Tetrasubstituted C-glycosylidenes and C-glycosyl compounds from Di-and Monobromo-substituted exo-glycals

Article abstract of DOI:10.1002/ejoc.201100949

Efficient methods for functionalization of readily available exo-glycals have been developed. Sequential palladium-catalysed cross-coupling of dibromo-substituted exo-glycals was first explored and allowed the formation of new disubstituted exo-glycals as

Full text of DOI:10.1002/ejoc.201100949

FULL PAPER
DOI: 10.1002/ejoc.201100949
Tetrasubstituted C-Glycosylidenes and C-Glycosyl Compounds from Di- and
Monobromo-Substituted exo-Glycals
Hoang-Trang Tran Thien,[a] Alexandre Novoa,[a] Nadia Pellegrini-Moïse,[a]
Françoise Chrétien,[a] Claude Didierjean,[b] and Yves Chapleur*[a]
Keywords: Carbohydrates / Glycals / C-glycosides / Palladium / Cross-coupling
Efficient methods for functionalization of readily available
exo-glycals have been developed. Sequential palladium-cat-
mides were used in carbon-carbon bond formation through
palladium-catalysed reactions, leading to a new series of pre-
alysed cross-coupling of dibromo-substituted exo-glycals viously unknown exo-glycals. Further chemical manipulation
was first explored and allowed the formation of new disubsti-
tuted exo-glycals as single stereoisomers. Bromination of fu-
rano- and pyrano-methoxycarbonyl-exo-glycals led to a new
series of monobrominated derivatives. These vinylic bro-
of the methoxycarbonyl functionalities and stereoselective
hydrogenation of the exocyclic double bond led to C-glycosyl
compounds with high stereocontrol.
dibromomethylenation[9] of sugar lactones, leading to exo-
glycals of type A (Figure 1). New applications of the Wittig
reaction with stabilized phosphoranes led to exo-glycals of
type B as more functionalized representatives.[10] Subse-
quent reduction of these anomeric olefins (A and B) gave
the corresponding C-glycosides with high stereocontrol.[6,11]
We have demonstrated the interest of exo-glycals of type
B in syntheses of spironucleosides,[12] β-amino acids[13] and
peptidomimetics.[14]
Introduction
Carbohydrates play an indispensable role in various bio-
logical processes and are also a source of fascination for
synthetic chemists. The field of carbohydrate chemistry has
developed widely during the last thirty years.[1–3] Carbo-
hydrates have been used as starting materials in total syn-
theses and more recently as scaffolds for the construction
of new active compounds. Mimicry of bioactive carbo-
hydrates is also a longstanding area of interest of carbo-
hydrate chemists and has led to the development of new
and efficient synthetic strategies for carbohydrate modifica-
tion,[2] although this remains a challenging task for the
many researchers in the field. C-Glycosyl derivatives are
among the most intensely studied compounds, because they
provide high chemical and biological stabilities toward en-
zymatic hydrolysis in carbohydrate moieties. Of the numer-
ous synthetic methods for the synthesis of C-glycosyl com-
pounds, double bond reduction of C-glycosylidene com-
pounds – commonly called exo-glycals[4] – represents a
promising approach. The formation of exo-glycals is a long-
standing interest of our research group. Some time ago we
introduced direct methods for exo-glycal formation through
direct olefination of readily available sugar lactones. We
also developed an efficient means for the formation of car-
bon–carbon bonds at anomeric centres by dichloro-[5–8] and
Figure 1. Different types of substituted exo-glycals.
Since our pioneering exploration of the formation and
use of exo-glycals, several other indirect methods based on
addition/elimination have been proposed.[15–22] Most of
these methods give exo-glycals of defined structure. Lopez’s
group’s elegant works based on chemoselective transforma-
tions of functionalized exo-glycals opened the way to exo-
glycal manipulation.[23,24] In particular, Suzuki and Stille
cross-coupling reactions have been successfully applied to
1Ј-halo-substituted exo-glycals obtained by halogenation of
methylene-exo-glycals.[25] Various aryl, heteroaryl, vinyl or
alkynyl groups have been introduced stereoselectively onto
exo-glycal vinyl halide functionalities.[26]
[a] UMR 7565 SRSMC, Nancy Université – CNRS,
Groupe SUCRES, B. P. 70239, 54506 Nancy Vandœuvre,
France
Fax: +33-3-83684780
E-mail: yves.chapleur@srsmc.uhp-nancy.fr
[b] UMR 7036 CRM2, Nancy Université – CNRS,
B. P. 70239, 54506 Nancy Vandoeuvre, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100949 or from
the author.
The one-step synthesis of exo-glycals developed in our
group seemed attractive for further functionalization, offer-
ing access to more complex representatives of this interest-
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Y. Chapleur et al.
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ing class of compounds (Figure 1). Indeed, chemical manip-
ulations of the readily available exo-glycals A and B might
provide an interesting approach to difunctionalized olefinic
sugars of type C. Ample precedents in the functionalization
of 1,1-dihaloalkenes with organozinc, organotin and or-
ganoboron reagents[27–29] led us to consider exo-glycals of
type A as possible substrates.[30] This study reports in full
our results obtained in the functionalization of readily
available exo-glycals leading to new disubstituted exo-gly-
cals in a completely stereoselective manner. Furthermore,
introduction of molecular diversity on a functionalized
methoxycarbonyl exo-glycal (type B) has been investigated.
Bromination was explored first, and led to vinylic bromo
esters as completely new furano- and pyrano-exo-glycals of
type D. The reactivity of activated bromo-exo-glycals of this
new type towards carbon–carbon bond formation through
palladium-catalysed reactions was explored.
Scheme 1. Palladium-catalysed cross-coupling reactions with the
dibromo-exo-glycal 1. Reagents and conditions: i) Suzuki cross-
coupling: RB(OH)2 (1.5 or 2 equiv.), DME, K2CO3 (2 m, 2 equiv./
equiv. boronic acid), PdCl2(PPh3)2 (5 mol-%), TFP (30 mol-%),
85 °C, 24 h. Stille cross-coupling: RSnBu3 (1.5 equiv.), toluene,
Pd2(dba)3 (5 mol-%), TFP (30 mol-%), 100 °C, 24 h or 140 °C, mi-
crowave irradiation in a sealed tube, 45 min.
Results and Discussion
DME with aqueous potassium carbonate solution (2 m) at
85 °C over 24 h; the quantity of palladium catalyst was al-
ways 5 mol-%. The quantity of boronic acid was adapted in
Functionalization of Dibromo-furano-exo-glycals
Preliminary Suzuki cross-coupling experiments[31] car- response the preliminary results obtained, in particular the
ried out on dichloro olefins[8] showed that these were poorly ratio of bis-coupled compounds and starting material.
reactive and did not undergo modifications of the carbon– Table 1 summarizes the most significant results reflecting
chlorine bond other than reduction.[6,32] We turned to the the increase in the stereoselectivity.
dibromo-exo-glycols, readily available from the correspond-
Firstly, the reactions performed with Pd0 [Pd(PPh3)4,
ing protected d-gulono-γ-lactone by dibromomethylenation Method A] showed modest stereoselectivity, the Z isomers
with (bromomethylene)triphenylphosphorane.[9] The di- 2 always being the major isomers formed, but accompanied
bromo derivative 1 was chosen as the model compound by some bis-substituted compounds 4 or unreacted 1 in sig-
(Scheme 1).
nificant amounts (Entries 1, 4, 6, 8, 10). Trifurylphosphane
Five different boronic acids were selected as coupling (TFP) was then chosen for its property as a soft ligand,
partners and a series of experiments was performed to find being used at a level of 30 mol-% with two different sources
the best experimental conditions. The presence of the two of PdII catalyst: Pd2(dba)3 and PdCl2(PPh3)2. When per-
bromide moieties prompted us to carry out a systematic formed with TFP/Pd2(dba)3 the reactions showed improved
investigation of the reaction conditions in order to differen- Z/E ratios in the monosubstituted isomers (results not
tiate these two reactive sites. The presence of the ring oxy- shown). Finally, the combination of TFP/PdCl2(PPh3)2
gen might influence the reactivity of the vinylic system. In (Method B) appeared to represent the best coupling condi-
principle, three compounds could be obtained: the mono- tions, with excellent conversion rates and good to excellent
substituted compounds 2 and 3, resulting from single cross- stereoselectivities. The palladium-catalysed reactions of the
couplings of the (E)- or the (Z)-bromide, respectively, and dibromo-furano-exo-glycal 1 first took place at the trans
the disubstituted exo-glycal 4 obtained by the double cou- carbon–halogen bond, meaning that the first oxidative ad-
pling reaction (Scheme 1). All reactions were carried out in dition takes place on the carbon–bromine bond trans to the
Table 1. Suzuki cross-coupling reactions of the dibromo-exo-glycal 1.
Entry
R
Method/R(BOH)2 (equiv.)
Product (yield, %)[a]
Conversion rate (%)
Ratio[b] 2/3/4
1
2
3
4
5
6
7
8
C6H5
A/2
B/1.5
B/2
A/2
B/1.5
A/2
2a
2a
2a (50)
2b
2b (62)
2c
2c (60)
2d
87
74
100
59
100
100
100
74
100
20
3:1:5
5:1:1
1:0:1
1:0:2
5:1:1
6:2:1
4:1:0
5:1:1
6:1:2
1:0:0
9:0:1
4-MeOC6H4
2-thienyl
B/2
3-O2NC6H4
2-furyl
A/1.5
B/1.5
A/1.5
B/2
9
10
11
2d (61)
2e
2e (60)
100
1
[a] Yields after purification. [b] Estimated by H NMR from H-3 chemical shifts. A: Pd(PPh3)4, B: PdCl2(Ph3)2, TFP (30%).
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C-Glycosylidenes and C-Glycosyl Compounds
Table 2. Stille cross-coupling reactions with the dibromo-exo-glycal 1.
Entry
R
Method
Product (yield, %)[a]
Conversion rate (%)
Ratio[d] 2/3/4
1
2
3
4
5
6
7
8
C6H5
A
B
A
B
A
B
B
B
2a[b]
2a (33)
2c[b]
94
74
0
5:1:1
2:1:0
0:0:0
2:1:1
9:1:0
7:1:1
10:1:3
10:1:3
2-thienyl
2c (60)
2f (40)
2f (60)
2g[c]
95
(E)-MeO2C–CH=CH
100
100
100
100
(E)-Me3SiCH=CH
(E)-PhCH=CH
2h[c]
[a] Yields of pure products. [b] Yields not calculated, due to difficulties in purification. [c] Decomposed on chromatography column.
[d] Estimated by 1H NMR from H-3 chemical shifts. A: thermal activation 140 °C, 24 h, B: microwave activation in a sealed tube, 45 min.
ring oxygen because of steric and/or stereoelectronic effects. the major product with a Z/E ratio of 9:1 (Entry 5), but
Monosubstituted isomers were formed with good to excel- purification gave only a low yield of pure compound. Mi-
lent ratios in favour of compounds 2a–e. Because of the crowave activation with methyl (E)-(tributylstannyl)acrylate
similar chromatographic mobilities of the monocoupled increased the yield with almost the same good stereoselec-
compounds 2 and 3 and the exo-glycal 1, purification of the tivity (Entry 6). Here, purification of the crude mixture was
crude mixtures was possible only when the starting di- again performed by preparative column chromatography
bromide 1 was totally consumed (Entries 3, 5, 6, 7, 9, 11). and only the major monosubstituted compound 2g was
The major products 2a–e were isolated as pure compounds fully characterized. Coupling with the more highly elabo-
by preparative column chromatography and fully charac- rated tributylstannanes led to the monosubstituted Z iso-
terized. The amounts of E isomers 3 and bis-substituted mers 2g and 2h in excellent Z/E ratios (Entries 7 and 8), but
compounds 4 were low or just traces. The use of microwave these unsaturated compounds proved very sensitive to
activation to perform these Suzuki cross-coupling reactions acidic media and decomposed extensively on purification.
did not improve their yields or stereoselectivities.
The stereochemistry of the major compounds 2 was first
In view of the good results obtained in the Suzuki cross- established as Z by observation of strong NOE interactions
coupling reactions of the monosubstituted furano-exo-gly- between H-3 and two aromatic protons (See Figure S3 in
cals 2a–e, Stille cross-coupling reactions[33] with the di- the Supporting Information). No significant correlation
bromo-exo-glycal 1 (Scheme 1, Table 2) were also investi- was observed for the minor isomer 3d. Moreover, the H-3
gated. The Stille reaction has gained wide acceptance in chemical shift signal for the Z isomer 2d appears upfield (δ
synthetic organic chemistry thanks to the ease of prepara- = 5.00 ppm) from that of the E isomer (3d, δ H-3 =
tion of organostannanes and the mild reaction conditions, 5.52 ppm). The configurations of the monosubstituted exo-
compatible with many functional groups. All reactions were glycals 2a–h and 3a–h were therefore assigned on the basis
carried out in toluene in the presence of TFP (30 mol-%) of this H-3 chemical shift difference. This attribution was
and Pd2(dba)3 (5 mol-%) as catalyst. As previously ob- confirmed by X-ray crystallographic analysis of compound
served with the Suzuki cross-couplings, the Z isomers 2 2a.[30]
were always mostly formed in preference to the E isomers.
Thermal (100 °C, 24 h, Method A) or microwave activation
(140 °C, sealed tube, 45 min, CEM Discover®, Method B) Stereoselective Formation of C-Glycosyl Compounds
were used to perform the reactions. As can be seen in
One useful application of exo-glycals is their stereoselec-
Table 2, commercially available and more highly elaborated
stannanes such as methyl (E)-(tributylstannyl)acrylate, tri-
butyl-[(E)-2-phenylethenyl]stannane or tributyl-[(E)-2-(tri-
methylsilyl)ethenyl]stannane (prepared by hydrostan-
tive reduction to C-glycosyl compounds. This transforma-
tion has been widely documented by our group[6,11,34] and
others.[35] We investigated double reduction of the mono-
substituted exo-glycals 2 by catalytic hydrogenation under
nylation of the corresponding alkynes) were used (Entries 5,
7 and 8, Table 2).
With phenyltributylstannane, the Z isomer 2a was
formed as the major product together with the bis-substi-
tuted compound 4a and some remaining starting material,
as already observed in the case of Suzuki cross-coupling
(Entry 1). No reaction occurred with the 2-thienylstannane
(Entry 3) under thermal reaction conditions. Microwave ac-
tivation did not improve the formation of compound 2a
(Entry 2) but allowed the formation of the 2-thienyl deriva-
tive 2c with good selectivity (Entry 4). In the coupling reac-
tion with methyl (E)-(tributylstannyl)acrylate an excellent
Scheme 2. C-Glycosyl compounds from the monosubstituted exo-
stereoselectivity was obtained, with the Z isomer 2f being glycals 2.
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Y. Chapleur et al.
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pressure (10 bar) over Raney nickel in ethyl acetate thienyl- and (3-nitrophenyl)boronic acids (Entries 4 and 5).
(Scheme 2). This gave the C-glycosyl compounds 5 in good The disubstituted exo-glycals 6 were obtained in stereo-
to excellent yields. The coupling constants between H-2 and chemically pure form and in good to excellent yields.
H-3 (J = 3.5 Hz) confirmed the positions of the anomeric
chains on the α faces. As expected and already observed by
us, these reductions proceed with high stereocontrol owing
to the presence of the isopropylidene groups on the α faces
Vinylic Bromination of Methoxycarbonyl-exo-glycals
Several years ago we described a new class of Wittig reac-
tions with lactones, leading in excellent yields to meth-
oxycarbonyl-exo-glycals as mixtures of Z and E olefins, in
most cases easily separable.[10] We reasoned that more
highly functionalized exo-glycals, each bearing a bromine
atom and a methoxycarbonyl group, could be useful for the
synthesis of complex exo-glycals and C-glycosyl derivatives.
Chlorine addition to exo-glycals is an efficient process de-
scribed by us several years ago.[36] Similarly, vinylic bromi-
nation through addition/elimination could be envisaged.
This was applied to several furano- and pyrano-glycosylid-
enes of d-gulo, d-manno and d-ribo configuration
(Scheme 4, Table 4). Particular attention was paid to the
configurations (Z and E) of the bromo esters 12–15.
of the sugar templates.
Disubstituted exo-Glycals by Cross-Coupling
The remaining bromine atoms on the vinylic derivatives
2 could be used to introduce second points of molecular
diversity through palladium-catalysed cross-coupling. A
wide selection of variously substituted (aromatic, heteroaro-
matic and ethylenic) exo-glycals were obtained in good to
excellent yields (Scheme 3, Table 3). Suzuki cross-coupling
was performed with boronic acids (2 equiv.) and Pd-
(PPh3)4 as catalyst. The experimental conditions for Stille
cross-coupling were the same as described above: namely
two equivalents of stannane and Pd2dba3/TFP as the cata-
lyst. This approach is highly versatile, because any stereo-
isomer can be synthesized in a stereochemically pure form
simply by modifying the order of introduction of the radi-
cals. This was illustrated in one case with the use of 2-
Scheme 3. Palladium-catalysed cross-coupling with the bromo exo-
glycals 2. Reagents and conditions: i) Suzuki cross-coupling
RЈB(OH)2 (2 equiv.), DME, K2CO3 (2 m, 4 equiv.), Pd(PPh3)4
(5 mol-%), 85 °C, 24 h. Stille cross-coupling: RЈSnBu3 (2 equiv.),
toluene, Pd2dba3 (5 mol-%), TFP (30 mol-%), 140 °C, microwave
irradiation in a sealed tube, 45 min.
Table 3. Disubstituted exo-glycals by sequential cross-coupling.
Entry Starting
RЈB(OH)2 or RЈSnBu3
Product
exo-glycal
(yield, %)[a]
1
2
3
4
5
6
2d
2d
2d
2d
2c
2e
C6H5B(OH)2
6a (85)
6b (95)
6c (66)
6d (60)
6e (85)
6f (85)
Scheme 4. Bromination of methoxycarbonyl-exo-glycals. Reagents
and conditions: i) Br2, NEt3, CCl4, room temperature.
4-MeOC6H4B(OH)2
(E)-MeOOCCH=CHSnBu3
2-thienyl–B(OH)2
3-NO2C6H4B(OH)2
4-MeOC6H4B(OH)2
The reactions were first explored with the d-gulo deriva-
tives 7(E) and 7(Z). No bromination occurred on treatment
of either isomer with NBS in chlorinated solvents. Treat-
[a] Yields after purification.
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C-Glycosylidenes and C-Glycosyl Compounds
Table 4. Bromination of methoxycarbonyl-exo-glycals.
Entry
Starting exo-glycals
Product (yield, %)[a]
Z/E ratio[b]
H-4 chemical shift (ppm)
1
2
3
4
5
6
7
7(Z)
7(E)
8(Z)
8(E)
9(Z)
9(E)
11(Z)
12(Z), 12(E) (86)
12(Z), 12(E) (91)
13(Z), 13(E) (70)
13(Z), 13(E) (81)
14(Z), 14(E) (55)
14(Z), 14(E) (77)
15(Z), 15(E) (62)
4:6
6:4
6:4
6:4
4:6
3:7
4:6
5.79 [12(Z)]
5.39 [12(E)]
5.77 [13(Z)]
5.39 [13(E)]
5.79 [14(Z)]
5.38 [14(E)]
5.63 [15(Z)]
5.15 [15(E)]
1
[a] Yields of pure compounds. [b] Estimated by H NMR from H-4 chemical shifts.
ment, however, of 7(E) or 7(Z) with Br2 followed by hydro- drogen bromide from B occurs by a E2 mechanism on the
gen bromide elimination in the presence of NEt3 in CCl4 most favoured rotamer, leading to the corresponding Z de-
gave the expected separable vinylic bromo esters 12(Z) and rivative.[23] In our case the acidity of the proton is strongly
12(E) in roughly the same ratio (Table 4). To transform the enhanced by the carboxyl group and this proton is abstrac-
Z isomer 7(Z) took about 20 h (Entry 1). In contrast, a pro- ted by the NEt3 base. The initial double bond stereochemis-
longed reaction time (about 72 h) was necessary for the E try is lost in the intermediate enolates C and D. Elimination
isomer 7(E) (Entry 2). Efficient separation of the two iso- leads, through an E1CB mechanism, to a mixture of Z and
mers was performed by high-pressure preparative column E isomers in slightly different ratios, depending on the start-
chromatography.
ing double bond configuration of the exo-glycal and the
The manno and ribo derivatives 8 and 9 were treated un- sugar configuration.
der the same conditions, starting from stereochemically
pure isomers (Z and E), giving mixtures of the correspond- glycosylidenes, and so we turned to the tetra-O-benzyl-
ing bromo esters in good yields (Entries 3–4, 5–6). No sig- glucopyrano-exo-glycal 10 prepared by a literature pro-
nificant difference in reaction time between the E and Z
isomers was observed in either case.
We planned to extend this vinylic bromination to pyrano-
Because of the difficulties in separation of the pairs of
isomers, even with preparative high-pressure column
chromatography, only the major bromo esters 13(Z) and
14(E) were characterized. A mixture of Z and E isomers
was obtained in each case, in sharp contrast with the halo-
genation of methylene-exo-glycals which gave single Z iso-
mers as described by Lopez’s group.[23] These results could
be explained by the mechanism depicted in Figure 2. Bro-
mine addition to the double bond leads to a bromonium
ion (intermediate A). Opening of this bromonium ion leads
to the dibromo derivative B. These two steps are likely to
be highly stereospecific, occurring trans to the O-2 substitu-
ent. In the case of methylene-exo-glycal, elimination of hy-
Scheme 5. Functionalization of methoxycarbonyl-exo-glycals.
i) RB(OH)2 (2 equiv.), Pd(PPh3)4, K2CO3 (2 m), 1,4-dioxane,
Figure 2. Proposed mechanism for bromination of methoxy-
carbonyl-exo-glycals.
110 °C, 24 h.
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Y. Chapleur et al.
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cedure from tetra-O-benzyl-d-glucono-1,5-lactone and ob-
.[37,38]
tained as a single Z stereoisomer
Use of various sets
of experimental conditions to perform the vinylic bromina-
tion was explored, but without success. No starting material
was recovered and no bromo derivative was isolated. We
turned to the six-membered-ring exo-glycal 11 obtained as
the major Z isomer through a Wittig reaction with the cor-
responding protected lactone.[10] Bromination of 11 with
Br2 in CCl4 in the presence of NEt3 led to the correspond-
ing vinylic bromo esters in 62% yield as a separable mixture
of isomers 15(Z) and 15(E) (Entry 7).
The common double bond configuration of the furano
bromo esters 12(Z) to 14(Z) was assigned as Z from the
NMR spectroscopic data. For the Z isomers the H-4 signal
appears downfield, because of the proximity of the meth-
oxycarbonyl function (Table 4). A single-crystal X-ray
analysis of compound 13(Z) confirmed a cis relationship
between the oxygen and the bromine atoms, establishing the
Z configuration (Sit>) and 15(E), the double bond configu-
rations were again established by NMR spectroscopy. The
proximity of the methoxycarbonyl function to the H-4 pro-
ton led to a downfield signal (5.63 ppm) for the Z isomer
15(Z) relative to 15(E) (5.15 ppm). Confirmation was ob-
tained later on: no significant correlation in a NOESY ex-
periment was observed for the coupled compound 18a
Scheme 6. Reduction of methoxycarbonyl-exo-glycals. i) DIBAL
(2 equiv.), toluene, –30 °C, ii) Ac2O, NEt3, DMAP, CH2Cl2.
Treatment of 7(E) with DIBAL in toluene at –30 °C af-
(Scheme 5), obtained from 15(Z), whereas a strong nOe in- forded a mixture of the alcohol 21 and another compound
teraction between H-4 and two aromatic protons was ob- identified as the open sugar 20. The formation of the olefin
served for 19a, obtained from the E isomer 15(E).
20 was also observed, together with that of the allylic
alcohol 22, on the corresponding treatment of 7(Z). The
21 (or 22)/20 ratio was found to depend on the reaction
temperature. Acetylation of 20 gave compound 23 in quan-
titative yield. The NMR spectra of 23 showed the presence
of two acetoxy groups (δ = 2.11 and 2.14 ppm) and con-
firmed the presence of two hydroxy groups in 20. The H-2
and H-3 coupling constant (J = 15.5 Hz) established the E
configuration of the double bond.
Methoxycarbonyl group reduction was examined with
the substituted exo-glycals 16a and 17a as pure E and Z
isomers (Scheme 7). Treatment with DIBAL in toluene at
–30 °C led to mixtures of closed and open sugars. The re-
duction of the E isomer 16a gave 24 and 25 in 55 and 35%
yields, respectively. With 17a, the major compound ob-
tained by reduction with DIBAL was the allylic alcohol 26,
obtained in 71% yield together with the open compound
24 in 10% yield. In this case the double bond configuration
was determined by NOESY spectroscopy, which showed an
interaction between H-4 and H-ar in favour of the E config-
uration depicted (Scheme 7). The use of LiAlH4 in THF on
7(E)/7(Z) and 16a/17a led exclusively to the open sugars
20 or 24, respectively, previously formed on treatment with
DIBAL (results not shown).
Functionalization of Methoxycarbonyl-exo-glycals
Palladium-catalysed cross-coupling of furano- and pyr-
ano-bromomethoxycarbonyl-exo-glycals as pure Z isomers
[12(Z) and 15(Z)] or E isomers [12(E) and 15(E)] was inves-
tigated (Scheme 5). Suzuki cross-coupling was carried out
with four different boronic acids in 1,4-dioxane at reflux for
24 h with Pd(PPh3)4 as catalyst. The new disubstituted exo-
glycals 16–19 were obtained in good yields (Table 5).
Table 5. Palladium-catalysed cross-coupling of 13(Z), 15(Z) and
15(E).
Entry
R
Products (yield, %)[a]
1
2
3
4
C6H5
16a (71)
16b (68)
16c (64)
16d (81)
18a (56)
19a (51)
19b (65)
19c (79)
19d (74)
3-O2NC6H4
4-MeOC6H4
2-naphthyl
–
18c (82)
18d (78)
[a] Yields after purification.
Chemical Manipulation of exo-Glycals Containing
Methoxycarbonyl Moieties
The formation of the allylic alcohols 21, 22, 25 and 26 is
clearly the result of a simple ester reduction by DIBAL.
The exo-glycals 16–19, each bearing an ester function on The formation of the open compounds 20 and 24, however,
the exocyclic double bond, could be interesting intermedi- is the result of a more complex mechanism. The first step
ates in total synthesis or the preparation of carbohydrate is probably a 1,4-addition of hydride, as suggested by the
mimics. The reduction of the methoxycarbonyl-exo-glycals exclusive formation of these compounds on treatment with
7 as model compounds was investigated (Scheme 6).
LiAlH4, a reagent known to be efficient in 1,4-addition.
6944
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Eur. J. Org. Chem. 2011, 6939–6951

C-Glycosylidenes and C-Glycosyl Compounds
stituted exo-glycals in sequential stereoselective reactions.
We have shown that activated exo-glycals bearing meth-
oxycarbonyl groups can be brominated to produce vinylic
bromo esters as separable mixtures of isomers both in the
furanose and in the pyranose series. Activated bromo-exo-
glycals of this new type are suitable for C–C bond forma-
tion through palladium-catalysed cross-coupling reactions.
Chemical manipulation of the tetrasubstituted double
bonds in these new exo-glycals led to the formation of more
highly elaborated C-glycosyl compounds by catalytic re-
duction. Chemical reduction of the activated ester proved
to be complex, giving allylic alcohols and open-chain deriv-
atives demonstrating that these anomeric tetrasubstituted
double bonds are susceptible to hydride 1,4 addition.
Experimental Section
General: TLC analyses were performed by standard procedures on
kieselgel 60 F254 plates (Merck). Compounds were visualized with
UV light (254 nm) and (or) 30% methanolic H2SO4/heat as de-
veloping agent. Column chromatography was performed on silica
gel SI 60 (63–200 μm, Merck). High-pressure column chromatog-
raphy were performed on an axially compressed 20 mm i.d. steel
column (Separex-Novasep). FTIR spectra were recorded with a
Perkin–Elmer spectrum 1000 (NaCl window). Melting points were
determined with a Tottoli apparatus. Optical rotations were mea-
Scheme 7. Reduction and stereoselective hydrogenation of disubsti-
tuted exo-glycals. i) DibalH, toluene, –30 °C, ii) Ac2O, NEt3,
DMAP, CH2Cl2 iii) H2, PtO2, EtOAc, 40 bar.
Such facile oxygen and nitrogen nucleophile 1,4-addition at
the anomeric centres of exo-glycals is well documen-
ted.[13a,39] The enolates resulting from the hydride addition
would be susceptible to β-elimination of ring oxygen, lead-
ing to unsaturated esters which would then be conven-
tionally reduced to the corresponding alcohols. Such sugar
ring opening has also been reported by our group.[12a] It is
noteworthy that unsaturated esters of exo-glycals are better
acceptors than the intermediate open-chain esters. The dif-
ference in the reactivities of 16a and 17a could be explained
in terms of oxygen complexation, which would favour hy-
dride 1,4-addition on 16a and 1,2-addition on 17a (see Fig-
ure S4 in the Supporting Information).
Reduction of the C=C bond of a disubstituted exo-glycal
was next examined. This was done with the coupled com-
pound 25 as an example in the furanoid series (Scheme 7).
For easier chemical manipulation and purification, the
alcohol function in the exo-glycal 25 was transformed into
the acetate 27 in excellent yield. Hydrogenation of 27 was
successfully accomplished in ethyl acetate in the presence of
PtO2 as the catalyst. As already observed with the bromo-
exo-glycals 2 (Scheme 2), the double-bond reduction pro-
ceeded with high stereocontrol, compound 28 being ob-
tained as single isomer. From the geometry of the double
1
sured with an Anton Paar MC300 polarimeter. H and 13C NMR
spectra were recorded with Bruker DPX 250 (250 MHz and
62.9 MHz, respectively) and DRX 400 (400 MHz and 100.6 MHz,
respectively) spectrometers. For complete assignment of 1H and 13
C
signals, two-dimensional 1H,1H COSY and 1H,13C correlation
spectra were recorded. Chemical shifts (δ) are given in ppm relative
to the solvent residual peak. The following abbreviations are used
for multiplicity of NMR signals: s singlet, d doublet, dd double
doublet, t triplet, q quadruplet, m multiplet, br. broad signal.
HRMS spectra were recorded with a Bruker MicroTOFQ appara-
tus. Microwave syntheses were performed with a CEM Discover
mono-mode oven, the temperature being monitored with a stan-
dard external IR sensor.
General Procedure for Suzuki Couplings with Dibromo- or Mono-
bromo-Substituted exo-Glycals: A solution of the dibromo-substi-
tuted exo-glycal 1 or a monobromo derivative 2 (0.36 mmol) in dry
DME (5 mL) was added to the boronic acid (1.5 or 2 equiv.) and
aqueous K2CO3 solution (2 m, 2 equiv./equiv. of boronic acid). The
solution was stirred for 10 min and tri(2-furyl)phosphane (26 mg,
0.109 mmol, 0.3 equiv.) and PdCl2(PPh3)2 (13 mg, 0.018 mmol,
0.05 equiv.) were then added [Pd(Ph3)4 for the second cross-cou-
pling]. The reaction mixture was stirred and heated at 85 °C for
24 h. It was then allowed to cool to room temperature and concen-
bond in the starting olefin 27, the corresponding reduced trated to dryness under reduced pressure. The residue was diluted
with EtOAc (50 mL) and washed with NH4Cl (2ϫ5 mL). The
dried organic layer was evaporated under reduced pressure and the
residue was purified by silica gel chromatography.
compound 28 was obtained with an R configuration at the
newly created asymmetric centre, as confirmed by X-ray
analysis (see Figure S6 in the Supporting Information).
General Procedure for Stille Couplings with Dibromo- or Mono-
bromo-Substituted exo-Glycals: Toluene (5 mL), the dibromo exo-
glycal 1 or a monobromo derivative 2 (0.24 mmol), n-tributylstan-
nane (1.5 or 2 equiv.), tris(2-furyl)phosphane (17 mg, 0.072 mmol,
0.3 equiv.) and Pd2dba3 (10 mg, 0.018 mmol, 0.05 equiv.) were
placed in a sealed tube. The tube was sealed and heated by micro-
wave irradiation at 140 °C for 45 minutes. The reaction mixture was
Conclusions
In summary, we have shown that readily available bromo
exo-glycals can be transformed into more highly elaborated
ones through palladium-catalysed cross-coupling through
the vinylic bromide. Dibromo-exo-glycals gave new disub- then allowed to cool to room temperature, filtered through celite
Eur. J. Org. Chem. 2011, 6939–6951
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6945

Y. Chapleur et al.
FULL PAPER
and diluted with EtOAc (40 mL). The filtrate was concentrated un-
der reduced pressure and the residue was purified by silica gel
chromatography.
(dt, J = 8.0, 7.0 Hz, 1 H), 4.84 (dd, J = 6.0, 4.5 Hz, 1 H), 5.40 (d,
J = 6.0 Hz, 1 H), 6.42 (dd, J = 3.5, 2.0 Hz, 1 H), 6.66 (dd, J = 3.5,
1.0 Hz, 1 H), 7.47 (dd, J = 2.0, 1.0 Hz, 1 H) ppm. 13C NMR
(CDCl3, 62.9 MHz): δ = 25.8, 26.2, 26.8, 27.2, 66.3, 76.1, 79.9, 80.0,
86.0, 89.8, 110.6 (2 C), 111.7, 113.9, 143.1, 149.4, 154.0 ppm. IR
(6Z)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-bromo-7-
deoxy-7-phenyl-L-gluco-hept-6-enitol (2a): Yield 50 %, as a white
(NaCl): ν = 2986, 2938, 1656 cm–1. HRMS (ESI+) calculated for
˜
amorphous solid. Rf = 0.58 (hexane/EtOAc 7:3). [α]D = –236 (c =
0.87, CHCl3). 1H NMR (CDCl3, 400 MHz): δ = 1.33 (s, 3 H), 1.45
(s, 3 H),1.52 (s, 3 H), 1.55 (s, 3 H), 3.78 (dd, J = 8.5, 7.0 Hz, 1 H),
4.18 (dd, J = 8.0, 4.5 Hz, 1 H), 4.27 (dd, J = 8.7, 7.0 Hz, 1 H), 4.53
(dt, J = 8.0, 7.0 Hz, 1 H), 4.79 (dd, J = 6.0, 4.5 Hz, 1 H), 4.98 (d,
C17H21BrNaO6 [M + Na]+: 423.0414; found 423.0414.
Methyl (2E,4Z)-5,8-Anhydro-6,7:9,10-bis-O-(1-methylethylidene)-4-
bromo-2,3,4-trideoxy-D-gulo-deca-2,4-dienonate (2f): Yield 60% as
a white amorphous solid. Rf = 0.36 (hexane/EtOAc 7:3). [α]D
=
J = 6.0 Hz, 1 H), 7.27–7.40 (m, 3 H), 7.59–7.63 (m, 2 H) ppm. 13
C
1
–117 (c = 1.09, CHCl3). H NMR (CDCl3, 250 MHz): δ = 1.38 (s,
3 H), 1.41 (s, 6 H), 1.48 (s, 3 H), 3.76 (s, 3 H), 3.75–3.85 (m, 1 H),
4.24 (dd, J = 8.5, 6.5 Hz, 1 H), 4.37 (dd, J = 8.0, 4.0 Hz, 1 H), 4.47
(dt, J = 8.0, 6.5 Hz, 1 H), 4.83 (dd, J = 6.0, 4.0 Hz, 1 H), 5.48 (d,
J = 6.0 Hz, 1 H), 6.11 (d, J = 14.5 Hz, 1 H), 7.64 (d, J = 14.5 Hz,
1 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 25.5, 26.2, 26.8, 26.9,
51.8, 66.0, 75.6, 79.3, 79.6, 86.7, 96.9, 110.6, 114.9, 118.9, 139.1,
NMR (CDCl3, 100.6 MHz): δ = 25.7, 25.8, 26.6, 27.2, 66.3, 76.2,
79.3, 79.9, 85.8, 100.8, 110.5, 113.7, 128.4 (2 C), 128.5, 130.0 (2 C),
137.5, 152.8 ppm. IR (NaCl): ν = 2987, 2936, 1654 cm–1. HRMS
˜
(ESI+) calculated for C19H23BrNaO5 [M + Na]+: 433.0627; found
433.0614.
(6Z)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-bromo-7-
161.8, 167.6 ppm. IR (NaCl): ν = 2987, 2938, 1717, 1624 cm–1
.
˜
deoxy-7-(4-methoxyphenyl)-L-gluco-hept-6-enitol (2b): Yield 62% as
HRMS (ESI+) calculated for C17H24BrO7 [M + H]+: 419.0623;
found 423.0705.
a white amorphous solid. Rf = 0.51 (hexane/EtOAc 7:3). [α]D
=
1
–185 (c = 0.32, CHCl3). H NMR (CDCl3, 250 MHz): δ = 1.30 (s,
3 H), 1.42 (s, 3 H), 1.49 (s, 3 H), 1.52 (s, 3 H), 3.75 (m, 1 H), 3.82
(s, 3 H), 4.13 (dd, J = 8.5, 4.5 Hz, 1 H), 4.24 (dd, J = 8.5, 7.0 Hz,
1 H), 4.50 (dt, J = 8.5, 7.0 Hz, 1 H), 4.76 (dd, J = 6.0, 4.5 Hz, 1
H), 4.93 (d, J = 6.0 Hz, 1 H), 6.87 (d, J = 8.5 Hz, 2 H), 7.52 (d, J
= 8.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 25.3, 25.4,
26.2, 26.7, 55.3, 65.9, 75.8, 78.8, 79.5, 85.2, 100.3, 110.0, 113.2,
(6E)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-deoxy-7-
(3-nitrophenyl)-7-phenyl-L-gluco-hept-6-enitol (6a): Yield 85% as a
white amorphous solid. Rf = 0.40 (hexane/EtOAc 7:3). [α]D = –251
(c = 0.36, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 1.28 (s, 3 H),
1.41 (s, 3 H), 1.50 (s, 3 H), 1.52 (s, 3 H), 3.81 (dd, J = 8.5, 6.5 Hz,
1 H), 4.18 (dd, J = 8.0, 4.5 Hz, 1 H), 4.25 (dd, J = 8.5, 6.5 Hz, 1
H), 4.51 (dt, J = 8.0, 6.5 Hz, 1 H), 4.72 (dd, J = 6.0, 4.5 Hz, 1 H),
4.99 (d, J = 6.0 Hz, 1 H), 7.15–7.40 (m, 5 H), 7.51 (t, J = 8.0 Hz,
1 H), 7.65 (m, 1 H), 8.15 (m, 1 H), 8.26 (t, J = 2.0 Hz, 1 H) ppm.
13C NMR (CDCl3, 62.9 MHz): δ = 25.4, 25.5, 26.4, 26.9, 65.9, 75.7,
78.3, 80.3, 85.4, 110.0, 113.3, 117.0, 121.9, 125.8, 127.0, 128.2,
113.4 (2 C), 129.6, 130.9 (2 C), 151.7, 159.4 ppm. IR (NaCl): ν =
˜
2986, 2934, 1654, 1606, 1510 cm–1. HRMS (ESI+) calculated for
C20H25BrNaO6 [M + Na]+: 463.0727; found 463.0707.
(6Z)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-bromo-7-
deoxy-7-(2-thienyl)-L-gluco-hept-6-enitol (2c): Yield 60% as a white
128.8, 129.3, 137.1, 137.9, 141.2, 148.2, 152.8 ppm. IR (NaCl): ν =
˜
amorphous solid. Rf = 0.58 (hexane/EtOAc 7:3). [α]D = –315 (c =
1.04, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 1.37 (s, 3 H), 1.43
(s, 3 H), 1.49 (s, 3 H), 1.51 (s, 3 H), 3.77 (dd, J = 8.5, 7.0 Hz, 1 H),
4.18 (dd, J = 8.0, 4.5 Hz, 1 H), 4.25 (dd, J = 8.5, 7.0 Hz, 1 H), 4.50
(dt, J = 8.0, 7.0 Hz, 1 H), 4.84 (dd, J = 6.0, 4.5 Hz, 1 H), 5.18 (d,
J = 6.0 Hz, 1 H), 7.01 (dd, J = 5.0, 3.5 Hz, 1 H), 7.32 (dd, J = 5.0,
1.0 Hz, 1 H), 7.39 (dd, J = 3.5, 1.0 Hz, 1 H) ppm. 13C NMR
(CDCl3, 62.9 MHz): δ = 25.5, 25.8, 26.5, 27.0, 66.1, 75.9, 79.3, 79.9,
85.6, 93.5, 110.4, 113.8, 126.6, 127.3, 127.6, 140.8, 153.1 ppm. IR
2986, 2927, 1647, 1526, 1349 cm–1. HRMS (ESI+) calculated for
C25H27NNaO7 [M + Na]+: 476.1680; found 476.1698.
(6E)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-deoxy-7-
(4-methoxyphenyl)-7-(3-nitrophenyl)-L-gluco-hept-6-enitol (6b):
Yield 95% as a pale yellow amorphous solid. Rf = 0.38 (hexane/
EtOAc 7:3). [α]D = –261 (c = 0.64, CHCl3). 1H NMR (CDCl3,
400 MHz): δ = 1.27 (s, 3 H), 1.41 (s, 3 H), 1.50 (s, 3 H), 1.51 (s, 3
H), 3.80 (m, 1 H), 3.81 (s, 3 H), 4.15 (dd, J = 8.0, 4.5 Hz, 1 H),
4.25 (dd, J = 8.5, 6.5 Hz, 1 H), 4.51 (dt, J = 8.0, 6.5 Hz, 1 H), 4.70
(dd, J = 6.0, 4.5 Hz, 1 H), 4.95 (d, J = 6.0 Hz, 1 H), 6.84 (d, J =
9.0 Hz, 2 H), 7.28 (d, J = 9.0 Hz, 2 H), 7.50 (t, J = 8.0 Hz, 1 H),
7.67 (ddd, J = 8.0, 2.0, 1.0 Hz, 1 H), 8.15 (ddd, J = 8.0, 2.0, 1.0 Hz,
1 H), 8.25 (t, J = 2.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 62.9 MHz):
δ = 25.4, 25.5, 26.4, 26.9, 55.2, 65.9, 75.8, 78.4, 80.2, 85.3, 109.9,
113.2, 113.6 (2 C), 116.8, 121.9, 125.7, 128.8, 130.4, 130.5 (2 C),
(NaCl): ν = 2987, 2936, 1637 cm–1. HRMS (ESI+) calculated for
˜
C17H21BrNaO5S [M + Na]+: 439.0185; found 439.0193.
(6Z)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-bromo-7-
deoxy-7-(3-nitrophenyl)-L-gluco-hept-6-enitol (2d): Yield 61% as an
amorphous solid. Rf = 0.37 (hexane/EtOAc 7:3). [α]D = –208 (c =
0.60, CHCl3). 1H NMR (CDCl3, 400 MHz): δ = 1.32 (s, 3 H), 1.43
(s, 3 H), 1.50 (s, 3 H), 1.53 (s, 3 H), 3.78 (dd, J = 8.5, 7.0 Hz, 1 H),
4.20–4.30 (m, 2 H), 4.51 (dt, J = 8.0, 7.0 Hz, 1 H), 4.83 (dd, J =
6.0, 4.5 Hz, 1 H), 5.00 (d, J = 6.0 Hz, 1 H), 7.53 (t, J = 8.0 Hz, 1
H), 7.94 (ddd, J = 8.0, 2.0, 1.0 Hz, 1 H), 8.14 (ddd, J = 8.0, 2.0,
1.0 Hz, 1 H), 8.53 (t, J = 2.0 Hz, 1 H) ppm. 13C NMR (CDCl3,
62.9 MHz): δ = 25.5, 25.6, 26.4, 27.0, 66.0, 75.9, 79.1, 79.8, 85.9,
96.8, 110.4, 114.1, 122.9, 124.7, 129.3, 135.7, 139.1, 148.2,
137.1, 141.5, 148.1, 151.7, 158.4 ppm. IR (NaCl): ν = 2986, 2932,
˜
1607, 1530, 1508, 1349 cm–1. HRMS (ESI+) calculated for
C26H29NNaO8 [M + Na]+: 506.1785; found 506.1760.
Methyl (2E,4E)-5,8-Anhydro-6,7:9,10-bis-O-(1-methylethylidene)-4-
(3-nitrophenyl)-2,3,4-trideoxy-D-gulo-deca-2,4-dienonate (6c): Yield
66% as a pale yellow amorphous solid. Rf = 0.25 (hexane/EtOAc
154.8 ppm. IR (NaCl): ν = 2988, 2936, 1654, 1530, 1349 cm–1
.
˜
1
7:3). [α]D = –180 (c = 0.35, CHCl3). H NMR (CDCl3, 400 MHz):
HRMS (ESI+) calculated for C19H22BrNNaO7 [M + Na]+:
478.0477; found 478.0419.
δ = 1.21 (s, 3 H), 1.44 (s, 3 H), 1.46 (s, 3 H), 1.50 (s, 3 H), 3.70 (s,
3 H), 3.77 (dd, J = 8.5, 6.5 Hz, 1 H), 4.25 (dd, J = 8.5, 6.5 Hz, 1
H), 4.26 (dd, J = 8.0, 4.5 Hz, 1 H), 4.49 (dt, J = 8.0, 6.5 Hz, 1 H),
4.66 (dd, J = 6.0, 4.5 Hz, 1 H), 4.90 (d, J = 6.0 Hz, 1 H), 5.30 (d,
J = 15.5 Hz, 1 H), 7.50–7.60 (m, 2 H), 8.09 (d, J = 15.5 Hz, 1 H),
(6Z)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-bromo-7-
deoxy-7-(2-furanyl)-L-gluco-hept-6-enitol (2e): Yield 60% as a white
amorphous solid. Rf = 0.53 (hexane/EtOAc 7:3). [α]D = –289 (c =
0.94, CHCl3). 1H NMR (CDCl3, 400 MHz): δ = 1.39 (s, 3 H), 1.43 8.14 (m, 1 H), 8.19 (dt, J = 7.5, 2.0 Hz, 1 H) ppm. 13C NMR
(s, 3 H), 1.47 (s, 3 H), 1.50 (s, 3 H), 3.79 (dd, J = 8.5, 7.0 Hz, 1 H),
4.19 (dd, J = 8.0, 4.5 Hz, 1 H), 4.27 (dd, J = 8.5, 7.0 Hz, 1 H), 4.51
(CDCl3, 62.9 MHz): δ = 25.3, 25.6, 26.5, 26.7, 51.4, 65.8, 75.6, 78.0,
79.6, 86.5, 110.2, 113.8, 113.9, 117.9, 122.7, 126.0, 129.2, 136.7,
6946
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6939–6951

C-Glycosylidenes and C-Glycosyl Compounds
137.3, 140.6, 148.2, 159.4, 167.4 ppm. IR (NaCl): ν = 2986, 2943,
= 13.0, 9.5 Hz, 1 H), 3.51 (dd, J = 8.0, 4.0 Hz, 1 H), 3.67–3.74 (m,
2 H), 4.24 (dd, J = 8.0, 6.5 Hz, 1 H), 4.42 (dt, J = 8.0, 6.5 Hz, 1
H), 4.48 (dd, J = 6.0, 3.5 Hz, 1 H), 4.57 (dd, J = 6.0, 4.0 Hz, 1 H),
7.23–7.31 (m, 1 H), 7.28–7.34 (m, 4 H) ppm. 13C NMR (CDCl3,
62.9 MHz): δ = 25.1, 25.4, 26.0, 26.7, 34.3, 66.0, 75.6, 80.5, 81.0,
83.5, 83.6, 109.8, 112.6, 126.3, 128.3, 129.5, 137.9 ppm. IR (NaCl):
˜
1712, 1607, 1529, 1348 cm–1. HRMS (ESI+) calculated for
C23H27NNaO9 [M + Na]+: 484.1578; found 484.1569.
(6Z)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-deoxy-7-
(3-nitrophenyl)-7-(2-thienyl)-L-gluco-hept-6-enitol (6d): Yield 60%
as a pale yellow amorphous solid. Rf = 0.58 (hexane/EtOAc 7:3).
ν = 2986, 2926, 2854, 1655 cm–1. HRMS (ESI+) calculated for
˜
1
[α]D = –176 (c = 0.35, CHCl3). H NMR (CDCl3, 250 MHz): δ =
C19H26NaO5 [M + Na]+: 357.1672; found 357.1676.
1.25 (s, 3 H), 1.46 (s, 3 H), 1.49 (s, 3 H), 1.54 (s, 3 H), 3.86 (dd, J
= 8.5, 6.0 Hz, 1 H), 4.26 (dd, J = 8.5, 6.0 Hz, 1 H), 4.29 (dd, J = 2,5-Anhydro-3,4:6,7-bis-O-(1-methylethylidene)-1-deoxy-1-(4-
8.0, 4.5 Hz, 1 H), 4.58 (dt, J = 8.0, 6.0 Hz, 1 H), 4.71 (dd, J = 6.0,
4.5 Hz, 1 H), 4.93 (d, J = 6.0 Hz, 1 H), 6.76 (dd, J = 3.5, 1.0 Hz,
1 H), 6.95 (dd, J = 5.0, 3.5 Hz, 1 H), 7.29 (dd, J = 5.0, 1.0 Hz, 1
H), 7.58 (t, J = 8.0 Hz, 1 H), 7.76 (dt, J = 8.0, 1.0 Hz, 1 H), 8.24
methoxyphenyl)-D-glycero-L-galacto-heptitol (5b): Yield 77% as a
white amorphous solid. Rf = 0.54 (hexane/EtOAc 1:1). [α]D = –28
(c = 0.47, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 1.29 (s, 3 H),
1.40 (s, 3 H), 1.46 (s, 3 H), 1.53 (s, 3 H), 3.04 (dd, J = 13.0, 4.5 Hz,
(m, 1 H), 8.30 (t, J = 2.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 1 H), 3.14 (dd, J = 13.0, 9.5 Hz, 1 H), 3.50 (dd, J = 8.0, 4.0 Hz, 1
62.9 MHz): δ = 25.5, 25.6, 26.5, 27.0, 66.0, 75.7, 78.5, 80.0, 85.8,
110.1, 111.7, 113.4, 122.6, 125.8, 126.2, 126.3, 126.4, 129.0, 137.5,
H), 3.61–3.74 (m, 2 H), 3.78 (s, 3 H), 4.23 (dd, J = 8.0, 6.5 Hz, 1
H), 4.41 (dt, J = 8.0, 6.5 Hz, 1 H), 4.47 (dd, J = 6.0, 3.5 Hz, 1 H),
4.56 (dd, J = 6.0, 4.0 Hz, 1 H), 6.83 (d, J = 8.5 Hz, 2 H), 7.23 (d,
J = 8.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 25.1,
25.4, 26.0, 26.7, 33.3, 55.2, 66.0, 75.6, 80.5, 81.0, 83.6, 83.7, 109.8,
139.3, 141.0, 148.1, 151.1 ppm. IR (NaCl): ν = 2987, 2933, 1648,
˜
1529, 1349 cm–1. HRMS (ESI+) calculated for C23H25NNaO7S [M
+ Na]+: 482.1244; found 482.1261.
112.6, 113.8 (2 C), 129.9, 130.5 (2 C), 158.2 ppm. IR (NaCl): ν =
˜
(6E)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-deoxy-7-
2986, 2930, 2853, 1612, 1514 cm–1. HRMS (ESI+) calculated for
C20H28NaO6 [M + Na]+: 387.1778; found 387.1775.
(3-nitrophenyl)-7-(2-thienyl)-L-gluco-hept-6-enitol (6e): Yield 85% as
a pale yellow amorphous solid. Rf = 0.56 (hexane/EtOAc 7:3).
1
[α]D = –224 (c = 0.43, CHCl3). H NMR (CDCl3, 250 MHz): δ = 2,5-Anhydro-3,4:6,7-bis-O-(1-methylethylidene)-1-deoxy-1-(3-
1.36 (s, 3 H), 1.39 (s, 3 H), 1.50 (s, 3 H), 1.51 (s, 3 H), 3.83 (dd, J aminophenyl)- -glycero- -galacto-heptitol (5d): Yield 46 % as a
= 8.5, 6.5 Hz, 1 H), 4.19 (dd, J = 8.5, 4.5 Hz, 1 H), 4.23 (dd, J = white amorphous solid. Rf = 0.32 (hexane/EtOAc 1:1). [α]D = –36
D
L
8.5, 6.5 Hz, 1 H), 4.48 (dt, J = 8.5, 6.5 Hz, 1 H), 4.78 (dd, J = 6.0,
4.5 Hz, 1 H), 5.23 (d, J = 6.0 Hz, 1 H), 7.05 (dd, J = 5.0, 3.5 Hz,
1 H), 7.24 (dd, J = 3.5, 1.0 Hz, 1 H), 7.33 (dd, J = 5.0, 1.0 Hz, 1
H), 7.45 (t, J = 8.0 Hz, 1 H), 7.71 (dt, J = 8.0, 1.0 Hz, 1 H), 8.14
(c = 0.48, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 1.30 (s, 3 H),
1.40 (s, 3 H), 1.46 (s, 3 H), 1.52 (s, 3 H), 3.01 (dd, J = 13.0, 4.5 Hz,
1 H), 3.12 (dd, J = 13.0, 9.5 Hz, 1 H), 3.50 (dd, J = 8.0, 4.0 Hz, 1
H), 3.65–3.74 (m, 2 H), 4.23 (dd, J = 8.0, 6.5 Hz, 1 H), 4.41 (dt, J
(ddd, J = 8.0, 2.0, 1.0 Hz, 1 H), 8.40 (t, J = 2.0 Hz, 1 H) ppm. 13C = 8.0, 6.5 Hz, 1 H), 4.51 (dd, J = 6.0, 3.5 Hz, 1 H), 4.57 (dd, J =
NMR (CDCl3, 62.9 MHz): δ = 25.3, 25.5, 26.4, 26.9, 65.9, 75.4,
78.2, 80.3, 85.6, 110.1, 110.6, 113.4, 121.7, 124.3, 126.3, 127.0,
6.0, 4.0 Hz, 1 H), 6.59 (dd, J = 8.0, 1.5 Hz, 1 H), 6.70 (t, J =
1.5 Hz, 1 H), 6.75 (d, J = 8.0 Hz, 1 H), 7.09 (t, J = 8.0 Hz, 1
H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 25.1, 25.4, 26.0, 26.7,
128.7, 128.9, 135.3, 140.0, 140.4, 148.1, 154.0 ppm. IR (NaCl): ν =
˜
2987, 2959, 2938, 1641, 1528, 1349 cm–1. HRMS (ESI+) calculated 34.2, 66.0, 75.6, 80.6, 81.0, 83.4, 83.5, 109.8, 112.6, 113.7, 116.8,
for C23H25NNaO7S [M + Na]+: 482.1244; found 482.1284.
120.5, 129.3, 139.2, 145.3 ppm. IR (NaCl): ν = 3455, 3369, 3234,
˜
2991, 2965, 2922, 2852, 1626, 1607 cm–1. HRMS (ESI+) calculated
for C19H27NNaO5 [M + Na]+: 372.1781; found 372.1781.
(6E)-3,6-Anhydro-1,2:4,5-bis-O-(1-methylethylidene)-7-deoxy-7-
(2-furanyl)-7-(4-methoxyphenyl)-
L-gluco-hept-6-enitol (6f): Yield
85% as a white amorphous solid. Rf = 0.52 (hexane/EtOAc 7:3).
[α]D = –246 (c = 0.22, CHCl3). H NMR (CDCl3, 400 MHz): δ = trideoxy-D-glycero-L-galacto-deconate (5f): Yield 69% as a pale yel-
Methyl 5,8-Anhydro-6,7:9,10-bis-O-(1-methylethylidene)-2,3,4-
1
1.37 (s, 3 H), 1.38 (s, 3 H), 1.46 (s, 3 H), 1.49 (s, 3 H), 3.80 (m, 1
H), 3.81 (s, 3 H), 4.05 (dd, J = 8.0, 4.5 Hz, 1 H), 4.23 (dd, J = 8.5,
low gum. Rf = 0.55 (hexane/EtOAc 1:1). [α]D = –9 (c = 0.72,
CHCl3). H NMR (CDCl3, 400 MHz): δ = 1.26 (s, 3 H), 1.37 (s, 3
1
6.5 Hz, 1 H), 4.44 (dt, J = 8.0, 6.5 Hz, 1 H), 4.75 (dd, J = 6.0, H), 1.43 (s, 6 H), 1.70–1.83 (m, 4 H), 2.34 (t, J = 7.0 Hz, 2 H), 3.46
4.5 Hz, 1 H), 5.42 (d, J = 6.0 Hz, 1 H), 6.40 (dd, J = 3.5, 2.0 Hz,
1 H), 6.45 (dd, J = 3.5, 1.0 Hz, 1 H), 6.87 (d, J = 9.0 Hz, 2 H),
(dd, J = 8.0, 3.0 Hz, 1 H), 3.48–3.52 (m, 1 H), 3.64 (s, 3 H), 3.67
(m, 1 H), 4.20 (dd, J = 8.0, 6.5 Hz, 1 H), 4.34 (dt, J = 7.5, 6.5 Hz,
7.32 (d, J = 9.0 Hz, 2 H), 7.41 (br. s, 1 H) ppm. 13C NMR (CDCl3, 1 H), 4.56–4.62 (m, 2 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ =
62.9 MHz): δ = 25.4, 25.7, 26.4, 26.9, 55.2, 66.0, 75.8, 78.5, 80.3,
21.4, 24.9, 25.3, 25.8, 26.7, 27.7, 34.1, 51.4, 66.0, 75.6, 81.1, 81.2,
85.0, 109.8, 109.9, 110.0, 110.8, 112.9, 113.4 (2 C), 128.6, 130.7 (2
81.8, 83.4, 109.7, 112.5, 173.8 ppm. IR (NaCl): ν = 2987, 2936,
˜
C), 141.8, 151.8, 152.5, 158.5 ppm. IR (NaCl): ν = 2986, 2933,
1737 cm–1. HRMS (ESI+) calculated for C17H28NaO7 [M + Na]+:
˜
1607, 1513 cm–1. HRMS (ESI+) calculated for C24 h28O7Na [M + 367.1727; found 367.1722.
Na]+: 451.1727; found 451.1722.
Bromination of Methoxycarbonyl-exo-Glycals: Bromine (90 μL,
General Procedure for Hydrogenation of Monobromo-Substituted
exo-Glycals: Freshly prepared Raney nickel was added to a solution
of a monobromo-substituted exo-glycal 2 (0.1 mmol) in EtOAc
(10 mL). The suspension was stirred overnight under hydrogen (10
bar). After filtration through a pad of celite, the solvent was re-
moved in vacuo and the resulting product was purified by silica gel
chromatography.
1.75 mmol, 1.1 equiv.) was added to a CCl4 solution (18 mL) of 7–
11 (1.60 mmol, 1 equiv.). Et3N (177 mg, 1.75 mmol, 1.1 equiv.) was
added dropwise at 0 °C with stirring. After 24 h at room tempera-
ture, a aqueous saturated solution of NH4Cl (10 mL) was added to
the mixture. The layers were separated and the organic layer was
washed with saturated aqueous solutions of NH4Cl (2ϫ10 mL)
and Na2S2O3 (2ϫ 10 mL). The combined organic extracts were
dried with MgSO4 and filtered and the filtrate was concentrated in
vacuo. The residue was purified by silica gel chromatography.
2,5-Anhydro-3,4:6,7-bis-O-(1-methylethylidene)-1-deoxy-1-phenyl-
D-glycero-L-galacto-heptitol (5a): Yield 88% as a white amorphous
solid. Rf = 0.54 (hexane/EtOAc 7:3). [α]D = –27 (c = 0.24, CHCl3).
1H NMR (CDCl3, 250 MHz): δ = 1.30 (s, 3 H), 1.41 (s, 3 H), 1.46
(s, 3 H), 1.54 (s, 3 H), 3.11 (dd, J = 13.0, 4.5 Hz, 1 H), 3.21 (dd, J
Methyl (2Z)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-
bromo-2-deoxy-D-gulo-oct-2-enonate [12(Z)]: Yield 35% from 7(Z),
56% from 7(E) as a colourless oil. Rf = 0.55 (hexane/EtOAc 1:1).
Eur. J. Org. Chem. 2011, 6939–6951
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6947

Y. Chapleur et al.
[α]D = –141 (c = 0.61, CHCl3). H NMR (CDCl3, 250 MHz): δ = 1 H), 4.22 (dd, J = 8.5, 6.5 Hz, 1 H), 5.63 (d, J = 6.5 Hz, 1 H) ppm.
FULL PAPER
1
1.39 (s, 3 H), 1.41 (s, 6 H), 1.47 (s, 3 H), 3.76 (m, 1 H), 3.82 (s, 3
H), 4.24 (dd, J = 8.9, 6.5 Hz, 1 H), 4.32 (dd, J = 8.0, 4.5 Hz, 1 H),
4.47 (dt, J = 8.0, 6.5 Hz, 1 H), 4.84 (dd, J = 6.0, 4.5 Hz, 1 H), 5.79
(d, J = 6.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 25.3,
25.7, 26.5, 26.7, 52.8, 65.8, 75.4, 78.5, 79.8, 80.9, 86.7, 110.4, 113.6,
13C NMR (CDCl3, 100 MHz): δ = 18.9, 25.7, 27.9, 28.9, 53.2, 61.5,
69.8, 70.9, 71.2, 75.4, 99.3, 100.2, 110.5, 157.9, 163.7 ppm. IR: ν =
˜
2918, 2362, 1719, 1655, 1604 cm– 1 . HRMS (ESI+ ) for
C15H21BrNaO7 [M + Na]+: calculated: 417.0344; found 417.0328.
General Procedure for Suzuki Reactions with Bromo Methoxycarb-
onyl-exo-Glycals: A solution of the bromo methoxycarbonyl-exo-
glycal 12 or 15 (0.180 mmol) in dry 1,4-dioxane (5 mL) was added
to a boronic acid (2 equiv.) and aqueous K2CO3 (2 m, 2 equiv./
equiv. of boronic acid). The solution was stirred for 10 min, and
163.6, 167.8 ppm. IR (NaCl): ν = 2986, 2938, 1712, 1629 cm–1
.
˜
HRMS (ESI+) calculated for C15H21BrNaO7 [M + Na]+: 415.0363;
found 415.0397.
Methyl (2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-
bromo-2-deoxy-
D
-gulo-oct-2-enonate [12(E)]: Yield 52% from 7(Z), Pd(PPh3)4 (10 mg, 0.009 mmol, 0.05 equiv.) was added. The reac-
tion mixture was stirred and heated at 110 °C for 24 h. It was then
[α]D = –182 (c = 2.35, CHCl3). H NMR (CDCl3, 250 MHz): δ = allowed to cool to room temperature and concentrated to dryness
35% from 7(E) as a colourless oil. Rf = 0.50 (hexane/EtOAc 1:1).
1
1.36 (s, 3 H), 1.37 (s, 3 H), 1.42 (s, 6 H), 1.43 (s, 3 H), 3.75 (dd, J
= 9.0, 7.0 Hz, 1 H), 3.77 (s, 3 H, CO2Me), 4.20 (dd, J = 9.0, 7.0 Hz,
under reduced pressure. The residue was diluted with EtOAc
(50 mL) and washed with saturated aqueous NH4Cl (2ϫ5 mL).
1 H), 4.37 (dd, J = 8.0, 4.0 Hz, 1 H), 4.47 (dt, J = 8.0, 7.0 Hz, 1 The dried organic layer was concentrated under reduced pressure
H), 4.72 (dd, J = 6.0, 4.0 Hz, 1 H), 5.38 (d, J = 6.0 Hz, 1 H) ppm.
13C NMR (CDCl3, 62.9 MHz): δ = 25.7, 26.2, 27.0, 27.0, 53.2, 66.1,
75.6, 77.6, 83.8, 88.6, 90.8, 110.7, 114.3, 163.1, 165.6 ppm. IR
and the residue was purified by silica gel chromatography.
Methyl (2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-phenyl-D-gulo-oct-2-enonate (16a): Yield 71% as a colourless
oil. Rf = 0.5 (hexane/EtOAc 4:1). [α]D = –180 (c = 1.15, CHCl3).
1H NMR (CDCl3, 400 MHz): δ = 1.38 (s, 3 H), 1.40 (s, 3 H), 1.44
(s, 3 H), 1.50 (s, 3 H), 3.75 (s, 3 H), 3.78 (dd, J = 9.0, 7.0 Hz, 1 H),
(NaCl): ν = 2950, 2359, 1698, 1621 cm–1. HRMS (ESI+) calculated
˜
for C15H21BrNaO7 [M + Na]+: 415.0363; found 415.0361.
Methyl (2Z)-3,6-Anhydro-2-bromo-2-deoxy-4,5:7,8-bis-O-(1-methyl-
ethylidene)-
48% from 8(E), as a pale yellow oil. Rf = 0.53 (hexane/EtOAc 1:1)
[α]D = 145 (c = 0.21, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = (d, J = 6.0 Hz, 1 H), 7.27–7.40 (m, 5 H) ppm. 13C NMR (CDCl3,
1.40 [s, 3 H, C(CH3)2], 1.42 (s, 6 H), 1.48 (s, 3 H), 3.82 (s, 3 H), 100 MHz): δ = 25.8, 26.4, 27.1, 27.2, 52.2, 66.3, 76.0, 78.2, 81.4,
4.11–4.22 (m, 2 H), 4.30 (dd, J = 7.5, 4.0 Hz, 1 H), 4.52 (dt, J = 86.3, 109.3, 110.4, 113.7, 127.4, 128.2, 130.3, 134.5, 166.2,
D-manno-oct-2-enonate [13(Z)]: Yield 42% from 8(Z), 4.19 (dd, J = 8.0, 4.0 Hz, 1 H, H), 4.23 (dd, J = 9.0, 7.0 Hz, 1 H),
4.41 (dt, J = 8.0, 7.0 Hz, 1 H), 4.75 (dd, J = 6.0, 4.0 Hz, 1 H), 5.96
7.5, 5.0 Hz, 1 H), 4.96 (dd, J = 6.0, 4.0 Hz, 1 H), 5.78 (d, J =
168.4 ppm. IR (NaCl): ν = 2989, 2938, 1708, 1637, 1602 cm–1
.
˜
6.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 25.5, 25.9, HRMS (ESI+) for C21H26NaO7 [M + Na]+: calculated: 413.1571;
26.9, 27.1, 53.1, 66.6, 73.0, 78.6, 81.3, 84.0, 89.2, 110.0, 113.7, found 413.1579.
163.7, 168.2 ppm. IR (NaCl): ν = 2991, 2943, 1715, 1631 cm–1
.
˜
Methyl (2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-(3-nitrophenyl)- -gulo-oct-2-enonate (16b): Yield 68% as a
HRMS (ESI+) calculated for C15H21BrNaO7 [M + Na]+: 417.0034;
found 417.0018.
D
pale yellow amorphous solid. Rf = 0.22 (hexane/EtOAc 1:1). [α]D
1
Methyl (2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-
= –121 (c = 0.45, CHCl3). H NMR (CDCl3, 250 MHz): δ = 1.35
bromo-2-deoxy-D-ribo-oct-2-enonate [14(E)]: Yield 33% from 9(Z),
(s, 3 H), 1.39 (s, 3 H), 1.43 (s, 3 H), 1.49 (s, 3 H), 3.76 (s, 3 H),
54% from 9(E) as a pale yellow oil. Rf = 0.47 (hexane/EtOAc 1:1).
[α]D = –149 (c = 1.62, CHCl3). H NMR (CDCl3, 250 MHz): δ = (dd, J = 8.0, 4.0 Hz, 1 H), 4.41 (dt, J = 8.0, 6.5 Hz, 1 H), 4.79 (dd,
3.77 (dd, J = 8.5, 6.5 Hz, 1 H), 4.22 (dd, J = 8.5, 6.5 Hz, 1 H), 4.25
1
1.42 (s, 3 H), 1.47 (s, 3 H), 2.06 (s, 3 H), 3.81 (s, 3 H), 4.19 (dd, J
= 12.0, 3.0 Hz, 1 H), 4.36 (dd, J = 12.0, 3.0 Hz, 1 H), 4.70 (dd, J
= 6.0, 0.5 Hz, 1 H), 4.98 (td, J = 3.0, 0.5 Hz, 1 H), 5.38 (d, J =
J = 6.0, 4.0 Hz, 1 H), 5.96 (d, J = 6.0 Hz, 1 H), 7.49 (t, J = 8.0 Hz,
1 H), 7.64 (dt, J = 8.0, 1.0 Hz, 1 H), 8.11 (ddd, J = 8.0, 2.0, 1.0 Hz,
1 H), 8.21 (m, 1 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 25.3,
6.0 Hz, 1 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 20.6, 25.7, 25.8, 26.6, 26.8, 52.0, 65.8, 75.4, 77.6, 81.1, 86.4, 106.8, 110.2,
26.8, 52.7, 63.8, 79.0, 83.3, 87.2, 89.5, 113.5, 162.8, 166.1, 113.6, 122.0, 125.2, 128.6, 135.8, 136.3, 147.9, 166.8, 167.6 ppm.
169.8 ppm. IR (NaCl): ν = 2991, 2954, 1747, 1709, 1623 cm–1
.
IR (NaCl): ν = 2983, 2962, 1712, 1637, 1529, 1350 cm–1. HRMS
˜
˜
HRMS (ESI+) calculated for C13H17BrNaO7 [M + Na]+: 387.0050;
found 387.0078.
(ESI+) calculated for C21H25NNaO9 [M + Na]+: 458.1422; found
458.1444.
Methyl (2E)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-
Methyl (2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-de-
bromo-2-deoxy-
as a colourless oil. Rf = 0.30 (hexane/EtOAc 4:1). [α]D = +53 (c =
0.29, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 1.45 (s, 3 H), 1.47 [α]D = –102 (c = 0.50, CHCl3). H NMR (CDCl3, 250 MHz): δ =
D-manno-oct-2-enonate [15(E)]: Yield 37% from 11
oxy-2-(4-methoxyphenyl)-D-gulo-oct-2-enonate (16c): Yield 64% as
a pale yellow amorphous solid. Rf = 0.54 (hexane/EtOAc 1:1).
1
(s, 6 H), 1.56 (s, 3 H) 1.59 (s, 3 H), 3.50 (ddd, J = 6.0, 5.5, 5 Hz, 1
H), 3.82 (s, 3 H), 3.80–3.91 (m, 2 H), 4.05 (dd, J = 11.0, 6.0 Hz, 1
H), 4.20 (dd, J = 8.0, 6.0 Hz, 1 H), 5.16 (d, J = 6.0 Hz, 1 H) ppm.
1.36 (s, 3 H), 1.39 (s, 3 H), 1.41 (s, 3 H), 1.46 (s, 3 H), 3.74 (s, 3
H), 3.77 (m, 1 H), 3.81 (s, 3 H), 4.16 (m, 1 H), 4.22 (dd, J = 8.5,
6.5 Hz, 1 H), 4.40 (dt, J = 8.0, 6.5 Hz, 1 H), 4.73 (dd, J = 6.0,
13C NMR (CDCl3, 62.9 MHz): δ = 19.1, 26.2, 28.1, 29.0, 53.3, 61.7, 4.5 Hz, 1 H), 5.92 (d, J = 6.0 Hz, 1 H), 6.88 (d, J = 9.0 Hz, 2 H),
70.5, 71.2, 72.7, 76.2, 100.4, 102.0, 111.1, 155.0, 161.0 ppm. IR: ν
7.26 (d, J = 9.0 Hz, 2 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ =
25.4, 26.0, 26.7, 26.8, 51.8, 55.2, 65.9, 75.6, 77.8, 80.9, 85.7, 108.6,
110.0, 113.2, 113.3 (2 C), 126.3, 131.0 (2 C), 158.4, 165.1,
˜
= 2918, 2362, 1719 cm–1. HRMS (ESI+) for C15H21BrNaO7 [M +
Na]+: calculated: 417.0344; found 417.0315.
168.2 ppm. IR (NaCl): ν = 2986, 2938, 1712, 1637, 1610,
˜
Methyl (2Z)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-
1513 cm–1. HRMS (ESI+) calculated for C22H28NaO8 [M + Na]+:
443.1676; found 443.1688.
bromo-2-deoxy-D-manno-oct-2-enonate [15(Z)]: Yield 25% from 11
as a colourless oil. Rf = 0.35 (hexane/EtOAc 4:1). [α]D = +172 (c
= 0.53, CHCl3). 1H NMR (CDCl3, 400 MHz): δ = 1.46 (s, 3 H), Methyl (2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-de-
1.48 (s, 3 H), 1.56 (s, 3 H), 1.57 (s, 3 H), 3.62 (dt, J = 5.5, 8.5 Hz,
1 H), 3.83 (s, 3 H), 3.89–3.96 (m, 2 H), 4.13 (dd, J = 11.0, 5.5 Hz,
oxy-2-(2-naphthyl)-
yellow gum. Rf = 0.57 (hexane/EtOAc 1:1). [α]D = –93 (c = 0.56,
D-gulo-oct-2-enonate (16d): Yield 81% as a pale
6948
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6939–6951

C-Glycosylidenes and C-Glycosyl Compounds
1
CHCl3). H NMR (CDCl3, 400 MHz): δ = 1.35 (s, 3 H), 1.38 (s, 3 Methyl (2Z)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-de-
H), 1.44 (s, 3 H), 1.52 (s, 3 H), 3.75 (s, 3 H), 3.76 (m, 1 H), 4.19–
4.23 (m, 2 H), 4.42 (m, 1 H), 4.78 (dd, J = 6.0, 4.5 Hz, 1 H), 6.00
(d, J = 6.0 Hz, 1 H), 7.40–7.47 (m, 3 H), 7.78–7.84 (m, 4 H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 25.8, 26.4, 27.1, 27.2, 52.3, 66.3,
75.6, 78.2, 81.4, 86.3, 109.3, 110.4, 113.8, 126.1, 126.2, 127.6, 127.9,
128.5 (2 C), 129.4, 132.0, 132.9, 133.6, 166.7, 168.4 ppm. IR
oxy-2-phenyl-D-manno-oct-2-enonate (19a): Yield 51% as a pale yel-
low gum. Rf = 0.35 (hexane/EtOAc 4:1). [α]D = +245 (c = 2.43,
1
CHCl3). H NMR (CDCl3, 400 MHz): δ = 1.28 [s, 3 H, C(CH3)2],
1.47 (s, 3 H), 1.57 (s, 3 H), 1.61 (s, 3 H), 3.47 (dt, J = 6.0, 4.5 Hz,
1 H), 3.77 (s, 3 H), 3.89 (dd, J = 10.5, 6.0 Hz, 1 H), 3.98 (dd, J =
10.5, 6.0 Hz, 1 H), 3.96–4.09 (m, 2 H), 4.51 (d, J = 5.5 Hz, 1 H),
(NaCl): ν = 2986, 2932, 1710, 1637 cm–1. HRMS (ESI+) calculated 7.35–7.40 (m, 3 H), 7.49 (d, 2 H, J = 6.0 Hz) ppm. 13C NMR
˜
for C25H28NaO7 [M]+: 463.1727; found 463.1717.
(CDCl3, 100 MHz): δ = 19.2, 26.3, 28.7, 29.3, 52.6, 62.0, 70.7, 71.4,
71.8, 76.6, 100.3, 110.6, 124.8, 128.7, 128.8, 129.5, 133.0, 149.5,
Methyl (2Z)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-phenyl-D-gulo-oct-2-enonate (17a): Yield 70% as a colourless
167.7 ppm. IR (NaCl): ν = 2991, 2361, 1729, 1648 cm–1. HRMS
˜
(ESI+) for C21H26KO7 [M + K]+: calculated: 429.1310; found
429.1332.
oil. Rf = 0.45 (hexane/EtOAc 4:1). [α]D = –275 (c = 1.07, CHCl3).
1H NMR (CDCl3, 400 MHz): δ = 1.24 (s, 3 H), 1.42 (s, 3 H), 1.48
(s, 3 H), 1.49 (s, 3 H), 3.72 (s, 3 H), 3.78 (dd, J = 9.0, 7.0 Hz, 1 H),
4.24 (dd, J = 9.0, 7.0 Hz, 1 H), 4.30 (dd, J = 8.0, 4.5 Hz, 1 H), 4.53
(dt, J = 7.0, 8.0 Hz, 1 H), 4.64 (dd, J = 6.0, 4.5 Hz, 1 H), 4. 98
(d, J = 6.0 Hz, 1 H), 7.27–7.40 (m, 5 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 25.8, 25.9, 26.8, 27.2, 52.2, 66.3, 76.0, 77.7, 81.2,
87.2, 110.5, 110.8, 113.9, 127.8, 128.3, 131.0, 134.9, 163.0,
Methyl (2Z)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-(3-nitrophenyl)-D-manno-oct-2-enonate (19b): Yield 65% as a
pale yellow gum. Rf = 0.27 (hexane/EtOAc 4:1). [α]D = 92 (c =
1.74, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 1.46 (s, 3 H), 1.52
(s, 3 H), 1.55 (s, 3 H), 1.63 (s, 3 H), 3.78 (s, 3 H), 3.45–4.16 (m, 4
H), 4.61 (dd, J = 7.5, 6.0 Hz, 1 H), 4.82 (d, J = 7.5 Hz, 1 H), 7.54
(t, J = 8.0 Hz, 1 H), 7.69 (d, J = 6.5 Hz, 1 H), 8.19 (d, J = 8.0 Hz,
1 H), 8.26 (s, 1 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 16.9,
25.4, 27.0, 28.8, 49.2, 52.8, 62.2, 67.7, 71.3, 71.9, 73.6, 99.7, 113.8,
122.0, 124.6, 128.7, 129.1, 130.8, 135.4, 137.8, 148.2, 169.7 ppm.
167.1 ppm. IR (NaCl): ν = 2989, 2940, 1714, 1636, 1602 cm–1
.
˜
HRMS (ESI+) for C21H26NaO7 [M + Na]+: calculated: 413.1571;
found 413.1591.
Methyl (2E)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-phenyl-D-manno-oct-2-enonate (18a): Yield 56% as a pale yel-
IR (NaCl): ν = 2992, 2938, 1747 cm–1. HRMS (ESI+) for
˜
C21H25NNaO9 [M + Na]+: calculated: 458.1422; found 458.1448.
low gum. Rf = 0.35 (hexane/EtOAc 4:1). [α]D = 107 (c = 1.58,
Methyl (2Z)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-(4-methoxyphenyl)-D-manno-oct-2-enonate (19c): Yield 79 %
1
CHCl3). H NMR (CDCl3, 400 MHz): δ = 1.47 (s, 3 H), 1.52 (s, 3
H), 1.56 (s, 3 H), 1.62 (s, 3 H), 3.46 (dt, J = 6.0, 8.0 Hz, 1 H), 3.71
(dd, J = 11.0, 6.0 Hz, 1 H), 3.75 (s, 3 H), 3.85 (dd, J = 11.0, 6.0 Hz,
1 H), 3.93 (dd, J = 8.0, 8.0 Hz, 1 H), 4.26 (dd, J = 8.0, 6.5 Hz, 1
H), 5.59 (d, J = 6.5 Hz, 1 H), 7.25–7.30 (m, 3 H), 7.33 (d, J =
6.0 Hz, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 19.2, 26.2,
28.3, 29.2, 52.6, 61.8, 69.6, 71.5, 71.8, 76.4, 100.3, 110.7, 120.7,
as a pale yellow gum. Rf = 0.3 (hexane/EtOAc 4:1). [α]D = +173 (c
= 0.69, CHCl3). 1H NMR (CDCl3, 400 MHz): δ = 1.56 (s, 3 H),
1.62 [s, 3 H, C(CH3)2], 1.65 (s, 3 H), 1.68 (s, 3 H), 3.54 (dt, J = 6.0,
10.0 Hz, 1 H), 3.78 (s, 3 H), 3.85 (s, 3 H), 3.91–4.17 (m, 4 H), 4.55
(d, J = 5.5 Hz, 1 H), 6.89 (d, J = 8.5 Hz, 2 H), 7.43 (d, J = 8.5 Hz,
2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 16.7, 25.8, 28.3, 29.7,
52.2, 55.2, 61.8, 69.5, 71.2, 72.4, 76.0, 98.9, 110.2, 113.5, 124.6,
127.8, 128.3, 129.8, 134.4, 155.2, 168.2 ppm. IR (NaCl): ν = 2992,
˜
2944, 1716, 1628 cm–1. HRMS (ESI+) for C21H26KO7 [M + K]+:
calculated: 429.1310; found 413.1292.
130.3, 130.4, 147.7, 159.8, 167.5 ppm. IR (NaCl): ν = 2987, 2936,
˜
1727, 1654 cm–1. HRMS (ESI+) for C22H28NaO8 [M + Na]+ calcu-
lated: 443.1676; found 443.1692.
Methyl (2E)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-(4-methoxyphenyl)-D-manno-oct-2-enonate (18c): Yield 82 %
Methyl (2Z)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-(2-naphthyl)-D-manno-oct-2-enonate (19d): Yield 74% as a
as a pale yellow gum. Rf = 0.3 (hexane/EtOAc 4:1). [α]D = +95 (c
= 1.16, CHCl3). 1H NMR (CDCl3, 400 MHz): δ = 1.45 (s, 3 H),
1.49 (s, 3 H), 1.55 (s, 3 H), 1.60 (s, 3 H), 3.54 (dt, J = 6.0, 10.0 Hz,
1 H), 3.78 (s, 3 H), 3.85 (s, 3 H), 3.91–4.17 (m, 3 H), 4.25 (dd, J =
6.0, 6.0 Hz, 1 H), 5.52 (d, J = 6.0 Hz, 1 H), 6.89 (d, J = 8.5 Hz, 2
H), 7.22 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 18.8, 25.8, 27.9, 28.8, 52.1, 55.2, 61.5, 69.2, 71.3, 71.5, 76.0,
99.9, 110.2, 113.5, 120.1, 126.1, 130.6 (2 C), 130.4 (2 C), 153.7,
pale yellow gum. Rf = 0.39 (hexane/EtOAc 4:1). [α]D = +175 (c =
0.44, CHCl3). 1H NMR (CDCl3, 250 MHz): δ = 1.29 (s, 3 H), 1.47
(s, 3 H), 1.59 (s, 3 H), 1.66 (s, 3 H), 3.46 (dt, J = 10.0, 6.0 Hz, 1
H), 3.81 (s, 3 H), 3.93 (dd, J = 10.5, 10.0 Hz, 1 H), 3.99–4.12 (m,
3 H), 4.59 (d, J = 5.0 Hz, 1 H), 7.50–7.55 (m, 3 H), 7.83 (m, 3 H),
8.06 (m, 1 H) ppm. 13C NMR (CDCl3, 62.9 MHz): δ = 18.8, 26.0,
28.3, 28.9, 52.2, 61.6, 70.4, 71.1, 71.4, 76.1, 99.9, 110.3, 124.5,
126.4, 126.5, 126.6, 127.6, 127.9, 128.1, 128.5, 130.0, 133.0, 133.1,
158.8, 168.1 ppm. IR (NaCl): ν = 2991, 2942, 1718, 1609 cm–1
.
˜
HRMS (ESI+) for C22H28NaO8 [M + Na]+: calculated: 443.1676;
found 443.1696.
149.4, 167.4 ppm. IR (NaCl): ν = 2990, 2932, 2360, 1728,
˜
1653 cm–1. HRMS (ESI+) for C25H28NaO7 [M + Na]+: calculated:
463.1727; found 463.1745.
Methyl (2E)-3,7-Anhydro-4,5:6,8-bis-O-(1-methylethylidene)-2-de-
oxy-2-(2-naphthyl)-D-manno-oct-2-enonate (18d): Yield 78 % as a
General Procedure for Ester Reduction
pale yellow gum. Rf = 0.39 (hexane/EtOAc 4:1). [α]D = +43 (c =
0.57, CHCl3). 1H NMR (CDCl3, 400 MHz): δ = 1.43 (s, 3 H), 1.54
(s, 3 H), 1.58 (s, 3 H), 1.63 (s, 3 H), 3.46 (dt, J = 10.0, 6.0 Hz, 1
H), 3.71 (dd, J = 11.0, 10.0 Hz, 1 H), 3.77 (s, 3 H), 3.81 (dd, J =
8.3, 6.0 Hz, 1 H), 3.95 (dd, J = 11.0, 10.0 Hz, 1 H), 4.29 (dd, J =
8.2, 6.0 Hz, 1 H), 5.64 (d, J = 6.0 Hz, 1 H), 7.38 (d, J = 7.0 Hz, 1
H, 1 H), 7.49 (m, 2 H), 7.81–7.85 (m, 4 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 19.2, 26.2, 28.3, 29.2, 52.6, 61.8, 69.7, 71.6, 71.8,
76.4, 100.3, 110.8, 120.6, 126.4, 126.5, 127.7, 127.9, 128.0, 128.5,
DIBAL: DIBAL (2 equiv., 1.2 m in toluene) was added under argon
at –30 °C to a solution of the methoxycarbonyl-exo-glycal 7, 16a
or 17a (0.26 mmol) in dry toluene (4 mL) and the mixture was
stirred at that temperature. After completion of the reaction, water
(10 mL) was added. The resulting solid was removed by filtration
and washed with dichloromethane. The filtrate was diluted with
water and extracted with dichloromethane. After drying, the com-
bined extracts were concentrated. The residue was chromato-
graphed on a silica gel column.
128.9, 131.9, 132.9, 133.5, 155.7, 168.2 ppm. IR (NaCl): ν = 2990,
˜
2935, 1716, 1624 cm– 1 . HRMS (ESI+ ) for C2 5 H2 8 NaO7
[M + Na]+: calculated: 463.1727; found 463.1741.
LiAlH4: LiAlH4 (2 equiv.) was added under argon at 0 °C to a solu-
tion of the methoxycarbonyl-exo-glycal 7, 16a or 17a (0.26 mmol)
Eur. J. Org. Chem. 2011, 6939–6951
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6949

Y. Chapleur et al.
FULL PAPER
in dry THF (4 mL) and the mixture was stirred at that temperature.
After completion of the reaction, EtOAc (10 mL) was added and
then water (10 mL). The resulting solid was removed by filtration
and washed with EtOAc. The filtrate was diluted with water and
was extracted with EtOAc. After drying, the combined extracts
were concentrated. The residue was chromatographed on a silica
gel column.
400 MHz): δ = 25.3, 25.5, 26.5, 26.5, 61.7, 65.9, 76.4, 78.7, 80.5,
85.5, 109.7, 113.2, 113.5, 126.2, 128.0, 128.6, 138.7, 155.6 ppm. IR
(NaCl): ν = 3435, 2986, 2937, 1654 cm–1. HRMS (ESI+) for
˜
C20H26NaO6 [M + Na]+: calculated: 385.1622; found 385.1601.
(2Z)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-deoxy-2-
phenyl-D-gulo-oct-2-ene-1-itol (26): Yield 71% as a white solid; m.p.
102–105 °C. Rf = 0.2 (hexane/EtOAc 7:3). [α]D = –36 (c = 0.44,
CHCl3). 1H NMR (acetone, 250 MHz): δ = 1.30 [s, 3 H, C(CH3)2],
1.37 [s, 3 H, C(CH3)2], 1.42 [s, 3 H, C(CH3)2], 1.49 [s, 3 H, C(CH3)
2], 2.87 (br. s, 1 H, OH), 3.78 (dd, J = 8.5, 7.0 Hz, 1 H, H), 4.07
(dd, J = 8.0, 4.5 Hz, 1 H), 4.20 (dd, J = 8.5, 7.0 Hz, 1 H), 4.40 (dd,
(2E)-4,5:7,8-Bis-O-(1-methylethylidene)-2,3-deoxy-D-gulo-oct-2-en-
1-itol (20): Colourless oil. [α]D = 11 (c = 1.9, CHCl3). Rf = 0.2
(hexane/EtOAc 1:2). 1H NMR (CDCl3, 250 MHz): δ = 1.40 (s, 3
H), 1.42 (s, 3 H), 1.47 (s, 3 H), 1.57 (s, 3 H), 2.47 (d, J = 7 Hz, 1
H), 3.60 (m, 1 H), 3.85 (dd, J = 8, 7.5 Hz, 1 H), 4.06 (dd, J = 8 Hz, J = 7.0, 8.0 Hz, 1 H), 4.48 (d, J = 12.0 Hz, 1 H), 4.64 (d, J =
1 H), 4.13–4.24 (m, 4 H), 4.72 (dd, J = 7 Hz, 1 H), 5.98–6.00 (m,
12.0 Hz, 1 H), 4.90 (dd, J = 6.0, 4.5 Hz, 1 H), 4.98 (d, J = 6.0 Hz,
2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 25.4, 25.7, 26.9, 27.4,
1 H), 7.22–7.37 (m, 3 H, H-Ar), 7.56 (m, 2 H, H-Ar) ppm. 13C
63.1, 66.3, 70.3, 77.6, 77.9, 78.8, 109.5, 110.0, 127.2, 135.6 ppm. IR NMR (acetone, 62.9 MHz): δ = 25.2, 25.8, 26.5, 27.1, 60.8, 66.4,
(NaCl): ν = 3435, 2989, 1634 cm–1. HRMS (ESI+) for C H NaO
77.1, 79.6, 79.9, 85.7, 110.1, 113.2, 119.7, 127.3, 128.3, 129.7, 139.4,
˜
14 24
6
[M + Na]+: calculated: 311.1465; found 311.1474.
153.5 ppm. IR (NaCl): ν = 3450, 2956, 2360, 1654 cm–1. HRMS
˜
(ESI+) for C20H26NaO6 [M + Na]+ calculated: 385.1622; found
385.1622.
(2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-deoxy-
D
-
gulo-oct-2-ene-1-itol (21): Yield 32 % as a white solid; m.p. 74–
73 °C. [α]D = –117 (c = 0.34, CHCl3). Rf = 0.3 (hexane/EtOAc 1:2).
1H NMR [(CD3)2CO, 250 MHz]: δ = 1.33 (s, 3 H), 1.34 (s, 3 H),
General Procedure for Alcohol Acetylation: Anhydride acetic
(0.02 mL, 0.17 mmol), triethylamine (0.05 mL, 0.33 mmol) and di-
1.37 (s, 3 H), 1.42 (s, 3 H), 3.80 (dd, J = 8, 7 Hz, 1 H), 4.08 (dd, J methylaminopyridine (catalytic amount) were added at 0 °C under
= 4, 4.5 Hz, 1 H), 4.12–4.20 (m, 3 H), 4.32 (m, 1 H), 4.88 (dd, J = argon to a solution of the alcohol 20 or 25 (0.083 mmol) in dry
6, 4.5 Hz, 1 H), 5.11 (dd, J = 7, 1.5 Hz, 1 H), 5.34 (dd, J = 6, dichloromethane (5 mL). The mixture was stirred at room tempera-
1.5 Hz, 1 H) ppm. 13C NMR [(CD3)2CO, 62.9 MHz]: δ = 25.7,25.9, ture overnight. After completion of the reaction, saturated ammo-
26.9, 27.0, 58.3, 66.3, 76.9, 78.9, 79.8, 85.1, 103.1, 110.1, 113.7,
nium chloride solution (50 mL) was added and the mixture was
extracted with ethyl acetate. After drying, the combined extracts
were concentrated. The residue was chromatographed on silica gel.
158.2 ppm. IR (NaCl): ν = 3435, 1637 cm–1. HRMS (ESI+) for
˜
C14H22NaO6 [M + Na]+: calculated: 309.1309; found 309.1315.
(2Z)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-deoxy-
D
-
(2E)-1-O-Acetyl-4,5:7,8-bis-O-(1-methylethylidene)-2,3-deoxy-D-
gulo-oct-2-ene-1-itol (22): Yield 40 % as a white solid; m.p. 74– gulo-oct-2-en-1-itol (23): Yield 95% as a colourless oil. Rf = 0.5
73 °C. [α]D = –77 (c = 1.4, CHCl3). Rf = 0.4 (hexane/EtOAc 1:2).
(hexane/EtOAc 1:1). 1H NMR (CDCl3, 250 MHz): δ = 1.35 (s, 3
H), 1.39 (s, 3 H), 1.45 (s, 3 H), 1.53 (s, 3 H), 2.11 (s, 3 H), 2.14 (s,
1H NMR (CDCl3, 250 MHz): δ = 1.36 (s, 3 H), 1.43 (s, 3 H), 1.48
(s, 6 H), 3.75 (dd, J = 9, 7 Hz, 1 H), 4.05 (dd, J = 8, 4 Hz, 1 H), 3 H), 3.85 (dd, J = 9, 6 Hz, 1 H), 4.01 (dd, J = 9, 7 Hz, 1 H), 4.25
4.15–4.28 (m, 2 H), 4.35–4.45 (m, 2 H), 4.65 (dd, J = 6, 4 Hz, 1 (m, 1 H), 4.45 (dd, J = 7, 5 Hz, 1 H), 4.62 (d, J = 5 Hz, 2 H), 4.69
H), 4.93 (dd, J = 7, 4 Hz, 1 H), 5.05 (d, J = 6 Hz, 1 H) ppm. 13C
NMR (CDCl3, 62.9 MHz): δ = 25.3, 25.6, 26.5, 26.8, 57.3, 65.8,
(dd, J = 7.0, 5.0 Hz, 1 H), 5.00 (dd, J = 7, 5 Hz, 1 H), 5.77 (dd, J
= 15, 7 Hz, 1 H), 5.90 (td, J = 15, 5 Hz, 1 H) ppm. 13C NMR
(CDCl3, 62.9 MHz): δ = 20.9, 21.2, 25.4, 25.6, 26.1, 27.3, 63.7, 65.6,
70.8, 74.4, 76.3, 77.3, 109.3, 109.7, 128.8, 128.9, 170.1,170.6 ppm.
75.9, 78.2, 80.3, 85.3, 102.7, 110.0, 112.9, 155.7 ppm. IR (NaCl): ν
˜
= 3435, 2988, 1645 cm–1. HRMS (ESI+) for C14H22NaO6
[M + Na]+: calculated: 309.1309; found 309.1317.
IR (NaCl): ν = 2990, 1735, 1651 cm–1. HRMS (ESI+) for
˜
C18H28NaO8 [M + Na]+: calculated: 395.1676; found 395.1687.
(2Z)-4,5:7,8-Bis-O-(1-methylethylidene)-2,3-deoxy-2-phenyl-D-gulo-
oct-2-en-1-itol (24): Yield 55% from 16a as a colourless oil. Rf =
0.2 (hexane/EtOAc 1:1). [α]D = +59 (c = 0.86, CHCl3). H NMR
(2E)-1-O-Acetyl-3,6-anhydro-4,5:7,8-bis-O-(1-methylethylidene)-
1
2-deoxy-2-phenyl-D-gulo-oct-2-ene-1-itol (27): Yield 92% as a white
(CHCl3, 400 MHz): δ = 1.30 (s, 3 H), 1.36 (s, 3 H), 1.46 (s, 3 H),
solid; m.p. 108–110 °C. Rf = 0.3 (hexane/EtOAc 3:1). [α]D = –121
1.57 (s, 3 H), 3.56 (br. s, 1 H), 3.70 (br. s, 1 H), 3.83 (dd, J = 8.0, (c = 1.68, CHCl3). 1H NMR (acetone, 400 MHz): δ = 1.29 (s, 3 H),
7.0 Hz, 1 H), 4.00 (dd, J = 7.0, 3.5 Hz, 1 H), 4.05 (dd, J = 8.0, 1.33 (s, 3 H), 1.35 (s, 3 H), 1.41 (s, 3 H), 1.92 (s, 3 H), 3.85 (dd, J
7.0 Hz, 1 H), 4.18 (dd, J = 7.0, 8.0 Hz, 1 H), 4.40 (s, 2 H), 4.71 = 9.0, 6.5 Hz, 1 H), 4.18 (dd, J = 9.0, 6.5 Hz, 1 H), 4.35–4.45 (m,
(dd, J = 7.0, 9.5 Hz, 1 H, H), 6.05 (d, J = 9.5 Hz, 1 H) 7.22–7.36
(m, 5 H) ppm. 13C NMR (CHCl3, 400 MHz): δ = 25.2, 25.2, 26.2,
27.4, 65.7, 66.2, 69.6, 74.8, 77.0, 79.1, 108.5, 109.0, 122.3, 127.8,
2 H), 4.89 (d, J = 13.0 Hz, 1 H), 4.96 (dd, J = 6.0, 4.0 Hz, 1 H),
5.24 (d, J = 13.0 Hz, 1 H), 5.72 (d, J = 6.0 Hz, 4-H), 7.21 (t, J =
7.5 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 2 H), 7.65 (d, J = 8 Hz, 2 H) ppm.
13C NMR (acetone, 100 MHz): δ = 20.00, 25.3, 25.8, 26.5, 26.6,
63.7, 65.9, 76.4, 78.7, 80.7, 85.8, 107.8, 109.8, 113.3, 126.6, 128.3,
128.6, 128.8, 138.6, 146.5 ppm. IR (NaCl): ν = 3460, 2986, 2937,
˜
1654, 1600 cm–1. MS (ESI+) for C20H28NaO6 [M]+ calculated:
387.1778; found 387.1760.
128.4, 137.6, 157.8, 170.6 ppm. IR (NaCl): ν = 2987, 2934, 2360,
˜
1736, 1654 cm–1. HRMS (ESI+) for C22H28NaO7 [M + Na]+: calcu-
lated: 427.1727; found 427.1731.
(2E)-3,6-Anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-deoxy-2-
phenyl-D-gulo-oct-2-ene-1-itol (25): Yield 35% as a white solid; m.p.
103.3 °C. Rf = 0.2 (hexane/EtOAc 7:3). [α]D = –137 (c = 1.11,
1-O-Acetyl-3,6-anhydro-4,5:7,8-bis-O-(1-methylethylidene)-2-deoxy-
CHCl3). 1H NMR (acetone, 400 MHz): δ = 1.32 [s, 3 H, C(CH3)2], 2-phenyl-
D-threo-L-gluco-oct-1-itol (28): PtO2 (10%) was added to
1.36 [s, 3 H, C(CH3)2], 1.40 (s, 3 H), 1.45 (s, 3 H), 3.29 (br. s, 1 H), a solution of the exo-glycal 27 (0.1 mmol) in EtOAc (10 mL). The
3.84 (dd, J = 8.5, 7.0 Hz, 1 H), 4.18 (dd, J = 8.5, 7.0 Hz, 1 H), 4.26
(dd, J = 8.0, 4.0 Hz, 1 H), 4.40 (m, 1 H), 4.45 (d, J = 12.0 Hz, 1
H), 4.48 (d, J = 12.0 Hz, 1 H), 4.95 (dd, J = 6.0, 4.0 Hz, 1 H), 5.68
suspension was stirred overnight under hydrogen (40 bar). After
filtration through a pad of Celite, the solvent was removed in vacuo
and the resulting product was purified by silica gel chromatography.
(d, J = 6.0 Hz, 1 H, H), 7.18 (t, J = 7.5 Hz, 1 H), 7.32 (t, J = Yield 44% as a colourless oil. [α]D = –59 (c = 0.3, CHCl3). Rf =
7.5 Hz, 2 H), 7.73 (d, J = 7.5 Hz, 2 H) ppm. 13C NMR (acetone, 0.3 (hexane/EtOAc 3:1). 1H NMR (acetone, 400 MHz): δ = 1.17 (s,
6950
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Eur. J. Org. Chem. 2011, 6939–6951

C-Glycosylidenes and C-Glycosyl Compounds
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3 H), 1.32 (s, 3 H), 1.37 (s, 3 H), 1.47 (s, 3 H), 1.87 (s, 3 H), 3.51
(dt, J = 9.5, 4.0 Hz, 1 H), 3.59 (dd, J = 8.0, 3.5 Hz, 1 H), 3.73 (t,
J = 8.5, 7.0 Hz, 1 H), 3.92 (dd, J = 7.1, 4.0 Hz, 1 H), 4.14 (dd, J
= 8.5, 7.0 Hz, 1 H), 4.29–4.40 (m, 3 H), 4.62 (dd, J = 11.0, 9.5 Hz,
1 H), 4.71 (dd, J = 6.0, 3.5 Hz, 1 H), 7.24 (t, J = 7.5 Hz, 1 H), 7.34
(t, J = 7.5, 8.0 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR
(acetone, 100 MHz): δ = 20.2, 24.6, 25.3, 25.8, 26.5, 44.4, 66.1,
66.4, 76.2, 81.2, 81.3, 82.7, 84.1, 109.4, 112.2, 127.3, 128.6,129.1,
139.6, 170.3 ppm. IR (NaCl): ν = 2923, 2852, 2360, 1739,
˜
1654 cm–1. HRMS (ESI+) for C22H30NaO7 [M + Na]+: calculated:
429.1884; found 428.1897.
Supporting Information (see footnote on the first page of this arti-
1
1
cle): H and 13C NMR spectra, NOESY NMR spectra, H NMR
spectra of crude reaction mixtures, NOEs observed, proposed
mechanism, ORTEP diagrams.
Acknowledgments
We thank F. Dupire and B. Fernette for technical assistance.
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Published Online: October 6, 2011
Eur. J. Org. Chem. 2011, 6939–6951
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6951