Regioselective Sulfonylation/Acylation of Carbohydrates Catalyzed by FeCl3 Combined with Benzoyltrifluoroacetone and Its Mechanism Study

Article abstract of DOI:10.1021/acs.joc.9b03128

A catalytic amount of FeCl₃ combined with benzoyl trifluoroacetone (Hbtfa) (FeCl₃/Hbtfa = 1/2) was used to catalyze sulfonylation/acylation of diols and polyols using diisopropylethylamine (DIPEA) or potassium carbonate (K₂CO₃) as a base. The catalytic system exhibited high catalytic activity, leading to excellent isolated yields of sulfonylation/acylation products with high regioselectivities. Mechanism studies indicated that FeCl₃ initially formed [Fe(btfa)₃] (btfa = benzoyl trifluoroacetonate) with twice the amount of Hbtfa under basic conditions in the solvent acetonitrile at room temperature. Then, Fe(btfa)₃ and two hydroxyl groups of the substrates formed a five- or six-membered ring intermediate in the presence of the base. The subsequent reaction between the cyclic intermediate and a sulfonylation reagent led to the selective sulfonylation of the substrate. All key intermediates were captured in the high-resolution mass spectrometry assay, therefore demonstrating this mechanism for the first time.

Full text of DOI:10.1021/acs.joc.9b03128

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Article
Regioselective Sulfonylation/Acylation of Carbohydrates Catalyzed
by FeCl3 Combined with Benzoyltrifluoroacetone and Its Mechanism
Study
Jian Lv,# Jia-Jia Zhu,# Yu Liu, and Hai Dong*
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ABSTRACT: A catalytic amount of FeCl3 combined with benzoyl trifluor-
oacetone (Hbtfa) (FeCl3/Hbtfa = 1/2) was used to catalyze sulfonylation/
acylation of diols and polyols using diisopropylethylamine (DIPEA) or potassium
carbonate (K2CO3) as a base. The catalytic system exhibited high catalytic
activity, leading to excellent isolated yields of sulfonylation/acylation products
with high regioselectivities. Mechanism studies indicated that FeCl3 initially
formed [Fe(btfa)3] (btfa = benzoyl trifluoroacetonate) with twice the amount of
Hbtfa under basic conditions in the solvent acetonitrile at room temperature.
Then, Fe(btfa)3 and two hydroxyl groups of the substrates formed a five- or six-membered ring intermediate in the presence of the
base. The subsequent reaction between the cyclic intermediate and a sulfonylation reagent led to the selective sulfonylation of the
substrate. All key intermediates were captured in the high-resolution mass spectrometry assay, therefore demonstrating this
mechanism for the first time.
organotin reagents (Figure 1a). We have attempted to use
[Fe(dibm)3], [Fe(dipm)3], or [Fe(acac)3] to catalyze selective
INTRODUCTION
■
Regioselective protection strategies are as important as
glycosylation strategies in carbohydrate chemistry due to the
requirements of both the preparation of glycosyl donors and
acceptors1 and the modification of carbohydrates2 to obtain
valuable intermediates. One-pot selective protection strategies
are particularly beneficial for the highly efficient synthesis of
glycosyl donors and acceptors.3 Many chiral or achiral catalysts
with complex structures were developed to control site-
selectivity, where researchers are less concerned about whether
the catalysts are readily available and inexpensive.4 Few
catalysts with a simple structure5 were developed to substitute
toxic organotin reagents,6 where researchers, such as our
group,7 are more concerned about the commercial availability,
the low price, and the environmental friendliness of the used
reagents. Our group has therefore recently developed green
Fe(III) catalysts, [Fe(dibm)3] (dibm = diisobutyrylmethane)
for regioselective alkylation7 and [Fe(acac)3] (acac =
acetylacetonate) for regioselective acylation.8 [Fe(dipm)3]
(dipm = dipivaloylmethane) can play the same role as
[Fe(dibm)3], and it is less expesenve.9 These methods have
the advantages of green, convenient manipulation, high
efficiency, high selectivity, good yield, and broad substrate
scope. However, the mechanism has never been demonstrated.
Regioselective sulfonylation strategies are also important
because selective sulfonated products are widely used as
precursors for the synthesis of various biologically significant
compounds and novel functional materials.10 Organotin
reagents were used in the earliest reports,11 and organoboron
catalysts12 were later developed to avoid the use of toxic
Figure 1. Regioselective sulfonylation of carbohydrate cis-diols. (a)
Previously reported methods. (b) This method.
Received: November 20, 2019
https://dx.doi.org/10.1021/acs.joc.9b03128
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
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sulfonylation but failed. It is difficult to investigate such
catalysts in which various metals coordinate acylacetone
ligands due to availability, although we assumed that certain
catalysts should be good catalysts for selective sulfonylation.
Recently, we found that FeCl3 combined with acetylacetone
could be directly used as a catalyst to catalyze selective
benzoylation with diisopropylethylamine (DIPEA) as a base.13
Based on this, we investigated the effects of acylacetone ligands
and various metal salts on the regioselective sulfonylation to
find an optimal catalytic system. The challenge is addressed in
this study (Figure 1b). We found that the combination of
FeCl3 and benzoyl trifluoroacetone (Hbtfa) (FeCl3/Hbtfa = 1/
2) was a good catalytic system for regioselective sulfonylation
of substrates containing a cis-vicinal diol, a 1,2-diol, or a 1,3-
diol. The method is superior to the reported methods, which
uses only inorganic bases (K2CO3) instead of organic bases.
The isolated yields and selectivities were similar or better than
previous methods in most cases (Table S1 in the Supporting
Information). This system also exhibited a higher catalytic
activity for selective acylation than the use of FeCl3 and
acetylacetone. FeCl3 is readily available in the laboratory.
Benzoyl trifluoroacetone is also an inexpensive ($1−2/g) and
nontoxic reagent (Table S2 in the Supporting Information).
Furthermore, the catalytic mechanism was studied using high-
resolution mass spectrometry (HRMS) to capture all key
intermediates in the HRMS assay, therefore demonstrating the
mechanism for the first time.
Table 1. Comparison of Sulfonylation/Acylation of 1 under
Various Conditions
a
catalytic system
(0.1 equiv)
base
(1.9 equiv)
isolated yield recovered 1
entry
(%)
(%)
b
1
2
3
4
5
6
7
8
FeCl3/L1−6 (1/3)
FeCl3/L7 (1/3)
FeCl3 (0.1)
DIPEA
DIPEA
DIPEA
DIPEA
-
80−86
-
b
2a: 86
b
-
-
84
85
b
L7 (0.3)
c
b
Fe(btfa)3 (0.1)
FeBr3/L7 (1/3)
Fe(OTf)3/L7 (1/3)
FeCl2/L7 (1/2)
CuCl2/L7 (1/2)
BiCl3/L7 (1/3)
MnCl2/L7 (1/2)
ZnCl2/L7 (1/2)
CoCl2/L7 (1/2)
FeCl3/L7 (1/3)
FeCl3/L7 (1/3)
FeCl3/L7 (1/3)
FeCl3/L7 (1/2)
FeCl3/L7 (1/1)
DIPEA
2a: 92
2a: 27
2a: 35
2a: 34
2a: 90
2a: 85
2a: 63
2a: 51
2a: 60
2a: 83
2a: 91
2a: 80
2a: 89; 2b: 90
2a: 67
2a: 85e, 93f
2a: 91; 2b: 92
-
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
TEA
K2CO3
Ag2O
DIPEA
DIPEA
DIPEA
K2CO3
62
56
56
b
9
-
b
10
11
12
13
14
15
16
17
18
19
20
-
30
40
32
RESULTS AND DISCUSSION
■
b
-
Based on our studies on FeCl3-catalyzed selective benzoylation
with acetylacetone as a ligand, we started to explore the
optimal catalytic system for selective sulfonylation of methyl-6-
O-(tert-butyldimethylsilyl)-α-D-mannopyranoside 1 (Table 1).
Therefore, 0.1 equiv of FeCl3 was first tested with 0.3 equiv of
various acylacetone-type ligands (L1−L7) in the presence of
1.5 equiv of para-toluenesulfonyl chloride (TsCl) and 1.9
equiv of diisopropylethylamine (DIPEA) in acetonitrile
(entries 1and 2 in Table 1). After 6 h at room temperature,
the sulfonylation products and the recovered 1 were isolated.
The experimental results showed that FeCl3 with the assistance
of L1−L6 could not exhibit any catalytic activity on the
sulfonylation since 80−86% yields of recovered 1 were isolated
(entry 1). To our delight, FeCl3 with the assistance of L7,
benzoyl trifluoroacetone (Hbtfa), exhibited high catalytic
activity for the selective sulfonylation (entry 2). Most of the
starting material 1 was consumed, and 86% yield of 3-
sulfonylated product 2a was isolated. No or trace byproducts
were observed, indicating a high site-selectivity. The absence of
L7 (entries 3 and 4) or the absence of FeCl3 resulted in low or
no reaction conversion. We assumed that 0.1 equiv of FeCl3
and 0.3 equiv of L7 initially form approximately 0.1 equiv of
Fe(btfa)3 in the presence of a base, which subsequently
catalyzes the sulfonylation. As expected, Fe(btfa)3 showed high
catalytic activity in the sulfonylation, and only 1.5 equiv of
DIPEA was used, thus leading to 92% isolated yield of 2a
(entry 5). FeBr3, Fe(OTf)3, and FeCl2 exhibited lower catalytic
activity than FeCl3 (entries 6−8). Next, various metal salts in
lieu of iron salts were tested in the sulfonylation. It was
observed that AlCl3, NiCl2, CrCl3, SnCl4, Ce(SO4)2, or
Ce(NO3)4 did not exhibit any catalytic activity; CuCl2 and
BiCl3 also exhibited high catalytic activity (entries 9 and 10);
and MnCl2, ZnCl2, and CoCl2 exhibited moderate catalytic
activity for this reaction (entries 11−13). We also used other
b
-
b
-
b
-
27
d
b
FeCl3/L7 (1/2)
-
b
FeCl3/L7 (1/2)
-
a
Substrate 1 (0.1 mmol), RCl (1.5 equiv), MeCN (0.5 mL), room
b
c
temperature (rt), 6 h. Observation of no or trace compound. 1.5
equiv. 0.05 equiv. 12 h. Large scale: substrate 1 (4 mmol, 1.232 g),
d
e
f
TsCl (1.5 equiv), MeCN (20 mL), rt, 8 h.
bases (TEA, K2CO3, and Ag2O) instead of DIPEA (entries
14−16). Good results were observed, especially when K2CO3
was used as the base (entry 15). An unexpected result is that
FeCl3 combined with 2 equiv of L7 exhibited the same catalytic
activity as with 3 equiv of L7 (entry 17). However, FeCl3
combined with 1 equiv of L7 exhibited lower catalytic activity
(entry 18). We initially assumed that Fe(btfa)2Cl is formed
from FeCl3 and 2 equiv of L7 and Fe(btfa)Cl2 is formed from
FeCl3 and 1 equiv of L7. Fe(btfa)2Cl exhibits the same catalytic
activity as Fe(btfa)3, but Fe(btfa)Cl2 does not. Therefore, the
optimum ratio of FeCl3 to L7 is 1/2 for this catalytic system.
The amount of the catalyst could be decreased to 0.05 equiv
(entry 19). In this case, the 3-sulfonylated product 2a was
isolated in 85% yield when the reaction time was prolonged to
12 h. For a large scale (gram scale), 2a was isolated in 93%
yield within 8 h. All the reactions exhibited high site-selectivity
since no or trace byproducts were observed. Selective acylation
could also be catalyzed by this catalytic system, leading to 3-
benzoylated product 2b in 90% yield (entry 17). Similar results
were obtained when K2CO3 was used as the base where 2a and
2b were isolated in 91 and 92% yield, respectively (entry 20).
B
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Figure 2. Regioselective sulfonylation and acylation of substrates containing cis-,1,2-, or 1,3-diol.a Reaction conditions: aK2CO3 (1.9 equiv), L7 (0.2
b
c
equiv), FeCl3 (0.1 equiv), RCl (1.5 equiv), MeCN (0.5 mL), rt, 1−12 h. DIPEA (1.9 equiv). DIPEA (1.6 equiv), AcCl (1.2 equiv), 2−4 h.
dDIPEA (1.9 equiv), 50 °C, 5 h. eK2CO3 (4.0 equiv), RCl (3.0 equiv), 4−12 h. fDIPEA (4.0 equiv), RCl (3.0 equiv), 3 h. gSubstrate (8 mmol, 1.104
g), DIPEA (1.9 equiv), L7 (0.02 equiv), FeCl3 (0.01 equiv), TsCl (1.5 equiv), MeCN (20 mL), 3 h.
Acetylation showed much poorer selectivity than benzoylation
likely due to relative ease of acetyl migration.8,14
ing both cis-diol and 1,3-diol, such as free methyl galactosides
and mannosides, there is no or poor selectivity between the
equatorial hydroxyl group and the primary hydroxyl group in
the reaction. Therefore, with 4 equiv of base and 3 equiv of
TsCl/BzCl for these substrates, leading to isolated 91−96%
yields of products 17−19 where both 3- and 6-positions
reacted. For free methyl glucosides, 2 equiv of base and 1.9
equiv of TsCl were used, leading to isolated 61−65% yields of
6-position protected products 20 and 21 since no cis-diol
competed with 1,3-diol in the sulfonylation. The relative low
yields of 20 and 21 are likely due to the poor solubility of the
substrates in acetonitrile. The sulfonylation of phenylene glycol
was also tested in a large scale. The catalytic system exhibited
very high catalytic activity to this substrate. Thus, FeCl3 (0.01
equiv) and L7 (0.02 equiv) were used in this reaction, and the
primary group sulfonylated product 24a was isolated in 92%
yield within only 3 h of reaction.
The catalytic system does not catalyze or accelerate the
sulfonylation of glycoside trans-diols, monohydroxy substrates,
and diols as shown with glycoside trans-diols 29 and 30,
alcohol 31, and 1,4-butanediol 32 with this method (Figure 3).
The competitive sulfonylation of a mixture of diol 33 and its
corresponding monohydric alcohol 31 only led to 24a, the
sulfonylation product of 33. The sulfonylation of a mixture of
ethylene glycol 35 and1,4-butanediol 32 in a competitive
We further evaluated the substrate scope of this method
(Figure 2). Thus, L7 (0.2 equiv), FeCl3 (0.1 equiv), K2CO3/
DIPEA (1.9 equiv), and the substrates containing a cis-diol
moiety, a 1,2-diol moiety, or a 1,3-diol moiety were mixed in
the solvent. Subsequently, a sulfonylation or acylation reagent
(1.2−1.5 equiv) was added, and these reactions were
proceeding at room temperature for 1−12 h. Methyl 4,6-
benzylidine α-mannoside 3 was first chosen to be tested with
TsCl and various acylation reagents, such as BzCl, AcCl, PivCl,
PMBzCl, and C15H31COCl. The 3-protected products 4a−f
were isolated in 62−97% yields, indicating the generality of the
method.
All glycosides containing a cis-diol were selectively
sulfonylated, benzoylated, or acetylated at the equatorial
hydroxyl groups, leading to 76−97% yields of products 5−
13. However, the catalytic system could not exhibit any
catalytic activity to glycoside trans-diols. The catalytic system
also exhibited high catalytic activity to substrates containing
1,2-diol or 1,3-diol. Thus, the 6-protected products 14−16
were isolated in 83−93% yields starting from glycoside
substrates where 4- and 6-positions are free, and the products
22−28 were isolated in 71−95% yields starting from
noncarbohydrate substrates. For glycoside substrates contain-
C
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substituted by the thienyl group) were further tested in the
sulfonylation of 1 (Figure 4). It was observed that FeCl3
combined with L8 or L10 exhibited no or low catalytic activity,
FeCl3 combined with L9 or L11 exhibited moderate catalytic
activity, and FeCl3 combined with L12 exhibited as high
catalytic activity as FeCl3 combined with L7. FeCl3 combined
with L11 exhibited lower catalytic activity than FeCl3 combined
with L7, which is likely due to the weaker electron-donating
ability of the p-chloride phenyl group than the phenyl group.
In order to confirm whether Fe(btfa)2Cl is formed by the
reaction of FeCl3 and 2 equiv of L7, we crystallized a product
from the reaction of FeCl3 with 2.0 equiv of L7 and crystallized
the other product of FeCl3 with 3.0 equiv of L7, respectively.
However, these two products are identical by comparison with
their X-ray diffraction (XRD) spectrum (Figure S1 in the
Supporting Information). The mixture of FeCl3 with 2.0 equiv
of L7 in the presence of DIPEA in acetonitrile was tested by
HRMS. The strong signals of 740.0030 and 724.0272 were
observed, indicating a Fe(btfa)3 molecule with a K+ and a Na+
(calculated values: 739.9941 and 724.0201), respectively. A
weak signal of 486.0015 was found, which likely represents
+Fe(btfa)2 (the calculated value: 485.9984). These results
indicated that Fe(btfa)3 instead of Fe(btfa)2Cl is formed from
the reaction of FeCl3 and 2 equiv of L7. Supposed that L7 is
completely consumed during the reaction, 0.067 and 0.1 equiv
of Fe(btfa)3 would be formed from the reaction of 0.1 equiv of
FeCl3 with 0.2 and 0.3 equiv of L7, respectively. One question
is why the identical catalytic activity was observed under these
two conditions. Based on these facts, a catalytic mechanism
was proposed in Figure 5. In the first step, the key iron catalyst
FeX3 is formed by FeCl3 and ligand X in the presence of a base.
FeX3 then forms a cyclic intermediate (a or b) with a diol
substrate in the presence of the base while releasing an X
molecule. The cyclic intermediate will further react with the
sulfonylation/acylation reagent to produce a regioselective
sulfonylated/acylated product going through the intermediate
c. This explains why the catalytic system (FeCl3/L7 = 1/2)
exhibits the same catalytic activity as the catalytic system
(FeCl3/L7 = 1/3) since the ratio of Fe to X is 1/2 in the cyclic
intermediate. We could not crystallize intermediate a nor study
the mechanism by NMR due to the existence of the iron(III).
We envisioned whether the intermediate a, b, or c could be
captured by HRMS detection. If this was the case, the
mechanism shown in Figure 5 would be confirmed. We first
Figure 3. Competitive experiments.
reaction only led to 22, the sulfonylation product of 35. These
experiments may support the formation of cyclic intermediates
with five- and six-membered rings by the iron catalyst and
diols. The sulfonylation of a mixture of a 1,2-diol (35/38) and
a 1,3-diol (37/39) in a competitive reaction led mainly to
sulfonylation of the 1,2-diol. The ratios of the sulfonylated
products of 1,2-diol and 1,3-diol are 7.44/1 (22/23) and 6.25/
1 (25a/28). These results support the formation of five-
membered ring intermediates more easily than the formation
of six-membered ring chelates between diols and the iron
catalyst.
By comparing the structures of L5, L6, and L7, it seems that a
ligand having an electron-withdrawing group at one end and an
electron-donating group at the other side plays a key role for
the good sulfonylation activity of the catalytic system.
Therefore, L8 (the trifluoromethyl group of L7 being
substituted by the methyl group), L9 (the trifluoromethyl
group of L7 being substituted by the ethoxide group), L10 (the
phenyl group of L7 being substituted by the methyl group), L11
(the phenyl group of L7 being substituted by the p-chloride
phenyl group), and L12 (the phenyl group of L7 being
Figure 4. Comparing the catalytic activity of FeCl3 combined with L5−L12.
D
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Figure 5. Proposed mechanism for FeCl3-catalyzed sulfonylation and acylation in the presence of L7.
Figure 6. HRMS detection for (a) mannoside 1 with 1.0 equiv of Fe(btfa)3 in the presence of 2.0 equiv of DIPEA in acetonitrile, and b) 0.5 equiv
of TsCl was added in the abovementioned mixture.
mixed mannoside 1 with 1.0 equiv of Fe(btfa)3 in the presence
of 2.0 equiv of DIPEA in acetonitrile. The mixture was
subjected to HRMS analysis after stirring at room temperature
for 5 h. To our delight, two strong signals of 331.1599 (raw
material 1, the calculated value with Na+: 331.1547) and
724.0226 (Fe(btfa)3) and two weak signals of 816.1404
(intermediate a, the calculated value with Na+: 816.1458) and
838.1291 (intermediate b, the calculated value with 2Na+:
838.1278) were observed (Figure 6a). After 0.5 equiv of TsCl
was added at rt for 5 h, this mixture was subjected to HRMS
detection. The strong signals of 331.1546 (raw material 1),
485.1628 (sulfonylation product 2a, the calculated value with
Na+: 485.1636), and 724.0198 (Fe(btfa)3) and a weak signal of
970.1531 (intermediate c, the calculated value with Na+:
970.1547) were observed (Figure 6b). However, the signal
around 816.1458−838.1278 (intermediate a or b) could not
be observed in this case, which might indicate that
intermediate a or b is extremely active and difficult to survive
in the presence of an acylation reagent. Consequently, the
capture of the intermediates a, b, and c by HRMS
demonstrated the proposed mechanism in Figure 5.
Based on this mechanism, the formation rate of products is
approximately proportional to the amount of the cyclic
intermediate in light of a kinetic analysis (Figure S4 in the
Supporting Information). Furthermore, the formation rate of
products is approximately proportional to the ligand when the
ratio of ligand is less than twice the amount of FeCl3, whereas
the formation rate of products remained unchanged when the
amount of the ligand is larger than or equal to twice the
amount of FeCl3. Under low conversion conditions, the ratio
of product yields should be approximately equal to the ratio of
the corresponding ligand amounts when two reactions proceed
for the same reaction time. To further validate this conjecture,
we explored the catalytic effects at various ratios of FeCl3/L7
1
(FeCl3/L7 = 1/3, 1/2, 1/1.5, 1/1.2, and 1/1) where the H
NMR yield for sulfonylation of 1 was detected after 1 h of
reaction (Figure 7). As expected, the yields of 2a were 86 and
84%, respectively, with the ratios of FeCl3/L7 being 1/3 and 1/
2. The yields of 2a decreased to 77, 67, and 56%, respectively,
with the ratios of FeCl3/L7 being 1/1.5, 1/1.2, and 1/1.
Comparing the two reactions in which the ratio of their ligand
amounts equal to 1.2, we found that the ratio of their
E
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General Method for Regioselective Sulfonylation/Acylation
of Diols and Polyols. Substrates were allowed to react with TsCl or
acyl chloride (1.2−3.0 equiv) in the presence of FeCl3 (0.01−0.1
equiv), benzoyl trifluoroacetone (0.02−0.2 equiv), and N,N-
diisopropylethylamine or K2CO3 (1.6−4.0 equiv) in dry acetonitrile
at room temperature for 1−12 h. The concentrated reaction mixture
was directly purified by flash column chromatography, affording the
pure sulfonylation/acylation products.
Methyl-3-O-(4-toluenesulfonyl)-6-O-(tert-butyldimethylsilyl)-α-
D-mannopyranoside (2a).12b Methyl-6-O-(tert-butyldimethylsilyl)-α-
D-mannopyranoside (0.1 mmol, 30.8 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl chloride (28.6 mg,
1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature for 6 h in
the presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone
(4.4 mg, 0.2 equiv). The reaction mixture was directly purified by
flash column chromatography (ethyl acetate/petroleum ether = 1/3),
affording compound 2a as a viscous pale yellow oil (42.0 mg, 91%).
1H NMR (400 MHz, CD3OD): δ 7.84 (d, J = 8.0 Hz, 2H), 7.41 (d, J
Figure 7. Yields of 2a with various ratios of FeCl3/L7.
corresponding yields (67%/56%) just equal to 1.2, supporting
our assumptions.
= 8.4 Hz, 2H), 4.56 (d, J = 1.2 Hz, 1H), 4.48 (dd, J = 9.2 and 3.2 Hz,
1H), 3.91−3.85 (m, 2H), 3.78−3.72 (m, 2H), 3.48−3.43 (m, 1H),
3.33 (s, 3H), 2.44 (s, 3H), 0.90 (s, 9H), 0.07 (s, 6H).
Methyl-3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-α-D-manno-
pyranoside (2b).5a Methyl-6-O-(tert-butyldimethylsilyl)-α-D-manno-
pyranoside (0.1 mmol, 30.8 mg) was allowed to react with K2CO3
(26.3 mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 4 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
CONCLUSIONS
■
It was demonstrated that FeCl3 could catalyze the
regioselective sulfonylation/acylation with the help of
acylacetone ligands having an electron-withdrawing group at
one end and an electron-donating group on the other side.
High isolated yields and selectivities for sulfonylation/acylation
were achieved, where the scope of substrates and acylation
reagents are wide. FeCl3 initially forms [FeL3] with an
acylacetone ligand in the presence of a base and then [FeL3]
catalyzed the sulfonylation/acylation. The optimized ratio of
FeCl3 to the ligand is 1/2. Mechanism studies have
demonstrated that [Fe(btfa)3] was formed from FeCl3 with 2
equiv of benzoyl trifluoroacetone under basic conditions in the
solvent acetonitrile at room temperature. [Fe(btfa)3] further
reacted with two hydroxyl groups of a substrate in the presence
of the base to form a five- or six-membered ring intermediate
while releasing a benzoyl trifluoroacetonate molecule. The
cyclic intermediate subsequently reacted with a sulfonylation/
acylation reagent, leading to regioselective sulfonylation/
acylation of the substrate. The released benzoyl trifluoroacet-
onate could react with excess FeCl3 to form [Fe(btfa)3] again
until FeCl3 is completely consumed in this cycle. All key
intermediates have been observed by HRMS detection,
therefore confirming the mechanism for the first time. In
comparison with the reaction using the catalyst, Fe(acac)3,
similar or higher isolated yields and selectivities were achieved
for benzoylation in most cases. Either FeCl3 or benzoyl
trifluoroacetonate is a common, cheap, and nontoxic reagent in
the laboratory. In particular, K2CO3 can be used instead of
DIPEA as a base in this catalytic system, thereby making the
process much greener.
1
compound 2b as a yellow oil (37.9 mg, 92%). H NMR (400 MHz,
CD3OD): δ 8.13−8.11 (m, 2H), 7.62−7.59 (m, 1H), 7.50−7.46 (m,
2H), 5.20 (dd, J = 9.6 and 3.2 Hz, 1H), 4.67 (d, J = 0.8 Hz, 1H), 4.09
(dd, J = 2.8 and 1.2 Hz, 1H), 4.02 (dd, J = 11.2 and 1.6 Hz, 1H), 3.96
(t, J = 10.0 Hz, 1H), 3.86 (dd, J = 10.8 and 6.4 Hz, 1H), 3.69−3.64
(m, 1H), 3.43 (s, 3H), 0.94 (s, 9H), 0.13 (s, 3H), 0.13 (s, 3H).
Methyl-3-O-(4-toluenesulfonyl)-4,6-O-benzylidene-α-D-manno-
pyranoside (4a).15 Methyl-4,6-O-benzylidene-α-D-mannopyranoside
(0.1 mmol, 28.2 mg) was allowed to react with K2CO3 (26.3 mg, 1.9
equiv) and p-toluenesulfonyl chloride (28.6 mg, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 6 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/2), affording
1
compound 4a as a light yellow oil (42.3 mg, 97%). H NMR (400
MHz, CDCl3): δ 7.72 (d, J = 8.0 Hz, 2H), 7.38−7.30 (m, 3H), 7.20
(d, J = 7.2 Hz, 2H), 7.04 (d, J = 7.6 Hz, 2H), 5.40 (s, 1H), 4.78−4.76
(m, 2H), 4.33 (s, 1H), 4.25−4.18 (m, 1H), 4.09 (t, J = 8.8 Hz, 1H),
3.83−3.74 (m, 2H), 3.38 (s, 3H), 2.31 (s, 3H).
Methyl-3-O-benzoyl-4,6-O-benzylidene-α-D-mannopyranoside
(4b).13 Methyl-4,6-O-benzylidene-α-D-mannopyranoside (0.1 mmol,
28.2 mg) was allowed to react with K2CO3 (26.3 mg, 1.9 equiv) and
benzoyl chloride (18 μL, 1.5 equiv) in dry acetonitrile (0.5 mL) at
room temperature for 2.5 h in the presence of FeCl3 (1.6 mg, 0.1
equiv) and phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction
mixture was directly purified by flash column chromatography (ethyl
acetate/petroleum ether = 1/2), affording compound 4b as a white
solid (34.4 mg, 89%). 1H NMR (400 MHz, CDCl3): δ 8.07−8.05 (m,
2H), 7.58−7.53 (m, 1H), 7.45−7.41 (m, 4H), 7.33−7.30 (m, 3H),
5.60 (s, 1H), 5.55 (dd, J = 10.4 and 3.2 Hz, 1H), 4.78 (d, J = 1.6
Hz,1H), 4.34−4.25 (m, 3H), 4.03−3.97 (m, 1H), 3.93−3.88 (m,
1H), 3.43 (s, 3H).
Methyl-3-O-acetyl-4,6-O-benzylidene-α-D-mannopyranoside
(4c).16 Methyl-4,6-O-benzylidene-α-D-mannopyranoside (0.1 mmol,
28.2 mg) was allowed to react with N,N-diisopropylethylamine (28
μL, 1.6 equiv) and acetyl chloride (9 μL, 1.2 equiv) in dry acetonitrile
(0.5 mL) at room temperature for 2 h in the presence of FeCl3 (1.6
mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The
reaction mixture was directly purified by flash column chromatog-
raphy (ethyl acetate/petroleum ether = 1/2), affording compound 4c
as a colorless syrup (20.0 mg, 62%). 1H NMR (400 MHz, CDCl3): δ
EXPERIMENTAL SECTION
■
General Methods. All chemicals were purchased as reagent grade
and used without further purification. The solvents were purified
before use. CH3CN was distilled over CaH2. Chemical reactions were
monitored by thin-layer chromatography using precoated silica gel 60
(0.25 mm in thickness) plates. Flash column chromatography was
performed on silica gel 60 (SDS 0.040−0.063 mm). Spots were
visualized by UV light (254 nm) and charred with a solution of
1
H2SO4 in ethanol. H NMR and 13C NMR spectra were recorded at
298 K in CDCl3 or CD3OD using the residual signals from CDCl3
(1H: δ = 7.26 ppm) or CD3OD (1H: δ = 3.31 ppm) as an internal
standard. Peak assignments of 1H were determined by analysis of
1
coupling constants and assisted by 2D H COSY.
F
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7.46−7.44 (m, 2H), 7.39−7.35 (m, 3H), 5.55 (s, 1H), 5.33 (dd, J =
3.2 and 10.4 Hz, 1H), 4.75 (d, J = 0.8 Hz, 1H), 4.29 (dd, J = 4.0 and
9.6 Hz, 1H), 4.15 (s, 1H), 4.09 (t, J = 9.6 Hz, 1H), 3.96−3.90 (m,
1H), 3.88−3.83 (m, 1H), 3.41 (s, 3H), 2.13 (s, 3H).
(m, 2H), 3.72 (t, J = 5.2 Hz, 1H), 3.38 (s, 3H), 2.42 (s, 3H), 0.87 (s,
9H), 0.06 (s, 6H).
Methyl-3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-α-D-galacto-
pyranoside (5b).5a Methyl-6-O-(tert-butyldimethylsilyl)-α-D-galacto-
pyranoside (0.1 mmol, 30.8 mg) was allowed to react with K2CO3
(26.3 mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/2), affording
Methyl-3-O-pivaloyl-4,6-O-benzylidene-α-D-mannopyranoside
(4d).17 Methyl-4,6-O-benzylidene-α-D-mannopyranoside (0.1 mmol,
28.2 mg) was allowed to react with N,N-diisopropylethylamine (34
μL, 1.9 equiv) and pivaloyl chloride (19 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at 50 °C for 5 h in the presence of FeCl3 (1.6
mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The
reaction mixture was directly purified by flash column chromatog-
raphy (ethyl acetate/petroleum ether = 1/2), affording compound 4d
1
compound 5b as a pale yellow solid (40.0 mg, 97%). H NMR (400
MHz, CDCl3): δ 8.11−8.09 (m, 2H), 7.57−7.54 (m, 1H), 7.45−7.41
(m, 2H), 5.26 (dd, J = 10.0 and 2.0 Hz, 1H), 4.89 (d, J = 3.6 Hz, 1H),
4.31 (s, 1H), 4.24 (dd, J = 10 and 3.2 Hz, 1H), 3.95−3.84 (m, 3H),
3.45 (s, 3H), 0.89 (s, 9H), 0.09 (s, 6H).
1
as a white powder (30.0 mg, 82%). H NMR (400 MHz, CDCl3): δ
7.43−7.42 (m, 2H), 7.35−7.33 (m, 3H), 5.57 (s, 1H), 5.32 (dd, J =
10.0 and 2.4 Hz, 1H), 4.75 (s, 1H), 4.30 (dd, J = 9.2 and 3.2 Hz, 1H),
4.13−4.08 (m, 2H), 3.95−3.84 (m, 2H), 3.40 (s, 3H), 2.15 (br s,
1H), 1.23 (s, 9H).
Methyl-3-O-(4-toluenesulfonyl)-6-O-(tert-butyldimethylsilyl)-β-D-
galactopyranoside (6a).12b Methyl-6-O-(tert-butyldimethylsilyl)-β-D-
galactopyranoside (0.1 mmol, 30.8 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl chloride (28.6 mg,
1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature for 12 h
in the presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyl-
trifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/2), affording compound 6a as a white solid (38.8
mg, 84%). 1H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.4 Hz, 2H),
7.32 (d, J = 8.0 Hz, 2H), 4.44 (dd, J = 9.6 and 3.2 Hz, 1H), 4.16 (d, J
= 7.6 Hz, 1H), 4.14 (d, J = 3.2 Hz, 1H), 3.89−3.79 (m, 3H), 3.50 (s,
3H), 3.46−3.43 (m, 1H), 2.42 (s, 3H), 0.86 (s, 9H), 0.05 (s, 6H).
Methyl-3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-β-D-galacto-
pyranoside (6b).13 Methyl-6-O-(tert-butyldimethylsilyl)-β-D-galacto-
pyranoside (0.1 mmol, 30.8 mg) was allowed to react with K2CO3
(26.3 mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2.5 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
compound 6b as a colorless oil (37.9 mg, 92%). 1H NMR (400 MHz,
CDCl3): δ 8.11−8.09 (m, 2H), 7.58−7.54 (m, 1H), 7.45−7.41 (m,
2H), 5.07 (dd, J = 10.0 and 3.2 Hz, 1H), 4.32−4.28 (m, 2H), 4.04
(dd, J = 10.0 and 7.6 Hz, 1H), 3.96 (dd, J = 10.4 and 5.6 Hz, 1H),
3.90 (dd, J = 10.8 and 4.8 Hz, 1H), 3.61−3.57 (m, 4H), 0.89 (s, 9H),
0.08 (s, 6H).
Methyl-3-O-(4-methoxybenzoyl)-4,6-O-benzylidene-α-D-manno-
pyranoside (4e). Methyl-4,6-O-benzylidene-α-D-mannopyranoside
(0.1 mmol, 28.2 mg) was allowed to react with N,N-diisopropylethyl-
amine (34 μL, 1.9 equiv) and p-methoxybenzoyl chloride (25.6 mg,
1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature for 5 h in
the presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone
(4.4 mg, 0.2 equiv). The reaction mixture was directly purified by
flash column chromatography (ethyl acetate/petroleum ether = 1/1),
1
affording compound 4e as a colorless oil (36.6 mg, 88%). H NMR
(400 MHz, CDCl3): δ 8.03−8.00 (m, 2H, ArH), 7.44−7.42 (m, 2H,
ArH), 7.33−7.30 (m, 3H, ArH), 6.92−6.88 (m, 2H, ArH), 5.60 (s,
1H, PhCH), 5.52 (dd, J = 10.4 and 3.6 Hz, 1H, H-3), 4.79 (d, J = 1.6
Hz, 1H, H-1), 4.34−4.23 (m, 3H, H-2, H-4, H-6a), 4.03−3.88 (m,
2H, H-5, H-6b), 3.84 (s, 3H, PhOCH3), 3.44 (s, 3H, OCH3).
13C{1H} NMR (101 MHz, CDCl3): δ 165.4, 163.7, 137.4, 132.4,
132.0, 129.1, 128.3, 126.3, 122.2, 113.8, 102.0, 101.6, 77.3, 76.3, 71.3,
70.0, 69.0, 63.9, 55.6, 55.3 ppm. Rf: 0.75 (ethyl acetate/petroleum
ether = 1/1). HRMS (ESI-TOF) m/z calcd. for C22H24O8Na [M +
Na]+: 439.1363; found: 439.1361.
Methyl-3-O-palmitoyl-4,6-O-benzylidene-α-D-mannopyranoside
(4f). Methyl-4,6-O-benzylidene-α-D-mannopyranoside (0.1 mmol,
28.2 mg) was allowed to react with N,N-diisopropylethylamine (34
μL, 1.9 equiv) and palmitoyl chloride (41.2 mg, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/2), affording
compound 4f as a colorless oil (48.4 mg, 93%). 1H NMR (400 MHz,
CDCl3): δ 7.45−7.43 (m, 2H, ArH), 7.36−7.33 (m, 3H, ArH), 5.55
(s, 1H, PhCH), 5.35 (dd, J = 10 and 3.2 Hz, 1H, H-3), 4.74 (d, J =
1.2 Hz, 1H, H-1), 4.29 (dd, J = 9.6 and 4.4 Hz, 1H, H-6a), 4.14−4.13
(m, 1H, H-2), 4.09 (t, J = 9.6 Hz, 1H, H-4), 3.96−3.90 (m, 1H, H-
6b), 3.88−3.83 (m, 1H, H-5), 3.41 (s, 3H, OCH3), 2.39−2.35 (m,
2H, CH3(CH2)14CO), 1.65−1.58 (m, 2H, CH3(CH2)14CO), 1.32−
1.21 (m, 24H, CH3(CH2)14CO), 0.90−0.86 (m, 3H,
CH3(CH2)14CO). 13C{1H} NMR (101 MHz, CDCl3): δ 172.8,
137.3, 129.1, 128.3, 126.2, 101.9, 101.5, 76.3, 70.5, 70.0, 69.0, 63.8,
55.2, 34.5, 32.0, 29.8, 29.8, 29.8, 29.8, 29.7, 29.5, 29.5, 29.4, 29.1,
25.2, 22.8, 14.2 ppm. Rf: 0.8 (ethyl acetate/petroleum ether = 1/2).
HRMS (ESI-TOF) m/z calcd. for C30H48O7Na [M + Na]+: 543.3292;
found: 543.3296.
Methyl-3-O-(4-toluenesulfonyl)-α-L-fucopyranoside (7a).12b
Methyl-α-L-fucopyranoside (0.1 mmol, 17.8 mg) was allowed to
react with K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl chloride
(28.6 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 2.5 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/1), affording compound 7a as a viscous pale
yellow oil (30.2 mg, 91%). 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J
= 8.0 Hz, 2H), 7.33 (d, J = 7.6 Hz, 2H), 4.74 (d, J = 3.6 Hz, 1H), 4.63
(dd, J = 10.0 and 2.8 Hz, 1H), 4.00−3.90 (m, 3H), 3.38 (s, 3H), 2.43
(s, 3H), 1.27 (d, J = 6.4 Hz, 3H).
Methyl-3-O-benzoyl-α-L-fucopyranoside (7b).5a Methyl-α-L-fuco-
pyranoside (0.1 mmol, 17.8 mg) was allowed to react with K2CO3
(26.3 mg, 1.9 equiv) and benzoyl chloride (17.5 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/2), affording
Methyl-3-O-(4-toluenesulfonyl)-6-O-(tert-butyldimethylsilyl)-α-
D-galactopyranoside (5a).12b Methyl-6-O-(tert-butyldimethylsilyl)-
α-D-galactopyranoside (0.1 mmol, 30.8 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl chloride (28.6 mg,
1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature for 5 h in
the presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone
(4.4 mg, 0.2 equiv). The reaction mixture was directly purified by
flash column chromatography (ethyl acetate/petroleum ether = 1/3),
1
compound 7b as a pale yellow solid (26.2 mg, 93%). H NMR (400
MHz, CD3OD): δ 8.12 (d, J = 7.6 Hz, 2H), 7.62−7.59 (m, 1H),
7.50−7.46 (m, 2H), 5.23 (dd, J = 10.4 and 2.8 Hz, 1H), 4.75 (d, J =
3.6 Hz, 1H), 4.15 (dd, J = 10.4 and 3.6 Hz, 1H), 4.06 (dd, J = 12.8
and 6.4 Hz, 1H), 3.96 (d, J = 2.0 Hz, 1H), 3.44 (s, 3H), 1.25 (d, J =
6.4 Hz, 3H).
1
affording compound 5a as a white solid (42.0 mg, 91%). H NMR
(400 MHz, CDCl3): δ 7.85 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz,
2H), 4.79 (d, J = 4.0 Hz, 1H), 4.63 (dd, J = 10.0 and 2.8 Hz, 1H),
4.20 (d, J = 2.4 Hz, 1H), 4.05 (dd, J = 9.6 and 3.6 Hz, 1H), 3.87−3.77
Methyl-3-O-(4-toluenesulfonyl)-α-L-rhamnopyranoside (8a).12b
Methyl-α-L-rhamnopyranoside (0.1 mmol, 17.8 mg) was allowed to
react with K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl chloride
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(28.6 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 2 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture
was directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/1), affording compound 8a as a viscous pale
yellow oil (30.9 mg, 93%). 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J
= 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.61−4.58 (m, 2H), 3.97 (br
s, 1H), 3.71−3.58 (m, 2H), 3.32 (s, 3H), 2.82 (d, J = 2.8 Hz, 1H),
2.62 (d, J = 3.2 Hz, 1H), 2.43 (s, 3H), 1.30 (d, J = 6.0 Hz, 3H).
Methyl-3-O-benzoyl-α-L-rhamnopyranoside (8b).5a Methyl-α-L-
rhamnopyranoside (0.1 mmol, 17.8 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv)
in dry acetonitrile (0.5 mL) at room temperature for 2 h in the
presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4
mg, 0.2 equiv). The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether = 1/2),
25.9, 21.7, 21.2, 18.2, −5.4 ppm. Rf: 0.4 (ethyl acetate/petroleum
ether = 1/3). HRMS (ESI-TOF) m/z calcd. for C26H38O7S2SiNa [M
+ Na]+: 577.1720; found: 577.1712.
p-Tolyl-3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-β-D-gal-
actopyranoside (10b).13 p-Tolyl-6-O-(tert-butyldimethylsilyl)-1-thio-
β-D-galactopyranoside (0.1 mmol, 40.1 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv)
in dry acetonitrile (0.5 mL) at room temperature for 2 h in the
presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4
mg, 0.2 equiv). The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether = 1/3),
affording compound 10b as a viscous pale yellow oil (42.4 mg, 84%).
1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.0 Hz, 2H), 7.57−7.40
(m, 5H), 7.13 (d, J = 7.6 Hz, 2H), 5.10 (dd, J = 9.6 and 2.4 Hz, 1H),
4.58 (d, J = 9.6 Hz, 1H), 4.35 (s, 1H), 4.07−3.91 (m, 3H), 3.63−3.60
(m, 1H), 2.35 (s, 3H), 0.91 (s, 9H), 0.12 (s, 3H), 0.10 (s, 3H).
p-Tolyl-3-O-acetyl-6-O-(tert-butyldimethylsilyl)-1-thio-β-D-gal-
actopyranoside (10c).8 p-Tolyl-6-O-(tert-butyldimethylsilyl)-1-thio-
β-D-galactopyranoside (0.1 mmol, 40.1 mg) was allowed to react with
N,N-diisopropylethylamine (28 μL, 1.6 equiv) and acetyl chloride (9
μL, 1.2 equiv) in dry acetonitrile (0.5 mL) at room temperature for 3
h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyl-
trifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/2), affording compound 10c as a viscous pale
yellow oil (34.6 mg, 78%). 1H NMR (400 MHz, CDCl3): δ 7.47 (d, J
= 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 4.85 (dd, J = 9.2 Hz and 2.4
Hz, 1H), 4.50 (d, J = 9.6 Hz, 1H), 4.22 (d, J = 2.0 Hz, 1H), 3.98 (dd,
J = 10.8 and 4.8 Hz, 1H), 3.92−3.83 (m, 2H), 3.53 (t, J = 3.6 Hz,
1H), 2.33 (s, 3H), 2.14 (s, 3H), 0.90 (s, 9H), 0.12 (s, 3H), 0.10 (s,
3H).
Isopropylthio-3-O-(4-toluenesulfonyl)-6-O-(tert-butyldimethylsil-
yl)-β-D-galactopyranoside (11a).12b Isopropylthio-6-O-(tert-butyldi-
methylsilyl)-β-D-galactopyranoside (0.1 mmol, 35.2 mg) was allowed
to react with K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl
chloride (28.6 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room
temperature for 5 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 11a as a viscous yellow
oil (47.1 mg, 93%). 1H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.4
Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 4.50 (dd, J = 9.2 and 2.8 Hz, 1H),
4.37 (d, J = 10.0 Hz, 1H), 4.21 (s, 1H), 3.89−3.78 (m, 3H), 3.48 (t, J
= 5.2 Hz, 1H), 3.22−3.15 (m, 1H), 2.43 (s, 3H), 1.29 (d, J = 6.8 Hz,
6H), 0.86 (s, 9H), 0.05 (s, 6H).
1
affording compound 8b as a yellow oil (26.8 mg, 95%). H NMR
(400 MHz, CDCl3): δ 8.04 (d, J = 7.6 Hz, 2H), 7.57−7.53 (m, 1H),
7.43−7.39 (m, 2H), 5.23 (d, J = 6.0 Hz, 1H), 4.66 (s, 1H), 4.12 (s,
1H), 3.80−3.75 (m, 2H), 3.37 (s, 3H), 1.35 (d, J = 5.2 Hz, 3H).
Phenyl-3-O-(4-toluenesulfonyl)-4,6-O-benzylidene-1-thio-α-D-
mannopyranoside (9a). Phenyl-4,6-O-benzylidene-1-thio-α-D-man-
nopyranoside (0.1 mmol, 36.0 mg) was allowed to react with K2CO3
(26.3 mg, 1.9 equiv) and p-toluenesulfonyl chloride (28.6 mg, 1.5
equiv) in dry acetonitrile (0.5 mL) at room temperature for 4 h in the
presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4
mg, 0.2 equiv). The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether = 1/3),
affording compound 9a as a light yellow oil (42.1 mg, 82%). 1H NMR
(400 MHz, CDCl3): δ 7.76 (d, J = 8.0 Hz, 2H, ArH), 7.47−7.45 (m,
2H, ArH), 7.39−7.29 (m, 6H, ArH), 7.23−7.21 (m, 2H, ArH), 7.09
(d, J = 8.0 Hz, 2H, ArH), 5.57 (d, J = 0.8 Hz, 1H, H-1), 5.41 (s, 1H,
PhCH), 4.82 (dd, J = 10.0 and 3.2 Hz, 1H, H-3), 4.58 (s, 1H, H-2),
4.33−4.27 (m, 1H, H-5), 4.18−4.13 (m, 2H, H-4, H-6a), 3.80 (t, J =
10.0 Hz, 1H, H-6b), 3.13 (br s, 1H, OH), 2.34 (s, 3H, ArCH3).
13C{1H} NMR (101 MHz, CDCl3): δ 145.0, 137.0, 132.9, 132.8,
132.1, 129.8, 129.4, 129.2, 128.3, 128.2, 126.3, 101.9, 88.3, 78.6, 75.7,
72.1, 68.4, 65.4, 21.9 ppm. Rf: 0.6 (ethyl acetate/petroleum ether = 1/
3). HRMS (ESI-TOF) m/z calcd. for C26H26O7S2Na [M + Na]+:
537.1012; found: 537.1001.
Phenyl-3-O-benzoyl-4,6-O-benzylidene-1-thio-α-D-mannopyra-
noside (9b).8 Phenyl-4,6-O-benzylidene-1-thio-α-D-mannopyranoside
(0.1 mmol, 36.0 mg) was allowed to react with K2CO3 (26.3 mg, 1.9
equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry acetonitrile (0.5
mL) at room temperature for 2 h in the presence of FeCl3 (1.6 mg,
0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The
reaction mixture was directly purified by flash column chromatog-
raphy (ethyl acetate/petroleum ether = 1/3), affording compound 9b
as a white solid (37.6 mg, 81%). 1H NMR (400 MHz, CDCl3): δ 8.08
(d, J = 8.0 Hz, 2H), 7.60−7.57 (m, 1H), 7.52−7.44 (m, 6H), 7.34−
7.30 (m, 6H), 5.62−5.58 (m, 3H), 4.59−4.51 (m, 2H), 4.37 (t, J =
9.6 Hz), 4.27 (dd, J = 10.4 and 4.8 Hz, 1H), 3.92 (t, J = 10.0 Hz, 1H).
p-Tolyl-3-O-(4-toluenesulfonyl)-6-O-(tert-butyldimethylsilyl)-1-
thio-β-D-galactopyranoside (10a). p-Tolyl-6-O-(tert-butyldimethyl-
silyl)-1-thio-β-D-galactopyranoside (0.1 mmol, 40.1 mg) was allowed
to react with K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl
chloride (28.6 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room
temperature for 5 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 10a as a colorless oil
(50.5 mg, 91%). 1H NMR (600 MHz, CDCl3): δ 7.83 (d, J = 8.4 Hz,
2H, ArH), 7.41 (d, J = 7.8 Hz, 2H, ArH), 7.30 (d, J = 7.8 Hz, 2H,
ArH), 7.06 (d, J = 7.8 Hz, ArH), 4.49 (dd, J = 9.6 and 3.0 Hz, 1H, H-
3), 4.45 (d, J = 9.6 Hz, 1H, H-1), 4.20 (s, 1H, H-4), 3.90−3.83 (m,
3H, H-2, H-6a, H-6b), 3.48 (t, J = 4.8 Hz, 1H, H-5), 2.40 (s, 3H,
ArCH3), 2.30 (s, 3H, ArCH3), 0.88 (s, 9H, Si(C(CH3)3)(CH3)2),
0.08 (s, 3H, Si(C(CH3)3)(CH3)2), 0.07 (s, 3H, Si(C(CH3)3)-
(CH3)2). 13C{1H} NMR (150 MHz, CDCl3): δ 145.1, 138.3, 133.6,
133.3, 129.8, 129.8, 128.0, 127.9, 88.6, 84.3, 77.6, 68.8, 66.7, 62.9,
Isopropylthio-3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-β-D-gal-
actopyranoside (11b).13 Isopropylthio-6-O-(tert-butyldimethylsilyl)-
β-D-galactopyranoside (0.1 mmol, 35.2 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv)
in dry acetonitrile (0.5 mL) at room temperature for 1 h in the
presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4
mg, 0.2 equiv). The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether = 1/3),
1
affording compound 11b as a viscous yellow oil (43.0 mg, 94%). H
NMR (400 MHz, CDCl3): δ 8.11 (d, J = 7.6 Hz, 2H), 7.57 (t, J = 7.2
Hz, 1H), 7.46−7.42 (m, 2H), 5.11 (dd, J = 9.6 and 2.0 Hz, 1H), 4.51
(d, J = 9.6 Hz, 1H), 4.33 (s, 1H), 4.07 (t, J = 9.6 Hz, 1H), 3.96−3.86
(m, 2H), 3.62 (t, J = 4.4 Hz, 1H), 3.29−3.23 (m, 1H), 1.37 (s, 3H),
1.35 (s, 3H), 0.88 (s, 9H), 0.08 (s, 6H).
Isopropylthio-3-O-acetyl-6-O-(tert-butyldimethylsilyl)-β-D-galac-
topyranoside (11c).8 Isopropylthio-6-O-(tert-butyldimethylsilyl)-β-D-
galactopyranoside (0.1 mmol, 35.2 mg) was allowed to react with
N,N-diisopropylethylamine (28 μL, 1.6 equiv) and acetyl chloride (9
μL, 1.2 equiv) in dry acetonitrile (0.5 mL) at room temperature for
3.5 h in the presence of FeCl3 (1.62 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture
was directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/2), affording compound 11c as a viscous pale
yellow oil (29.9 mg, 76%). 1H NMR (400 MHz, CDCl3): δ 4.85 (dd,
J = 9.2 and 2.0 Hz, 1H), 4.44 (d, J = 10.0 Hz, 1H), 4.21 (d, J = 1.6
H
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Hz, 1H), 3.92−3.83 (m, 3H), 3.53 (t, J = 4.4 Hz, 1H), 3.26−3.19 (m,
1H), 2.17 (s, 3H), 1.33 (d, J = 6.4 Hz, 6H), 0.87 (s, 9H), 0.07 (s,
3H), 0.07 (s, 3H).
Hz, 1H), 4.52−4.48 (m, 2H), 4.29 (d, J = 2.0 Hz, 1H), 4.09−4.05 (m,
1H), 3.94−3.89 (m, 4H), 3.69−3.58 (m, 3H), 3.44−3.35 (m, 2H),
0.90 (s, 9H), 0.87 (s, 9H), 0.09 (s, 6H), 0.07 (s, 6H).
Phenyl-3-O-(4-toluenesulfonyl)-6-O-(tert-butyldimethylsilyl)-1-
thio-β-D-galactopyranoside (12a). Phenyl-6-O-(tert-butyldimethyl-
silyl)-1-thio-β-D-galactopyranoside (0.1 mmol, 36.8 mg) was allowed
to react with K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl
chloride (28.6 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room
temperature for 2 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 12a as a light yellow oil
(49.1 mg, 91%). 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 8.4 Hz,
2H, ArH), 7.55−7.50 (m, 2H, ArH), 7.33−7.26 (m, 5H, ArH), 4.51−
4.48 (m, 2H, H-3, H-1), 4.23 (t, J = 2.8 Hz, 1H, H-4), 3.93−3.84 (m,
3H, H-2, H-6a, H-6b), 3.50 (t, J = 5.2 Hz, 1H, H-5), 2.43 (s, 3H,
ArCH3), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.08 (s, 3H, Si(C-
(CH3)3)(CH3)2), 0.07 (s, 3H, Si(C(CH3)3)(CH3)2). 13C{1H} NMR
(101 MHz, CDCl3): δ 145.2, 133.7, 132.8, 131.8, 129.9, 129.1, 128.3,
128.1, 88.6, 84.2, 77.8, 68.9, 66.9, 63.0, 25.9, 21.8, 18.3, −5.3 ppm. Rf:
0.6 (ethyl acetate/petroleum ether = 1/3). HRMS (ESI-TOF) m/z
calcd. for C25H36O7S2SiNa [M + Na]+: 563.1564; found: 563.1569.
Phenyl-3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-β-D-gal-
actopyranoside (12b).13 Phenyl-6-O-(tert-butyldimethylsilyl)-1-thio-
β-D-galactopyranoside (0.1 mmol, 36.8 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv)
in dry acetonitrile (0.5 mL) at room temperature for 2 h in the
presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4
mg, 0.2 equiv). The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether = 1/3),
affording compound 12b as a viscous pale yellow oil (45.6 mg, 93%).
1H NMR (400 MHz, CDCl3): δ 8.10−8.08 (m, 2H), 7.62−7.54 (m,
Methyl-2,3-di-O-benzyl-6-O-(4-toluenesulfonyl)-α-D-glucopyra-
noside (14a).18 Methyl-2,3-di-O-benzyl-α-D-glucopyranoside (0.1
mmol, 37.4 mg) was allowed to react with K2CO3 (26.3 mg, 1.9
equiv) and p-toluenesulfonyl chloride (28.6 mg, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 12 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
1
compound 14a as a gummy liquid (48.6 mg, 92%). H NMR (400
MHz, CDCl3): δ 7.77 (d, J = 8.4 Hz, 2H), 7.38−7.29 (m, 12H), 4.99
(d, J = 11.2 Hz, 1H), 4.77−4.62 (m, 3H), 4.55 (d, J = 3.6 Hz, 1H),
4.23−4.22 (m, 2H), 3.76−3.69 (m, 2H), 3.48−3.41 (m, 2H), 3.33 (s,
3H), 2.43 (s, 3H).
Methyl-2,3-di-O-benzyl-6-O-benzoyl-α-D-glucopyranoside
(14b).19 Methyl-2,3-di-O-benzyl-α-D-glucopyranoside (0.1 mmol,
37.4 mg) was allowed to react with N,N-diisopropylethylamine (34
μL, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2.5 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
1
compound 14b as a colorless oil (44.5 mg, 93%). H NMR (400
MHz, CDCl3): δ 8.03 (d, J = 8.0 Hz, 2H), 7.58−7.54 (m, 1H), 7.45−
7.32 (m, 12H), 5.02 (d, J = 11.2 Hz, 1H), 4.80−4.76 (m, 2H), 4.69−
4.60 (m, 3H), 4.52 (d, J = 12 Hz, 1H), 3.89−3.82 (m, 2H), 3.56−
3.52 (m, 2H), 3.45 (s, 3H).
Methyl-2,3-di-O-benzyl-6-O-(4-toluenesulfonyl)-α-D-galactopyr-
anoside (15a).20 Methyl-2,3-di-O-benzyl-α-D-galactopyranoside (0.1
mmol, 37.4 mg) was allowed to react with K2CO3 (26.3 mg, 1.9
equiv) and p-toluenesulfonyl chloride (28.6 mg, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 12 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
3H), 7.45−7.41 (m, 2H), 7.33−7.30 (m, 3H), 5.11 (dd, J = 9.6 and
3.2 Hz, 1H), 4.65 (d, J = 9.6 Hz, 1H), 4.36 (d, J = 2.8 Hz, 1H), 4.09
(t, J = 9.6 Hz, 1H), 4.02−3.91 (m, 2H), 3.64 (t, J = 4.8 Hz, 1H), 0.91
(s, 9H), 0.12 (s, 3H), 0.10 (s, 3H).
Phenyl-3′-O-(4-toluenesulfonyl)-6,6′-di-O-(tert-butyldimethylsil-
yl)-1-S-β-D-lactoside (13a). Phenyl-6,6′-di-O-(tert-butyldimethylsil-
yl)-1-S-β-D-lactoside (0.1 mmol, 66.3 mg) was allowed to react with
K2CO3 (26.3 mg, 1.9 equiv) and p-toluenesulfonyl chloride (28.6 mg,
1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature for 6 h in
the presence of FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone
(4.4 mg, 0.2 equiv). The reaction mixture was directly purified by
flash column chromatography (ethyl acetate/petroleum ether = 1/1),
1
compound 15a as a colorless syrup (46.5 mg, 88%). H NMR (400
MHz, CDCl3): δ 7.78 (d, J = 8.4 Hz, 2H), 7.38−7.28 (m, 12H), 4.77
(d, J = 12.0 Hz, 2H), 4.68−4.61 (m, 2H), 4.59 (d, J = 3.6 Hz, 1H),
4.22−4.11 (m, 2H), 3.95−3.92 (m, 2H), 3.84 (dd, J = 9.6 and 3.2 Hz,
1H), 3.75 (dd, J = 9.6 and 3.6 Hz, 1H), 3.33 (s, 3H), 2.43 (s, 3H).
Methyl-2,3-di-O-benzyl-6-O-benzoyl-α-D-galactopyranoside
(15b).19 Methyl-2,3-di-O-benzyl-α-D-galactopyranoside (0.1 mmol,
37.4 mg) was allowed to react with N,N-diisopropylethylamine (34
μL, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 6 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
compound 15b as a white amorphous solid (40.1 mg, 84%). 1H NMR
(400 MHz, CDCl3): δ 8.03 (d, J = 8.0 Hz, 2H), 7.57 (t, J = 7.2 Hz,
1H), 7.46−7.29 (m, 12H), 4.83 (d, J = 11.2 Hz, 2H), 4.73−4.66 (m,
3H), 4.58−4.48 (m, 2H), 4.07−4.04 (m, 2H), 3.93−3.85 (m, 2H),
3.37 (s, 3H).
1
affording compound 13a as a light yellow oil (67.8 mg, 83%). H
NMR (600 MHz, CDCl3): δ 7.82 (d, J = 7.8 Hz, 2H, ArH), 7.54−
7.53 (m, 2H, ArH), 7.30 (d, J = 8.4 Hz, 2H, ArH), 7.28−7.24 (m, 3H,
ArH), 4.49 (d, J = 9.6 Hz, 1H, H-1), 4.34−4.32 (m, 2H, H-1′, H-3′),
4.15 (br s, 1H, H-4′), 3.89−3.80 (m, 5H, H-2′, H-6a, H-6b, H-6a′,
H-6b′), 3.63 (t, J = 9.0 Hz, 1H, H-3), 3.54−3.48 (m, 2H, H-4, H-5′),
3.35 (d, J = 9.6 Hz, 1H, H-5), 3.31 (t, J = 9.0 Hz, 1H, H-2), 2.42 (s,
3H, ArCH3), 0.86 (s, 9H, Si(C(CH3)3)(CH3)2), 0.85 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.05 (s, 3H, Si(C(CH3)3)(CH3)2), 0.03 (s,
9H, Si(C(CH3)3)(CH3)2). 13C{1H} NMR (150 MHz, CDCl3): δ
145.1, 133.3, 133.3, 129.9, 129.8, 128.9, 128.2, 128.1, 103.8, 87.3,
83.3, 80.3, 78.9, 76.2, 74.5, 71.7, 67.7, 62.7, 61.7, 26.0, 26.0, 25.9,
25.8, 21.8, 18.4, 18.3, −3.5, −5.1, −5.2, −5.4, −5.4 ppm. Rf: 0.7 (ethyl
acetate/petroleum ether = 1/1). HRMS (ESI-TOF) m/z calcd. for
C37H60O12S2Si2Na [M + Na]+: 839.2957; found: 839.2975.
Methyl-2,3-di-O-benzyl-6-O-(4-toluenesulfonyl)-α-D-mannopyr-
anoside (16a). Methyl-2,3-di-O-benzyl-α-D-mannopyranoside (0.1
mmol, 37.4 mg) was allowed to react with K2CO3 (26.3 mg, 1.9
equiv) and p-toluenesulfonyl chloride (28.6 mg, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
Phenyl-3′-O-benzoyl-6,6′-di-O-(tert-butyldimethylsilyl)-1-S-β-D-
lactoside (13b).13 Phenyl-6,6′-di-O-(tert-butyldimethylsilyl)-1-S-β-D-
lactoside (0.1 mmol, 66.3 mg) was allowed to react with K2CO3 (26.3
mg, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 1 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/1), affording
1
compound 16a as a light yellow oil (46.5 mg, 88%). H NMR (600
MHz, CDCl3): δ 7.80 (d, J = 7.8 Hz, 2H, ArH), 7.36−7.27 (m, 12H,
ArH), 4.71 (s, 1H, H-1), 4.65 (d, J = 12.0 Hz, 1H, CH2Ph), 4.61 (d, J
= 12.0 Hz, 1H, CH2Ph), 4.56 (d, J = 11.4 Hz, 1H, CH2Ph), 4.43 (d, J
= 12.0 Hz, 1H, CH2Ph), 4.39 (d, J = 10.8 Hz, 1H, H-6a), 4.24 (dd, J
= 10.8 and 6.6 Hz, 1H, H-6b), 3.87 (t, J = 9.6 Hz, 1H, H-4), 3.77−
3.73 (m, 2H, H-2, H-5), 3.65 (dd, J = 9.6 and 3.0 Hz, 1H, H-3), 3.30
1
compound 13b as a viscous colorless oil (65.2 mg, 85%). H NMR
(400 MHz, CDCl3): δ 8.10 (d, J = 7.6 Hz, 2H), 7.59−7.55 (m, 3H),
7.46−7.42 (m, 2H), 7.29−7.26 (m, 3H), 5.02 (dd, J = 10.0 and 2.4
I
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(s, 3H, OCH3), 2.42 (s, 3H, ArCH3). 13C{1H} NMR (150 MHz,
CDCl3): δ 144.7, 138.0, 137.9, 133.1, 129.8, 128.6, 128.5, 128.1,
128.0, 127.9, 127.9, 99.1, 79.5, 73.7, 72.7, 71.7, 70.5, 69.6, 66.4, 55.1,
21.7 ppm. Rf: 0.4 (ethyl acetate/petroleum ether = 1/3). HRMS (ESI-
TOF) m/z calcd. for C28H32O8SNa [M + Na]+: 551.1710;
found:551.1701.
Methyl-3,6-di-O-(4-toluenesulfonyl)-α-D-mannopyranoside
(19a).11c Methyl-α-D-mannopyranoside (0.1 mmol, 19.4 mg) was
allowed to react with K2CO3 (55.3 mg, 4.0 equiv) and p-
toluenesulfonyl chloride (57.2 mg, 3.0 equiv) in dry acetonitrile
(0.5 mL) at room temperature for 12 h in the presence of FeCl3 (1.6
mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The
reaction mixture was directly purified by flash column chromatog-
raphy (methanol/dichloromethane = 1/20), affording compound 19a
as a pale yellow oil (46.7 mg, 93%). 1H NMR (400 MHz, CDCl3): δ
7.84 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.34 (t, J = 9.6 Hz,
4H), 4.63−4.59 (m, 2H), 4.33−4.25 (m, 2H), 4.03−3.97 (m, 2H),
3.71 (d, J = 6.4 Hz, 1H), 3.29 (s, 3H), 2.44 (s, 3H), 2.43 (s, 3H).
Methyl-3,6-di-O-benzyl-α-D-mannopyranoside (19b).13 Methyl-
α-D-mannopyranoside (0.1 mmol, 19.4 mg) was allowed to react with
N,N-diisopropylethylamine (70 μL, 4.0 equiv) and benzoyl chloride
(35.0 μL, 3.0 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 2.5 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/1), affording compound 19b as a colorless oil
(38.6 mg, 96%). 1H NMR (400 MHz, CDCl3): δ 8.07−8.04 (m, 4H),
7.57−7.52 (m, 2H), 7.44−7.38 (m, 4H), 5.35 (dd, J = 9.6 and 2.8 Hz,
1H), 4.77−4.70 (m, 2H, H-1), 4.60 (dd, J = 11.6 and 0.8 Hz, 1H),
4.17−4.10 (m, 2H), 4.01−3.97 (m, 1H), 3.41 (s, 3H).
Methyl-2,3-di-O-benzyl-6-O-benzoyl-α-D-mannopyranoside
(16b).19 Methyl-2,3-di-O-benzyl-α-D-mannopyranoside (0.1 mmol,
37.4 mg) was allowed to react with N,N-diisopropylethylamine (34
μL, 1.9 equiv) and benzoyl chloride (18 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2 h in the presence of
FeCl3 (1.6 mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
1
compound 16b as a colorless oil (39.7 mg, 83%). H NMR (400
MHz, CDCl3): δ 8.06 (d, J = 7.6 Hz, 2H), 7.54 (t, J = 7.2 Hz, 1H),
7.40−7.28 (m, 12H), 4.82 (s, 1H), 4.70−4.61 (m, 5H), 4.52 (d, J =
11.6 Hz, 1H), 4.12 (t, J = 9.6 Hz, 1H), 3.87−3.82 (m, 2H), 3.75 (dd,
J = 9.2 and 2.0 Hz, 1H), 3.38 (s, 3H).
Methyl-3,6-di-O-(4-toluenesulfonyl)-α-D-galactopyranoside
(17a).11c Methyl-α-D-galactopyranoside (0.1 mmol, 19.4 mg) was
allowed to react with K2CO3 (55.3 mg, 4.0 equiv) and p-
toluenesulfonyl chloride (57.2 mg, 3.0 equiv) in dry acetonitrile
(0.5 mL) at room temperature for 4.5 h in the presence of FeCl3 (1.6
mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The
reaction mixture was directly purified by flash column chromatog-
raphy (ethyl acetate/petroleum ether = 2/1), affording compound
17a as a light yellow oil (45.7 mg, 91%). 1H NMR (400 MHz,
CDCl3): δ 7.82 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 7.6 Hz, 2H), 7.34 (d,
J = 7.6 Hz, 4H), 4.72 (d, J = 2.0 Hz, 1H), 4.55 (d, J = 8.8 Hz, 1H),
4.21−4.13 (m, 3H), 3.99−3.92 (m, 2H), 3.35 (s, 3H), 2.44 (s, 6H).
Methyl-3,6-di-O-benzyl-α-D-galactopyranoside (17b).13 Methyl-
α-D-galactopyranoside (0.1 mmol, 19.4 mg) was allowed to react with
N,N-diisopropylethylamine (70 μL, 4.0 equiv) and benzoyl chloride
(35.0 μL, 3.0 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 2.5 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/1), affording compound 17b as a colorless oil
(37.0 mg, 92%). 1H NMR (400 MHz, CDCl3): δ 8.10−8.00 (m, 4H),
7.58−7.53 (m, 2H), 7.45−7.41 (m, 4H), 5.34 (dd, J = 10.0 and 1.6
Hz, 1H), 4.93 (d, J = 2.4 Hz, 1H), 4.62−4.58 (m, 1H), 4.53−4.49 (m,
1H), 4.25−4.20 (m, 3H), 3.47 (s, 3H).
Methyl-6-O-(4-toluenesulfonyl)-α-D-glucopyranoside (20).22
Methyl-α-D-glucopyranoside (0.2 mmol, 38.8 mg) was allowed to
react with N,N-diisopropylethylamine (67 μL, 1.9 equiv) and p-
toluenesulfonyl chloride (57.2 mg, 1.5 equiv) in dry acetonitrile (1
mL) at room temperature for 8 h in the presence of FeCl3 (3.2 mg,
0.1 equiv) and phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The
reaction mixture was directly purified by flash column chromatog-
raphy (ethyl acetate), affording compound 20 as a colorless oil (42.4
mg, 61%). 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 8.4 Hz, 2H),
7.33 (d, J = 8.4 Hz, 2H), 4.66 (d, J = 3.6 Hz, 1H), 4.32−4.22 (m,
2H), 3.74−3.68 (m, 2H), 3.50−3.41 (m, 2H), 3.32 (s, 3H), 2.42 (s,
3H).
Methyl-6-O-(4-toluenesulfonyl)-β-D-glucopyranoside (21). Meth-
yl-β-D-glucopyranoside (0.2 mmol, 38.8 mg) was allowed to react with
N,N-diisopropylethylamine (67 μL, 1.9 equiv) and p-toluenesulfonyl
chloride (57.2 mg, 1.5 equiv) in dry acetonitrile (1 mL) at room
temperature for 4 h in the presence of FeCl3 (3.2 mg, 0.1 equiv) and
phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate),
1
affording compound 21 as a colorless oil (45.2 mg, 65%). H NMR
Methyl-3,6-di-O-(4-toluenesulfonyl)-β-D-galactopyranoside
(18a).21 Methyl-β-D-galactopyranoside (0.1 mmol, 19.4 mg) was
allowed to react with K2CO3 (55.3 mg, 4.0 equiv) and p-
toluenesulfonyl chloride (57.2 mg, 3.0 equiv) in dry acetonitrile
(0.5 mL) at room temperature for 4.5 h in the presence of FeCl3 (1.6
mg, 0.1 equiv) and phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The
reaction mixture was directly purified by flash column chromatog-
raphy (ethyl acetate/petroleum ether = 2/1), affording compound
18a as a light yellow oil (47.7 mg, 95%). 1H NMR (400 MHz,
CDCl3): δ 7.83 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 7.6 Hz, 2H), 7.34 (d,
J = 7.2 Hz, 4H), 4.38 (dd, J = 9.6 and 1.6 Hz, 1H), 4.23−4.17 (m,
2H), 4.14−4.11 (m, 2H), 3.76−3.71 (m, 2H), 3.44 (s, 3H), 2.43 (s,
6H).
(400 MHz, CDCl3): δ 7.78 (d, J = 8.4 Hz, 2H, ArH), 7.31 (d, J = 8.0
Hz, 2H, ArH), 4.27 (d, J = 2.4 Hz, 2H, H-6a, H-6b), 4.18 (d, J = 7.6
Hz, 1H, H-1), 3.52−3.45 (m, 3H, H-3, H-4, H-5), 3.42 (s, 3H,
OCH3), 3.31 (t, J = 8.0 Hz, 1H, H-2), 2.41 (s, 3H, ArCH3). 13C{1H}
NMR (101 MHz, CDCl3): δ 145.1, 132.8, 130.0, 128.1, 103.4, 76.3,
73.4, 73.3, 69.7, 69.3, 57.1, 21.8 ppm. Rf: 0.45 (ethyl acetate). HRMS
(ESI-TOF) m/z calcd. for C14H20O8SNa [M + Na]+: 371.0771;
found: 371.0772.
2-Hydroxyethyl 4-toluenesulfonate (22). 1,2-Ethanediol (0.2
mmol, 12.4 mg) was allowed to react with N,N-diisopropylethylamine
(67.0 μL, 1.9 equiv) and p-toluenesulfonyl chloride (57.2 mg, 1.5
equiv) in dry acetonitrile (0.5 mL) at room temperature for 6 h in the
presence of FeCl3 (3.2 mg, 0.1 equiv) and phenyltrifluoroacetone (8.8
mg, 0.2 equiv). The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether = 1/2),
affording compound 22 as a pale yellow oil (35.4 mg, 82%). 1H NMR
(400 MHz, CDCl3): δ 7.77 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.0 Hz,
2H), 4.09 (t, J = 4.4 Hz, 2H), 3.77 (t, J = 4.8 Hz, 2H), 2.42 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3): δ 145.2, 132.6, 130.0, 128.0, 71.8,
60.5, 21.7 ppm. Rf: 0.3 (ethyl acetate/petroleum ether = 1/2). HRMS
(ESI-TOF) m/z calcd. for C9H12O4SNa [M + Na]+: 239.0349; found:
239.0350.
Methyl-3,6-di-O-benzyl-β-D-galactopyranoside (18b).13 Methyl-
β-D-galactopyranoside (0.1 mmol, 19.4 mg) was allowed to react with
N,N-diisopropylethylamine (70 μL, 4.0 equiv) and benzoyl chloride
(35.0 μL, 3.0 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 2.5 h in the presence of FeCl3 (1.6 mg, 0.1 equiv) and
phenyltrifluoroacetone (4.4 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/1), affording compound 18b as a white solid
(37.4 mg, 93%). 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 7.6 Hz,
2H), 8.01 (d, J = 7.6 Hz, 2H), 7.58−7.51 (m, 2H), 7.44−7.37 (m,
4H), 5.13 (dd, J = 10.0 and 2.8 Hz, 1H), 4.65−4.54 (m, 2H), 4.35 (d,
J = 7.6 Hz, 1H), 4.24 (d, J = 2.8 Hz, 1H), 4.09−4.05 (m, 1H), 3.97−
3.94 (m, 1H), 3.57 (s, 3H).
3-Hydroxypropyl 4-toluenesulfonate (23).23 1,3-Propanediol (0.2
mmol, 15.2 mg) was allowed to react with N,N-diisopropylethylamine
(67.0 μL, 1.9 equiv) and p-toluenesulfonyl chloride (57.2 mg, 1.5
equiv) in dry acetonitrile (0.5 mL) at room temperature for 6 h in the
J
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J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
presence of FeCl3 (3.2 mg, 0.1 equiv) and phenyltrifluoroacetone (8.8
mg, 0.2 equiv). The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether = 1/2),
petroleum ether = 1/3), affording compound 26b as a colorless oil
(44.6 mg, 82%). 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 7.6 Hz,
2H), 7.60−7.56 (m, 1H), 7.47−7.43 (m, 2H), 7.32−7.28 (m, 2H),
7.01−6.93 (m, 3H), 4.59−4.51 (m, 2H), 4.42−4.36 (m, 1H), 4.16−
4.08 (m, 2H), 2.73 (br s, 1H).
1
affording compound 23 as a colorless oil (34.5 mg, 75%). H NMR
(400 MHz, CDCl3): δ 7.77 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz,
2H), 4.16 (t, J = 6.4 Hz, 2H), 3.68 (t, J = 6.0 Hz, 2H), 2.43 (s, 3H),
1.89−1.83 (m, 2H).
2-Hydroxy-3-allyloxypropyl 4-Toluenesulfonate (27a).25 3-Ally-
loxy-1,2-propanediol (0.2 mmol, 26.4 mg) was allowed to react with
N,N-diisopropylethylamine (67.0 μL, 1.9 equiv) and p-toluenesulfonyl
chloride (57.2 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room
temperature for 12 h in the presence of FeCl3 (3.2 mg, 0.1 equiv) and
phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 27a as a pale yellow oil
(53.2 mg, 93%). 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.0 Hz,
2H), 7.34 (d, J = 8.4 Hz, 2H), 5.87−5.77 (m, 1H), 5.24−5.16 (m,
2H), 4.11−3.94 (m, 5H), 3.50−3.42 (m, 2H), 2.44 (s, 3H), 2.32 (br
s, 1H).
2-Hydroxy-2-phenylethyl 4-toluenesulfonate (24a).12b 1-Phenyl-
1,2-ethanediol (0.2 mmol, 27.6 mg) was allowed to react with N,N-
diisopropylethylamine (67.0 μL, 1.9 equiv) and p-toluenesulfonyl
chloride (57.2 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room
temperature for 12 h in the presence of FeCl3 (3.2 mg, 0.1 equiv) and
phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 24a as a colorless oil
(55.5 mg, 95%). 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 8.0 Hz,
2H), 7.36−7.27 (m, 7H), 4.97 (dd, J = 8.0 and 2.4 Hz, 1H), 4.14 (dd,
J = 10.4 and 2.8 Hz, 1H), 4.06−4.01 (m, 1H), 2.44 (s, 3H).
2-Hydroxy-2-phenylethyl Benzoate (24b).12b 1-Phenyl-1,2-etha-
nediol (0.2 mmol, 27.6 mg) was allowed to react with N,N-
diisopropylethylamine (67.0 μL, 1.9 equiv) and benzoyl chloride
(35.0 μL, 1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 2 h in the presence of FeCl3 (3.2 mg, 0.1 equiv) and
phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture
was directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 24b as a beige solid
(44.0 mg, 91%). 1H NMR (400 MHz, CDCl3): δ 8.05 (dd, J = 7.6 Hz,
2H), 7.59−7.56 (m, 1H), 7.46−7.31 (m, 7H), 5.10 (dd, J = 8.0 and
2.8 Hz, 1H), 4.52 (dd, J = 11.2 and 3.2 Hz, 1H), 4.45−4.40 (m, 1H),
2.80 (br s, 1H).
2-Hydroxy-3-allyloxypropyl Benzoate (27b).13 3-Allyloxy-1,2-
propanediol (0.2 mmol, 26.4 mg) was allowed to react with N,N-
diisopropylethylamine (67.0 μL, 1.9 equiv) and benzoyl chloride
(35.0 μL, 1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 2 h in the presence of FeCl3 (3.2 mg, 0.1 equiv) and
phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture
was directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 27b as a colorless oil
(37.8 mg, 80%). 1H NMR (400 MHz, CDCl3): δ 8.06−8.04 (m, 2H),
7.58−7.55 (m, 1H), 7.46−7.42 (m, 2H), 5.95−5.85 (m, 1H), 5.31−
5.19 (m, 2H), 4.45−4.37 (m, 2H), 4.19−4.14 (m, 1H), 4.06−4.04
(m, 2H), 3.63−3.53 (m, 2H), 2.54 (br s, 1H).
3-Hydroxybutyl 4-toluenesulfonate (28).12b 1,3-Butanediol (0.2
mmol, 18.0 mg) was allowed to react with N,N-diisopropylethylamine
(67.0 μL, 1.9 equiv) and p-toluenesulfonyl chloride (57.2 mg, 1.5
equiv) in dry acetonitrile (0.5 mL) at room temperature for 12 h in
the presence of FeCl3 (3.2 mg, 0.1 equiv) and phenyltrifluoroacetone
(8.8 mg, 0.2 equiv). The reaction mixture was directly purified by
flash column chromatography (ethyl acetate/petroleum ether = 1/2),
1-O-(4-Toluenesulfonyl)-2-propanol (25a).12b 1,2-Propanediol
(0.2 mmol, 15.2 mg) was allowed to react with N,N-diisopropylethyl-
amine (67.0 μL, 1.9 equiv) and p-toluenesulfonyl chloride (57.2 mg,
1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature for 12 h
in the presence of FeCl3 (3.2 mg, 0.1 equiv) and phenyl-
trifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/2), affording compound 25a as a colorless oil
(36.8 mg, 80%). 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.6 Hz,
2H), 7.34 (d, J = 8.0 Hz, 2H), 4.02−3.96 (m, 2H), 3.86−3.82 (m,
1H), 2.44 (s, 3H), 2.38 (br s, 1H), 1.14 (d, J = 6.0 Hz, 3H).
1-O-Benzoyl-2-propanol (25b).13 1,2-Propanediol (0.2 mmol,
15.2 mg) was allowed to react with N,N-diisopropylethylamine
(67.0 μL, 1.9 equiv) and benzoyl chloride (35.0 μL, 1.5 equiv) in dry
acetonitrile (0.5 mL) at room temperature for 2 h in the presence of
FeCl3 (3.2 mg, 0.1 equiv) and phenyltrifluoroacetone (8.8 mg, 0.2
equiv). The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether = 1/3), affording
1
affording compound 28 as a colorless oil (34.6 mg, 71%). H NMR
(400 MHz, CDCl3): δ 7.77 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.6 Hz,
2H), 4.24−4.18 (m, 1H), 4.12−4.07 (m, 1H), 3.94−3.89 (m, 1H),
2.43 (s, 3H), 2.00 (br s, 1H), 1.83−1.77 (m, 1H), 1.72−1.64 (m,
1H), 1.16 (d, J = 6.4 Hz, 3H).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b03128.
■
sı
Copies of NMR spectra of products (PDF)
1
compound 25b as a colorless oil (33.5 mg, 93%). H NMR (400
MHz, CDCl3): δ 8.05−8.03 (m, 2H), 7.58−7.54 (m, 1H), 7.45−7.41
(m, 2H), 4.35−4.30 (m, 1H), 4.22−4.15 (m, 2H), 2.50 (br s, 1H),
1.29−1.27 (m, 3H).
AUTHOR INFORMATION
Corresponding Author
■
1-O-(4-Toluenesulfonyl)-3-phenoxy-2-propanol (26a).24 3-Phe-
noxy-1,2-propanediol (0.2 mmol, 33.6 mg) was allowed to react with
N,N-diisopropylethylamine (67.0 μL, 1.9 equiv) and p-toluenesulfonyl
chloride (57.2 mg, 1.5 equiv) in dry acetonitrile (0.5 mL) at room
temperature for 12 h in the presence of FeCl3 (3.2 mg, 0.1 equiv) and
phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether = 1/3), affording compound 26a as a white crystal
(56.0 mg, 87%). 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.4 Hz,
2H), 7.31−7.25 (m, 4H), 6.97 (t, J = 7.2 Hz, 1H), 6.82 (d, J = 8.0 Hz,
2H), 4.25−4.17 (m, 3H), 3.97 (d, J = 3.6 Hz, 2H), 2.41 (s, 3H).
1-O-Benzoyl-3-phenoxy-2-propanol (26b).13 3-Phenoxy-1,2-pro-
panediol (0.2 mmol, 33.6 mg) was allowed to react with N,N-
diisopropylethylamine (67.0 μL, 1.9 equiv) and benzoyl chloride
(35.0 μL, 1.5 equiv) in dry acetonitrile (0.5 mL) at room temperature
for 3.5 h in the presence of FeCl3 (3.2 mg, 0.1 equiv) and
phenyltrifluoroacetone (8.8 mg, 0.2 equiv). The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
Hai Dong − Key Laboratory of Material Chemistry for Energy
Conversion and Storage, Ministry of Education, School of
Chemistry & Chemical Engineering and Hubei Key Laboratory
of Bioinorganic Chemistry and Materia Medica, Huazhong
University of Science & Technology, Wuhan 430074, PR
China; orcid.org/0000-0002-9794-1805; Email: hdong@
mail.hust.edu.cn
Authors
Jian Lv − Key Laboratory of Material Chemistry for Energy
Conversion and Storage, Ministry of Education, School of
Chemistry & Chemical Engineering, Huazhong University of
Science & Technology, Wuhan 430074, PR China
Jia-Jia Zhu − Key Laboratory of Material Chemistry for Energy
Conversion and Storage, Ministry of Education, School of
Chemistry & Chemical Engineering, Huazhong University of
Science & Technology, Wuhan 430074, PR China
K
https://dx.doi.org/10.1021/acs.joc.9b03128
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Solvent-Free One-Pot Sequences Based on Regioselective Silylations.
Beilstein J. Org. Chem. 2016, 12, 2748−2756. (c) Ko, Y.-C.; Tsai, C.-
F.; Wang, C.-C.; Dhurandhare, V. M.; Hu, P.-L.; Su, T.-Y.; Lico, L. S.;
Zulueta, M. M. L.; Hung, S.-C. Microwave-Assisted One-Pot
Synthesis of 1,6-Anhydrosugars and Orthogonally Protected Thio-
glycosides. J. Am. Chem. Soc. 2014, 136, 14425−14431. (d) Patil, P.
S.; Lee, C.-C.; Huang, Y.-W.; Zulueta, M. M. L.; Hung, S.-C.
Regioselective and Stereoselective Benzylidene Installation and One-
Pot Protection of D-Mannose. Org. Biomol. Chem. 2013, 11, 2605−
2612. (e) Joseph, A. A.; Verma, V. P.; Liu, X. Y.; Wu, C. H.;
Dhurandhare, V. M.; Wang, C. C. TMSOTf-Catalyzed Silylation:
Streamlined Regioselective One-Pot Protection and Acetylation of
Carbohydrates. Eur. J. Org. Chem. 2012, 744−753. (f) Tran, A. T.;
Jones, R. A.; Pastor, J.; Boisson, J.; Smith, N.; Galan, M. C. Copper
(II) Triflate: A Versatile Catalyst for the One-Pot Preparation of
Orthogonally Protected Glycosides. Adv. Synth. Catal. 2011, 353,
Yu Liu − Key Laboratory of Material Chemistry for Energy
Conversion and Storage, Ministry of Education, School of
Chemistry & Chemical Engineering, Huazhong University of
Science & Technology, Wuhan 430074, PR China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.9b03128
Author Contributions
#J.L. and J.-J.Z. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This study was supported by the National Nature Science
Foundation of China (nos. 21772049 and 21708010). The
authors are also grateful to the staffs in the Analytical and Test
Center of School of Chemistry & Chemical Engineering at
HUST for support with the NMR instruments.
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Protection of Glycopyranosides. Chem. Commun. 2011, 47, 2146−
2148. (h) Franea̧ is, A.; Urban, D.; Beau, J. M. Tandem Catalysis for a
One-Pot Regioselective Protection of Carbohydrates: The Example of
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C.; Lee, J. C.; Luo, S. Y.; Kulkarni, S.-S.; Huang, Y. W.; Lee, C.-C.;
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