Using DMF as Both a Catalyst and Cosolvent for the Regioselective Silylation of Polyols and Diols

Article abstract of DOI:10.1002/ejoc.201901195

Highly regioselective silylation of primary hydroxyl groups of unprotected polyols and diols was obtained by the use of a mixed solvent of MeCN/DMF (10:1) in this study. DMF was discovered to be a good catalyst in this reaction, although the silylation us

Full text of DOI:10.1002/ejoc.201901195

DOI: 10.1002/ejoc.201901195
Full Paper
Carbohydrate
Using DMF as Both a Catalyst and Cosolvent for the
Regioselective Silylation of Polyols and Diols
Jian Lv,[a] Tao Luo,[a] Dapeng Zou,[b] and Hai Dong*[a]
Abstract: Highly regioselective silylation of primary hydroxyl DMF for the silylation was also proposed herein after intensive
groups of unprotected polyols and diols was obtained by the investigation of the reaction by NMR techniques. It has been
use of a mixed solvent of MeCN/DMF (10:1) in this study. DMF demonstrated that a complex with a 1:1 ratio of the binding
was discovered to be a good catalyst in this reaction, although partners can be formed between TBSCl and DMF and has an
the silylation using DMF as a solvent has been a common association constant of 12/M, thus activating the silylation.
method for more than 40 years. The catalytic mechanism of
Introduction
catalyzed by Lewis acid B(C6F5)3[9] or transition metal[10] includ-
ing palladium, nickel, and ruthenium, have been developed
(Figure 1b). However, all of these methods have their own
shortcomings, such as long reaction times, use of toxic rea-
gents, harsh reaction conditions, and so on. Our group has long
been committed to developing environmental-friendly meth-
ods for regioselective protection of carbohydrates.[11,12] The
methyl 6-monosilylated pyranosides of glucose, mannose, and
galactose were often used as substrates to demonstrate the
effectiveness of these methods. For example, the 3-acylated 6-
Selective protection and semiprotection of carbohydrates for
the synthesis of oligosaccharides and glycoconjugates are of
great importance in carbohydrate chemistry.[1] Silyl ethers and
derivatives are widely applied as protecting groups in carbo-
hydrate synthesis due to their relative stability toward basic and
acidic hydrolysis and high specificity for fluoride-mediated
cleavage.[2] The most common silylation procedures involve the
reaction of hydroxyl groups with silyl chlorides in the presence
of an excess of a base, typically either imidazole in N,N-di-
methylformamide (DMF) solvent[3] or pyridine[4] (Figure 1a). tert-
Butyldimethylsilyl chloride (TBSCl) and tert-butyldiphenylsilyl
chloride (TBDPSCl) have emerged as the silylation reagents of
choice due to the right balance of the resulting silyl ethers be-
tween stability against acid or base. The method using imidaz-
ole in DMF is more popular likely due to the odor of pyridine
being annoying. By this method, regioselective silylation of un-
protected methyl pyranosides, with moderate yields for silyl-
ation of primary hydroxyl groups, has been achieved.[5] For ex-
ample, the silylation of unprotected methyl α-glucopyranosides
by TBSCl or TBDPSCl in the presence of imidazole in DMF usu-
ally gives the 6-monosilylated product in 75–80 % yield.[5] In
order to improve the regioselectvity, the methods using equi-
molar amounts of dibutyltin oxide[6] and catalytic amounts of
TBAF in the presence of N,O-bis(tert-butyldimethylsilyl)acet-
amide (BTBSA),[7] based on the silane alcoholysis reaction,[8] and
[a] Key Laboratory for Large-Format Battery Materials and System,
Ministry of Education, School of Chemistry & Chemical Engineering,
Huazhong University of Science & Technology,
Luoyu Road 1037, 430074 Hongshan, Wuhan, P.R. China.
E-mail: hdong@mail.hust.edu.cn.
http://faculty.hust.edu.cn/donghai/en/index/1380857/list/index.htm
[b] The College of Chemistry and Molecular Engineering,
Zhengzhou University,
Zhengzhou 450052, P. R. China
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201901195.
Figure 1. Comparison of this method with previously reported methods.
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O-TBS pyranosides and the 3-alkylated 6-O- TBS pyranosides
have been obtained by our developed selective acylation,[11]
and alkylation,[12] respectively. These 3-acylated-6-silylated
pyranosides can be used to develop double parallel or double
serial inversion strategies.[13]
Table 1. Optimization of the silylation of 1 with using a mixed solvent of
acetonitrile/DMF.[a]
In the present study (Figure 1c), we reported an efficient and
convenient method for the highly regioselective silylation of
primary hydroxyl groups of diols and polyols (particularly un-
protected pyranosides). In this method, the treatment of a sub-
strate with 1.5 equiv. of tert-butyldimethylsilyl chloride (TBSCl)
and 1.8 equiv. of triethylamine (TEA) in a mixed solvent of
MeCN and DMF (VMeCN/VDMF = 10:1) for 30 minutes at room
temperature gave the primary hydroxyl group silylated product
in an excellent yield in most cases. Furthermore, to our best
knowledge, we first discovered that DMF was a good catalyst
in addition to being a good solvent for silylation, although it
had been used as a solvent in silylation for 40 years.[3a] It has
been demonstrated by NMR techniques that a complex with a
1:1 ratio of the binding partners can be formed between TBSCl
and DMF and has an association constant of 12/M, thus activat-
ing the silylation. We also theoretically explained why the most
common silylation procedure (Figure 1a) led to relatively poor
yields and was an unreasonable choice for regioselective silyl-
ation.
Entry Various conditions
Reaction
time/h
Isolated
yield [%]
1
1.8 equiv. TEA, 1.5 equiv. TBSCl
0.5 h
0.5 h
2.0 h
0.5 h
91
88
80
85
89
31
18
–
2
3
4
1.5 equiv. TEA, 1.5 equiv. TBSCl
1.8 equiv. TEA, 1.2 equiv. TBSCl
1.8 equiv. DIPEA, 1.5 equiv. TBSCl
5
1.8 equiv. Pyridine, 1.5 equiv. TBSCl 0.5 h
6
1.8 equiv. K2CO3, 1.5 equiv. TBSCl
1.8 equiv. TEA, 1.5 equiv. TBSCl
1.8 equiv. TEA, 1.5 equiv. TBSCl
3.0 h
3.0 h
0.5 h
7[b]
8[c]
[a] Reactant conditions: substrate (0.2 mmol) in 1.1 mL of solvent [MeCN/
DMF = 10:1 (v/v)]. [b] MeCN alone as the solvent. [c] No or trace reaction
with using THF as the solvent.
(Figure 2). Under the optimal condition, the silylation of the
most substrates gave excellent yields of the desired products.
Some substrates such as methyl ꢀ-
D
-glucopyranoside 3, methyl
-thiogalactopyranoside 12
α- -galactopyranoside 4, and α-
D
D
showed a little lower reactivity in the reaction. However, satis-
factory yields of 3a, 4a and 12a (89–91 %) were still obtained
Results and Discussion
The preparation of differentially protected monosaccharide
building blocks is typically achieved by the gradual introduction
of each protecting group, which results in low overall yield and
poor efficiency of synthesis. Therefore, the one-pot method for
regioselective multistep protection is very attractive due to the
absence of separation and purification of the intermediates.[14]
We wondered if we could develop a one-pot method, by which
the primary and the secondary hydroxyl groups of unprotected
pyranosides would be serially silylated and acylated.
We have developed several regioselective protection meth-
ods where a mixed solvent of acetonitrile/DMF (V/V = 10:1) was
often used with unprotected methyl pyranosides as sub-
strates.[11a,11b,12b,12c] Thus, we first thought of whether the
regioselective silylation of the primary hydroxyl group could be
carried out in this mixed solvent (MeCN/DMF = 10:1). For this
purpose, methyl-α- -glucopyranoside 1 was tested with TBSCl
D
in the solvent (MeCN/DMF = 10:1) in the presence of excess
amounts of bases (Table 1). To our surprise, excellent isolated
yields of methyl 6-O-TBS-α- -glucopyranoside 2 (up to 91 %)
D
were obtained within only half an hour in most cases (Entries
1–5 in Table 1). High regioselectivities to the primary hydroxyl
group were acquired since only the product 2 and the unre-
acted starting material 1 were observed in all the reactions.
When K2CO3 was used instead of organic bases, or the mixed
solvent (MeCN/DMF = 10:1) was displaced with MeCN or THF,
the reactivity of the silylation dramatically decreased (Entries 6–
8 in Table 1).
Figure 2. Regioselective silylation of varies substrates containing a primary
hydroxyl group. [a]Reaction conditions: substrate (0.2 mmol), TEA (1.8 equiv.),
TBSCl (1.5 equiv.), MeCN/DMF (1 mL:0.1 mL), r.t., 0.5 h. [b] The use of increased
amount of TEA (2.5–5.0 equiv.) and TBSCl (2.0–4.0 equiv.). [c] Yields on a gram
The use of 1.5 equiv. of TBSCl and 1.8 equiv. of TEA in the
mixed solvent (Entry 1 in Table 1) was applied as the optimized
condition. We next examined the scope of this methodology
[d]
[e]
scale.
MeCN alone as the solvent, 12 h.
TEA (2.5 equiv.), TBDPSCl or
TIPSCl (2.0 equiv.), MeCN/DMF (1 mL:0.1 mL), r.t., 8–12 h.
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with the increased amounts of TBSCl and TEA. Thiophenyl
pyranosides were often used as donors for glycosylation. Thus,
Table 2. Silylation of 1 under various reaction conditions.
thiophenyl ꢀ-
D
-galactopyranoside 11 and thiophenyl ꢀ-D-
glucopyranoside 13 were silylated under the optimized condi-
tions on a gram scale, yielding 11a in 91 % yield and 13a in
89 % yield, respectively. Thiophenyl lactoside 16 was silylated
with 4.0 equiv. of TBSCl in the presence of 5.0 equiv. of TEA,
yielding 16a with two primary hydroxyl groups silylated in 89 %
yield. All 1,2- and 1,3-diols 17–22 showed high reactivity under
the optimal condition. Glycerol 22 was silylated with 2.2 equiv.
of TBSCl in the presence of 3.0 equiv. of TEA, yielding 22a with
two primary hydroxyl groups silylated in 92 % yield. The silyl-
ation by tert-butyldiphenylsilyl chloride (TBDPSCl) or triiso-
propylsilyl (TIPSCl) was also explored. Thiogalactosides 8, 10
and 11 were silylated with 2.0 equiv. of TBDPSCl/TIPSCl in the
presence of 2.5 equiv. of TEA, giving 8b, 10b, 10c and 11b in
88–95 % yields.
Entry
Various condition
Conversion [%]
NMR yield [%]
(2/by-products)
1[a]
2[b]
3
4
5
6
7
8
9
10
11[a,c]
12[c]
13[d]
DMF (0.1 mL)
–
100
21
40
69
100
56
100
100
71
62
90
100:0
21:0
40:0
DMF (0.2 equiv.)
DMF (0.5 equiv.)
DMF (1.0 equiv.)
DMSO (0.1 mL)
DMAP (0.1 equiv.)
Pyridine (0.1 mL)
Pyridine (1.0 equiv.)
Imidazole (1.0 equiv.)
Imidazole (1.8 equiv.)
Imidazole (1.8 equiv.)
Imidazole (2.2 equiv.)
69:0
100:0
30:26
93:7
100:0
71:0
58:4
65:25
63:36
85:8
99
93
During studies on the silylation of 1,2-diols 17–22, we no-
ticed that they had good solubility in acetonitrile. Thus, the
silylation of 19, 20 or 21 by TBSCl was tested in acetonitrile
alone since DMF was not required to increase the solubility of
the substrates. Unexpectedly, all these reactions showed low
reactivities in the absence of DMF and required 12 hours' reac-
tion (Figure 2), giving only moderate yields of 19a, 20a, and
21a (61–81 %). These results inspired us to think about if DMF
plays a more important role than a good solvent in the silyl-
ation. Therefore, the role of DMF was further studied through
the silylation of 1 by TBSCl in the presence of TEA (Table 2).
Both the conversion rate for silylation of 1 and the selectivity
for 2 were 100 % (reaction proceeding for 1 h, entry 1 in
Table 2) with the addition of 0.1 mL of DMF (6.5 equiv.). How-
ever, the conversion rate for silylation of 1 was 21 % (reaction
proceeding for 4 h) in the absence of DMF (Entry 2 in Table 2)
though the selectivity for 2 were 100 %. With the addition of
0.2 equiv. of DMF, the conversion rate for silylation of 1 in-
creased to 40 % (reaction proceeding for 4 h) due to the in-
creased reaction rate, indicating that DMF does catalyze this
silylation. With the addition of 0.5 equiv. and 1.0 equiv. of DMF,
the conversion rate for silylation of 1 increased to 69 % and
100 %, respectively (Entries 4 and 5 in Table 2). None of these
silylations gave any by-products, indicating 100 % regioselecti-
vity for 2 in the presence of DMF. However, DMSO could not
improve the silylation as DMF did though DMSO was also a
good solvent for glycoside 1 (Entry 6 in Table 2). It has been
reported that 4-dimethylaminopyridine (DMAP) was a good cat-
alyst for silylation.[15] The silylation of 1 was completed within
four hours in the presence of 0.1 equiv. of DMAP, however, giv-
ing 7 % yield of by-products (Entry 7 in Table 2). These results
indicated that DMF acted as a catalyst in the silylation as DMAP
did but exhibited lower catalytic activity than DMAP. Pyridine
and imidazole might have a similar catalytic mechanism to
DMAP for the silylation. However, the silylation results (Entries
8, 9 and 10 in Table 2) seemed to show that either pyridine or
imidazole is a worse catalyst than DMF.
[a]Reaction conditions: Reaction proceeding for 1 h. [b] MeCN (1.1 mL).
[c] Without TEA. [d] The most common used condition: DMF (1 mL), TBSCl
(1.1 equiv.), Imidazole (2.2 equiv.), r.t., 4 h.
were found to shift with the addition of TBSCl by NMR titration
experiments using TBSCl and DMF in d-acetonitrile (Figure S1a).
The NMR titration experiments supported the formation of a
complex (A) between TBSCl and DMF. The association constant
amounted to 12/M, and Job's analysis indicated a 1:1 ratio of
the binding partners (Figure 3). The delocalization of the lone
pair electrons of nitrogen to carbonyl group in the complex A
accounts for why the signals for the protons of DMF shift to
downfield. Thus, we proposed that DMF catalyzes the silylation
of hydroxyl groups through the formation of the complex A
(Figure 4). The similar mechanism was also proposed in reac-
tions where DMF had catalyzed the reaction of oxalyl chloride
with carboxylic acids to form acyl chlorides.[16] We also com-
pared the 13C NMR spectrum of TBSCl alone with the 13C NMR
spectrum of TBSCl in the presence of five times DMF in d-aceto-
nitrile. It was observed that the signals for the carbons connect-
ing silicon slightly shifted to downfield, likely to indicating the
activation of the silicon of TBS group due to the formation of
the complex A (Figure S1b). By the NMR experiments (Figure
S2a) and gas chromatograph-mass analysis (Figure S2b), it was
also observed that a small amount of TBSCl was immediately
hydrolyzed to TBSOH by traces of water in the solvent once
TBSCl was added into a solvent. After that, slow formation of
tert-butyldimethylsiloxane (TBSOTBS) in the presence of DMF
was observed. We proposed that the complex A should also
play a key role during the formation of TBSOTBS (Figure 4).
When TEA and methanol were subsequently added to this sol-
vent, rapid consumption of TBSCl to form TBSOMe was ob-
served, while both TBSOH and TBSOTBS are inactive for the
silylation (Figure S3a). Interestingly, when imidazole was added
to the d-acetonitrile solution instead of TEA, a stable intermedi-
ate formed from imidazole and TBSCl was observed (Figure
S3b). With the subsequent addition of methanol, the intermedi-
In order to explore the catalytic mechanism of DMF for the
silylation, an intensive investigation of the reaction by NMR ate was rapid consumed to form TBSOMe. It seemed to indicate
techniques was performed. The signals for the protons of DMF that imidazole is a better catalyst than DMF for the silylation,
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which contradicts the experimental result shown in entry 10 in presence of TEA and catalyze the silylation (Figure 5b). However,
Table 2.
for imidazole, its hydrochloride salt E should be more stable
than the hydrochloride salt of TEA. Thus, imidazole cannot be
regenerated in the presence of TEA (Figure 5c). Based on this,
we guessed that using1.8 equiv. of imidazole in the absence of
TEA should lead to silylation of 1 efficiently. The further experi-
ments supported our hypothesis (Entries 11 and 12 in Table 2).
The conversion rates for silylation of 1 were 90 % (reaction pro-
ceeding for 1 h) and 99 % (reaction proceeding for 4 h) with
the use of 1.8 equiv. of imidazole and 1.5 equiv. of TBSCl in
acetonitrile. However, 25 % (reaction for 1 h) and 36 % (reaction
for 4 h) yields of other silylation by-products were also gener-
ated in these reactions. The poor regioselectivity must be
caused by the high reactivity of the counterion D shown in
Figure 5a. The silylation of 1 gave 85 % yield of 2 and 8 % yield
of other silylation by-products when using the most common
silylation procedure (Entry 13 in Table 2). Therefore, the forma-
tion of TBSOTBS and TBOH leads to insufficient silylation rea-
gents and the use of imidazole leads to poor regioselectivity,
which accounts for why only moderate silylation yields are ob-
tained when using the most common silylation procedure (Fig-
ure 1a). However, the moderate reactivity of the complex A
(Figure 4) and the less steric effect of primary hydroxyl groups
lead to 100 % selectivity for the silylation of primary hydroxyl
groups with DMF as a catalyst (Entries 1–5 in Table 2).
Figure 3. NMR titration and Job's plot for TBSCl with DMF in acetonitrile. K =
12/M, R2 = 0.9774.
We have reported that acetate/benzoate could catalyze the
regioselective acetylation/benzoylation of carbohydrates.[11a,11b]
It was further found that a catalytic amount of DIPEA could
trigger the catalytic process.[17] Excellent isolated yields of
3-position acylated products were obtained with using methyl
6-O-TBS pyranosides as substrates. Based on this result and the
present silylation method, we believed that we could proceed
serially the silylation and the acylation in one-pot. In the one-
pot reaction, DIPEA can both act as a base for silylation and
Figure 4. The proposed mechanism for silylation of hydroxyl group catalyzed
by DMF.
trigger the following acylation. Therefore, methyl α-
anoside 1 was initially silylated by TBSCl in the presence of
Either imidazole, DMAP or pyridine should easily form a 2.0 equiv. of DIPEA, followed by the addition of 1.2 equiv. of
highly electrophilic N-TBS counterion (B, C, or D in Figure 5a) benzoic anhydride. Consequently, methyl 3-O-Bz-6-O-TBS-α-
D-glucopyr-
D
-
with TBSCl. The counterion B, C, or D then reacts with hydroxyl glucopyranoside 2a was isolated in 76 % yield after 12 hours'
groups, thereby activating the silylation. The counterion D has reaction at 40 °C (Entry 1 in Table 3), indicating the one-pot
been observed from the above NMR experiments. The hydro- reaction was feasible. The use of TEA led to poor yield of 2a
chloride salt of DMAP should be less stable than the hydro- (55 %) due to poor acylation (Entry 2 in Table 3). The use of
chloride salt of TEA. Thus, DMAP can be regenerated in the 2.2 equiv. of DIPEA was the optimum condition under which
Figure 5. The proposed mechanism for silylation of hydroxyl group catalyzed by DMF.
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2a was isolated in 80 % yield (Entry 3 in Table 3). Methyl 3-O- 95 % yields). The method was further used in a one-pot reac-
Ac-6-O-TBS-α- -glucopyranoside 2b was isolated in 77 % yield tion to obtain 3-acylated-6-silylated pyranosides (71–91 %
D
by the one-pot reaction when acetic anhydride was used in- yields) from unprotected pyranosides under very mild condi-
stead of benzoic anhydride. Encouraged by this attempt, unpro- tions. Through comprehensive mechanistic studies, DMF was
tected O-glycosides 3, 4, 5, and 6 and thio-glycosides 7, 8, 9, first discovered to be a good catalyst in these silylation proc-
10, 11, 13, and 16 were subjected to the one-pot reaction, esses. NMR titration experiments demonstrated that a complex
giving corresponding orthogonally protected glycosides in with a 1:1 ratio of the binding partners was formed between
good to excellent yields (71–91 %). The one-pot reaction of TBSCl and DMF and had an association constant of 12/M. DMF
methyl ꢀ-
D
-glucopyranoside 3, methyl α- -galactopyranoside 4 might also catalyze the formation of TBSOTBS from TBSCl and
D
or thiolactoside 16 required greater amounts of TBSCl and TBSOH via this complex. Imidazole was observed to form a
DIPEA for the most complete silylation. TBDPSCl and TIPSCl had highly active intermediate for silylation with TBSCl thus leading
also been successfully applied as the silylation reagent in the to poor regioselectivity. Consequently, the most common silyl-
one-pot reaction, giving desired products 10ba, 10bb, 10ca, ation procedure was theoretically demonstrated to be an unrea-
and 10cb in 73–80 % yields.
sonable choice for regioselective silylation herein, since the for-
mation of TBSOTBS and TBOH led to insufficient silylation rea-
gents, and the use of imidazole and long reaction time led to
poor regioselectivity.
Table 3. One-pot tandem silylation/acylation reactions.[a]
Experimental Section
General: All commercially available starting materials and solvents
were of reagent grade and used without further purification. Chem-
ical reactions were monitored with thin-layer chromatography using
precoated silica gel 60 (0.25 mm thickness) plates. High resolution
mass spectra (HRMS) were obtained by electrospray ionization (ESI)
and TOF detection. Flash column chromatography was performed
on silica gel 60 (SDS 0.040–0.063 mm). 1H NMR spectra were re-
corded at 298K in CDCl3, CD3OD, (CD3)2SO, CD3CN and [D7]DMF
using the residual signals from CDCl3 (1H: δ = 7.26 ppm; 13C:
δ = 77.16 ppm), CD3OD (1H: δ = 3.31 ppm), (CD3)2SO (1H: δ =
2.49 ppm), CD3CN (1H: δ = 1.94 ppm; 13C: δ = 118.26 ppm) and
1
[D7]DMF (δ = 8.03 ppm) as internal standard. H peak assignments
were made by first order analysis of the spectra, supported by stan-
1
dard H-1H correlation spectroscopy (COSY).
General Procedure A for the Silylation of Substrates: To a mix-
ture of the substrate (0.2 mmol) in 1.1 mL of solvent (VMeCN/VDMF
=
10:1), triethylamine (TEA) (1.8–5.0 equiv.) and tert-butyldimethylsilyl
chloride (TBSCl)(1.5–4.0 equiv.) were added and then stirred at
room temperature for 0.5 hours. The reaction mixture was directly
purified by flash column chromatography, affording the pure selec-
tively protected derivatives.
General Procedure A′ for the Silylation of Substrates 11 and 13
in Large-scale: To a mixture of the substrate (4.0 mmol) in 11.0 mL
of solvent (VMeCN/VDMF = 10:1), triethylamine (TEA) (1.8 equiv.) and
tert-butyldimethylsilyl chloride (TBSCl)(1.5 equiv.) were added and
then stirred at room temperature for 0.5 hours. The reaction mixture
was directly purified by flash column chromatography, affording the
pure selectively protected derivatives.
General Procedure B for Silylation and Acylation of Substrates
in One-pot: To a mixture of the substrate (0.2 mmol) in 1.1 mL of
solvent (VMeCN/VDMF = 10:1), N,N-diisopropylethylamine (DIPEA)
(2.2–6.0 equiv.) and tert-butyldimethylsilyl chloride (TBSCl) (1.5–
4.0 equiv.) were added and then stirred at room temperature for
0.5 hours. Upon complete silylation as shown by TLC, anhydride
(1.2 equiv.) was added and the mixture was left stirring at 40 °C for
8–12 h. The crude product was directly purified by flash column
chromatography, affording the pure selectively protected deriva-
tives.
[a] Reaction conditions: i) substrate (0.2 mmol), DIPEA (2.2 equiv.), TBSCl
(1.5 equiv.), MeCN/DMF (1 mL:0.1 mL), r.t., 0.5 h; ii) Bz2O/Ac2O (1.2 equiv.),
40 °C, 8–12 h. [b] The use of increased amount of DIPEA (3.0–6.0 equiv.) and
TBSCl (2.0–4.0 equiv.). [c] The use of DIPEA (2.6–3.0 equiv.) and TBDPSCl/
TIPSCl (2.0 equiv.), 12 h.
Conclusions
In this study, we developed a highly regioselective silylation
Methyl 6-O-(tert-Butyldimethylsilyl)-α-D-glucopyranoside (2):[6]
method for primary hydroxyl groups of diols and polyols (85– Following the general procedure A, the reaction was carried out
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with methyl-α-
D
-glucopyranoside 1 (0.2 mmol), TEA (50.0 μL, mixture was directly purified by flash column chromatography
1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent (1.1 mL) at
room temperature for 0.5 h. The reaction mixture was directly puri-
(ethyl acetate/petroleum ether: 3:1), afforded compound 7a as vis-
cous colorless oil (64.8 mg, 92 %). 1H NMR (400 MHz, CDCl3):
fied by flash column chromatography (ethyl acetate/petroleum δ = 4.38 (d, J = 9.6 Hz, 1H, H-1), 4.03 (br s, 1H, H-4), 3.85–3.77 (m,
ether: 5:1), afforded compound 2 as white solid (56.1 mg, 91 %). 1H
NMR (400 MHz, CDCl3): δ = 4.71 (d, J = 3.6 Hz, 1H, H-1), 4.29 (br
s, 3H, -OH), 3.87 (dd, J = 10.8 Hz and 3.2 Hz, 1H, H-6a), 3.81–3.73
2H, H-6a and H-6b), 3.71–3.47 (m, 6H, H-2, H-3, H-5 and OH × 3),
3.25–3.15 (m, 1H, CH(CH3)2), 1.30 (dd, J = 6.4 Hz and 2.4 Hz,
6H, CH(CH3)2), 0.87 (s, 9H, Si(C(CH3)3)(CH3)2), 0.06 (s, 3H,
(m, 2H, H-6b and H-3), 3.58–3.53 (m, 1H, H-4), 3.49 (dd, J = 9.6 Hz Si(C(CH3)3)(CH3)2), 0.05 (s, 3H, Si(C(CH3)3)(CH3)2).
and 3.6 Hz, 1H, H-2), 3.43–3.37 (m, 4H, H-5 and OCH3), 0.89 (s, 9H,
Ethyl 6-O-(tert-Butyldimethylsilyl)-1-thio-ꢀ-D-galactopyranos-
Si(C(CH3)3)(CH3)2), 0.07 (s, 6H, Si(C(CH3)3)(CH3)2).
ide (8a): Following the general procedure A, the reaction was car-
ried out with ethyl-ꢀ- -thiogalactopyranoside 8 (0.2 mmol), TEA
D
Methyl
6-O-(tert-Butyldimethylsilyl)-ꢀ-D-glucopyranoside
(3a):[8a] Following the general procedure A, the reaction was carried
(50.0 μL, 1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature for 0.5 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 3:1), afforded compound 8a as viscous colorless
oil (62.8 mg, 93 %). 1H NMR (400 MHz, CDCl3): δ = 4.32 (d,
J = 9.6 Hz, 1H, H-1), 4.04 (d, J = 2.4 Hz, 1H, H-4), 3.87–3.70 (m, 6H,
H-2, H-6a, H-6b and OH × 3), 3.58 (dd, J = 8.8 Hz and 2.8 Hz, 1H,
H-3), 3.49 (t, J = 5.2 Hz, 1H, H-5), 2.79–2.65 (m, 2H, SCH2CH3), 1.30–
1.26 (m, 3H, SCH2CH3), 0.87 (s, 9H, Si(C(CH3)3)(CH3)2), 0.06 (s, 6H,
Si(C(CH3)3)(CH3)2). 13C NMR (100 MHz, CDCl3): δ = 86.0, 78.6, 75.2,
70.4, 69.4, 62.8, 25.9, 24.4, 18.3, 15.4, –5.3, –5.3 ppm; HRMS (ESI-
TOF): Calculated for [C14H30O5SSiNa]+: 361.1475, found 361.1481.
out with methyl-ꢀ- -glucopyranoside 3 (0.2 mmol), TEA (69.5 μL,
D
2.5 equiv.), TBSCl (61.5 mg, 2.0 equiv.) in dry solvent (1.1 mL) at
room temperature for 0.5 h. The reaction mixture was directly puri-
fied by flash column chromatography (ethyl acetate/petroleum
ether: 5:1), afforded compound 3a as white solid (56.0 mg, 91 %).
1H NMR (400 MHz, CDCl3): δ = 4.18 (d, J = 7.6 Hz, 1H, H-1), 3.89
(dd, J = 10.8 Hz and 4.0 Hz, 1H, H-6a), 3.82 (dd, J = 10.8 Hz and
5.6 Hz, 1H, H-6b), 3.54–3.41 (m, 5H, H-3, H-4 and OCH3), 3.35–3.30
(m, 2H, H-2 and H-5), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.08 (s, 6H,
Si(C(CH3)3)(CH3)2).
Methyl
(4a):[4c] Following the general procedure A, the reaction was carried
out with methyl-α- -galactopyranoside 4 (0.2 mmol), TEA (111.5 μL,
6-O-(tert-Butyldimethylsilyl)-α-D-galactopyranoside
Ethyl 6-O-(tert-Butyldiphenylsilyl)-1-thio-ꢀ-D-galactopyranos-
ide (8b): Following the general procedure A, the reaction was car-
D
ried out with ethyl-ꢀ- -thiogalactopyranoside 8 (0.2 mmol), TEA
D
4.0 equiv.), TBSCl (92.3 mg, 3.0 equiv.) in dry solvent (1.1 mL) at
room temperature for 0.5 h. The reaction mixture was directly puri-
fied by flash column chromatography (ethyl acetate/petroleum
ether: 5:1), afforded compound 4a as white crystalline solid
(54.8 mg, 89 %). 1H NMR (400 MHz, CDCl3): δ = 4.81 (d, J = 3.6 Hz,
1H, H-1), 4.09 (br s, 1H, H-4), 3.92–3.83 (m, 3H, H-2, H-6a and
H-6b), 3.75–3.72 (m, 2H, H-3 and H-5), 3.41 (s, 3H, OCH3), 0.89 (s,
9H, Si(C(CH3)3)(CH3)2), 0.09 (s, 6H, Si(C(CH3)3)(CH3)2).
(69.5 μL, 2.5 equiv.), TBDPSCl (104.0 μL, 2.0 equiv.) in dry solvent
(1.1 mL) at room temperature for 12 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 10:1), afforded compound 8b as viscous colorless
oil (86.8 mg, 94 %). 1H NMR (400 MHz, CDCl3): δ = 7.71–7.66 (m,
4H, ArH), 7.44–7.35 (m, 6H, ArH), 4.30 (d, J = 9.6 Hz, 1H, H-1), 4.10
(d, J = 2.4 Hz, 1H, H-4), 3.93–3.85 (m, 2H, H-6a and H-6b), 3.72 (t,
J = 9.2 Hz, 1H, H-2), 3.58 (dd, J = 8.8 Hz and 2.8 Hz, 1H, H-3), 3.53
(t, J = 5.6 Hz, 1H, H-5), 3.27 (br s, 3H, OH × 3), 2.78–2.63 (m, 2H,
SCH2CH3), 1.27 (t, J = 7.6 Hz, 3H, SCH2CH3), 1.05 (s, 9H, Si(C(CH3)3)).
13C NMR (100 MHz, CDCl3): δ = 135.8, 135.7, 133.2, 133.0, 129.9,
127.9, 127.8, 86.0, 78.5, 77.4, 75.1, 70.5, 69.4, 63.4, 26.9, 24.3, 19.3,
15.4 ppm; HRMS (ESI-TOF): Calculated for [C24H34O5SSiNa]+:
485.1788, found 485.1789.
Methyl
(5a):[8a] Following the general procedure A, the reaction was carried
out with methyl-ꢀ- -galactopyranoside 5 (0.2 mmol), TEA (50.0 μL,
6-O-(tert-Butyldimethylsilyl)-ꢀ-D-galactopyranoside
D
1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent (1.1 mL) at
room temperature for 0.5 h. The reaction mixture was directly puri-
fied by flash column chromatography (ethyl acetate/petroleum
ether: 5:1), afforded compound 5a as viscous colorless oil (57.3 mg,
93 %). 1H NMR (400 MHz, CDCl3): δ = 4.14 (d, J = 7.6 Hz, 1H, H-1),
3.97 (d, J = 2.4 Hz, 1H, H-4), 3.89 (dd, J = 10.4 Hz and 6.4 Hz, 1H,
H-6a), 3.82 (dd, J = 10.4 Hz and 5.6 Hz, 1H, H-6b), 3.69–3.64 (m, 1H,
H-2), 3.58–3.52 (m, 4H, H-3 and OCH3), 3.46 (t, J = 5.6 Hz, 1H, H-5),
0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.07 (s, 6H, Si(C(CH3)3)(CH3)2).
Benzyl 6-O-(tert-Butyldimethylsilyl)-1-thio-ꢀ-D-galactopyranos-
ide (9a): Following the general procedure A, the reaction was car-
ried out with benzyl-ꢀ- -thiogalactopyranoside 9 (0.2 mmol), TEA
D
(50.0 μL, 1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature for 0.5 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 3:1), afforded compound 9a as viscous colorless
oil (76.0 mg, 95 %). 1H NMR (400 MHz, CDCl3): δ = 7.31–7.18 (m,
5H, ArH), 4.12 (d, J = 9.6 Hz, 1H, H-1), 3.98–3.91 (m, 2H, H-4, CH2),
3.86–3.80 (m, 3H, H-6a, H-6b and CH2), 3.70 (t, J = 9.2 Hz, 1H, H-
2), 3.44–3.35 (m, 2H, H-3 and H-5), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2),
0.08 (s, 6H, Si(C(CH3)3)(CH3)2). 13C NMR (100 MHz, CDCl3):
δ = 137.7, 129.2, 128.7, 127.3, 84.3, 78.5, 75.1, 70.5, 69.4, 63.0, 33.8,
26.0, 18.4, –5.2, –5.2 ppm; HRMS (ESI-TOF): Calculated for
[C19H32O5SSiNa]+: 423.1632, found 423.1633.
Methyl
(6a):[4c] Following the general procedure A, the reaction was carried
out with methyl-α- -mannopyranoside 6 (0.2 mmol), TEA (50.0 μL,
6-O-(tert-Butyldimethylsilyl)-α-D-mannopyranoside
D
1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent (1.1 mL) at
room temperature for 1 h. The reaction mixture was directly purified
by flash column chromatography (ethyl acetate/petroleum ether:
4:1), afforded compound 6a as white solid (52.4 mg, 85 %). 1H NMR
(400 MHz, CD3OD): δ = 4.61 (br s, 1H, H-1), 3.98 (dd, J = 11.2 Hz
and 1.8 Hz, 1H, H-6a), 3.79–3.75 (m, 2H, H-2, H-6b), 3.64 (dd, J =
8.8 Hz and 3.2 Hz, 1H, H-3), 3.56–3.64 (m, 2H, H-4, H-5), 3.36 (s, 3H,
OCH3), 0.92 (s, 9H, Si(C(CH3)3)(CH3)2), 0.10 (s, 6H, Si(C(CH3)3)(CH3)2).
p-Tolyl 6-O-(tert-Butyldimethylsilyl)-1-thio-ꢀ-D-galactopyranos-
ide (10a): Following the general procedure A, the reaction was car-
Isopropyl 6-O-(tert-Butyldimethylsilyl)-1-thio-ꢀ-D-galactopyr-
anoside (7a):[4c]Following the general procedure A, the reaction
ried out with p-tolyl-ꢀ- -thiogalactopyranoside 10 (0.2 mmol), TEA
(50.0 μL, 1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
D
was carried out with isopropyl-ꢀ-
D
-thiogalactopyranoside
7
(1.1 mL) at room temperature for 0.5 h. The reaction mixture was
(0.2 mmol), TEA (50.0 μL, 1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in directly purified by flash column chromatography (ethyl acetate/
dry solvent (1.1 mL) at room temperature for 0.5 h. The reaction petroleum ether: 3:1), afforded compound 10a as a viscous color-
Eur. J. Org. Chem. 2019, 6383–6395
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less oil (73.6 mg, 92 %). 1H NMR (400 MHz, CDCl3): δ = 7.44 (d, J =
8.0 Hz, 2H, ArH), 7.07 (d, J = 8.0 Hz, 2H, ArH), 4.47 (d, J = 9.6 Hz,
1H, H-1), 4.04 (d, J = 2.4 Hz, 1H, H-3), 3.91–3.83 (m, 2H, H-6a, H-
6b), 3.71 (t, J = 9.2 Hz, 1H, H-2), 3.60–3.46 (m, 5H, H-4, H-5 and
OH × 3), 2.31 (s, 3H, PhCH3), 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 NMR
(100 MHz, CDCl3): δ = 138.2, 133.1, 129.8, 128.7, 89.0, 78.3, 75.1,
70.0, 69.5, 63.3, 25.9, 21.3, 18.4, –5.3, –5.3 ppm; HRMS (ESI-TOF):
Calculated for [C19H32O5SSiNa]+: 423.1632, found 423.1630.
4), 3.93 (d, J = 5.2 Hz, 2H, H-6a and H-6b), 3.74 (t, J = 9.2 Hz, 1H,
H-2), 3.60–3.53 (m, 2H, H-3 and H-5), 3.37 (br s, 3H, OH × 3), 1.05
(s, 9H, Si(C(CH3)3)).
Phenyl 6-O-(tert-Butyldimethylsilyl)-1-thio-α-D-galactopyranos-
ide (12a): Following the general procedure A, the reaction was car-
ried out with phenyl-α- -thiogalactopyranoside 12 (0.2 mmol), TEA
D
(69.5 μL, 2.5 equiv.), TBSCl (55.3 mg, 1.8 equiv.) in dry solvent
(1.1 mL) at room temperature for 0.5 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 3:1), afforded compound 12a as viscous colorless
oil (69.5 mg, 90 %). 1H NMR (400 MHz, CDCl3): δ = 7.49–7.46 (m,
2H, ArH), 7.33–7.24 (m, 3H, ArH), 5.48 (d, J = 2.4 Hz, 1H, H-1), 4.22–
4.17 (m, 2H, H-2 and H-3), 4.13–4.11 (m, 1H, H-4), 3.91–3.86 (m, 1H,
H-5), 3.76–3.71 (m, 1H, H-6a), 3.69–3.65 (m, 1H, H-6b), 0.89 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.08 (s, 6H, Si(C(CH3)3)(CH3)2). 13C NMR
(100 MHz, CDCl3): δ = 133.9, 131.9, 129.2, 127.7, 92.9, 85.4, 81.6,
79.2, 72.2, 64.2, 25.9, 18.4, –5.2, –5.3 ppm; HRMS (ESI-TOF): Calcu-
lated for [C18H30O5SSiNa]+: 409.1475, found 409.1478.
p-Tolyl 6-O-(tert-Butyldiphenylsilyl)-1-thio-ꢀ-D-galactopyranos-
ide (10b):[18]Following the general procedure A, the reaction was
carried out with p-tolyl-ꢀ- -thiogalactopyranoside 10 (0.2 mmol),
D
TEA (69.5 μL, 2.5 equiv.), TBDPSCl (104.0 μL, 2.0 equiv.) in dry solvent
(1.1 mL) at room temperature for 8 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 2:1), afforded compound 10b as a white solid
1
(99.6 mg, 95 %). H NMR (400 MHz, CDCl3): δ = 7.73–7.68 (m, 4H,
ArH), 7.45–7.35 (m, 8H, ArH), 7.05–7.03 (m, 2H, ArH), 4.44 (d, J =
9.6 Hz, 1H, H-1), 4.09 (d, J = 2.4 Hz, 1H, H-4), 3.96–3.91 (m, 2H, H-
6a, H-6b), 3.67 (t, J = 9.2 Hz, 1H, H-2), 3.59–3.53 (m, 2H, H-3 and H-
5), 2.97 (s, 3H, OH × 3), 2.30 (s, 3H, PhCH3), 1.06 (s, 9H, Si(C(CH3)3)).
Phenyl 6-O-(tert-Butyldimethylsilyl)-1-thio-ꢀ-D-glucopyranos-
ide (13a):[20] Following the general procedure A, the reaction was
carried out with phenyl-ꢀ- -thioglucopyranoside 13 (0.2 mmol),
D
p-Tolyl
(10c): Following the general procedure A, the reaction was carried
out with p-tolyl-ꢀ- -thiogalactopyranoside 10 (0.2 mmol), TEA
6-O-(Triisopropylsilyl)-1-thio-ꢀ-D-galactopyranoside
TEA (50.0 μL, 1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature for 0.5 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 3:1), afforded compound 13a as viscous colorless
oil (71.8 mg, 93 %). 1H NMR (400 MHz, CDCl3): δ = 7.52–7.50 (m,
2H, ArH), 7.26–7.25 (m, 3H, ArH), 4.54 (d, J = 9.6 Hz, 1H, H-1), 3.87
(d, J = 4.4 Hz, 2H, H-6a and H-6b), 3.60–3.47 (m, 2H, H-3 and H-4),
3.39–3.31 (m, 2H, H-2 and H-5), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.09
(s, 6H, Si(C(CH3)3)(CH3)2).
D
(69.5 μL, 2.5 equiv.), TIPSCl (85.5 μL, 2.0 equiv.) in dry solvent
(1.1 mL) at room temperature for 16 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 2:1), afforded compound 10c as a viscous colorless
oil (77.8 mg, 88 %). 1H NMR (400 MHz, CDCl3): δ = 7.45 (d, J =
8.0 Hz, 2H, ArH), 7.09 (d, J = 8.0 Hz, 2H, ArH), 4.45 (d, J = 9.6 Hz,
1H, H-1), 4.11 (d, J = 2.4 Hz, 1H, H-4), 4.03 (dd, J = 10.4 Hz and
5.6 Hz, 1H, H-6a), 3.96 (dd, J = 10.4 Hz and 4.8 Hz, 1H, H-6b), 3.67
(t, J = 9.2 Hz, 1H, H-2), 3.58 (dd, J = 9.2 Hz and 2.8 Hz, 1H, H-3),
3.51 (t, J = 4.8 Hz, 1H, H-5), 2.92 (br s, 3H, OH × 3), 2.33 (s, 3H,
SPhCH3), 1.11–1.05 (m, 21H, Si(CH(CH3)2) × 3). 13C NMR (100 MHz,
CDCl3): δ = 138.3, 133.2, 129.8, 128.6, 88.9, 78.3, 77.4, 75.2, 70.0,
69.6, 63.7, 21.3, 18.1, 18.0, 11.9 ppm; HRMS (ESI-TOF): Calculated
for [C22H38O5SSiNa]+: 465.2101, found 465.2102.
Allyl 6-O-(tert-Butyldimethylsilyl)-ꢀ-D-glucopyranoside (14a):[21]
Following the general procedure A, the reaction was carried out
with allyl-ꢀ- -glucopyranoside 14 (0.2 mmol), TEA (50.0 μL,
D
1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent (1.1 mL) at
room temperature for 0.5 h. The reaction mixture was directly puri-
fied by flash column chromatography (ethyl acetate/petroleum
ether: 3:1), afforded compound 14a as viscous colorless oil
1
(59.5 mg, 89 %). H NMR (400 MHz, CDCl3): δ = 5.98–5.88 (m, 1H),
Phenyl 6-O-(tert-Butyldimethylsilyl)-1-thio-ꢀ-D-galactopyranos-
ide (11a):[19]Following the general procedure A, the reaction was
5.30 (d, J = 17.2 Hz, 1H), 5.20 (d, J = 10.4 Hz, 1H), 4.36–4.31 (m, 2H),
4.10 (dd, J = 12.8 Hz and 6.4 Hz, 1H), 3.87–3.85 (m, 2H), 3.63–3.32
(m, 7H), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.09 (s, 6H, Si(C(CH3)3)(CH3)2).
carried out with phenyl-ꢀ- -thiogalactopyranoside 11 (0.2 mmol),
D
TEA (50.0 μL, 1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature for 0.5 h. The reaction mixture was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 3:1), afforded compound 11a as viscous colorless
oil (72.6 mg, 94 %). 1H NMR (400 MHz, (CD3)2SO): δ = 7.44–7.41
(m, 2H, ArH), 7.28–7.16 (m, 3H, ArH), 5.16 (d, J = 5.6 Hz, 1H, OH),
4.95 (d, J = 5.2 Hz, 1H, OH), 4.59 (d, J = 9.2 Hz, 1H, H-1), 4.53 (d, J =
4.0 Hz, 1H, OH), 3.69–3.26 (m, 3H, H-4, H-6a and H-6b), 3.55–3.52
(m, 1H, H-5), 3.44–3.37 (m, 2H, H-2 and H-3), 0.85 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.02 (s, 3H, Si(C(CH3)3)(CH3)2), 0.01 (s, 3H,
Si(C(CH3)3)(CH3)2).
6-O-(tert-Butyldimethylsilyl)-D-glucal (15a):[22] Following the
general procedure A, the reaction was carried out with -glucal 15
D
(0.2 mmol), TEA (50.0 μL, 1.8 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in
dry solvent (1.1 mL) at room temperature for 0.5 h. The reaction
mixture was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 3:1), afforded compound 15a as col-
1
orless syrup (40.6 mg, 78 %). H NMR (400 MHz, CDCl3): δ = 6.31–
6.29 (m, 1H), 4.71 (dd, J = 6.0 Hz and 2.0 Hz, 1H), 4.24 (br s, 1H),
3.99–3.89 (m, 2H), 3.80–3.75 (m, 2H), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2),
0.09 (s, 6H, Si(C(CH3)3)(CH3)2).
Phenyl 6-O-(tert-Butyldiphenylsilyl)-1-thio-ꢀ-D-galactopyranos-
ide (11b):[18] Following the general procedure A, the reaction was
Phenyl 6,6′-Di-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-lactoside
(16a): Following the general procedure A, the reaction was carried
carried out with phenyl-ꢀ-
D
-thiogalactopyranoside 11 (0.2 mmol),
out with phenyl-1-thio-ꢀ-D-lactoside 16 (0.2 mmol), TEA (139.0 μL,
TEA (69.5 μL, 2.5 equiv.), TBDPSCl (104.0 μL, 2.0 equiv.) in dry solvent
5.0 equiv.), TBSCl (123.0 mg, 4.0 equiv.) in dry solvent (1.1 mL) at
(1.1 mL) at room temperature for 8 h. The reaction mixture was
room temperature for 3 h. The reaction mixture was directly purified
directly purified by flash column chromatography (ethyl acetate/ by flash column chromatography (ethyl acetate/petroleum ether:
petroleum ether: 3:1), afforded compound 11b as an amorphous
solid (93.8 mg, 92 %). 1H NMR (400 MHz, CDCl3): δ = 7.72–7.68 (m,
4H, ArH), 7.55–7.52 (m, 2H, ArH), 7.43–7.33 (m, 6H, ArH), 7.23–7.21
10:1), afforded compound 16a as viscous colorless oil (117.8 mg,
89 %). 1H NMR (400 MHz, CDCl3): δ = 7.55–7.52 (m, 2H, ArH), 7.27–
7.24 (m, 3H, ArH), 4.49 (d, J = 9.6 Hz, 1H, H-1), 4.34 (d, J = 8.0 Hz,
(m, 3H, ArH), 4.53 (d, J = 9.6 Hz, 1H, H-1), 4.07 (d, J = 2.0 Hz, 1H, H- 1H, H-1′), 3.94 (d, J = 2.4 Hz, 1H, H-6a′), 3.89 (br s, 1H, H-6b′), 3.82–
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3.75 (m, 2H, H-6a and H-6b), 3.70–3.57 (m, 4H, H-2′, H-3, H-4′ and
H-4), 3.50–3.45 (m, 2H, H-3′ and H-5′), 3.41–3.39 (m, 1H, H-5), 3.33–
3.28 (m, 1H, H-2), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.85 (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), 0.04 (s, 6H, Si(C(CH3)3)(CH3)2). 13C NMR
(100 MHz, CDCl3): δ = 133.3, 131.9, 128.9, 128.1, 103.3, 87.3, 79.3,
78.6, 77.4, 76.2, 75.4, 74.0, 71.5, 68.5, 62.4, 61.8, 26.1, 25.9, 18.4,
18.3, –4.9, –5.1, –5.3, –5.3 ppm; HRMS (ESI-TOF): Calculated for
[C30H54O10SSi2Na]+: 685.2868, found 685.2874.
129.6, 121.1, 114.7, 70.3, 68.5, 63.9, 26.0, 18.4, –5.3 ppm; HRMS (ESI-
TOF): Calculated for [C15H26O3SiNa]+: 305.1543, found 305.1550.
1,3-Di-O-(tert-butyldimethylsilyl)propane-2-ol (22a):[27] Follow-
ing the general procedure A, the reaction was carried out with glyc-
erol 22 (0.212 mmol), TEA (88.5 μL, 3.0 equiv.), TBSCl (72.5 mg,
2.2 equiv.) in dry solvent (1.1 mL) at room temperature for 5 min-
utes. The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether: 1:8), afforded com-
pound 22a as colorless oil (62.4 mg, 92 %). 1H NMR (400 MHz,
CDCl3): δ = 3.67–3.61 (m, 5H), 0.89 (s, 18H, 2 × Si(C(CH3)3)(CH3)2),
1-O-(tert-Butyldimethylsilyl)propanediol (17a):[23] Following the
general procedure A, the reaction was carried out with 1,2-propane- 0.06 (s, 12H, 2 × Si(C(CH3)3)(CH3)2).
diol 17 (0.177 mmol), TEA (44.5 μL, 1.8 equiv.), TBSCl (42.5 mg,
Methyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-α-D-glucopyr-
1.5 equiv.) in dry solvent (1.1 mL) at room temperature for 5 min-
utes. The reaction mixture was directly purified by flash column
chromatography (ethyl acetate/petroleum ether: 1:10), afforded
compound 17a as colorless oil (32.0 mg, 95 %). 1H NMR (400 MHz,
CDCl3): δ = 3.85–3.78 (m, 1H), 3.59 (dd, J = 10.0 Hz and 3.2 Hz, 1H),
3.34 (dd, J = 9.6 Hz and 8.4 Hz, 1H), 1.11 (d, J = 6.0 Hz, 3H), 0.91 (s,
9H, Si(C(CH3)3)(CH3)2), 0.07 (s, 6H, Si(C(CH3)3)(CH3)2).
anoside (2a):[11b] Following the general procedure B, the reaction
was carried out with methyl-α- -glucopyranoside 1 (0.2 mmol), DI-
D
PEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature. Upon completion as shown by TLC,
benzoic anhydride (55.5 mg, 1.2 equiv.) was added and the reaction
mixture was left stirring at 40 °C for 10 h. The crude product was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 1:5), afforded compound 2a as a viscous colorless
4-O-(tert-Butyldimethylsilyl)-butan-2-ol (18a):[24] Following the
general procedure A, the reaction was carried out with 1,3-butane- oil (65.9 mg, 80 %). 1H NMR (400 MHz, CDCl3): δ = 8.09–8.06 (m,
diol 18 (0.216 mmol), TEA (54.5 μL, 1.8 equiv.), TBSCl (40.5 mg, 2H, ArH), 7.58–7.53 (m, 1H, ArH), 7.46–7.40 (m, 2H, ArH), 5.35 (t, J =
1.2 equiv.) in dry solvent (1.1 mL) at room temperature for 5 min- 9.6 Hz, 1H, H-3), 4.81 (d, J = 3.6 Hz, 1H, H-1), 3.94–3.86 (m, 2H, H-
utes. The reaction mixture was directly purified by flash column
6a and H-6b), 3.78–3.68 (m, 3H, H-2, H-4 and H-5), 3.46 (s, 3H,
chromatography (ethyl acetate/petroleum ether: 1:10), afforded OCH3), 0.91 (s, 9H, Si(C(CH3)3)(CH3)2), 0.10 (s, 6H, Si(C(CH3)3)(CH3)2).
compound 18a as colorless oil (40.2 mg, 91 %). 1H NMR (400 MHz,
Methyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-α-D-glucopyr-
CDCl3): δ = 4.05–3.96 (m, 1H), 3.89–3.75 (m, 2H), 1.70–1.56 (m, 2H),
anoside (2b):[11a]Following the general procedure B, the reaction
1.17 (d, J = 6.0 Hz, 3H), 0.88 (s, 9H, Si(C(CH3)3)(CH3)2), 0.06 (s, 6H,
was carried out with methyl-α- -glucopyranoside 1 (0.2 mmol), DI-
D
Si(C(CH3)3)(CH3)2).
PEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature. Upon completion as shown by TLC,
acetic anhydride (23.0 μL, 1.2 equiv.) was added and the reaction
1-Allyl-3-O-(tert-Butyldimethylsilyl)-rac-glycerol (19a):[25] Fol-
lowing the general procedure A, the reaction was carried out with
1-allyloxy-propane-2,3-diol 19 (0.216 mmol), TEA (54.0 μL, mixture was left stirring at 40 °C for 12 h. The crude product was
1.8 equiv.), TBSCl (50.0 mg, 1.5 equiv.) in dry solvent (1.1 mL) at
room temperature for 5 minutes. The reaction mixture was directly
purified by flash column chromatography (ethyl acetate/petroleum
ether: 1:8), afforded compound 19a as colorless oil (48.5 mg, 91 %).
1H NMR (400 MHz, CDCl3): δ = 5.94–5.84 (m, 1H), 5.29–5.23 (m,
1H), 5.19–5.15 (m, 1H), 4.00 (dt, J = 6.0 Hz and 1.2 Hz, 2H), 3.84–
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 1:3), afforded compound 2b as a viscous colorless
oil (53.9 mg, 77 %). 1H NMR (400 MHz, CDCl3): δ = 5.08 (t, J =
9.2 Hz, 1H, H-3), 4.74 (d, J = 3.6 Hz, 1H, H-1), 3.87 (dd, J = 10.8 Hz
and 4.4 Hz, H-6a), 3.82 (dd, J = 10.8 Hz and 3.6 Hz, H-6b), 3.67–
3.53 (m, 3H, H-2, H-4 and H-5), 3.43 (s, 3H, OCH3), 2.15 (s, 3H, OAc),
3.79 (m, 1H), 3.67–3.60 (m, 2H), 3.51–3.42 (m, 2H), 0.89 (s, 9H, 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.08 (s, 6H, Si(C(CH3)3)(CH3)2).
Si(C(CH3)3)(CH3)2), 0.06 (s, 6H, Si(C(CH3)3)(CH3)2).
Methyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyr-
2-O-(tert-Butyldimethylsilyl)-1-phenylethanol (20a):[26] Follow- anoside (3aa):[11b] Following the general procedure B, the reaction
ing the general procedure A, the reaction was carried out with 1-
phenyl-1,2-ethanediol 20 (0.2 mmol), TEA (50.0 μL, 1.8 equiv.), TBSCl
(46.5 mg, 1.5 equiv.) in dry solvent (1.1 mL) at room temperature
for 20 minutes. The reaction mixture was directly purified by flash
column chromatography (ethyl acetate/petroleum ether: 1:10), af-
forded compound 20a as colorless oil (46.4 mg, 92 %). 1H NMR
(400 MHz, CDCl3): δ = 7.39–7.27 (m, 5H), 4.76 (dd, J = 8.4 Hz and
3.2 Hz, 1H), 3.77 (dd, J = 10.0 Hz and 3.2 Hz, 1H), 3.58–3.53 (m, 1H),
0.92 (s, 9H, Si(C(CH3)3)(CH3)2), 0.07 (s, 3H, Si(C(CH3)3)(CH3)2), 0.07 (s,
3H, Si(C(CH3)3)(CH3)2).
was carried out with methyl-ꢀ-D-glucopyranoside 3 (0.2 mmol), DI-
PEA (105.5 μL, 3.0 equiv.), TBSCl (61.5 mg, 2.0 equiv.) in dry solvent
(1.1 mL) at room temperature. Upon completion as shown by TLC,
benzoic anhydride (55.5 mg, 1.2 equiv.) was added and the reaction
mixture was left stirring at 40 °C for 12 h. The crude product was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 1:5), afforded compound 3aa as a viscous colorless
oil (64.3 mg, 78 %). 1H NMR (400 MHz, CDCl3): δ = 8.11–8.07 (m,
2H, ArH), 7.58–7.54 (m, 1H, ArH), 7.46–7.41 (m, 2H, ArH), 5.22 (t, J =
9.6 Hz, 1H, H-3), 4.33 (d, J = 7.6 Hz, 1H, H-1), 3.96 (dd, J = 10.4 Hz
and 4.8 Hz, 1H, H-6a), 3.90 (dd, J = 10.4 Hz and 5.2 Hz, 1H, H-6b),
3.82 (t, J = 9.2 Hz, 1H, H-4), 3.63–3.45 (m, 5H, H-2, H-5 and OCH3),
0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.10 (s, 6H, Si(C(CH3)3)(CH3)2).
3-Phenoxy-1-O-(tert-butyldimethylsilyl)propane-2-ol (21a): Fol-
lowing the general procedure A, the reaction was carried out with
3-phenoxy-1,2-propanediol 21 (0.2 mmol), TEA (50.0 μL, 1.8 equiv.),
TBSCl (46.5 mg, 1.5 equiv.) in dry solvent (1.1 mL) at room tempera- Methyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-ꢀ-D-glucopyr-
ture for 20 minutes. The reaction mixture was directly purified by
anoside (3ab):[11a] Following the general procedure B, the reaction
-glucopyranoside 3 (0.2 mmol), DI-
flash column chromatography (ethyl acetate/petroleum ether: 1:8), was carried out with methyl-ꢀ-
D
afforded compound 21a as colorless oil (48.0 mg, 85 %). 1H NMR
(400 MHz, CDCl3): δ = 7.31–7.27 (m, 2H), 6.98–6.90 (m, 3H), 4.07–
4.00 (m, 3H), 3.82–3.74 (m, 2H), 0.91 (s, 9H, Si(C(CH3)3)(CH3)2), 0.08
(s, 3H, Si(C(CH3)3)(CH3)2). 13C NMR (100 MHz, CDCl3): δ = 158.7,
PEA (105.5 μL, 3.0 equiv.), TBSCl (61.5 mg, 2.0 equiv.) in dry solvent
(1.1 mL) at room temperature. Upon completion as shown by TLC,
acetic anhydride (23.0 μL, 1.2 equiv.) was added and the reaction
mixture was left stirring at 40 °C for 12 h. The crude product was
Eur. J. Org. Chem. 2019, 6383–6395
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6390
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Full Paper
directly purified by flash column chromatography (ethyl acetate/ directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 1:5), afforded compound 3ab as a viscous color-
less oil (52.5 mg, 75 %). 1H NMR (400 MHz, CDCl3): δ = 4.95 (t, J =
9.6 Hz, 1H, H-3), 4.24 (d, J = 7.6 Hz, 1H, H-1), 3.92 (dd, J = 10.4 Hz
and 4.8 Hz, 1H, H-6a), 3.84 (dd, J = 10.4 Hz and 5.2 Hz, 1H, H-6b),
3.65 (t, J = 9.2 Hz, 1H, H-2), 3.53 (s, 3H, OCH3), 3.45–3.37 (m, 2H, H-
4 and H-5), 2.16 (s, 3H, OAc), 0.88 (s, 9H, Si(C(CH3)3)(CH3)2), 0.08 (s,
6H, Si(C(CH3)3)(CH3)2).
petroleum ether: 1:2), afforded compound 5ab as a viscous color-
less oil (51.8 mg, 74 %). 1H NMR (400 MHz, CDCl3): δ = 4.80 (dd,
J = 10.0 Hz and 2.8 Hz, 1H, H-3), 4.22 (d, J = 7.6 Hz, 1H, H-1), 4.14
(d, J = 2.4 Hz, 1H, H-4), 3.93–3.83 (m, 3H, H-2, H-6a and H-6b),
3.54–3.46 (m, 4H, H-5 and OCH3), 2.16 (s, 3H, OAc), 0.87 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.07 (s, 6H, Si(C(CH3)3)(CH3)2).
Methyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-α-D-manno-
pyranoside (6aa):[11e] Following the general procedure B, the reac-
Methyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-α-D-galacto-
pyranoside (4aa):[4c] Following the general procedure B, the reac- tion was carried out with methyl-α-
D-mannopyranoside 6
tion was carried out with methyl-α-
D
-galactopyranoside
4
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 10 h. The
crude product was directly purified by flash column chromatogra-
phy (ethyl acetate/petroleum ether: 1:5), afforded compound 6aa
as a viscous colorless oil (64.3 mg, 78 %). 1H NMR (400 MHz,
CDCl3): δ = 8.11–8.08 (m, 2H, ArH), 7.59–7.55 (m, 1H, ArH), 7.46–
7.42 (m, 2H, ArH), 5.36 (dd, J = 10.0 Hz and 3.2 Hz, 1H, H-3), 4.74
(0.2 mmol), DIPEA (140.5 μL, 4.0 equiv.), TBSCl (78.8 mg, 2.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 12 h. The
crude product was directly purified by flash column chromatogra-
phy (ethyl acetate/petroleum ether: 1:4), afforded compound 4aa
as a viscous colorless oil (68.4 mg, 83 %). 1H NMR (400 MHz,
CDCl3): δ = 8.12–8.07 (m, 2H, ArH), 7.61–7.53 (m, 1H, ArH), 7.47–
7.41 (m, 2H, ArH), 5.27 (dd, J = 10.4 Hz and 2.4 Hz, 1H, H-3), 4.91 (d, J = 1.6 Hz, 1H, H-1), 4.16–4.10 (m, 2H, H-2 and H-4), 3.98–3.89
(d, J = 3.6 Hz, 1H, H-1), 4.32 (d, J = 1.6 Hz, 1H, H-4), 4.25 (dd, J =
10.4 Hz and 3.6 Hz, 1H, H-2), 3.96–3.85 (m, 3H, H-5, H-6a and H-
(m, 2H, H-6a and H-6b), 3.75–3.70 (m, 1H, H-5), 3.42 (s, 3H, OCH3),
0.91 (s, 9H, Si(C(CH3)3)(CH3)2), 0.11 (s, 3H, Si(C(CH3)3)(CH3)2), 0.11 (s,
6b), 3.46 (s, 3H, OCH3), 0.90 (s, 9H, Si(C(CH3)3)(CH3)2), 0.10 (s, 6H, 3H, Si(C(CH3)3)(CH3)2).
Si(C(CH3)3)(CH3)2).
Methyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-α-D-mannopyr-
Methyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-α-D-galactopyr-
anoside (4ab):[11a] Following the general procedure B, the reaction
anoside (6ab):[11a] Following the general procedure B, the reaction
was carried out with methyl-α- -mannopyranoside 6 (0.2 mmol),
D
was carried out with methyl-α-
D
-galactopyranoside 4 (0.2 mmol),
DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature. Upon completion as shown by TLC,
acetic anhydride (23.0 μL, 1.2 equiv.) was added and the reaction
mixture was left stirring at 40 °C for 12 h. The crude product was
directly purified by flash column chromatography (ethyl acetate/
petroleum ether: 1:2), afforded compound 6ab as a viscous color-
less oil (53.2 mg, 76 %). 1H NMR (400 MHz, CDCl3): δ = 5.07–5.04
(m, J = 10.0 Hz and 2.8 Hz, 1H, H-3), 4.73–4.67 (m, 1H, H-1), 3.98–
3.84 (m, 4H, H-2, H-4, H-6a and H-6b), 3.69–3.61 (m, 1H, H-5), 3.37
DIPEA (140.5 μL, 4.0 equiv.), TBSCl (78.8 mg, 2.5 equiv.) in dry sol-
vent (1.1 mL) at room temperature. Upon completion as shown by
TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and the reac-
tion mixture was left stirring at 40 °C for 12 h. The crude product
was directly purified by flash column chromatography (ethyl acet-
ate/petroleum ether: 1:2), afforded compound 4ab as a viscous col-
orless oil (49.7 mg, 71 %). 1H NMR (400 MHz, CDCl3): δ = 5.03 (dd,
J = 10.0 Hz and 2.4 Hz, 1H, H-3), 4.85 (d, J = 3.6 Hz, 1H, H-1), 4.19
(d, J = 2.0 Hz, 1H, H-4), 4.07 (dd, J = 10.0 Hz and 3.6 Hz, 1H, H-2), (s, 3H, OCH3), 2.15 (s, 3H, OAc), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.09
3.94–3.86 (m, 2H, H-6a and H-6b), 3.77–3.75 (m, 1H, H-5), 3.43 (s,
3H, OCH3), 2.17 (s, 3H, OAc), 0.89 (s, 9H, Si(C(CH3)3)(CH3)2), 0.09 (s,
6H, Si(C(CH3)3)(CH3)2).
(s, 6H, Si(C(CH3)3)(CH3)2).
Isopropyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-
galactopyranoside (7aa):[4c] Following the general procedure B,
Methyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-ꢀ-D-galacto-
pyranoside (5aa):[11b] Following the general procedure B, the reac-
tion was carried out with methyl-ꢀ-D-galactopyranoside 5
the reaction was carried out with isopropylthio-ꢀ-D-galactopyranos-
ide 7 (0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg,
1.5 equiv.) in dry solvent (1.1 mL) at room temperature. Upon com-
pletion as shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.)
was added and the reaction mixture was left stirring at 40 °C for
8 h. The crude product was directly purified by flash column chro-
matography (ethyl acetate/petroleum ether: 1:6), afforded com-
pound 7aa as a viscous colorless oil (81.2 mg, 89 %). 1H NMR
(400 MHz, CDCl3): δ = 8.11–8.05 (m, 2H, ArH), 7.61–7.52 (m, 1H,
ArH), 7.46–7.39 (m, 2H, ArH), 5.12 (dd, J = 9.6 Hz and 2.8 Hz, 1H, H-
3), 4.52 (d, J = 9.6 Hz, 1H, H-1), 4.34 (d, J = 2.0 Hz, 1H, H-4), 4.08 (t,
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 10 h. The
crude product was directly purified by flash column chromatogra-
phy (ethyl acetate/petroleum ether: 1:4), afforded compound 5aa
as a viscous colorless oil (69.2 mg, 84 %). 1H NMR (400 MHz,
CDCl3): δ = 8.10–8.02 (m, 2H, ArH), 7.59–7.52 (m, 1H, ArH), 7.45–
7.39 (m, 2H, ArH), 5.07 (dd, J = 10.0 Hz and 2.8 Hz, 1H, H-3), 4.36– J = 9.6 Hz, 1H, H-2), 3.95–3.85 (m, 2H, H-6a and H-6b), 3.63 (t, J =
4.28 (m, 2H, H-1 and H-4), 4.05 (dd, J = 9.6 Hz and 8.0 Hz, 1H, H- 4.4 Hz, 1H, H-5), 3.28–3.22 (m, 1H, SCH(CH3)2), 1.34 (d, J = 6.8 Hz,
2), 3.95 (dd, J = 10.8 Hz and 6.0 Hz, 1H, H-6a), 3.89 (dd, J = 10.8 Hz
and 4.4 Hz, 2H, H-6b), 3.61–3.57 (m, 4H, H-5, OCH3), 0.89 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.08 (s, 6H, Si(C(CH3)3)(CH3)2).
6H, SCH(CH3)2), 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).
Isopropyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-
galactopyranoside (7ab):[11d]Following the general procedure B,
the reaction was carried out with isopropylthio-ꢀ-D-galactopyranos-
Methyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-ꢀ-D-galactopyr-
anoside (5ab):[11a] Following the general procedure B, the reaction
was carried out with methyl-ꢀ-
D
-galactopyranoside 5 (0.2 mmol),
ide 7 (0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg,
1.5 equiv.) in dry solvent (1.1 mL) at room temperature. Upon com-
pletion as shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was
added and the reaction mixture was left stirring at 40 °C for 12 h.
The crude product was directly purified by flash column chromatog-
DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.) in dry solvent
(1.1 mL) at room temperature. Upon completion as shown by TLC,
acetic anhydride (23.0 μL, 1.2 equiv.) was added and the reaction
mixture was left stirring at 40 °C for 12 h. The crude product was
Eur. J. Org. Chem. 2019, 6383–6395
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6391
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
raphy (ethyl acetate/petroleum ether: 1:3), afforded compound 7ab
as a viscous colorless oil (61.5 mg, 78 %). 1H NMR (400 MHz,
CDCl3): δ = 4.83 (dd, J = 9.6 Hz and 2.4 Hz, 1H, H-3), 4.42 (d, J =
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and
the reaction mixture was left stirring at 40 °C for 8 h. The crude
9.6 Hz, 1H, H-1), 4.18 (d, J = 2.4 Hz, 1H, H-4), 3.89–3.80 (m, 3H, H- product was directly purified by flash column chromatography
2, H-6a and H-6b), 3.52 (t, J = 4.8 Hz, 1H, H-5), 3.26–3.17 (m, 1H,
SCH(CH3)2), 2.15 (s, 3H, OAc), 1.31 (d, J = 6.8 Hz, 6H, SCH(CH3)2),
0.86 (s, 9H, Si(C(CH3)3)(CH3)2), 0.06 (s, 3H, Si(C(CH3)3)(CH3)2), 0.05 (s,
3H, Si(C(CH3)3)(CH3)2).
(ethyl acetate/petroleum ether: 1:3), afforded compound 9ab as a
viscous colorless oil (71.6 mg, 81 %). 1H NMR (400 MHz, CDCl3):
δ = 7.32–7.24 (m, 5H, ArH), 4.76 (dd, J = 9.6 Hz and 2.8 Hz, 1H, H-
3), 4.24 (d, J = 9.6 Hz, 1H, H-1), 4.19 (d, J = 2.0 Hz, 1H, H-4), 3.99–
3.84 (m, 5H, H-2, PhCH2, H-6a and H-6b), 3.46 (t, J = 4.4 Hz, 1H,
H-5), 2.15 (s, 3H, OAc), 0.90 (s, 9H, Si(C(CH3)3)(CH3)2), 0.11 (s, 3H,
Si(C(CH3)3)(CH3)2), 0.10 (s, 3H, Si(C(CH3)3)(CH3)2).
Ethyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (8aa):[11d] Following the general procedure B, the
reaction was carried out with ethyl-ꢀ- -thiogalactopyranoside 8
D
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:6), afforded compound 8aa as a
viscous colorless oil (71.6 mg, 81 %). 1H NMR (400 MHz, CDCl3):
δ = 8.12–8.10 (m, 2H, ArH), 7.59–7.54 (m, 1H, ArH), 7.46–7.42 (m,
2H, ArH), 5.10 (dd, J = 9.6 Hz and 3.2 Hz, 1H, H-3), 4.44 (d, J =
9.6 Hz, 1H, H-1), 4.36 (d, J = 2.8 Hz, 1H, H-4), 4.12 (t, J = 9.6 Hz, 1H,
H-2), 3.96 (dd, J = 10.8 Hz and 5.6 Hz, 1H, H-6a), 3.89 (dd, J =
10.8 Hz and 4.4 Hz, 1H, H-6b), 3.62 (t, J = 5.2 Hz, 1H, H-5), 2.85–
2.70 (m, 2H, SCH2CH3), 1.33 (t, J = 7.2 Hz, 3H, SCH2CH3), 0.89 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.09 (s, 3H, Si(C(CH3)3)(CH3)2), 0.08 (s, 3H,
Si(C(CH3)3)(CH3)2).
p-Tolyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (10aa):[11d] Following the general procedure B,
the reaction was carried out with p-tolyl-ꢀ-D-thiogalactopyranoside
10 (0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:6), afforded compound 10aa as a
viscous colorless oil (88.7 mg, 88 %). 1H NMR (400 MHz, CDCl3):
δ = 8.09–8.05 (m, 2H, ArH), 7.57–7.40 (m, 5H, ArH), 7.14–7.11 (m,
2H, ArH), 5.10 (dd, J = 9.2 Hz and 2.4 Hz, 1H, H-3), 4.58 (d, J =
9.6 Hz, 1H, H-1), 4.35 (d, J = 2.0 Hz, 1H, H-4), 4.07–3.91 (m, 3H, H-
2, H-6a and H-6b), 3.62 (t, J = 4.0 Hz, 1H, H-5), 2.35 (s, 3H, SPhCH3),
0.91 (s, 9H, Si(C(CH3)3)(CH3)2), 0.12 (s, 3H, Si(C(CH3)3)(CH3)2), 0.10 (s,
3H, Si(C(CH3)3)(CH3)2).
Ethyl
lactopyranoside (8ab):[11d] Following the general procedure B, the
reaction was carried out with ethyl-ꢀ- -thiogalactopyranoside 8
3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
p-Tolyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (10ab):[11d] Following the general procedure B,
D
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and
the reaction mixture was left stirring at 40 °C for 12 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:3), afforded compound 8ab as a
viscous colorless oil (60.8 mg, 80 %). 1H NMR (400 MHz, CDCl3):
δ = 4.84 (dd, J = 9.6 Hz and 3.2 Hz, 1H, H-3), 4.36 (d, J = 6.0 Hz, 1H,
H-1), 4.23 (d, J = 2.4 Hz, 1H, H-4), 3.97–3.85 (m, 3H, H-2, H-6a and
H-6b), 3.53 (t, J = 4.4 Hz, 1H, H-5), 2.78–2.68 (m, 2H, SCH2CH3), 2.17
(s, 3H, OAc), 1.33–1.28 (m, 3H, SCH2CH3), 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).
the reaction was carried out with p-tolyl-ꢀ-D-thiogalactopyranoside
10 (0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and
the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:3), afforded compound 10ab as a
viscous colorless oil (72.5 mg, 82 %). 1H NMR (400 MHz, CDCl3):
δ = 7.46 (d, J = 8.0 Hz, 2H, ArH), 7.10 (d, J = 8.0 Hz, 2H, ArH), 4.85
(dd, J = 9.6 Hz and 2.8 Hz, 1H, H-3), 4.49 (d, J = 9.6 Hz, 1H, H-1),
4.22 (d, J = 2.0 Hz, 1H, H-4), 3.98 (dd, J = 10.8 Hz and 4.8 Hz, 1H,
H-6a), 3.92–3.83 (m, 2H, H-2 and H-6b), 3.53 (t, J = 4.0 Hz, 1H,
H-5), 2.33 (s, 3H, SPhCH3), 2.14 (s, 3H, OAc), 0.90 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.12 (s, 3H, Si(C(CH3)3)(CH3)2), 0.10 (s, 3H,
Si(C(CH3)3)(CH3)2).
Benzyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (9aa):[11d] Following the general procedure B, the
reaction was carried out with benzyl-ꢀ- -thiogalactopyranoside 9
D
p-Tolyl 3-O-Benzoyl-6-O-(tert-butyldiphenylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (10ba): Following the general procedure B, the
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:6), afforded compound 9aa as a
viscous colorless oil (90.7 mg, 90 %). 1H NMR (400 MHz, CDCl3):
δ = 8.11–8.06 (m, 2H, ArH), 7.59–7.55 (m, 1H, ArH), 7.47–7.42 (m,
2H, ArH), 7.36–7.26 (m, 5H, ArH), 5.03 (dd, J = 9.2 Hz and 2.8 Hz,
1H, H-3), 4.34–4.32 (m, 2H, H-1 and H-4), 4.14 (t, J = 9.2 Hz, 1H, H-
2), 4.03–3.88 (m, 4H, PhCH2, H-6a and H-6b), 3.56 (t, J = 4.8 Hz, 1H,
H-5), 0.91 (s, 9H, Si(C(CH3)3)(CH3)2), 0.12 (s, 3H, Si(C(CH3)3)(CH3)2),
0.11 (s, 3H, Si(C(CH3)3)(CH3)2).
reaction was carried out with p-tolyl-ꢀ- -thiogalactopyranoside 10
D
(0.2 mmol), DIPEA (91.5 μL, 2.6 equiv.), TBDPSCl (104.0 μL, 2.0 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 12 h. The
crude product was directly purified by flash column chromatogra-
phy (ethyl acetate/petroleum ether: 1:6), afforded compound 10ba
as a viscous colorless oil (104.2 mg, 80 %). 1H NMR (400 MHz,
CDCl3): δ = 8.12–8.09 (m, 2H, ArH), 7.77–7.69 (m, 4H, ArH), 7.51–
7.38 (m, 11H, ArH), 7.10–7.08 (m, 2H, ArH), 5.12 (dd, J = 9.6 Hz and
2.8 Hz, 1H, H-3), 4.59 (d, J = 9.6 Hz, 1H, H-1), 4.40 (d, J = 2.8 Hz, 1H,
H-4), 4.07 (t, J = 9.6 Hz, 1H, H-2), 4.02 (dd, J = 10.8 Hz and 5.2 Hz,
1H, H-6a), 3.95 (dd, J = 10.8 Hz and 4.4 Hz, 1H, H-6b), 3.68 (t, J =
4.8 Hz, 1H, H-5), 2.34 (s, 3H, SPhCH3), 1.07 (s, 9H, Si(C(CH3)3)).
13C NMR (100 MHz, CDCl3): δ = 166.4, 138.5, 135.8, 135.7, 133.5,
133.4, 132.8, 132.6, 130.1, 129.8, 128.6, 128.5, 128.0, 127.9, 89.4, 77.9,
Benzyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (9ab):[11d]Following the general procedure B, the
reaction was carried out with benzyl-ꢀ-
D
-thiogalactopyranoside 9
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
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77.2, 68.9, 67.3, 64.3, 26.9, 21.3, 19.2 ppm; HRMS (ESI-TOF): Calcu-
11 (0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:6), afforded compound 11aa as a
viscous colorless oil (89.2 mg, 91 %). 1H NMR (400 MHz, CDCl3):
δ = 8.09–8.05 (m, 2H, ArH), 7.61–7.53 (m, 3H, ArH), 7.47–7.39 (m,
2H, ArH), 7.32–7.30 (m, 3H, ArH), 5.12 (dd, J = 9.2 Hz and 2.4 Hz,
1H, H-3), 4.66 (d, J = 10.0 Hz, 1H, H-1), 4.36 (d, J = 2.4 Hz, 1H, H-4),
4.10 (t, J = 9.6 Hz, 1H, H-2), 3.99 (dd, J = 10.8 Hz and 4.8 Hz, 1H,
H-6a), 3.93 (dd, J = 10.8 Hz and 4.0 Hz, 1H, H-6b), 3.66–3.63 (m, 1H,
H-5), 0.91 (s, 9H, Si(C(CH3)3)(CH3)2), 0.12 (s, 3H, Si(C(CH3)3)(CH3)2),
0.10 (s, 3H, Si(C(CH3)3)(CH3)2).
lated for [C36H40O6SSiNa]+: 651.2207, found 651.2207.
p-Tolyl 3-O-Acetyl-6-O-(tert-butyldiphenylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (10bb): Following the general procedure B, the
reaction was carried out with p-tolyl-ꢀ- -thiogalactopyranoside 10
D
(0.2 mmol), DIPEA (91.5 μL, 2.6 equiv.), TBDPSCl (104.0 μL, 2.0 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and
the reaction mixture was left stirring at 40 °C for 12 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:3), afforded compound 10bb as a
viscous colorless oil (90.7 mg, 77 %). 1H NMR (400 MHz, CDCl3):
δ = 7.76–7.68 (m, 4H, ArH), 7.49–7.38 (m, 8H, ArH), 7.08–7.06 (m,
2H, ArH), 4.87 (dd, J = 9.6 Hz and 3.2 Hz, 1H, H-3), 4.50 (d, J =
9.6 Hz, 1H, H-1), 4.28 (d, J = 2.8 Hz, 1H, H-4), 4.00 (dd, J = 10.8 Hz
and 4.8 Hz, 1H, H-6a), 3.94–3.86 (m, 2H, H-2 and H-6b), 3.58 (t, J =
4.4 Hz, 1H, H-5), 2.32 (s, 3H, SPhCH3), 2.17 (s, 3H, OAc), 1.07 (s, 9H,
Si(C(CH3)3)). 13C NMR (100 MHz, CDCl3): δ = 170.9, 138.7, 135.8,
135.7, 133.6, 132.7, 132.4, 130.1, 129.9, 128.0, 127.9, 127.6, 89.1, 76.6,
69.0, 66.9, 64.6, 26.8, 21.3, 19.2 ppm; HRMS (ESI-TOF): Calculated
for [C31H38O6SSiNa]+: 589.2051, found 589.2049.
Phenyl 3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (11ab):[11d] Following the general procedure B,
the reaction was carried out with phenyl-ꢀ-D-thiogalactopyranoside
11 (0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and
the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:3), afforded compound 11ab as a
viscous colorless oil (71.0 mg, 83 %). 1H NMR (400 MHz, CDCl3):
δ = 7.58–7.56 (m, 2H, ArH), 7.30–7.28 (m, 3H, ArH), 4.86 (dd, J =
9.6 Hz and 2.8 Hz, 1H, H-3), 4.56 (d, J = 9.6 Hz, 1H, H-1), 4.23 (d,
J = 2.0 Hz, 1H, H-4), 3.98 (dd, J = 10.8 Hz and 1.2 Hz, 1H, H-6a),
3.93–3.88 (m, 2H, H-2 and H-6b), 3.55 (t, J = 4.0 Hz, 1H, H-5), 2.15
(s, 3H, OAc), 0.90 (s, 9H, Si(C(CH3)3)(CH3)2), 0.11 (s, 3H,
Si(C(CH3)3)(CH3)2), 0.09 (s, 3H, Si(C(CH3)3)(CH3)2).
p-Tolyl 3-O-Benzoyl-6-O-(triisopropylsilyl)-1-thio-ꢀ-D-galacto-
pyranoside (10ca): Following the general procedure B, the reaction
was carried out with p-tolyl-ꢀ- -thiogalactopyranoside 10
D
(0.2 mmol), DIPEA (105.5 μL, 3.0 equiv.), TIPSCl (86.0 μL, 2.0 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 12 h. The
crude product was directly purified by flash column chromatogra-
phy (ethyl acetate/petroleum ether: 1:6), afforded compound 10ca
as a viscous colorless oil (85.4 mg, 75 %). 1H NMR (400 MHz,
CDCl3): δ = 8.10–8.08 (m, 2H, ArH), 7.56–7.41 (m, 5H, ArH), 7.12 (d,
J = 8.0 Hz, 2H, ArH), 5.11 (dd, J = 9.6 Hz and 2.8 Hz, 1H, H-3), 4.58
(d, J = 9.6 Hz, 1H, H-1), 4.39 (d, J = 2.8 Hz, 1H, H-4), 4.13–3.99 (m,
3H, H-2, H-6a and H-6b), 3.63 (t, J = 4.4 Hz, 1H, H-5), 2.35 (s, 3H,
SPhCH3), 1.13–1.07 (m, 21H, Si(CH(CH3)2)3). 13C NMR (100 MHz,
CDCl3): δ = 166.5, 138.6, 133.6, 133.4, 130.1, 129.9, 129.8, 128.5,
127.8, 89.4, 77.8, 77.3, 69.0, 67.2, 64.2, 21.3, 18.1, 18.0, 11.9 ppm;
HRMS (ESI-TOF): Calculated for [C29H42O6SSiNa]+: 569.2364, found
569.2364.
Phenyl
glucopyranoside (13aa): Following the general procedure B, the
reaction was carried out with phenyl-ꢀ- -thioglucopyranoside 13
3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-
D
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, benzoic anhydride (55.5 mg, 1.2 equiv.) was added
and the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:6), afforded compound 13aa as a
viscous colorless oil (77.4 mg, 79 %). 1H NMR (400 MHz, CDCl3):
δ = 8.09–8.04 (m, 2H, ArH), 7.58–7.56 (m, 3H, ArH), 7.45–7.41 (m,
2H, ArH), 7.33–7.32 (m, 3H, ArH), 5.24 (t, J = 9.2 Hz, 1H, H-3), 4.65
(d, J = 9.6 Hz, 1H, H-1), 3.98 (dd, J = 10.8 Hz and 4.8 Hz, 1H, H-6a),
3.91 (dd, J = 10.4 Hz and 4.8 Hz, 1H, H-6b), 3.82 (t, J = 9.2 Hz, 1H,
H-4), 3.59 (t, J = 9.2 Hz, 1H, H-2), 3.55–3.50 (m, 1H, H-5), 0.91 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.11 (s, 3H, Si(C(CH3)3)(CH3)2), 0.10 (s, 3H,
Si(C(CH3)3)(CH3)2). 13C NMR (100 MHz, CDCl3): δ = 167.8, 133.6,
133.1, 131.8, 130.2, 129.6, 129.2, 128.5, 128.4, 88.5, 79.8, 79.1, 71.1,
70.6, 64.3, 26.0, 18.4, –5.3 ppm; HRMS (ESI-TOF): Calculated for
[C25H34O6SSiNa]+: 513.1738, found 513.1730.
p-Tolyl 3-O-Acetyl-6-O-(triisopropylsilyl)-1-thio-ꢀ-D-galactopyr-
anoside (10cb): Following the general procedure B, the reaction
was carried out with p-tolyl-ꢀ- -thiogalactopyranoside 10
D
(0.2 mmol), DIPEA (105.5 μL, 3.0 equiv.), TIPSCl (86.0 μL, 2.0 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and
the reaction mixture was left stirring at 40 °C for 12 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:3), afforded compound 10cb as a
viscous colorless oil (74.0 mg, 73 %). 1H NMR (400 MHz, CDCl3):
δ = 7.48–7.46 (m, 2H, ArH), 7.11–7.09 (m, 2H, ArH), 4.87 (dd, J =
9.6 Hz and 2.8 Hz, 1H, H-3), 4.49 (d, J = 9.6 Hz, 1H, H-1), 4.26 (d,
J = 2.8 Hz, 1H, H-4), 4.09 (dd, J = 10.8 Hz and 4.4 Hz, 1H, H-6a),
3.99 (dd, J = 10.8 Hz and 3.6 Hz, 1H, H-6b), 3.87 (t, J = 9.6 Hz, 1H,
H-2), 3.53 (t, J = 4.0 Hz, 1H, H-5), 2.33 (s, 3H, SPhCH3), 2.15 (s, 3H,
OAc), 1.09–1.07 (m, 21H, Si(CH(CH3)2)3). 13C NMR (100 MHz,
CDCl3): δ = 170.9, 138.7, 133.8, 129.9, 127.5, 89.1, 77.4, 76.6, 69.1,
66.9, 64.6, 21.3, 21.3, 18.1, 18.0, 11.9 ppm; HRMS (ESI-TOF): Calcu-
lated for [C24H40O6SSiNa]+: 507.2207, found 507.2209.
Phenyl
glucopyranoside (13ab): Following the general procedure B, the
reaction was carried out with phenyl-ꢀ- -thioglucopyranoside 13
3-O-Acetyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-
D
(0.2 mmol), DIPEA (77.5 μL, 2.2 equiv.), TBSCl (46.2 mg, 1.5 equiv.)
in dry solvent (1.1 mL) at room temperature. Upon completion as
shown by TLC, acetic anhydride (23.0 μL, 1.2 equiv.) was added and
the reaction mixture was left stirring at 40 °C for 8 h. The crude
product was directly purified by flash column chromatography
(ethyl acetate/petroleum ether: 1:3), afforded compound 13ab as a
viscous colorless oil (68.5 mg, 80 %). 1H NMR (400 MHz, CDCl3):
δ = 7.55–7.52 (m, 2H, ArH), 7.32–7.30 (m, 3H, ArH), 4.98 (t, J = 9.2 Hz,
1H, H-3), 4.57 (d, J = 9.6 Hz, 1H, H-1), 3.95 (dd, J = 10.8 Hz and
Phenyl 3-O-Benzoyl-6-O-(tert-butyldimethylsilyl)-1-thio-ꢀ-D-ga-
lactopyranoside (11aa):[11d] Following the general procedure B,
the reaction was carried out with phenyl-ꢀ-
D
-thiogalactopyranoside
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Xiong, J.-S. Sun, J. Am. Chem. Soc. 2017, 139, 12736–12744; i) S. J. Danish-
efsky, Y. K. Shue, M. N. Chang, C. H. Wong, Acc. Chem. Res. 2015, 48, 643–
652; j) H. Dong, M. Rahm, T. Brinck, O. Ramström, J. Am. Chem. Soc. 2008,
130, 15270–15271; k) C. C. Wang, J. C. Lee, S. Y. Luo, S. S. Kulkarni, Y. W.
Huang, C.-C. Lee, K. L. Chang, S. C. Hung, Nature 2007, 446, 896–899.
a) M. Lalonde, T. H. Chan, Synthesis 1985, 817–845; b) C. Rücker, Chem.
Rev. 1995, 95, 1009–1064; c) J. Mulzer, B. Schöllhorn, Angew. Chem. Int.
Ed. Engl. 1990, 29, 431–432; Angew. Chem. 1990, 102, 433; d) M.-Y. Chen,
K.-C. Lu, A. S.-Y. Lee, C.-C. Lin, Tetrahedron Lett. 2002, 43, 2777–2780;
e) R. D. Crouch, Tetrahedron 2013, 69, 2383–2417.
a) E. J. Corey, A. Venkateswarlu, J. Am. Chem. Soc. 1972, 94, 6190–6191;
b) S. Hanessian, P. Lavallee, Can. J. Chem. 1975, 53, 2975–2977; c) M. S.
Arias-Pérez, M. J. Santos, Tetrahedron 1996, 52, 10785–10798.
a) F. Franke, R. D. Guthrie, Aust. J. Chem. 1997, 30, 639–647; b) A. P.
Mehta, S. H. Abdelwahed, T. P. Begley, J. Am. Chem. Soc. 2013, 135,
10883–10885; c) D. Lee, M. S. Taylor, J. Am. Chem. Soc. 2011, 133, 3724–
3727.
a) H. H. Brandstetter, E. Zbiral, Helv. Chim. Acta 1980, 63, 327–343; b)
H. H. Brandstetter, E. Zbiral, Helv. Chim. Acta 1978, 61, 1832–1841; c) E.
Sasaki, C.-I. Lin, K.-Y. Lin, H.-W. Liu, J. Am. Chem. Soc. 2012, 134, 17432–
17435; d) J. C. Lee, S. Francis, D. Dutta, V. Gupta, Y. Yang, J.-Y. Zhu, J. S.
Tash, E. Schönbrunn, G. I. Georg, J. Org. Chem. 2012, 77, 3082–3098; e)
T. K. Kotammagari, R. G. Gonnade, A. K. Bhattacharya, Org. Lett. 2017,
19, 3564–3567; f) C.-Y. Li, G.-J. Liu, W. Du, Y. Zhang, G.-W. Xing, Tetrahe-
dron Lett. 2017, 58, 2109–2112; g) L. Legentil, Y. Cabezas, O. Tasseau,
C. Tellier, F. Daligault, V. Ferrières, J. Org. Chem. 2017, 82, 7114–7122;
h) V. Dimakos, M. S. Taylor, Chem. Rev. 2018, 118, 11457–11517.
M. W. Bredenkamp, S. Afr. J. Chem. 1995, 48, 154–156.
D. A. Johnson, L. M. Taubner, Tetrahedron Lett. 1996, 137, 605–608.
a) M.-K. Chung, G. Orlova, J. D. Goddard, M. Schlaf, R. Harris, T. J. Beve-
ridge, G. White, F. R. Hallett, J. Am. Chem. Soc. 2002, 124, 10508–10518;
b) M.-K. Chung, M. Schlaf, J. Am. Chem. Soc. 2005, 127, 18085–18092.
J. M. Blackwell, K. L. Foster, V. H. Beck, W. E. Piers, J. Org. Chem. 1999, 64,
4887–4892.
4.8 Hz, 1H, H-6a), 3.86 (dd, J = 10.8 Hz and 5.2 Hz, 1H, H-6b), 3.66
(t, J = 9.2 Hz, 1H, H-4), 3.47–3.39 (m, 2H, H-2 and H-5), 2.15 (s, 3H,
OAc), 0.90 (s, 9H, Si(C(CH3)3)(CH3)2), 0.10 (s, 3H, Si(C(CH3)3)(CH3)2),
0.09 (s, 3H, Si(C(CH3)3)(CH3)2). 13C NMR (100 MHz, CDCl3): δ =
172.4, 133.1, 131.6, 129.2, 128.4, 88.4, 79.0, 78.9, 70.9, 70.4, 64.3,
25.9, 21.2, 18.4, –5.3 ppm; HRMS (ESI-TOF): Calculated for
[C20H32O6SSiNa]+: 451.1581, found 451.1576.
[2]
Phenyl 6,6′-Di-O-(tert-butyldimethylsilyl)-3′-benzoyl-1-thio-ꢀ-D-
lactoside (16aa):[11d] Following the general procedure B, the reac-
[3]
[4]
tion was carried out with phenyl-1-thio-ꢀ- -lactoside 16 (0.2 mmol),
D
DIPEA (211.0 μL, 6.0 equiv.), TBSCl (123.0 mg, 4.0 equiv.) in dry
solvent (1.1 mL) at room temperature. Upon completion as shown
by TLC, benzoic anhydride (23.0 mg, 1.2 equiv.) was added and the
reaction mixture was left stirring at 40 °C for 12 h. The crude prod-
uct was directly purified by flash column chromatography (ethyl
acetate/petroleum ether: 1:2), afforded compound 16aa as a vis-
[5]
1
cous colorless oil (112.0 mg, 73 %). H NMR (400 MHz, CDCl3): δ =
8.11–8.08 (m, 2H, ArH), 7.62–7.56 (m, 3H, ArH), 7.49–7.43 (m, 2H,
ArH), 7.30–7.28 (m, 3H, ArH), 5.03 (dd, J = 10.0 Hz and 2.8 Hz, 1H,
H-3′), 4.56–4.49 (m, 2H, H-1 and H-1′), 4.30 (d, J = 2.0 Hz, 1H, H-4′
), 4.08 (dd, J = 9.6 Hz and 8.0 Hz, H-2′), 3.96–3.90 (m, 4H, H-6a, H-
6b, H-6a′ and H-6b′), 3.71–3.58 (m, 3H, H-3, H-4 and H-5′), 3.45–
3.36 (m, 2H, H-2 and H-5), 0.90 (s, 9H, Si(C(CH3)3)(CH3)2), 0.88 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.09 (s, 6H, Si(C(CH3)3)(CH3)2), 0.08 (s, 6H,
Si(C(CH3)3)(CH3)2).
[6]
[7]
[8]
Phenyl-6,6′-Di-O-(tert-butyldimethylsilyl)-3′-acetyl-1-thio-ꢀ-D-
lactoside (16ab):[11d] Following the general procedure B, the reac-
tion was carried out with phenyl-1-thio-ꢀ- -lactoside 16 (0.2 mmol),
D
DIPEA (211.0 μL, 6.0 equiv.), TBSCl (123.0 mg, 4.0 equiv.) in dry
solvent (1.1 mL) at room temperature. Upon completion as shown
by TLC, acetic anhydride (55.5 mg, 1.2 equiv.) was added and the
reaction mixture was left stirring at 40 °C for 12 h. The crude prod-
uct was directly purified by flash column chromatography (ethyl
acetate/petroleum ether: 1:1), afforded compound 16ab as a vis-
[9]
[10]
a) L. H. Sommer, J. E. Lyons, J. Am. Chem. Soc. 1969, 91, 7061–7066;
b) E. Lukevics, M. Dzintara, J. Organomet. Chem. 1985, 295, 265–315;
c) M. P. Doyle, K. G. High, V. Bagheri, R. J. Pieters, P. J. Lewis, M. M. Pearson,
J. Org. Chem. 1990, 55, 6082–6086.
1
cous colorless oil (104.2 mg, 74 %). H NMR (400 MHz, CDCl3): δ =
[11]
[12]
a) B. Ren, M. Rahm, X. L. Zhang, Y. X. Zhou, H. Dong, J. Org. Chem. 2014,
79, 8134–8142; b) X. L. Zhang, B. Ren, J.-T. Ge, Z. C. Pei, H. Dong, Tetrahe-
dron 2016, 72, 1005–1010; c) Y. C. Lu, C. X. Hou, J. L. Ren, X. T. Xin, H. F.
Xu, Y. X. Pei, H. Dong, Z. C. Pei, Molecules 2016, 21, 641–649; d) J. Lv, J.-
T. Ge, T. Luo, H. Dong, Green Chem. 2018, 20, 1987–1991; e) J. Lv, T. Luo,
Y. Zhang, Z. C. Pei, H. Dong, ACS Omega 2018, 3, 17717–17723.
a) B. Ren, M. Y. Wang, J. Y. Liu, J. T. Ge, H. Dong, ChemCatChem 2015, 7,
761–765; b) B. Ren, O. Ramström, Q. Zhang, J.-T. Ge, H. Dong, Chem. Eur.
J. 2016, 22, 2481–2486; c) H. F. Xu, B. Ren, W. Zhao, Y. C. Lu, Y. X. Pei, H.
Dong, Z. C. Pei, Tetrahedron 2016, 72, 3490–3499; d) B. Ren, J. Lv, Y.
Zhang, J. Tian, H. Dong, ChemCatChem 2017, 9, 950–953; e) H. F. Xu, Y.
Zhang, H. Dong, Y. C. Lu, Y. X. Pei, Z. C. Pei, Tetrahedron Lett. 2017, 58,
4039–4042.
a) B. Wu, J.-T. Ge, B. Ren, Z.-C. Pei, H. Dong, Tetrahedron 2015, 71, 4023–
4030; b) M. Emmadi, S. S. Kulkarni, Org. Biomol. Chem. 2013, 11, 4825–
4830; c) H. Dong, Z. C. Pei, O. Ramström, Chem. Commun. 2008, 1359–
1361; d) H. Dong, Z. C. Pei, M. Angelin, S. Byström, O. Ramström, J. Org.
Chem. 2007, 72, 3694–3701.
a) A. Français, D. Urban, J.-M. Beau, Angew. Chem. Int. Ed. 2007, 46, 8662–
8665; Angew. Chem. 2007, 119, 8816; b) Y. Vohra, M. Vasan, A. Venot, G.-
J. Boons, Org. Lett. 2008, 10, 3247–3250; c) K.-K. T. Mong, C.-S. Chao, M.-
C. Chen, C.-W. Lin, Synlett 2009, 4, 603–606; d) R. A. Jones, R. Davison,
A. T. Tran, N. Smith, M. C. Galan, Carbohydr. Res. 2010, 345, 1842–1845;
e) A. T. Tran, R. A. Jones, J. Pastor, J. Boisson, N. Smith, M. C. Galan, Adv.
Synth. Catal. 2011, 353, 2593–2598; f) J.-T. Ge, L. Zhou, T. Luo, J. Lv, H.
Dong, Org. Lett. 2019, 21, 5903–5906.
7.57–7.54 (m, 2H, ArH), 7.30–7.27 (m, 3H, ArH), 4.77 (dd, J = 10.0 Hz
and 2.8 Hz, 1H, H-3′), 4.52 (d, J = 9.6 Hz, 1H, H-1), 4.41 (d, J = 8.0 Hz,
1H, H-1′), 4.16 (d, J = 2.8 Hz, H-4′), 3.94–3.86 (m, 5H, H-2′, H-6a, H-
6b, H-6a′ and H-6b′), 3.67–3.54 (m, 3H, H-3, H-4 and H-5′), 3.44–
3.33 (m, 2H, H-2 and H-5), 2.17 (s, 3H, OAc), 0.89 (s, 9H,
Si(C(CH3)3)(CH3)2), 0.87 (s, 9H, Si(C(CH3)3)(CH3)2), 0.09–0.06 (m, 12H,
2 × Si(C(CH3)3)(CH3)2).
Acknowledgments
This study was supported by the National Nature Science Foun-
dation of China (Nos. 21772049, 21708010). The authors are also
grateful to the staffs in the Analytical and Test Center of HUST
for support with the NMR instruments and mass spectrometers.
[13]
[14]
Keywords: Homogeneous catalysis · One-pot reactions ·
Regioselectivity · Silylation · Synthetic methods
[1] a) T. W. Greene, P. G. M. Wuts, Greene's Protective Groups in Organic Syn-
thesis, 4rd ed. Wiley: New York, 2006; b) S. S. Kulkarni, C.-C. Wang, N. M.
Sabbavarapu, A. R. Podilapu, P.-H. Liao, S.-C. Hung, Chem. Rev. 2018, 118,
8025–8104; c) C. S. Bennett, M. C. Galan, Chem. Rev. 2018, 118, 7931–
7985; d) B. Dhakal, D. Crich, J. Am. Chem. Soc. 2018, 140, 15008–15015;
e) Y. Zhang, F.-L. Zhao, T. Luo, Z. Pei, H. Dong, Chem. Asian J. 2019, 14,
223–234; f) J.-T. Ge, L. Zhou, F.-L. Zhao, H. Dong, J. Org. Chem. 2017, 82,
12613–12623; g) J.-T. Ge, Y.-Y. Li, J. Tian, R.-Z. Liao, H. Dong, J. Org. Chem.
2017, 82, 7008–7014; h) Y. Hu, K. Yu, L.-L. Shi, L. Liu, J.-J. Sui, D.-Y. Liu, B.
[15]
[16]
S. K. Chaudhary, O. Hernandez, Tetrahedron Lett. 1979, 20, 99–102.
a) A. Wissner, C. V. Grudzinskas, J. Org. Chem. 1978, 43, 3972–3974; b)
D. E. Ward, C. K. Rhee, Tetrahedron Lett. 1991, 32, 7165–7166.
B. Ren, L. Gan, L. Zhang, N.-N. Yan, H. Dong, Org. Biomol. Chem. 2018,
16, 5591–5597.
[17]
Eur. J. Org. Chem. 2019, 6383–6395
www.eurjoc.org
6394
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[18] Z. Tu, H.-W. Hsieh, C.-M. Tsai, C.-W. Hsu, S.-G. Wang, K.-J. Wu, K.-I. Lin,
C.-H. Lin, Chem. Asian J. 2013, 8, 1536–1550.
[24]
[25]
K. C. Calvo, J. Am. Chem. Soc. 1985, 107, 3690–3694.
H.-K. Kim, H. Wei, A. Kulkarni, R. M. Pogranichniy, D. H. Thompson,
[19] A. Keliris, T. Ziegler, R. Mishra, R. Pohmann, M. G. Sauer, K. Ugurbil, J.
Engelmann, Bioorg. Med. Chem. 2011, 19, 2529–2540.
[20] M.-K. Chung, M. Schlaf, J. Am. Chem. Soc. 2004, 126, 7386–7392.
[21] M. Kishida, H. Akita, Tetrahedron: Asymmetry 2005, 16, 2625–2630.
[22] G. Sabitha, S. S. S. Reddy, J. S. Yadav, Tetrahedron Lett. 2010, 51, 6259–
6261.
Biomacromolecules 2012, 13, 636–644.
D. Markovic, W. A. Tchawou, I. Novosjolova, S. Laclef, D. Stepanovs, M.
Turks, P. Vogel, Chem. Eur. J. 2016, 22, 4196–4205.
K. V. Baratha, A. Nourry, J.-F. Pilard, Eur. Polym. J. 2015, 70, 317–330.
[26]
[27]
[23] Y. Zhang, Y. Zhang, Y.-L. Sun, X. Du, J.-Y. Shi, W. D. Wang, W. Wang, Chem.
Eur. J. 2012, 18, 6328–6334.
Received: August 13, 2019
Eur. J. Org. Chem. 2019, 6383–6395
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6395
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim