A rapid synthesis of pyranoid glycals promoted by β-cyclodextrin and ultrasound

Article abstract of DOI:10.1002/cjoc.201180263

A convenient and environmentally benign procedure for the synthesis of glycals from glycosyl bromides with very low zinc dust loading (1.5 equiv.) is described. The process is activated by β-cyclodextrin and ultrasound. Based on 19 samples, this method has been demonstrated to be highly effective for a broad range of glycosyl bromides, including acid- or base-sensitive and disaccharide glycosyl bromides. A yield of 85%-96% of glycals was obtained. Copyright

Full text of DOI:10.1002/cjoc.201180263

FULL PAPER
A Rapid Synthesis of Pyranoid Glycals Promoted by
β-Cyclodextrin and Ultrasound
Zhao, Jinzhong*,a(赵晋忠)
Shao, Huawub(邵华武)
Shi, Shaojinga(史少静)
Wu, Xina(武鑫)
a Shanxi Agricultural University, Taigu, Shanxi 030801, China
b Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences,
Chengdu, Sichuan 610041, China
A convenient and environmentally benign procedure for the synthesis of glycals from glycosyl bromides with
very low zinc dust loading (1.5 equiv.) is described. The process is activated by β-cyclodextrin and ultrasound.
Based on 19 samples, this method has been demonstrated to be highly effective for a broad range of glycosyl bro-
mides, including acid- or base-sensitive and disaccharide glycosyl bromides. A yield of 85%— 96% of glycals was
obtained.
Keywords ultrasound, β-cyclodextrin, glycal, znic, glycosyl bromide, carbohydrate
Introduction
Protected glycopyranosyl bromides are readily trans-
formed to the high yields of the corresponding glycals,
using more than 10 equiv. of zinc dust in phosphate
buffer at room temperature. Under these conditions, a
longer reaction time is necessary to support conver-
sion.13 Herein, a highly efficient alternative procedure
for Fischer-Zach glycal synthesis is proposed. The pro-
cedure involved only 1.5 equiv. of zinc dust, and the
transformation was promoted by the combined effects of
β-CD and ultrasound in water at room temperature
(Scheme 1). This procedure is especially efficient for the
synthesis of disaccharide glycals.
Glycals are useful substrates in the synthesis of bio-
logically active carbohydrates and their analogs.1 Due to
the double bond between C-1 and C-2, glycals show
remarkable properties in glycosidation, and can react
with various aglycons to provide O-glycosides,2
C-glycosides,3 S-glycosides,4 N-glycosides,5 cyclopro-
panated carbohydrates6 and 2-amino sugars.7 The
preparation of glycals is generally based on the radical-
induced elimination of glycosyl bromides, glycosyl
chlorides, 1-thioglycosides and their S-oxides, and
1-telluroglycosides, using agents such as zinc dust, tita-
nium(III), chromium(II), and aluminum amalgam. The
classic Fischer-Zach glycal synthesis, which treats gly-
cosyl bromide with zinc in acetic acid, has been one of
the most popular methods, it has been widely investi-
gated and modified. Usually, large amounts of zinc dust
or toxic, expensive metal reagents are used under vig-
orous conditions to enhance the activity of zinc.8 Re-
cently, the Fischer-Zach procedure was found to be fea-
sible in neutral PEG-600/H2O at room temperature us-
ing a slight excess of zinc dust (2.0 equiv.).9
Scheme 1 Synthesis of glycals promoted by β-CD and ultra-
sound
β-Cyclodextrin (β-CD) is a torus-shaped molecule
with a hydrophobic interior cavity and a hydrophilic
surface. It has been used in reactions requiring covalent
catalysis, general acid-base catalysis, or non-covalent
catalysis.10 It has attracted interests of synthetic chem-
ists in recent years.11 Ultrasound, which minimizes
waste production and the use of hazardous reagents by
enhancing the rate, yield, and selectivity of reactions,
has emerged as an environmentally benign technology.12
Experimental
General methods
Sonochemical reactions were carried out in a com-
mercially available ultrasound cleaning bath (40 kHz,
600 W) equipped with an automatic thermally regulated
heating/cooling circulation system. Reactions were
*
E-mail: zhaojz@sxau.edu.cn; Fax: 0086-0354-6286959
Received March 1, 2011; revised April 11, 2011; accepted May 10, 2011.
Project supported by the Project of Science and Technology of Shanxi Province (No. 20100311069) and the Scientific Research Foundation of
Shanxi Agricultural University (No. XB2009013).
1434
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1434— 1440

A Rapid Synthesis of Pyranoid Glycals Promoted by β-Cyclodextrin and Ultrasound
monitored by thin layer chromatography using silica gel
HSGF254 plates. Flash chromatography was performed
4.84 (dd, J＝6.1, 3.3 Hz, 1H), 5.01 (dd, J＝10.6, 3.5 Hz,
1H), 5.19 (dd, J＝10.4, 8.0 Hz, 1H), 5.37 (d, J＝2.6 Hz,
1H), 5.41 (dd, J＝4.1, 3.9 Hz, 1H), 6.41 (d, J＝6.1 Hz,
1H).
1
using silica gel HG/T2354-92. H NMR and 13C NMR
(600 and 150 MHz, respectively) spectra were recorded
1
in CDCl3. H NMR chemical shifts are reported in δ
3,4,6-Tri-O-acetyl-D-glucal (23) White power,
m.p. 50—51 ℃ (lit.14c m.p. 50—52 ℃); [α]2D5 －22
relative to tetramethylsilane (TMS), with the solvent
resonance employed as the internal standard (CDCl3,
δ＝7.26). Data are reported as follows: chemical shift,
multiplicity (s＝singlet, d＝doublet, t＝triplet, m＝
multiplet), integration, and coupling constants (Hz). 13C
NMR chemical shifts are reported from tetramethylsi-
lane (TMS) with the solvent resonance as the internal
standard (CDCl3, δ＝77.0). ESI-HRMS spectra were
recorded on a BioTOF Q instrument. Optical rotations
were examined on a Perkin Elmer-341 digital polarime-
ter. Glycals 2, 21—37 are known compounds and their
1H NMR data matched the literature data.14,15 D-Glucose,
D-mannose, D-galactose, D-arabinose, L-rhamnose,
D-maltose, D-lactose, and D-cellobiose were commer-
cially available and used without further purification.
Glycopyranosyl bromide 1, 3—20 were prepared ac-
cording to the reported procedure.16
1
(c 4.1, CHCl3) [lit.14c [α]D25 －22 (c 2.1, CHCl3)]; H
NMR (CDCl3) δ: 2.05 (s, 3H), 2.08 (s, 3H), 2.10 (s, 3H),
4.20 (dd, J＝12.4, 3.1 Hz, 1H), 4.26 (m, 1H), 4.40 (dd,
J＝12.2, 5.8 Hz, 1H), 4.85 (dd, J＝9.5, 3.3 Hz, 1H),
5.22 (dd, J＝7.5, 6.0 Hz, 1H), 5.35 (dd, J＝4.2, 3.7 Hz,
1H), 6.47 (d, J＝6.2 Hz, 1H).
3,4,6-Tri-O-acetyl-D-galactal (24)
Colorless
syrup, [α]2D5 －9 (c 0.1, EtOAc) [lit.14a [α]2D5 －17 (c
1.1, CHCl3)]; 1H NMR (CDCl3) δ: 2.03 (s, 3H), 2.09 (s,
3H), 2.13 (s, 3H), 4.22 (dd, J＝11.6, 5.2 Hz, 1H), 4.28
(dd, J＝11.6, 7.2 Hz, 1H), 4.32—4.33 (m, 1H), 4.72—
4.74 (m, 1H), 5.43 (dd, J＝3.8, 1.1 Hz, 1H), 5.56 (d, J＝
1.0 Hz, 1H), 6.46 (d, J＝5.2 Hz, 1H).
3,4-Di-O-acetyl-D-arabinal (25) Colorless syrup,
[α]2D5 ＋200 (c 0.9, CH2Cl2) [lit.14c [α]2D5 ＋262 (c 0.9,
1
CHCl3)]; H NMR (CDCl3, 600 MHz) δ: 2.07 (s, 3H),
2.08 (s, 3H), 3.98 (dd, J＝10.6, 9.6 Hz, 1H), 3.97—4.04
(m, 1H), 4.85 (dd, J＝5.8, 5.2 Hz, 1H), 5.18—5.20 (m,
1H), 5.44 (dd, J＝4.8, 4.2 Hz, 1H), 6.50 (d, J＝6.0 Hz,
1H). HR-ESIMS calcd for C9H12NaO5 [M ＋ Na]
223.0577, found 223.0564.
General procedure
β-Cyclodextrin (0.2 mmol) and zinc dust (1.5 mmol)
were added to a solution of glycopyranosyl bromide (1
mmol) in H2O (20.0 mL) under ultrasound irradiation.
TLC was used to monitor the reaction. Usual workup
and purification provided the corresponding compounds.
3,6,2',3',4',6'-Hexa-O-acetyl-α-D-maltal (2) Col-
orless syrup, [α]2D5 ＋169 (c 0.6, CHCl3) [lit.14a [α]2D5
＋66 (c 1.0, CHCl3)]; 1H NMR (CDCl3) δ: 2.01 (s, 3H),
2.03 (s, 3H), 2.05 (s, 3H), 2.06 (s, 3H), 2.10 (s, 3H),
2.13 (s, 3H), 4.03—4.05 (m, 2H), 4.11 (dd, J＝12.3, 2.0
Hz, 1H), 4.23 (dd, J＝12.3, 4.1 Hz, 1H), 4.29—4.32 (m,
1H), 4.33—4.39 (m, 2H), 4.82—4.84 (m, 2H), 5.06 (dd,
J＝10.0, 9.9 Hz, 1H), 5.18 (dd, J＝4.2, 4.1 Hz, 1H),
5.41 (dd, J＝10.0, 9.9 Hz, 1H), 5.50 (d, J＝4.0 Hz, 1H),
6.44 (d, J＝6.2 Hz, 1H).
3,4-Di-O-acetyl-D-xylal (26)
Colorless syrup,
[α]2D5 －301 (c 1.9, CHCl3) [lit.14c [α]2D5 －303 (c 2.3,
CHCl3)]; 1H NMR (CDCl3) δ: 2.07 (s, 3H), 2.10 (s, 3H),
3.98 (dd, J＝12.3, 1.4 Hz, 1H), 4.18—4.20 (m, 1H),
4.95—4.97 (m, 2H), 5.00 (s, 1H), 6.60 (d, J＝6.3 Hz,
1H).
3,4-Di-O-acetyl-L-rhamnal (27) Colorless syrup,
[α]2D5 ＋65 (c 1.1, CH2Cl2) [lit.14d [α]2D5 ＋55 (c 1.0,
1
CHCl3)]; H NMR (CDCl3) δ: 1.31 (d, J＝6.6 Hz, 3H),
2.04 (s, 3H), 2.08 (s, 3H), 4.09—4.13 (m, 1H), 4.78 (dd,
J＝6.2, 3.1 Hz, 1H), 5.03 (dd, J＝8.2, 6.2 Hz, 1H),
5.34—5.35 (m, 1H), 6.43 (d, J＝6.0 Hz, 1H).
3,6,2',3',4',6'-Hexa-O-acetyl-α-D-cellobial (21)14b
3,4-Di-O-acetyl-6-O-mesyl-D-glucal (28) Color-
less syrup, [α]2D5 －4 (c 0.3, CHCl3) [lit.15a [α]2D5
1
Colorless syrup, [α]2D5 －4 (c 0.3, CHCl3); H NMR
1
(CDCl3) δ: 2.00 (s, 3H), 2.02 (s, 3H), 2.05 (s, 3H), 2.06
(s, 3H), 2.09 (s, 3H), 2.12 (s, 3H), 3.68—3.70 (m, 1H),
3.99 (dd, J＝7.4, 5.6 Hz, 1H), 4.07 (dd, J＝12.3, 2.2 Hz,
1H), 4.13—4.16 (m, 1H), 4.19 (dd, J＝11.9, 6.2 Hz, 1H),
4.31 (dd, J＝12.4, 4.5 Hz, 1H), 4.44 (dd, J＝11.7, 2.5
Hz, 1H), 4.69 (d, J＝8.0 Hz, 1H), 4.82 (dd, J＝6.1, 3.3
Hz, 1H), 4.98 (dd, J＝9.4, 8.0 Hz, 1H), 5.09 (dd, J＝
10.0, 9.4 Hz, 1H), 5.19 (dd, J＝9.6, 9.4 Hz, 1H), 5.42
(m, 1H), 6.41 (d, J＝6.1 Hz, 1H).
＋15 (c 1.6, EtOH)]; H NMR (CDCl3) δ: 2.06 (s, 3H),
2.10 (s, 3H), 3.07 (s, 3H), 4.33—4.37 (m, 2H), 4.47 (dd,
J＝11.6, 6.2 Hz, 1H), 4.89 (dd, J＝6.2, 3.5 Hz, 1H),
5.21 (dd, J＝7.4, 5.6 Hz, 1H), 5.34—5.36 (m, 1H), 6.48
(d, J＝6.2 Hz, 1H).
3,4-Di-O-acetyl-6-O-tosyl-D-glucal (29)
White
power, m.p. 106—107 ℃ (lit.15b 106—107 ℃); [α]2D5
＋16 (c 1.5, CHCl3) [lit.15b [α]D25 ＋14 (c 1.0, CHCl3)];
1H NMR (CDCl3) δ: 2.03 (s, 3H), 2.04 (s, 3H), 2.46 (s,
3H), 4.19—4.27 (m, 3H), 4.82 (dd, J＝6.2, 3.5 Hz, 1H),
5.13 (dd, J＝3.7, 3.7 Hz, 1H), 5.27 (dd, J＝6.2, 5.5 Hz,
1H), 6.35 (d, J＝6.0 Hz, 1H), 7.35 (d, J＝7.9 Hz, 2H),
7.80 (d, J＝8.4 Hz, 2H).
3,6,2',3',4',6'-Hexa-O-acetyl-α-D-lactal (22) Col-
orless syrup, [α]2D5 －9 (c 0.5, CHCl3) [lit.14a [α]2D3
－16 (c 1.4, CHCl3)]; 1H NMR (CDCl3) δ: 1.98 (s, 3H),
2.05 (s, 3H), 2.06 (s, 3H), 2.09 (s, 3H), 2.12 (s, 3H),
2.16 (s, 3H), 3.91 (dd, J＝7.1, 6.4 Hz, 1H), 4.00 (dd,
J＝7.4, 5.5 Hz, 1H), 4.09 (dd, J＝11.2, 7.2 Hz, 1H),
4.14—4.17 (m, 2H), 4.20 (dd, J＝11.8, 6.1 Hz, 1H),
4.44 (dd, J＝11.7, 2.5 Hz, 1H), 4.66 (d, J＝8.0 Hz, 1H),
3,4-Di-O-acetyl-6-O-mesyl-D-galactal (30) Color-
less syrup, [α]D25 －5 (c 0.4, CH2Cl2); 1H NMR (CDCl3)
δ: 2.06 (s, 3H), 2.10 (s, 3H), 3.07 (s, 3H), 4.33—4.37 (m,
2H), 4.48 (dd, J＝6.0, 2.9 Hz, 1H), 4.89 (dd, J＝6.0, 3.3
Chin. J. Chem. 2011, 29, 1434— 1440
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1435

Zhao et al.
FULL PAPER
Hz, 1H), 5.21 (dd, J＝7.2, 5.5 Hz, 1H), 5.35 (dd, J＝4.3,
3.5 Hz, 1H), 6.48 (d, J＝6.2 Hz, 1H); 13C NMR (CDCl3)
δ: 20.8, 20.9, 37.8, 65.6, 66.9, 67.0, 73.6, 99.4, 145.3,
169.8, 170.3. HR-ESIMS calcd for C11H16Na1O8S1
[M＋Na] 331.0458, found 331.0474.
Results and discussion
Initially, acetobromo-α-D-maltose (1) was chosen to
survey the sonochemical effects and catalytic effects of
β-CD on the synthesis of D-maltal (2) at room tempera-
ture (Scheme 2). This reaction was carried out in an ul-
trasound cleaning bath (40 kHz, 600 W) equipped with
an automatic thermally regulated heating/cooling circu-
lation system.
Compound 1 was treated in phosphate buffer,
PEG600-H2O or β-CD-H2O under ultrasound irradiation
and high-speed magnetic stirring (Table 1, Entries 1—3).
A low yield of 2 was obtained in phosphate buffer, and a
high yield was obatined in water and β-CD. The reaction
time was also significantly shortened under ultrasound
irradiation. The yield obtained by ultrasound irradiation
with high-speed magnetic stirring increased by more
than 7% (Table 1, Entry 3). Hence, the sensitivity of 1
toward acid hydrolysis and nucleophilic substitution led
to the low yield and the appearance of by-products in
phosphate buffer. In addition, water mixed with β-CD
was more efficient than PEG600-H2O. The
1,4-glycosidic bond of 1 and 2 cannot be cleaved by
hydrolysis in β-CD-H2O, thus, this method can offer a
general route for the preparation of glycals substituted
with both acid- and base-labile functionalities.
3,4-Di-O-acetyl-6-O-tosyl-D-galactal (31) Color-
less syrup, [α]D25 ＋3 (c 1.8, CH2Cl2); 1H NMR (CDCl3) δ:
2.01 (s, 3H), 2.05 (s, 3H), 2.46 (s, 3H), 4.14 (dd, J＝10.5,
4.4 Hz, 1H), 4.28 (dd, J＝10.6, 7.7 Hz, 1H), 4.31—4.32
(m, 1H), 4.72 (dd, J＝6.1, 3.1 Hz, 1H), 5.37 (s, 1H), 5.48
(s, 1H), 6.35 (d, J＝6.1 Hz, 1H), 7.36 (d, J＝8.2 Hz, 2H),
7.79 (d, J＝8.2 Hz, 2H); 13C NMR (CDCl3) δ: 20.5, 20.7,
21.7, 63.5, 63.8, 66.7, 72.4, 98.9, 128.0, 129.9, 132.6,
145.2, 169.8, 170.1. HR-ESIMS calcd for C17H20Na1O8S1
[M＋Na] 407.0771, found 407.0779.
3,4-Di-O-acetyl-6-azide-D-glucal (32) Colorless
syrup, [α]2D5 －46 (c 0.1, CH2Cl2) [lit.15c [α]2D5 －6 (c
1.9, CHCl3)]; 1H NMR (CDCl3) δ: 2.06 (s, 3H), 2.10 (s,
3H), 3.56 (dd, J＝11.0, 6.5 Hz, 1H), 3.61 (dd, J＝11.2,
5.0 Hz, 1H), 4.29 (dd, J＝11.8, 6.0 Hz, 1H), 4.87 (dd,
J＝6.0, 3.5 Hz, 1H), 5.28—5.31 (m, 2H), 6.50 (d, J＝
6.1 Hz, 1H).
3,4,6-Tri-O-benzyol-D-glucal (33)14b
Colorless
1
syrup, [α]2D5 －59 (c 1.5, CHCl3); H NMR (CDCl3) δ:
4.68—4.71 (m, 3H), 5.12 (dd, J＝6.2, 3.6 Hz, 1H), 5.72
(dd, J＝4.4, 4.0 Hz, 1H), 5.80 (dd, J＝5.6, 5.3 Hz, 1H),
6.60 (dd, J＝6.1, 0.8 Hz, 1H), 7.39—7.44 (m, 6H),
7.52—7.57 (m, 3H), 7.99—8.05 (m, 6H).
Afterward, the effects of zinc and β-CD were tested.
When the reaction was carried out using 1.0 mmol sub-
strate in β-CD-H2O (Table 1, Entries 1—11), 1.5 equiv.
of zinc and 0.2 mmol of β-CD produced a 95% yield
(Table 1, Entry 11).
3,4,6-Tri-O-benzyol-D-galactal (34)9
Colorless
syrup, [α]2D5 －43 (c 0.43, CHCl3); 1H NMR (CDCl3) δ:
4.57 (dd, J＝11.8, 4.8 Hz, 1H), 4.70—4.71 (m, 1H),
4.80 (dd, J＝11.8, 7.7 Hz, 1H), 4.99 (dd, J＝6.1, 1.7 Hz,
1H), 5.92—5.94 (m, 2H), 6.62 (d, J＝6.2 Hz, 1H), 7.33
(dd, J＝7.9, 7.7 Hz, 2H), 7.42 (dd, J＝7.7, 7.7 Hz, 4H),
7.50 (dd, J＝7.5, 7.3 Hz, 1H), 7.54—7.58 (m, 2H), 7.89
(d, J＝7.3 Hz, 2H,), 8.00—8.07 (m, 4H).
Since 2 was readily obtained from 1 using 1.5 equiv.
of Zn and β-CD in water, the syntheses of all the glycals
shown in Scheme 1 and Table 2 were explored under
same conditions. In the beginning, acetylated maltal,
cellobial, and lactal could be obtained in excellent yield
(Table 2, Entries 1—3), and the 1,4-glycosidic bond
could not be hydrolyzed. Based on this result, the acety-
lated bromoglycosides were treated with Zn and β-CD
in water, in order to obtain an excellent yield of the gly-
cals 23—27 (Table 2, Entries 4—9). Furthermore, the
generality of the synthesis of the benzyolated glycals,
6-O-mesyl, 6-O-tosyl, 6-azide glycals, and benzylated
glycals under the same conditions was investigated. The
results show that benzyolated glycals 33—37, 6-O-mesyl
28, 31, 6-O-tosyl 29, 30, 6-azide glycals 32, and benzy-
lated rhamnal 37 were also obtained in excellent yields
(Table 2, Entries 10—19). Compared with previous
method, the yields of peracetylated and benzoylated
rhamnal, 6-azido glycals, and benzylated rhamnal in
β-CD and water under ultrasound irradiation were im-
proved. Moreover, ultrasound irradiation improved the
yield of glycals and markedly shortened the reaction
time in water and β-CD (Table 2, Entries 1—4, 7—9, 14,
18, and 19). In all cases, the glycals (2, 21—37) were
obtained in 85%—96% isolated yields (Table 2, Entries
1—19).
3,4-Di-O-benzyol-D-arabinal (35)9
Colorless
1
syrup, [α]2D5 ＋226 (c 2.9, CHCl3); H NMR (CDCl3) δ:
4.22—4.28 (m, 2H), 5.07 (dd, J＝5.6, 5.3 Hz, 1H), 5.44
(m, 1H), 5.81 (s, 1H), 6.62 (d, J＝5.9 Hz, 1H), 7.34 (d,
J＝7.7 Hz, 1H), 7.36 (d, J＝7.6 Hz, 1H), 7.41 (d, J＝7.7
Hz, 1H), 7.42 (d, J＝7.6 Hz, 1H), 7.50—7.56 (m, 2H),
7.93 (d, J＝7.3 Hz, 1H), 8.02 (d, J＝7.4 Hz, 1H).
3,4-Di-O-benzyol-L-rhamnal (36) Colorless syrup,
[α]2D5 ＋209 (c 0.6, CHCl3) [lit.15d [α]2D2 ＋229 (c 0.6,
1
CHCl3)]; H NMR (CDCl3) δ: 1.45 (d, J＝6.5 Hz, 3H),
4.36 (m, 1H), 5.00 (dd, J＝5.9, 2.9 Hz, 1H), 5.51 (dd,
J＝7.1, 6.7 Hz, 1H), 5.71 (m, 1H), 6.53 (d, J＝6.1 Hz,
1H), 7.40—7.44 (m, 4H), 7.52—7.57 (m, 2H), 8.01 (dd,
J＝19.1, 7.9 Hz, 4H)
3,4-Di-O-benzyl-L-rhamnal (37) Colorless syrup,
[α]2D5 ＋37 (c 0.9, CH2Cl2) [lit.15e [α]2D5 ＋64 (c 1.0,
1
CHCl3)]; H NMR (CDCl3) δ: 1.40 (d, J＝6.5 Hz, 3H),
3.51 (dd, J＝9.0, 7.3 Hz, 1H), 3.95—3.99 (m, 1H),
4.23—4.24 (m, 1H), 4.59 (d, J＝11.7 Hz, 1H), 4.68 (d,
J＝11.8 Hz, 1H), 4.73 (d, J＝11.3 Hz, 1H), 4.8—4.91
(m, 2H), 6.38 (d, J＝6.1 Hz, 1H), 7.29—7.38 (m, 10H).
1436
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1434— 1440

A Rapid Synthesis of Pyranoid Glycals Promoted by β-Cyclodextrin and Ultrasound
Scheme 2 Synthesis of maltal (2) from acetylated maltosyl bromide (1)
Table 1 Optimization of reaction conditions for the synthesis of 2a
Entry
1
Solvent
NaH2PO4-H2O
PEG600-H2O
H2O
Zn/mmol
β-CD/mmol
Time (stir.b)/h
Isolated yield (stir.b)/%
6
2
0
0
2 (6)
3 (8)
1.5 (4)
1.5
26 (20)
83 (81)
89 (82)
92
3
4
2
2
5
H2O
2
1
6
H2O
2
0.5
0.2
0.1
0.05
0
1.5
90
7
H2O
2
1.5
95
8
H2O
2
1.5
91
9
H2O
2
1.5
85
10
11
12
H2O
2
1.5
59
H2O
1.5
1
0.2
0.2
1.5
95
H2O
1.5
76
a Acetylated maltosyl bromide (1 mmol), H2O (20 mL) under ultrasound irradiation at room temperature. b Using magnetic stirrer under
silent conditions.
Table 2 Synthesis of various substituted glycals from pyranosyl bromidesa
Entry
1
Substrate
Product
Time (stir.b)/h
Isolated yield (stir.b)/%
1.5 (4)
92 (89)
2
1
3
4
5
6
2
3
4
5
2 (5)
1.5 (4)
0.5 (0.5)
0.5
90 (83)
91 (85)
96 (93)
92
21
22
23
23
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Zhao et al.
FULL PAPER
Continued
Entry
Substrate
Product
Time (stir.b)/h
0.5
Isolated yield (stir.b)/%
6
93
24
7
7
8
9
0.5 (0.5)
0.5 (1)
0.5 (1)
95 (90)
85 (70)
91 (80)
25
26
27
8
9
10
11
12
13
14
15
16
17
10
11
12
13
14
15
16
1
95
90
28
29
30
31
32
33
34
1
1
92
1
94
1 (1.5)
89 (78)
1
1
95
92
1438
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Chin. J. Chem. 2011, 29, 1434— 1440

A Rapid Synthesis of Pyranoid Glycals Promoted by β-Cyclodextrin and Ultrasound
Continued
Isolated yield (stir.b)/%
Entry
17
Substrate
Product
Time (stir.b)/h
1
93
35
18
19
20
18
19
1 (3)
89 (83)
86 (75)
36
37
0.5 (1)
a Glycosyl bromide (1.0 mmol), zinc (1.5 mmol), β-CD (0.2 mmol), and water (20 mL) under ultrasound irradiation at room temperature.
b Using magnetic stirrer under silent conditions.
Conclusions
(c) Saeeng, R.; Isobe, M. Org. Lett. 2005, 7, 1585.
(d) Lehmann, U.; Awasthi, S.; Minehan, T. Org. Lett. 2003,
5, 2405.
(e) Yadav, J. S.; Reddy, B. V. S.; Raman, J. V.; Niranjan, N.;
Kiran Kumar, S.; Kunwar, A. C. Tetrahedron Lett. 2002, 43,
2095.
(f) Thorn, S. N.; Gallagher, T. Synlett 1996, 856.
(a) Boulineau, F. P.; Wei, A. Org. Lett. 2004, 6, 119.
(b) Seeberger, P. H.; Eckhardt, M.; Gutteridge, C. E.; Dan-
ishefsky, S. J. J. Am. Chem. Soc. 1997, 119, 10064.
(a) Ding, F. Q.; William, R.; Gorityala, B. K.; Ma, J. M.;
Wang, S. M.; Liu, X. W. Tetrahedron Lett. 2010, 51, 3146.
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dron Lett. 2010, 51, 5372.
In summary, combining β-CD and ultrasound to ac-
tivate zinc dust in situ is an efficient development of the
Fischer-Zach glycal synthesis. The present method in-
volves nontoxic species, neutral conditions and simple
operations. It is a low-cost procedure with a high yield.
All of these make it an attractive strategy for the synthe-
sis of glycals, especially for peracetylated and benzoy-
lated rhamnal, 6-azido glycals, and benzylated pyranoid
glycals, as their glycosyl bromide precursors are sensi-
tive to acidic or basic medium.
4
5
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Chin. J. Chem. 2011, 29, 1434— 1440