Domino reactions of 5-deoxy-5-iodo-d-xylo- and -l-arabinofuranose derivatives with organometallic reagents. A way towards polyfunctionalized building-blocks

Article abstract of DOI:10.1016/j.tet.2010.04.013

Domino reactions involving metal-halogen exchange, furanose ring-opening and nucleophilic addition from 3-O-benzyl-5-deoxy-5-iodo-1,2-O-isopropylidene-α-d-xylofuranose and the epimeric l-arabino derivative with various organometallic reagents are reported. In anhydrous conditions, with a large excess of organolithium or Grignard reagents, vicinal diols are obtained with good yields and a fair diastereoselectivity. Interestingly, with α-trimethylsilyl organolithium reagents, the fragmentation of the furanose ring to the substituted pent-4-enal is followed by a Peterson olefination giving dienic compounds in a four-step one-pot process.

Full text of DOI:10.1016/j.tet.2010.04.013

Tetrahedron 66 (2010) 4109–4114
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Domino reactions of 5-deoxy-5-iodo-
D
-xylo- and -
L
-arabinofuranose derivatives
with organometallic reagents. A way towards polyfunctionalized building-blocks
*
*
Ariane Bercier, Richard Plantier-Royon , Charles Portella
Universite´ de Reims Champagne-Ardenne, Institut de Chimie Mole´culaire de Reims (I.C.M.R.), CNRS UMR 6229, U.F.R. Sciences Exactes et Naturelles,
BP 1039, 51687 Reims Cedex 2, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Domino reactions involving metal–halogen exchange, furanose ring-opening and nucleophilic addition
Received 16 November 2009
Received in revised form 1 April 2010
Accepted 1 April 2010
from 3-O-benzyl-5-deoxy-5-iodo-1,2-O-isopropylidene-a-D-xylofuranose and the epimeric L-arabino
derivative with various organometallic reagents are reported. In anhydrous conditions, with a large
excess of organolithium or Grignard reagents, vicinal diols are obtained with good yields and a fair
Available online 7 April 2010
diastereoselectivity. Interestingly, with a-trimethylsilyl organolithium reagents, the fragmentation of the
furanose ring to the substituted pent-4-enal is followed by a Peterson olefination giving dienic
compounds in a four-step one-pot process.
Keywords:
Domino reactions
Ó 2010 Elsevier Ltd. All rights reserved.
D
-xylofuranosides
Metal–halogen exchange
Organometallic reagents
Peterson olefination
1. Introduction
derivative 2 surprisingly afforded the target pent-4-enal 3, isolated
as its benzyl oxime ether 4 (Scheme 1). The difference in reactivity
As part of a broad research program devoted to the valorization
of wheat hemicelluloses, we have been interested in the chemical
of these two iodo pentofuranoses, obviously related to the stereo-
chemistry at C-4, was studied in more details.1a
transformation of their two main components,
D-xylose and L-
arabinose, into higher added-value products.1 On the other hand,
domino reactions have become a very attractive tool for enhancing
synthetic efficiency with the formation of several bonds in a single
step.2 Such a strategy is particularly interesting in carbohydrate
chemistry, due to the complexity and the high degree of func-
tionalization of these molecules.3
O
O
O
I
BnO
O
1
activated
zinc
BnO OH
O
THF/H2O
O
O
I
3
4:1
In previous reports,1 we have described the zinc-mediated ring
BnO
BnO-NH2
THF
N
2
opening (Vasella–Bernet reaction) of 5-deoxy-5-iodo-
anosides and - -arabinofuranosides, bearing different protecting
groups at C-2 and C-3 positions, to produce the same -un-
saturated aldehyde whatever the starting pentose. Our results have
shown that reaction of the -xylo-derived iodo compound 1 with
D-xylofur-
OBn
L
g,d
BnO OH
D
4
activated zinc was unsuccessful whatever the reaction conditions
(Scheme 1). Compound 1 proved to be so inert that even the simple
reduction of the carbon–iodine bond, which was previously
observed using the Zn/Ag–graphite complex,4 did not occur. In
Scheme 1.
As the zinc-mediated reductive elimination was not effective
with both these epimeric 5-iodo pentofuranoses, we have
attempted to induce the furanose ring-opening with n-butyl-
lithium, via a halogen–metal exchange. Such a reaction has been
contrast, the same reaction carried out on the epimeric L-arabino
described with halogenated
sides,6 but was never reported in
The results observed led us to a more general study of the domino
D
-glucopyranosides5 or
-xylose and -arabinose series.
D-ribofurano-
* Corresponding authors. Tel.: þ33 326913308; fax: þ33 326913166; e-mail
addresses: richard.plantier-royon@univ-reims.fr (R. Plantier-Royon), charles.
portella@univ-reims.fr (C. Portella).
D
L
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.013

4110
A. Bercier et al. / Tetrahedron 66 (2010) 4109–4114
reaction involving metal–halogen exchange–ring opening–alkyl-
ation with organolithium and organomagnesium reagents. In
M
O
OBn
OH
H
re-face
attack
O
H
OH
R
addition, we have considered reactions with
a-silylated organo-
lithium reagents to extend the domino character of these trans-
formations. We report here a full account of this work.
BnO
H
H
R-M
syn-configuration
Figure 1. Major diastereomer according to -chelated model.
2. Results and discussion
a
The iodinated 1,2-O-isopropylidene D-xylo derivative 1 did not
The domino zinc-mediated reductive elimination–Barbier-type
reaction of -iodoglycosides with unsaturated alkyl halides was
react under the reported experimental conditions (n-BuLi, 1 equiv,
THF, ꢀ78 ꢁC),6 and remained inert at a temperature of ꢀ20 ꢁC. At
0 ꢁC, compound 1 was partially transformed (48% conversion) into
diol 5 with 33% overall yield as an inseparable 7/1 mixture of
diastereomers (Scheme 2 and Table 1, entry 1). The reductive
elimination occurred and the released carbonyl group was trapped
in situ by the organolithium reagent. Interestingly, treatment under
u
widely developed by Madsen3,11 and others.12 These reactions be-
ing performed in aqueous THF, the nucleophilic addition step
proceeds via a non-chelated Felkin–Anh transition state,13 giving
selectively the anti-epimer.11a,b Our domino transformation with
organolithium reagents may be considered as a complementary
methodology, justifying its optimisation and extension to other
organometallics.
the same conditions of the iodinated methyl
protected with a MEM group at the 2-position, led to the pent-4-
enal without subsequent alkylation (Scheme 2). Several
D
-xylofuranoside 6,1b
Using a 2.5fold-excess of n-butyllithium, conversion of 1 was
completed and diol 5 was obtained in 64% yield (Table 1, entry 2).
Addition of an excess of O-benzyl hydroxylamine hydrochloride
and 4 Å molecular sieves to the reaction mixture before the work-
up showed the presence of remaining pent-4-enal 3 isolated as
its O-benzyl oxime ether 4 in 15% yield (ratio 5/4: 80:20). This in-
complete transformation of the intermediate enal could be due to
the presence of two electrophilic by-products in the reaction me-
dium: 1-iodobutane and acetone. Using 3.5 equiv of n-BuLi in THF
at 0 ꢁC, the overall yield for compound 5 eventually raised to 88%
with the same diastereomeric ratio (7:1) (Table 1, entry 3). In the
same reaction conditions, two other commercially available orga-
nolithium reagents (MeLi and PhLi) were successfully used to afford
the corresponding diols 8,9 as inseparable mixtures of
diastereomers in excellent yields (Table 1, entries 4 and 5). The
7
attempts for a selective ring-opening of compound 1 without
a subsequent alkylation by using more hindered organolithium
reagents such as sec-BuLi or tert-BuLi failed.
O
OR1
OR2
I
BnO
1
(R1,R2 = CMe2)
6
(R1 = Me, R2 = MEM)
Bu-Li
THF, 0 °C
8 h
Bu
O
OH
BnO OMEM
epimeric 5-iodo L-arabino derivative 2 reacted similarly (Table 1,
entry 6), and the transformation can therefore be applied to
a mixture of epimers.
BnO OH
5
7
Scheme 2.
To the best of our knowledge, the tandem reductive ring-
opening–alkylation of 5-deoxy-5-iodo-pentofuranosides with
Grignard reagents was not reported so far. However, it has to be
mentioned that a somewhat similar transformation was previously
Table 1
Tandem reaction of the 5-deoxy-5-iodo pentofuranoses 1,2 with organolithium
reagents
described starting from 1,2:3,4-di-O-isopropylidene-a-D-gal-
R
actopyranose derivatives bearing an heteroarylsulfanyl group at the
primary position to afford vinyl sulfides in a one-step sequence
with acceptable yields.10 As a wide range of organomagnesium
reagents are commercially available, it was relevant to extend the
scope of the domino transformation of 5-deoxy-5-iodo-pentofur-
R-Li
O
OH
O
*
I
THF, 0 °C
8 h
O
BnO
1-2
BnO OH
5, 8-9
Entry
Starting material
R-Li
Product
dra
Yieldb (%)
anosides with Grignard reagents.
A
larger excess of
organomagnesium reagents was required for a complete conver-
sion (Table 2, entries 1–3). Using allylmagnesium bromide as
a model, best results were obtained in anhydrous diethyl ether at
1
2
3
4
5
6
1
1
1
1
1
2
n-BuLi (1 equiv)
n-BuLi (2.5 equiv)
n-BuLi (3.5 equiv)
MeLi (3.5 equiv)
PhLi (3.5 equiv)
n-BuLi (3.5 equiv)
5
5
5
8
9
5
7:1
7:1
7:1
4:1
6:1
6:1
33c
64d
88
90
90
83
Table 2
Tandem reaction of 5-deoxy-5-iodo
D
-xylofuranose 1 with Grignard reagents
a
Determined by 1H NMR and HPLC.
Isolated yield, mixture of diastereomers.
Conversion: 48%.
b
c
R
R-MgX
O
OH
*
O
O
I
BnO
d
Intermediate aldehyde isolated (15%) as its benzyl oxime.
Et2O, 0 °C
8 h
BnO OH
8-11
1
Hence, the fast nucleophilic addition occurring in the case of
compound 1 was probably due to a -chelation of lithium by the
oxygen atoms of the generated alcoholate and of the carbonyl
group,7 enhancing the electrophilicity of the latter. Such a
-che-
lation should also control the diastereoselectivity of the nucleo-
philic addition (Fig. 1), as already reported for similar situation of
organometallic additions on aldose derivatives.8–10 Thus the syn-
configuration (R for the new stereogenic center) was assigned to
the major diastereomer. Further experimental observations cor-
roborate this assignment (vide infra).
a
Entry
R-MgX
Conversion (%)
Product
dra
Yieldb (%)
1
2
3
4
5
6
AllMgBr (2.8 equiv)
AllMgBr (4 equiv)
AllMgBr (5.5 equiv)
MeMgCl (5.5 equiv)
PhMgBr (5.5 equiv)
i-PrMgCl(5.5 equiv)
44
78
98
94
95
96
10
10
10
8
9
11
6:1
6:1
6:1
4:1
6:1
4:1
33
69
91
88
87
92
a
a
Determined by 1H NMR and HPLC.
Isolated yield, mixture of diastereomers.
b

A. Bercier et al. / Tetrahedron 66 (2010) 4109–4114
4111
0 ꢁC with 5.5 equiv of the Grignard reagent leading to an in-
separable mixture of the expected diol 10 with 91% yield and a 6:1
diastereomeric ratio. Under these optimal conditions, the same
transformation was achieved with several other organomagnesium
reagents (Table 2, entries 4–6). As observed by HPLC and 1H NMR
analyses, the major diastereoisomers obtained from PhMgBr and
CH3MgCl were identical to the ones derived from reactions with the
corresponding organolithium reagents.
conditions. A better overall yield (78%) of diene 14 was obtained
when the transformation was conducted with 2.4 equiv of the lith-
ium reagent and without isolation of the intermediate 13. Under the
same conditions, the lithium reagent derived from methyl trime-
thylsilylacetate did not react with 1, probably because the metal–
halogen exchange failed.
Treatment of
1
with
a
-lithio-
a
-trimethylsilyl dithioacetals
-unsaturated ketene
(2.4 equiv) led directly to the expected
g
In order to further support the predicted stereochemical out-
come of the reaction, we took advantage of the possibility of iso-
lating by HPLC a pure sample of the major diastereomer 11maj of
the diol 11 resulting from the reaction with i-PrMgCl. Attempts to
obtain X-ray diffraction data from 11maj or from the corresponding
p-nitrobenzoyl ester were unsuccessful. Derivatization into a cyclic
acetal was expected to afford stereochemical information via the
observed coupling constants. Unfortunately, the 1H NMR spectrum
of the isopropylidene derivative from 11maj in various solvents
(CDCl3, benzene-d6, acetone-d6) exhibited an overlap between
protons H3, H4 and H5, preventing any interpretation regarding the
configuration. In order to circumvent this problem, the cyclic car-
bonate 12 was prepared from 11maj.14 The resolution of its 1H NMR
dithioacetals 15,16 in 52–86% yield, as a result of a four-step domino
reaction (Scheme 4). Under the same experimental conditions,
compound 16 was achieved in 82% yield starting from the 5-deoxy-
5-iodo
L-arabinofuranoside 2. A similar reaction sequence took
place when compound 1 was reacted with a
a
-lithio- -trime-
a
thylsilyl thioether, to afford the corresponding enol thioether 17 in
66% yield (Scheme 4).
MeS SMe
OH SMe
Me3Si
Li
1
1
SMe
52%
OBn
15
86%
82%
OH S
spectrum allowed to discriminate protons H4 (
d
¼4.36 ppm) and H5
S
S
Li
¼4.28 ppm) and to read their coupling constant (3J¼4.1 Hz).
S
(d
Me3Si
OBn
Owing to the discrepancies of literature NMR data for similar cyclic
carbonates,15 a reliable assignment could not be deduced by
a simple comparison of the coupling constants. Thus, correlation
was attempted between our experimental result and those result-
ing from molecular modelling. Optimization16 of the conforma-
tional structure of syn-12 affords the calculated dihedral angle H4–
C4–C5–H5¼ꢀ111ꢁ and a coupling constant Jsyn¼3.6 Hz (Fig. 2).
Similar modelisation for anti-12 affords a dihedral angle of 28.9ꢁ
and Janti¼5.7 Hz. The observed coupling constant (J¼4.1 Hz) cor-
roborates the anticipated syn-configuration for the major di-
astereomer (Fig. 1).
16
2
1
OH
PhS Li
66%
SPh
OBn
17
Scheme 4.
3. Conclusions
A three-step domino transformation of 5-deoxy-5-iodo-pento-
furanoside derivatives, involving a halogen–metal exchange with
an organolithium or magnesium reagent, a b-fragmentation and
a nucleophilic addition was achieved, leading to high yields of 1-
vinyl-3-alkyl(aryl)-propanetriol derivatives. The last step is fairly
stereoselective towards the (R)-diastereomer resulting from a che-
lated–Cram type transition state model. In contrast to the reductive
elimination using zinc metal, which was previously shown to work
3J4,5 (measured) = 4.1 Hz
5
O
3
4
3J4,5 (calculated) = 3.6 Hz
O
O
BnO
syn-12
3
Figure 2. Measured and calculated J4,5 for the cyclic carbonate 12.
only with 3-O-benzyl-5-deoxy-5-iodo-1,2-O-isopropylidene-
binofuranose, this organometallic-mediated transformation works
with the corresponding -xylo epimer as well, and thus could be
L-ara-
Finally, the reaction of 5-deoxy-5-iodopentofuranosides with a-
D
silyl organolithium reagents was investigated in order to attempt
a domino reaction including a further olefination step. Indeed, in that
case, a Peterson reaction should occur after addition on the in-
termediate aldehyde. When 1 was treated with a commercially
available (trimethylsilyl)methyllithium solution (2 equiv) in THF at
0 ꢁC, the domino sequence stopped at the nucleophilic addition
stage, giving the vicinal diol 13 in 69% yield and a high di-
astereomeric excess (Scheme 3). Compound 13 was easily and
quantitatively converted into the 1,5-diene 14 under acidic
applied to the mixture of epimers. Despite their generality and the
high yields, the preparative interest of these transformations is
somewhat limited by the obtention of a mixture of diastereomers
most of them being inseparable. In contrast,
a-silylated organo-
lithium reagents afforded, by means of a further Peterson step,
diastereo- and enantiopure functionalized 1,5-dienes, which may
be viewed as interesting new enantiopure building-blocks.
4. Experimental
OH
4.1. General methods
SiMe3
BnO
OH
13
All air- and moisture-sensitive reactions were carried out under
an argon atmosphere. THF and Et2O were distilled over Na/benzo-
phenone before use. All commercially available chemicals were
used as received unless otherwise noted. Commercial organo-
lithium reagents (Acros) were titrated before use with diphenyl-
acetic acid in THF.17 Commercial Grignard reagents (Acros, Aldrich)
were titrated before use in THF against menthol in the presence of
1,10-phenanthroline.17
Me3Si
Li
2 equiv
THF, 0 °C
THF
H2SO4
quant.
69%
Me3Si
2.4 equiv
THF, 0 °C
Li
1)
OH
1
2) aq H2SO4
78%
OBn
14
All reported NMR spectra were recorded with a Bruker AC 250.
Scheme 3.
Chemical shifts are reported as
d values relative to CHCl3 peak

4112
A. Bercier et al. / Tetrahedron 66 (2010) 4109–4114
defined at
d
¼7.27 (1H NMR) or
d
¼77.0 (13C NMR). IR spectra were
3406, 3078, 2960, 2904, 2838, 1363, 1071; 1H NMR (250 MHz,
CDCl3): 7.35–7.26 (m, 5H, C6H5), 5.92–5.86 (m, 1H, H-5), 5.42–5.33
recorded using NaCl film or KBr pellets on an AVATAR 320 FT-IR
(Nicolet) spectrometer. Optical rotations were recorded using
a Perkin–Elmer 241 polarimeter with a thermally jacketed 10 cm
cell in the specified solvents. HRMS was performed on a Q-TOF
Micro micro-mass positive ESI (CV¼30 V) instrument. Optical
rotations were determined at 23 ꢁC on a Perkin–Elmer Model 241
polarimeter. Analytical TLC was performed on Merck 60 PF254 silica
gel pre-coated plates. Preparative flash silica gel chromatography
d
(m, 2H, H-6), 4.53 (d, 1H, J¼11.7 Hz, CHPh), 4.31 (d, 1H, J¼11.6 Hz,
CHPh), 4.01–3.83 (m, 2H, H-2, H-4), 3.32 (br s, 1H, H-3), 2.86 (br s,
1H, OH), 2.64 (br s, 1H, OH), 1.13 (d, 3H, J¼10.3 Hz, CH3); 13C NMR
(62.9 MHz, CDCl3):
d 138.2 (Cq arom.), 135.5, 135.4 (C-5), 129.1–
128.2 (CH arom.), 120.9, 120.8 (C-6), 82.2, 81.3 (C-3), 70.9 (C-2), 70.8
(C-4), 69.0, 68.0 (CH2Ph), 23.5, 20.5 (CH3); ESIHRMS calcd for
C13H18O3Na ([MþNa]þ) 245.1154; found 245.1154.
was performed using Merck Kieselgel 60 (40–63 mm). Petroleum
ether refers to the fraction with bp 40–65 ꢁC. Gas chromatography
(GC) analyses were performed on a polydimethylsiloxane HP ultra I
column and a flame ionisation detector. High-performance liquid
chromatography (HPLC) separations (analytical or semi-
4.3.3. (2R, 3S)-3-Benzyloxy-1-phenylpent-4-ene-1,2-diol (9) (mix-
ture of diastereomers 6:1). Pale yellow oil. Yield: 90%. IR (film) nmax
cmꢀ1: 3426, 3083, 3058, 3022, 2971, 2909, 2863, 1204, 1117, 1055,
1030; 1H NMR (250 MHz, CDCl3þD2O):
d 7.55–7.23 (m, 10H, C6H5),
preparative) were performed on a LiChrospher Si60 (5
umn with mixtures hexane/ethyl acetate as eluents.
m
m) col-
5.92–5.85 (m, 1H, H-4), 5.39–5.20 (m, 2H, H-5), 4.80 (d, 0.15H,
J¼5.6 Hz, H-1 minor dia.), 4.70 (d, 0.85H, J¼4.8 Hz, H-1 major dia.),
4.62 (d, 1H, J¼11.4 Hz, CHPh), 4.29 (d, 1H, J¼11.4 Hz, CHPh), 3.87–
3.82 (m, 0.15H, H-3 minor dia.), 3.79 (dd, 0.85H, J¼7.9, 4.2 Hz, H-3
major dia.), 3.64–3.58 (m, 1H, H-2); 13C NMR (62.9 MHz,
Compounds 1, 2, 4, 6 and 7 were previously reported.1
4.2. General procedure for the reactions with organolithium
reagents
CDCl3þD2O):
d 141.4, 138.2 (Cq arom.), 135.4 (C-4), 129.1–126.9
(CH arom.), 120.6 (C-5), 80.8, 80.7 (C-2), 78.1, 76.7 (C-3), 74.3 (C-1),
71.0, 69.9 (CH2Ph); ESIHRMS calcd for C18H20O3Na ([MþNa]þ)
307.1310; found 307.1304.
The 5-deoxy-5-iodo pentofuranose 1 or 2 (0.3 g, 0.77 mmol) was
dissolved in freshly distilled THF (3 mL) and the mixture was stirred
under argon. The organolithium reagent (2.7 mmol, titrated solu-
tions in Et2O) was then added dropwise at 0 ꢁC. After total disap-
pearance of the starting material (TLC monitoring, 7:3 petroleum
ether/EtOAc), the reaction mixture was poured in Et2O (20 mL) and
extracted twice with a saturated NH4Cl solution (2ꢂ5 mL) and
water (10 mL). The organic layer was dried over anhydrous Na2SO4
and the solvent was removed under vacuum. The residue was then
purified by flash chromatography on silica gel (7:3 petroleum ether/
EtOAc) to afford the pure unsaturated diol as a mixture of in-
separable diastereomers.
4.3.4. (3S, 4S)-3-Benzyloxyocta-1,7-diene-4,5-diol (10) (mixture of
diastereomers 6:1). Colourless oil. Yield: 91%. IR (film) nmax cmꢀ1
:
3442, 3068, 3032, 2976, 2925, 1199, 1061; 1H NMR (250 MHz,
CDCl3): 7.39–7.27 (m, 5H, C6H5), 5.79–5.74 (m, 2H, H-2, H-7), 5.42–
d
5.33 (m, 2H, H-1), 5.13–5.05 (m, 2H, H-8), 4.67–4.63 (m, 1H, CHPh),
4.37 (d, 0.15H, J¼11.6 Hz, CHPh minor dia.), 4.32 (d, 0.85H,
J¼11.6 Hz, CHPh major dia.), 4.07 (dd, 0.85H, J¼8.0, 6.3 Hz, H-3
major dia.), 4.02 (dd, 0.15H, J¼7.9, 4.1 Hz, H-3 minor dia.), 3.72–3.64
(m, 1H, H-5), 3.48–3.42 (m, 1H, H-4), 2.95 (d, 1H, J¼3.9 Hz, OH), 2.66
(br s, 1H, OH), 2.34–2.25 (m, 2H, H-6); 13C NMR (62.9 MHz, CDCl3):
4.3. General procedure for the reactions with
organomagnesium reagents
d 138.2, 138.1 (Cq arom.), 135.3, 135.2 (C-2), 129.1–127.5 (CH arom.),
121.1, 120.2 (C-1), 118.4, 118.2 (C-8), 82.8, 80.6 (C-4), 76.1, 74.9 (C-3),
72.0, 71.1 (C-5), 71.0 (CH2Ph), 39.2, 38.1 (C-6); ESIHRMS calcd for
C15H20O3Na ([MþNa]þ) 271.1310; found 271.1315. Anal. Calcd for
C15H20O3: C, 72.56; H, 8.12%. Found: C, 72.52; H, 7.91%.
The 5-deoxy-5-iodo pentofuranose 1 (0.3 g, 0.77 mmol) was
dissolved in freshly distilled Et2O (4 mL) and the mixture was
stirred under argon. The Grignard reagent (4.24 mmol, titrated
solutions in Et2O) was then added dropwise at 0 ꢁC. After total
disappearance of the starting material (TLC monitoring, 7:3 petro-
leum ether/EtOAc), the reaction mixture was poured in Et2O
(20 mL) and extracted twice with a saturated NH4Cl solution
(2ꢂ5 mL) and water (10 mL). The organic layer was dried over
anhydrous Na2SO4 and the solvent was removed under vacuum.
The residue was then purified by flash chromatography on silica gel
(7:3 petroleum ether/EtOAc) to afford pure unsaturated diols as
mixtures of inseparable diastereomers, except for compound 11.
4.3.5. (3S, 4S)-3-Benzyloxy-6-methylhept-1-ene-4,5-diol (11) (mix-
ture of diastereomers 6:1). Colourless oil. Yield: 92%. 1H NMR
(250 MHz, CDCl3):
d
7.38–7.27 (m, 5H, C6H5), 6.05 (ddd, 0.15H, J¼17.4,
10.1, 8.0 Hz, H-2 minor dia.), 5.91–5.71 (m, 0.85H, H-2 major dia.),
5.52–5.38 (m, 2H, H-1), 4.65 (d, 0.15H, J¼11.7 Hz, CHPh minor dia.),
4.64 (d, 0.85H, J¼11.7 Hz, CHPh major dia.), 4.35 (d, 0.85H, J¼11.5 Hz,
CHPh major dia.), 4.33 (d, 0.15H, J¼11.5 Hz, CHPh minor dia.), 4.07
(dd, 0.15H, J¼7.8, 2.6 Hz, H-3 minordia.), 3.95 (t, 0.85H, J¼7.4 Hz, H-3
major dia.), 3.79–3.70 (m, 0.15H, H-5 minor dia.), 3.61 (dd, 0.85H,
J¼6.6, 3.6 Hz, H-5 major dia.), 3.39 (dd, 0.15H, J¼12.8, 6.4 Hz, H-4
minor dia.), 3.18 (t, 0.85H, J¼7.4 Hz, H-4 major dia.), 2.84 (d, 0.85H,
J¼3.6 Hz, OH major dia.), 2.57 (d, 0.15H, J¼8.2 Hz, OH minor dia.),
2.46 (d, 0.85H, J¼7.5 Hz, OH major dia.), 2.25 (d, 0.15H, J¼12.6 Hz, OH
minor dia.), 1.85–1.80 (m, 1H, H-6), 0.99–0.87 (m, 6H, H-7).
4.3.1. (3S, 4S)-3-Benzyloxynon-1-ene-4,5-diol (5) (mixture of di-
astereomers 7:1). Colourless oil. Yield: 88%. IR (film) nmax cmꢀ1
:
3432, 3083, 2955, 2930, 2853, 1378, 1204, 1061; 1H NMR (250 MHz,
CDCl3): 7.37–7.26 (m, 5H, C6H5), 5.86–5.80 (m, 1H, H-2), 5.41–5.27
d
(m, 2H, H-1), 4.57 (d, 1H, J¼11.6 Hz, CHPh), 4.32 (d, 1H, J¼11.6 Hz,
CHPh), 3.87 (dd, 1H, J¼14.0, 7.5 Hz, H-3), 3.61–3.55 (m, 1H, H-5),
3.50–3.46 (m, 0.12H, H-4 minor dia.), 3.42–3.38 (m, 0.88H, H-4
major dia.), 2.97 (br s, 1H, OH), 2.91 (br s, 1H, OH), 1.67–1.15 (m, 6H,
4.3.6. (3S,
4S,
5R)-3-Benzyloxy-6-methylhept-1-ene-4,5-diol
(11maj). The major diastereomer was separated by semi-
preparative HPLC (eluent: hexane/EtOAc 75:25). White powder,
mp 59 ꢁC; [
23
CH2), 0.92–0.89 (m, 3H, CH3); 13C NMR (62.9 MHz, CDCl3):
d
138.1
a
]
ꢀ4 (c 0.60, CHCl3); 1H NMR (250 MHz, CDCl3):
D
(Cq arom.), 135.4 (C-2), 129.0–127.5 (CH arom.), 121.1, 120.1 (C-1),
82.6, 81.1 (C-4), 76.2, 75.5 (C-3), 73.2, 71.6 (C-5), 70.8, 70.6 (CH2Ph),
34.3, 32.9, 28.4, 23.1 (CH2), 14.5 (CH3); ESIHRMS calcd for
C16H24O3Na ([MþNa]þ) 287.1623; found 287.1631.
d 7.33–7.29 (m, 5H, C6H5), 5.84–5.71 (m, 1H, H-2), 5.44–5.38 (m, 2H,
H-1), 4.64 (d, 1H, J¼11.4 Hz, CHPh), 4.34 (d, 1H, J¼11.4 Hz, CHPh),
3.94 (t, 1H, J¼7.3 Hz, H-3), 3.66–3.60 (m, 1H, H-5), 3.18 (t, 1H,
J¼7.3 Hz, H-4), 2.88 (br s, 1H, OH), 2.49 (d, 1H, J¼7.2 Hz, OH), 1.85–
1.80 (m, 1H, H-6), 0.97 (d, 3H, J¼13.5 Hz, H-7), 0.88 (d, 3H,
4.3.2. (3S, 4S)-4-Benzyloxyhex-5-ene-2,3-diol (8) (mixture of
J¼13.5 Hz, H-7); 13C NMR (62.9 MHz, CDCl3):
d 138.4 (Cq arom.),
diastereomers 4:1). Pale yellow oil. Yield: 90%. IR (film) nmax cmꢀ1
:
135.1 (C-2), 129.2–128.5 (CH arom.), 121.3 (C-1), 83.4 (C-4), 76.6

A. Bercier et al. / Tetrahedron 66 (2010) 4109–4114
4113
(C-5), 73.1 (C-3), 71.1 (CH2Ph), 31.9 (C-6), 19.6, 19.5 (C-7); ESIHRMS
(250 MHz, CDCl3):
d
7.38–7.26 (m, 5H, C6H5), 5.85 (d, 1H, J¼8.6 Hz,
calcd for C15H22O3Na ([MþNa]þ) 273.1467; found 273.1474. Anal.
H-1), 5.71 (ddd, 1H, J¼17.0, 10.5, 7.3 Hz, H-4), 5.37–5.26 (m, 2H, H-
5), 4.57 (d, 1H, J¼11.7 Hz, CHPh), 4.53 (dd, 1H, J¼8.6, 7.3 Hz, H-2),
4.38 (d, 1H, J¼11.7 Hz, CHPh), 3.65 (t, 1H, J¼7.3 Hz, H-3), 2.94–2.63
(m, 5H, SCH2, OH), 2.10–1.95 (m, 2H, CH2); 13C NMR (62.9 MHz,
Calcd for C15H22O3: C, 71.97; H, 8.86%. Found: C, 71.61; H, 9.29%.
4.4. Reaction with a-lithiotrimethylsilyl reagents
CDCl3):
d 138.1 (Cq arom.), 134.3 (C-4), 133.4 (SCS), 128.9 (C-1),
To a solution of the silylated reagent (1.85 mmol) in anhydrous
THF (1.5 mL) was added at 0 ꢁC under argon a solution of n-butyl-
lithium (2.4 equiv). After stirring for 2 h at 0 ꢁC, a solution of the
iodofuranose 1 (or 2) in THF (1.5 mL) was slowly added. The mix-
ture was left at rt until completion of the reaction (TLC monitoring;
petroleum ether/EtOAc 70/30). Diethyl ether (15 mL) was added
and the resulting mixture was washed with a saturated aqueous
NH4Cl solution (2 mL) then with water (2ꢂ2 mL). The organic layer
was dried over Na2SO4, the solvent was evaporated and the crude
product was purified on silica gel chromatography (75:25 petro-
leum ether/EtOAc).
128.3,127.8,127.6 (CH arom.),119.9 (C-5), 83.4 (C-3), 70.6 (C-2), 70.5
(CH2Ph), 29.4, 29.1 (CH2-S), 24.4 (CH2); ESIHRMS calcd for
C16H20O2S2Na ([MþNa]þ) 331.0802; found 331.0793.
4.4.5. (3S,4S)-4-Benzyloxy-1-(phenylsulfanyl)hexa-1,5-dien-3-ol
(17). Mixture 1:1 of stereomers. Yellow oil. Yield: 66%. 1H NMR
(250 MHz, CDCl3):
d 7.35–7.26 (m, 5H, C6H5), 6.51 (d, 0.5H,
J¼15.1 Hz, H-1E), 6.42 (d, 0.5H, J¼9.6 Hz, H-1Z), 5.88–5.67 (m, 2H, H-
2, H-5), 5.42–5.32 (m, 2H, H-6), 4.70 (d, 0.5H, J¼8.5 Hz, CHPh), 4.66
(d, 0.5H, J¼8.5 Hz, CHPh), 4.59 (m, 1H, H-3), 4.41 (d, 0.5H, J¼9.7 Hz,
CHPh), 4.36 (d, 0.5H, J¼9.7 Hz, CHPh), 3.77 (t, 0.5H, J¼7.7 Hz, H-4),
3.66 (t, 0.5H, J¼7.6 Hz, H-4), 2.84 (d, 1H, 14.4 Hz, OH); 13C NMR
4.4.1. (3S,4S)-4-Benzyloxy-1-trimethylsilylhex-5-ene-2,3-diol
(13). Colourless oil. Yield: 69%. Single isomer (only traces of the
other diastereomer were detected in the 1H NMR spectrum). 1H
(62.9 MHz, CDCl3): d 138.4, 137.5 (Cq arom.), 134.0, 133.8 (C-5),
129.5–126.0 (C-2, CH arom.), 120.1, 119.9 (C-6), 83.2, 83.1 (C-4), 73.7,
70.7 (C-3), 70.1, 70.0 (CH2Ph).
NMR (250 MHz, CDCl3):
d 7.38–7.27 (m, 5H, C6H5), 5.86 (ddd, 1H,
J¼16.8, 10.8, 7.9 Hz, H-5), 5.43–5.32 (m, 2H, H-6), 4.63 (d, 1H,
J¼11.6 Hz, CHPh), 4.31 (d, 1H, 11.6 Hz, CHPh), 3.88 (dd, 1H, J¼8.2,
5.7 Hz, H-4), 3.80 (ddd, 1H, J¼8.2, 5.7, 2.4 Hz, H-2), 3.28 (dd, 1H,
J¼5.7, 2.4 Hz, H-3), 2.74 (br s, 1H, OH), 2.37 (d, 1H, J¼5.7 Hz, OH),
0.92 (dd, 1H, J¼14.4, 5.7 Hz, H-1), 0.75 (dd, 1H, J¼14.4, 9.1 Hz, H-1),
Acknowledgements
´
´
This work was supported by the ‘Contrat de Plan Etat-Region’
(GlycoVal program). The authors are grateful to the ‘Region
Champagne-Ardenne’ and C.N.R.S. for a doctoral fellowship (A.B.)
and to Europol’Agro for its help in managing the programme. The
0.01 (s, 9H, Si(CH3)3); 13C NMR (62.9 MHz, CDCl3):
d 138.4
(Cq arom.), 136.3 (C-5), 129.8, 129.3, 129.2 (C arom), 121.6 (C-6), 83.1
(C-4), 78.7 (C-3), 71.6 (CH2Ph), 70.5 (C-2), 23.8 (C-1), 0.4 (Si(CH3)3).
Anal. Calcd for C16H26O3Si: C, 65.31; H, 8.84. Found C, 65.05; H, 9.03.
starting materials D-xylose and L-arabinose were generously sup-
plied by A.R.D. company. We thank Dr. J.-M. Nuzillard and A. Mar-
tinez for their help in modelling the relationship structure/NMR of
diastereomers of compound 12, and H. Baillia and D. Harakat for
their assistance in obtaining NMR and mass spectra.
4.4.2. (3S,4S)-3-Benzyloxyhexa-1,5-dien-4-ol (14). Compound 13
(110 mg, 0.37 mmol) was treated for 48 h at rt in THF (4 mL) con-
taining H2SO4 (80 mL). Then, THF was removed under vacuum, the
Supplementary data
residue was dissolved in DCM (20 mL) and the resulting solution
was neutralized with a saturated aqueous NaHCO3 solution, then
with water. After drying over Na2SO4, filtration and evaporation,
the product was purified by chromatography over silica gel (85:15
petroleum ether–EtOAc), yielding the diene 14 (85 mg, 100%) as an
oil. Diene 14 was obtained in 78% overall yield (two steps from 1)
starting from 2.4 equiv of (trimethylsilyl)methyllithium without
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2010.04.013.
References and notes
1. (a) He´non, E.; Bercier, A.; Plantier-Royon, R.; Harakat, D.; Portella, C. J. Org.
Chem. 2007, 72, 2271–2278; (b) Bercier, A.; Plantier-Royon, R.; Portella, C.
Carbohydr. Res. 2007, 342, 2450–2455.
2. For some recent reviews, see: (a) Enders, D.; Grondal, C.; Hu¨ttl, M. R. M. Angew.
Chem., Int. Ed. 2007, 46, 1570–1581; (b) Pellissier, H. Tetrahedron 2006, 62,
2143–2173; (c) Pellissier, H. Tetrahedron 2006, 62, 1619–1665; (d) Tietze, L. F.;
Brasche, G.; Gerike, K. Domino Reactions in Organic Chemistry; Wiley-VCH:
Weinheim, 2006; (e) Wasilke, J.-C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C. Chem.
Rev. 2005, 105, 1001–1020; (f) Ramon, D. J.; Yus, M. Angew. Chem., Int. Ed. 2005,
44, 1602–1634.
purification of the intermediate 13.
23
Oil. Yield: quantitative. [
(250 MHz, CDCl3):
a]
þ10 (c 1.10, CHCl3); 1H NMR
D
d
7.33–7.20 (m, 5H, C6H5), 5.83–5.61 (m, 2H, H-2,
H-5), 5.34–5.11 (m, 4H, H-1, H-6), 4.57 (d, 1H, J¼11.6 Hz, CHPh), 4.29
(d, 1H, J¼11.6 Hz, CHPh), 3.99 (m, 1H, H-4), 3.61 (t, 1H, J¼7.8 Hz, H-
3), 2.81 (br s, OH); 13C NMR (62.9 MHz, CDCl3):
d 138.4 (Cq arom.),
136.7, 135.2 (C-2, C-5), 128.9, 128.5, 128.4, 128.3 (CH arom.), 120.7,
117.4 (C-1, C-6), 84.5 (C-4), 75.2 (C-3), 71.0 (CH2Ph); ESIHRMS calcd
for C13H16O2Na ([MþNa]þ) 227.1048; found 227.1044.
3. For a recent review, see: Madsen, R. Eur. J. Org. Chem. 2007, 399–415 and ref-
erences cited therein.
4. (a) Fu¨ rstner, A.; Baumgartner, J.; Jumbam, D. N. J. Chem. Soc., Perkin Trans. 11993,
131–138; (b) Fu¨rstner, A.; Jumbam, D. N.; Teslic, J.; Weidmann, H. J. Org. Chem.
1991, 56, 2213–2217; (c) Fu¨rstner, A. Tetrahedron Lett. 1990, 31, 3735–3738.
5. Bernet, B.; Vasella, A. Helv. Chim. Acta 1979, 62, 1990–2016.
6. (a) Palmer, A. M.; Ja¨ger, V. Eur. J. Org. Chem. 2001, 1293–1308; (b) Ja¨ger, V.;
Bicrer, L.; Dong, H.-Q.; Palmer, A. M.; Shaw, D.; Frey, W. J. Heterocycl. Chem.
2000, 37, 455–465.
7. Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1984, 23, 556–569.
8. We refer to additions of organometallic reagents on similar
a-alkoxy and a-
hydroxy aldoses, where the stereochemistry was established by chemical
correlations.
4.4.3. (3S,4S)-4-Benzyloxy-1,1-bis(methylsulfanyl)hexa-1,5-dien-3-ol
23
(15). Yellow oil. Yield: 52%. [
(250 MHz, CDCl3):
a
]
D
þ62 (c 1.20, CHCl3); 1H NMR
d
7.35–7.26 (m, 5H, C6H5), 5.74 (m, 1H, H-5), 5.66
(d, 1H, J¼8.5 Hz, H-2), 5.37–5.27 (m, 2H, H-6), 4.79 (ddd, 1H, J¼8.5,
7.0, 2.9 Hz, H-3), 4.68 (d, 1H, J¼11.7 Hz, CHPh), 4.38 (d, 1H,
J¼11.7 Hz, CHPh), 3.72 (t,1H, J¼7.0 Hz, H-4), 2.84 (d, 1H, 2.9 Hz, OH),
2.32 (s, CH3), 2.28 (s, CH3); 13C NMR (62.9 MHz, CDCl3):
d 138.3
9. (a) Luchetti, G.; Ding, K.; d’Alarcao, M.; Kornienko, A. Synthesis 2008,
3142–3147; (b) Hansen, F. G.; Bundgaard, E.; Madsen, R. J. Org. Chem. 2005, 70,
10139–10142.
10. Brochard, L.; Lorin, C.; Spiess, N.; Rollin, P. Tetrahedron Lett. 1998, 39,
4267–4270.
11. (a) Monrad, R. N.; Fanefjord, M.; Hansen, F. G.; Jensen, N. M. E.; Madsen, R. Eur. J.
Org. Chem. 2009, 396–402; (b) Keinicke, L.; Madsen, R. Org. Biomol. Chem. 2005,
3, 4124–4128; (c) Skaanderup, P. R.; Madsen, R. J. Org. Chem. 2003, 68,
2115–2122; (d) Poulsen, C. S.; Madsen, R. J. Org. Chem. 2002, 67, 4441–4449; (e)
(Cq arom.), 134.8 (C-5), 134.5 (C-1), 129.3 (C-2), 129.2, 128.7, 128.4,
127.4 (CH arom.), 121.0 (C-6), 83.2 (C-4), 71.3 (C-3), 70.5 (CH2Ph),
16.5 (CH3), 15.0 (CH3); ESIHRMS calcd for C15H20O2S2Na ([MþNa]þ)
319.0802; found 319.0796.
4.4.4. (2S,3S)-3-Benzyloxy-1-(1,3-dithian-2-ylidene)pent-4-en-2-ol
24
(16). Yellow oil. Yield: 86%. [
a]
þ103 (c 0.60, CHCl3); 1H NMR
D

4114
A. Bercier et al. / Tetrahedron 66 (2010) 4109–4114
Hyldtoft, L.; Madsen, R. J. Am. Chem. Soc. 2000, 122, 8444–8452; (f) Hyldtoft, L.;
Poulsen, C. S.; Madsen, R. Chem. Commun. 1999, 2101–2102.
(m, 5H, C6H5), 5.92–5.77 (m, 1H, H-2), 5.55–5.40 (m, 2H, H-1), 4.69 (d, 1H,
J¼11.8 Hz, CHPh), 4.39 (d, 1H, J¼11.8 Hz, CHPh), 4.36 (t, 1H, J¼4.1 Hz, H-4), 4.
28 (dd, 1H, J¼6.0, 4.1 Hz, H-5), 3.88 (dd, 1H, J¼7.8, 4.1 Hz, H-3), 1.95–1.79
(m, 1H, H-6), 0.98 (d, 3H, J¼7.0 Hz, CH3), 0.92 (d, 3H, J¼6.8 Hz, CH3); 13C NMR
12. (a) Verhelst, S. H. L.; Wennekes, T.; van der Marel, G. A.; Overkleeft, H. S.; van
Boeckel, C. A. A.; van Boom, J. H. Tetrahedron 2004, 60, 2813–2822; (b) Verhelst,
S. H. L.; Magne´e, L.; Wennekes, T.; Wiedenhof, W.; van der Marel, G. A.;
Overkleeft, H. S.; van Boeckel, C. A. A.; van Boom, J. H. Eur. J. Org. Chem. 2004,
2404–2410; (c) Verhelst, S. H. L.; Martinez, B. P.; Timmer, M. S. M.; Lodder, G.;
van der Marel, G. A.; Overkleeft, H. S.; van Boom, J. H. J. Org. Chem. 2003, 68,
9598–9603; (d) Boyer, F.-D.; Hanna, I.; Nolan, S. P. J. Org. Chem. 2001, 66,
4094–4096; (e) Boyer, F.-D.; Hanna, I.; Ricard, L. Org. Lett. 2001, 3, 3095–3098;
(f) Hanna, I.; Ricard, L. Org. Lett. 2000, 2, 2651–2654.
(62.9 MHz, CDCl3):
d 155.1 (CO), 137.9 (Cq arom.), 132.5 (C-2), 129.0–128.3
(CH arom.), 122.8 (C-1), 82.8 (C-5), 79.8 (C-4), 79.3 (C-3), 71.0 (CH2Ph), 32.1
(C-6), 17.7, 17.1 (CH3).
15. (a) Ke´roure´dan, E.; Percy, J. M.; Rinaudo, G.; Singh, K. Synthesis 2008,
3903–3918; (b) Radha Krishna, P.; Narasimha Reddy, P. V.; Sreeshailam, A.;
Uday Kiran, M.; Jagdeesh, B. Tetrahedron Lett. 2007, 48, 6466–6470; (c) Ahmed,
M. M.; O’Doherty, G. A. Carbohydr. Res. 2006, 34, 1505–1521; (d) Nogawa, M.;
Sugawara, S.; Iizuka, R.; Shimojo, M.; Ohta, H.; Hatanaka, M.; Matsumoto, K.
Tetrahedron 2006, 62, 12071–12083.
13. (a) Che´rest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 9, 2199–2204; (b)
Anh, N. T. Top. Curr. Chem. 1980, 88, 145–162.
14. Cyclic carbonate 12 was prepared using triphosgene and Et3N in dichloro-
16. Modelisation using MacroModel, version 9.7; Schro¨dinger, LLC: New York, NY, 2009.
17. Lin, H.-S.; Paquette, L. A. Synth. Commun. 1994, 24, 2503–2506.
methane. Selected spectral data: 1H NMR (250 MHz, CDCl3):
d 7.39–7.28