Studies on the Zn(II)-mediated electrophilic selenocyclization and elimination of 3,4-O-isopropylidene-protected hydroxyalkenyl sulfides: synthesis of a 2-phenylselenenyl glycal

Article abstract of DOI:10.1016/j.carres.2010.03.001

Herein, we describe a mild and efficient Zn(II)-mediated electrophilic selenocyclization reaction of readily available and stable 3,4-O-isopropylidene-protected hydroxyalkenyl sulfides to 2-deoxy-2-phenylselenenyl-1-thio-glycosides. This material was transformed into a 2-phenylselenenyl glycal in a controlled manner using an activation-elimination sequence.

Full text of DOI:10.1016/j.carres.2010.03.001

Carbohydrate Research 345 (2010) 1041–1045
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Studies on the Zn(II)-mediated electrophilic selenocyclization and
elimination of 3,4-O-isopropylidene-protected hydroxyalkenyl sulfides:
synthesis of a 2-phenylselenenyl glycal
*
*
Omar Boutureira , Miguel A. Rodríguez, Yolanda Díaz, M. Isabel Matheu, Sergio Castillón
Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, C/Marcelꢀlí Domingo s/n, 43007 Tarragona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Herein, we describe a mild and efficient Zn(II)-mediated electrophilic selenocyclization reaction of read-
ily available and stable 3,4-O-isopropylidene-protected hydroxyalkenyl sulfides to 2-deoxy-2-phenylse-
lenenyl-1-thio-glycosides. This material was transformed into a 2-phenylselenenyl glycal in a controlled
manner using an activation–elimination sequence.
Received 17 January 2010
Received in revised form 17 February 2010
Accepted 1 March 2010
Available online 4 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Thioglycosides
Glycals
Cyclization
Elimination
Selenium
Selenoglycals
Selenonium-induced cyclization of functionalized hydroxyl-
and carboxylic acid-alkenes leading to cyclic ethers and lactones,
as well as several cyclization reactions leading to nitrogen hetero-
cycles, are useful methods for the construction of complex organic
molecules.1 Recently, in the context of our ongoing program on the
stereoselective synthesis of 2-deoxyglycosides, we have described
mechanistic and synthetic studies toward the preparation of 2-
deoxy-2-iodo- and 2-deoxy-2-phenylselenenyl-1-thio-glycosides
III and IV from furanoses I through a sequence involving olefination
and electrophile-induced 6-endo cyclization reactions2 (Scheme 1).
In particular, although we have successfully demonstrated high
regio- and stereoselectivity in the preparation of 2-deoxy-2-phe-
nylselenenyl-1-thio-glycosides IV enhanced by employing 3,4-O-
isopropylidene as a cyclic bifunctional protecting group, there are
some limitations associated with the complex product distribution
(thioglycosides, glycals, and 2-phenylselenenyl glycals) obtained
under certain conditions (i.e., using ZnI2 as a promoter) giving
low overall preparative yields.2a We have also demonstrated that
2-deoxy-2-iodopyranoses V can be efficiently converted into 2-iod-
oglycals VII (Scheme 1). Interestingly, glycals and 2-substituted
glycals are useful building blocks in the preparation of biologically
important molecules especially those with configurations difficult
to access (e.g., D-talal, D-gulal, and D
-allal).3 However, only one pub-
lication dealing with the synthesis of 2-phenylselenenyl glycals
have been reported to date despite the fact that these products
are good candidates for a wide range of selenium-based organic
transformations.4
Herein, we present the results of our studies aimed toward the
development of a mild and efficient Zn(II)-mediated5 electrophilic
selenocyclization of readily available and stable 3,4-O-isopropyli-
dene-protected hydroxyalkenyl sulfides. Furthermore, we also report
our preliminary results on the sulfonium-mediated elimination of 1-
thioglycosides that provide access to 2-phenylselenenyl glycals.
Encouraged by the previous results,2a we postulated that the
presence of a non-nucleophilic counter-ion in the Lewis acid would
provide milder cyclization conditions in order to improve the yield
and control the product distribution.
Initial cyclization reactions were carried out using hydroxyalke-
nyl sulfide 1 and N-(phenylselenenyl)phthalimide (NPSP) in the
absence of a promoter (Table 1, entry 1). Under these conditions,
heptopyranoside 3 (11%) was obtained with complete
a-selectivity
together with 2-phenylselenenyl glycal 5b (34%). Cyclization with
ZnI2 (2 equiv) as the promoter proceeded smoothly and afforded de-
sired product 3 in good yield (60%) maintaining the same regio- and
Other selenenylating agents (e.g., PhSeOTf) in combination with promoters such
as ( )-camphor-10-sulfonic acid (CSA), Mg(ClO4)2, SnCl4, and I2 proved ineffective for
the cyclization of the corresponding tri-O-benzyl-protected hydroxyalkenyl
derivatives.
* Corresponding authors. Tel.: +34 977 559556; fax: +34 977 558446.
E-mail addresses: omar.boutureira@urv.cat (O. Boutureira), sergio.castillon@
urv.cat (S. Castillón).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.03.001

1042
O. Boutureira et al. / Carbohydrate Research 345 (2010) 1041–1045
Olefination
Ph2P(O)CH2SPh
base, THF
As we have previously noted,2a this product distribution (gly-
cals and 2-phenylselenenyl glycals) can probably be attributed to
the reaction between oxocarbenium-ion intermediate VIII, in turn
obtained upon activation of thioglycosides 3 and 4 with [SePh+],
and the different species present in the reaction media (e.g., base
and nucleophilic counter-ions) as depicted in Scheme 2. The con-
version of VIII into IX represents an overall base-promoted PhSH
elimination process, whereas the production of X might be ex-
plained in terms of reductive elimination of PhSSePh–PhSeX.
Interestingly, catalyst loading was successfully reduced to
0.1 equiv without significant erosion of either yield or selectivity
when ZnI2 was used as a promoter, although longer reaction times
were required (Table 1, entry 3). Furthermore, the use of a catalytic
amount of promoter allows the reaction to proceed under milder
conditions and therefore reduces the formation of undesired gly-
cals. With this result in hand, we extended our study to other Zn(II)
catalysts possessing non-nucleophilic counter-ions. The develop-
ment of such a cyclization reaction under mild, catalytic conditions
would considerably facilitate access to this synthetically useful
class of 2-deoxy-2-phenylselenenyl-1-thio-glycosyl donors. Thus,
we observed that Zn(OAc)2, Zn(NO3)2, and Zn(SO4)2 promoted 6-
endo electrophilic selenocyclization of hydroxyalkenyl sulfides in
moderate to good yields (Table 1, entries 5–8 and 11–13), with
Zn(NO3)2 affording products in higher yields (61% and 80% for 3
and 4, respectively) (Table 1, entries 6 and 11). Additionally, the
use of other promoters such as Zn(OTf)2 (0.1 equiv), any increase
in the catalyst loading (up to 1 equiv), and changes in solvent
polarity (e.g., CH3CN) were detrimental for the efficiency of the
R
R
OH SPh
O
R
OH
R
R
R
II
I
[E+]
R
R
O
R
SPh
E
R
R
O
OH
I
NIS
6-endo
Cyclization
H2O
R
III E=I
V
IV E=SePh
Ph2SO
TF2O
Ref. 3d
this work
R
R
O
R
R
R
O
R
SePh
VI
I
VII
Scheme 1. Proposed synthetic sequence for the preparation of 2-iodo- and 2-
phenylselenenyl glycals from furanoses.
stereoselectivity (Table 1, entry 2). ZnCl2 (2 equiv) was also exam-
ined as a promoter but resulted in an unsuccessful cyclization reac-
tion (Table 1, entry 4). Under similar conditions, D-ribo derivative 2
afforded thioglycoside 4 in low yield (15%) and complete b-selectiv-
ity together with glycal 6a2a (74%) as the major product (Table 1, en-
try 11).
Table 1
Zn(II)-mediated electrophilic selenocyclization of hydroxyalkenyl sulfides 1 and 2 to obtain 2-deoxy-2-phenylselenenyl thioglycosides 3 and 4a
O
O
O
O
SePh
OTBDPS
OH
OTBDPS
O
O
O
OH
O
SPh
SPh
SPh
O
O
O
O
SePh
O
O
SPh
1
2
3
4
O
O
OTBDPS
O
O
O
O
O
O
X
X
5a X = H
6a X = H
5b X = SePh
6b X = SePh
Entry
Z/E ratiob
Promoter (equiv)
T (°C)
t (h)
Productc (%)
1d
2d
3
1 0:1
1 0:1
1 1:4
1 1:4
1 1:4
1 1:4
1 1:4
1 1:4
1 1:4
2 1:33
2 1:9
2 1:9
2 1:9
—
rt
15
3
3 (11) + 5b (34)
3 (60) + 5a (10)
3 (57)
ZnI2 (2)
ZnI2 (0.1)
ZnCl2 (2)
ꢁ65 to ꢁ10
ꢁ65 to ꢁ10
ꢁ65 to reflux
ꢁ60 to rt
ꢁ60 to rt
rt
ꢁ60 to rt
ꢁ60 to rt
ꢁ78 to ꢁ30
ꢁ60 to rt
rt
23
43
144
28
8
50
8
6.5
96
96
6
4d
5
Mixture
Zn(OAc)2 (0.1)
Zn(NO3)2 (0.1)
Zn(NO3)2 (0.1)
Zn(SO4)2 (0.1)
Zn(OTf)2 (0.1)
ZnI2 (2)
Zn(NO3)2 (0.1)
Zn(NO3)2 (0.1)
Zn(NO3)2 (1)
3 (37)e
6
3 (61)
Mixture
7f
8
9
3 (7)
g
10d
11
12f
13
4 (15) + 6a (74)
4 (80)h
Mixture
ꢁ30 to rt
Mixture
a
b
c
General conditions: hydroxyalkenyl sulfide (1 equiv), NPSP (1 equiv), promoter (0.1 equiv) in dry CH2Cl2 unless otherwise indicated (see Section 1 for full details).
Starting material Z/E ratio determined by integration of the olefinic proton signals in the 1H NMR spectrum.
Yield based on E-isomer.
Reaction conducted with NPSP (2 equiv).
50% of unreacted starting material was recovered.
Reaction conducted in dry CH3CN.
The corresponding 2-phenylselenenyl pyranose was obtained in ca. 50% yield.
Reaction product obtained as a 1:1 a/b mixture.
d
e
f
g
h

O. Boutureira et al. / Carbohydrate Research 345 (2010) 1041–1045
1043
O
With these practical electrophilic selenocyclization conditions
in hand, we turned our attention to the elimination reaction. As
previously noted, the reaction of 1 with NPSP in the absence of a
promoter lead to the formation of 2-phenylselenenyl glycal 5b in
34% unoptimized yield (Table 1, entry 1). Motivation to develop
this new transformation in a controlled manner prompted us to
investigate the conditions for the activation and subsequent
elimination of 3,4-O-isopropylidene-protected 2-phenylselenenyl-
1-thioglycosides 3 and 4. Eventually, such substrates might allow
direct access to 2-phenylselenenyl glycals 5b and 6b, an approach
not previously explored. Gratifyingly, the treatment of thioglyco-
side 3 under ‘dehydrative glycosylation’ conditions with Ph2SO,
Tf2O, and 2,4,6-tri-tert-butylpyrimidine (TTBP) in CH2Cl2 from
ꢁ60 °C to room temperature promoted the activation of the
anomeric phenylsulfanyl group and subsequent elimination of
conformational constrained10 oxocarbenium-ion XI yielding 2-
phenylselenenyl glycal 5b in good yield (57%) after quenching with
triethylphosphite11 (Scheme 3). This positive result gives an alter-
native to the work described by Schmidt and Preuss.12 Although
these authors reported the preparation of related 2-phenylsulfa-
3, 4
N
O
A
OR
OR
H
O
RO
RO
O
O
Path B
(ZnX2)
Path A
RO
RO
(no promoter)
SePh
SePh
IX
X
VIII
OZnX
B
N
+
X
O
Scheme 2. Plausible mechanism for the observed product distribution during the
cyclization of 3,4-O-isopropylidene-protected alkenyl sulfides induced by electro-
philic selenium species.
cyclization reaction, and no final product was obtained under these
conditions (Table 1, entries 7, 9, 12, and 13). All these transforma-
tions provided the corresponding thioglycosyl donors with com-
nyl-D-glucal in good yield (70%) by reaction of 3,4,6-tri-O-benzyl-
plete regio- and stereoselectivity, except for D-ribo derivative 2
D-glucal with PhSCl and 1,8-diazabicyclo[5.4.0]undec-7-ene
which afforded 4 as a 1:1 a/b mixture due to an in situ anomeriza-
tion (Table 1, entry 11).6 The use of Zn(OAc)2 provided moderate
yields but the reaction was very slow (Table 1, entry 5).
(DBU), in our hands an analogous reaction with PhSeCl and subse-
quent elimination with either N-ethyldiisopropylamine (DIPEA) or
DIPEA/AgOTf proved ineffective, and only hydrolyzed products
were recovered in both cases.
From these results, the following trends were noted; (a) the use
of catalytic amounts of promoter, typically 0.1 equiv, afforded
clean reactions with no significant changes in either yield or selec-
tivity although the reaction were slow. Moreover, the formation of
undesired glycals is also dramatically reduced and/or suppressed.
Although the mechanistic details of this transformation are not
fully understood, studies on Zn(II) halide-mediated cyclization of
propargylic N-hydroxylamines7 and alkynl ketones8 suggested that
Zn(II) is likely to coordinate to the corresponding nucleophile (ie.
unprotected OH of the hydroxyalkenyl sulfide) therefore facilitat-
ing the intramolecular cyclization. Consequently, it would seem
reasonable that the nature of the counter-ions9 affects the equilib-
rium between free and coordinated Zn(II), thereby influencing the
rate of cyclization; (b) the initial reaction temperature is crucial for
a successful cyclization. The reaction proceeded smoothly when
the temperature was slowly raised from ꢁ60 °C to room tempera-
ture; however attempts performed at higher temperatures gave
complex mixtures of products; (c) since the Z/E mixtures of start-
ing alkenes proved to be inseparable, the cyclization reactions
were assayed directly on the mixture of diastereomers. Interest-
ingly, only E-isomers reacted and the corresponding Z-isomers
were recovered unaltered in all cases. These results were in agree-
ment with those obtained in our laboratory with iodine electro-
philes.2d In that case, Z-isomers underwent cyclization at lower
rates and this can be explained by the stereoelectronic effect
known as inside-alkoxy effect.à This effect not only predicts the dif-
ferent reactivity observed between E- and Z-isomers but also pro-
vides a rational explanation of the highly stereochemical outcome
of this transformation (e.g., relative disposition between SePh and
alkoxy at C-3). Specifically, the inside-alkoxy conformation of the
Z-alkenes is sterically crowded and, therefore, the activation energy
that must be overcome to form the transition state in the cyclization
will be higher than that for the corresponding E-alkenes. Although
such compounds could also undergo cyclization via the outside-alk-
oxy conformation, this conformation is insufficiently reactive to pro-
mote cyclization.
Similarly, another promoter system (Me2S2/Tf2O/TTBP)13 which
has been shown to efficiently activate 1-thioglycosides was success-
fully applied to our controlled activation-elimination sequence
affording 5b in 55% yield (Scheme 3). Attempts made to improve
the yield and expand this protocol to the synthesis of 6b proved to
be problematic and extensive decomposition was observed
although several reaction conditions were examined. These in-
cluded different thiophilic agents (NPSP, NIS, and Tf2O/Ph2SO) in
combination with various promoters (ZnI2, Zn(NO3)2, HMPT,14 and
AcOH), bases (DIPEA and NaH), and solvents (CH2Cl2 and CH3CN).
In summary, we have developed
a novel electrophilic
selenocyclization reaction of readily available and stable 3,4-O-
isopropylidene-protected hydroxyalkenyl sulfides to 2-deoxy-2-
phenylselenenyl-1-thio-glycosides under mild conditions in the
presence of catalytic amounts (10 mol %) of Zn(II) salts. Manipula-
tion of the 2-phenylselenenyl-1-thioglycoside moiety allowed the
synthesis of a 2-selenenyl glycal in a controlled manner. Impor-
tantly, the use of 1-thioglycosides instead of lactols as starting
materials prevents the formation of 1,10-disaccharides by dimer-
ization reactions.3d In addition, the PhSe moiety cannot be
eliminated under the reaction conditions tested, therefore avoiding
the formation of the undesired glycals. Moreover, this mild and
O
O
O
SePh
RO
H
O
talo XI
O
O
O
SePh
O
O
O
O
Promoter
O
O
CH2Cl2, TTBP
4Å MS
SPh
3
PhSe
5b
Ph2SO, Tf2O =
11% No P(OEt)3 quench
57% P(OEt)3 quench
à
This effect favors cyclization from the most reactive conformation, in which the
Me2S2, Tf2O =
55% No P(OEt)3 quench
allylic alkoxy group is placed inside the plane that configures the framework of the
double bond. In this conformation, the
r*
is perpendicular to the p-system of the
C–O
double bond, which minimizes the electron-withdrawing effect, causing the double
bond to be more electron-rich and hence more reactive toward electrophiles.
Scheme 3. Sulfonium-mediated elimination of 1-thioglycosides leading to 2-
phenylselenenyl glycal 5b.

1044
O. Boutureira et al. / Carbohydrate Research 345 (2010) 1041–1045
efficient cyclization–elimination protocol provides the opportunity
for the synthesis of particularly challenging tri- and tetrasubstitut-
ed15 dihydropyrane analogues by metal-mediated C–C bond-form-
ing reactions that maybe useful in the synthesis of biologically
active compounds.
0.009 mmol) in dry CH2Cl2 (400 lL). The reaction mixture was stir-
red from ꢁ60 °C to room temperature for 28 h. After standard work-
up, the crude was purified by radial chromatography (from hexane
to 1:3 EtOAc/hexane) to afford 3 (22.4 mg, 49%, 61% based on E-iso-
mer) as a yellowish syrup: ½a D20
ꢂ
+45.7 (c 0.005, CH2Cl2); Rf 0.54 (1:3
EtOAc/hexane); 1H NMR (CDCl3, 400 MHz): d 7.78–7.24 (m, 10H,
Ar), 5.57 (d, 1H, J1,2 10.0 Hz, H-1), 4.73 (dd, 1H, J2,3 2.4, J3,4 7.8 Hz,
H-3), 4.36 (dd, 1H, J3,4 7.8, J4,5 1.8 Hz, H-4), 4.20–4.16 (m, 1H, H-6),
3.94 (dd, 1H, J7a,6 6.0, J7a,b 8.5 Hz, H-7a), 3.85 (dd, 1H, J7b,6 4.2, J7a,b
8.5 Hz, H-7b), 3.60 (dd, 1H, J4,5 1.8, J5,6 8.2 Hz, H-5), 3.05 (dd, 1H,
J1,2 10.0, J2,3 2.4 Hz, H-2), 1.48–1.33 (s, 12H, 4CH3); 13C NMR (CDCl3,
100.6 MHz): d 136.0, 134.6, 131.8, 131.7, 129.4, 129.1, 128.9, 128.8,
127.5 (C, CH, Ar), 110.0, 109.7 (Cketal), 88.3 (C-1), 75.7 (C-5), 74.0 (C-
6), 73.3 (C-4), 70.5 (C-3), 67.2 (C-7), 43.8 (C-2), 27.2, 26.3, 25.4, 25.3
(4CH3); Anal. Calcd for C25H30O5SeS: C, 57.57; H, 5.80; S, 6.15. Found:
C, 57.59; H, 5.78; S, 6.15. Spectroscopic data are consistent with
those reported.2a Z-Isomer 1 was also recovered (6.3 mg, 20%, 98%
based on Z-isomer).
1. Experimental
1.1. General remarks
1H and 13C NMR spectra were recorded using Varian Gemini
300 MHz and Varian Mercury 400 MHz spectrometers. In all the
1H NMR spectra, TMS was used as an internal reference. In the
13C NMR spectra, the residual solvent signal was used as an inter-
nal reference (CDCl3, triplet at 77.23 ppm) unless otherwise stated.
Elemental analysis (C, H, N, and S) was performed with a Carlo Erba
EA 1108 Analyzer in the Servei de Recursos Científics (URV). Opti-
cal rotations were recorded on a Perkin–Elmer 241 MC polarimeter
in a 1 dm cell at 20 °C. Flash column chromatography was per-
1.5. Phenyl 6-(O-tert-butyldiphenylsilyl)-2-deoxy-3,4-O-
formed with Silica Gel 60 (E. Merck, 40–63 lm). Radial chromatog-
isopropylidene-2-phenylselenenyl-1-thio-
(4)
a/b-D-allopyranoside
raphy was performed on 1, 2, or, 4 mm plates of Kieselgel 60 PF254
silica gel (E. Merck), depending on the amount of product. Solvents
were purified using standard procedures. Thin layer chromatogra-
phy (TLC) was performed on aluminum sheets coated with Silica
Gel 60 F254 (E. Merck). Compounds were visualized by UV
(254 nm), and also by spraying the TLC plates with either 6%
H2SO4 in EtOH, or 2% PdCl2 and 15% H2SO4 in water, followed by
charring at 150 °C for a few minutes. Iodonium dicollidine perchlo-
rate (IDCP) was prepared following the method reported by Lemi-
eux and Morgan.16 Starting materials 1 and 2 were prepared as
described in the literature.2d All other reagents were used as re-
ceived from commercial suppliers.
The title compound was prepared following the general proce-
dure for the Zn(II)-mediated electrophilic selenocyclization, starting
from 2 (Z/E ratio 1:9) (83.5 mg, 0.16 mmol), N-(phenylselene-
nyl)phthalimide (47.2 mg, 0.16 mmol), and Zn(NO3)2 (3.0 mg,
0.016 mmol) in dry CH2Cl2 (800 lL). The reaction mixture was stir-
red from ꢁ60 °C to room temperature for 96 h. After standard work-
up, the crude was purified by radial chromatography (from hexane
to 1:3 EtOAc/hexane) to afford 4 (77.7 mg, 72%, 80% based on E-iso-
mer) as an inseparable 1:1
a/b mixture as a white solid. Data ob-
tained from the mixture; Rf 0.86 (1:3 EtOAc/hexane). Data for 4
a
:
1H NMR (CDCl3, 400 MHz): d 7.72–7.18 (m, 20H, Ar), 5.59 (d, 1H,
J1,2 3.6 Hz, H-1), 4.39 (dd, 1H, J2,3 4.6, J3,4 4.6 Hz, H-3), 4.23–4.20
(m, 1H, H-4), 3.85–3.77 (m, 3H, H-5,6a,6b), 3.69–3.65 (m, 1H, H-2),
1.48, 1.27 (s, 6H, 2CH3), 1.08 (s, 9H, t-Bu); 13C NMR (CDCl3,
100.6 MHz): d 136.2–127.1 (C, CH, Ar), 109.4 (Cketal), 87.7 (C-1),
75.9 (C-3), 71.5 (C-5), 70.6 (C-4), 64.2 (C-6), 45.4 (C-2), 28.3, 26.5
(2CH3), 27.0 (CH3, t-Bu), 19.4 (C, t-Bu). Data for 4b: 1H NMR (CDCl3,
400 MHz): d 7.72–7.18 (m, 20H, Ar), 5.12 (d, 1H, J1,2 11.2 Hz, H-1),
4.31 (dd, 1H, J2,3 4.0, J3,4 4.0 Hz, H-3), 3.84 (m, 1H, H-4), 3.76 (dd,
1H, J6a,5 6.2, J6a,b 11.4 Hz, H-6a), 3.65–3.61 (m, 1H, H-5), 3.55 (dd,
1H, J1,2 11.2, J2,3 4.0 Hz, H-2), 1.39, 1.17 (s, 6H, 2CH3), 1.05 (s, 9H, t-
Bu); 13C NMR (CDCl3, 100.6 MHz): d 135.0–127.4 (C, CH, Ar), 109.4
(Cketal), 86.0 (C-1), 79.6 (C-5), 75.4 (C-3), 71.5 (C-4), 64.0 (C-6), 43.4
(C-2), 28.5, 26.2 (2CH3), 27.0 (CH3, t-Bu), 19.4 (C, t-Bu). Spectroscopic
data for 4b are consistent with those reported.2a Z-Isomer 2 was also
recovered (6.5 mg, 8%, 78% based on Z-isomer).
1.2. General procedure for the Zn(II)-mediated electrophilic
selenocyclization
To a solution of alkene (1 mmol) in dry solvent (5 mL) at low
temperature was added in one portion a mixture of N-(phenylse-
lenenyl)phthalimide (1–2 mmol) and promoter (0.1–2 mmol).
The reaction temperature was left to increase depending on the
reactivity of the substrate. After several hours of continuous stir-
ring, the reaction mixture was poured into 10% aqueous NaOH
solution and extracted with CH2Cl2. The combined organic layers
were dried over MgSO4 and concentrated. The residue was purified
by chromatographic techniques.
1.3. General procedure for the sulfonium-mediated elimination
of 1-thioglycosides
To
a solution of 1-thioglycoside (1 mmol), promoter (1–
1.6. 3,4:6,7-Di-O-isopropylidene-2-phenylselenenyl-
-talal (5b)
D-glycero-
2 mmol), TTBP (2–3 mmol), and 4 Å molecular sieves in dry CH2Cl2
(25 mL) at low temperature was added Tf2O (1.1 mmol). The reac-
tion mixture was gradually warmed up to room temperature and
stirred for several hours. The reaction was quenched with Et3N
and washed with saturated aqueous NaHCO3. The combined organ-
ic layers were dried over MgSO4 and concentrated. The residue was
purified by chromatographic techniques.
D
The title compound was prepared following the general proce-
dure for the sulfonium-mediated elimination of 1-thioglycosides,
starting from 3 ( /b ratio 1:0) (10 mg, 0.019 mmol), Ph2SO (8 mg,
0.038 mmol), TTBP (14.7 mg, 0.058 mmol), 4 Å molecular sieves
(8 mg), and Tf2O (4 L, 0.021 mmol) in dry CH2Cl2 (475 L). The
a
l
l
reaction mixture was stirred from ꢁ60 °C to room temperature
for 24 h. After standard workup, the crude was purified by radial
chromatography (1:5 EtOAc/hexane) to afford 5b (4.5 mg, 57%) as
1.4. Phenyl 2-deoxy-3,4:6,7-di-O-isopropylidene-2-
phenylselenenyl-1-thio-D-glycero-a-D-talo-heptopyranoside (3)
a yellowish solid: mp 80–82 °C; ½a D25
ꢂ
+133.4 (c 1.3, CH2Cl2); Rf
0.37 (1:3 EtOAc/hexane); 1H NMR (CDCl3, 400 MHz): d 7.50–7.19
(m, 5H, Ar), 6.90 (s, 1H, H-1), 4.58 (d, 1H, J3,4 6.0 Hz, H-3), 4.51
(dd, 1H, J3,4 6.0, J4,5 0.8 Hz, H-4), 4.40 (dt, 1H, J6,7a = J6,7b 5.6, J6,5
7.6 Hz, H-6), 4.13 (d, 2H, J6,7a = J6,7b 5.6 Hz, H-7ab), 3.91 (dd, 1H,
The title compound was prepared following the general proce-
dure for the Zn(II)-mediated electrophilic selenocyclization, starting
from 1 (Z/E ratio 1:4) (32.1 mg, 0.09 mmol), N-(phenylselene-
nyl)phthalimide (26.5 mg, 0.09 mmol), and Zn(NO3)2 (1.7 mg,

O. Boutureira et al. / Carbohydrate Research 345 (2010) 1041–1045
1045
J5,6 7.6, J4,5 0.8 Hz, H-5), 1.45, 1.38 (s, 12H, 4CH3); 13C NMR (CDCl3,
100.6 MHz): d 151.1 (C-1), 131.1, 129.3, 127.0 (C, CH, Ar), 111.1,
109.8 (Cketal), 106.4 (C-2), 75.7 (C-5), 74.1 (C-6), 72.8 (C-4), 71.6
(C-3), 66.7 (C-7), 28.0, 27.1, 27.0, 25.4 (4CH3); Anal. Calcd for
C19H24O5Se: C, 55.48; H, 5.88. Found: C, 55.43; H, 5.86. Spectro-
scopic data are consistent with those reported.2a
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Acknowledgments
The authors gratefully acknowledge the financial support of DGI
CTQ2005-03124 (Ministerio de Ciencia y Tecnología, Spain), tech-
nical assistance from the Servei de Recursos Cientifics (URV), and
Javier Castilla for preliminary studies. Fellowships from DURSI
(Generalitat de Catalunya) and Fons Social Europeu to O.B. and
M.A.R. are also acknowledged.
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