Halobenzoyl groups in glycosylation: Effect on stereoselectivity and reactivity of glycosyl donors

Article abstract of DOI:10.1007/s11172-015-0987-2

Described herein is the synthesis and evaluation of a series of glycosyl donors equipped with halobenzoyl substituents at O(4) and O(6) to study their properties in glycosylations. Among possible effects that may include carbonyl participation or H-bond m

Full text of DOI:10.1007/s11172-015-0987-2

Russian Chemical Bulletin, International Edition, Vol. 64, No. 5, pp. 1107—1118, May, 2015
1107
Halobenzoyl groups in glycosylation:
effect on stereoselectivity and reactivity of glycosyl donors*
S. Visansirikul, J. P. Yasomanee, and A. V. Demchenko
Department of Chemistry and Biochemistry, University of Missouri—St. Louis,
One University Blvd., St. Louis, MO 63121, USA.
Eꢀmail: demchenkoa@umsl.edu
Described herein is the synthesis and evaluation of a series of glycosyl donors equipped with
halobenzoyl substituents at O(4) and O(6) to study their properties in glycosylations. Among
possible effects that may include carbonyl participation or Hꢀbond mediated aglycone delivery,
our results indicate that halobenzoyls act via a different mode.
Key words: carbohydrates, glycosylation, stereoselectivity, thioglycosides, activation.
Scheme 1
The necessity to perform glycosylation reactions with
complete stereoselectivity has been the major hurdle that
consistently captured the attention of many carbohydrate
chemists. The Kochetkov laboratory has made a number
of seminal contributions to the glycosylation method deꢀ
velopment1 introducing many significant improvements
into this research field.2 Many factors affect the outcome
of chemical glycosylations.3 For instance, the stereoselecꢀ
tivity of glycosylation can be profoundly influenced by
protecting groups.4 Neighboring protecting groups at O(2),
traditionally known as participating groups for the syntheꢀ
sis of 1,2ꢀtrans glycosides,5 can now assist in the formaꢀ
tion of either 1,2ꢀcis6 or 1,2ꢀtrans glycosides.7 Remote
protecting groups at positions O(3), O(4), and/or O(6)
may also affect the stereoselectivity by means of participaꢀ
tion,8 conformational restriction,9 Hꢀbond mediated agꢀ
lycone delivery (vide infra),10 steric hindrance,11 and/or
electron withdrawal.12
X = CH2 (picolinyl), C=O (picoloyl)
The HAD approach has already been successfully apꢀ
plied to the stereoselective synthesis of glucosides, galacꢀ
tosides, rhamnosides,10 and mannosides13 by our group,
arabinofuranosides by the Young group,14 and 2ꢀdeoxy
glycosides by Mong and coꢀworkers.15 The utility of this
approach was extended to the synthesis of a ꢀmannan13
and a series of linear and branched ꢀglucans (up to
a pentasaccharide).16a Recently, K. Le Mai Hoang and
X.ꢀW. Liu reported on HAD involving 2ꢀcyanobenzyl
group neighboring the anomeric center.16b More recently,
we investigated the effect of various leaving groups
(Sꢀphenyl, Sꢀtolyl, S/Oꢀimidates) and devised an effecꢀ
tive ꢀglycosylation protocol with bromine activation at
ambient temperature.17 In conjunction with this effort,
herein we report our first attempt to diversify protecting
groups that may have an effect on the stereoselectivity of
glycosylation. This study was prompted by an idea of usꢀ
Recently, our laboratory has been investigating the
stereodirecting effect of remote picolinyl (Pic) and picoꢀ
loyl (Pico) substituents. Picolinyl at O(2) formally particꢀ
ipates at the anomeric center and gives 1,2ꢀtrans glycoꢀ
sides via the sixꢀmembered ring intermediate.7b The acꢀ
tion of the remote picolinyl and related picoloyl substituꢀ
ents is totally different. Not being able to participate at the
anomeric center directly, picolinyl nitrogen forms the hyꢀ
drogen bond with the incoming glycosyl acceptor (Scheme 1).
As a result, a very high facial selectivity, always syn in
respect to the picolinyl substituent at O(6), is observed.10
This, rather unexpected involvement of remote picolinyl
substituents, was termed as Hꢀbondꢀmediated aglycone
delivery (HAD).
* On the occasion of the 100th anniversary of the birth of Acadeꢀ
mician N. K. Kochetkov (1915—2005).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1107—1118, May, 2015.
1066ꢀ5285/15/6405ꢀ1107 © 2015 Springer Science+Business Media, Inc.

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Visansirikul et al.
Scheme 2
R = 2ꢀF (a), 3ꢀF (b), 4ꢀF (c), H (d)
Reagents and conditions: promoter, 1,2ꢀdichloroethane, molecular sieves 4 Å, –30 C20 C.
ing the fluorinated benzoyl substituents in lieu of picoloyl
substituents that are prone to side reactions with excess
electrophile in glycosylation.10 We anticipated that the
electronegative fluorine would act as the hydrogen bond
acceptor site and hence would promote Hꢀbond mediated
synꢀstereoselectivity like in the traditional HAD reactions
with picoloyl groups.
To probe this concept, we obtained 6ꢀOꢀ(2ꢀfluoroꢀ
benzoyl) glycosyl donor 1a and investigated its reactivity
and stereoselectivity using glycosyl acceptor 218 under
standard HAD reaction conditions10 (Scheme 2). It should
be noted that HAD reactions give higher synꢀselectivity in
high dilution conditions (5 mmol L–1), yet the high diluꢀ
tion has practically no effect on the reaction rate. Occaꢀ
sionally, HADꢀmediated reactions proceed even faster in
high dilution. This trend drastically differs from reactions
with conventional glycosyl donors that are incapable of
HAD, although stereoselectivity enhancement at lower
concentrations has been observed in other applications.19
Consistently with previous observations made with HAD,
glycosidation of glycosyl donor 1a with glycosyl accepꢀ
tor 2 in high dilution (glycosyl donor concentration of
5 mmol L–1) or regular concentration (glycosyl donor conꢀ
centration of 50 mmol L–1) conditions proceeded equally
fast. Disaccharide 3a was obtained in 6 h in both cases in
a high yield of 91—95% (Table 1, entries 1 and 2). The
stereoselectivity in these experiments was very dissimilar,
but it was opposite to that expected from the HADꢀmediꢀ
ated reactions. Thus, both experiments preferentially gave
ꢀlinked disaccharide 3a, antiꢀselectivity in respect to the
fluorobenzoyl substituent, and the high dilution experiꢀ
ment was much more selective ( :  = 7.2 : 1, entry 1
versus  :  = 2.3 : 1, entry 2). Likewise, 3ꢀfluorobenzoyl
(1b) and 4ꢀfluorobenzoyl (1c) glycosyl donors gave comꢀ
parable results in terms of reactivity, yield, and stereoꢀ
selectivity (see Table 1, entries 3—6). Conversely, reacꢀ
Table 1. Glycosylation of glycosyl acceptor 2 with glycosyl donors 1a—d
Entry
Glycosyl
donor
Donor concentration
/mmol L–1
Promoter
t/h
Product
Yield (%)
( : )
1
2
3
4
5
6
7*
8*
9*
10
11
12
1a
1a
1b
1b
1c
1c
1d
1d
1b
1b
1b
1b
15
50
15
50
15
50
15
50
15
15
15
15
DMTST
DMTST
DMTST
DMTST
DMTST
DMTST
DMTST
DMTST
IDCP
16
16
15
20
16
18
72
72
72
11
13
15
3a
3a
3b
3b
3c
3c
3d
3d
3b
3b
3b
3b
91 (7.2 : 1)
95 (2.3 : 1)
87 (8.2 : 1)
92 (3.1 : 1)
85 (5.4 : 1)
85 (2.9 : 1)
68 (4.9 : 1)
58 (2.8 : 1)
47 (3.1 : 1)
87 (9.0 : 1)
95 (7.3 : 1)
94 (9.7 : 1)
NIS/TfOH
NIS/TMSOTf
NIS/TESOTf
Note. DMTST is dimethyl(methylthio)sulfonium trifluoromethanesulfonate, IDCP is iodonium dicollidine perchlorate,
NIS is Nꢀiodosuccinimide, TfOH is triflic acid, TMSOTf is trimethylsilyl triflate, TESOTf is triethylsilyl triflate.
* Incomplete reaction.

Halobenzoyl groups in glycosylation
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1109
tions of glycosyl donor 1d20 equipped with unsubstituted
6ꢀOꢀbenzoyl substituent were very sluggish under these
reaction conditions and failed to go to completion even
after 72 h (entries 7 and 8). Although the stereoselectivity
trend with glycosyl donor 1d was similar, stereoselectivity
provided by glycosyl donor 1d was lower than that obꢀ
served with fluorinated glycosyl donors 1a—c, particularly
evident in the high dilution experiment (cf. entries 1, 3, 5,
and 7).
In attempt to optimize the reaction conditions, we
selected glycosyl donor 1b that gave the best results in the
preliminary experiments with dimethyl(methylthio)sulfꢀ
onium trifluoromethanesulfonate (DMTST). Having inꢀ
vestigated various promoters (see Table 1, entries 9—12)
we observed no drastic difference in stereoselectivity and
yields. However, the decrease in stereoselectivity obtained
with iodonium dicollidine perchlorate (IDCP), that is
known to favor the formation of ꢀlinked products, was
somewhat puzzling (entry 9). Reactions with NIS/TfOH,
NIS/TMSOTf and NIS/TESOTf (NIS is Nꢀiodosuccinꢀ
imide; TfOH, TMSOTf, and TESOTf are triflic acid and
its trimethylsilyl and triethylsilyl ethers, respectively), all
of which are amongst the strongest promoters for thioꢀ
glycosides, proceeded swiftly and provided 3b in high yields
and stereoselectivities (entries 10—12: yield 87—95%,
 :  = (7.3—9.7) : 1).
The preliminary set of experiments indicates that fluꢀ
orinated 6ꢀOꢀbenzoyl group can enhance the reactivity of
glycosyl donors and provide higher ꢀstereoselectivity in
glycosylation reactions in comparison to that of 6ꢀOꢀ
benzoylated donor. Although the stereoselectivity observed
is not consistent with the general concept of the HAD, we
cannot entirely rule out a possibility of HAD from the
ꢀface of the oxacarbenium intermediate ring (Fig. 1,
structure A). Other modes of action can be also anticipated:
the formal participation of the carbonyl via acyloxonium B
or the formal coordination to fluorine (intermediate C).
To delineate between the possible pathways and probe
the reaction mechanism we set up a number of test experꢀ
iments. We initially thought that if the aglycone delivery is
occurring via the bottom face (see Fig. 1, intermediate A),
ꢀdonor 4 would help to obtain enhanced ꢀselectivity
(Scheme 3, equation (2) and Table 2, entries 13, 14). Howꢀ
ever, no significant difference was detected, and the slight
enhancement of ꢀselectivity could be indicative of the
departed leaving group blocking the bottom face and hence
shielding it from the nucleophilic attack. To gain a better
insight, we performed glycosylation of TMSꢀprotected glyꢀ
cosyl acceptor 5 (see Scheme 3, equation (2) and Table 2,
entry 15)21, which has a profound effect on HADꢀmediatꢀ
ed reactions. That is because the TMSꢀgroup excludes the
possibility of Hꢀbonding between the glycosyl donor and
the glycosyl acceptor components.10 In this application,
no difference was observed in comparison to the earlier
experiments with glycosyl acceptor 2 indicating that the
selectivity observed is not due to the HAD from the botꢀ
tom face. Hence, we believe that the intermediate A can
be excluded from further consideration.
We cannot completely rule out the possibility of the
acyloxonium intermediate B formation. The result of glyꢀ
cosylation of glycosyl acceptor 2 with glycosyl donor 6
(see Scheme 3, equation (3)) indicates the importance of
the carbonyl group. Although its actual mode of action
can relate to electronic factors or the restricted rotation of
ester versus ether at O(6). This may be somewhat insignifꢀ
icant with unsubstituted benzoyl/benzyl, but becomes
much more profound in the substituted derivatives. We
believe that intermediate C offers a viable explanation of
the enhanced stereoselectivity and reactivity. In this
context, 3ꢀfluorobenzylated glycosyl donor 6 has no such
effect (or a much weaker effect) due to the much more
flexible nature of methylene versus carbonyl. The role
of the halogen may also relate to its ability to repel the
nucleophile from the top face either electronically or
sterically.
Since the role of 6ꢀOꢀfluorobenzoyl via the HAD is
unlikely, we decided to investigate other halogenated benꢀ
zoyls to acquire possible relationships between electroneꢀ
gativity, bulkiness, stereoselectivity, and reactivity. Thereꢀ
fore, we obtained a series of glycosyl donors equipped with
all positional isomers of chlorinated and brominated 6ꢀOꢀ
benzoyl group (glycosyl donors 1e—j) (Scheme 4, Table 3).
It should be noted that in all cases faster reactions and
higher ꢀstereoselectivity were observed in high dilution
experiments. Therefore, only these experiments are preꢀ
sented in Table 3 and more detail (including experiments
Fig. 1. Possible modes of action of 6ꢀOꢀfluorobenzoyl group in glycosylation.

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Visansirikul et al.
Scheme 3
Reagents and conditions: i. promoter (see Table 2), 1,2ꢀdichloroethane, molecular sieves 4 Å, –30 C20 C.
under regular conditions) is given in Experimental. Thus,
glycosidation of 6ꢀOꢀ(2ꢀchlorobenzoyl) glycosyl donor 1e
with glycosyl acceptor 2 gave good ꢀselectivity and the
corresponding disaccharide 3e was isolated in 95% yield
with  :  = 6.9 : 1 (see Table 3, entry 18). Similarly, 3ꢀ (1f)
and 4ꢀchlorobenzoylated (1g) glycosyl donors gave high
ꢀselectivity and excellent yields (yields of 91 and 90%,
 :  = 7.3 : 1 and 6.0 : 1, respectively; see entries 19 and 20,
respectively). A very similar set of results was obtained
with a series of bromobenzoyl derivatives (entries 21—23).
The results in Tables 1 and 3 indicate that the presence of
a halogen in the benzoyl ring at O(6) has a profound effect
on the donor reactivity in comparison to that of 6ꢀOꢀ
benzoylated counterpart. However, the nature of the haloꢀ
gen and even its position on the benzoyl ring has practiꢀ
cally effect on neither the stereoselectivity nor reactivity.
Table 2. Probing the glycosylation mechanism*
Entry
Glycosyl
donor
Donor
concentration
/mmol L–1
Glycosyl
acceptor
Promoter
t/h
Product
Yield (%)
( : )
13
14
15
16
17
4
1b
1b
6
15
15
15
15
50
2
5
5
2
2
DMTST
NIS/TfOH
DMTST
DMTST
DMTST
4.0
2.5
8.0
3.0
4.5
3b
3b
3b
7
98 (5.8 : 1)
90 (9.0 : 1)
70 (5.7 : 1)
61 (1.2 : 1)
85 (1 : 1.3)
6
7
* Reaction conditions: 1,2ꢀdichloroethane, molecular sieves 4 Å, –30 C20 C.

Halobenzoyl groups in glycosylation
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1111
Scheme 4
R = 2ꢀCl (e), 3ꢀCl (f), 4ꢀCl (g), 2ꢀBr (h), 3ꢀBr (i), 4ꢀBr (j)
Reagents and conditions: DMTST, 1,2ꢀdichloroethane, molecular sieves 4 Å, –30 C20 C.
Scheme 5
To diversify this further, we investigated the effect of
halobenzoyl group at O(4) on glycosylation (Scheme 5).
For this purpose, we obtained a range of glycosyl doꢀ
nors 8a—f (the key results are summarized in Table 4).
Again, faster reactions and higher stereoselectivities
were observed in high dilution experiments. All of the
4ꢀOꢀhalobenzoyl glycosyl donors 8a—e showed insignifiꢀ
cant ꢀselectivity:  :  ratio range from 1 : 1.4 to 1 : 2.7
(see Table 4, entries 24—28). Note that 4ꢀOꢀbenzoyl glycꢀ
Table 3. 6ꢀOꢀHalobenzoyl (1e—g) and 6ꢀOꢀbromobenzoyl (1h—j)
glycosyl donors in glycosylation of glycosyl acceptor 2*
Entry
Glycosyl
donor
t/h
Product
Yield (%)
( : )
18
19
20
21
22
23
1e
1f
1g
1h
1i
9
6
6
6
5
4
3e
3f
3g
3h
3i
95 (6.9 : 1)
91 (7.3 : 1)
90 (6.0 : 1)
96 (5.5 : 1)
87 (6.1 : 1)
96 (7.9 : 1)
R = 2ꢀF (a), 3ꢀF (b), 4ꢀF (c), 2ꢀBr (d), 3ꢀBr (e), H (f)
Reagents and conditions: DMTST, 1,2ꢀdichloroethane, molecuꢀ
lar sieves 4 Å, –30 C20 C.
1j
3j
* Concentration of glycosyl donor is 5 mmol L–1
.
osyl donor 8f22 gave stereoselectivity (entry 29) comparaꢀ
ble with halobenzoyl glycosyl donors 8a—e, yet much slowꢀ
er reaction.
Table 4. 4ꢀOꢀHalobenzoyl glycosyl donors 8a—f in glycosylation
of glycosyl acceptor 2*
In conclusion, we observed a very unusual effect of
halobenzoyl substituents on the reactivity and stereoselecꢀ
tivity of thioglucosyl donors. The effect varies drastically
from the expected disarming effect of electronꢀwithꢀ
drawing substituents that would be expected less reacꢀ
tive in glycosylations. We already performed a variety
of mechanistic experiments and ruled out the involvement
of HAD in enhancing the reactivity and controlling
the stereoselectivity. Further studies to elucidate the
exact nature of this unusual participation of halobenzoyl
substituents in glycosylation are currently underway in
our laboratory.
Entry
Glycosyl
donor
t/h
Product
Yield (%)
( : )
24
25
26
27
28
29**
8a
8b
8c
8d
8e
8f
6
6
5
6
4
9a
9b
9c
9d
9e
9f
98 (1 : 1.4)
81 (1 : 2.4)
83 (1 : 2.0)
75 (1 : 2.7)
95 (1 : 2.5)
64 (1 : 3.0)
72
* Concentration of glycosyl donor is 5 mmol L–1
** Incomplete reaction.
.

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Visansirikul et al.
purified by column chromatography on silica gel (gradient eluꢀ
tion with ethyl acetate—hexane) to afford the title compound 1b
as a white amorphous solid (561 mg, 90%). Rf 0.70 (ethyl aceꢀ
tate—hexane, 2 : 3 (v/v)), []D26 +35.9 (c 1, CHCl3). 1H NMR,
: 1.23 (t, 3 H, SCH2CH3, J = 7.4 Hz); 2.68 (m, 2 H, SCH2CH3);
3.42 (dd, 1 H, H(2), J2,3 = 8.7 Hz); 3.55 (m, 2 H, H(4), H(5));
Experimental
The reactions were performed using commercial reagents
(Aldrich or Acros) and the ACS grade solvents were purified and
dried according to standard procedures. Column chromatography
was performed on silica gel 60 (EM Science, 70—230 mesh),
reactions were monitored by TLC on Kieselgel 60 F254 (EM
Science). The compounds were detected by examination under
UV light and by charring with 10% sulfuric acid in methanol.
Solvents were removed under reduced pressure at <40 C.
Dichloromethane and 1,2ꢀdichloroethane were distilled from
CaH2 directly prior to application. Molecular sieves (4 Å), used
for reactions, were crushed and activated in vacuo at 390 C
during 8 h in the first instance and then for 2—3 h at 390 C
directly prior to application. Optical rotations were measured at
Jasco Pꢀ1020 polarimeter. 1H NMR spectra were recorded at
300 MHz (Bruker Avance 300), 13C NMR spectra were recordꢀ
ed at 75 MHz (Bruker Avance 300) or at 125 MHz (Bruker
ARXꢀ500) in CDCl3. The 1H chemical shifts are referenced to
the residual solvent signal (CHCl3, H 7.27) and the 13C chemiꢀ
cal shifts are referenced to the central signal of CDCl3 (C 77.23).
High resolution fastꢀatom bombardment (FAB) mass spectroꢀ
metry were made with the a JMSꢀ700 (JEOL MStation).
3.69 (dd, 1 H, H(3), J3,4 = 8.8 Hz); 4.34 (dd, 1 H, H(6a), J5,6a
=
= 5.0 Hz, J6a,6b = 12.0 Hz); 4.46 (d, 1 H, H(1), J1,2 = 9.8 Hz);
4.52 (dd, 1 H, H(6b), J5,6b = 2.6 Hz); 4.69 (dd, 2 H, CH2Ph,
2J = 11.8 Hz); 4.79 (dd, 2 H, CH2Ph, 2J = 10.2 Hz); 4.86 (dd, 2 H,
2
CH2Ph, J = 10.1 Hz); 7.16—7.35 (m, 17 H, aromatic); 7.61
(dd, 1 H, aromatic, J = 9.3 Hz); 7.74 (dd, 1 H, aromatic, J = 6.6 Hz).
13C NMR, : 15.4, 25.3, 64.3, 75.4, 75.8, 76.1, 77.1, 77.9,
81.9, 85.3, 86.8, 116.6, 116.9, 120.2, 120.5, 125.6, 128.0 (3 C),
128.1, 128.2, 128.3 (2 C), 128.5 (2 C), 128.6 (2 C), 128.7 (2 C),
130.2, 132.2, 132.3, 137.7, 138.0, 138.4, 164.3. MS (FAB),
m/z: 639.2183 [M + Na]+. Calculated for C36H37FO6SNa:
639.2192.
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(4ꢀfluorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1c). 4ꢀFluorobenzoic acid (170 mg, 1.21 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 10 (300 mg,
0.61 mmol) in CH2Cl2 (20 mL) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (100 mL) and washed with saturated aqueꢀ
ous NaHCO3 (20 mL) and water (220 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 1c as a white amorphous solid (351 mg, 94%).
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2ꢀfluorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1a). 2ꢀFluorobenzoic acid (112 mg, 0.80 mmol),
3ꢀ(3ꢀdimethylaminopropyl)ꢀ1ꢀethylcarbodiimide hydrochloride
(EDC) (115 mg, 0.60 mmol), and DMAP (12 mg, 0.10 mmol)
were added to a stirred solution of ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ1ꢀ
thioꢀꢀDꢀglucopyranoside (10)23 (200 mg, 0.40 mmol) in CH2Cl2
(10 mL) and the resulting mixture was stirred at room temperaꢀ
ture for 18 h. The reaction mixture was diluted with CH2Cl2
26
Rf 0.70 (ethyl acetate—hexane, 2 : 3 (v/v)), []D +48.2
(c 1, CHCl3). 1H NMR, : 1.23 (t, 3 H, SCH2CH3, J = 7.4 Hz);
2.68 (m, 2 H, SCH2CH3); 3.42 (dd, 1 H, H(2), J2,3 = 9.1 Hz);
3.58 (m, 2 H, H(4), H(5)); 3.69 (dd, 1 H, H(3), J3,4 = 8.7 Hz);
4.35 (dd, 1 H, H(6a), J5,6a = 4.7 Hz, J6a,6b = 11.9 Hz); 4.46 (d, 1 H,
H(1), J1,2 = 10.8 Hz); 4.52 (dd, 1 H, H(6b), J5,6b = 1.5 Hz); 4.68
(50 mL) and washed with saturated aqueous NaHCO3 (10 mL)
and water (210 mL). The organic phase was separated, dried
with MgSO4, and concentrated in vacuo. The residue was puriꢀ
fied by column chromatography on silica gel (gradient elution
with ethyl acetate—hexane) to afford the title compound 1a as
a white amorphous solid (226 mg, 92%). Rf 0.70 (ethyl acetate—
2
2
(dd, 2 H, CH2Ph, J = 10.8 Hz); 4.79 (dd, 2 H, CH2Ph, J =
= 10.2 Hz); 4.87 (dd, 2 H, CH2Ph, 2J = 10.2 Hz); 7.04 (dd, 2 H,
aromatic, J = 8.7 Hz); 7.16—7.35 (m, 15 H, aromatic); 7.96 (dd,
2 H, aromatic, J = 5.5 aromatic). 13C NMR, : 15.3, 25.3, 64.1,
75.4, 75.8, 76.1, 77.2, 77.4, 77.8, 81.9, 85.3, 86.8, 115.6, 115.9,
126.2, 126.4, 128.0, 128.1 (3 C), 128.2, 128.3 (2 C), 128.5 (2 C),
128.6 (2 C), 128.7 (2 C), 130.2, 132.3, 132.4, 137.7, 138.0, 138.4,
165.4. MS (FAB), m/z: 639.2187 [M + Na]+. Calculated for
C36H37FO6SNa: 639.2192.
hexane, 2 : 3 (v/v)), []D +21.6 (c 1, CHCl3). 1H NMR, :
27
1.23 (t, 3 H, SCH2CH3, J = 7.4 Hz); 2.68 (m, 2 H, SCH2CH3);
3.42 (dd, 1 H, H(2), J2,3 = 8.8 Hz); 3.55 (m, 2 H, H(4), H(5));
3.69 (dd, 1 H, H(3), J3,4 = 8.7 Hz); 4.34 (dd, 1 H, H(6a), J5,6a
= 4.8 Hz, J6a,6b = 11.9 Hz); 4.46 (d, 1 H, H(1), J1,2 = 9.7 Hz);
4.52 (dd, 1 H, H(6b), J5,6b = 1.5 Hz); 4.70 (dd, 2 H, CH2Ph,
2J = 10.7 Hz); 4.79 (dd, 2 H, CH2Ph, 2J = 10.2 Hz); 4.86 (dd, 2 H,
=
2
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2ꢀchlorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1e). 2ꢀChlorobenzoic acid (190 mg, 1.22 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 10 (300 mg,
0.61 mmol) in CH2Cl2 (20 mL) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (100 mL) and washed with saturated aqueꢀ
ous NaHCO3 (20 mL) and water (220 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 1e as a white amorphous solid (345 mg, 90%).
CH2Ph, J = 10.9 Hz); 7.02—7.32 (m, 17 H, aromatic); 7.43
(m, 1 H, aromatic); 7.84 (dd, 1 H, aromatic, J = 7.6 Hz). 13C NMR,
: 15.3, 25.1, 64.2, 75.3, 75.7, 79.1, 77.1, 77.8, 81.9, 85.2, 86.8,
117.0, 117.3, 118.6, 118.7, 124.1, 128.0 (3 C), 128.1, 128.2, 128.3
(2 C), 128.5 (2 C), 128.6 (2 C), 128.7 (2 C), 132.4, 134.8, 134.9,
137.8, 138.0, 138.5, 164.3. MS (FAB), m/z: 639.2196 [M + Na]+.
Calculated for C36H37FO6SNa: 639.2192.
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀfluorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1b). 3ꢀFluorobenzoic acid (283 mg, 2.02 mmol),
EDC (291 mg, 1.52 mmol), and DMAP (24 mg, 0.20 mmol) were
added to a stirred solution of compound 10 (500 mg, 1.01 mmol)
in CH2Cl2 (20 mL) and the resulting mixture was stirred at room
temperature for 18 h. The reaction mixture was diluted with
CH2Cl2 (100 mL) and washed with saturated aqueous NaHCO3
(20 mL) and water (220 mL). The organic phase was separated,
dried with MgSO4, and concentrated in vacuo. The residue was
27
Rf 0.69 (ethyl acetate—hexane, 2 : 3 (v/v)), []D +19.0 (c 1,
CHCl3). 1H NMR, : 1.23 (t, 3 H, SCH2CH3, J = 7.4 Hz);
2.68 (m, 2 H, SCH2CH3); 3.42 (dd, 1 H, H(2), J2,3 = 8.8 Hz);
3.58 (m, 2 H, H(4), H(5)); 3.69 (dd, 1 H, H(3), J3,4 = 8.8 Hz);

Halobenzoyl groups in glycosylation
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1113
4.38 (dd, 1 H, H(6a), J5,6a = 4.7 Hz, J6a,6b = 11.9 Hz); 4.46 (d, 1 H,
H(1), J1,2 = 9.7 Hz); 4.57 (dd, 1 H, H(6b), J5,6b = 2.0 Hz); 4.70
(dd, 2 H, CH2Ph, 2J = 10.8 Hz); 4.79 (dd, 2 H, CH2Ph,
2J = 10.2 Hz); 4.86 (dd, 2 H, CH2Ph, 2J = 10.8 Hz); 7.18—7.38
(m, 18 H, aromatic); 7.75 (dd, 1 H, aromatic, J = 8.2 Hz).
13C NMR, : 15.3, 25.1, 64.4, 75.4, 75.7, 76.1, 77.1, 77.8, 81.9,
85.2, 86.8, 126.7, 128.0 (3 C), 128.1, 128.2, 128.3 (2 C), 128.5
(2 C), 128.6 (2 C), 128.7 (4 C), 129.8, 131.3, 131.9, 132.9, 134.1,
137.7, 138.0, 138.4, 165.4. MS (FAB), m/z: 655.1892 [M + Na]+.
Calculated for C36H37ClO6SNa: 655.1897.
128.6 (2 C), 128.7 (4 C), 128.9 (2 C), 131.2 (2 C), 137.6, 137.9,
138.4, 139.7, 165.4. MS (FAB), m/z: 655.1885 [M + Na]+. Calꢀ
culated for C36H37ClO6SNa: 655.1897.
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2ꢀbromobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1h). 2ꢀBromobenzoic acid (243 mg, 1.21 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 10 (300 mg,
0.61 mmol) in CH2Cl2 (15 mL) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (70 mL) and washed with saturated aqueꢀ
ous NaHCO3 (15 mL) and water (215 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 1h as a white amorphous solid (383 mg, 93%).
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀchlorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1f). 3ꢀChlorobenzoic acid (190 mg, 1.22 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 10 (300 mg,
0.61 mmol) in CH2Cl2 (20 mL) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (100 mL) and washed with saturated aqueꢀ
ous NaHCO3 (20 mL) and water (220 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 1f as a white amorphous solid (368 mg, 96%).
27
Rf 0.69 (ethyl acetate—hexane, 2 : 3 (v/v)), []D +19.8 (c 1,
CHCl3). 1H NMR, : 1.23 (t, 3 H, SCH2CH3, J = 7.4 Hz);
2.68 (m, 2 H, SCH2CH3); 3.41 (dd, 1 H, H(2), J2,3 = 8.8 Hz);
3.58 (m, 2 H, H(4), H(5)); 3.69 (dd, 1 H, H(3), J3,4 = 8.8 Hz);
4.38 (dd, 1 H, H(6a), J5,6a = 4.9 Hz, J6a,6b = 11.9 Hz); 4.45 (d, 1 H,
H(1), J1,2 = 9.8 Hz); 4.57 (dd, 1 H, H(6b), J5,6b = 1.7 Hz); 4.70
(dd, 2 H, CH2Ph, 2J = 10.7 Hz); 4.79 (dd, 2 H, CH2Ph,
2J = 10.2 Hz); 4.86 (dd, 2 H, CH2Ph, 2J = 10.8 Hz); 7.20—7.32
(m, 17 H, aromatic); 7.61 (m, 1 H, aromatic); 7.73 (m, 1 H,
aromatic). 13C NMR, : 15.3, 25.2, 64.5, 75.4, 75.7, 76.1, 77.1,
77.9, 81.9, 85.2, 86.8, 122.1, 127.3, 127.9, 128.0 (2 C), 128.1,
128.2, 128.3 (2 C), 128.5 (2 C), 128.6 (2 C), 128.7 (4 C), 131.7,
131.8, 131.9, 132.9, 134.6, 137.7, 138.0, 138.4, 165.4. MS (FAB),
m/z: 699.1390 [M + Na]+. Calculated for C36H37BrO6SNa:
699.1391.
26
Rf 0.69 (ethyl acetate—hexane, 2 : 3 (v/v)), []D +43.4 (c 1,
CHCl3). 1H NMR, : 1.24 (t, 3 H, SCH2CH3, J = 7.4 Hz);
2.68 (m, 2 H, SCH2CH3); 3.42 (dd, 1 H, H(2), J2,3 = 9.0 Hz);
3.58 (m, 2 H, H(4), H(5)), 3.69 (dd, 1 H, H(3), J3,4 = 8.6 Hz);
4.32 (dd, 1 H, H(6a), J5,6a = 5.1 Hz, J6a,6b = 10.9 Hz); 4.46 (d, 1 H,
H(1), J1,2 = 9.7 Hz); 4.54 (dd, 1 H, H(6b), J5,6b = 1.7 Hz); 4.69
(dd, 2 H, CH2Ph, 2J = 10.8 Hz); 4.79 (dd, 2 H, CH2Ph,
2J = 10.2 Hz); 4.86 (dd, 2 H, CH2Ph, 2J = 10.8 Hz); 7.16—7.34
(m, 16 H, aromatic); 7.46 (dd, 1 H, aromatic, J = 8.0 Hz);
7.83 (dd, 1 H, aromatic, J = 7.8 Hz); 7.90 (dd, 1 H, aromatic,
J = 1.8 Hz). 13C NMR, : 15.4, 25.3, 64.4, 75.3, 75.8, 76.1,
77.1, 77.8, 81.9, 85.3, 86.8, 127.9, 128.0 (3 C), 128.1, 128.2,
128.3 (2 C), 128.5 (2 C), 128.6 (2 C), 128.7 (4 C), 129.8 (2 C),
131.8, 133.3, 134.6, 137.6, 137.9, 138.4, 165.4. MS (FAB),
m/z: 655.1887 [M + Na]+. Calculated for C36H37ClO6SNa:
655.1897.
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀbromobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1i). 3ꢀBromobenzoic acid (406 mg, 2.02 mmol),
EDC (291 mg, 1.52 mmol), and DMAP (24 mg, 0.20 mmol) were
added to a stirred solution of compound 10 (500 mg, 1.01 mmol)
in CH2Cl2 (20 mL) and the resulting mixture was stirred at room
temperature for 18 h. The reaction mixture was diluted with
CH2Cl2 (100 mL) and washed with saturated aqueous NaHCO3
(20 mL) and water (220 mL). The organic phase was separated,
dried with MgSO4, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (gradient eluꢀ
tion with ethyl acetate—hexane) to afford the title compound 1i
as a white amorphous solid (619 mg, 91%). Rf 0.69 (ethyl aceꢀ
tate—hexane, 2 : 3 (v/v)), []D27 +34.8 (c 1, CHCl3). 1H NMR,
: 1.24 (t, 3 H, SCH2CH3, J = 7.4 Hz); 2.68 (m, 2 H, SCH2CH3);
3.43 (dd, 1 H, H(2), J2,3 = 9.2 Hz); 3.56 (m, 2 H, H(4), H(5));
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(4ꢀchlorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1g). 4ꢀChlorobenzoic acid (190 mg, 1.22 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 10 (300 mg,
0.61 mmol) in CH2Cl2 (20 mL) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (100 mL) and washed with saturated aqueꢀ
ous NaHCO3 (20 mL) and water (220 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 1g as a white amorphous solid (377 mg, 98%).
3.69 (dd, 1 H, H(3), J3,4 = 8.6 Hz); 4.31 (dd, 1 H, H(6a), J5,6a
=
= 5.3 Hz, J6a,6b = 11.9 Hz); 4.46 (d, 1 H, H(1), J1,2 = 9.7 Hz);
4.53 (dd, 1 H, H(6b), J5,6b = 1.8 Hz); 4.68 (dd, 2 H, CH2Ph,
2J = 10.9 Hz); 4.79 (dd, 2 H, CH2Ph, 2J = 10.2 Hz); 4.86 (dd, 2 H,
2
CH2Ph, J = 10.7 Hz); 7.17—7.34 (m, 16 H, aromatic); 7.62
27
Rf 0.69 (ethyl acetate—hexane, 2 : 3 (v/v)), []D +30.5 (c 1,
(d, 1 H, aromatic, J = 8.1 Hz); 7.87 (d, 1 H, aromatic, J = 7.8 Hz);
7.87 (d, 1 H, aromatic, J = 1.5 Hz). 13C NMR, : 15.4, 25.3,
64.4, 75.3, 75.8, 76.1, 77.1, 77.8, 81.9, 85.3, 86.8, 122.6, 128.0
(3 C), 128.1, 128.2, 128.3 (2 C), 128.4, 128.5 (2 C), 128.6 (2 C),
128.7 (4 C), 130.1, 131.9, 132.8, 136.2, 137.6, 138.0, 138.3,
165.4. MS (FAB), m/z: 699.1380 [M + Na]+. Calculated for
C36H37BrO6SNa: 699.1391.
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(4ꢀbromobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (1j). 4ꢀBromobenzoic acid (243 mg, 1.21 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 10 (300 mg,
CHCl3). 1H NMR, : 1.23 (t, 3 H, SCH2CH3, J = 7.4 Hz);
2.68 (m, 2 H, SCH2CH3); 3.42 (dd, 1 H, H(2), J2,3 = 8.8 Hz);
3.57 (m, 2 H, H(4), H(5)); 3.69 (dd, 1 H, H(3), J3,4 = 8.7 Hz);
4.35 (dd, 1 H, H(6a), J5,6a = 4.7 Hz, J6a,6b = 11.9 Hz); 4.46 (d, 1 H,
H(1), J1,2 = 9.7 Hz); 4.53 (dd, 1 H, H(6b), J5,6b = 1.5 Hz); 4.68
(dd, 2 H, CH2Ph, 2J = 10.8 Hz); 4.79 (dd, 2 H, CH2Ph,
2J = 10.1 Hz); 4.86 (dd, 2 H, CH2Ph, 2J = 10.8 Hz); 7.18—7.35
(m, 17 H, aromatic); 7.87 (dd, 1 H, aromatic, J = 6.8 Hz).
13C NMR, : 15.4, 25.3, 64.2, 75.3, 75.8, 76.1, 77.1, 77.8, 81.9,
85.3, 86.8, 128.0 (3 C), 128.1, 128.2, 128.3 (2 C), 128.5 (3 C),

1114
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Visansirikul et al.
0.61 mmol) in CH2Cl2 (15 ml) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (70 mL) and washed with saturated aqueꢀ
ous NaHCO3 (15 mL) and water (215 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 1j as a white amorphous solid (405 mg, 99%).
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (gradient elution with ethyl aceꢀ
tate—hexane) to afford the title compound 6 as a white amorꢀ
phous solid (212 mg, 87%). Rf 0.78 (ethyl acetate—hexane, 2 : 3
27
(v/v)), []D +3.55 (c 1, CHCl3). 1H NMR, : 1.28 (t, 3 H,
SCH2CH3, J = 7.4 Hz); 2.72 (m, 2 H, SCH2CH3); 3.37—3.46
(m, 2 H, H(2), H(5), J2,3 = 8.6 Hz); 3.52—3.72 (m, 4 H,
H(3), H(4), H(6a), H(6b), J3,4 = 8.9 Hz); 4.43 (d, 1 H, H(1),
J1,2 = 9.7 Hz); 4.50 (br.s, 2 H, CH2Ph); 4.67 (dd, 2 H, CH2Ph,
2J = 13.1 Hz); 4.79 (dd, 2 H, CH2Ph, 2J = 10.2 Hz); 4.85 (dd, 2 H,
27
Rf 0.69 (ethyl acetate—hexane, 2 : 3 (v/v)), []D +28.6 (c 1,
CHCl3). 1H NMR, : 1.22 (t, 3 H, SCH2CH3, J = 7.4 Hz);
2.68 (m, 2 H, SCH2CH3); 3.42 (dd, 1 H, H(2), J2,3 = 8.9 Hz);
3.57 (m, 2 H, H(4), H(5)); 3.69 (dd, 1 H, H(3), J3,4 = 8.8 Hz);
4.34 (dd, 1 H, H(6a), J5,6a = 4.8 Hz, J6a,6b = 11.9 Hz); 4.45 (d, 1 H,
H(1), J1,2 = 9.8 Hz); 4.53 (dd, 1 H, H(6b), J5,6b = 1.3 Hz); 4.68
(dd, 2 H, CH2Ph, 2J = 10.8 Hz); 4.79 (dd, 2 H, CH2Ph,
2J = 10.2 Hz); 4.86 (dd, 2 H, CH2Ph, 2J = 10.8 Hz); 7.17—7.34
(m, 16 H, aromatic); 7.62 (d, 2 H, aromatic, J = 8.6 Hz); 7.87
(d, 1 H, aromatic, J = 8.5 Hz). 13C NMR, : 15.4, 25.3, 64.2,
75.3, 75.8, 76.1, 77.1, 77.8, 81.9, 85.3, 86.8, 128.0 (3 C), 128.1,
128.2, 128.3 (2 C), 128.4, 128.5 (2 C), 128.6 (2 C), 128.7 (4 C),
128.9, 131.4 (2 C), 131.8 (2 C), 137.6, 138.0, 138.4, 165.4.
2
CH2Ph, J = 10.9 Hz); 6.91 (m, 1 H, aromatic); 7.03 (m, 2 H,
aromatic); 7.13—7.34 (m, 16 H, aromatic). 13C NMR,  15.4,
25.2, 69.5, 72.7, 72.8, 75.3, 75.9, 78.1, 79.2, 81.9, 85.2, 86.8,
114.3, 114.4, 114.6, 114.7, 123.1, 127.8, 127.9 (2 C), 128.0 (2 C),
128.5 (2 C), 128.6 (4 C), 129.9, 130.1, 138.1 (2 C), 138.6, 141.0,
141.1, 161.5. MS (FAB), m/z: 625.2397 [M + Na]+. Calculated
for C36H39FO5SNa: 625.2400.
Ethyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2ꢀfluorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (8a). 2ꢀFluorobenzoic acid (170 mg, 1.21 mmol),
EDC (176 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of ethyl 2,3,6ꢀtriꢀOꢀbenzylꢀ1ꢀ
thioꢀꢀDꢀglucopyranoside (11)25 (300 mg, 0.61 mmol) in CH2Cl2
(15 mL) and the resulting mixture was stirred at room temperaꢀ
ture for 18 h. The reaction mixture was diluted with CH2Cl2
(75 mL) and washed with saturated aqueous NaHCO3 (15 mL)
and water (215 mL). The organic phase was separated, dried
with MgSO4, and concentrated in vacuo. The residue was puriꢀ
fied by column chromatography on silica gel (gradient elution
with ethyl acetate—hexane) to afford the title compound 8a as
a white amorphous solid (342 mg, 92%). Rf 0.75 (ethyl acetate—
MS (FAB), m/z: 699.1385 [M
+
Na]+. Calculated for
C36H37BrO6SNa: 699.1391.
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀfluorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (4). 3ꢀFluorobenzoic acid (102 mg, 0.73 mmol),
EDC (104 mg, 0.54 mmol), and DMAP (12 mg, 0.10 mmol) were
added to a stirred solution of ethylꢀ2,3,4ꢀtriꢀOꢀbenzylꢀ1ꢀthioꢀꢀ
Dꢀglucopyranoside24 (180 mg, 0.36 mmol) in CH2Cl2 (20 mL)
and the resulting mixture was stirred at room temperature for 18 h.
The reaction mixture was diluted with CH2Cl2 (100 mL) and
washed with saturated aqueous NaHCO3 (20 mL) and water
(220 mL). The organic phase was separated, dried with MgSO4,
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (gradient elution with ethyl aceꢀ
tate—hexane) to afford the title compound 4 as a white amorꢀ
phous solid (211 mg, 95%). Rf 0.80 (ethyl acetate—hexane, 2 : 3,
hexane, 2 : 3 (v/v)), []D –32.0 (c 1, CHCl3). 1H NMR, :
26
1.49 (t, 3 H, SCH2CH3, J = 7.4 Hz); 2.92 (m, 2 H, SCH2CH3);
3.69 (dd, 1 H, H(2), J2,3 = 9.0 Hz); 3.77 (m, 2 H, H(6a), H(6b));
3.84 (dd, 1 H, H(5), J5,6b = 3.7 Hz); 3.93 (dd, 1 H, H(3),
J3,4 = 9.2 Hz); 4.63 (br.s, 2 H, CH2Ph); 4.69 (d, 1 H, H(1),
J1,2 = 9.8 Hz); 4.87 (dd, 2 H, CH2Ph, 2J = 11.2 Hz); 4.97 (dd, 2 H,
(v/v)), []D +131.4 (c 1, CHCl3). 1H NMR, : 1.26 (t, 3 H,
CH2Ph, J = 10.2 Hz); 5.44 (dd, 2 H, CH2Ph, J4,5 = 9.6 Hz);
27
2
SCH2CH3, J = 7.4 Hz); 2.48 (m, 2 H, SCH2CH3); 3.57 (dd, 1 H,
H(2), J4,5 = 9.0 Hz); 3.86 (dd, 2 H, H(2), J2,3 = 9.5 Hz); 3.94
(dd, 1 H, H(3), J3,4 = 9.3 Hz); 4.42 (dd, 1 H, H(5), J5,6a = 3.2 Hz,
J5,6b = 6.7 Hz); 4.51 (m, 2 H, H(6a), H(6b)); 4.71 (dd, 2 H,
7.19—7.53 (m, 17 H, aromatic); 7.62 (m, 1 H, aromatic); 7.91
(dd, 1 H, aromatic, J = 7.6 Hz). 13C NMR, : 15.3, 25.3, 70.0,
71.8, 73.7, 75.6, 75.8, 77.7, 81.7, 83.9, 85.3, 117.0, 117.3, 118.3,
118.5, 124.1, 124.2, 127.6, 127.7, 127.8 (2 C), 128.0 (2 C), 128.4
(2 C), 128.5 (2 C), 128.6 (2 C), 132.4, 134.8, 134.9, 137.9, 138.0,
138.1, 163.5. MS (FAB), m/z: 639.2182 [M + Na]+. Calculated
for C36H37FO6SNa: 639.2192.
2
2
CH2Ph, J = 11.7 Hz); 4.77 (dd, 2 H, CH2Ph, J = 10.8 Hz);
4.91 (dd, 2 H, CH2Ph, 2J = 10.8 Hz); 5.40 (d, 1 H, H(1), J1,2
=
= 5.3 Hz); 7.21—7.41 (m, 17 H, aromatic); 7.65 (d, 1 H, aroꢀ
matic, J = 9.3 Hz); 7.77 (d, 1 H, aromatic, J = 7.6 Hz).
13C NMR, : 14.9, 23.8, 64.1, 69.1, 72.5, 75.2, 76.0, 77.4,
79.8, 82.7, 83.0, 116.5, 116.8, 120.2, 120.4, 125.4, 125.5, 127.9,
128.0, 128.1, 128.2 (2 C), 128.3 (2 C), 128.6 (3 C), 128.7, 130.1,
130.2, 132.1, 132.2, 137.8, 137.9, 138.5, 165.2. MS (FAB),
m/z: 639.2180 [M + Na]+. Calculated for C36H37FO6SNa:
639.2192.
Ethyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀfluorobenzyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (6). 3ꢀFluorobenzyl bromide (153 mg, 0.81 mmol)
and NaH (60% dispersion in mineral oil, 49 mg, 1.20 mmol)
were added to a solution of compound 10 (200 mg, 0.40 mmol)
in DMF (5.0 mL) and the resulting mixture was stirred at room
temperature for 3 h. The reaction mixture was quenched with
iceꢀwater (5 mL), stirred for 30 min, and then extracted with
ethyl acetate—diethyl ether (1 : 1 (v/v), 3×20 mL). The comꢀ
bined organic extract (60 mL) was washed with cold water
(3×10 mL). The organic phase was separated, dried with MgSO4,
Ethyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(3ꢀfluorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (8b). 3ꢀFluorobenzoic acid (170 mg, 1.21 mmol),
EDC (176 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 11 (300 mg, 0.61
mmol) in CH2Cl2 (15 mL) and the resulting mixture was stirred
at room temperature for 18 h. The reaction mixture was diluted
with CH2Cl2 (75 mL) and washed with saturated aqueous
NaHCO3 (15 mL) and water (215 mL). The organic phase was
separated, dried with MgSO4, and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(gradient elution with ethyl acetate—hexane) to afford the title
compound 8b as a white amorphous solid (326 mg, 87%). Rf 0.75
26
(ethyl acetate—hexane, 2 : 3 (v/v)), []D –50.8 (c 1, CHCl3).
1H NMR, : 1.43 (t, 3 H, SCH2CH3, J = 7.4 Hz); 2.87 (m, 2 H,
SCH2CH3); 3.69 (dd, 1 H, H(2), H(6a), H(6b), J2,3 = 8.9 Hz);
3.77 (dd, 1 H, H(5), J5,6b = 4.5 Hz); 3.85 (dd, 1 H, H(3),
J3,4 = 9.1 Hz); 4.53 (br.s, 2 H, CH2Ph); 4.63 (d, 1 H, H(1),

Halobenzoyl groups in glycosylation
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1115
J1,2 = 9.8 Hz); 4.78 (dd, 2 H, CH2Ph, 2J = 10.3 Hz); 4.92 (dd, 2 H,
CH2Ph, J = 10.2 Hz); 5.34 (dd, 1 H, H(4), J4,5 = 9.6 Hz);
Ethyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(3ꢀbromobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (8e). 3ꢀBromobenzoic acid (245 mg, 1.22 mmol),
EDC (175 mg, 0.92 mmol) and DMAP (15 mg, 0.12 mmol) were
added to a stirred solution of compound 11 (300 mg, 0.61 mmol)
in CH2Cl2 (15 mL) and the resulting mixture was stirred at room
temperature for 18 h. The reaction mixture was diluted with
CH2Cl2 (70 mL) and washed with saturated aqueous NaHCO3
(15 mL) and water (2×15 mL). The organic phase was separated,
dried with MgSO4, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel as described
above to afford the title compound 8e as a white amorphous solid
2
7.17—7.48 (m, 17 H, aromatic); 7.62 (dd, 1 H, aromatic, J= 9.3 Hz);
7.77 (dd, 1 H, aromatic, J = 7.7 Hz). 13C NMR, : 15.3, 25.3,
70.0, 72.0, 73.7, 75.5, 75.8, 77.5, 81.8, 83.5, 85.3, 116.6, 116.9,
120.2, 120.5, 125.6, 127.7, 127.8 (2 C), 128.1 (2 C), 128.3 (2 C),
128.4 (2 C), 128.5 (2 C), 128.6 (2 C), 130.1, 130.2, 131.8, 131.9,
137.8, 137.9, 164.3. MS (FAB), m/z: 639.2197 [M + Na]+. Calꢀ
culated for C36H37FO6SNa: 639.2192.
Ethyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(4ꢀfluorobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (8c). 4ꢀFluorobenzoic acid (170 mg, 1.21 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 11 (300 mg,
0.61 mmol) in CH2Cl2 (20 mL) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (100 mL) and washed with saturated aqueꢀ
ous NaHCO3 (20 mL) and water (220 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 8c as a white amorphous solid (344 mg, 92%).
27
(332 mg, 81%). Rf 0.71 (ethyl acetate—hexane, 2 : 3 (v/v)), []D
–50.1 (c 1, CHCl3). 1H NMR, : 1.43 (t, 3 H, SCH2CH3,
J = 7.4 Hz); 2.87 (m, 2 H, SCH2CH3); 3.60—3.66 (m, 3 H,
H(2), H(6a), H(6b), J2,3 = 8.9 Hz); 3.76 (dd, 1 H, H(5), J5,6a
=
= 4.5 Hz); 3.84 (dd, 1 H, H(3), J3,4 = 9.1 Hz); 4.52 (br.s, 2 H,
CH2Ph); 4.63 (d, 1 H, H(1), J1,2 = 9.8 Hz); 4.77 (dd, 2 H,
2
2
CH2Ph, J = 11.4 Hz); 4.92 (dd, 2 H, CH2Ph, J = 10.4 Hz);
5.33 (dd, 1 H, H(4), J4,5 = 9.7 Hz); 7.16—7.50 (m, 16 H, aroꢀ
matic); 7.72—7.76 (m, 1 H, aromatic); 7.89 (dd, 1 H, aromatic,
J = 7.8 Hz); 8.01 (m, 1 H, aromatic). 13C NMR, : 15.3, 25.3,
70.0, 71.9, 73.7, 75.4, 75.8, 77.7, 81.9, 83.4, 85.3, 122.6, 127.7,
127.8 (3 C), 128.1, 128.2 (2 C), 128.4 (4 C), 128.5, 128.6 (4 C),
130.0, 131.7, 132.8, 136.2, 137.8, 137.9, 164.2. MS (FAB),
m/z: 699.1383 [M + Na]+. Calculated for C36H37BrO6SNa:
699.1391.
27
Rf 0.75 (ethyl acetate—hexane, 2 : 3 (v/v)), []D –42.8 (c 1,
CHCl3). 1H NMR, : 1.43 (t, 3 H, SCH2CH3, J = 7.4 Hz); 2.87
(m, 2 H, SCH2CH3); 3.64 (dd, 1 H, H(2), H(6a), H(6b),
J2,3 = = 8.9 Hz); 3.78 (dd, 1 H, H(5), J5,6b = 4.6 Hz); 3.85
(dd, 1 H, H(3), J3,4 = 9.1 Hz); 4.53 (br.s, 2 H, CH2Ph); 4.63 (d,
1 H, H(1), J1,2 = 9.8 Hz); 4.77 (dd, 2 H, CH2Ph, 2J = 11.3 Hz);
4.91 (dd, 2 H, CH2Ph, 2J = 10.2 Hz); 5.33 (dd, 1 H, H(4),
J4,5 = 9.7 Hz); 7.10—7.49 (m, 17 H, aromatic); 7.96—8.00
(m, 2 H, aromatic). 13C NMR, : 15.3, 25.3, 70.1, 71.8, 73.7,
75.5, 75.8, 77.8, 81.8, 83.7, 85.3, 115.5, 115.8, 126.0 (3 C), 127.7,
127.8 (2 C), 128.1 (2 C), 128.2 (2 C), 128.4 (4 C), 128.5 (2 C),
128.6 (2 C), 132.4, 132.5, 137.9 (2 C), 137.9, 164.5. MS (FAB),
m/z: 639.2183 [M + Na]+. Calculated for C36H37FO6SNa:
639.2192.
Synthesis of disaccharides (general procedure). A mixture of
a glycosyl donor (0.05 mmol), glycosyl acceptor (0.038 mmol),
and freshly activated molecular sieves (4 Å, 200 mg) in 1,2ꢀdiꢀ
chloroethane (1 mL for glycosyl donor concentration of
50 mmol L–1 or 10 mL for glycosyl donor concentration of
5 mmol L–1) was stirred under argon for 1 h. The mixture was
then cooled to –30 C and promoter (DMTST (0.1 mmol)
or IDCP (0.1 mmol) or mixtures NIS (0.1 mmol)—TfOH
(0.01 mmol) or NIS (0.1 mmol)—TMSOTf (0.01 mmol) or NIS
(0.1 mmol)—TESOTf (0.01 mmol), see Tables 1—4) was added.
Cooling was removed and the resulting mixture was allowed to
warm to room temperature. Upon completion, the solid was
filtered off and successively washed with CH2Cl2. The comꢀ
bined filtrate (30—40 mL) was washed with saturated aqueous
Na2S2O3 (10 mL) and water (310 mL). The organic phase was
separated, dried with Na2SO4, and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(gradient elution with ethyl acetate—hexane). Anomeric ratios
(or anomeric purity) were determined by comparison of the inꢀ
tegral intensities of relevant signals in 1H NMR spectra.
Ethyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2ꢀbromobenzoyl)ꢀ1ꢀthioꢀꢀDꢀ
glucopyranoside (8d). 2ꢀBromobenzoic acid (245 mg, 1.22 mmol),
EDC (175 mg, 0.92 mmol), and DMAP (15 mg, 0.12 mmol)
were added to a stirred solution of compound 11 (300 mg,
0.61 mmol) in CH2Cl2 (15 mL) and the resulting mixture was
stirred at room temperature for 18 h. The reaction mixture was
diluted with CH2Cl2 (70 mL) and washed with saturated aqueꢀ
ous NaHCO3 (15 mL) and water (215 mL). The organic phase
was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica
gel (gradient elution with ethyl acetate—hexane) to afford the
title compound 8d as a white amorphous solid (323 mg, 79%).
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2ꢀfluorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(3a) was obtained as a colorless syrup from glycosyl donor 1a and
glycosyl acceptor 2 in the presence of DMTST. Yields and
anomeric ratios are given in Table 1 (entries 1 and 2). Rf 0.64
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1041.4193
[M + Na]+. Calculated for C62 H63O12FNa: 1041.4201.
27
Rf 0.71 (ethyl acetate—hexane, 2 : 3 (v/v)), []D –24.9 (c 1,
CHCl3). 1H NMR, : 1.37 (t, 3 H, SCH2CH3, J = 7.4 Hz); 2.81
(m, 2 H, SCH2CH3); 3.57 (dd, 1 H, H(2), J2,3 = 8.9 Hz);
3.67—3.75 (m, 3 H, H(5), H(6a), H(6b)); 3.81 (dd, 1 H, H(3),
J3,4 = 9.1 Hz); 4.52 (dd, 2 H, CH2Ph, 2J = 11.7 Hz); 4.57 (d, 1 H,
H(1), J1,2 = 9.7 Hz); 4.76 (dd, 2 H, CH2Ph, 2J = 11.2 Hz); 4.85
(dd, 2 H, CH2Ph, 2J = 10.2 Hz); 5.31 (dd, 1 H, H(4), J4,5 = 9.6 Hz);
7.17—7.41 (m, 17 H, aromatic); 7.55 (dd, 1 H, aromatic,
J = 7.6 Hz); 64 (dd, 1 H, aromatic, J = 7.9 Hz). 13C NMR, :
15.3, 25.3, 70.2, 72.3, 73.8, 75.5, 75.7, 77.5, 81.7, 83.7, 85.3,
122.1, 127.3, 127.7, 127.8, 127.9 (2 C), 128.0 (2 C), 128.1, 128.4
(2 C), 128.5 (2 C), 128.6 (4 C), 131.6, 131.7, 132.9, 134.6, 137.9,
138.0, 138.1, 165.0. MS (FAB), m/z: 699.1398 [M + Na]+. Calꢀ
culated for C36H37BrO6SNa: 699.1391.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀfluorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(3b) was obtained as a colorless syrup from glycosyl donor 1b and
glycosyl acceptor 2 in the presence of various promoters. Yields
and anomeric ratios obtained under high dilution reaction conꢀ
ditions (5 mmol L–1) are given in Table 1 (entries 3, 4, 9—12)
and Table 2 (entries 13 (using glycosyl donor 4), 14, and 15).
Under regular concentration reaction conditions (50 mmol L–1
)

1116
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Visansirikul et al.
following yields and anomeric ratios were achieved: 92%,
 :  = 1.3 : 1 in the presence of IDCP; 81%,  :  = 3.4 : 1 in the
presence of NIS/TfOH; 85%,  :  = 2.8 : 1 in the presence of
NIS/TMSOTf; 89%,  :  = 2.9 : 1 in the presence of NIS/
TESOTf. Rf 0.65 (ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB),
m/z: 1041.4200 [M + Na]+. Calculated for C62H63O12FNa:
1041.4201.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(4ꢀfluorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(3c) was obtained as a colorless syrup from glycosyl donor 1c and
glycosyl acceptor 2 in the presence of DMTST. Yields and anoꢀ
meric ratios are given in Table 1 (entries 5 and 6). Rf 0.65
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1041.4103
[M + Na]+. Calculated for C62H63O12FNa: 1041.4201.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀbenzoylꢀDꢀglucopyranoꢀ
syl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside (3d) was obꢀ
tained as a colorless syrup from glycosyl donor 1d and glycosyl
acceptor 2 in the presence of DMTST.22 Yields and anomeric
ratios are given in Table 1 (entries 7 and 8).
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2ꢀchlorobenzoyl)ꢀDꢀglucoꢀ
pyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranosyde (3e)
was obtained as a colorless syrup from glycosyl donor 1e and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 3 (entry 18). Under regular
concentration reaction conditions (50 mmol L–1) following yield
and anomeric ratio were achieved: 92%,  :  = 2.8 : 1. Rf 0.64
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1057.3900
[M + Na]+. Calculated for C62H63O12ClNa: 1057.3906.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀchlorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside (3f)
was obtained as a colorless syrup from glycosyl donor 1f and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 3 (entry 19). Under regular
concentration reaction conditions (50 mmol L–1) the following
yield and anomeric ratio were achieved: 88%,  :  = 2.1 : 1.
Rf 0.64 (ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB),
m/z: 1057.3905 [M + Na]+. Calculated for C62H63O12ClNa:
1057.3906.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(4ꢀchlorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(3g) was obtained as a colorless syrup from glycosyl donor 1g and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 3 (entry 20). Under regular conꢀ
centration reaction conditions (50 mmol L–1) the following
yield and anomeric ratio were achieved: 98%,  :  = 2.7 : 1.
Rf 0.64 (ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB),
m/z: 1057.3897 [M + Na]+. Calculated for C62H63O12ClNa:
1057.3906.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2ꢀbromobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(3h) was obtained as a colorless syrup from glycosyl donor 1h and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 3 (entry 21). Under regular conꢀ
centration reaction conditions (50 mmol L–1) following yield
and anomeric ratio were achieved: 72%,  :  = 2.8 : 1. Rf 0.63
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1101.3407
[M + Na]+. Calculated for C62H63O12BrNa: 1101.3401.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀbromobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside (3i)
was obtained as a colorless syrup from glycosyl donor 1i and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 3 (entry 22). Under regular conꢀ
centration reaction conditions (50 mmol L–1) following yield
and anomeric ratio were achieved: 96%,  :  = 2.6 : 1. Rf 0.63
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1101.3400
[M + Na]+. Calculated for C62H63O12BrNa: 1101.3401.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(4ꢀbromobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside (3j)
was obtained as a colorless syrup from glycosyl donor 1j and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 3 (entry 23). Under regular conꢀ
centration reaction conditions (50 mmol L–1) following yield
and anomeric ratio were achieved: 96%,  :  = 3.3 : 1. Rf 0.63
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1101.3395
[M + Na]+. Calculated for C62H63O12BrNa: 1101.3401.
Methyl Oꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3ꢀfluorobenzyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside (7)
was obtained as a colorless syrup from glycosyl donor 6 and
glycosyl acceptor 2 in the presence of DMTST. Yields and anoꢀ
meric ratios are given in Table 2 (entries 16 and 17). Rf 0.72
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1027.4418
[M + Na]+. Calculated for C62H65O11FNa: 1027.4408.
Methyl Oꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2ꢀfluorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(9a) was obtained as a colorless syrup from glycosyl donor 8a and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 4 (entry 24). Under regular conꢀ
centration reaction conditions (50 mmol L–1) following yield
and anomeric ratio were achieved: 96%,  :  = 1 : 1. Rf 0.69
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1041.4194
[M + Na]+. Calculated for C62H63O12FNa: 1041.4201.
Methyl Oꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(3ꢀfluorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(9b) was obtained as a colorless syrup from glycosyl donor 8b and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 4 (entry 25). Under regular conꢀ
centration reaction conditions (50 mmol L–1) the following yield
and anomeric ratio were achieved: 51%,  :  = 1 : 1.6. Rf 0.69
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1041.4199
[M + Na]+. Calculated for C62H63O12FNa: 1041.4201.
Methyl Oꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(4ꢀfluorobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(9c) was obtained as a colorless syrup from glycosyl donor 8c and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 4 (entry 26). Under regular conꢀ
centration reaction conditions (50 mmol L–1) the following yield
and anomeric ratio were achieved: 96%,  :  = 1 : 1.6. Rf 0.69
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1041.4189
[M + Na]+. Calculated for C62H63O12FNa: 1041.4201.
Methyl Oꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(2ꢀbromobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(9d) was obtained as a colorless syrup from glycosyl donor 8d and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ

Halobenzoyl groups in glycosylation
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1117
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 4 (entry 27). Under regular conꢀ
centration reaction conditions (50 mmol L–1) the following yield
and anomeric ratio were achieved: 53%,  :  = 1 : 2.8. Rf 0.67
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1101.3409
[M + Na]+. Calculated for C62H63O12BrNa: 1101.3401.
Methyl Oꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(3ꢀbromobenzoyl)ꢀDꢀgluꢀ
copyranosyl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside
(9e) was obtained as a colorless syrup from glycosyl donor 8e and
glycosyl acceptor 2 in the presence of DMTST. Yield and anoꢀ
meric ratio obtained under high dilution reaction conditions
(5 mmol L–1) are given in Table 4 (entry 28). Under regular conꢀ
centration reaction conditions (50 mmol L–1) the following yield
and anomeric ratio were achieved: 86%,  :  = 1 : 3.1. Rf 0.67
(ethyl acetate—hexane, 2 : 3 (v/v)). MS (FAB), m/z: 1101.3402
[M + Na]+. Calculated for C62H63O12BrNa: 1101.3401.
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Methyl Oꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀbenzoylꢀDꢀglucopyranoꢀ
syl)ꢀ(16)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀꢀDꢀglucopyranoside (9f)22 was
obtained as a colorless syrup from glycosyl donor 8f and glycosyl
acceptor 2 in the presence of DMTST. Yield and anomeric ratio
obtained under high dilution reaction conditions (5 mmol L–1
)
are given in Table 4 (entry 29). Under regular concentration
reaction conditions (50 mmol L–1) the following yield and anoꢀ
meric ratio were achieved: 55%,  :  = 1 : 2.4.
The authors are indebted to the National Science
Foundation (CHEꢀ1058112) for support of this work.
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Received March 11, 2015