Synthesis of carbohydrate-based vinyl selenides via Wittig-type reactions

Article abstract of DOI:10.1016/j.carres.2007.01.006

Carbohydrate-based vinyl selenides of the arabino, ribo and 2-deoxy-ribo configuration have been prepared by Wittig-type reactions of various protected furanoses. Moderate yields were always obtained due to the nature and reactivity of both carbohydrate lactols and selenium-based olefinating reagents under the conditions tested. A detailed study of the olefination reaction and the behaviour of vinyl selenides towards the electrophilic-induced cyclization will be discussed.

Full text of DOI:10.1016/j.carres.2007.01.006

Carbohydrate Research 342 (2007) 736–743
Note
Synthesis of carbohydrate-based vinyl selenides
via Wittig-type reactions
*
´
´
Omar Boutureira, M. Isabel Matheu, Yolanda Dıaz and Sergio Castillon
`
´
Departament de Quı´mica Analı´tica i Quı´mica Organica, Facultat de Quımica, Universitat Rovira i Virgili,
c/o MarcelÆlı´ Domingo s/n, E-43007 Tarragona, Spain
Received 31 August 2006; received in revised form 2 January 2007; accepted 9 January 2007
Available online 14 January 2007
Abstract—Carbohydrate-based vinyl selenides of the arabino, ribo and 2-deoxy-ribo configuration have been prepared by Wittig-
type reactions of various protected furanoses. Moderate yields were always obtained due to the nature and reactivity of both car-
bohydrate lactols and selenium-based olefinating reagents under the conditions tested. A detailed study of the olefination reaction
and the behaviour of vinyl selenides towards the electrophilic-induced cyclization will be discussed.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Selenium; Seleno-carbohydrates; Vinyl selenides; Olefination; Wittig
Organic chalcogenides are compounds of increasing
importance in organic synthesis due to their particular
reactivity1 and their attractive biological properties.2
Selenium chemistry has been shown to provide highly
efficient and selective transformations, and therefore
has been widely used in the synthesis of natural prod-
ucts.3,4 Among the various organoselenium compounds,
vinyl selenides are particularly useful intermediates
in the stereoselective preparation of functionalized
alkenes,5 carbonyl compounds,6 as well as suitable sub-
strates in carbon–carbon bond formation.7 A wide vari-
ety of methods have been developed for the synthesis of
vinyl selenides involving the reactions of organo-
selenium compounds with alkynes,8 vinyl halides9 or
boranes,10 and Wittig-type reactions.11 Surprisingly, no
paper dealing with the synthesis of carbohydrate-based
vinyl selenides has been issued to date despite the fact
that these products are good candidates for the prepara-
tion of complex 1,6- and 1,3-enediynes,12 enantiome-
rically pure 1,2-diol derivatives13 and commonly
occurring fragments in natural products.14
Recently, we have reported a new procedure for the
synthesis of 2-deoxy-2-iodo-1-thio-glycosides from pen-
toses through a short synthetic route that involves olef-
ination and iodonium-ion-mediated 6-endo cyclization,
and discussed the use of these glycosides as glycosyl do-
nors for the stereocontrolled synthesis of 2-deoxy-2-
iodo-disaccharides.15 As part of our ongoing projects
on the chemistry of natural and synthetic 2-deoxy- and
2,6-dideoxy-glycosides, we became interested in the
development of useful glycosyl donors such as 2-
deoxy-2-iodo-1-seleno-glycosides,16 and exploit their
high reactivity in developing milder stereoselective gly-
cosylation protocols by using this methodology (Scheme
1).
Encouraged by the previous results,15 we postulated
that the presence of a selenium atom would provide
milder glycosylation conditions in order to improve
the yield and stereoselectivity. Therefore, it was deemed
interesting to investigate the synthesis of carbohydrate-
based vinyl selenides and explore their reactivity with
electrophiles.
Among the methods developed for synthesizing vinyl
selenides,8–11 Wittig-type reactions seem to be the best
strategy as this would avoid complex manipulation on
the carbohydrate scaffold (Scheme 2).
*
Corresponding author. Tel.: +34 977 559556; fax: +34 977 558446;
e-mail: sergio.castillon@urv.net
0008-6215/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.01.006

O. Boutureira et al. / Carbohydrate Research 342 (2007) 736–743
737
RO
O
OH
RO
X
RO
X
RO
X
RO
R'
OR
OH
OR
OR
OH
[E]+
O
SePh
SePh
X
E
X = OR, H
1,3-enediynes
E = I, SePh, SPh
Scheme 1. Possible applications of carbohydrate-based vinyl selenides.
A
2n Y-CH2SePh
2.2n Base
Furanose
Y = -PPh3
-POPh2
Preformed
olefinating
reagents
-PO(OEt)2
-SO2Ph
-SiMe3
C
B
RO
X
OR
OH
2n [Ph3PCH3]Br
n PhSeCl
Transylidation
PhSeCH2Cl
2n t-BuOK
1.5n Ph3P
1.5n Furanose
Carbene-type
One-Pot
SePh
2.2n Base
Furanose
X = OR, H
Y = -PPh3
-POPh2
-PO(OEt)2
One-Pot
D
n Y-CH3
n PhSeBr
2.2n Base
Furanose
Scheme 2. Wittig-type olefination strategies towards the synthesis of carbohydrate-based vinyl selenides.
We initially decided to focus on the classical Wittig-
type methodology (Scheme 2, A). The appropriate a-
seleno preformed phosphorus reagents are the obvious
starting materials for these reactions. Thus, chloro-
methyl phenylselenide 4 was readily obtained from di-
phenyl diselenide according to the method reported in
the literature by Huang and co-workers17 (Scheme 3).
The preparation of the corresponding a-selenophos-
phine oxide 5 was accomplished starting from derivative
4 under Michaelis–Arbuzov reaction conditions.18 Next
O
S
O
O
Cl
Se
Se
Y
a
b
c
Se
P
Se
d
X
1 X = H, Y = SePh
2 X = Y = SePh
3 X = Y = H
4
5
Scheme 3. Reagents and conditions: (a) PhSO2CH2Br, NaH, THF, reflux, 3 h, 1 (54%), 2 (9%) and 3 (27%); (b) KBH4, EtOH, CH2Cl2, reflux, 3 h,
51%; (c) Ph2POEt, 150 °C, 3 h, 31%; (d) Ph2POEt, TBAI, 150 °C, 4.5 h, 39%.

738
O. Boutureira et al. / Carbohydrate Research 342 (2007) 736–743
we tried the synthesis of the selenosulfone derivative 119
(Julia–Lythgoe olefinating reagent), which was obtained
from bromomethyl phenyl sulfone, diphenyl diselenide
and sodium hydride20 in 54% yield together with small
amounts of products 2 and 3,21 which were separated
by standard chromatographic procedures.
Table 1. Olefination of arabinofuranose 6 to obtain alkenyl selenides 7
and 8 containing reagents
OBn
OH
OBn
OH
OBn
BnO
O
BnO
OH
SePh
SePh
BnO
OBn
6
BnO
7
8
The reaction conditions for olefination11,22 were
optimized by starting from the commercially available
arabinose derivative 6. The reactions of 6 with Me3-
SiCH2SePh (Peterson) (Table 1, entry 7), with 5
(Wittig–Horner) (Table 1, entry 8), and 1 (Julia–
Lythgoe) (Table 1, entry 9) were unsuccessful even
though different bases were used.23 Three one-pot proce-
dures were considered (Scheme 2, B–D). Vinyl selenides
have been previously prepared11a by addition of t-BuOK
to a solution of chloromethylphenyl selenide 4 and
triphenylphosphine in THF, followed by addition of
an aldehyde (Scheme 2, B). Unfortunately, no reaction
product was detected using arabinose derivative 6
(Table 1, entry 1).
Entry Olefination conditionsa Olefination Yield Z/E
(equiv)
product
Mixture
(%)
—
Ratiob
—
1c
PhSeCH2Cl (1)
PH3P (1.5)
t-BuOK (2)
rt to reflux, 14 h
2
[Ph3PCH3]Br (2)
PhSeCl (1)
n-BuLi (2.2)
reflux, 17 h
7
8
8
55
3:2d
1:12
1:9
3
[Ph3PCH3]Br (6)
PhSeCl (3)
n-BuLi (6.6)
rt, 14 h
29e
30e
4
[Ph3PCH3]Br (6)
PhSeCl (3)
The second method (Scheme 2, C) consisted in the
transylidation reaction between alkylidene triphenyl-
phosphorane (Ph3P@CH2) and phenylselenenyl chlo-
ride. In this case, the subsequent reaction with the
carbohydrate derivative 6 furnished vinyl selenide 8 in
moderate yield and Z/E ratio of up to 1:12 (Table 1, en-
try 3). Forcing the reaction conditions by refluxing the
mixture for prolonged reaction time did not afford the
desired compound; rather it led to the formation of
diene 7 in 55% yield and 3:2 3Z,5E/3Z,5Z ratio (Table
1, entry 2) as a result of benzyl alcohol elimination in
the open-ring sugar followed by Wittig reaction of the
resulting enal as reported previously.24 The same group
has described the use of Bu3SnCl to avoid the benzylic
elimination. Under these conditions, when n-BuLi was
used at room temperature, 8 was obtained in moderate
yield as a 1:9 Z/E mixture (Table 1, entries 4 and 5).
It is worthy to note that while increasing the equivalents
of olefinating reagent and base the yield is increased, an
enitol impurity (R–CH@CH2) appears as a result of
alkylidene triphenylphosphorane (Ph3P@CH2) forma-
tion25 followed by reaction with the carbohydrate lactol
moiety (Table 1, entries 3, 4 and 6). Furthermore, the
presence of the Bu3SnCl has no influence either in the
yield or in the enitol impurity formation, but affects
the stereochemical outcome of the reaction.
n-BuLi (6.6)
Bu3SnCl (0.5)
rt, 14 h
5
[Ph3PCH3]Br (4)
PhSeCl (2)
n-BuLi (4.4)
Bu3SnCl (0.5)
rt, 14 h
8
19
1:9
6
7
[Ph3PCH3]Br (2)
PhSeBr (2)
n-BuLi (4.4)
À78 °C to rt, 14 h
Me3SiCH2SePh (2)
n-BuLi or LDA or
KHMDS (3.3)
À78 °C to rt, 14 h
Ph2P(O)CH2SePH (4)
n-BuLi (4.4)
À78 °C to rt, 20 h
PhSO2CH2SePh (2)
n-BuLi (4.4)
8
30e
—
1:7
—
Mixture
8
9
Mixture
—
—
—
—
6
À78 °C to rt, 14 h
a Solvent = THF.
b Determined by integration of the olefinic proton signals in the 1H
NMR spectrum of the crude reaction mixture.
c Starting material (1.5 equiv) was used.
d 3Z,5E/3Z,5Z ratio.
e Trace amounts of the corresponding enitol (R–CH@CH2).
Finally, we focused on a third method (Scheme 2, D)
consisting in the generation of an a-seleno triphenyl-
phosphonium reagent by the reaction of equimolar
amounts of arylselenenyl bromides and phosphonium
salts. In this case, the use of two equivalents of base with
respect to the olefinating reagent was critical for obtain-
ing the corresponding vinyl selenide instead of the unde-
sired 1,1-bis-selenides.11b Thus, under these conditions,
vinyl selenide 8 was obtained in 30% yield as a 1:7
Z/E mixture (Table 1, entry 6). The behaviour observed
was similar to that found using more equivalents of olef-
inating reagent and base (Table 1, entries 3–5). Thus,
this protocol provided the best result due to the use of
less equivalents of base which is important to avoid
not only the observed degradation of the a-seleno olefi-
nating reagent due to C–Se bond lithiation, but also to
prevent any epimerization at C-2 during the Wittig reac-
tion.26 In order to confirm the degradation of these com-

O. Boutureira et al. / Carbohydrate Research 342 (2007) 736–743
739
pounds, stability tests of the in situ generated a-seleno
olefinating reagents were performed following the proce-
dure reported in the experimental section without add-
ing any carbonyl compound. The reaction mixture was
quenched after 12 h stirring at room temperature. GC–
EIMS, 1H, 13C and 31P NMR analysis of the crude
products showed signals corresponding to degradation
products such as PhSeBu, PhSeCH2SePh and PhSeSePh
due to C–Se cleavage occurring in highly basic media.
This protocol was extended to different protected
furanoses in order to determine the generality of the
reaction and the influence of the stereochemistry at po-
sition C-2. In the case of xylose derivative 9, all the reac-
tion conditions tested were unsuccessful and only the
starting material was recovered (Table 2, entry 1). The
reaction of ribose derivative 10 under Wittig conditions
led to the formation of the desired alkene 13 in low yield
(74% starting material was also recovered and could be
further re-used) regardless of the base used as already
observed for the reaction of isopropylidene and silyl-
protected lyxofuranoses with Li-bases.15b The Z-isomer
was detected as the major component in the mixture, in
accordance with the known stereochemical course of
Wittig olefinations under lithium salt free conditions12a
Table 2. Olefination of furanoses 9–12 to obtain alkenyl selenides 13–15
RO
RO
OR
OH
OR
OH
O
OH
X
SePh
SePh
RO
X
X
X = OR
X = H
Entry
Starting material
Olefination conditionsa (equiv)
Olefination product
Yield (%)
Z/E Ratiob
Me3SiCH2SePh (2) or
[Ph3PCH3]Br (2) or
Ph2P(O)CH3 (2) or
(EtO)2P(O)CH3 (2)
PhSeBr (2)
OBn
BnO
O
OH
1
9
—
—
OBn
n-BuLi or LDA or KHMDS (4.4)
À78 °C to rt, 14–48 h
9
2
[Ph3PCH3]Br (2)
PhSeBr (2)
KHMDS (4.4)
À78 °C to rt, 6 days
15c
11:1
TBDPSO
OTBDPS
OH
O
OH
SePh
O
O
O
O
13
10
3
[Ph3PCH3]Br (2)
PhSeBr (2)
KHMDS (4.4)
À78 °C to rt, 6 days
Mixtured
—
—
O
O
TBDPSO
BnO
O
OH
11
4
5
[Ph3PCH3]Br (2) or
(EtO)2P(O)CH3 (2)
PhSeBr (2)
n-BuLi (4.4)
À78 °C to rt, 32 h
13
1:1e
OBn
OH
O
OH
SePh
SePh
OBn
14
12
12
Ph3P(O)CH3 (2)
PhSeBr (2)
n-BuLi (4.4)
34f
1:1
OBn
OH
BnO
À78 °C to rt, 31 h
15
a Solvent = THF.
b Determined by integration of the olefinic proton signals in the 1H NMR spectrum of the crude reaction mixture.
c 74% Starting material was recovered.
d 25% Starting material was recovered.
e 3E,5E/3E,5Z Ratio.
f Trace amounts of the corresponding diene.

740
O. Boutureira et al. / Carbohydrate Research 342 (2007) 736–743
(Table 2, entry 2). In contrast, when the same reaction
was carried out using lyxose derivative 11, only 25% of
the starting material was recovered together with some
other minor side products (Table 2, entry 3).
85% H3PO4 and CFCl3, respectively, as external stan-
dards. Elemental analyses (C, H, N, S) were performed
with a Carlo Erba EA 1108 Analyser in the Servei de
´
Recursos Cientıfics (URV). Optical rotations were re-
Despite the use of 2-deoxyribose derivative 12 which
has less steric hindrance at C-2, diene 14 was obtained
under Wittig and Horner–Wadsworth–Emmons condi-
tions (Table 2, entry 4). The expected alkene 15 was
obtained in 34% yield as a 1:1 Z/E mixture under
Wittig–Horner conditions (Table 2, entry 5).
At this point, having synthesized different protected
vinyl selenides from carbohydrate precursors and dem-
onstrated the influence of C-2 substitution in the reac-
tion course, we next turned our attention to study
their reactivity with the electrophiles. In all cases, the
Z/E mixtures of alkenes proved to be inseparable;
hence, the cyclization reactions were assayed directly
on the mixture of diastereomers.
Electrophile-induced cyclization was studied for
derivative 8. Initial attempts using iodine electrophiles
such as I2, IDCP, NIS and IPy2BF4 gave an inseparable
mixture of products. Since selenoglycosides are acti-
vated under milder conditions than thioglycosides, we
assumed that if any electrophilic cyclization occurred,
the excess of electrophile would promote the activation
of the phenylselenenyl moiety. In order to trap any
oxocarbenium ion formed, the reaction mixture was
quenched by addition of a few drops of methanol. How-
ever, no reaction product was detected by TLC analysis.
Electrophilic cyclization using other electrophiles such
as SelectfluorÒ, p-TsOH and PhSeCl has also been
examined, but complex mixtures were always obtained.
In conclusion, the proposed method allows synthesiz-
ing vinyl selenides in the arabino, ribo and 2-deoxy-ribo
series. The modest yield observed with the vinyl sele-
nides reported herein is probably related to the nature
and reactivity of both carbohydrate lactols and selenium
based olefinating reagents under the conditions tested.
The reaction with electrophiles proved to be challenging,
but no cyclization products were obtained. The prepara-
tion of vinyl selenides proved to be much more difficult
than the related vinyl sulfides, which can be prepared in
good yields using Wittig–Horner reaction.
corded on a Perkin–Elmer 241 MC polarimeter in a
1 dm cell at 20 °C. Melting points were determined on
a Tottoli Buchi 510 melting point apparatus and are re-
¨
ported uncorrected. FT-IR was obtained with a Bruker
Equinox 55 spectrophotometer. GC–EIMS spectrome-
try was performed on a HP 5890 (Ti 75 °C (2) and
20 °C/min to 250 °C) gas chromatograph with an HP
5989A quadrupolar detector (45–600, 70 eV) in the Ser-
´
vei de Recursos Cientıfics (URV). Flash column chro-
matography was performed with Silica Gel 60 (E.
Merck, 40–63 lm). Medium-pressure liquid chromatog-
raphy (MPLC) was performed using Silica Gel 60 ACC
(SDS, 6–35 lm). Radial chromatography was per-
formed on 1, 2 or 4 mm plates of Kieselgel 60 PF254
(E. Merck), depending on the amount of product. The
solvents were purified using standard procedures. Thin
layer chromatography (TLC) was performed on alumin-
ium sheets coated with Silica Gel 60 F254 (E. Merck).
The compounds were visualized by UV (254 nm), and
also by spraying the TLC plates with 6% H2SO4 in
EtOH, or 2% PdCl2 and 15% H2SO4 in water, followed
by charring at 150 °C for a few minutes. Starting mate-
rials 1, 4, 6, 9, 11 and 12 were prepared as described in
the literature.17,19,27 Iodonium dicollidine perchlorate
(IDCP) was prepared following the method reported
by Lemieux and Morgan.28 All other reagents were used
as received from commercial suppliers without further
purification.
1.2. Diphenyl phenylselenylphosphine oxide (5)
Ethyl diphenylphosphinite (330 lL, 1.5 mmol), chloro-
methyl phenyl selenide 4 (257 mg, 1.25 mmol) and TBAI
(470 mg, 1.25 mmol) were heated together under argon
at 150 °C for 4.5 h. The crude reaction product was puri-
fied by radial chromatography (from 1:1 EtOAc–hexane
to EtOAc) to afford 5 (182 mg, 39%) as a white crystal-
line solid; mp: 121–123 °C; Rf (EtOAc): 0.36; FT-IR
(KBr):
m
3048, 2971, 2916, 1573, 1475, 1435,
1
1190 cmÀ1; H NMR (CDCl3, 400 MHz): d 7.78–7.17
(m, 15H, Ar), 3.60 (s, 2H, JH,P 7.6 Hz, CH2); 13C
NMR (CDCl3, 100.6 MHz): d 133.6–127.9 (C, CH,
Ar), 25.6 (d, JC,P 69 Hz, CH2); 31P NMR (CDCl3,
1. Experimental
1.1. General procedures
162 MHz):
d
28.8 (s, P@O). Anal. Calcd for
C19H17OPSe: C, 61.47; H, 4.62. Found: C, 61.23; H, 4.60.
1H, 13C, 19F and 31P NMR spectra were acquired using
Varian Gemini and Varian Mercury 400 MHz spec-
1.3. General Wittig olefination of furanoses via
transylidation reaction
1
trometers. In all the H NMR spectra, TMS was used
as an internal reference. In the 13C NMR spectra, the
residual solvent signal was used as an internal reference
(CDCl3, triplet at 77.23 ppm) unless otherwise stated.
All the 31P and 19F NMR spectra were referenced to
To a dispersion of methyltriphenylphosphonium bro-
mide (2 mmol) in dry THF (3.5 mL/mmol) at À78 °C
was added the corresponding base (2.2 mmol) under

O. Boutureira et al. / Carbohydrate Research 342 (2007) 736–743
741
an atmosphere of argon. PhSeCl (1 mmol) in dry THF
(3.5 mL/mmol) was added and the mixture was left with
stirring at low temperature for 30 min. A soln of the
corresponding furanose (1 mmol) in dry THF (2 mL)
was then added dropwise. The mixture was allowed to
warm to room temperature overnight. The crude reac-
tion was filtered through CeliteÒ 545, diluted with petro-
leum ether and washed with saturated aqueous NH4Cl
and brine. The combined organic layers were dried over
MgSO4, filtered and concentrated under diminished
pressure. The crude product was purified by chromato-
graphic techniques.
(CDCl3, 100.6 MHz): d 154.3–126.9 (C, CH, Ar, C-
4,6), 123.1 (C-5), 115.6 (C-3), 74.0–73.1 (2CH2Ph, C-
1), 65.8 (C-2). Compound 7Z: 1H NMR (CDCl3,
400 MHz): d 7.58–7.28 (m, 15H, Ar), 6.79 (d, 1H, J5,6
10 Hz, H-6), 6.37 (d, 1H, J5,6 10 Hz, H-5), 5.04 (d, 1H,
J2,3 8.4 Hz, H-3), 4.89–4.82 (m, 2H, CH2Ph), 4.78–4.69
(m, 1H, H-2), 4.66 (s, 2H, CH2Ph), 3.39–3.28 (m, 2H,
H-1a,b), 2.22 (br s, 1H, OH); 13C NMR (CDCl3,
100.6 MHz): d 154.3–126.9 (C, CH, Ar, C-4,6), 133.7
(C-5), 116.2 (C-3), 74.0-73.1 (2CH2Ph, C-1), 65.1 (C-2).
1.6. (Z/E)-3,4,6-Tri-O-benzyl-1,2-dideoxy-1-phenyl-
selenenyl-D-arabino-hex-1-enitol (8)
1.4. General Wittig-type olefination of furanoses in a
one-pot reaction
As described in the general procedure for the Wittig-type
olefination of furanoses by one-pot reaction, a soln
To a dispersion of the corresponding methyl phospho-
nium salt, phosphine oxide or phosphonate (2 mmol)
in dry THF (4 mL) at À78 °C was added the corre-
sponding base (4.4 mmol) under an atmosphere of
argon. PhSeBr (2 mmol) in dry THF (4 mL) was added
and the mixture was left to stir at low temperature for
30 min. A soln of the corresponding furanose (1 mmol)
in dry THF (2 mL) was then added dropwise. The
mixture was allowed to warm to room temperature
overnight. A saturated aqueous soln of NH4Cl was then
added and the mixture was extracted with Et2O. The
combined organic layers were dried over MgSO4,
filtered and concentrated under diminished pressure.
The crude reaction was purified by chromatographic
techniques.
of 2,3,5-tri-O-benzyl-b-D-arabinofuranose
6
(3.5 g,
8.3 mmol) in dry THF (16.6 mL) was olefinated by reac-
tion with methyltriphenylphosphonium bromide (6 g,
16.5 mmol) in dry THF (33 mL), PhSeBr (3.96 g,
16.8 mmol) in dry THF (33.6 mL), and 1.6 M n-BuLi
in hexane (23 mL, 36.8 mmol). After 14 h stirring at
room temperature, the reaction mixture was quenched
and the crude product was purified by flash chromato-
graphy (1:3 EtOAc–hexane) to afford 8 (1.43 g, 30%) as
a yellow syrup containing an inseparable mixture of 1:7
Z/E isomers. Data obtained from the mixture; Rf (1:3
EtOAc–hexane): 0.29; FT-IR (neat): m 3472, 3061,
3029, 2864, 1951, 1875, 1809, 1606, 1558 cmÀ1. Anal.
Calcd for C33H34O4Se: C, 69.10; H, 5.97. Found: C,
69.38; H, 5.99. Compound 8E: 1H NMR (CDCl3,
400 MHz): d 7.49–7.19 (m, 20H, Ar), 6.69 (d, 1H, J1,2
15.6 Hz, H-1), 5.98 (dd, 1H, J1,2 15.6 Hz, J2,3 7.6 Hz,
H-2), 4.64 (d, 1H, JAB 12 Hz, CH2Ph), 4.53 (d, 2H, JAB
8 Hz, CH2Ph), 4.49 (s, 2H, CH2Ph), 4.37 (d, 1H, JAB
12 Hz, CH2Ph), 4.14 (dd, 1H, J2,3 7.6 Hz, J3,4 3.6 Hz,
H-3), 3.99 (m, 1H, H-5), 3.58 (m, 3H, H-4, H-6a,b),
2.71 (d, 1H, J5,OH 5.6 Hz, OH); 13C NMR (CDCl3,
100.6 MHz): d 138.1–137.8 (C, Ar), 133.2–127.8 (CH,
Ar), 132.0 (C-1), 123.6 (C-2), 80.6 (C-4), 80.1 (C-3),
74.4, 73.5 (2CH2Ph), 70.9 (C-6, CH2Ph), 70.3 (C-5).
1.5. (3Z,5E,2R/3Z,5Z,2R)-1,4-Di-O-benzyl-6-phenyl-
selenenyl-hexa-3,5-dien-2-ol (7)
As described in the general procedure for the Wittig
olefination of furanoses-transylidation reaction, a soln
of 2,3,5-tri-O-benzyl-b-D-arabinofuranose
6 (2.20 g,
5.2 mmol) in dry THF (10.5 mL) was olefinated by reac-
tion with methyltriphenylphosphonium bromide (3.81 g,
10.5 mmol) in dry THF (73 mL), PhSeCl (1 g, 5.2 mmol)
in dry THF (18 mL) and 1.6 M n-BuLi in hexane
(7.2 mL, 11.5 mmol) for 17 h under refluxing conditions.
The crude was purified by flash chromatography (1:3
EtOAc–hexane) to afford diene 7 (1.33 g, 55%) as an or-
ange syrup composed of an inseparable 3:2 mixture of
3Z,5Z/3Z,5E isomers. Data obtained from the mixture;
Rf (1:3 EtOAc–hexane): 0.18; FT-IR (neat): m 3383,
3063, 3030, 2862, 1952, 1687, 1578, 1438 cmÀ1. Anal.
Calcd for C26H26O3Se: C, 67.09; H, 5.63. Found: C,
67.34; H, 5.65. Compound 7E: 1H NMR (CDCl3,
400 MHz): d 7.58–7.28 (m, 15H, Ar), 6.99 (d, 1H, J5,6
15.6 Hz, H-6), 6.16 (d, 1H, J5,6 15.6 Hz, H-5), 4.96 (d,
1H, J2,3 8.4 Hz, H-3), 4.89–4.82 (m, 2H, CH2Ph),
4.78–4.69 (m, 1H, H-2), 4.51 (s, 2H, CH2Ph), 3.39–
3.28 (m, 2H, H-1a,b), 2.22 (br s, 1H, OH); 13C NMR
1
Selected signals for 8Z: H NMR (CDCl3, 400 MHz): d
6.79 (d, 1H, J1,2 9.2 Hz, H-1), 6.22 (dd, 1H, J1,2 = J2,3
9.2 Hz, H-2), 2.89 (d, 1H, J5,OH 4.4 Hz, OH).
1.7. (Z/E)-6-O-(tert-Butyldiphenylsilyl)-3,4-O-isopropyl-
idene-1,2-dideoxy-1-phenylselenenyl-D-ribo-hex-1-enitol
(13)
As described in the general procedure for the Wittig-
type olefination of furanoses by one-pot reaction,
a soln of 5-O-(tert-butyldiphenylsilyl)-2,3-O-isopropyl-
idene-a,b-D-ribo-furanose 10 (100 mg, 0.233 mmol)
in dry THF (0.5 mL) was olefinated by reaction
with methyltriphenylphosphonium bromide (170.1 mg,
0.467 mmol) in dry THF (1 mL), PhSeBr (113.5 mg,

742
O. Boutureira et al. / Carbohydrate Research 342 (2007) 736–743
0.467 mmol) in dry THF (1 mL), and KHMDS (209 mg,
1.03 mmol). After 6 days stirring at room temperature
the reaction mixture was quenched and the crude prod-
uct was purified by radial chromatography (hexane to
1:3 EtOAc–hexane) to afford 13 (20 mg, 15%) as an
inseparable 11:1 Z/E mixture observed as a colourless
syrup. Data obtained from the mixture; Rf (1:3
EtOAc–hexane): 0.45. Anal. Calcd for C31H38O4SeSi:
C, 64.01; H, 6.58. Found: C, 64.00; H, 6.60. Compound
13E: 1H NMR (CDCl3, 400 MHz): d 7.71–7.26 (m, 15H,
Ar), 6.80 (dd, 1H, J1,2 15.2 Hz, J1,3 1.2 Hz, H-1), 6.11
(dd, 1H, J1,2 15.2 Hz, J2,3 7.2 Hz, H-2), 4.75 (m, 1H,
H-3), 4.13 (dd, 1H, J3,4 9.2 Hz, J4,5 6 Hz, H-4), 3.88–
3.80 (m, 2H, H-6a,b), 3.67 (m, 1H, H-5), 2.51 (d, 1H,
J5,OH 5.6 Hz, OH), 1.36, 1.33 (s, 6H, 2CH3), 1.07 (s,
9H, t-Bu); 13C NMR (CDCl3, 100.6 MHz): d 136.0–
127.6 (C, CH, Ar, C-1,2), 109.3 (Cketal), 79.3 (C-3),
77.7 (C-4), 70.2 (C-5), 65.7 (C-6), 28.2, 25.8 (2CH3),
CH2Ph), 4.38 (m, 1H, H-2), 3.56, 3.39 (m, 2H, H-1a,b),
2.51 (br s, 1H, OH); 13C NMR (CDCl3, 100.6 MHz): d
134.6–123.8 (C, CH, Ar, C-3,4,5,6), 74.1 (CH2Ph), 71.0
(C-2), 70.3 (C-1).
1.9. (Z/E)-4,6-Di-O-benzyl-1,2,3-trideoxy-1-phenyl-
selenenyl-D-ribo-hex-1-enitol (15)
As described in the general procedure for the Wittig-
type olefination of furanoses by one-pot reaction, a
soln of 3,5-di-O-benzyl-2-deoxy-a,b-D-ribofuranose 12
(80 mg, 0.25 mmol) in dry THF (0.5 mL) was olefinated
by reaction with diphenyl methyl phosphine oxide
(112 mg, 0.51 mmol) in dry THF (1 mL), PhSeBr
(124 mg, 0.51 mmol) in dry THF (1 mL), and 1.6 M n-
BuLi in hexane (0.7 mL, 1.12 mmol). After 31 h stirring
at room temperature the reaction mixture was quenched
and the crude product was purified by radial chromato-
graphy (from hexane to 1:3 EtOAc–hexane) to afford 15
(40 mg, 34%) as an inseparable 1:1 Z/E mixture as a yel-
lowish syrup. Data obtained from the mixture; Rf (1:3
EtOAc–hexane): 0.26. Compound 15E: 1H NMR
(CDCl3, 400 MHz): d 7.50–7.22 (m, 15H, Ar), 6.51 (d,
1H, J1,2 15 Hz, H-1), 6.13 (ddd, 1H, J1,2 15 Hz,
J2,3a = J2,3b 8.4 Hz, H-2), 4.67–4.48 (m, 4H, 2CH2Ph),
3.86 (m, 1H, H-4), 3.70–3.51 (m, 3H, H-5,6a,b), 2.61–
2.48 (m, 2H, H-3a,b), 2.41 (d, 1H, J5,OH 5 Hz, OH);
13C NMR (CDCl3, 100.6 MHz): d 135.0 (C-2), 134.6-
127.1 (C, CH, Ar), 119.6 (C-1), 78.9 (C-5), 73.7
(2CH2Ph), 71.6 (C-4), 71.1 (C-6), 35.4 (C-3). Compound
15Z: 1H NMR (CDCl3, 400 MHz): d 7.50–7.22 (m, 15H,
Ar), 6.57 (d, 1H, J1,2 9 Hz, H-1), 6.16 (ddd, 1H, J1,2
15 Hz, J2,3a = J2,3b 8.8 Hz, H-2), 4.67–4.48 (m, 4H,
2CH2Ph), 3.86 (m, 1H, H-4), 3.70–3.51 (m, 3H, H-
5,6a,b), 2.61–2.48 (m, 2H, H-3a,b), 2.45 (d, 1H, J5,OH
5.6 Hz, OH); 13C NMR (CDCl3, 100.6 MHz): d 135.0
(C-2), 134.6–127.1 (C, CH, Ar, C-1), 78.7 (C-5), 72.6,
72.4 (2CH2Ph), 71.6 (C-4), 71.2 (C-6), 32.1 (C-3).
1
27.2 (CH3, t-Bu), 19.7 (C, t-Bu). Compound 13Z: H
NMR (CDCl3, 400 MHz): d 7.71–7.26 (m, 15H, Ar),
6.77 (dd, 1H, J1,2 9.6 Hz, J1,3 0.8 Hz, H-1), 6.15 (dd,
1H, J1,2 9.6 Hz, J2,3 8.4 Hz, H-2), 5.09 (m, 1H, H-3),
4.21 (dd, 1H, J3,4 8.8 Hz, J4,5 6.4 Hz, H-4), 3.88–3.80
(m, 2H, H-6a,b), 3.72 (m, 1H, H-5), 2.61 (d, 1H, J5,OH
5.2 Hz, OH), 1.42, 1.37 (s, 6H, 2CH3), 1.07 (s, 9H, t-
Bu); 13C NMR (CDCl3, 100.6 MHz): d 136.0–127.6 (C,
CH, Ar), 129.6 (C-2), 126.1 (C-1), 109.5 (Cketal), 77.8
(C-4), 77.2 (C-3), 70.7 (C-5), 65.5 (C-6), 28.2, 25.8
(2CH3), 27.2 (CH3, t-Bu), 19.7 (C, t-Bu).
1.8. (3E,5E,2R/3E,5Z,2R)-1-O-Benzyl-6-phenyl-
selenenyl-hexa-3,5-dien-2-ol (14)
As described in the general procedure for the Wittig-type
olefination of furanoses one-pot reaction, a soln of
3,5-di-O-benzyl-2-deoxy-a,b-D-ribofuranose 12 (80 mg,
0.25 mmol) in dry THF (0.5 mL) was olefinated by
reaction with methyltriphenylphosphonium bromide
(186 mg, 0.51 mmol) in dry THF (1 mL), PhSeBr
(124 mg, 0.51 mmol) in dry THF (1 mL), and 1.6 M n-
BuLi in hexane (0.7 mL, 1.12 mmol). After 32 h stirring
at room temperature, the reaction mixture was quenched
and the crude product was purified by radial chromato-
graphy (from hexane to 1:3 EtOAc–hexane) to afford 14
(12 mg, 13%) as an inseparable 1:1 3E,5E/3E,5Z mixture
contained in an orange syrup. Data obtained from the
mixture; Rf (1:3 EtOAc–hexane): 0.21. Compound 14E:
1H NMR (CDCl3, 400 MHz): d 7.50–7.26 (m, 10H,
Ar), 6.71–6.31 (m, 3H, H-4,5,6), 5.57 (dd, 1H, J3,4
15 Hz, J2,3 6 Hz, H-3), 4.59 (m, 2H, CH2Ph), 4.42 (m,
1H, H-2), 3.56, 3.39 (m, 2H, H-1a,b), 2.47 (br s, 1H,
OH); 13C NMR (CDCl3, 100.6 MHz): d 134.6–123.8
(C, CH, Ar, C-3,4,5,6), 74.0 (CH2Ph), 71.3 (C-2), 70.3
Acknowledgements
The authors acknowledge the financial support of
DGESIC BQU2005-01188 (Ministerio de Ciencia y
´
Tecnologıa, Spain), technical assistance from the Servei
de Recursos Cientifics (URV) and a fellowship from
DURSI (Generalitat de Catalunya) to O.B.
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