Phenyl 2-Deoxy-2-iodo-1-thio-glycosides: New Glycosyl Donors for the Stereo-selective Synthesis of 2-Deoxy-oligosaccharides

Article abstract of DOI:10.1055/s-2003-42066

Phenyl 2-deoxy-2-iodo-1-thioglycosides, prepared from simple pentoses by olefination and iodine-induced cyclization, have proved to be efficient glycosyl donors for the stereoselective synthesis of 2-deoxy-2-iodo- oligosaccharides, which are precursors of

Full text of DOI:10.1055/s-2003-42066

LETTER
2143
Phenyl 2-Deoxy-2-iodo-1-thio-glycosides: New Glycosyl Donors for the Stereo-
selective Synthesis of 2-Deoxy-oligosaccharides
New
Glycosyl
D
on
a
ors for the
v
S
tereoselective Syn
e
thesis of 2-
r
D
eoxy-oligosa
A
ccharides rnés, Yolanda Díaz,* Sergio Castillón*
Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virigili, 43005 Tarragona, Spain
Fax +34(977)559563.; E-mail: ydiaz@quimica.urv.es; E-mail: castillon@quimica.urv.es
Received 29 July 2003
R'O
R'O
R'O
R'O
R'O
R'O
R'O
R'O
I
ROH
Abstract: Phenyl 2-deoxy-2-iodo-1-thioglycosides, prepared from
simple pentoses by olefination and iodine-induced cyclization, have
proved to be efficient glycosyl donors for the stereoselective syn-
thesis of 2-deoxy-2-iodo-oligosaccharides, which are precursors of
2-deoxy-oligosaccharides.
O
O
ROH
O
O
OR
R'O
[I+]
[RS+]
[RSe+]
XR
OR
X= S, Se
H+, ROH
Key words: 2-deoxy-oligosaccharides, glycosylation, stereoselec-
tivity, cyclizations, iodine
O
R'O
R'O
R'O
OR
Digitoxine
R'O
Scheme 1 Synthesis of 2-deoxy-a- and 2-deoxy-b-glycosides from
The stereocontrolled formation of the glycosidic linkage
in 2-deoxy-oligosaccharides has been found to be one of
the most challenging tasks in glycosylation reactions,1 be-
cause of the absence of a stereodirecting group at C-2.
This problem can be overcome by using electrondonor
groups (such as iodo, phenylsulfanyl, and phenylselene-
nyl) at position 2. Once the corresponding glycosides
have been obtained, they are further reductively removed
to provide 2-deoxy-glycosides.
glycals.
The key step for the synthesis of 2-deoxy-2-iodo-1-thio-
glycosides is a cyclization of alkenols induced by iodine
electrophiles. These alkenols can be prepared starting
from different protected pentoses by means of an olefina-
tion reaction.
Thus, 2,3,5-tri-O-benzyl-arabinose (1) was initially sub-
mitted to a Peterson olefination reaction by treatment with
Me3SiCH2SPh to afford compound 212 as an E/Z-mixture
in 65% yield (Scheme 2) (entry 1, Table 1). Compound 2
(E-isomer) was then reacted with KH, I2 in diethyl ether
to obtain isomer 313 only (61%) through a regio- and
stereoselective 6-endo-cyclization. The regioselectivity is
governed by the sulfur atom, which stabilizes a positive
charge in the neighbouring carbon. The stereoselectivity
observed is consistent with that reported for alkenols
with an allylic alkoxy group, the iodine atom being cis
to that group (C-3 alkoxy substituent) in the cyclization
product.14 Moreover, the relative stereochemistry of C-1
and C-2 in thioglycoside 3 depends on the configuration
of the starting alkene: thus, from trans-alkenylsulfide 2E
(Scheme 2), the iodine atom and the phenylsulfanyl group
in the cyclization product 3 are in a trans arrangement.
Isomer Z, in turn, did not cyclize in any of the conditions
tested.
Glycosylation can be performed from glycals by activa-
tion with iodine,2 sulfanyl3 and selenenyl4 electrophiles
through a one-pot procedure to afford mainly trans-diaxi-
al (I+) or trans-diequatorial addition (S+, Se+) products
(Scheme 1). Glycosylation is also performed in a two-step
procedure first by isolating a 2-deoxy-2-X-glycosyl donor
(X = I, SR, SeR) and subsequent activation in the pres-
ence of a glycosyl acceptor.5 Acid-catalyzed addition of
an alcohol to a glycal is also a direct method for synthesis-
ing 2-deoxyglycosides, as exemplified in the synthesis of
digitoxine, where the starting 6-deoxy-allal is prepared
from a non-carbohydrate precursor (Scheme 1).6
2-Deoxy-phosphites,7 -phosphoroimidates8 and -dithio-
phosphates9 have also been used as glycosyl donors to
provide mainly the a-derivative. Thio-glycosides10 are
useful glycosyl donors and 2-deoxy-thioglycosides have
recently been used as glycosyl donors in a solid-phase-as-
sisted synthesis of 2-deoxyconjugates.11
We then attempted to improve the E/Z-selectivity by per-
forming a Horner reaction. Both yield and stereoselectiv-
ity were higher in these conditions, the E-alkene being the
major isomer (entry 2, Table 1).15
We report here a new procedure for synthesizing phenyl
2-deoxy-2-iodo-1-thio-glycosides of manno- and allo-
configuration and their use as glycosyl donors for the ste-
reocontrolled synthesis of 2-deoxy-2-iodo-a-manno- and
2-deoxy-2-iodo-b-allo-disaccharides, respectively.
Similarly, 2,3,5-tri-O-benzyl-ribose (4) was converted
into compound 516 (Scheme 2) by reaction with
Me3SiCH2SPh in basic medium. The yield was 48% and
the selectivity was similar to that of entry 1. In this case,
small amounts of a second product were also isolated,
as a result of epimerization at the allylic position.17
When pentose 4 was reacted with PhSCH2P(O)Ph2 in a
SYNLETT 2003, No. 14, pp 2143–2146
0
6
.1
1
.2
0
0
3
Advanced online publication: 07.10.2003
DOI: 10.1055/s-2003-42066; Art ID: G18903ST.pdf
© Georg Thieme Verlag Stuttgart · New York

2144
X. Arnés et al.
LETTER
These new glycosyl donors 3 and 6 have proved to be fair-
ly stable and can be stored in the refrigerator for several
months without significant decomposition (Scheme 3).
OH OBn
BnO
OBn
OH
a
O
BnO
SPh
OBn
OBn
1
2 E/Z
OH
7b
PhCH2OH
7a
I
BnO
BnO
BnO
O
b
2 E
O
Ph
O
SPh
O
BnO
3
OH
OMe
HO
OH OBn
BnO
7c
a
7d
O
BnO
OH
SPh
Figure 1
OBn
OBn
BnO
5 E/Z
BnO
BnO
I
4
I
ROH / NIS TfOH
see Table 2
O
O
BnO
BnO
BnO
BnO
BnO
BnO
c
SPh
O
OR
3
8
SPh
I
OBn
BnO
BnO
BnO
BnO
6
ROH / NIS TfOH
see Table 3
O
I
O
SPh
OR
Scheme 2 Synthesis of phenyl 2-deoxy-2-iodo-thioglycosydes
from pentoses. Reagents: a) See Table 1; b) KH, I2, Et2O, –78 ºC,
61%; c) NIS, NaHCO3 in acetonitrile. From 5E: 63% yield of 6b.
From 5E/5Z = 2:3, 45% yield of 6b/a (2:3).
I
OBn
OBn
6
9
Scheme 3 Glycosylation of 3, 6.
Horner-type olefination, both the yield and E-stereoselec-
tivity improved (entry 4).
We initially tested the benzyl alcohol (7a, Figure 1) gly-
cosylation with the 2-deoxy-2-iodo-manno derivative 3.
We selected the typical reaction conditions used in glyco-
sylation starting from thioglycosides.19 Thus, when 3 was
treated with benzyl alcohol in the presence of NIS/
TfOH,20 2-deoxy-2-iodo-a-glycoside (8a) was obtained in
excellent yield and stereoselectivity (entry 1, Table 2).
Cyclohexanol (7b), cholesterol (7c) and the glucoside 7d
gave 8b, 8c and 8d in a/b-ratios higher than 95:5 with
yields of 70% (entries 2, 3, 4, Table 2).
Compound 5 (E-isomer) rendered 2-deoxy-2-iodo-b-1-
thio-allo-pyranoside 6b by treatment with NIS in acetoni-
trile in a 63% yield.
Starting from a 2:3 E/Z-mixture, 5 cyclized in the same
conditions to give 2-deoxy-2-iodo-1-thio-glycoside 618 as
a 2:3 b/a-mixture in a 45% yield. The iodine atom was
also cis to the neighboring alkoxy chain at C-3, and the b/
a-ratio was the same as the E/Z-ratio in the starting mate-
rial 5, thus indicating that the cis olefin was also reactive
towards cyclization. The less reactive Z-alkene, though,
required higher temperatures to cyclize and this may
well explain the lower yields observed when starting from
a E/Z-mixture of vinylsulfide 5.
Alcohols 7a–d were also glycosylated with the glycosyl
donor 6 in similar conditions (Table 3). The reaction be-
haved like the reaction with the glycosyl donor 3, al-
though the stereoselectivities were slightly lower. Thus,
the yield was best and the stereoselectivity poorest with
the less bulky alcohol 7a (entry 1, Table 3). For the bulk-
ier alcohols 7b–d glycosylation with 6 provided lower
yields than for 7a, as expected. However, the a/b-stereo-
selectivity reached values of 10:90.
Table 1 Olefination of Pentoses 1, 4
Entry Sub-
strate
Reagent
Product Yield
(%)
E/Z-
ratiob
a
Furthermore, the conditions for activating thioglycosides
are almost the same as those for the cyclization itself. This
means that, with an optimun control of the reaction condi-
tions the cyclization and, by consecutive addition of triflic
acid and the glycosyl acceptor, the glycosylation can be
carried out in a one-pot reaction to afford the 2-deoxy-2-
iodo-glycoside.
1
2
3
4
1
1
4
4
PhSCH2SiMe3
2
2
5
5
65%
80%
48%
72%
38:62
87:13
38:62
80:20
b
b
PhSCH2P(O)Ph2
a
PhSCH2SiMe3
PhSCH2P(O)Ph2
a Conditions: BuLi, THF, –78 ºC to r.t.
b Conditions: BuLi, THF, –78 ºC to r.t., (1), reflux (4). Determined by
NMR by integration of olefinic protons.
Synlett 2003, No. 14, 2143–2146 © Thieme Stuttgart · New York

LETTER
New Glycosyl Donors for the Stereoselective Synthesis of 2-Deoxy-oligosaccharides
2145
Table 2 Glycosylation of Alcohols 7a–d with 3a
Chem. 1990, 154, 285. (e) Danishesky, S.; Bilodeau, M. T.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1380.
Yield (%) Ratio a/bb
(3) (a) Ito, Y.; Ogawa, T. Tetrahedron Lett. 1987, 28, 4701.
(b) Ramesh, S.; Franck, S. W. J. Chem. Soc., Chem.
Commun. 1989, 960. (c) Preuss, R.; Schmidt, R. R.
Synthesis 1988, 694. (d) Grewal, G.; Kaila, N.; Franck, R.
W. J. Org. Chem. 1992, 57, 2084.
Entry Glycosyl Alcohol
donor
Product
1
2
3
4
3
3
3
3
7a
7b
7c
7d
8a
8b
8c
8d
88
68
70
70
94:6
>95:5
>95:5
>95:5
(4) Perez, M.; Beau, J. M. Tetrahedron Lett. 1989, 30, 75.
(5) (a) Chong, P. Y.; Roush, W. R. Org. Lett. 2002, 4, 4523.
(b) Kirschning, A.; Jesberger, M.; Schöning, K.-U. Org.
Lett. 2001, 53, 3623. (c) Roush, W. R.; Narayan, S.;
Bennett, C. E.; Briner, K. Org. Lett. 1999, 1, 895.
(d) McDonald, F. E.; Reddy, K. S.; Díaz, Y. J. Am. Chem.
Soc. 2000, 122, 4304. (e) Blanchard, N.; Roush, W. R. Org.
Lett. 1999, 1, 895. (f) Kirschning, A. Eur. J. Org. Chem.
1998, 63, 2267. (g) Roush, W. R.; Sebesta, D. P.; James, R.
A. Tetrahedron 1997, 53, 8837. (h) Roush, W. R.; Sebesta,
D. P.; Bennett, C. E. Tetrahedron 1997, 53, 8825.
(i) Roush, W. R.; Bennett, C. E. J. Am. Chem. Soc. 1999,
121, 3541.
a Glycosyl donor (1 mmol), alcohol (2 mmol), NIS (3 mmol), TfOH
(0.2 mmol), CH2Cl2 (4 mL), –78 to –40 ºC, 2–4 h.
b Determined by NMR by integration of anomeric protons.
Table 3 Glycosylation of Alcohols 7a–d with 6a
Entry Glycosyl Alcohol
donor
Product
Yield (%) Ratio a/bb
(6) McDonald, F. E.; Reddy, K. S. Angew. Chem. Int. Ed. 2001,
40, 3653.
(7) Hashimoto, S. I.; Sano, A.; Sakamoto, H.; Nakajima, I.;
Yanagiya, Y.; Ikegami, S. Synlett 1995, 1271.
(8) Li, H.; Chan, M.; Zhao, K. Tetrahedron Lett. 1997, 38, 6143.
(9) Bielawska, H.; Michalska, M. Tetrahedron Lett. 1998, 39,
9761.
1
2
3
4
6
6
6
6
7a
7b
7c
7d
9a
9b
9c
9d
90
75
72
70
14:86
11:89
10:90
10:90
(10) (a) Oscarson, S. In Carbohydrates in Chemistry and
Biology, Part I, Vol. 1; Ernst, B.; Hart, G. W.; Sinaÿ, P.,
Eds.; Wiley: Weinheim, 2000, 93. (b) Garegg, P. J. Adv.
Carbohydr. Chem. Biochem. 1997, 52, 172.
a Glycosyl donor (1 mmol), alcohol (2 mmol), NIS (3 mmol), TfOH
(0.2 mmol) CH2Cl2 (4 mL), –78 to –40 ºC, 2–4 h.
b Determined by NMR by integration of anomeric protons.
(11) Jaumzens, J.; Hofer, E.; Jesberger, M.; Sourkouni-Argirusi,
G.; Kirschning, A. Angew. Chem. Int. Ed. 2003, 42, 1166.
(12) Compound 2: To a solution of 4 mmol of the phosphine
oxide in 26 mL of THF at –78 ºC, 4.2 mmol of BuLi were
added. The mixture was left to stir at low temperature for 30
min. A solution of 1 mmol of 1 in 2 mL of THF was then
added dropwise. The mixture was allowed to warm to r.t.
overnight. A sat. solution of NH4Cl was then added and the
olefination product extrated with Et2O. The combination of
ethereal layers was dried with MgSO4 and concentrated. The
reaction crude was purified by MPLC (hexane to EtOAc/
hexane = 1:3) to render 2 (80% yield) as a mixture of
diastereoisomers (E/Z-ratio = 87:13) as a syrup. Compound
2E: 1H NMR (400 MHz, CDCl3): d = 7.40–7.15 (m, 20 H,
aromatics), 6.46 (d, 1 H, J2,1 = 15.2 Hz, H-1), 5.87 (dd, 1 H,
J1,2 = 15.2 Hz, J3,2 = 7.6 Hz, H-2), 4.65 (d, 1 H, J = 12.0 Hz,
CH2Ph), 4.57 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.52 (d, 1 H,
J = 11.4 Hz, CH2Ph), 4.49 (s, 2 H, CH2Ph), 4.38 (d, 1 H,
J = 12.0 Hz, CH2Ph), 4.16 (dd, 1 H, J5,4 = 8.0 Hz, J3,4 = 3.6
Hz, H-4), 4.00 (m, 1 H, H-5), 3.58 (m, 3 H, H-3, H-6), 2.76
(d, 1 H, J = 5.2 Hz, OH). 13C NMR (100.6 MHz, CDCl3):
d = 140.8, 137.7, 137.5, 134.0 (C, aromatics), 130.2–126.0
(CH aromatics, C-1, C-2), 80.4 (C-3), 79.1 (C-4), 74.1, 73.2,
70.7 (CH2Ph), 70.1 (C-6), 69.9 (C-5). Compound 2Z:
1H NMR (400 MHz, CDCl3): d = 7.50–7.15 (m, 20 H,
aromatics), 6.67 (d, 1 H, J2,1 = 9.9 Hz, H-1), 6.12 (dd, 1 H,
In this context, the 2-iodo-glycoside (8c) was obtained in
a 35% yield from 2E in a one-pot reaction by treatment
with NIS and then TfOH and cholesterol (7c). Additional
studies on the refinement and application of this method-
ology are in progress.
In conclusion, we have developed a procedure for synthe-
sizing phenyl 2-deoxy-2-iodo-1-thio-glycosides. These
new glycosyl donors have provided excellent yields and
stereoselectivities in the glycosylation of several alcohols.
This methodology provides a new access to 2-deoxy-oli-
gosaccarides.
Acknowledgment
Financial support from DGESIC BQU2002-01188 (Ministerio de
Ciencia y Tecnología, Spain) is acknowledged. Technical assi-
stance from the Servei de Recursos Cientifics (URV) is acknowled-
ged.
References
(1) (a) Kirschning, A.; Jesberger, M.; Schöning, K.-U. Synthesis
2001, 507. (b) Veyrières, A. In Carbohydrates in Chemistry
and Biology, Part I, Vol. 1; Ernst, B.; Hart, G. W.; Sinaÿ, P.,
Eds.; Wiley: Weinheim, 2000, 367. (c) Marzabadi, H.;
Franck, R. W. Tetrahedron 2000, 56, 8385. (d) Castro-
Palomino, J. C.; Schmidt, R. R. Synlett 1998, 501.
(e) Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
(2) (a) Lemieux, R. U.; Levine, S. Can. J. Chem. 1964, 42,
1473. (b) Lemieux, R. U.; Morgan, A. R. Can. J. Chem.
1965, 43, 2190. (c) Thiem, J.; Karl, H.; Schwentner, J.
Synthesis 1978, 696. (d) Thiem, J.; Klaffke, W. Top. Curr.
J1,2 = 9.9 Hz, J3,2 = 9.3 Hz, H-2), 4.88 (d, 1 H, J = 11.0 Hz,
CH2Ph), 4.84 (d, 1 H, J = 11.5 Hz, CH2Ph), 4.73 (d, 1 H,
J = 11.0 Hz, CH2Ph), 4.68 (d, 1 H, J = 12.0 Hz, CH2Ph),
4.63 (d, 1 H, J = 11.5 Hz, CH2Ph), 4.58 (d, 1 H, J = 12.0 Hz,
CH2Ph), 4.21 (m, 1 H, H-5), 3.85 (dd, 1 H, J5,4 = 6.9 Hz,
J3,4 = 3.9 Hz, H-4), 3.77 (m, 3 H, H-3, H-6), 3.12 (d, 1 H,
J = 5.1 Hz, OH). 13C NMR (100.6 MHz, CDCl3): d = 140.8,
137.7, 137.5, 134.0 (C, aromatics), 130.2–126.0 (CH
aromatics, C-1, C-2), 80.4 (C-3), 79.1 (C-4), 74.1, 73.2, 70.7
(CH2Ph), 70.1 (C-5), 64.9 (C-6).
Synlett 2003, No. 14, 2143–2146 © Thieme Stuttgart · New York

2146
X. Arnés et al.
LETTER
(13) Compound 3: A 0.175 M suspension of 1.3 mol of KH 30%
in dry Et2O was added dropwise to a 0.085 M solution of 2
(1 mol) in dry Et2O at 0 ºC, and the resulting mixture was
allowed to stir for 30 min until complete formation of the
alcoholate. The mixture was cooled to –78 ºC and a 0.43 M
solution of iodine (3 mol) in Et2O was then added. The
reaction was allowed to stir at low temperature for 1 h. A
solution of Na2S3O3 was then added and the reaction product
extracted with Et2O. The combination of the etheral layers
was concentrated and the residue purified by radial
3.91 (m, 1 H, H-5), 3.83 (dd, 1 H, J54 = 7.6 Hz, J34 = 3.4 Hz,
H-4), 3.71 (dd, 1 H, J23 = 9.6 Hz, J43 = 3.4 Hz, H-3), 3.67 (m,
2 H, H-6), 2.85 (bs, 1 H, OH). 13C NMR (100.6 MHz,
CDCl3): d = 138.1, 137.8, 135.5, 134.4 (C, aromatics),
129.8–126.5 (CH, aromatics, C-1, C-2), 80.9 (C-3), 77.1 (C-
4), 74.1, 73.3 (CH2Ph), 71.0, 70.8, 70.5 (C-5, C-6, CH2Ph).
(17) Freeman, F.; Robarge, K. D. Carbohydr. Res. 1986, 154,
270.
(18) Compound 6: To a 0.5 M solution of 5 (0.084 g, 0.16 mmol)
(E/Z = 2:3) in CH3CN, NaHCO3 (0.48 mmol) was added.
The mixture was cooled to 0 ºC and left to stir at this
temperature for 5 min. NIS (0.48 mol) was then added and
the reaction mixture was allowed to warm to r.t. and stirred
for 8 h. The mixture was diluted with Et2O and washed with
a sat. solution of Na2S3O3. The combined aqueous layer was
extracted with Et2O. The combination of ethereal layers was
dried with MgSO4 and concentrated. The residue was
purified by radial chromatography to afford 0.060 g (58%
yield) as a b/a mixture = 2:3. Compound 6b: [a]D25 +16.0 (c
0.7708, CH2Cl2). 1H NMR (400 MHz, CDCl3): d = 7.70–
7.20 (m, 20 H, aromatics), 5.11 (d, 1 H, J2,1 = 10.6 Hz, H-1),
4.92 (d, 1 H, J = 10.4 Hz, CH2Ph), 4.75 (d, 1 H, J = 10.4 Hz,
CH2Ph), 4.62 (d, 1 H, J = 11.4 Hz, CH2Ph), 4.60 (d, 1 H,
J = 12.4 Hz, CH2Ph), 4.52 (d, 1 H, J = 11.4 Hz, CH2Ph),
4.51 (d, 1 H, J = 12.4 Hz, CH2Ph), 4.18 (m, 1 H, H-3, H-5),
4.02 (dd, 1 H, J1,2 = 10.4 Hz, J3,2 = 2.4 Hz, H-2), 3.72 (m, 1
H, H-4, H-6a, H-6b). 13C NMR (100.6 MHz, CDCl3): d =
138.4, 138.1, 137.6 (C, aromatics), 133.2 (CH, aromatic),
131.7 (C, aromatic), 128.7–127.4 (CH, aromatics), 84.3
(C-1), 78.7 (C-3), 76.1 (C-4), 75.9 (C-5), 75.7, 73.3, 72.2
(CH2Ph), 69.3 (C-6), 31.8 (C-2). Compound 6a
chromatography to afford 3 (61%) as a yellowish syrup.
Compound 3: [a]D25 +67.8 (c 0.0217, CH2Cl2). 1H NMR
(400 MHz, CDCl3): d = 7.70–7.10 (m, 20 H, aromatics), 5.68
(s, 1 H, H-1), 4.88 (d, 1 H, J = 10.4 Hz, CH2Ph), 4.87 (d, 1
H, J3,2 = 3.6 Hz, H-2), 4.72 (d, 1 H, J = 11.2 Hz, CH2Ph),
4.70 (d, 1 H, J = 11.6 Hz, CH2Ph), 4.54 (d, 1 H, J = 11.2 Hz,
CH2Ph), 4.52 (d, 1 H, J = 10.4 Hz, CH2Ph), 4.48 (d, 1 H,
J = 11.6 Hz, CH2Ph), 4.41 (ddd, 1 H, J4,5 = 8.8 Hz, J6a,5 = 4.4
Hz, J6b,5 = 1.6 Hz, H-5), 3.99 (dd, 1 H, J5,4 = 8.8 Hz,
J
3,4 = 8.4 Hz, H-4), 3.85 (dd, 1 H, J6b,6a = 10.8 Hz, J5,6a = 4.4
Hz, H-6a), 3.73 (dd, 1 H, J6a,6b = 10.8 Hz, J5,6b = 1.6 Hz, H-
6b), 3.10 (dd, 1 H, J4,3 = 8.4 Hz, J2,3 = 3.6 Hz, H-3). 13
C
NMR (100.6 MHz, CDCl3): d = 138.0, 137.2, 133.9 (C,
aromatics), 132.0–127.4 (CH, aromatics), 89.6 (C-1), 77.5
(C-3), 76.2 (C-4), 75.3 (CH2Ph), 73.3 (CH2Ph, C-5), 71.0
(CH2Ph), 68.7 (C-6), 34.8 (C-2).
(14) (a) Landais, Y.; Panchenault, D. Synlett 1995, 1191.
(b) Bravo, F.; Castillón, S. Eur. J. Org. Chem. 2001, 507.
(15) Suzuki, K.; Mukaiyama, T. Chem. Lett. 1982, 1525.
(16) Compound 5: To a solution of 4 mmol of the phosphine
oxide in 26 mL of THF at –78 ºC, 4.2 mmol of BuLi were
added. The mixture was left to stir at low temperature for 30
min. A solution of 1 mmol of the 4 in 2 mL of THF was then
added dropwise. The mixture was allowed to warm to r.t.
first and then heated to reflux. A sat. solution of NH4Cl was
then added and the olefination product extrated with Et2O.
The combination of ethereal layers was dried with MgSO4
and concentrated. The reaction crude was purified by MPLC
(hexane to EtOAc/hexane = 1:3) to render 5 (72% yield) as
a mixture of diastereoisomers (E/Z-ratio = 80:20) as a syrup.
Compound 5E: 1H NMR (400 MHz, CDCl3): d = 7.39–7.25
(m, 20 H, aromatics), 6.54 (d, 1 H, J2,1 = 15.1 Hz, H-1), 5.94
(dd, 1 H, J1,2 = 15.1 Hz, J3,2 = 8.4 Hz, H-2), 4.75 (d, 1 H,
J = 10.8 Hz, CH2Ph), 4.67 (d, 1 H, J = 12.0 Hz, CH2Ph),
4.56 (d, 1 H, J = 10.8 Hz, CH2Ph), 4.51 (d, 1 H, J = 12.0 Hz,
CH2Ph), 4.48 (d, 1 H, J = 12.0 Hz, CH2Ph), 4.40 (d, 1 H,
J = 12.0 Hz, CH2Ph), 4.22 (dd, 1 H, J2,3 = 8.4 Hz, J4,3 = 4.4
Hz, H-3), 3.82 (m, 1 H, H-5), 3.69 (dd, 1 H, J5,4 = 7.6 Hz,
J3,4 = 4.4 Hz, H-4), 3.61 (m, 2 H, H-6), 2.78 (bs, 1 H, OH).
13C NMR (100.6 MHz, CDCl3): d = 138.2, 138.1, 137.8,
134.6 (C, aromatics), 129.1–126.9 (CH, aromatics), 128.8
(C-1), 128.4 (C-2), 81.3 (C-3), 80.8 (C-4), 74.2, 73.4
(CH2Ph), 70.9 (C-6), 70.8 (C-5), 70.5 (CH2Ph). Compound
5Z: 1H NMR (400 MHz, CDCl3): d = 7.39–7.25 (m, 20 H,
aromatics), 6.62 (d, 1 H, J21 = 9.6 Hz, H-1), 6.00 (pseudo t,
1 H, J12 = J32 = 9.6 Hz, H-2), 4.89–4.35 (m, 6 H, CH2Ph),
(spectroscopical data extracted from the a/b-mixture
spectrum): 1H NMR (400 MHz, CDCl3): d = 7.70–7.20 (m,
20 H, aromatics), 5.32 (d, 1 H, J2,1 = 5.4 Hz, H-1), 4.91 (d, 1
H, J = 11.6 Hz, CH2Ph), 4.79 (d, 1 H, J = 10.8 Hz, CH2Ph),
4.68 (ddd, 1 H, J4,5 = 10.0 Hz, J6a,5 = 2.8 Hz, J6b,5 = 2.4 Hz,
H-5), 4.57 (dd, J1,2 = 5.6 Hz, J3,2 = 2.4 Hz, H-2), 4.52 (d, 2
H, J = 10.4 Hz, CH2Ph), 4.42 (d, 1 H, J = 11.2 Hz, CH2Ph),
4.40 (d, 1 H, J = 12.4 Hz, CH2Ph), 4.09 (dd, 1 H, J2,3 = 2.4
Hz, J4,3 = 2.4 Hz, H-3), 3.77 (m, 2 H, H-4, H-6a), 3.62 (dd, 1
H, J6a,6b = 10.8 Hz, J5,6b = 2.4 Hz, H-6b). 13C NMR (100.6
MHz, CDCl3): d = 131.4–126.8 (C, CH, aromatics), 90.0 (C-
1), 78.1, 76.3, 75.6, 73.5, 72.0, 68.8, 67.7 (C-3, C-4, C-5, C-
6, 3 × CH2Ph), 27.0 (C-2).
(19) General Procedure of Glycosylation: A solution of the
glycosyl donor (1 mmol) and the glycosyl acceptor (2 mmol)
in CH2Cl2 (4 mL) were allowed to stir with 4 Å molecular
sieves for 2 h. The mixture was then cooled to –78 ºC, and
NIS (3 mmol) and TfOH (0.2 mmol) were added. The
mixture was allowed to warm to –40 ºC and stirred for 2–4
h. The reaction mixture was then diluted with CH2Cl2 and
washed with a solution of Na2S3O3. The ethereal layer was
dried with Na2SO4 and concentrated. The residue was then
purified by radial chromatography.
(20) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H.
Tetrahedron Lett. 1990, 31, 1331.
Synlett 2003, No. 14, 2143–2146 © Thieme Stuttgart · New York