ZnCl2/alumina impregnation catalyzed Ferrier rearrangement: an expedient synthesis of pseudoglycosides

Article abstract of DOI:10.1016/j.tet.2009.04.099

An improved method for the synthesis of 2,3-unsaturated-O-glycosides has been developed. ZnCl₂ impregnated on activated alumina acts as an excellent reagent system for the conversion of 2,4,6-tri-O-acetyl-d-glucal to 2,3-unsaturated-O-glycosides with high α-selectivity.

Full text of DOI:10.1016/j.tet.2009.04.099

Tetrahedron 65 (2009) 5844–5848
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
ZnCl2/alumina impregnation catalyzed Ferrier rearrangement: an expedient
synthesis of pseudoglycosides
*
Bala Kishan Gorityala, Rujee Lorpitthaya, Yaguang Bai, Xue-Wei Liu
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
An improved method for the synthesis of 2,3-unsaturated-O-glycosides has been developed. ZnCl2 im-
pregnated on activated alumina acts as an excellent reagent system for the conversion of 2,4,6-tri-O-
Received 11 February 2009
Received in revised form 9 April 2009
Accepted 30 April 2009
acetyl-
D-glucal to 2,3-unsaturated-O-glycosides with high
a
-selectivity.
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 8 May 2009
1. Introduction
2. Results and discussion
2,3-Unsaturated-O-glycosides or pseudoglucals are known as
versatile chiral intermediates in the synthesis of antibiotics, nu-
cleosides, complex carbohydrates, and various natural products.1
Moreover, the unsaturated part of the sugar ring allows many
straightforward modifications such as hydrogenation, hydroxyl-
ation, epoxidation, and aminohydroxylation, which contribute to
their diversities and complexities. To date, many continuous efforts
to develop expedient syntheses of 2,3-unsaturated-O-glycosides
have been extensively made. One of the most common procedures
to achieve pseudoglucals is the acid-catalyzed allyl rearrangement
of glucals, which was discovered by Ferrier et al.2 The Ferrier rear-
rangement is a reliable procedure for the formation of unsaturated
glycoside derivatives, which has seen expensive development over
decades. This rearrangement typically occurs by treatment of glu-
cals and alcohols with Lewis acids or oxidants such as ZnCl2,3
H3PO4,4 InCl3,5 SnCl4,6 Yb(OTf)3,7 FeCl3,8 montmorillionite K-10,9
A facile and highly stereoselective preparation of 2,3-un-
saturated-O-glycoside derivatives from 3,4,6-tri-O-acetyl- -glucal
D
was initially investigated by examining the incorporation of Lewis
acid on different solid supports. Pursuing the environmental im-
pact, all reactions were carried out with minimal solvent and at
ambient temperature. We surveyed the catalytic activity of various
Lewis acids in the glycosylation of glucal by employing ethanol as
a glucal acceptor and Al2O3 as a solid media (Table 1). Among them,
ZnCl2 was found to be superior to other catalysts in terms of yield,
reaction profile and selectivity. However, strong Lewis acids [FeCl3,
SnCl2, AlCl3 and BF3$OEt2] also provided pseudoglucal products,
albeit with moderate yields and selectivities (Table 1, entries 1–4).
Table 1
Optimized conditions for Ferrier rearrangement with Lewis acids/solid supportsa
OAc
11
LiBF4,10 Dy(OTf)3, DDQ,12 I2,13 I(Coll)2ClO4,14 CAN,15 CeCl3$7H2O,16
OAc
Lewis Acid
O
HClO4/SiO2,17 and N-iodosuccinamide.18 These methods could
generate rearrangement products in one-step from glycoside de-
rivatives, but they often suffer from incomplete stereoselectivity
and the limited uses of acid-labile glucal donors and acceptors. The
oxidants are usually required in stoichiometric amounts, and
stringent conditions, long reaction times, and high temperatures
are unavoidable. Thus, any further improvement must be judged
against the vast background of current knowledge. Here, we wish to
report a new synthetic component of Ferrier reaction, which de-
AcO
O
Solid Support
EtOH
AcO
AcO
OEt
c
Entry
Lewis Acid/solid supportb
Time
% Yield (a/b)
1
2
3
4
5
6
7
8
9
FeCl3$6H2O/Al2O3
SnCl2/Al2O3
AlCl3/Al2O3
BF3$OEt2/Al2O3
ZnCl2/Al2O3
ZnCl2/SiO2
ZnCl2/MgO
ZnCl2/4 Å molecular sieve
ZnCl2/MnO
30 min
45 min
80 min
30 min
10 min
2 h
6 h
4 h
6 h
86 (1:1)
32 (6:1)
60 (8:1)
56 (8:1)
92 (20:1)
48 (6:1)
72 (2:1)
Trace
livers the desired products with exclusive
high yield and in a short reaction time.
a-stereoselectivity in
75(1:1)
a
Ethanol (10 equiv) was used.
b
Lewis acid (1 equiv) on 5.3 equiv of solid support was used per 1 equiv of tri-O-
acetyl- -glucal.
ratio was confirmed by the anomeric proton ratio on 500 MHz NMR.
* Corresponding author. Tel.: þ65 63168901; fax: þ65 67911961.
E-mail address: xuewei@ntu.edu.sg (X.-W. Liu).
D
c
a/b
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.099

B.K. Gorityala et al. / Tetrahedron 65 (2009) 5844–5848
5845
Table 2
To study the effect of the solid media, a wide range of solid supports
Ferrier reaction of 2,3-tri-O-acetyl-
D
-glucal with alcohols in the presence of the
such as silical gel, MgO, 4 Å molecular sieves, MnO, and Al2O3 were
examined by mixing with 1 equiv of ZnCl2. The results showed that
silica gel and molecular sieves had no impact on the rearrange-
ment, whereas MgO and MnO found to be less efficient in both
conversion and anomeric selectivity (Table 1, entries 6–9). ZnCl2
impregnated on activated alumina was conclusively the best
combination in this synthetic transformation giving rise to a good
ZnCl2/Al2O3 reagent systema
Entry
1b
Product
OAc
Time (min)
10
Yield (%)
922c
a/
bd
O
AcO
20:3
OMe
2a
anomeric ratio (
shown in Table 1, entry 5.
a
/
b
¼20:1) and short reaction time (10 min) as
OAc
O
According to the published results, most of the Ferrier reactions
AcO
2c
20
20
30
94
a
a
a
of 3,4,6-tri-O-acetyl-D
-glycal conducted in the solution phase3 and
O
2b
15
the miscellaneous system17 were sluggish (12 h) and showed the
low level of the anomeric selectivity. Moreover, some reactions
required considerable care when using toxic and moisture sensitive
catalysts. These cause problems, the tedious procedures and work-
up and require special equipments. On the other hand, the solvent
free ZnCl2/Al2O3 system19 acts as a potential tool for synthesis of
2,3-unsaturated glycosides. The purification could be easily done
after the completion of the reaction (10–30 min) by silica gel col-
umn chromatography.
OAc
O
3
8311
AcO
O
2c
OAc
O
AcO
4
78
O
O
2d
Having the optimized conditions for the glycosylation of glucal
over ZnCl2/alumina impregnation in hand we proceeded to screen
a wide range of alcohols and thiols (Table 2). In a typical reaction,
a mixture of glucal and alcohol was added to the ZnCl2/alumina
impregnation and stirred. In order to maintain the proper stirring of
the reaction mixture excess of alcohol was used (3 equiv). When
the reaction was completed, the solid mass was simply filtered off,
rinsed with dichloromethane (or ethyl acetate). Evaporation of the
solvent and subsequent elution of the crude product on the short
column chromatography afforded the desired 2,3-unsaturated
glycosides (2a–p) in excellent yields. All reactions gave best yields
when 1 equiv of ZnCl2 used with 5.3 equiv of activated alumina.
Using methanol and ethanol as nucleophiles gave a mixture of
OAc
O
AcO
5
6
10
20
8811
a
a
O
2e
OAc
O
AcO
82
O
Ph
2f
OAc
O
AcO
anomeric diastereomers (up to
of size and nature furnished desired
compliment could be cooperated with a glucose derivative to give
a
/b
20:1), while others irrespective
7
45
70
a
Ph
O
a-glycosides. Moreover, this
2g
the corresponding disaccharide 2p in 94% yield and 20:1 of a/b ratio
(entry 16).
OAc
O
AcO
AcO
AcO
AcO
8
10
10
10
20
85
a
a
a
a
Most of the glycosylated products were obtained in exclusively
pure diastereomers as resulted in Table 2. The significance of the
highly stereoselective glycosylation has been highlighted in this
report. We then explored the scope of this concise route for the
synthesis of pseudoglucals connected to various biologically im-
O
2h
OAc
O
9
85
portant natural products. For example, citronellol,23 -menthol,24
L
O
2i
borneol,24 endo-fenchol, and pregnenolone25 glycosides, these all
have served as challenging targets to study and transform because
of their diversity of the biological activities and their structural
complexity.
OAc
O
10
11
8520
Some of them were generally synthesized by enzymatic26 as
well as Koenigs–Knorr–Zemplen24 methods, which are expensive,
lengthy, and tedious procedures. We envisioned that our solid
support system would offer an easy access to natural products
O
2j
OAc
O
82
containing
glucal to the corresponding 2,3-unsaturated glycosides was rapid
and the desired compounds were formed exclusively with
anomeric selectivity within 10–15 min of reaction time (Table 3,
entries 1–4). Pregnenolone glycoside, which was first isolated from
Nerium Odorum,25 operates as a powerful neurosteroid in the brain,
modulating the transmission of messages from neuron to neuron
and strongly influencing learning and memory. The synthesis of
pregnenolone 2,3-unsaturated glycoside was also success with
a-selective sugar moiety. As expected, transformation of
O
2k
a
-
OAc
O
AcO
AcO
12
13
15
10
9011
a
a
O
2l
OAc
O
OMe
7521
excellent a-selectivity (88% yield and 20:1 a/b selectivity) as de-
O
scribed in Table 3, entry 5. Furthermore, its structure was eluci-
dated by NMR spectroscopic data and confirmed by X-ray
crystallography (Fig. 1).
2m
(continued on next page)

5846
B.K. Gorityala et al. / Tetrahedron 65 (2009) 5844–5848
Table 2 (continued)
Entry
Product
Time (min)
10
Yield (%)
62
a
a
/
bd
OAc
O
AcO
14
S
OMe
2n
OAc
O
AcO
15
10
20
6522
a
S
2o
Figure 1. X-ray structure of pregnenolone 2,3-unsaturated glycoside 3e.
OAc
O
AcO
advantages of this method concern high anomeric selectivity, rapid
reaction time, and friendly environmental conditions. Low cost
reagents and no aqueous work-up are required and the alumina
could be recycled (up to three times).
16c
94
20:1
O
O
OBn
BnO
BnO
OBn
2p
a
b
c
Unless otherwise noted, 3 equiv of nucleophiles were used.
10 Equiv of methanol was used.
As nucleophile is solid, glucal, 1 equiv of alcohol and ZnCl2/Al2O3 impregnation
4. Experimental
4.1. General
were mixed and grinded by using a mortar.
d
a/b
ratio was confirmed by the anomeric proton ratio on 1H NMR spectra.
Product purification by flash column chromatography was ac-
complished using silica gel 60 (0.010–0.063 nm). The 1H and 13C
NMR data was obtained on a 300 MHz Bruker ACF 300 and 500 MHz
Bruker AMX 500 NMR spectrometers. For 1H NMR, chemical shifts
are reported in parts per million (ppm) downfield from tetrame-
thylsilane and are, in all cases, referenced to the residual proton
3. Conclusion
We have demonstrated a new protocol for forming a glycosidic
linkage in high diastereoselective fashion. Many complex alcohols
and thiols could be incorporated with glucal donor in a single
process. Eleven new compounds, which include five natural prod-
uct-like compounds, were successfully prepared. The main
resonance peaks:
reported in parts per million relative to the center peak of the
multiplet for deuterated solvents: 77.0 (t) for CDCl3. Coupling
d
7.26 for CHCl3. The 13C NMR chemical shifts were
d
constants (J) for all spectra are reported in hertz. Following abbre-
viations classify the multiplicity: s¼singlet, d¼doublet, t¼triplet,
q¼quartet, m¼multiplet or unresolved, br¼broad signal. Infrared
spectra were measured on a Bio-RAD FTS 165 FT-IR Spectrometer as
thin films on sodium bromide plates and are recorded in units of
cmꢀ1. HRMS (ESI) spectra were recorded on a Finnigan/MAT LCQ
quadrupole ion trap mass spectrometer, coupled with the TSP4000
HPLC system and the Crystal 310 CE system. X-ray crystallographic
data were collected by using a Bruker X8Apex diffractometer with
Table 3
Ferrier reaction of 2,3-tri-O-acetyl-
the presence of the ZnCl2/Al2O3 reagent system
D-glucal with various natural products alcohols in
Entry
1
Natural product alcohols
Product
Time (min)
15
Yield (%)
8526
a
a
/b
HO
H
3a
S-(-)-β-Citronellol
Mo Ka radiation (graphite monochromator).
2a
3b
10
92
a
4.2. General procedure for preparation 2,3-unsaturated
glycosides
OH
L-Menthol
To a stirred mixture of tri-O-acetyl-D-glucal (100 mg, 0.37 mmol)
and an alcohol (1 equiv) was added 250 mg of ZnCl2/Al2O3 at am-
bient temperature. The mixture was stirred for appropriate time
(Tables 2 and 3), and completion of the reaction was monitored by
TLC analysis. The reaction mixture was then filtered and washed
with dichloromethane, and the combined organic extract was con-
centrated under vacuum. All the products were purified by silica gel
column chromatography (30% EtOAc/hexane).
3a
3c
10
15
80
84
a
a
HO
(+)-Borneol
4a
3d
HO
(+)-endo-Fenchol
4.2.1. Nonadecanyl 4,6-di-O-acetyl-2,3-dideoxy-a-D-erythro-hex-
O
2-enopyranoside (2b)
24
Rf (30% EtOAc/hexane) 0.67; [
(500 MHz, CDCl3)
a]
þ83.3 (c 0.7, CHCl3); 1H NMR
D
5a
3e
20
88
20:1
H
d
5.84 (d, J¼10 Hz, 1H), 5.80 (d, J¼10 Hz, 1H), 5.29
(d, J¼10 Hz, 1H), 5.0 (s, 1H), 4.23 (dd, J¼12.1, 5.4 Hz, 1H), 4.15 (dd,
J¼12.1, 2.2 Hz, 1H), 4.10–4.08 (m, 1H), 3.75 (dt, J¼9.4, 6.9 Hz, 1H),
3.48 (dt, J¼9.5, 6.6 Hz, 1H), 2.07 (s, 3H), 2.06 (s, 3H), 1.61–1.52 (m,
2H), 1.29–1.23 (m, 30H), 0.86 (t, J¼6.9 Hz, 3H); 13C NMR (125 MHz,
H
H
HO
Pregnenolone
a
As these nucleophiles are solids, 1 equiv of them and glucal, ZnCl2/Al2O3
impregnation were mixed and grinded by using a mortar.
CDCl3)
d 170.7, 170.2, 128.9, 127.9, 94.3, 69.0, 66.8, 65.3, 63.0, 32.8,

B.K. Gorityala et al. / Tetrahedron 65 (2009) 5844–5848
5847
31.9, 29.7, 29.6, 29.6, 29.4, 29.3, 26.2, 26.0, 25.7, 22.6, 20.9, 20.7, 14.1;
4.2.7. 2-Methoxybenzenethainyl 4,6-di-O-acetyl-2,3-dideoxy-a-D-
IR (NaCl neat) nmax/cmꢀ11747, 1226, 1039; HRMS (ESI) m/z [MþNa]þ
erythro-hex-2-enopyranoside (2n)
24
calcd for C28H50O7Na 505.3505, found 505.3509.
Rf (30% EtOAc/hexane) 0.45; [
(500 MHz, CDCl3)
2H), 6.40 (d, J¼5.8 Hz, 1H), 5.13 (dd, J¼10.1, 4.5 Hz, 1H), 4.94 (t,
J¼5.8 Hz, 1H), 4.54 (m, 1H), 4.38 (dd, J¼12.2, 4.4 Hz, 1H), 4.32 (dd,
J¼12.2, 2.1 Hz, 1H), 3.88 (s, 1H), 2.06 (s, 6H), 1.47 (s, 3H); 13C NMR
a
]
þ262.6 (c 0.5, CHCl3); 1H NMR
D
d
7.42 (dd, J¼7.5, 1.6 Hz, 1H), 7.24 (m, 1H), 6.8 (m,
4.2.2. 2-(Allyloxy)ethanyl 4,6-di-O-acetyl-2,3-dideoxy-
a-D
-
erythro-hex-2-enopyranoside (2d)
24
Rf (30% EtOAc/hexane) 0.35; [
(500 MHz, CDCl3)
a
]
þ272.2 (c 0.4, CHCl3); 1H NMR
D
d
5.90 (ABX system, JAX¼17.2 Hz, JBX¼9.6 Hz,
(125 MHz, CDCl3) d 170.7, 169.8, 158.7, 144.7, 133.6, 129.1, 122.9,
JAB¼5.4 Hz, 1H), 5.85 (br s, 2H), 5.30 (d, J¼9.7 Hz, 1H) 5.26 (dd,
J¼17.2, 1.6 Hz, 1H), 5.16 (d, J¼9.5 Hz, 1H), 5.06 (s, 1H), 4.23 (dd,
J¼12.1, 5.2 Hz, 1H), 4.15 (dd, J¼12.1, 2.3 Hz, 1H), 4.12–4.10 (m, 1H),
4.0 (d, J¼5.0 Hz, 2H), 3.89 (dt, J¼11.0, 4.5 Hz, 1H), 3.72–3.68 (m, 1H),
3.61 (t, J¼4.8 Hz, 2H), 2.07 (s, 3H), 2.05 (s, 3H); 13C NMR (125 MHz,
120.8, 111.0, 98.7, 70.8, 69.8, 62.3, 55.8, 40.4, 20.7, 19.8; IR (NaCl
neat) nmax/cmꢀ1 1743, 1370, 1232, 1037; HRMS (ESI) m/z [MþNa]þ
calcd for C17H20O6SNa 375.0878, found 375.0871.
4.2.8. Benzyl-O-(40,60-di-O-acetyl-20-30-dideoxy-
a
-D
-erythro-hex-
CDCl3)
d
170.7, 170.2, 134.6, 129.1, 127.7, 117.1, 94.6, 72.1, 69.2, 67.8,
20-enopyranosyl)-(1/6)-2,3,4-tri-O-benzyl-
a-D-glucopyranoside
66.8, 65.2, 62.9, 20.9, 20.7; IR (NaCl neat) nmax/cmꢀ1 1743, 1317,
1234, 1047; HRMS (ESI) m/z [MþNa]þ calcd for C15H22O7Na
337.1263, found 337.1252.
(2p)
24
Rf (30% EtOAc/hexane) 0.45; [
(500 MHz, CDCl3)
a
]
þ20.8 (c 1.0, CHCl3); 1H NMR
D
d
7.34–7.21 (m, 20H), 5.85 (s, 2H), 5.30 (d,
J¼9.6 Hz, 1H), 5.14 (s, 1H), 4.96–4.90 (m, 4H), 4.81–4.76 (m, 2H),
4.67–4.62 (m, 3H), 4.51 (d, J¼7.8 Hz, 1H), 4.13–4.07 (m, 2H), 3.84–
3.71 (m, 1H), 3.68–3.64 (m, 2H), 3.60–3.55 (m, 1H), 3.51–3.45 (m,
4.2.3. 3-Phenylprop-2-ynyl 4,6-di-O-acetyl-2,3-dideoxy-a-D-
erythro-hex-2-enopyranoside (2f)
24
Rf (50% EtOAc/hexane) 0.52; [
(500 MHz, CDCl3)
a
]
þ196.0 (c 0.5, CHCl3); 1H NMR
2H), 2.07 (s, 3H), 2.06 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 170.8,
D
d
7.46–7.42 (m, 2H), 7.32–7.29 (m, 3H), 5.93 (d,
170.3, 135.5, 138.4, 137.4, 129.0, 128.5, 128.5, 128.4, 128.4, 128.2,
128.1, 128.1, 127.9, 127.9, 127.8, 127.8, 127.7, 127.7, 127.7, 102.8, 102.5,
94.8, 84.7, 84.5, 82.4, 78.0, 77.6, 75.7, 75.1, 75.1, 75.0, 74.9, 74.6, 71.6,
J¼17.5 Hz, 1H), 5.42–5.33 (m, 2H), 4.53 (s, 1H), 4.28 (dd, J¼12.1,
5.1 Hz, 1H), 4.20 (dd, J¼12.1, 2.4 Hz, 1H), 4.19–4.11 (m, 1H), 2.09 (s,
3H), 2.07 (s, 3H); 13C NMR (125 MHz, CDCl3)
d
170.7, 170.2, 131.8,
71.2, 67.2, 67.0, 65.2, 62.8, 62.0, 60.4, 21.0, 20.8; IR (NaCl neat) nmax/
129.6, 128.6, 128.4, 128.3, 127.4, 122.3, 92.7, 86.5, 67.2, 65.2, 62.8,
55.8, 20.9, 20.7; IR (NaCl neat) nmax/cmꢀ1 1743, 1371, 1234, 1037;
HRMS (ESI) m/z [MþNa]þ calcd for C19H21O6Na 345.1338, found
345.1339.
cmꢀ1 1733, 1455, 1259, 1061; HRMS (ESI) m/z [MþNa]þ calcd for
C44H48O11Na 775.3094, found 775.3085.
4.2.9. S-(ꢀ)-
b-Citronellyl 4,6-di-O-acetyl-2,3-dideoxy-a-D-erythro-
hex-2-enopyranoside (3a)
24
4.2.4. 3-Pentanyl 4,6-di-O-acetyl-2,3-dideoxy-
a
-D-erythro-hex-2-
Rf (30% EtOAc/hexane) 0.64; [
(500 MHz, CDCl3)
a
]
D
þ41.5 (c 0.5, CHCl3); 1H NMR
enopyranoside (2h)
d
5.86 (d, J¼10.4 Hz, 1H), 5.87 (d, J¼10.4 Hz, 1H),
24
Rf (50% EtOAc/hexane) 0.66; [
a
]
þ313.9 (c 0.2, CHCl3); 1H NMR
5.29 (dd, J¼9.6, 1.1 Hz, 1H), 5.08 (t, J¼7.0 Hz, 1H), 5.01 (s, 1H), 4.23
(dd, J¼12.1, 5.4 Hz, 1H), 4.16 (dd, J¼12.1, 2.2 Hz, 1H), 4.10–4.07 (m,
1H), 3.82 (dd, J¼7.4, 2.2 Hz,1H), 3.55–3.50 (m, 1H), 2.08 (s, 3H), 2.07
(s, 3H), 1.99–1.93 (m, 2H), 1.67–1.65 (m, 4H), 1.59–1.55 (m, 4H),
1.41–1.30 (m, 2H), 1.17–1.12 (m, 1H), 0.88 (d, J¼6.6 Hz, 3H); 13C NMR
D
(300 MHz, CDCl3)
d
5.85 (d, J¼10.5 Hz, 1H), 5.82 (d, J¼10.5 Hz, 1H),
5.29 (dt, J¼9.3, 1.4 Hz, 1H), 5.11 (s, 1H), 4.24 (dd, J¼12.1, 5.7 Hz, 1H),
4.11–4.12 (m, 3H), 3.56 (p, J¼5.9 Hz, 1H), 2.08 (s, 3H), 2.07 (m, 3H),
1.60–1.55 (m, 3H), 0.94 (t, J¼7.4 Hz, 3H), 0.91 (t, J¼7.4 Hz, 3H); 13C
NMR (75 MHz, CDCl3)
d
170.8, 170.3, 128.7, 128.2, 93.4, 81.2, 66.9,
(125 MHz, CDCl3) d 170.8, 170.2, 131.2, 128.9, 127.9, 124.6, 94.3, 67.0,
65.3, 63.1, 27.1, 26.2, 20.9, 20.7, 10.0, 9.3; IR (NaCl neat) nmax/cmꢀ1
1743, 1369, 1230, 1033; HRMS (ESI) m/z [MþNa]þ calcd for
C15H24O7Na 323.1471, found 323.1462.
66.9, 65.3, 63.0, 37.2, 36.5, 29.5, 25.7, 25.4, 20.9, 20.7, 19.3, 17.6; IR
(NaCl neat) nmax/cmꢀ1 1743, 1371, 1232, 1035; HRMS (ESI) m/z
[MþNa]þ calcd for C20H32O6Na 391.2097, found 391.2086.
4.2.5. Cyclohex-2-enyl 4,6-di-O-acetyl-2,3-dideoxy-
a
-D-erythro-
4.2.10. L-Menthyl 4,6-di-O-acetyl-2,3-dideoxy-a-D-erythro-hex-2-
hex-2-enopyranoside (2i)
enopyranoside (3b)
24
24
Rf (30% EtOAc/hexane) 0.50; [
(500 MHz, CDCl3)
a]
þ38.7 (c 0.5, CHCl3); 1H NMR
Rf (30% EtOAc/hexane) 0.61; [
a
]
D
þ142.5 (c 0.5, CHCl3); 1H NMR
D
d
5.83–5.82 (m, 3H), 5.77–5.76 (m, 1H), 5.29 (d,
(500 MHz, CDCl3)
d
5.85 (s, 2H), 5.26 (d, J¼10 Hz, 1H), 5.08 (s, 1H),
J¼8.8 Hz, 1H), 5.19 (d, J¼17.4 Hz, 1H), 4.25–4.20 (m, 2H), 4.19–4.17
(m, 2H), 2.09 (d, J¼2.7 Hz, 3H), 2.08 (d, J¼1.3 Hz, 2H), 2.07–2.03 (m,
2H), 1.97–1.88 (m, 2H), 1.83–1.66 (m, 2H), 1.91–1.53 (m, 1H); 13C
4.18 (dd, J¼12.3, 6.7 Hz, 1H), 4.17–4.14 (m, 2H), 3.39 (dt, J¼10.6, 4.4
Hz, 1H), 2.17 (d, J¼4.0 Hz, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 1.67–1.59
(m, 2H), 1.44–1.37 (m, 1H), 1.25–1.20 (m, 1H), 1.03 (dd, J¼23.2,
12.2 Hz, 1H), 0.95 (dd, J¼12.1, 3.0 Hz, 1H), 0.92–0.87 (m, 7H), 0.85–
0.79 (m, 1H), 0.75 (d, J¼7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
NMR (125 MHz, CDCl3)
d 170.8, 170.3, 131.5, 128.9, 128.7, 128.4,
128.3, 94.0, 72.7, 66.8, 65.3, 63.1, 30.1, 25.0, 21.0, 19.2; IR (NaCl neat)
nmax/cmꢀ1 1743, 1371, 1230, 1033; HRMS (ESI) m/z [MþNa]þ calcd
for C16H22O6Na 333.1314, found 323.1310.
d
170.8, 170.3, 128.5, 128.0, 96.1, 81.0, 66.6, 65.3, 63.3, 48.8, 43.3,
34.2, 31.7, 25.6, 23.1, 22.3, 21.1, 20.9, 20.8, 16.2; IR (NaCl neat) nmax
/
cmꢀ1 1743, 1369, 1234, 1035; HRMS (ESI) m/z [MþNa]þ calcd for
4.2.6. Cyclooctanyl 4,6-di-O-acetyl-2,3-dideoxy-
a
-D-erythro-hex-
C20H32O6Na 391.2097, found 391.2089.
2-enopyranoside (2k)
24
Rf (50% EtOAc/hexane) 0.54; [
(500 MHz, CDCl3)
a
]
þ156.7 (c 1.0, CHCl3); 1H NMR
4.2.11. (þ)-Bornyl 4,6-di-O-acetyl-2,3-dideoxy-
a-D-erythro-hex-2-
D
d
5.83 (d, J¼10.2 Hz, 1H), 5.76 (dt, J¼10.2, 2.3 Hz,
enopyranoside (3c)
24
1H), 5.26 (dd, J¼9.6, 1.4 Hz, 1H), 5.09 (s, 1H), 4.20 (d, J¼12.1 Hz, 1H),
4.12 (dd, J¼12.1, 5.9 Hz, 1H), 4.16–4.11 (m, 1H), 3.83 (h, J¼4.2 Hz,
1H), 2.07 (s, 3H), 2.05 (s, 3H), 1.86–1.83 (m, 1H), 1.78–1.63 (m, 4H),
Rf (30% EtOAc/hexane) 0.61; [
a
]
þ72.6 (c 0.8, CHCl3); 1H NMR
D
(500 MHz, CDCl3)
d
5.84–5.79 (m, 2H), 5.27 (d, J¼9.8 Hz, 1H), 4.99
(s, 1H), 4.21 (dd, J¼12.2, 5.6 Hz, 1H), 4.12 (dd, J¼12.2, 2.2 Hz, 1H),
4.10–4.09 (m, 1H), 3.82 (dt, J¼6.6, 2.1 Hz, 1H), 2.24–2.22 (m, 1H),
2.07 (s, 3H), 2.06 (s, 3H), 1.96–1.90 (m, 1H), 1.70–1.64 (m, 2H), 1.59
(t, J¼4.5 Hz, 1H), 1.23–1.17 (m, 2H), 1.11 (dd, J¼13.4, 3.4 Hz, 1H),
0.94–0.82 (s, 3H), 0.81(s, 3H), 0.80 (s, 3H); 13C NMR (125 MHz,
1.59–1.40 (m, 9H); 13C NMR (125 MHz, CDCl3)
d 170.7, 170.2, 128.6,
128.4, 92.8, 78.6, 72.6, 66.8, 66.4, 64.5, 63.5, 63.2, 33.0, 31.2, 27.3,
25.3, 23.0, 20.7; IR (NaCl neat) nmax/cmꢀ1 1743, 1373, 1234, 1036;
HRMS (ESI) m/z [MþNa]þ calcd for C18H28O7Na 363.1784, found
345.1771.
CDCl3)
d 170.7, 170.2, 128.4, 128.2, 96.1, 85.8, 66.8, 66.7, 64.1, 48.8,

5848
B.K. Gorityala et al. / Tetrahedron 65 (2009) 5844–5848
47.7, 46.6, 38.9, 28.2, 28.2, 26.6, 20.9, 20.7, 19.7, 13.6; IR (NaCl neat)
nmax/cmꢀ1 1747, 1369, 1230, 1041; HRMS (ESI) m/z [MþNa]þ calcd
for C20H30O6Na 389.1940, found 389.1938.
References and notes
1. (a) Fraser-Reid, B. Acc. Chem. Res. 1985, 18, 347–354; (b) Ferrier, R. J. Adv. Car-
bohydr. Chem. Biochem.1969, 24,199–266; (c) Tolstikov, A. G. Russ. Chem. Rev.1993,
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(e) Borrachero-Moya, v.; Cabrera-Escribano, F.; Go´ mez-Guille´n, M.; Peredes-
4.2.12. (þ)-endo-Fenacholyl 4,6-di-O-acetyl-2,3-dideoxy-
a-D-
´
Leon, M. R. Carbohydr. Res. 1998, 308, 181–190; (f) Schmidt, R. R.; Angerbauer, R.
erythro-hex-2-enopyranoside (3d)
Carbohydr. Res. 1981, 89, 159–162; (g) Angerbauer, R.; Schmidt, R. R. Carbohydr.
Res. 1981, 89, 193–201; (h) Holder, N. Chem. Rev. 1982, 82, 287–332; (i) Liu, Z. J.;
Zhou, M.; Min, J. M.; Zhang, L. H. Tetrahedron: Asymmetry 1999, 10, 2119–2127;
(j) Brito, T. M. B.; Silva, L. P. V.; Siqueira, L.; Srivastava, R. M. J. Carbohydr. Chem.
1999, 18, 609–616.
2. (a) Ferrier, R. J.; Zubkov, O. A. Org. React. 2003, 62, 569–736 and references
therein; (b) Ferrier, R. J. Top. Curr. Chem. 2001, 215, 153–175; (c) Ferrier, R.;
Prasad, N. J. J. Chem. Soc. 1969, 570–575.
3. Bettadaiah, B. K.; Srinivas, P. Tetrahedron Lett. 2003, 44, 7257–7259.
4. Gorityala, B. K.; Cai, S.; Lorpitthaya, R.; Ma, J.; Pasunooti, K. K.; Liu, X. W. Tet-
rahedron Lett. 2009, 50, 676–679.
5. Babu, B. S.; Balasubramanian, K. K. Tetrahedron Lett. 2000, 41, 1271–1274.
6. (a) Grynkiewiez, G.; Priebe, W.; Zamojski, A. Carbohydr. Res. 1979, 68, 33–41; (b)
Bhate, P.; Horton, D.; Priebe, W. Carbohydr. Res. 1985, 144, 331–337.
7. Takhi, M.; Rahman, A.; Adel, A. H.; Schmidt, R. R. Tetrahedron Lett. 2001, 42,
4053–4056.
24
Rf (30% EtOAc/hexane) 0.61; [
(500 MHz, CDCl3)
a
]
þ48.7 (c 0.5, CHCl3); 1H NMR
D
d
5.83 (s, 2H), 5.25 (d, J¼10 Hz, 1H), 4.95 (s, 1H),
4.20 (dd, J¼12.2, 5.2 Hz, 1H), 4.13–4.09 (m, 2H), 3.42 (d, J¼1.5 Hz,
1H), 2.06 (s, 3H), 2.05 (2, 3H), 1.65–1.61 (m, 3H), 1.45 (dd, J¼10.1,
1.5 Hz,1H),1.08 (s, 3H), 1.07–1.06 (m,1H), 1.01 (s, 3H), 0.96–0.94 (m,
1H), 0.85 (s, 3H); 13C NMR (125 MHz, CDCl3) dC 170.8, 170.2, 128.5,
127.9, 94.1, 90.1, 66.8, 65.2, 63.1, 48.8, 48.7, 41.3, 39.4, 31.8, 25.9, 21.1,
20.9, 20.8, 19.7; IR (NaCl neat) nmax/cmꢀ1 1732, 1456, 1259, 1064;
HRMS (ESI) m/z [MþNa]þ calcd for C20H30O6Na 389.1940, found
389.1935.
4.2.13. Pregnenolonyl 4,6-di-O-acetyl-2,3-dideoxy-a-D-erythro-
8. Masson, C.; Soto, J.; Bessodes, M. Synlett 2000, 1281–1282.
9. (a) Toshima, K.; Ishizuka, T.; Matsuo, G.; Nakata, M. Synlett 1995, 306–308; (b)
Shanmugasundaram, B.; Bose, A. K.; Balasubramanian, K. K. Tetrahedron Lett.
2002, 43, 6795–6798; (c) De Oliviera, R. N.; De Freitas, J. R.; Srivastava, R. M.
Tetrahedron Lett. 2002, 43, 2141–2143.
10. Babu, B. S.; Balasubramnaian, K. K. Synth. Commun. 1998, 29, 4299–4305.
11. Yadav, J. S.; Subba Reddy, B. V.; Sunder Reddy, J. S. J. Chem. Soc., Perkin Trans. 1
2002, 2390–2394.
12. Toshima, K.; Ishizuka, T.; Matsuo, G.; Nakata, M.; Konoshita, M. J. Chem. Soc.,
Chem. Commun. 1993, 704–706.
13. Koreeda, M.; Houston, T. A.; Shull, B. K.; Klemke, E.; Tuinman, R. J. Synlett 1994,
90–92.
14. Lo’pez, J. C.; Fraser-Reid, B. J. Chem. Soc., Chem. Commun. 1992, 94–96.
15. Yadav, J. S.; Reddy, B. V. S.; Pandey, S. K. New J. Chem. 2001, 25, 538–540.
16. Yadav, J. S.; Reddy, B. V. S.; Reddy, K. B.; Satyanarayana, M. Tetrahedron Lett.
2002, 43, 7009–7012.
17. (a) Misra, A. K.; Tiwari, P.; Agnihotri, G. Synthesis 2005, 2, 260–266; (b) Agarwal,
A.; Rani, S.; Vankar, Y. D. J. Org. Chem. 2004, 69, 6137–6140.
18. Lopez, J. C.; Gomez, A. M.; Valverdi, S.; Fraser-Reid, B. J. Org. Chem. 1995, 60,
3851–3858.
hex-2-enopyranoside (3e)
20
Rf (30% EtOAc/hexane) 0.40; [
a
]
þ162.4 (c 0.5, CHCl3); 1H NMR
D
(500 MHz, CDCl3)
d
5.85 (d, J¼10.4 Hz, 1H), 5.78 (d, J¼10.4 Hz, 1H),
5.32 (s, 1H), 5.26 (d, J¼10.0 Hz, 1H), 5.14 (s, 1H), 4.20 (dd, J¼12.2,
5.9 Hz, 1H), 4.17–413 (m, 2H), 3.57–3.51 (m, 1H), 2.50 (t, J¼8.0 Hz,
1H), 2.38–2.34 (m, 1H), 2.32 (d, J¼11.0 Hz, 1H), 2.19–2.14 (m, 1H),
2.09 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.02 (d, J¼9.5 Hz, 1H), 1.99–
1.95 (m, 1H), 1.88–1.83 (m, 2H), 1.60–1.42 (m, 8H), 1.24–1.18 (m, 1H),
1.17–1.12 (m, 1H), 1.06–1.03 (m, 1H), 0.98–0.95 (m, 4H), 0.60 (s, 3H);
13C NMR (125 MHz, CDCl3)
d 209.5, 170.8, 170.3, 140.7, 128.9, 128.3,
121.5, 92.8, 78.0, 66.8, 65.3, 63.6, 63.1, 56.8, 49.9, 43.9, 40.3, 38.8,
37.1, 36.6, 31.8, 31.7, 31.5, 28.1, 24.4, 22.8, 21.0, 20.9, 20.8, 19.3, 13.2;
IR (NaCl neat) nmax/cmꢀ1 1745, 1699, 1371, 1228, 1035; HRMS (ESI)
m/z: calcd for C31H44O7Na: 551.2985 [MþNa]þ; found: 551.2994.
19. Sigma Aldrich aluminium oxide, neutral, 150 mesh, STD grade was used for all
reactions. Alumina was freshly prepared by heating at 200 ꢁC under vacuum for
5 h and flushed with nitrogen. Alumina (5.3 equiv) was combined with 1 equiv
of activated ZnCl2 (heated under vacuum at 160 ꢁC for 2 h) and to this mixture
about 3 mL of dry THF or DCM added and stirred for 5 min. Solvent was re-
moved then and the solid impregnation dried under vacuum. Thus, formed
ZnCl2/alumina impregnation can be directly used to facilitate the reaction.
20. Du, W.; Hu, Y. Synth. Commun. 2006, 36, 2035–2046.
Acknowledgements
The authors thank Dr. Yong-Xin Li for X-ray analyses and
gratefully acknowledge Nanyang Technological University and
Ministry of Education, Singapore for funding this research.
21. Yadav, J. S.; Reddy, B. V. S.; Geetha, V. Synth. Commun. 2003, 33, 717–722.
22. Oka, N.; Ikegami, A.; Ohki, M.; Sakata, K.; Yagi, A.; Watanabe, N. Phytochemistry
1998, 47, 1527–1529.
Supplementary data
23. Mastalic, J.; Jerkovic, I.; Vinkovic, v.; Dzolic, Z.; Vikic-Topic, D. Croat. Chem. Acta
2004, 77, 491–500.
24. Noguchi, K.; Nakagawa, H.; Yoshiyama, M.; Shimura, S.; Kirimura, K.; Usami, S.
J. Ferment. Bioeng. 1998, 85, 436–438.
25. Yamauchi, T.; Hara, M.; Mihashi, K. Phytochemistry 1972, 1, 3345–3347.
26. Hotha, V.; Tripathi, A. Tetrahedron Lett. 2005, 61, 4555–4558.
Crystallographic data of compound 3e and NMR spectra of new
compounds are available. Supplementary data associated with this
article can be found in the online version, at doi:10.1016/
j.tet.2009.04.099.