz, 1H, 9-H), 5.35 ppm (dd, J=3.3, 0.9 Hz, 1H, 3-H); 13C NMR
(75 MHz, CDCl3): d=20.6, 20.8, 21.0 (6q, OAc), 31.9 (t, C-13), 43.6 (d,
C-2), 51.6 (q, COOMe), 57.1 (q, OMe), 60.3, 60.8 (2t, C-6, C-12), 62.3,
66.7, 69.2, 70.6, 71.0, 72.7, 76.9 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11),
101.0, 103.1 (2d, C-1, C-7), 169.0, 170.0, 170.1, 170.3, 170.4, 171.8 ppm
(7s, OAc, COOMe); IR (film): n˜ =2957, 1751, 1372, 1229, 1050 cmꢀ1; ele-
mental analysis calcd (%) for C28H40O18 (664.61): C 50.60, H 6.07; found:
C 50.67, H 6.20.
;
(332.35): C 54.21, H 7.28; found: C 54.43, H 7.30.
Methyl3,4-di- O-acetyl-2-deoxy-2-C-[(methylethoxycarbonyl)methyl]-b-
d-arabinopyranoside (arabino-13b): Flash chromatography (cyclohexane/
ethyl acetate 4:1!3:1) gave the isopropyl ester arabino-13b as a color-
less syrup (270 mg, 81%); Rf =0.50 (cyclohexane/ethyl acetate 1:1);
[a]2D0 =ꢀ25.7 (c=1.08 in CHCl3); 1H NMR (300 MHz, CDCl3): d=1.22–
1.26 (m, 6H, COOCHACHTRE(UNG CH3)2), 2.02, 2.13 (2s, 3H each, OAc), 2.34 (dd,
J=15.3, 6.3 Hz, 1H, 6-H), 2.42 (dd, J=15.3, 4.8 Hz, 1H, 6’-H), 2.52
(dddd, J=11.4, 8.4, 6.3, 4.8 Hz, 1H, 2-H), 3.50 (s, 3H, OMe), 3.64 (dd,
J=13.2, 1.2 Hz, 1H, 5-H), 4.05 (dd, J=13.2, 2.4 Hz, 1H, 5’-H), 4.31 (d,
J=8.4 Hz, 1H, 1-H), 4.91 (dd, J=11.4, 3.3 Hz, 1H, 3-H), 4.96–5.04 (m,
1H, COOCH
13C NMR (75 MHz, CDCl3): d=20.6, 20.9 (2q, OAc), 21.7 (2q, COOCH-
(CH3)2), 32.2 (t, C-6), 39.0 (d, C-2), 57.0 (q, OMe), 64.2 (t, C-5), 66.9 (d,
COOCH(CH3)2), 67.9, 71.1 (2d, C-3, C-4), 103.9 (d, C-1), 170.1, 170.41,
171.1 ppm (3s, OAc, COOCHAHCTREU(GN CH3)2); IR (film): n˜ =2981, 2937, 1747,
ACHTRE(UNG CH3)2), 5.17 ppm (ddd, J=3.3, 2.4, 1.2 Hz, 1H, 4-H);
AHCTREUNG
AHCTREUNG
1374, 1246 cmꢀ1; elemental analysis calcd (%) for C15H24O8 (332.35): C
54.21, H 7.28; found: C 54.38, H 7.36.
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[(methylethoxycarbonyl)methyl]-
b-d-glucopyranoside (gluco-13b): Flash chromatography (cyclohexane/
ethyl acetate 4:1!3:1) gave the isopropyl ester gluco-13b as a white
solid (315 mg, 78%); Rf =0.45 (cyclohexane/ethyl acetate 1:1); m.p. 66–
Methyl3,6,8,9,10,12-hexa-
O-acetyl-2-deoxy-2-C-[(methylethoxycarbo-
nyl)methyl]-b-d-maltopyranoside (malto-13b): Flash chromatography
(cyclohexane/ethyl acetate 3:1!2:1) gave the isopropyl ester malto-13b
as a white solid (512 mg, 74%); Rf =0.28 (cyclohexane/ethyl acetate 1:1);
m.p. 146–1498C; [a]2D0 =+65.6 (c=1.00 in CHCl3); 1H NMR (300 MHz,
1
698C; [a]2D0 =+12.2 (c=1.01 in CHCl3); H NMR (300 MHz, CDCl3): d=
1.20–1.26 (m, 6H, COOCHACHTREU(GN CH3)2), 2.01, 2.03, 2.08 (3s, 3H each, OAc),
2.27 (dddd, J=10.8, 8.1, 5.7, 4.8 Hz, 1H, 2-H), 2.34 (dd, J=15.6, 5.7 Hz,
1H, 7-H), 2.41 (dd, J=15.6, 4.8 Hz, 1H, 7’-H), 3.50 (s, 3H, OMe), 3.68
(ddd, J=9.9, 4.8, 2.4 Hz, 1H, 5-H), 4.12 (dd, J=12.0, 2.4 Hz, 1H, 6-H),
4.31 (dd, J=12.0, 4.8 Hz, 1H, 6’-H), 4.47 (d, J=8.1 Hz, 1H, 1-H), 4.95–
CDCl3): d=1.21–1.25 (m, 6H, COOCHACHTRE(UNG CH3)2), 2.00, 2.02, 2.04, 2.06,
2.10, 2.14 (6 s, 3H each, OAc), 2.25 (dd, J=16.5, 5.7 Hz, 1H, 13-H), 2.30
(dddd, J=10.8, 8.7, 5.7, 5.1 Hz, 1H, 2-H), 2.36 (dd, J=16.5, 5.1 Hz, 1H,
13’-H), 3.47 (s, 3H, OMe), 3.66 (ddd, J=9.3, 4.5, 2.7 Hz, 1H, 5-H), 3.94
(dd, J=9.3, 8.7 Hz, 1H, 4-H), 3.99 (ddd, J=10.2, 3.8, 2.4 Hz, 1H, 11-H),
4.05 (dd, J=12.3, 2.4 Hz, 1H, 12-H), 4.24 (dd, J=12.3, 3.8 Hz, 1H, 12’-
H), 4.28 (dd, J=12.0, 4.5 Hz, 1H, 6-H), 4.48 (dd, J=12.0, 2.7 Hz, 1H, 6’-
H), 4.48 (d, J=8.7 Hz, 1H, 1-H), 4.90 (dd, J=10.7, 3.9 Hz, 1H, 8-H),
5.03 (m, 1H, COOCH
5.12 ppm (dd, J=10.8, 9.3 Hz, 1H, 3-H); 13C NMR (75 MHz, CDCl3): d=
20.6, 20.7 (3q, OAc), 21.7 (2q, COOCH(CH3)2), 32.1 (t, C-7), 43.2 (d, C-
2), 57.1 (q, OMe), 62.3 (t, C-6), 68.0 (d, COOCH(CH3)2), 69.8, 71.7, 72.9
(3d, C-3, C-4, C-5), 103.3 (d, C-1), 169.7, 170.2, 170.7 ppm (4s, OAc,
COOCH
(CH3)2); IR (film): n˜ =2980, 1748, 1720, 1371, 1250 cmꢀ1; ele-
ACHTRE(UNG CH3)2), 4.99 (dd, J=9.9, 9.3 Hz, 1H, 4-H),
AHCTREUNG
AHCTREUNG
4.96–5.08 (m, 1H, COOCHACHTREU(GN CH3)2), 5.02 (dd, J=10.7, 9.3 Hz, 1H, 10-H),
ACHTREUNG
5.20 (dd, J=10.8, 8.7 Hz, 1H, 3-H), 5.35 ppm (dd, J=10.7, 9.3 Hz, 1H, 9-
H), 5.36 (d, J=3.6 Hz, 1H, 7-H); 13C NMR (75 MHz, CDCl3): d=20.6,
mental analysis calcd (%) for C18H28O10 (404.41): C 53.46, H 6.98; found:
C 53.63, H 7.08.
20.8, 20.9 (6q, OAc), 21.7 (2q, COOCH
ACHTREUNG
C-2), 57.0 (q, OMe), 61.6, 63.3 (2t, C-6, C-12), 68.0 (d, COOCHACHTREUNG
Methyl3,4,6-tri- O-acetyl-2-deoxy-2-C-[(methylethoxycarbonyl)methyl]-
b-d-galactopyranoside (galacto-13b): Flash chromatography (cyclohex-
ane/ethyl acetate 4:1!3:1) gave the isopropyl ester galacto-13b as a col-
orless syrup (325 mg, 80%); Rf =0.47 (cyclohexane/ethyl acetate 1:1);
[a]2D0 =ꢀ3.4 (c=1.04 in CHCl3); 1H NMR (300 MHz, CDCl3): d=1.20–
68.1, 68.4, 69.5, 70.0, 72.2, 74.1, 75.3 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-
11), 95.5, 102.9 (2d, C-1, C-7), 169.4, 169.8, 170.3, 170.5, 170.8 ppm (7s,
(CH3)2); IR (film): n˜ =2980, 1747, 1373, 1231, 1045 cmꢀ1
OAc, COOCHCAHTREUNG ;
elemental analysis calcd (%) for C30H44O18 (692.66): C 52.02, H 6.40;
found: C 52.20, H 6.39.
1.26 (m, 6H, COOCHACHTREUNG(CH3)2), 2.00, 2.05, 2.13 (3s, 3H each, OAc), 2.32
(dd, J=15.3, 6.3 Hz, 1H, 7-H), 2.39 (dd, J=15.3, 4.8 Hz, 1H, 7’-H), 2.48
(dddd, J=11.7, 8.4, 6.3, 4.8 Hz, 1H, 2-H), 3.52 (s, 3H, OMe), 3.87 (ddd,
J=6.9, 6.6, 0.9 Hz, 1H, 5-H), 4.14 (dd, J=11.1, 6.9 Hz, 1H, 6-H), 4.20
(dd, J=11.1, 6.6 Hz, 1H, 6’-H), 4.40 (d, J=8.4 Hz, 1H, 1-H), 4.91 (dd,
Methyl3,6,8,9,10,12-hexa-
O-acetyl-2-deoxy-2-C-[(methylethoxycarbo-
nyl)methyl]-b-d-lactopyranoside (lacto-13b): Flash chromatography (cy-
clohexane/ethyl acetate 3:1!2:1) gave the isopropyl ester lacto-13b as a
white solid (492 mg, 71%); Rf =0.30 (cyclohexane/ethyl acetate 1:1); m.p.
48–518C; [a]2D0 =+17.0 (c=1.05 in CHCl3); 1H NMR (300 MHz, CDCl3):
J=11.7, 3.0 Hz, 1H, 3-H), 4.95–5.04 (m, 1H, COOCH
ACHTRE(UGN CH3)2), 5.30 ppm
(dd, J=3.0, 0.9 Hz, 1H, 4-H); 13C NMR (75 MHz, CDCl3): d=20.5, 20.6
d=1.21–1.28 (m, 6H, COOCHACHTREU(GN CH3)2), 1.96, 2.04, 2.05, 2.06, 2.12, 2.15
Chem. Eur. J. 2007, 13, 10152 – 10167
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10163

T. Linker et al.
(6 s, 3H each, OAc), 2.23 (dddd, J=10.8, 8.7, 6.0, 4.8 Hz, 1H, 2-H), 2.32
(dd, J=16.5, 6.0 Hz, 1H, 13-H), 2.37 (dd, J=16.5, 4.8 Hz, 1H, 13’-H),
3.36 (ddd, J=11.4, 6.6, 2.1 Hz, 1H, 5-H), 3.46 (s, 3H, OMe), 3.57 (ddd,
J=9.6, 4.8, 1.8 Hz, 1H, 11-H), 3.69 (dd, J=9.6, 9.0 Hz, 1H, 4-H), 3.84–
3.90 (m, 1H, 12-H), 4.08–4.18 (m, 3H, 6-H, 12’-H), 4.38 (d, J=8.7 Hz,
1H, 1-H), 4.95 (dd, J=7.8, 3.5 Hz, 1H, 8-H), 5.00–5.10 (m, 1H, COOCH-
ACHTREUNG(CH3)2), 5.17 (dd, J=10.8, 3.5 Hz, 1H, 10-H), 5.35 (d, J=7.8 Hz, 1H, 7-
H), 5.42 (dd, J=10.8, 3.5 Hz, 1H, 3-H), 5.48 ppm (dd, J=3.0, 0.9 Hz, 1H,
9-H); 13C NMR (75 MHz, CDCl3): d=20.5, 20.6, 20.8, 20.9 (6q, OAc),
5.0 Hz, 1H, 6’-H), 3.18 (dd, J=10.0, 5.0 Hz, 1H, 5-H), 3.36 (s, 3H, OMe),
3.39 (dd, J=10.5, 8.0 Hz, 1H, 5’-H), 3.49 (s, 3H, COOMe), 3.56 (ddd, J=
13.0, 8.0, 5.0 Hz, 1H, 4-H), 3.95 (dd, J=11.5, 5.0 Hz, 1H, 3-H), 4.18 (d,
J=8.5 Hz, 1H, 1-H), 4.54 (d, J=11.5 Hz, 1H, CH2-Ph), 4.55 (d, J=
11.5 Hz, 1H, CH2-Ph), 4.60 (d, J=11.5 Hz, 1H, CH2-Ph), 4.86 (d, J=
11.5 Hz, 1H, CH2-Ph), 7.20–7.28 ppm (m, 10H, arom. H); 13C NMR
(125 MHz, CDCl3): d=32.3 (t, C-6), 43.8 (d, C-2), 51.4 (q, COOMe), 56.7
(q, OMe), 63.4 (t, C-5), 72.7, 74.5 (2t, CH2-Ph), 79.5, 80.3 (2d, C-3, C-4),
103.9 (d, C-1), 127.6, 127.8, 128.0, 128.3, 128.5 (10d, arom, C-H), 138.1,
138.4 (2s, arom. C-CH2O), 172.7 ppm (s, COOMe); IR (film): n˜ =3030,
2951, 1733, 1454, 1202 cmꢀ1; elemental analysis calcd (%) for C23H28O6
(400.47): C 68.98, H 7.05; found: C 68.80, H 6.97.
21.7 (2q, COOCH
ACHTREUNG
60.4, 60.8 (2t, C-6, C-12), 62.3 (d, COOCHAHCTREUNG
71.1, 72.7 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11), 101.0, 103.4 (2d, C-1,
C-7), 169.0, 170.0, 170.1, 170.3, 170.4, 170.9 ppm (7s, OAc, COOCH-
Methyl3,4-di- O-benzyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-?-d-ara-
binopyranoside (arabino-14): Flash chromatography (cyclohexane/ethyl
acetate 8:1!6:1) gave the methyl ester arabino-14 as a colorless syrup
(332 mg, 83%); Rf =0.42 (cyclohexane/ethyl acetate 3:1); [a]2D0 =ꢀ2.0
ACHTREUNG
(CH3)2); IR (film): n˜ =2983, 2940, 1744, 1372, 1232, 1048 cmꢀ1; elemental
analysis calcd (%) for C30H44O18 (692.66): C 52.02, H 6.40; found: C
52.02, H 6.46.
1
Decarboxylation of the benzyl-protected 2-C-malonyl carbohydrates 12
under microwave irradiation (method F): A solution of the 2-C-malonyl
carbohydrate 12 (1.0 mmol) and lithium iodide (200 mg, 1.5 mmol) in
DMSO (6 mL) was heated to 1008C with a microwave oven (power:
200 W; pressure: 10 bar) and kept stirred for 10–18 minutes. DMSO was
removed at 0.01 mbar and the crude product was purified by flash chro-
matography (cyclohexane/ethyl acetate) to afford the glyco-acetic esters
14 in analytically pure form.
(c=1.04 in CHCl3); H NMR (500 MHz, CDCl3): d=2.49 (dddd, J=13.0,
8.0, 6.5, 4.0 Hz, 1H, 2-H), 2.42–2.55 (m, 2H, 6-H, 6’-H), 3.18 (dd, J=12.5,
3.0 Hz, 1H, 5-H), 3.39 (s, 3H, OMe), 3.45 (ddd, J=4.0, 3.0, 2.5 Hz, 1H,
4-H), 3.51 (s, 3H, COOMe), 3.60 (dd, J=12.5, 4.0 Hz, 1H, 5’-H), 4.09
(dd, J=13.0, 2.5 Hz, 1H, 3-H), 4.18 (d, J=8.0 Hz, 1H, 1-H), 4.24 (d, J=
11.5 Hz, 1H, CH2-Ph), 4.47 (d, J=11.5 Hz, 1H, CH2-Ph), 4.56 (d, J=
12.5 Hz, 1H, CH2-Ph), 4.69 (d, J=12.5 Hz, 1H, CH2-Ph), 7.18–7.33 ppm
(m, 10H, arom. H); 13C NMR (125 MHz, CDCl3): d=31.5 (t, C-6), 40.0
(d, C-2), 51.3 (q, COOMe), 56.7 (q, OMe), 63.2 (t, C-5), 70.8, 70.9 (2t,
CH2-Ph), 69.7, 78.0 (2d, C-3, C-4), 104.0 (d, C-1), 127.6, 127.7, 127.9,
128.3 (10d, arom, C-H), 137.8, 138.3 (2s, arom. C-CH2O), 173.0 ppm (s,
COOMe); IR (film): n˜ =2950, 1735, 1497, 1203 cmꢀ1; elemental analysis
calcd (%) for C23H28O6 (400.47): C 68.98, H 7.05; found: C 68.91, H 7.07.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-b-d-
glucopyranoside (gluco-14): Flash chromatography (cyclohexane/ethyl
acetate 10:1!8:1) gave the methyl ester gluco-14 as a colorless syrup
(480 mg, 92%); Rf =0.42 (cyclohexane/ethyl acetate 4:1); [a]2D0 =+14.2
1
(c=0.97 in CHCl3); H NMR (300 MHz, CDCl3): d=2.09 (dddd, J=10.8,
8.7, 5.7, 5.4 Hz, 1H, 2-H), 2.39 (dd, J=15.3, 5.7 Hz, 1H, 7-H), 2.47 (dd,
J=15.3, 5.4 Hz, 1H, 7’-H), 3.41 (s, 3H, OMe), 3.43 (ddd, J=9.3, 5.4,
3.9 Hz, 1H, 5-H), 3.45 (dd, J=10.8, 2.1 Hz, 1H, 3-H), 3.49 (s, 3H,
COOMe), 3.56 (dd, J=9.3, 2.1 Hz, 1H, 4-H), 3.67–3.70 (m, 2H, 6-H, 6’-
H), 4.22 (d, J=8.7 Hz, 1H, 1-H), 4.50 (d, J=12.3 Hz, 1H, CH2-Ph), 4.51
(d, J=11.1 Hz, 1H, CH2-Ph), 4.54 (d, J=11.7 Hz, 1H, CH2-Ph), 4.59 (d,
J=12.0 Hz, 1H, CH2-Ph), 4.71 (d, J=10.8 Hz, 1H, CH2-Ph), 4.84 (d, J=
11.1 Hz, 1H, CH2-Ph), 7.09–7.30 ppm (m, 15H, arom. H); 13C NMR
(75 MHz, CDCl3): d=31.9 (t, C-7), 44.8 (d, C-2), 51.4 (q, COOMe), 56.9
(q, OMe), 69.0 (t, C-6), 73.5, 74.7, 74.8 (3t, CH2-Ph), 75.2, 79.9, 82.1 (3d,
C-3, C-4, C-5), 103.4 (d, C-1), 127.6, 127.7, 127.8, 128.3, 128.4 (15d, arom,
C-H), 138.0, 138.2, 138.3 (3s, arom. C-CH2O), 172.6 ppm (s, COOMe);
IR (film): n˜ =3030, 2949, 1736, 1452, 1260 cmꢀ1; elemental analysis calcd
(%) for C31H36O7 (520.62): C 71.52, H 6.97; found: C 71.45, H 7.06.
Methyl3,6,8,9,10,12-hexa-
O-benzyl-2-deoxy-2-C-[(methoxycarbonyl)-
methyl]-b-d-maltopyranoside (malto-14): Flash chromatography (cyclo-
hexane/ethyl acetate 10:1!8:1) gave the methyl ester malto-14 as a col-
orless syrup (770 mg, 81%); Rf =0.38 (cyclohexane/ethyl acetate 4:1);
[a]2D0 =+4.0 (c=0.96 in CHCl3); 1H NMR (500 MHz, CDCl3): d=2.26
(dddd, J=12.5, 8.5, 6.5, 4.5 Hz, 1H, 2-H), 2.32 (d, J=15.5, 6.5 Hz, 1H,
13-H), 2.52 (d, J=15.5, 4.5 Hz, 1H, 13’-H), 3.38 (dd, J=6.5, 3.0 Hz, 2H,
12-H, 12’-H), 3.39 (s, 3H, OMe), 3.42 (ddd, J=6.5, 3.0, 2.5 Hz, 1H, 5-H),
3.52 (dd, J=10.0, 3.0 Hz, 1H, 11-H), 3.49 (1 s, 3H, COOMe), 3.56 (dd,
J=11.0, 2.5 Hz, 1H, 6-H), 3.63 (dd, J=10.5, 6.5 Hz, 1H, 4-H), 3.61–3.66
(m, 1H, 8-H), 3.70 (dd, J=11.0, 3.0 Hz, 1H, 6’-H), 3.76 (dd, J=10.5,
8.0 Hz, 1H, 10-H), 3.83 (dd, J=12.5, 6.5 Hz, 1H, 3-H), 4.01 (t, J=8.5 Hz,
1H, 9-H), 4.22 (d, J=8.5 Hz, 1H, 1-H), 4.29 (d, J=12.0 Hz, 1H, CH2-
Ph), 4.39 (d, J=11.0 Hz, 1H, CH2-Ph), 4.46 (d, J=12.0 Hz, 1H, CH2-Ph),
4.48 (d, J=4.5 Hz, 5H, CH2-Ph), 4.69 (d, J=10.5 Hz, 1H, CH2-Ph), 4.73
(d, J=11.0 Hz, 1H, CH2-Ph), 4.80 (d, J=10.5 Hz, 1H, CH2-Ph), 4.88 (d,
J=11.0 Hz, 1H, CH2-Ph), 5.33 (d, J=3.5, 1H, 7-H), 7.05–7.26 ppm (m,
30H, arom. H); 13C NMR (125 MHz, CDCl3): d=32.0 (t, C-13), 43.2 (d,
C-2), 51.4 (q, COOMe), 56.7 (q, OMe), 68.5, 69.5 (2t, C-6, C-12), 71.1,
73.1, 73.3, 73.4, 75.0, 75.5 (6t, CH2-Ph), 71.1, 74.4, 75.2, 77.7, 79.6, 81.7,
81.9 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11), 96.9, 103.4 (2d, C-1, C-7),
127.3, 127.4, 127.5, 127.6, 127.8, 128.0, 128.2, 128.3 (30d, arom, C-H),
138.0, 138.3, 138.4, 138.5, 138.7 (6 s, arom. C-CH2O), 172.6 ppm (s,
COOMe); IR (film): n˜ =3029, 2863, 1734, 1496, 1053 cmꢀ1; elemental
analysis calcd (%) for C58H64O12 (953.13): C 73.09, H 6.77; found: C
73.37, H 6.79.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-b-d-
galactopyranoside (galacto-14): Flash chromatography (cyclohexane/
ethyl acetate 10:1!8:1) gave the methyl ester galacto-14 as a colorless
syrup (440 mg, 85%); Rf =0.44 (cyclohexane/ethyl acetate 4:1); [a]D20
=
+47.5 (c=0.95 in CHCl3); 1H NMR (300 MHz, CDCl3): d=2.55 (dddd,
J=11.1, 8.4, 6.3, 4.8 Hz, 1H, 2-H), 2.44–2.66 (m, 2H, 7-H, 7’-H), 3.44 (s,
3H, OMe), 3.47 (dd, J=11.1, 6.9 Hz, 1H, 6-H), 3.55 (s, 3H, COOMe),
3.56 (dd, J=11.1, 5.4 Hz, 1H, 6’-H), 3.63 (dd, J=11.1, 3.3 Hz, 1H, 3-H),
3.66 (ddd, J=6.9, 5.4, 0.6 Hz, 1H, 5-H), 3.93 (d, J=2.4 Hz, 1H, 4-H),
4.27 (d, J=8.4 Hz, 1H, 1-H), 4.39 (d, J=11.4 Hz, 1H, CH2-Ph), 4.47 (d,
J=3.9 Hz, 2H, CH2-Ph), 4.58 (d, J=11.7 Hz, 1H, CH2-Ph), 4.68 (d, J=
11.4 Hz, 1H, CH2-Ph), 4.88 (d, J=11.7 Hz, 1H, CH2-Ph), 7.23–7.37 ppm
(m, 15H, arom. H); 13C NMR (75 MHz, CDCl3): d=31.5 (t, C-7), 39.9 (d,
C-2), 51.2 (q, COOMe), 56.8 (q, OMe), 69.1 (t, C-6), 70.6, 73.5, 73.6 (3t,
CH2-Ph), 71.5, 74.2, 80.3 (3d, C-3, C-4, C-5), 103.8 (d, C-1), 127.4, 127.8,
127.9, 128.0, 128.1, 128.4 (15d, arom, C-H), 137.7, 138.0, 138.7 (3s, arom.
C-CH2O), 173.0 ppm (s, COOMe); IR (film): n˜ =3030, 2919, 1735, 1453,
1259 cmꢀ1; elemental analysis calcd (%) for C31H36O7 (520.62): C 71.52,
H 6.97; found: C 71.58, H 7.01.
Methyl3,6,8,9,10,12-hexa-
O-benzyl-2-deoxy-2-C-[(methoxycarbonyl)-
methyl]-b-d-lactopyranoside (lacto-14): Flash chromatography (cyclohex-
ane/ethyl acetate 10:1!8:1) gave the methyl ester lacto-14 as a colorless
syrup (750 mg, 79%); Rf =0.39 (cyclohexane/ethyl acetate 4:1); [a]D20
=
+32.6 (c=1.01 in CHCl3); 1H NMR (500 MHz, CDCl3): d=2.04 (dddd,
J=12.5, 8.5, 6.0, 4.5 Hz, 1H, 2-H), 2.45 (d, J=15.5, 6.0 Hz, 1H, 13-H),
2.54 (d, J=15.5, 4.5 Hz, 1H, 13’-H), 3.25–3.29 (m, 1H, 11-H), 3.27 (ddd,
J=8.5, 4.5, 1.5 1H, 5-H), 3.32 (dd, J=9.5, 2.5 Hz, 2H, 12-H, 12’-H), 3.39
(s, 3H, OMe), 3.40 (dd, J=11.0, 8.5 Hz, 1H, 6-H), 3.49 (s, 3H, COOMe),
3.64 (dd, J=8.5, 6.5 Hz, 1H, 4-H), 3.69 (dd, J=9.5, 8.0 Hz, 1H, 8-H),
3.79 (dd, J=10.5, 4.0 Hz, 1H, 10-H), 3.83 (d, J=2.5 Hz, 1H, 6’-H), 3.94
(dd, J=12.5, 6.5 Hz, 1H, 3-H), 3.91 (t, J=9.0 Hz, 1H, 7-H), 4.15 (d, J=
11.5 Hz, 1H, CH2-Ph), 4.25 (d, J=12.0 Hz, 1H, CH2-Ph), 4.26 (d, J=
Methyl3,4-di- O-benzyl-2-deoxy-2-C-[(methoxycarbonyl)methyl]-b-d-xy-
lopyranoside (xylo-14): Flash chromatography (cyclohexane/ethyl acetate
8:1!6:1) gave the methyl ester xylo-14 as a colorless syrup (330 mg,
83%); Rf =0.40 (cyclohexane/ethyl acetate 3:1); [a]2D0 =ꢀ7.7 (c=0.98 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=2.01 (dddd, J=11.5, 8.5, 6.0,
5.0 Hz, 1H, 2-H), 2.40 (dd, J=15.5, 6.0 Hz, 1H, 6-H), 2.46 (dd, J=15.5,
10164
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Chem. Eur. J. 2007, 13, 10152 – 10167

Malonyl Carbohydrates
FULL PAPER
8.5 Hz, 1H, 1-H), 4.32 (d, J=12.0 Hz, 1H, CH2-Ph), 4.35 (d, J=3.5, 1H,
9-H), 4.39 (d, J=10.5 Hz, 1H, CH2-Ph), 4.45 (d, J=11.5 Hz, 1H, CH2-
Ph), 4.51 (d, J=12.0 Hz, 1H, CH2-Ph), 4.63 (d, J=1.5 Hz, 2H, CH2-Ph),
4.74 (d, J=4.5 Hz, 2H, CH2-Ph), 4.88 (d, J=11.5 Hz, 1H, CH2-Ph), 5.07
(d, J=10.5 Hz, 1H, CH2-Ph), 7.05–7.28 ppm (m, 30H, arom. H);
13C NMR (125 MHz, CDCl3): d=31.8 (t, C-13), 44.5 (d, C-2), 51.3 (q,
COOMe), 56.8 (q, OMe), 68.1, 68.3 (2t, C-6, C-12), 72.7, 73.1, 73.4, 74.4,
74.6, 75.3 (6t, CH2-Ph), 73.0, 73.8, 75.5, 77.5, 80.0, 80.1, 82.4 (7d, C-3, C-
4, C-5, C-8, C-9, C-10, C-11), 102.8, 103.4 (2d, C-1, C-7), 127.1, 127.2,
127.4, 127.5, 127.6, 127.8, 127.9, 128.1, 128.2, 128.3 (30d, arom, C-H),
138.1, 138.5, 138.6, 138.8, 138.9, 139.1 (6s, arom. C-CH2O), 172.8 ppm (s,
COOMe); IR (film): n˜ =3029, 2863, 1734, 1496, 1054 cmꢀ1; elemental
analysis calcd (%) for C58H64O12 (953.13): C 73.09, H 6.77; found: C
73.32, H 6.70.
Saponification of the benzyl-protected methyl esters 12 and 14: A solu-
tion of the benzyl-protected methyl ester 12 or 14 (1.0 mmol) and
LiOH·H2O (420 mg, 10.0 mmol) in MeOH/H2O 4:1 (10 mL) was heated
under reflux until TLC showed complete conversion of the starting mate-
rial. After cooling to room temperature, the pH value was adjusted to 3–
4 with Amberlite IR-120, and the solvent was removed under high
vacuum.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[malonic acid]-b-d-glucopyrano-
side (gluco-16): The malonic acid gluco-16 was isolated quantitatively
without chromatography as a light yellow syrup; [a]2D0 =ꢀ7.0 (c=0.92 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=2.43 (ddd, J=11.5, 9.0, 3.5 Hz,
1H, 2-H), 3.36 (s, 3H, OMe), 3.41 (ddd, J=11.5, 4.0, 3.0 Hz, 1H, 5-H),
3.59 (t, J=9.5 Hz, 1H, 3-H), 3.65 (d, J=3.5 Hz, 1H, 7-H), 3.68 (d, J=
2.5 Hz, 2H, 6-H, 6’-H), 3.87 (dd, J=11.5, 9.0 Hz, 1H, 4-H), 4.44 (d, J=
11.0 Hz, 1H, CH2-Ph), 4.45 (d, J=11.0 Hz, 1H, CH2-Ph), 4.46 (d, J=
9.0 Hz, 1H, 1-H), 4.54 (d, J=12.0 Hz, 1H, CH2-Ph), 4.62 (d, J=12.0 Hz,
1H, CH2-Ph), 4.69 (d, J=11.0 Hz, 1H, CH2-Ph), 4.86 (d, J=11.0 Hz, 1H,
CH2-Ph), 7.04–7.27 ppm (m, 15H, arom. H); 13C NMR (125 MHz,
CDCl3): d=45.2, 48.5 (2d, C-2, C-7), 57.2 (q, OMe), 68.4 (t, C-6), 73.4,
74.7, 75.0 (3t, CH2-Ph), 74.5, 79.9, 80.0 (3d, C-3, C-4, C-5), 101.9 (d, C-1),
127.6, 127.7, 127.8, 128.1, 128.4 (15d, arom, C-H), 137.3, 137.7, 137.9 (3s,
arom. C-CH2O), 171.7, 174.0 ppm (2s, COOH); IR (film): n˜ =3416, 2930,
Saponification of the acetyl-protected methyl esters 8a and 13a: A solu-
tion of the acetyl-protected methyl ester 8a or 13a (1.0 mmol) and
LiOH·H2O (420 mg, 10.0 mmol) in MeOH/H2O (1:4, 10 mL) was stirred
overnight at room temperature. Then the pH value was adjusted to 3–4
with amberlite IR-120. Finally the polar product was isolated after freeze
drying.
Methyl2-deoxy-2- C-[malonic acid]-b-d-glucopyranoside (gluco-15):
Freeze drying afforded the malonic acid gluco-15 quantitatively as a light
yellow syrup; [a]2D0 =ꢀ22.6 (c=1.03 in D2O); 1H NMR (300 MHz, D2O):
d=2.22 (ddd, J=11.1, 9.0, 4.2 Hz, 1H, 2-H), 3.23 (dd, J=9.6, 9.0 Hz, 1H,
4-H), 3.29 (ddd, J=9.6, 5.4, 2.1 Hz, 1H, 5-H), 3.32 (dd, J=11.1, 9.0 Hz,
1H, 3-H), 3.38 (s, 3H, OMe), 3.60 (dd, J=12.3, 5.4 Hz, 1H, 6-H), 3.65 (d,
J=4.2 Hz, 1H, 7-H), 3.84 (dd, J=12.3, 2.1 Hz, 1H, 6’-H), 4.57 ppm (d,
J=9.0 Hz, 1H, 1-H); 13C NMR (75 MHz, D2O): d=49.2 (2d, C-2, C-7),
57.7 (q, OMe), 61.4 (t, C-6), 71.6, 73.1, 76.2 (3d, C-3, C-4, C-5), 102.9 (d,
C-1), 174.8, 175.6 ppm (2s, COOH); IR (film): n˜ =3358, 2935, 1705, 1389,
1713, 1453, 1209 cmꢀ1
; elemental analysis calcd (%) for C31H34O9
(550.60): C 67.62, H 6.22; found: C 67.35, H 6.26.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[malonic acid]-b-d-galactopyrano-
side (galacto-16): The malonic acid galacto-16 was isolated quantitatively
without chromatography as a light yellow syrup; [a]2D0 =+6.7 (c=1.00 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=3.00 (ddd, J=12.5, 9.0, 4.5 Hz,
1H, 2-H), 3.19 (ddd, J=11.5, 4.0, 2.5 Hz, 1H, 5-H), 3.35 (s, 3H, OMe),
3.52 (dd, J=12.5, 6.5 Hz, 1H, 3-H), 3.56 (dd, J=11.5, 6.5 Hz, 1H, 4-H),
3.77–3.87 (m, 2H, 6-H, 6’-H), 4.30 (d, J=11.5 Hz, 1H, CH2-Ph), 4.40 (d,
J=9.0 Hz, 1H, 1-H), 4.42 (d, J=4.5 Hz, 1H, 7-H), 4.46 (d, J=11.0 Hz,
1H, CH2-Ph), 4.53 (d, J=11.0 Hz, 1H, CH2-Ph), 4.59 (d, J=11.0 Hz, 1H,
CH2-Ph), 4.62 (d, J=11.5 Hz, 1H, CH2-Ph), 4.75 (d, J=11.0 Hz, 1H,
CH2-Ph), 7.12–7.32 ppm (m, 15H, arom. H); 13C NMR (125 MHz,
CDCl3): d=43.9, 45.8 (2d, C-2, C-7), 57.0 (q, OMe), 68.7 (t, C-6), 72.0,
73.3, 74.3 (3t, CH2-Ph), 71.4, 73.2, 78.9 (3d, C-3, C-4, C-5), 102.5 (d, C-1),
127.6, 127.7, 127.8, 127.9, 128.0 128.1, 128.3, 128.6 (15d, arom, C-H),
137.3, 137.6, 138.1 (3s, arom. C-CH2O), 173.7, 175.1 ppm (2s, COOH);
IR (film): n˜ =2870, 1713, 1454, 1207 cmꢀ1; elemental analysis calcd (%)
for C31H34O9 (550.60): C 67.62, H 6.22; found: C 67.35, H 6.30.
1218 cmꢀ1
; HR-MS(ES): m/z: calcd for C10H16O9Li: 287.0954; found
287.0974 [M+Li]+.
Methyl2-deoxy-2- C-[malonic acid]-b-d-galactopyranoside (galacto-15):
Freeze drying afforded the malonic acid galacto-15 quantitatively as a
light yellow syrup; [a]D20 =ꢀ10.3 (c=0.82 in D2O); 1H NMR (500 MHz,
D2O): d=2.35 (ddd, J=11.5, 9.0, 3.5 Hz, 1H, 2-H), 3.34 (s, 3H, OMe),
3.46 (ddd, J=7.5, 4.5, 2.0 Hz, 1H, 5-H), 3.59 (dd, J=11.5, 7.5 Hz, 1H, 6-
H), 3.62 (dd, J=3.0, 2.0 Hz, 1H, 4-H), 3.65 (dd, J=11.5, 4.5 Hz, 1H, 6’-
H), 3.69 (d, J=3.5 Hz, 1H, 7-H), 3.80 (dd, J=11.5, 3.0 Hz, 1H, 3-H),
4.37 ppm (d, J=9.0 Hz, 1H, 1-H); 13C NMR (125 MHz, D2O): d=45.4,
45.5 (2d, C-2, C-7), 57.7 (q, OMe), 61.7 (t, C-6), 68.3, 70.2, 75.4 (3d, C-3,
C-4, C-5), 103.5 (d, C-1), 176.7, 177.5 ppm (2s, COOH); IR (film): n˜ =
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[acetic acid]-b-d-glucopyranoside
(gluco-18): Flash chromatography (cyclohexane/ethyl acetate 3:1!2:1)
gave the acetic acid gluco-18 quantitatively as a colorless syrup; Rf =0.40
(cyclohexane/ethyl acetate 1:1); [a]2D0 =+1.4 (c=1.07 in CHCl3);
1H NMR (300 MHz, CDCl3): d=2.16 (ddt, J=10.8, 8.7, 5.4 Hz, 1H, 2-H),
2.48 (dd, J=15.6, 5.4 Hz, 1H, 7-H), 2.55 (dd, J=15.6, 5.4 Hz, 1H, 7’-H),
3.48 (s, 3H, OMe), 3.50 (ddd, J=9.3, 5.4, 3.9 Hz, 1H, 5-H), 3.56 (dd, J=
10.8, 9.0 Hz, 1H, 3-H), 3.64 (dd, J=9.3, 9.0 Hz, 1H, 4-H), 3.76 (d, J=
2.4 Hz, 2H, 6-H), 4.30 (d, J=8.7 Hz, 1H, 1-H), 4.56 (d, J=12.3 Hz, 1H,
CH2-Ph), 4.58 (d, J=10.8 Hz, 1H, CH2-Ph), 4.64 (d, J=11.1 Hz, 1H,
CH2-Ph), 4.65 (d, J=12.3 Hz, 1H, CH2-Ph), 4.77 (d, J=10.5 Hz, 1H,
CH2-Ph), 4.91 (d, J=11.1 Hz, 1H, CH2-Ph), 7.16–7.37 ppm (m, 15H,
arom. H); 13C NMR (75 MHz, CDCl3): d=31.6 (t, C-7), 44.5 (d, C-2),
56.9 (q, OMe), 68.8 (t, C-6), 73.4, 74.7, 75.0 (3t, CH2-Ph), 74.6, 79.7, 81.6
(3d, C-3, C-4, C-5), 103.2 (d, C-1), 127.5, 127.7, 127.8, 128.3, 128.4 (15d,
arom, C-H), 137.9, 138.0 (3s, arom. C-CH2O), 178.3 ppm (s, COOH); IR
(film): n˜ =3027, 2947, 1735, 1462, 1263 cmꢀ1; elemental analysis calcd
(%) for C30H34O7 (506.59): C 71.13, H 6.76; found: C 71.32, H 6.89.
3370, 2941, 1699, 1386, 1237 cmꢀ1
; HR-MS(ES): m/z: calcd for
C10H16O9Na: 303.0692; found 303.0721 [M+Na]+.
Methyl2-deoxy-2- C-[acetic acid]-b-d-glucopyranoside (gluco-17): Freeze
drying afforded the acetic acid gluco-17 quantitatively as a light yellow
1
syrup; [a]2D0 =ꢀ23.1 (c=0.88 in D2O); H NMR (300 MHz, D2O): d=2.09
(dd, J=14.7, 7.2 Hz, 1H, 7-H), 2.37 (dd, J=14.7, 4.8 Hz, 1H, 7’-H), 3.22
(dddd, J=11.1, 8.7, 7.2, 4.8 Hz, 1H, 2-H), 3.24 (dd, J=9.6, 9.0 Hz, 1H, 4-
H), 3.25 (dd, J=11.1, 9.0 Hz, 1H, 3-H), 3.27 (ddd, J=9.6, 5.7, 1.8 Hz,
1H, 5-H), 3.35 (s, 3H, OMe), 3.59 (dd, J=12.3, 5.7 Hz, 1H, 6-H), 3.79
(dd, J=12.3, 1.8 Hz, 1H, 6’-H), 4.24 ppm (d, J=8.7 Hz, 1H, 1-H);
13C NMR (75 MHz, D2O): d=36.2 (t, C-7), 46.0 (d, C-2), 57.6 (q, OMe),
61.5 (t, C-6), 71.3, 75.1, 76.1 (3d, C-3, C-4, C-5), 105.0 (d, C-1), 181.6 ppm
(s, COOH); IR (film): n˜ =3226, 1561, 1409, 1074 cmꢀ1; HR-MS(ES): m/z:
calcd for C9H16O7Na: 259.0794; found 2596.0807 [M+Na]+.
Methyl2-deoxy-2- C-[acetic acid]-b-d-galactopyranoside (galacto-17):
Freeze drying afforded the acetic acid galacto-17 quantitatively as a light
yellow syrup; [a]2D0 =ꢀ9.0 (c=0.98 in D2O); 1H NMR (300 MHz, D2O):
d=2.08 (dddd, J=11.2, 8.7, 7.8, 4.5 Hz, 1H, 2-H), 2.27 (dd, J=15.3,
7.8 Hz, 1H, 7-H), 2.56 (dd, J=15.3, 4.5 Hz, 1H, 7’-H), 3.41 (s, 3H, OMe),
3.50 (dd, J=11.2, 3.3 Hz, 1H, 3-H), 3.55 (ddd, J=6.9, 5.4, 1.5 Hz, 1H, 5-
H), 3.66 (dd, J=11.7, 5.4 Hz, 1H, 6-H), 3.73 (dd, J=11.7, 6.9 Hz, 1H, 6’-
H), 3.69 (dd, J=3.3, 1.5 Hz, 1H, 4-H), 4.24 ppm (d, J=8.7 Hz, 1H, 1-H);
13C NMR (75 MHz, D2O): d=33.2 (t, C-7), 41.2 (d, C-2), 57.6 (q, OMe),
61.7 (t, C-6), 68.0, 71.9, 75.5 (3d, C-3, C-4, C-5), 105.0 (d, C-1), 178.2 ppm
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[acetic acid]-b-d-galactopyrano-
side (galacto-18): Flash chromatography (cyclohexane/ethyl acetate
3:1!2:1) gave the acetic acid galacto-18 quantitatively as a colorless
syrup; Rf =0.42 (cyclohexane/ethyl acetate 1:1); [a]2D0 =+48.3 (c=1.02 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=2.30 (dd, J=16.0, 5.0 Hz, 1H,
7-H), 2.59 (dd, J=16.0, 3.0 Hz, 1H, 7’-H), 2.78 (dddd, J=12.0, 8.5, 5.0,
3.0 Hz, 1H, 2-H), 3.22 (s, 3H, OMe), 3.54–3.57 (m, 1H, 5-H), 3.56 (dd,
J=9.0, 5.5 Hz, 2H, 6-H, 6’-H), 3.81 (t, J=6.5 Hz, 1H, 3-H), 3.88 (s, 1H,
4-H), 4.36 (d, J=12.0 Hz, 1H, CH2-Ph), 4.45 (d, J=8.5 Hz, 1H, 1-H),
(s, COOH); IR (film): n˜ =3367, 2939, 1704, 1387, 1228 cmꢀ1
MS(ES): m/z: calcd for C9H16O7Na: 259.0794; found 259.0793 [M+Na]+.
; HR-
Chem. Eur. J. 2007, 13, 10152 – 10167
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10165

T. Linker et al.
4.47 (d, J=11.5 Hz, 1H, CH2-Ph), 4.61 (d, J=12.0 Hz, 1H, CH2-Ph), 4.75
(d, J=3.5 Hz, 2H, CH2-Ph), 4.79 (d, J=11.5 Hz, 1H, CH2-Ph), 7.14–
7.28 ppm (m, 15H, arom. H); 13C NMR (125 MHz, CDCl3): d=32.3 (t,
C-7), 37.3 (d, C-2), 55.2 (q, OMe), 69.4 (t, C-6), 71.4, 73.5, 74.4 (3t, CH2-
Ph), 69.5, 71.8, 78.1 (3d, C-3, C-4, C-5), 100.1 (d, C-1), 127.5, 127.7, 127.8,
128.0, 128.2, 128.4 (15d, arom, C-H), 137.7, 138.0, 138.7 (3s, arom. C-
CH2O), 178.4 ppm (s, COOH); IR (film): n˜ =3030, 2913, 1706, 1454,
1077 cmꢀ1; elemental analysis calcd (%) for C30H34O7 (506.59): C 71.13,
H 6.76; found: C 71.27, H 6.86.
(m, 15H, arom. H); 13C NMR (125 MHz, CDCl3): d=30.7 (t, C-7), 45.9
(d, C-2), 56.7 (q, OMe), 61.8 (t, C-8), 69.0 (t, C-6), 73.5, 74.6, 75.0 (3t,
CH2-Ph), 75.2, 79.7, 83.2 (3d, C-3, C-4, C-5), 104.7 (d, C-1), 127.6, 127.8,
127.9, 128.3, 128.4 (15d, arom, C-H), 138.0, 138.2 ppm (3s, arom. C-
CH2O); IR (film): n˜ =3088, 2893, 2360, 1496, 1361, 1054 cmꢀ1; elemental
analysis calcd (%) for C30H36O6 (492.61): C 73.15, H 7.37; found: C 73.15,
H 7.33.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[ethanol]-b-d-galactopyranoside
(galacto-20): Flash chromatography (cyclohexane/ethyl acetate 3:1!2:1)
gave the alcohol galacto-20 as a white solid (400 mg, 81%); Rf =0.40 (cy-
clohexane/ethyl acetate 1:1); m.p. 67–698C; [a]2D0 =ꢀ20.9 (c=0.68 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=1.61 (dddd, J=11.5, 9.0, 6.0,
3.0 Hz, 1H, 2-H), 1.80–1.87 (m, 1H, 7-H), 2.14–2.22 (m, 1H, 7’-H), 2.71
(t, J=5.5 Hz, 1H, 8-H), 3.22 (dd, J=11.5, 2.5 Hz, 1H, 8’-H), 3.49 (s, 3H,
OMe), 3.53 (dt, J=5.5, 0.5 Hz, 1H, 5-H), 3.63 (dd, J=9.0, 5.5 Hz, 1H, 4-
H), 3.67 (dd, J=9.5, 7.5 Hz, 2H, 6-H, 6’-H), 3.93 (d, J=2.0 Hz, 1H, 3-H),
4.09 (d, J=9.0 Hz, 1H, 1-H), 4.42 (d, J=11.5 Hz, 1H, CH2-Ph), 4.45 (d,
J=11.5 Hz, 1H, CH2-Ph), 4.49 (d, J=11.5 Hz, 1H, CH2-Ph), 4.60 (d, J=
11.5 Hz, 1H, CH2-Ph), 4.73 (d, J=11.5 Hz, 1H, CH2-Ph), 4.86 (d, J=
11.5 Hz, 1H, CH2-Ph), 7.22–7.37 ppm (m, 15H, arom. H); 13C NMR
(125 MHz, CDCl3): d=30.7 (t, C-7), 41.2 (d, C-2), 56.7 (q, OMe), 62.2 (t,
C-8), 69.1 (t, C-6), 70.2, 73.6, 74.3 (3t, CH2-Ph), 71.5, 77.2, 81.7 (3d, C-3,
C-4, C-5), 105.1 (d, C-1), 127.5, 127.8, 127.9, 128.0, 128.1, 128.2, 128.4,
128.5 (15d, arom, C-H), 137.3, 137.9, 138.6 ppm (3s, arom. C-CH2O); IR
(film): n˜ =3088, 2894, 1496, 1361, 1053 cmꢀ1; elemental analysis calcd
(%) for C30H36O6 (492.61): C 73.15, H 7.37; found: C 73.25, H 7.46.
Reduction of the C-analogues 12 and 14 with lithium aluminum hydride
(method G): A suspension of the 2-C-analogue 12 or 14 (1.0 mmol) and
lithium aluminium hydride (115 mg, 3 mmol) in 1,4-dioxane (10 mL) was
stirred at reflux for 3–4 h until TLC showed complete conversion of the
starting material. Ethyl acetate (2 mL) and water (12 mL) were added se-
quentially. The mixture was filtered over Celite and was extracted with
dichloromethane (4”10 mL). The combined organic extracts were dried
(Na2SO4) and concentrated, and the alcohols 19 and 20 were isolated in
analytically pure form by column chromatography.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[bis-(methanol)methyl]-b-d-gluco-
pyranoside (gluco-19): Flash chromatography (cyclohexane/ethyl acetate
3:3!2:3) gave the diol gluco-19 as a white solid (445 mg, 85%); Rf =
0.40 (cyclohexane/ethyl acetate 1:3); m.p. 68–708C; [a]2D0 =+0.3 (c=0.94
in CHCl3); 1H NMR (500 MHz, CDCl3): d=1.88 (ddd, J=12.0, 9.0,
5.0 Hz, 1H, 2-H), 2.23 (t, J=5.5 Hz, 1H, 8-H), 2.94 (dd, J=7.0, 4.0 Hz,
1H, 8’-H), 3.47 (ddd, J=10.0, 6.5, 3.0 Hz, 1H, 5-H), 3.53 (s, 3H, OMe),
3.65 (dd, J=9.0, 8.5 Hz, 2H, 9-H, 9’-H), 3.72 (t, J=5.5 Hz, 1H, 3-H), 3.76
(d, J=3.5 Hz, 2H, 6-H, 6’-H), 3.79–3.84 (m, 1H, 4-H), 3.81 (d, J=5.0 Hz,
1H, 7-H), 4.38 (d, J=9.0 Hz, 1H, 1-H), 4.59 (d, J=12.5 Hz, 1H, CH2-
Ph), 4.61 (d, J=11.5 Hz, 1H, CH2-Ph), 4.67 (d, J=12.5 Hz, 1H, CH2-Ph),
4.70 (d, J=11.0 Hz, 1H, CH2-Ph), 4.79 (d, J=11.0 Hz, 1H, CH2-Ph), 4.98
(d, J=11.5 Hz, 1H, CH2-Ph), 7.16–7.39 ppm (m, 15H, arom. H);
13C NMR (125 MHz, CDCl3): d=39.8 (d, C-7), 49.1 (d, C-2), 56.4 (q,
OMe), 62.6, 66.0, 68.9 (3t, C-6, C-8, C-9), 73.5, 74.6 (3t, CH2-Ph), 75.1,
80.2, 80.3 (3d, C-3, C-4, C-5), 102.3 (d, C-1), 127.5, 127.6, 127.7, 127.8,
128.0, 128.3, 128.4, 128.5 (15d, arom, C-H), 138.0, 138.1 ppm (3s, arom.
C-CH2O); IR (film): n˜ =3089, 2864, 1495, 1450, 1070 cmꢀ1; elemental
analysis calcd (%) for C31H38O7 (522.63): C 71.24, H 7.33; found: C 71.44,
H 7.43.
Reduction of the C-analogues 14 with diisobutyl aluminum hydride
(method H): A solution of the 2-C-analogue 14 (1.0 mmol) in dry di-
chloromethane (10 mL) was cooled to ꢀ788C under an argon atmos-
phere. At this temperature DIBAL (1.2 mL, 1.2 mmol) was added to the
solution, which was stirred at low temperature until TLC showed com-
plete conversion of the starting material. 2-Propanol (2 mL) was added
to quench the reaction and water (10 mL) was added sequentially. The
mixture was extracted with dichloromethane (4”10 mL) and the com-
bined organic extracts were dried (Na2SO4) and concentrated. The crude
product was purified by column chromatography to afford the aldehydes
21 in analytically pure form.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-(formylmethyl)-b-d-glucopyrano-
side (gluco-21): Flash chromatography (cyclohexane/ethyl acetate 10:1!
8:1) afforded the aldehyde gluco-21 as a colorless syrup (403 mg, 82%);
Rf =0.40 (cyclohexane/ethyl acetate 4:1); [a]2D0 =+8.6 (c=1.05 in CHCl3);
1H NMR (500 MHz, CDCl3): d=2.21 (dddd, J=10.5, 8.5, 6.0, 2.5 Hz, 1H,
2-H), 2.31 (ddd, J=16.0, 6.0, 2.5 Hz, 1H, 7-H), 2.39 (ddd, J=16.0, 6.0,
2.5 Hz, 1H, 7’-H), 3.31 (dd, J=10.5, 9.0 Hz, 1H, 3-H), 3.38 (s, 3H, OMe),
3.38–3.41 (m, 1H, 6’-H), 3.40 (dt, J=9.5, 3.5 Hz, 1H, 5-H), 3.61 (dd, J=
9.5, 9.0 Hz, 1H, 4-H), 3.69 (d, J=3.5 Hz, 2H, 6-H, 6’-H), 4.08 (d, J=
8.5 Hz, 1H, 1-H), 4.47 (d, J=11.0 Hz, 1H, CH2-Ph), 4.49 (d, J=12.5 Hz,
1H, CH2-Ph), 4.50 (d, J=11.0 Hz, 1H, CH2-Ph), 4.58 (d, J=12.5 Hz, 1H,
CH2-Ph), 4.72 (d, J=10.5 Hz, 1H, CH2-Ph), 4.80 (d, J=11.5 Hz, 1H,
CH2-Ph), 7.09–7.30 (m, 15H, arom. H), 9.47 ppm (t, J=2.5 Hz, 1H,
CHO); 13C NMR (125 MHz, CDCl3): d=42.2 (t, C-7), 43.8 (d, C-2), 56.8
(q, OMe), 68.8 (t, C-6), 73.5, 74.7, 74.9 (3t, CH2-Ph), 75.2, 79.8, 82.3 (3d,
C-3, C-4, C-5), 103.7 (d, C-1), 127.6, 127.7, 127.8, 127.9, 128.0, 128.3,
128.4, 128.5 (15d, arom, C-H), 137.7, 137.9, 138.1 (3s, arom. C-CH2O),
201.0 ppm (s, CHO); IR (film): n˜ =3029, 2863, 1721, 1496, 1050 cmꢀ1; ele-
mental analysis calcd (%) for C30H34O6 (490.59): C 73.45, H 6.99; found:
C 72.98, H 7.04.
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-[bis-(methanol)methyl]-b-d-galac-
topyranoside (galacto-19): Flash chromatography (cyclohexane/ethyl ace-
tate 3:3!2:3) gave the diol galacto-19 as a white solid (435 mg, 83%);
Rf =0.42 (cyclohexane/ethyl acetate 1:3); m.p. 92–958C; [a]2D0 =ꢀ18.9 (c=
0.96 in CHCl3); 1H NMR (300 MHz, CDCl3): d=2.23 (ddd, J=11.7, 9.0,
5.4 Hz, 1H, 2-H), 2.15–2.30 (m, 2H, 8-H, 8’-H), 3.39 (s, 3H, OMe), 3.45
(ddd, J=11.7, 4.5, 2.4 Hz, 1H, 5-H), 3.65 (d, J=5.4 Hz, 1H, 7-H), 3.72
(dd, J=4.8, 0.9 Hz, 2H, 9-H, 9’-H), 3.56 (d, J=5.4 Hz, 2H, 6-H, 6’-H),
3.72 (dd, J=9.0, 5.0 Hz, 1H, 4-H), 3.81 (d, J=1.8 Hz, 1H, 3-H), 4.28 (d,
J=9.0 Hz, 1H, 1-H), 4.33 (d, J=11.4 Hz, 1H, CH2-Ph), 4.40 (d, J=
2.7 Hz, 2H, CH2-Ph), 4.52 (d, J=11.7 Hz, 1H, CH2-Ph), 4.66 (d, J=
11.4 Hz, 1H, CH2-Ph), 4.78 (d, J=11.7 Hz, 1H, CH2-Ph), 7.14–7.30 ppm
(m, 15H, arom. H); 13C NMR (75 MHz, CDCl3): d=39.3 (d, C-7), 44.4
(d, C-2), 56.4 (q, OMe), 63.6, 65.5, 69.0 (3t, C-6, C-8, C-9), 71.2, 73.5,
74.4 (3t, CH2-Ph), 70.4, 73.5, 78.8 (3d, C-3, C-4, C-5), 102.8 (d, C-1),
127.5, 127.8, 128.0, 128.1, 128.4, 128.6 (15d, arom, C-H), 137.1, 137.9,
138.6 ppm (3s, arom. C-CH2O); IR (film): n˜ =3085, 2851, 1453, 1277,
1067 cmꢀ1; elemental analysis calcd (%) for C31H38O7 (522.63): C 71.24,
H 7.33; found: C 71.46, H 7.40.
Methyl3,4,6-tri-
O-benzyl-2-deoxy-2-C-[ethanol]-b-d-glucopyranoside
Methyl3,4,6-tri- O-benzyl-2-deoxy-2-C-(formylmethyl)-b-d-galactopyra-
noside (galacto-21): Flash chromatography (cyclohexane/ethyl acetate
10:1!8:1) afforded the aldehyde galacto-21 as a colorless syrup (430 mg,
88%); Rf =0.44 (cyclohexane/ethyl acetate 4:1); [a]2D0 =+13.9 (c=0.96 in
CHCl3); 1H NMR (300 MHz, CDCl3): d=2.31 (ddd, J=16.8, 6.6, 3.0 Hz,
1H, 7-H), 2.53 (ddd, J=16.8, 6.6, 3.0 Hz, 1H, 7’-H), 2.86 (dddd, J=10.2,
7.8, 6.6, 3.0 Hz, 1H, 2-H), 3.21 (s, 3H, OMe), 3.47–3.54 (m, 1H, 3-H),
3.54 (d, J=4.5 Hz, 1H, 6-H), 3.57 (ddd, J=9.3, 6.9, 2.7 Hz, 1H, 5-H),
3.81 (t, J=6.9 Hz, 1H, 6’-H), 3.89 (d, J=1.2 Hz, 1H, 4-H), 4.34 (d, J=
11.7 Hz, 1H, CH2-Ph), 4.36 (d, J=11.7 Hz, 1H, CH2-Ph), 4.44 (d, J=
11.7 Hz, 1H, CH2-Ph), 4.46 (d, J=11.4 Hz, 1H, CH2-Ph), 4.57 (d, J=
(gluco-20): Flash chromatography (cyclohexane/ethyl acetate 3:1!2:1)
gave the alcohol gluco-20 as a colorless syrup (410 mg, 83%); Rf =0.38
(cyclohexane/ethyl acetate 1:1); [a]2D0 =+0.3 (c=0.87 in CHCl3);
1H NMR (500 MHz, CDCl3): d=1.63 (dddd, J=10.0, 8.5, 6.0, 2.0 Hz, 1H,
2-H), 1.76–1.88 (m, 2H, 7-H), 3.32–3.38 (m, 2H, 8-H), 3.46 (ddd, J=10.0,
4.5, 3.0 Hz, 1H, 5-H), 3.52 (s, 3H, OMe), 3.62–3.68 (m, 2H, 3-H, 4-H),
3.75 (t, J=2.8 Hz, 2H, 6-H), 4.14 (d, J=8.5 Hz, 1H, 1-H), 4.57 (d, J=
12.5 Hz, 1H, CH2-Ph), 4.59 (d, J=10.5 Hz, 1H, CH2-Ph), 4.64 (d, J=
12.5 Hz, 1H, CH2-Ph), 4.65 (d, J=11.0 Hz, 1H, CH2-Ph), 4.77 (d, J=
11.0 Hz, 1H, CH2-Ph), 4.95 (d, J=11.5 Hz, 1H, CH2-Ph), 7.17–7.36 ppm
10166
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 10152 – 10167

Malonyl Carbohydrates
FULL PAPER
11.4 Hz, 1H, CH2-Ph), 4.68 (d, J=7.8 Hz, 1H, 1-H), 4.78 (d, J=11.7 Hz,
1H, CH2-Ph), 7.15–7.30 (m, 15H, arom. H), 9.59 ppm (dd, J=5.0, 1.5 Hz,
1H, CHO); 13C NMR (75 MHz, CDCl3): d=36.2 (t, C-2), 42.3 (t, C-7),
55.1 (q, OMe), 69.3 (t, C-6), 71.3, 73.5, 74.4 (3t, CH2-Ph), 69.6, 71.9, 78.0
(3d, C-3, C-4, C-5), 100.4 (d, C-1), 127.5, 127.7, 127.8, 127.9, 128.2, 128.4,
128.5 (15d, arom, C-H), 137.6, 138.0, 138.6 (3s, arom. C-CH2O),
201.5 ppm (s, CHO); IR (film): n˜ =3030, 2870, 1721, 1496, 1050 cmꢀ1; ele-
mental analysis calcd (%) for C30H34O6 (490.59): C 73.45, H 6.99; found:
C 73.25, H 7.15.
[9] a) K. Krohn, U. Flçrke, D. Gehle, J. Carbohydr. Chem. 2002, 21,
431–443; b) H. Shao, S. Ekthawatchai, S.-H. Wu, W. Zou, Org. Lett.
2004, 6, 3497–3499.
[10] Review: G. S. Cousins, J. O. Hoberg, Chem. Soc. Rev. 2000, 29, 165–
174; a) C. V. Ramana, M. Nagarajan, Synlett 1997, 763–764; b) J.
Beyer, R. Madsen, J. Am. Chem. Soc. 1998, 120, 12137–12138; c) J.
Beyer, P. R. Skaanderup, J. Am. Chem. Soc. 2000, 122, 9575–9583;
d) P. R. Sridhar, K. C. Ashalu, S. Chandrasekaran, Org. Lett. 2004, 6,
1777–1779; e) S. D. Haveli, P. R. Sridhar, P. Suguna, S. Chandrase-
karan, Org. Lett. 2007, 9, 1331–1334.
[11] a) B. Giese, K. Grçninger, Tetrahedron Lett. 1984, 25, 2743–2746;
b) B. Giese, Pure Appl. Chem. 1988, 60, 1655–1658; c) B. Giese,
Angew. Chem. 1989, 101, 993–1172; Angew. Chem. Int. Ed. Engl.
1989, 28, 969–980; d) J. Cossy, S. Ibji, Carbohydr. Res. 1996, 291,
189–196.
[12] V. Gyꢁllai, D. Schanzenbach, L. Somsꢂk, T. Linker, Chem.
Commun. 2002, 1294–1295.
[13] T. Sommermann, B. G. Kim, K. Peters, E.-M. Peters, T. Linker,
Chem. Commun. 2004, 2624–2625.
Acknowledgements
This work was generously supported by the Deutsche Forschungsgemein-
schaft (Li 556/7-3). We thank Professor H.-J. Holdt for giving us access to
his microwave reactor.
[14] a) K. Hartmann, B. G. Kim, T. Linker, Synlett 2004, 2728–2731;
b) B. G. Kim, U. Schilde, T. Linker, Synthesis 2005, 1507–1513.
[15] J. Yin, J. Spindler, T. Linker, Chem. Commun. 2007, 2712–2713.
[16] a) R. U. Lemieux, R. M. Ratcliffe, Can. J. Chem. 1979, 57, 1244–
1251; b) V. Nair, J. Mathew, J. Chem. Soc. Perkin Trans. 1 1995,
1881–1882; c) V. Nair, J. Mathew, J. Prabhakaran, Chem. Soc. Rev.
1997, 26, 127–132; d) V. Nair, L. Balagopal, R. Rajan, J. Mathew,
Acc. Chem. Res. 2004, 37, 21–30.
[17] W. E. Holla, J. Carbohydr. Chem. 1990, 9, 113–119. We thank Dr.
Holla (Novartis) for a generous gift of crude glycal 6d.
[18] B. Fraser-Reid, S. Y.-K. Tam, B. Radatus, Can. J. Chem. 1975, 53,
2005–2016.
[19] a) B. Helferich, E. N. Mulcahy, H. Ziegler, Chem. Ber. 1954, 87,
233–237; b) B. K. Shull, Z. Wu, M. Koreeda, J. Carbohydr. Chem.
1996, 15, 955–964; c) S. A. Mitchell, M. R. Pratt, V. J. Hruby, R.
Polt. J. Org. Chem. 2001, 66, 2327–2342.
[20] P. G. M. Wuts, T. W. Greene, Greeneꢀs Protective Groups in Organic
Synthesis, 4th ed., Wiley, Hoboken, 2007.
[21] a) A. G. Tolstikov, N. V. Khakhalina, L. V. Spirikhin, Synthesis 1988,
221–222; b) M. Chmielewski, I. Fokt, J. Grodner, G. Grynkiewicz,
W. Szeja, J. Carbohydr. Chem. 1989, 8, 735–744; c) S. Messaoudi, F.
Anizon, B. Pfeiffer, R. Golsteyn, M. Prudhomme, Tetrahedron Lett.
2004, 45, 4643–4647; d) S. K. Madhusudan, G. Agnihotri, D. S. Negi,
A. K. Misra, Carbohydr. Res. 2005, 340, 1373–1377.
[22] a) R. J. Ferrier, N. Prasad, J. Chem. Soc. C 1969, 581–586; b) R. D.
Dawe, B. Fraser-Reid, J. Chem. Soc. Chem. Commun. 1981, 1180–
1181; c) K. Inaba, S. Matsumura, S. Yoshikawa, Chem. Lett. 1991,
485–488.
[23] R. Sustmann, H.-G. Korth in Houben-Weyl, Methoden der Organi-
schen Chemie, Vol. E5 (Ed.: J. Falbe), Thieme, Stuttgart, 1985,
pp. 193–470.
[24] Reviews: a) A. P. Krapcho, Synthesis 1982, 805–822; b) A. P. Krap-
cho, Synthesis 1982, 893–914.
[1] a) M. H. D. Postema, C-Glycoside Synthesis, CRC Press, Boca
Raton, 1995; b) D. E. Levy, C. Tang, The Chemistry of C-Glycosides,
Elsevier, Oxford, 1995.
[2] Reviews: a) S. Hanessian, A. G. Pernet, Adv. Carbohydr. Chem. Bio-
chem. 1976, 33, 111–188; b) M. H. D. Postema, Tetrahedron 1992,
48, 8545–8599; c) J.-M. Beau, T. Gallagher, Top. Curr. Chem. 1997,
187, 1–54; d) F. Nicotra, Top. Curr. Chem. 1997, 187, 55–83; e) Y.
Du, R. J. Linhardt, I. R. Vlahov, Tetrahedron 1998, 54, 9913–9959.
[3] Reviews of C-saccharide synthesis: a) M. McKee, L. Liu, M. H. D.
Postema, Curr. Org. Chem. 2001, 5, 1133–1167; b) X. Yuan, R. J.
Linhardt, Curr. Top. Med. Chem. 2005, 5, 1393–1430.
[4] a) M. H. D. Postema, D. Calimente, Tetrahedron Lett. 1999, 40,
4755–4759; b) M. H. D. Postema, D. Calimente, L. Liu, T. L. Behr-
mann, J. Org. Chem. 2000, 65, 6061–6068; c) L. Liu, M. H. D. Poste-
ma, J. Am. Chem. Soc. 2001, 123, 8602–8603; d) M. H. D. Postema,
J. L. Piper, L. Liu, J. Shen, M. Faust, P. Andreana, J. Org. Chem.
2003, 68, 4748–4754; e) M. H. D. Postema, J. L. Piper, V. Koman-
duri, L. Liu, Angew. Chem. 2004, 116, 2975–2978; Angew. Chem.
Int. Ed. 2004, 43, 2915–2918.
[5] Books: a) B. Giese, Radicals in Organic Synthesis: Formation of
ꢀ
Carbon Carbon Bonds, Pergamon Press, Oxford, 1986; b) J. Fossey,
D. Lefort, J. Sorba, Free Radicals in Organic Chemistry, Wiley, Chi-
chester, 1995; c) D. P. Curran, N. A. Porter, B. Giese, Stereochemistry
of Radical Reactions, VCH, Weinheim, 1996; d) T. Linker, M.
Schmittel, Radikale und Radikalionen in der Organischen Synthese,
Wiley-VCH, Weinheim, 1998; e) Radicals in Organic Synthesis
(Eds.: P. Renaud, M. P. Sibi), Wiley-VCH, Weinheim, 2001; f) S. Z.
Zard, Radical Reactions in Organic Synthesis, Oxford University
Press, New York, 2003; g) A. Gansäuer, Radicals in Synthesis, Top.
Curr. Chem. 2006, 263, whole volume.
[6] a) U. Linker, B. Kersten, T. Linker, Tetrahedron 1995, 51, 9917–
9926; b) T. Linker, B. Kersten, U. Linker, K. Peters, E.-M. Peters,
H.-G. von Schnering, Synlett 1996, 468–470; c) T. Linker, U. Linker,
Angew. Chem. 2000, 112, 934–936; Angew. Chem. Int. Ed. 2000, 39,
902–904; d) T. Linker, J. Organomet. Chem. 2002, 661, 159–167;
recent review of CAN in radical reactions: V. Nair, A. Deepthi,
Chem. Rev. 2007, 107, 1862–1891.
[7] a) T. Linker, K. Hartmann, T. Sommermann, D. Scheutzow, E.
Ruckdeschel, Angew. Chem. 1996, 108, 1819–1821; Angew. Chem.
Int. Ed. Engl. 1996, 35, 1730–1732; b) T. Linker, T. Sommermann, F.
Kahlenberg, J. Am. Chem. Soc. 1997, 119, 9377–9384.
[8] a) S. Hanessian, P. Dextraze, Can. J. Chem. 1972, 50, 226–232; b) B.
Fraser-Reid, L. Magdzinski, B. F. Molino, D. R. Mootoo, J. Org.
Chem. 1987, 52, 4495–4504; c) D. Kubota, O. Mitsunobu, Chem.
Lett. 1997, 517–518; d) X. Li, T. Uchiyama, C. R. H. Raetz, O.
Hindsgaul, Org. Lett. 2003, 5, 539–541.
[25] K.-I. Kim, R. I. Hollingsworth, Tetrahedron Lett. 1994, 35, 1031–
1032.
[26] Microwaves in Organic Synthesis (Ed.: A. Loupy), Wiley-VCH,
Weinheim, 2nd ed., 2006.
[27] a) L. I. Kudryashov, M. A. Cclenov, N. K. Kochetkov,Izvestiya Aka-
demii Nauk SSSR, Seria Khimicheskaya 1965, 1, 75–79; b) J. K.
Dickson, B. Fraser-Reid, J. Chem. Soc. Chem. Commun. 1990, 1440–
1443; c) O. Jarreton, T. Skrydstrup, J.-F. Espinosa, J. Jimꢃnez-Bar-
bero, J.-M. Beau, Chem. Eur. J. 1999, 5, 430–441; d) C. Clarke, R. J.
Woods, J. Gluska, A. Cooper, M. A. Nutley, G.-J. Boons, J. Am.
Chem. Soc. 2001, 123, 12238–12247.
[28] S. L. Krintel, J. Jimꢃnez-Barbero, T. Skrydstrup, Tetrahedron Lett.
1999, 40, 7565–7568.
Received: July 25, 2007
Published online: October 23, 2007
Chem. Eur. J. 2007, 13, 10152 – 10167
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10167