Studies on the selectivity between nickel-catalyzed 1,2- cis -2-Amino glycosylation of hydroxyl groups of thioglycoside acceptors with C(2)-Substituted benzylidene N -Phenyl trifluoroacetimidates and intermolecular aglycon transfer of the sulfide group

Article abstract of DOI:10.1021/jo301050q

The stereoselective synthesis of saccharide thioglycosides containing 1,2-cis-2-amino glycosidic linkages is challenging. In addition to the difficulties associated with achieving high α-selectivity in the formation of 1,2-cis-2-amino glycosidic bonds, th

Full text of DOI:10.1021/jo301050q

Article
pubs.acs.org/joc
Studies on the Selectivity Between Nickel-Catalyzed 1,2-cis-2-Amino
Glycosylation of Hydroxyl Groups of Thioglycoside Acceptors with
C(2)-Substituted Benzylidene N‑Phenyl Trifluoroacetimidates and
Intermolecular Aglycon Transfer of the Sulfide Group
Fei Yu and Hien M. Nguyen*
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United States
S
* Supporting Information
ABSTRACT: The stereoselective synthesis of saccharide thiogly-
cosides containing 1,2-cis-2-amino glycosidic linkages is challeng-
ing. In addition to the difficulties associated with achieving
high α-selectivity in the formation of 1,2-cis-2-amino glycosidic
bonds, the glycosylation reaction is hampered by undesired
transfer of the anomeric sulfide group from the glycosyl acceptor to the glycosyl donor. Overcoming these obstacles will pave the
way for the preparation of oligosaccharides and glycoconjugates bearing the 1,2-cis-2-amino glycosidic linkages because the
saccharide thioglycosides obtained can serve as donors for another coupling iteration. This approach streamlines selective
deprotection and anomeric derivatization steps prior to the subsequent coupling event. We have developed an efficient approach
for the synthesis of highly yielding and α-selective saccharide thioglycosides containing 1,2-cis-2-amino glycosidic bonds, via
cationic nickel-catalyzed glycosylation of thioglycoside acceptors bearing the 2-trifluoromethylphenyl aglycon with N-phenyl
trifluoroacetimidate donors. The 2-trifluoromethylphenyl group effectively blocks transfer of the anomeric sulfide group from the
glycosyl acceptor to the C(2)-benzylidene donor and can be easily installed and activated. The current method also highlights the
efficacy of the nickel catalyst selectively activating the C(2)-benzylidene imidate group in the presence of the anomeric sulfide
group on the glycosyl acceptors.
donors to control the α-selectivity and provide high yielding
oligosaccharides and glycoconjugates from a wide variety of
glycosyl donors and acceptors.
INTRODUCTION
■
Alkyl and aryl thioglycosides have been widely utilized as both
the acceptors and donors in the multistep synthesis of oligo-
saccharides and glycoconjugates.1 They are versatile in that their
anomeric sulfide groups are easy to install and stable under many
reaction conditions.2 As a result, the sulfide groups not only serve
as efficient protecting groups of anomeric centers but also act as
glycosyl acceptors in combination with a variety of glycosyl
donors such as trichloroacetimidates, halides and sulfoxides.3
The resulting saccharide thioglycosides can be subsequently
activated for another coupling iteration to generate the corres-
ponding oligosaccharides or glycoconjugates.3,4 Despite the
widespread synthetic utility of thioglycosides, intermolecular
aglycon transfer can be a serious side reaction. When an unreac-
tive thioglycoside acceptor is employed in the coupling process,
the anomeric sulfide group can be transferred from the glycosyl
acceptor to the glycosyl donor to give another thioglycoside.6
To prevent aglycon transfer, Li and Gildersleeve have recently
reported the use of 2,6-dimethylphenyl (DMP) group as an
efficient aglycon for thioglycoside acceptors.5 This bulky group
effectively blocks intermolecular aglycon transfer6 of the
anomeric sulfur atom in the glycosylation reaction.
In an effort to expand the capabilities of this method, we
targeted the development of a variant proceeding via chemo-
selective coupling to the hydroxyl groups of thioglycosides, as
depicted in Scheme 1b. A number of challenges have to be
addressed in developing such a chemoselective glycosylation
process. For instance, the nickel catalyst could fail to promote the
coupling due to the displacement of metal-bound benzonitrile
ligand by the anomeric sulfide group, producing an inactive
nickel catalyst.9 Second, the trihaloacetimidate group could
undergo [1,3]-rearrangement to provide the corresponding
glycosyl trihaloacetamide.10 Third, intermolecular aglycon
transfer of the anomeric sulfide group from the glycosyl acceptor
to the glycosyl donor provides undesired thioglycoside.6 We
report herein an efficient approach for the preparation of
saccharides containing 1,2-cis-2-amino glycosidic linkages via
nickel-catalyzed α-chemoselective glycosylation of the hydroxyl
groups of thioglycoside acceptors with C(2)-benzylidene N-
phenyl trifluoroacetimidates (Scheme 1b). This strategy over-
comes the challenges associated with intermolecular aglycon
transfer of the anomeric sulfide group from the acceptors to the
C(2)-benzylidene imidate donors and retains the unique features
We recently developed a novel strategy for the synthesis of 1,
2-cis-2-aminosugars via nickel-catalyzed coupling with the C(2)-
N-substituted benzylidene trichloroacetimidates (Scheme 1a).7,8
This method utilizes the nature of the nickel-ligand complex and
metal-bound functional group at the C(2)-position of glycosyl
Received: May 26, 2012
Published: July 30, 2012
© 2012 American Chemical Society
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Scheme 1. Nickel-Catalyzed 1,2-cis-2-Amino Glycosylation
Scheme 2. Initial Studies with Trichloroacetimidate Donors
of the nickel catalyst to control the α-selectivity at the newly
formed glycosidic bond.
product 7 (14%, entry 1), however, was still obtained in the
reaction.
Thus, the key to the optimization is to minimize aglycon
transfer. Unfortunately, we were unable to install the DMP
group5 onto the anomeric center of N-Troc glucosamine. We
then systematically examined the steric and electronic nature of
the substituents on the phenyl ring of a number of thioglycosides
12−17 (Table 1) in the coupling with imidate 10. While the
electron-rich 4-methoxyphenyl aglycon 14 (entry 5) significantly
increased the amount of transfer product 28, the electron-poor
groups 15−17 (entries 6−8) nearly blocked transfer. The most
efficient acceptor was 2-trifluoromethylphenyl thioglycoside 17
(entry 8), which completely prevented transfer and provided
disaccharide 24 (entry 8) in 61% yield and exclusively as the
α-isomer. Even with two equivalents of donor10, no aglycon trans-
fer product 31 (entry 9) was observed in the reaction. Overall,
the 2-trifluoromethylphenyl group is an excellent alternative
aglycon for thioglycoside acceptor. In addition, the nickel catalyst
not only selectively activates the C(2)-benzylidene imidate 10 in
the presence of the anomeric sulfide group on the glycosyl
acceptor 17 but also effectively controls the α-anomeric selec-
tivity in the synthesis of disaccharide thioglycoside 24 containing
1,2-cis-2-amino glycosidic bond.
RESULTS AND DISCUSSION
■
Optimization Studies. We initially explored the nickel-
catalyzed glycosylation of N-Troc protected thioglycoside 36f,g
with the C(2)-N-p-trifluoromethyl-benzylidene trichloroaceti-
midate 1 (Scheme 1) to probe issues of both aglycon transfer and
selectivity. Under previous nickel conditions (10 mol % Ni(4-F-
PhCN)4(OTf)2 at 25 °C in CH2Cl2),7 disaccharide 4 (Scheme 2)
was isolated in 33% along with aglycon transfer product 6 (33%)
and [1,3]-rearrangement trichloroacetamide 8 (20%). Switching
to C(2)-N-o-trifluoromethyl-benzylidene donor 2 improved
both the yield and α-selectivity of disaccharide 5 (57%) and
decreased the amount of transfer product 11 (12%) and tri-
chloroacetamide 9 (10%). Formation of the rearrangement pro-
ducts 8 and 9 indicate the disadvantage of utilizing trichloro-
acetimidates as glycosyl donors.
To prevent [1,3]-rearrangement of the imidate group, the N-
phenyl trifluoroacetimidate donor 10 (Table 1) was chosen due
to its attenuated reactivity in comparison to trichloroacetimi-
dates 1 and 2 (Scheme 2).11 Accordingly, coupling of thiogly-
coside 3 (Table 1) with 10 was first examined at 25 °C, and the
reaction was sluggish. Warming the reaction to 35 °C accelerated
the coupling process and provided 5 (entry 1) in 58% yield as a
single α-isomer. The undesired rearrangement acetamide (e.g., 9)
was not observed. In this experiment, both α- and β-isomers of
donor 10 reacted, highlighting another advantage of using this
glycosyl donor.12 A significant amount of aglycon transfer
To evaluate the unique features of the nickel catalyst as the
effective activating agent to promote the glycosylation reaction, a
number of catalysts (Table 2) were screened in the coupling of
2-trifluoromethylphenyl thioglycoside 3 with imidate donor 10.
Using TMSOTf (entry 1) resulted in 13% of disaccharide 5 with
α:β = 10:1 and 40% of transfer product 7. Similar results were
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a
Table 1. Studies with N-Phenyl Trifluoroacetimidate
b
c
entry
acceptors
3: R = Ph
donor/acceptor ratio
disaccharides yield (%) (α:β)
thioglycosides yield (%)
1
2
3
4
5
6
7
8
9
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
2/1
5: 58 (α only)
18: 43(10:1)
7: 14
25:22
26: 10
27: 20
28: 30
29: 9
11: R = Et
12: R = 1-Naphthyl
13: R = 4-Me-Ph
14: R = 4-MeO-Ph
15: R = 4-F-Ph
16: R = 2-F-Ph
17: R = 2-CF3-Ph
17: R = 2-CF3-Ph
19: 59 (α only)
20: 38(11:1)
21:37(11:1)
22: 58(20:1)
23: 60 (α only)
24: 61 (α only)
24: 58 (α only)
30: 4
31: 0
31: 0
a
b
c
All reactions were run in 10 mol % Ni(4-F-PhCN)4(OTf)2 at 35 °C for 12 h. Isolated Yield. 1H NMR ratio.
a
Table 2. Activation of Glycosyl Imidate with Various Catalysts
b
c
entry
catalysts
TMSOTf
disaccharide 5 yield (%) (α:β)
thioglycoside 7 yield (%)
1
2
3
4
5
6
7
13(10:1)
26(10:1)
43(6:1)
40
30
20
26
23
21
1
Cu(OTf)2
Rh(COD)2OTf
Ir(COD)2OTf
Pd(4-F-PhCN)2(OTf)
Ph3PAuOTf
45(8:1)
36(20:1)
43 (α only)
Fe(OTf)2
11(11:1)
a
b
c
All reactions were run in 10 mol % catalyst at 35 °C for 12 h. Isolated yield. 1H NMR ratio.
obtained with a milder Lewis acid, Cu(OTf)2 (entry 2). Use
of both Rh(COD)2OTf and Ir(COD)2OTf catalysts (entries 3
and 4) provided 5 in lower yield (43−45%) and α-selectivity
(α:β = 6:1−8:1) in comparison to the nickel catalyst whereas 7
was obtained in 58% yield and as a single α-isomer (Table 1,
entry 1). In addition, employing iridium as the activating agent
significantly increased the amount of transfer product
7 (14%→26%). The palladium catalyst (entry 5), Pd(4-F-
PhCN)2OTf2, decreased the yield of disaccharide 5 (40%) but
increased the yield of transfer product 7 (14%→24%). Gold
catalyst, Ph3PAuOTf (entry 6), provided exclusive α-dis-
accharide 5 in 43% yield, but a significant amount of sulfide
transfer 7 (21%) was still obtained in the reaction. Although
less than 1% of transfer product 7 was observed in the reaction
using Fe(OTf)2 as the catalyst (entry 7), the desired dis-
accharide 5 was only isolated in 11% yield.
Substrate Scope. We next examined the scope of the
glycosylation of a variety of thioglycosides with armed and
disarmed imidates 10, 32, and 33 (Table 3). In contrast to
disarmed donor 10 (Table 1, entry 1), coupling of armed donor
33 (Table 3, entry 1) with phenyl thioglycoside 3 resulted in no
transfer product 47; disaccharide 39 (entry 1) was isolated in
70% yield, albeit in lower α-selectivity (α:β = 6:1). Similarly,
coupling of phenyl D-galactosyl thioglycoside 34 with both
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glycosylation of the phenyl thioglycoside acceptor 36 with both
disarmed donor 10 (entry 5) and armed donor 32 (entry 6)
provided disaccharides 43 and 44, respectively, in good yields
(72−81%) and with complete α-selectivity, a significant amount
of transfer products 7 (15%) and 49 (9%) was still observed in
the coupling process. On the other hand, the electron deficient
2-trifluoromethylphenyl thioglycoside 37 completely blocked
sulfide transfer (entries 7 and 8), providing disaccharides
45 and 46 in high yield (78−98%) and as single α-isomers.
To further compare, the DMP group was incorporated into
L-rhamnose thioglycoside 38 (entry 9). In agreement with pre-
vious studies,5 no transfer product 51 was obtained in the
reaction. The modified disaccharide 47 (entry 9), however, was
obtained in lower yield than disaccharide 45 (entry 5) bearing
the 2-trifluoromethylphenyl aglycon. Overall, the results clearly
illustrate that the electron-withdrawing 2-trifluoromethylphenyl
aglycon completely prevents transfer of the anomeric sulfide
group from thioglycoside acceptors to both disarmed and armed
N-phenyl trifluoroacetimidate donors.
Table 3. Coupling of Thioglycosides with Glucosamine
Donors
a
The utility of the current method was further explored with
galactosamine donors 52 and 53 (Table 4). Coupling of phenyl
thioglycoside 3 with both disarmed and armed galactosamine
donors 52 and 53 (entries 1 and 2) provided disaccharides 54
and 55, respectively, in moderate yield (56 − 67%) and with
excellent α-selectivity (α:β = 14:1 to >20:1). As expected, a
significant amount of transfer products 60 and 61 (6−16%) was
also isolated in the reaction. On the other hand, employing
2-trifluoromethylphenyl thioglycoside 17 (entry 3) as a glycosyl
acceptor completely blocked formation of transfer product 62
and provided α-disaccharide 56 (entry 3) in 73% yield.
Derivative of disaccharides 54−56 (entries 1−3), GalNAc-α-
(1→3)-GlcNAc, is a part of the O-polysaccharide present in the
outer membrane of Gram-negative bacteria such as Salmonella
enterica13 and Providencia rustigianii.14 S. enterica is a major
pathogen of humans and animals.11 P. rustigianii invades human
intestinal mucosa and causes stomach infection particularly in
children.12 Next, phenyl thioglycoside 34 (entries 4 and 5) was
investigated with both glycosyl donors 52 and 53, and a
significant amount of transfer products 60 and 61 were obtained in
the glycosylation reaction. Under nickel conditions, the higher
amount of transfer product 61 (40%, entry 5) was obtained with
partially armed donor 53 than that of transfer product 60 (24%,
entry 4) with disarmed donor 52. Thioglycoside 35 (entry 6)
bearing the 2-trifluoromethylphenyl aglycon was then explored with
this problematic reaction. As expected, the modified disaccharide 59
(entry 6) was isolated in 62% yield and with exclusively α-selectivity.
Again, transfer product 62 was not observed with this 2-
trifluoromethylphenyl acceptor 35. Disaccharides 57−59 (entries
4−6), derivatives of GalNAc-α-(1→3)-Gal, are vital disaccharide
units of human blood group A antigens.15
One of the key concerns in reducing the reactivity of the sulfide
aglycon to prevent intermolecular transfer is that the modified
arylthiol group cannot be efficiently activated. To illustrate that
the 2-trifluoromethylphenyl aglycon can be sufficiently activated
with thiophilic reagents (Scheme 3), disaccharide thioglycoside
donor 45 was treated with the reagent combination of NIS and
AgOTf.16,17 Subsequent addition of a galactosyl acceptor 63
provided trisaccharide 64 in 84% yield, validating the ability
of the 2-trifluoromethylphenyl group as an excellent alterna-
tive aglycon for thioglycosides. Encouraged by this result, we
further explored the glycosylation of glycosyl acceptor 63 with
less reactive disaccharide thioglycoside donor 24 (Scheme 3b)
under similar nickel conditions. Gratifyingly, the coupling process
a
All reactions were conducted with 10 mol % Ni(4-F-PhCN)4(OTf)2
b
c
d
for 14 h. Donor/Acceptor = 1:2. Donor/Acceptor = 2:1. Isolated
e
f
yields. 1H NMR ratio. Transfer products were obtained as single
α-isomers.
donors 10 and 32 (entries 2 and 3) provided a large quantity
of sulfide transfer products 7 and 49, respectively. The armed
donor 32 provided less aglycon transfer than the disarmed donor
10 (8 vs 24%). The 2-trifluoromethylphenyl aglycon was then
incorporated into D-galactosyl thioglycoside 35 (entry 4).6 No
trace amount of transfer product 31 (entry 4) was observed, and
exclusive α-disaccharide 42 was isolated in 71% yield. The effi-
cacy of the nickel method was further evaluated with L-rhamnose
acceptors 36 and 37 (entries 5 and 8). As anticipated, although
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a
Table 4. Coupling of Thioglycosides with Galactosamine Donors
a
b
c
d
All reactions were conducted with 10 mol % Ni(4-F-PhCN)4(OTf)2 for 14 h. Donor/Acceptor = 1:2. Donor/Acceptor = 2:1. Isolated yields.
e
f
1H NMR ratio. Transfer products were obtained as single α-isomers.
proceeded smoothly to provide the desired trisaccharide 65 in 81%
glycosylations were performed with glycosyl N-phenyl trifluor-
oacetimidate 67 (Scheme 4).11,19 Accordingly, coupling of phenyl
thioglycoside acceptor 3 with imidate 67 in the presence of
10 mol % Ni(4-F-PhCN)4(OTf)2 provided sulfide transfer pro-
duct 69 (40%) as the major product (Scheme 4a). The desired
disaccharide 68 was obtained in 18% yield, albeit with excel-
lent α-selectivity. Although transfer product was not detected in
the reaction with the 2-trifluoromethyl-phenyl thioglycoside
acceptor 17, only 13% of the desired disaccharide 67 was iso-
lated (Scheme 4b).20 When L-rhamnoside 36 was employed
as the glycosyl donors in the reaction with C(2)-azido donor
67 (Scheme 4c), higher amount of transfer product 69 (28 vs
15%) and lower yield of the desired disaccharide 71 (49 vs 81%)
were obtained than those with C(2)-benzylidene donor 10
(Table 3, entry 5). Overall, these results suggest that the nickel
catalyst, Ni(4-F-PhCN)4(OTf)2, is the more efficient activating
yield and with exclusive β-selectivity. The results obtained in
Scheme 3 also illustrate the ability of the C(2)-N-substituted
benzylidene functionality to act as the efficient protecting
group. Next, it is essential to determine that these benzylidene
groups could be converted to the corresponding N-acetyl or other
functional groups. Accordingly, treatment of 65 with HCl, acetone/
CH2Cl2 at 25 °C for less than 5 min provided the corresponding
amine salt along with the concomitant removal of the benzylidene
protecting group. To ease the purification process, the resulting
amine salt intermediate was acetylated to afford the fully protected
trisaccharide 66 (Scheme 3b) in 99% yield over two steps.
Currently, the most common method for the synthesis of 1,
2-cis-2-aminosugars employs glycosyl donors bearing the
C(2)-azido functionality.18 To compare the ability of the nickel
catalyst to efficiently activate the C(2)-azido donor, a series of
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Scheme 3. Activation of 2-Trifluoromethylphenyl Thiolglycosides
Scheme 4. Glycosylation with C(2)-Azido Imidate Donor
reagent for C(2)-N-substituted benzylideneamino donors than
that for C(2)-azido donors.
prevent transfer of the sulfide group from the glycosyl acceptor to
the C(2)-benzylidene N-phenyl trifluoroacetimidate donors. In
addition, it can be easily introduced onto the glycosyl acceptor and
subsequently activated. This approach to the stereoselective
synthesis of saccharide thioglycosides also highlights the ability of
the C(2)-N-substituted benzylidene functionality as the efficient
protecting group. Efforts are underway in our group to adapt this
strategy for the preparation of biologically active oligosaccharides
and glycoconjugates.
CONCLUSION
■
In summary, we have developed an efficient strategy to chemo-
selective glycosylation for the preparation of various saccharide
thioglycoside building blocks in moderate to good yields and with
excellent levels of α-selectivity. This approach employs a method of
nickel-catalyzed 1,2-cis-2-amino glycosylation of thioglycoside
acceptors bearing the 2-trifluoromethylphenyl aglycon with
armed and disarmed C(2)-substituted N-phenyl trifluoroacetimi-
date donors. The resulting saccharide thioglycosides serve as gly-
cosyl donors for another coupling iteration to generate
oligosaccharides. Overall, the 2-trifluoromethylphenyl functionality
is a more efficient aglycon than its phenyl counterpart to completely
EXPERIMENTAL SECTION
■
General Procedure for the Preparation of Glycosyl Donors:
3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylbenzylidenea-
mino-D-glucopyranosyl N-Phenyl Trifluoroacetimidate 10. A
100 mL RBF was charged with triacetyl D-glucosamine hemiacetal 10A
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(4.9 g, 10.6 mmol, 1.0 equiv.),7b 2,2,2-Trifluoro-N-phenyl-ethanimidoyl
chloride (6.66 g, 31.9 mmol, 3.0 equiv), K2CO3 (2.93 g, 21.2 mmol, 2.0
equiv) and acetone (30.0 mL). The solution was stirred at room
temperature overnight. When the reaction was complete as monitored
by TLC (hexane/ethyl acetate = 3/1), the reaction mixture was filtered,
evaporated, and purified by flash chromatography on silica gel (hexane/
ethyl acetate = 5/1 → 3/1 with 1% Et3N) to afford 10 (5.26 g, 80%,
α:β = 1:4) as a viscous oil. 10α: 1H NMR (CDCl3, 400 MHz): δ = 8.68
(s, 1 H), 8.22 (d, J = 7.6 Hz, 1 H), 7.73−7.52 (m, 3 H), 7.25−7.13 (m,
2 H), 7.12−6.98 (m, 1 H), 6.88−6.65 (m, 2 H), 6.44 (brs, 1 H), 6.65 (t, J =
10.0 Hz, 1 H), 5.23 (app t, J = 10.0 Hz, 1 H), 4.48−4.27 (m, 2 H), 4.22−
4.08 (m, 1 H), 3.88−3.77 (m, 1 H), 2.10 (s, 3 H), 2.05 (s, 3 H), 1.89 (s, 3
H); 13C NMR (CDCl3, 100 MHz): δ = 170.4, 169.7, 169.5, 161.5, 143.2,
133.1, 132.1, 131.0, 129.4 (q, JC−F = 30.5 Hz), 128.64, 128.59, 125.6 (q,
JC−F = 5.6 Hz), 124.3, 124.0 (d, JC−F = 272 Hz), 119.4, 94.7, 71.1, 70.5,
68.0, 61.7, 20.55, 20.50, 20.2; IR (film, cm−1): ν = 2963, 1752, 1644,
1367, 1315, 1212; HRMS (ESI): calcd for C28H26F6N2O8Na (M + Na):
655.1491; found: 655.1497. 10β: 1H NMR (CDCl3, 400 MHz): δ = 8.68
(d, J = 2.4 Hz, 1 H), 8.11 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 7.2 Hz, 1 H),
7.68−7.51 (m, 2 H), 7.38−7.27 (m, 2 H), 7.19−7.07 (m, 1 H), 6.82 (d,
J = 7.6 Hz, 2 H), 6.02 (brs, 1 H), 5.46 (t, J = 10.0 Hz, 1 H), 5.19 (app t, J =
10.0 Hz, 1 H), 4.34 (dd, J = 12.4, 4.8 Hz, 1 H), 4.17 (dd, J = 12.4, 2.0 Hz,
1 H), 3.93−3.76 (m, 1 H), 3.71 (t, J = 8.8 Hz, 1 H), 2.10 (s, 3 H), 2.04 (s,
3 H), 1.93 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.4, 169.5,
143.2, 133.3, 132.1, 130.9, 129.3 (q, JC−F = 31.0 Hz), 128.7, 128.6, 125.6
(q, JC−F = 5.5 Hz), 124.4, 124.0 (d, JC−F = 272 Hz), 119.2, 95.7, 73.3,
72.9, 72.7, 68.0, 61.7, 20.53, 20.47, 20.2; IR (film, cm−1): ν = 2887, 1752,
1645, 1489, 1315, 1231; HRMS (ESI): calcd for C28H26F6N2O8Na (M +
Na) 655.1491; found 655.1511.
3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylbenzylide-
neamino-D-galactopyranosyl N-Phenyl Trifluoroacetimidate
52. Viscous oil: 276 mg, 94%, α:β = 1:4; 52α: 1H NMR (CDCl3, 400
MHz): δ = 8.70 (s, 1 H), 8.22 (d, J = 7.6 Hz, 1 H), 7.70 (d, J = 7.6 Hz,
1 H), 7.65−7.52 (m, 2 H), 7.31−7.18 (m, 2 H), 7.10−7.02 (m, 1 H),
6.89−6.66 (m, 2 H), 6.50 (brs, 1 H), 5.68−5.56 (m, 1 H), 5.51 (dd, J =
10.4, 2.8 Hz, 1 H), 4.53 (app t, J = 6.0 Hz, 1 H), 4.34−4.11 (m, 2 H),
4.09−3.93 (m, 1 H), 2.20 (s, 3 H), 2.08 (s, 3 H), 1.90 (s, 3 H); 13C NMR
(CDCl3, 100 MHz): δ = 170.3, 170.0, 169.7, 161.6, 143.3, 133.3 132.1,
130.9, 129.2 (q, JC−F = 31.0 Hz), 128.7, 128.5, 125.6 (q, JC−F = 5.5 Hz),
124.6, 124.1 (d, JC−F = 272 Hz), 119.4, 95.3, 69.4, 68.1, 66.3, 66.2, 61.6,
20.7, 20.6, 20.3; IR (film, cm−1): ν = 2968, 1750, 1713, 1645, 1488,
1314; HRMS (ESI): calcd for C28H26F6N2O8Na (M + Na) 655.1491;
found 655.1502. 52β: 1H NMR (CDCl3, 400 MHz): δ = 8.71 (s, 1 H),
8.10 (d, J = 7.6 Hz, 1 H), 7.69 (d, J = 7.6 Hz, 1 H), 7.66−7.48 (m, 2 H),
7.37−7.20 (m, 2 H), 7.17−7.02 (m, 1 H), 6.89−6.71 (m, 2 H), 6.00 (brs,
1 H), 5.53−5.41 (m, 1 H), 5.38−5.12 (m, 1 H), 4.42−4.16 (m, 2 H),
4.11−3.98 (m, 1 H), 3.84 (t, J = 8.4 Hz, 1 H), 2.20 (s, 3 H), 2.02 (s, 3 H),
1.91 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.2, 170.1, 169.6,
162.5, 143.2, 133.4, 132.1, 130.8, 129.2 (q, JC−F = 31.0 Hz), 128.7, 128.5,
125.6 (q, JC−F = 5.7 Hz), 124.4, 124.0 (d, JC−F = 272 Hz), 119.1, 96.0,
71.9, 70.9, 69.1, 65.5, 61.2, 20.6, 20.5, 20.2; IR (film, cm−1): ν = 2932,
1747, 1721, 1646, 1488, 1371, 1314, 1209; HRMS (ESI): calcd for
C28H26F6N2O8Na (M + Na) 655.1491; found 655.1501.
13C NMR (CDCl3, 100 MHz): δ = 164.9, 161.7, 131.9, 130.2, 113.7,
96.6, 75.6, 74.8, 72.6, 68.0, 62.8, 55.3, 25.8, 25.5, 18.2, 17.9, −4.3, −5.3,
−5.45, −5.51; IR (film, cm−1): ν = 3419, 2927, 1644, 1605, 1577, 1512,
1249.
3,4-Di-O-benzyl-1,6-di-O-tert-butyldimethylsilyl-2-deoxy-2-
p-Methoxybenzylideneamino-D-galactopyranoside 53C. A 250
mL RBF was charged with diol 53B (1.17 g, 2.2 mmol, 1.0 equiv), benzyl
bromide (0.78 mL, 6.6 mmol, 3.0 equiv) and DMF (10 mL). The
solution was cooled to −20 °C, and NaH (60%, 0.22 g, 5.5 mmol, 2.5
equiv.) was added in several portions. The reaction was allowed to warm
to room temperature and stirred overnight. The reaction mixture was
diluted with ethyl acetate, washed with brine (2 × 50 mL), dried over
Na2SO4, concentrated in vacuo. The residue was purified by silica gel
flash chromatography (hexane/ethyl acetate = 20/1 → 10/1 with 1%
Et3N) to afford 53C (1.158 g, 75%) as a viscous oil. 1H NMR (CDCl3,
400 MHz): δ = 8.30 (s, 1 H), 7.70 (d, J = 8.8 Hz, 2 H), 7.45−7.15 (m,
10 H), 6.94 (d, J = 8.8 Hz, 2 H), 4.97 (d, J = 11.6 Hz, 1 H), 4.82 (d, J = 7.2
Hz, 1 H), 4.56 (d, J = 11.6 Hz, 1 H), 4.62−4.53 (m, 2 H), 3.87 (s, 3 H),
3.88−3.83 (m, 1 H), 3.80−3.64 (m, 3 H), 3.60 (dd, J = 10.0, 7.2 Hz,
1 H), 3.49 (t, J = 6.4 Hz, 1 H), 0.91 (s, 9 H), 0.79 (s, 9 H), 0.07 (s, 3 H),
0.06 (s, 6 H), 0.01 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 163.2,
161.4, 138.9, 138.5, 129.8, 129.5, 128.2, 128.1, 128.0, 127.7, 127.4, 113.8,
97.2, 81.3, 75.7, 74.9, 74.3, 72.3, 72.3, 62.3, 55.3, 25.9, 25.6, 18.2, 18.0,
−4.1, −5.2, −5.4, −5.5; IR (film, cm−1): ν = 2928, 1847, 1606, 1512,
1248.
3,4-Di-O-benzyl-2-deoxy-2-amino-D-galactopyranose 53D. A
25 mL RBF was charged with 53C (105 mg, 0.15 mmol, 1.0 equiv), 6N
HCl (0.2 mL, 1.2 mmol, 8.0 equiv) and acetone (1.0 mL). The solution
was stirred at 50 °C overnight, concentrated in vacuo, and the residue
was purified by silica gel flash chromatography (CH2Cl2/MeOH = 20/1
1
→ 5/1) to afford 56 mg (95%) of 53D as a viscous oil. H NMR
(CD3OD, 400 MHz): δ = 7.51−7.24 (m, 10 H), 5.33 (d, J = 3.6 Hz,
1 H), 4.65−4.61 (m, 2 H), 4.59−4.52 (m, 2 H), 4.23−4.18 (m, 1 H),
4.11−4.02 (m, 2 H), 3.72−3.62 (m, 2 H), 3.57 (dd, J = 10.8, 3.6 Hz,
1 H); 13C NMR (CD3OD, 100 MHz): δ = 139.6, 138.6, 129.2, 129.1,
128.9, 128.8, 128.7, 128.4, 91.2, 77.1, 75.6, 73.5, 72.2, 72.1, 61.9, 52.1
1,6-Di-O-acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-D-galactopyranoside 53E. A 25 mL RBF
was charged with 53D (40 mg, 0.1 mmol, 1.0 equiv), 1 M NaOH (0.12
mL, 0.12 mmol, 1.2 equiv), and CH2Cl2 (0.5 mL). To this pale-yellow
solution was then added 2-trifluoromethylbenzylaldehyde (0.02 mL,
0.12 mmol, 1.2 equiv). The resulting mixture was stirred at room
temperature overnight. Then the mixture was diluted with ethyl acetate,
washed with brine, dried over Na2SO4, concentrated in vacuo. The crude
residue was used directly without further purification. A 25 mL RBF was
charged with the crude residue, acetic anhydride (0.15 mL), and
pyridine (0.30 mL). After the reaction mixture was stirred at room
temperature overnight, it was azeotroped with toluene for three times
(3 × 15 mL). The residue was then purified by silica gel flash
chromatography (hexane/ethyl acetate = 5/1 → 2/1 with 1% Et3N) to
afford 53E (45 mg, 75%) as a viscous oil. 1H NMR (CDCl3, 400 MHz):
δ = 8.76 (d, J = 2.4 Hz, 1 H), 8.11 (d, J = 7.6 Hz, 1 H), 7.70 (d, J = 7.6 Hz,
1 H), 7.62−7.47 (m, 2 H), 7.34−7.23 (m, 10 H), 5.85 (d, J = 7.2 Hz,
1 H), 4.99 (d, J = 11.6 Hz, 1 H), 4.67−4.53 (m, 3 H), 4.23 (dd,
J = 11.2, 6.8 Hz, 1 H), 4.15 (dd, J = 11.2, 6.4 Hz, 1 H), 3.96−3.88 (m,
4 H), 1.99 (s, 6 H); 13C NMR (CDCl3, 100 MHz): δ = 170.5, 169.1,
161.5, 138.0, 137.7, 133.9, 132.0, 130.4, 129.3, 129.0, 128.4, 128.3,
127.83, 127.77, 127.7, 125.6 (q, JC−F = 5.7 Hz), 124.0 (d, JC−F = 272 Hz),
93.3, 80.7, 74.4, 73.5, 72.6, 71.4, 63.1, 20.8, 20.6; IR (film, cm−1): ν =
2936, 1749, 1644, 1368, 1228.
1,6-Di-O-tert-butyldimethylsilyl-2-deoxy-2-p-methoxyben-
zylideneamino-D-galactopyranoside 53B. A 250 mL oven-dried
RBF was charged with 53A (3.36 g, 11.3 mmol, 1 equiv),7b TBSCl (3.58
g, 23.7 mmol, 2.1 equiv), imidazole (1.69 g, 24.9 mmol, 2.2 equiv) and
THF/DMF (40 mL/10 mL). The solution was stirred at room
temperature overnight. The solution was diluted with CH2Cl2/MeOH
(20:1), washed with brine (2 × 50 mL). The aqueous phase was then
extracted with CH2Cl2/MeOH (20:1, 2 × 100 mL). The organic phase
was combined, concentrated in vacuo. The resulting residue was purified
by silica gel flash chromatography (hexane/ethyl acetate = 10/1 → 5/1
→ 1/1 with 1% Et3N) to afford 53B (1.94 g, 35%) as a viscous oil. 1H
NMR (CDCl3, 400 MHz): δ = 8.26 (s, 1H), 7.67 (d, J = 9.2 Hz, 2H),
6.91 (d, J = 9.2 Hz, 2H), 4.79 (d, J = 7.2 Hz, 1 H), 4.06 (app t, J = 3.6 Hz,
1 H), 3.94 (dd, J = 10.4, 6.0 Hz, 1 H), 3.88 (dd, J = 10.4, 4.8 Hz, 1 H),
3.90−3.80 (m, 1 H), 3.85 (s, 3 H), 3.60 (t, J = 5.6 Hz, 1 H), 3.24 (dd, J =
9.6, 7.6 Hz, 1 H), 2.78 (d, J = 4.8 Hz, 1 H), 4.27 (brs, 1 H), 0.92 (s, 9 H),
0.78 (s, 9 H), 0.11 (s, 3 H), 0.10 (s, 3 H), 0.07 (s, 3 H), −0.01 (s, 3 H);
6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluoromethyl-
benzylideneamino-D-galactopyranose 53F. A 50 mL oven-dried
Schlenk flask was charged with 53E (500 mg, 0.83 mmol, 1.0 equiv) and
THF (5.0 mL). The solution was cooled to 0 °C, and a solution of NH3
in methanol (7 N, 3.6 mL, 25.0 mmol, 30 equiv) was added. The
resulting mixture was warmed to room temperature and stirred. When
the reaction was complete as monitored by TLC, the mixture was
evaporated and purified by flash chromatography on silica gel (hexane/
ethyl acetate = 2/1 → 1/2 with 1% Et3N) to afford 53F (300 mg, 65%)
as a viscousoil. 1H NMR (CDCl3, 400 MHz):δ = 8.77 (d, J = 2.4 Hz, 1 H),
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Article
6.19 (d, J = 8.0 Hz, 1 H), 7.70 (d, J = 7.2 Hz, 1 H), 7.63−7.52 (m, 2H),
7.38−7.21 (m, 10 H), 4.99 (d, J = 11.6 Hz, 1 H), 4.94 (d, J = 7.2 Hz,
1 H), 4.68−4.50 (m, 3 H), 4.32−4.11 (m, 2 H), 3.84−3.68 (m, 4 H),
2.02 (s, 3 H); IR (film, cm−1): ν = 3423, 2894, 1742, 1644, 1455, 1314.
6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluoromethyl-
benzylideneamino-D-galactopyranosyl N-Phenyl Trifluoroace-
timidate 53. Viscous oil: 377 mg, 99%;1H NMR (CDCl3, 400 MHz): δ
= 8.82 (d, J = 1.2 Hz, 1 H), 8.16 (d, J = 7.6 Hz, 1 H), 7.73 (d, J = 7.6 Hz,
1 H), 7.64−7.53 (m, 2 H), 7.37−7.21 (m, 12 H), 7.06 (t, J = 3.6 Hz,
1 H), 6.76 (d, J = 7.6 Hz, 2 H), 5.91 (brs, 1 H), 5.01 (d, J = 11.6 Hz, 1 H),
4.73−4.57 (m, 3 H), 4.28 (dd, J = 11.2, 6.8 Hz, 1 H), 4.17 (dd, J = 11.2,
5.6 Hz, 1 H), 4.07−4.01 (m, 1 H), 3.90−3.62 (m, 3 H), 1.97 (s, 3 H);
13C NMR (CDCl3, 100 MHz): δ = 170.5, 161.9, 143.6, 137.9, 137.6,
7.36−7.27 (m, 12 H), 7.17−7.09 (m, 3 H), 6.94 (d, J = 8.8 Hz, 1 H),
4.91−4.87 (m, 2 H), 4.68−4.55 (m, 5 H), 3.93 (t, J = 9.2 Hz, 1 H),
3.86 (s, 3 H), 3.80−3.62 (m, 4 H), 3.23 (dd, J = 9.2, 7.2 Hz, 1 H), 0.81
(s, 9 H), 0.10 (s, 3 H), 0.02 (s, 3 H).
3,4,6-Tri-O-benzyl-2-deoxy-2-amino-D-glucopyranose 33E. A
250 mL RBF was charged with 33D (15.1 g, 22.2 mmol, 1.0 equiv), 6N
HCl (18.5 mL, 110 mmol, 5.0 equiv) and acetone (200 mL). The
solution was stirred at 40 °C. When the reaction mixture was complete
as monitored by TLC, it was then evaporated and purified by flash
chromatography on silica gel (hexane/ethyl acetate = 2/1 → CH2Cl2/
MeOH = 10/1) to afford 33E (8.17 g, 82%) as a viscous oil. 1H NMR
(CDCl3 + CD3OD, 400 MHz): δ = 7.25−7.18 (m, 13 H), 7.03−6.98 (m,
2 H), 5.38 (s, 1 H), 4.86 (d, J = 10.4 Hz, 1 H), 4.69 (d, J = 10.4 Hz, 1 H),
4.62 (d, J = 10.4 Hz, 1 H), 4.47−4.36 (m, 2 H), 3.70−3.53 (m, 4 H), 3.10
(d, J = 7.2 Hz, 1 H); 13C NMR (CDCl3 + CD3OD, 100 MHz): δ = 137.3,
137.1, 137.0, 128.21, 128.17, 127.8, 127.7, 127.5, 127.4, 86.9, 78.5, 74.9,
74.5, 73.2, 69.9, 67.8, 54.0; IR (film, cm−1): ν = 3435, 2978, 1585, 1487.
3,4,6-Tri-O-benzyl-2-deoxy-2-o-trifluoromethylbenzylide-
neamino-D-glucopyranose 33F. A 250 mL RBF was charged with
33E (4.50 g, 10.0 mmol, 1.0 equiv), 2-trifluoromethylbenzylaldehyde
(1.5 mL, 11.0 mmol, 1.1 equiv), pyridine (8.1 mL, 100 mmol, 100 equiv)
and CH2Cl2 (100 mL). The resulting solution was stirred under reflux
overnight. The reaction mixture was azeotroped with toluene and purified
by flash chromatography on silica gel (Hexane/ethyl acetate = 2/1−1/2)
133.9, 131.9, 130.5, 128.5 (q, JC−F = 31.0 Hz), 128.6, 128.41, 128.38,
128.36, 127.9, 127.8, 127.7, 125.7 (q, JC−F = 5.6 Hz), 124.1, 124.0 (d,
JC−F = 272 Hz), 119.2, 96.3, 80.5, 74.5, 73.6, 72.6, 71.5, 71.3, 63.0, 20.7;
IR (film, cm−1): ν = 2890, 1744, 1598, 1368, 1315; HRMS (ESI): calcd
for C38H35F6N2O6 (M + H): 729.2399; found: 729.2405.
6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluoromethyl-
benzylideneamino-D-glucopyranosyl N-Phenyl Trifluoroaceti-
1
midate 32. Viscous oil: 7.76 g, 98%, β only; H NMR (CDCl3, 400
MHz): δ = 8.76 (s, 1 H), 8.20 (d, J = 7.6 Hz, 1 H), 7.73 (d, J = 7.6 Hz,
1 H), 7.63−7.54 (m, 2 H), 7.37−7.06 (m, 13 H), 6.83−6.74 (m, 2 H),
5.92 (brs, 1 H), 4.86 (d, J = 10.8 Hz, 1 H), 4.73−4.57 (m, 3 H), 4.40−
4.26 (m, 2 H), 4.06−3.94 (m, 1 H), 3.75−3.58 (m, 3 H), 2.05 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 170.7, 161.7, 143.3, 137.5, 137.4,
133.4, 132.0, 130.7, 128.6, 128.5, 128.3, 128.14, 128.09, 127.9, 127.8,
126.2, 125.7 (q, JC−F = 5.6 Hz), 124.3, 124.0 (d, JC−F = 272 Hz), 119.2,
95.6, 83.2, 76.1, 75.2, 75.1, 73.9, 73.0, 62.6, 20.8. IR (film, cm−1): ν =
3032, 2978, 1738, 1719, 1644, 1488, 1313. HRMS (ESI): calcd for
C38H34F6N2O6Na (M + Na): 751.2219; found: 751.2217.
1
to afford 3.11 g (52%) of 33F as a viscous oil. H NMR (CDCl3, 400
MHz): δ = 8.71 (d, J = 2.0 Hz, 1 H), 8.21 (d, J = 6.0 Hz, 1 H), 7.69 (d, J =
6.0 Hz, 1 H), 7.58−7.47 (m, 2 H), 7.35−7.05 (m, 15 H), 5.01 (d, J = 8.0
Hz, 1 H), 4.82 (d, J = 10.8 Hz, 1 H), 4.70−4.47 (m, 5 H), 3.92 (t, J = 8.0
Hz, 1 H), 3.83−3.65 (m, 3 H), 3.60 (dd, J = 9.6, 3.6 Hz, 1 H), 3.34 (dd, J =
8.0, 9.6 Hz, 1 H); IR (film, cm−1): ν = 3403, 2820, 1640, 1454, 1359, 1312.
3,4,6-Tri-O-benzyl-2-deoxy-2-o-trifluoromethylbenzylide-
neamino-D-glucopyranosyl N-Phenyl Trifluoroacetimidate
33.21 Viscous oil: 3.95 g, 98%, α:β = 1:3; 33α: 1H NMR (CDCl3, 400
MHz): δ = 8.77 (s, 1 H), 8.35 (d, J = 7.6 Hz, 1 H), 7.75 (d, J = 7.6 Hz,
1 H), 7.67−7.55 (m, 2 H), 7.43−6.55 (m, 20 H), 6.49 (brs, 1 H), 4.89 (d,
J = 10.8 Hz, 1 H), 4.77−4.68 (m, 2 H), 4.65−4.53 (m, 3 H), 4.32−4.20
(m, 2 H), 3.96−3.85 (m, 2 H), 3.83−3.72 (m, 2 H); 13C NMR (CDCl3,
100 MHz): δ = 160.6, 137.9, 137.8, 137.7, 133.4, 132.0, 130.7, 129.4 (q,
JC−F = 31.0 Hz), 128.5, 128.44, 128.38, 128.3, 128.2, 128.0, 127.92,
3,4,6-Tri-O-acetyl-1-tert-butyldimethylsilyl-2-deoxy-2-p-me-
thoxybenzylideneamino-D-glucopyranoside 33B. A 250 mL
oven-dried RBF was charged with 33A (13.0 g, 30.7 mmol, 1.0
equiv),2 TBSCl (5.10 g, 33.8 mmol, 1.1 equiv.), imidazole (4.2 g, 61.4
mmol, 2.0 equiv) and DMF (120 mL). The resulting mixture was stirred
at room temperature overnight. The reaction mixture was diluted with
ethyl acetate, washed with brine (2 × 50 mL), concentrated in vacuo.
The residue was purified by silica gel flash chromatography (hexane/
ethyl acetate =5/1 → 3/1 with 1% Et3N) to afford 33B (16.4 g, 99%) as a
viscous oil. 1H NMR (CDCl3, 400 MHz): δ = 8.13 (s, 1 H), 7.63 (d, J =
8.8 Hz, 2 H), 6.89 (d, J = 8.8 Hz, 2 H), 5.45 (t, J = 9.6, 1 H), 5.06 (app t,
J = 9.6 Hz, 1 H), 4.93 (d, J = 7.6 Hz, 1 H), 4.28 (dd, J = 12.0, 6.0 Hz, 1 H),
4.18−3.97 (m, 2 H), 3.84 (s, 3 H), 3.24 (dd, J = 7.6, 10.0 Hz, 1 H),
2.08 (s, 3 H), 2.03 (s, 3 H), 1.88 (s, 3 H), 0.79 (s, 9 H), 0.06 (s, 3 H), 0.00
(s, 3 H).
1-tert-Butyldimethylsilyl-2-deoxy-2-p-methoxybenzylide-
neamino-D-glucopyranoside 33C. A 250 mL oven-dried RBF was
charged with 33B (6.5 g, 12.0 mmol, 1.0 equiv), sodium methoxide
(0.52 g, 9.6 mmol, 0.8 equiv), and CH2Cl2/MeOH (50 mL/100 mL).
The resulting solution was stirred at room temperature. When the
reaction mixture was complete as monitored by TLC, it was evaporated
and then purified by flash chromatography on silica gel (ethyl acetate →
CH2Cl2/MeOH = 5/1) to afford 33C (4.80 g, 96%) as a viscous oil. 1H
NMR (CD3OD, 400 MHz): δ = 8.21 (s, 1 H), 7.72 (d, J = 8.8 Hz, 2 H),
6.98 (d, J = 8.8 Hz, 2 H), 4.88 (d, J = 7.2 Hz, 1 H), 3.92−3.86 (m, 1 H),
3.85 (s, 3 H), 3.76−3.72 (m, 1 H), 3.47−3.38 (m, 2 H), 2.97 (dd, J = 9.6,
7.2 Hz, 1 H), 0.78 (s, 9 H), 0.09 (s, 3 H), 0.02 (s, 3 H).
3,4,6-Tri-O-benzyl-1-tert-butyldimethylsilyl-2-deoxy-2-p-
methoxybenzylideneamino-D-glucopyranoside 33D. A 250 mL
RBF was charged with 33C (12.3 g, 30.0 mmol, 1.0 equiv), benzyl
bromide (16.2 mL, 135 mmol, 4.5 equiv) and DMF (100 mL). The
solution was cooled to −20 °C, and NaH (60%, 5.40 g, 135 mmol, 4.5
equiv) was added in several portions. The mixture was warmed to room
temperature and stirred overnight. The reaction mixture was diluted
with ethyl acetate (100 mL), washed with brine (2 × 30 mL), dried over
Na2SO4, concentrated in vacuo. The residue was purified by silica gel
flash chromatography (hexane/ethyl acetate = 20/1 → 10/1 → 5/1
with 1% Et3N) to afford 33D (15.6 g, 76%) as a viscous oil. 1H NMR
(CDCl3, 400 MHz): δ = 8.24 (s, 1 H), 7.68 (d, J = 8.8 Hz, 2 H),
127.88, 127.85, 127.7, 127.6, 125.6 (q, JC−F =5.6 Hz), 123.9 (d, JC−F
=
273 Hz), 95.7, 80.2, 75.3, 74.2, 73.8, 73.5, 60.4; IR (film, cm−1): ν =
2876, 1667, 1594, 1488, 1313; HRMS (ESI): calcd for C43H38F6N2O5Na
1
(M + Na): 799.2583; found: 799.2598. 33β: H NMR (CDCl3, 400
MHz): δ = 8.79 (s, 1 H), 8.22 (d, J = 7.6 Hz, 1 H), 7.75 (d, J = 7.6 Hz,
1 H), 7.63−7.54 (m, 2 H), 7.43−7.05 (m, 18 H), 6.85−6.74 (m, 2 H),
6.07 (brs, 1 H), 4.89 (d, J = 10.8 Hz, 1 H), 4.77−4.56 (m, 5 H), 4.10−3.63
(m, 6 H); 13C NMR (CDCl3, 100 MHz): δ = 161.5, 137.9, 137.8, 137.7,
135.2, 133.5, 131.9, 130.6, 129.5 (q, JC−F = 31.0 Hz), 129.3, 128.6, 128.4,
128.3, 128.2, 127.9, 127.8, 127.6, 126.2, 125.7 (q, JC−F = 5.5 Hz), 124.1,
123.9 (d, JC−F = 273 Hz), 95.8, 83.0, 76.2, 76.0, 75.2, 75.1, 73.4, 60.4; IR
(film, cm−1): ν = 3031, 2865, 1644, 1597, 1488, 1314; HRMS (ESI): calc.
for C43H38F6N2O5Na (M + Na): 799.2584; found: 799.2598.
General Glycosylation Procedure Using Ni(4-F-PhCN)4(OTf)2:
Formation of Disaccharide 5 and Transfer Product 7. A 10 mL
oven-dried Schlenk flask was charged with donor 10 (31 mg, 0.05 mmol,
1.0 equiv), thioglycoside acceptor 3 (53 mg, 0.10 mmol, 2.0 equiv), and
CH2Cl2 (0.3 mL). Then a 0.25 mL of preformed solution of Ni(4-F-
PhCN)4(OTf)2, which was generated in situ from a reaction of Ni(4-F-
PhCN)4Cl2 (12 mg, 0.02 mmol, 10 mol %) and AgOTf (11 mg, 0.4
mmol, 20 mol %) in dichloromethane (1.0 mL) for 30 min, was added to
the solution. The resulting mixture was stirred at 35 °C overnight. When
the reaction was complete as monitored by TLC (toluene/acetonitrile =
4/1), the mixture was evaporated, and purified by flash chromatography
on silica gel (hexane/ethyl acetate = 9/1 → 5/1 → 3/2 with 1% Et3N) to
afford disaccharide 5 (28 mg, 58%, α only) and thioglycoside 7 (4 mg,
14%, α only) as viscous oil.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-benzylidene-
2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-glucopyra-
noside 5. [α]24 = 28.2 (c = 2.1, CH2Cl2); 1H NMR (CDCl3,
D
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Article
400 MHz): δ = 8.43 (d, J = 2.0 Hz, 1 H), 8.22 (d, J = 7.6 Hz, 1 H), 7.62
(d, J = 7.6 Hz, 1 H), 7.56−7.33 (m, 7 H)., 7.23−7.16 (m, 1 H), 7.14−
7.03 (m, 2 H), 6.93 (d, J = 7.2 Hz, 2 H), 5.65−5.51 (m, 2 H), 5.37 (d, J =
3.6 Hz, 1 H), 5.19 (s, 1 H), 5.09 (t, J = 5.6 Hz, 2 H), 4.98 (d, J = 12.0 Hz,
1 H), 4.61 (d, J = 12.0 Hz, 1 H), 4.38−4.26 (m, 4 H), 4.06 (dd, J = 12.0,
2.0 Hz, 1 H), 3.92−3.65 (m, 3 H), 3.62 (dd, J = 10.4, 3.6 Hz, 1 H), 3.56−
3.49 (m, 1 H), 2.11 (s, 3 H), 2.02 (s, 3 H), 1.82 (s, 3 H); 13C NMR
(CDCl3, 100 MHz): δ = 170.7, 169.7, 169.6, 160.4, 153.8, 136.3, 132.4,
131.9, 130.7, 129.1, 128.9, 128.3, 128.2, 127.9, 126.3, 125.5, 101.5, 99.0,
95.2, 87.1, 82.0, 76.7, 74.6, 72.3, 70.7, 70.0, 68.7, 68.5, 67.8, 62.1, 55.7,
20.8, 20.7, 20.3; IR (film, cm−1): ν = 3335, 2872, 1746, 1643, 1523, 1368,
1314, 1226; HRMS (ESI): calcd for C42H43Cl3F3N2O13S (M + H):
977.1504; found: 977.1505.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-1-thiol-α-D-glucopyranoside 7. 1H NMR
(CDCl3, 400 MHz):22 δ = 8.66 (d, J = 2.0 Hz, 1 H), 8.27 (d, J = 7.6
Hz, 1 H), 7.70−7.47 (m 5 H), 7.33 −7.22 (m, 2 H), 5.72−5.62 (m, 2 H),
5.14 (app t, J = 9.6 Hz, 1 H), 4.72−4.65 (m, 1 H), 4.30 (dd, J = 5.6, 12.0
Hz, 1 H), 4.02 (dd, J = 5.6, 10.0 Hz, 1 H), 3.97 (dd, J = 2.0, 12.0 Hz, 1 H),
2.05 (s, 3 H), 2.00 (s, 3 H), 1.89 (s, 3 H). 13C NMR (CDCl3, 100 MHz):
δ = 170.6, 169.9, 169.7, 160.3, 133.2, 132.3, 131.7, 130.9, 129.2, 129.0,
127.3, 125.4, 86.3, 72.2, 71.7, 68.6, 68.4, 62.1, 20.7, 20.6, 20.4. IR (film,
cm−1): ν = 2932954, 1744, 1643, 1366, 1314, 1221. HRMS (ESI): calcd
for C26H27F3NO7S (M + H): 554.1460; found: 554.1473.
(m, 2 H), 5.58 (t, J = 9.6 Hz, 1 H), 5.41 (d, J = 5.6 Hz, 1 H), 5.13 (app t,
J = 10.0 Hz, 1 H), 4.64−4.57 (m, 1 H), 4.38 (dd, J = 12.0, 4.8 Hz, 1 H),
4.12 (dd, J = 12.0, 2.0 Hz, 1 H), 3.95 (dd, J = 10.0, 5.6 Hz, 1 H), 2.66−
2.48 (m, 2 H), 2.11 (s, 3 H), 2.04 (s, 3 H), 1.86 (s, 3 H), 1.30 (t, J = 7.2
Hz, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.7, 170.0, 169.7, 160.0,
133.2, 132.3, 130.8, 129.1, 125.4 (q, JC−F = 5.5 Hz), 83.5, 72.2, 71.8, 68.8,
67.7, 62.2, 23.6, 20.8, 20.7, 20.4, 14.4; IR (film, cm−1): ν = 2930, 1748,
1644, 1453, 1368, 1315, 1227; HRMS (ESI): calcd for C22H26F3NO7S
(M + H): 506.1460; found: 506.1456.
Naphthyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethyl-
benzylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-benzyli-
dene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-gluco-
pyranoside 19. Viscous oil: 30 mg, 59%, α only; [α]24D = 6.1 (c = 1.0,
CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.53−8.47 (m,1 H), 8.40
(d, J = 2.0 Hz, 1 H), 8.20 (d, J = 7.6 Hz, 1 H), 7.92−7.83 (m, 3 H), 7.64−
7.43 (m, 5 H), 7.18−7.13 (m, 1 H), 7.08−7.03 (m, 2 H), 6.89 (d, J = 7.2
Hz, 2 H), 5.63 (d, J = 8.4 Hz, 1 H), 5.54 (t, J = 9.6 Hz, 1 H), 5.34 (d, J = 4.0
Hz, 1 H), 5.17 (s, 1 H), 5.13−5.05 (m, 2 H), 4.99 (d, J = 12.0 Hz, 1 H),
4.62 (d, J = 12.0 Hz, 1 H), 4.34−4.23 (m, 4 H), 4.08−4.02 (m, 1 H),
3.81−3.65 (m, 3 H), 3.60 (dd, J = 10.4, 4.0 Hz, 1 H), 3.46 (td, J = 9.6, 4.8
Hz, 1 H), 2.10 (s, 3 H), 2.02 (s, 3 H), 1.82 (s, 3 H); 13C NMR (CDCl3,
100 MHz): δ = 170.7, 169.8, 169.7, 160.5, 153.7, 136.3, 134.1, 133.2,
131.9, 130.8, 129.7, 128.9, 128.7, 128.3, 127.9, 126.9, 126.4, 125.7, 125.5,
101.5, 99.1, 95.1, 82.1, 77.2, 74.7, 72.3, 70.6, 70.0, 68.6, 67.8, 62.1, 55.8,
20.8, 20.7, 20.4; IR (film, cm−1): ν = 3335, 2965, 1744, 1643, 1532, 1368,
1314, 1225; HRMS (ESI): calcd for C46H45Cl3F3N2O13S (M + H):
1027.1660; found: 1027.1650.
Naphthyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethyl-
benzylideneamino-1-thiol-α-D-glucopyranoside 26. Viscous oil:
3 mg, 10%, α only; 1H NMR (CDCl3, 400 MHz):22 δ = 8.71 (d, J = 2.0
Hz, 1 H), 8.57−8.46 (m, 2 H), 7.86−7.26 (m, 9 H), 5.77 (t, J = 9.6 Hz,
1 H), 5.65 (d, J = 5.6 Hz, 1 H), 4.83−4.74 (m, 1 H), 4.29 (dd, J = 12.0,
4.8 Hz, 1 H), 4.05 (dd, J = 10.0, 5.6 Hz, 1 H), 3.90−3.83 (m, 1 H), 3.63−
3.52 (m, 1 H), 2.07 (s, 3 H), 1.94 (s, 3 H), 1.92 (s, 3 H); 13C NMR
(CDCl3, 100 MHz): δ = 170.6, 169.8, 147.8, 134.1, 133.1, 132.3, 130.9,
129.14, 129.09, 128.9, 128.3, 127.2, 126.8, 126.2, 125.1, 124.1, 87.0, 74.1,
72.2, 71.8, 68.8, 62.1, 20.7, 20.5; IR (film, cm−1): ν = 2924, 1745, 1644,
1439, 1369, 1313, 1221; HRMS (ESI): calcd for C30H29F3NO7S (M +
H): 604.1617; found: 604.1615.
4-Methyphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-ben-
zylidene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-
glucopyranoside 20. Viscous oil: 37 mg, 38%, α:β =11:1; 1H NMR
(CDCl3, 400 MHz): δ = 8.42 (d, J = 2.0 Hz, 1 H), 8.20 (d, J = 7.2 Hz,
1 H), 7.63−7.52 (m, 3 H), 7.39 (d, J = 8.0 Hz, 2 H), 7.18−7.13 (m, 3 H),
7.07−7.04 (m, 2 H), 6.91 (d, J = 8.0 Hz, 2 H), 5.60−5.53(m, 2 H), 5.36 (d,
J = 4.0 Hz, 1 H), 5.17 (s, 1 H), 5.15−5.04 (m, 2 H), 5.00 (d, J = 12.0 Hz,
1 H), 4.59 (d, J = 12.0 Hz, 1 H), 4.36−4.23 (m, 4 H), 4.07−4.04 (m, 1 H),
3.78−3.66 (m, 2 H), 3.61 (dd, J = 10.4, 4.0 Hz, 1 H), 3.54−3.48 (m, 1 H),
2.36 (s, 3 H), 2.11 (s, 3 H), 2.02 (s, 3 H), 1.82 (s, 3 H); 13C NMR (CDCl3,
100 MHz): δ = 170.7, 169.8, 169.7, 160.5, 153.7, 138.6, 136.3, 133.2, 130.8,
129.9, 129.0, 128.3, 128.0, 125.5, 101.5, 99.0, 95.2, 82.1, 77.2, 74.6, 72.3,
70.6, 70.0, 68.6, 67.8, 62.1, 55.6, 21.2, 20.8, 20.7, 20.4; IR (film, cm−1): ν =
3383, 2958, 1746, 1642, 1539, 1368, 1314, 1224; HRMS (ESI): calcd for
C43H45Cl3F3N2O13S (M + H): 991.1660; found: 991.1673.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-p-trifluoromethylben-
zylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-benzylidene-
2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-glucopyra-
noside 4. Viscous oil: 16 mg, 33%, α:β = 21:1; 1H NMR (CDCl3, 400
MHz): δ = 8.17 (s, 1 H), 7.48−7.31 (m, 11 H), 7.16−7.14 (m, 2 H),
6.63−6.60 (m, 1 H), 5.65 (t, J = 9.6 Hz, 1 H), 5.55 (app t, J = 9.2 Hz,
1 H), 5.36 (d, J = 4.0 Hz, 1 H), 5.18−4.94 (m, 4 H), 4.60 (d, J = 12.0 Hz,
1 H), 4.42−4.03 (m, 5 H), 3.72−3.45 (m, 5 H), 2.12 (s, 3 H), 2.04 (s,
3 H), 1.83 (s, 3 H);13C NMR (CDCl3, 100 MHz): δ = 170.9, 170.8,
170.7, 132.7, 132.5, 129.2, 128.4, 128.0, 126.0, 125.7, 100.5, 99.6, 95.2,
77.2, 74.6, 71.0, 70.1, 70.0, 68.6, 68.5, 20.9, 20.7, 20.6; IR (film, cm−1):
ν = 3343, 2824, 1744, 1648, 1532, 1368, 1323, 1230; HRMS (ESI): calcd
for C42H43Cl3F3N2O13S (M + H): 977.1504; found: 977.1512.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-p-trifluoromethylben-
zylideneamino-1-thiol-α-D-glucopyranoside 6. Viscous oil: 9
1
mg, 33%, α only; H NMR (CDCl3, 400 MHz): δ = 8.34 (s, 1 H),
7.90 (d, J = 8.0 Hz, 2 H), 7.69 (d, J = 8.0 Hz, 2 H), 7.48−7.45 (m, 2 H),
7.33−7.24 (m, 3 H), 5.72−5.64 (m, 2 H), 5.13 (app t, J = 10.0 Hz, 1 H),
4.75−4.67 (m, 1 H), 4.32 (dd, J = 12.0, 5.2 Hz, 1 H), 4.00−3.93 (m,
2 H), 2.06 (s, 3 H), 2.00 (s, 3 H), 1.88 (s, 3 H); 13C NMR (CDCl3, 100
MHz): δ = 170.6, 170.2, 169.5, 162.4, 133.1, 131.8, 131.7, 129.0, 127.4,
125.7 (q, JC−F = 5.5 Hz), 86.5, 72.1, 71.9, 68.8, 68.4, 62.1, 20.74, 20.70,
20.6; IR (film, cm−1): ν = 2923, 1748, 1647, 1454, 1370, 1324, 1234;
HRMS (ESI): calcd for C26H27F3NO7S (M + H): 554.1460; found:
554.1463.
Ethyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylbenzyli-
deneamino-α-D-glucopyranosyl-(1→3)-4,6-O-benzylidene-2-
deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-glucopyrano-
side 18. Viscous oil: 32 mg, 43%, α:β = 10:1; 1H NMR (CDCl3, 400
MHz): δ = 8.42 (d, J = 2.0 Hz, 1 H), 8.23 (d, J = 7.6 Hz, 1 H), 7.64−7.33
(m, 4 H), 7.22−7.07 (m, 1 H), 7.11−7.04 (m, 2 H), 6.91 (d, J = 7.2 Hz,
2 H), 5.76 (t, J = 10.0 Hz, 1 H), 5.49 (d, J = 8.8 Hz, 1 H), 5.18 (s, 1 H),
5.09 (app t, J = 10.0 Hz, 2 H), 5.02 (d, J = 12.0 Hz, 1 H), 4.57 (d, J =
12.0 Hz, 1 H), 4.40−4.23 (m, 3 H), 4.19 (t, J = 9.2 Hz, 1 H), 4.10 (dd, J =
12.0, 2.0 Hz, 1 H), 3.85−3.73 (m, 2 H), 3.71 (t, J = 10.0 Hz, 1 H), 3.62
(dd, J = 10.0, 4.0 Hz, 1 H), 3.51 (td, J = 9.6, 4.8 Hz, 1 H), 2.76 (q, J =
7.2 Hz, 2 H), 2.12 (s, 3 H), 2.03 (s, 3 H), 1.83 (s, 3 H), 1.27 (t, J = 7.2 Hz,
3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.7, 169.8, 169.6, 160.4,
153.9, 136.3, 131.9, 130.8, 129.0, 128.3, 128.0, 126.2, 125.5, 101.5, 99.1,
95.2, 85.1, 82.2, 77.2, 74.6, 72.3, 70.7, 70.1, 68.6, 67.8, 62.3, 55.6,
24.3, 20.9, 20.8, 20.4, 14.8; IR (film, cm−1): ν = 3332, 2872, 1746, 1643,
1527, 1368, 1314, 1227; HRMS (ESI): calcd for C38H43Cl3F3N2O13S
(M + H): 929.1504; found: 929.1516.
4-Methylphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-1-thiol-α-D-glucopyranoside 27. Viscous
oil: 11 mg, 20%, α only; 1H NMR (CDCl3, 400 MHz): δ = 8.65 (d, J = 2.0
Hz, 1 H), 8.28 (d, J = 8.0 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.64−7.53 (m,
2 H), 7.38 (d, J = 8.0 Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 5.66 (t, J = 9.6 Hz,
1 H), 5.62 (d, J = 5.6 Hz, 1 H), 5.14 (app t, J = 10.0 Hz, 1 H), 4.73−4.68 (m,
1 H), 4.30 (dd, J = 12.0, 4.8 Hz, 1 H), 4.01 (dd, J = 10.0, 5.6 Hz, 1 H), 3.97
(dd, J = 12.0, 2.0 Hz, 1 H), 2.32 (s, 3 H), 2.06 (s, 3 H), 2.01 (s, 3 H), 1.89 (s,
3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.6, 170.0, 169.7, 137.6, 132.5,
130.9, 129.8, 129.2, 129.1, 86.7, 72.2, 71.7, 68.8, 68.2, 62.2, 21.1, 20.8, 20.7,
20.4; IR (film, cm−1): ν= 2924, 1748, 1643, 1492, 1369, 1315, 1228; HRMS
(ESI): calcd for C27H29F3NO7S (M + H): 568.1617; found: 568.1616.
4-Methoxyphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoro-
methylbenzylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-
benzylidene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-
D-glucopyranoside 21. Viscous oil: 37 mg, 38%, α:β =11:1; 1H NMR
Ethyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylbenzyli-
deneamino-1-thiol-α-D-glucopyranoside 25. Viscous oil: 11 mg,
22%, α only; 1H NMR (CDCl3, 400 MHz):22 δ = 8.61 (d, J = 2.0 Hz,
1 H), 8.21 (d, J = 7.6 Hz, 1 H), 7.67 (d, J = 7.6 Hz, 1 H), 7.62−7.53
7338
dx.doi.org/10.1021/jo301050q | J. Org. Chem. 2012, 77, 7330−7343

The Journal of Organic Chemistry
Article
(CDCl3, 400 MHz): δ = 8.41 (d, J = 2.0 Hz, 1 H), 8.20 (d, J = 7.2 Hz,
1 H), 7.63−7.44 (m, 5 H), 7.18−7.13 (m, 1 H), 7.09−7.04 (m, 2 H),
6.92−6.84 (m, 4 H), 5.62−5.52 (m, 2 H), 5.35 (d, J = 4.0 Hz, 1 H), 5.17
(s, 1 H), 5.10 (app t, J = 10.0 Hz, 1 H), 5.03−4.93 (m, 2 H), 4.62 (d, J =
12.0 Hz, 1 H), 4.35−4.22 (m, 4 H), 4.09−4.02 (m, 1 H), 3.83 (s, 3 H),
3.81−3.67 (m, 3 H), 3.61 (dd, J = 4.0, 10.4 Hz, 1 H), 3.53−3.44 (m,
1 H), 2.11 (s, 3 H), 2.02 (s, 3 H), 1.82 (s, 3 H); 13C NMR (CDCl3, 100
MHz): δ = 170.7, 169.8, 169.7, 160.2, 136.3, 135.9, 131.8, 130.7, 128.9,
128.3, 127.9, 127.1, 125.5, 121.6, 114.7, 101.5, 99.0, 95.2, 87.1, 82.0,
77.2, 76.4, 74.6, 72.3, 70.6, 70.0, 68.6, 67.8, 62.1, 55.5, 55.3, 20.8, 20.7,
20.4; IR (film, cm−1): ν = 3342, 2958, 1745, 1642, 1539, 1493, 1368,
1314, 1226; HRMS (ESI): calcd for C43H45Cl3F3N2O14S (M + H):
1007.1609; found: 1007.1597.
4-Methoxyphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoro-
methylbenzylideneamino-1-thiol-α-D-glucopyranoside 28. Vis-
cous oil: 17 mg, 30%, α only; 1H NMR (CDCl3, 400 MHz):22 δ = 8.65
(d, J = 2.0 Hz, 1 H), 8.32−8.25 (m, 1 H), 7.72−7.54 (m, 3 H), 7.42 (d,
J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 5.65 (t, J = 9.6 Hz, 1 H), 5.52
(d, J = 5.6 Hz, 1 H), 5.14 (app t, J = 6.0 Hz, 1 H), 4.77−4.71 (m, 1 H),
4.31 (dd, J = 12.0, 4.8 Hz, 1 H), 4.03−3.95 (m, 2 H), 3.79 (s, 3 H), 2.06
(s, 3 H), 2.03 (s, 3 H), 1.89 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ =
170.7, 169.9, 169.7, 160.2, 159.6, 134.9, 133.2, 132.3, 130.9, 129.2, 129.0,
125.4 (q, JC−F = 5.5 Hz), 124.1, 123.0, 114.6, 87.3, 72.2, 68.8, 68.1, 63.1,
60.9, 55.3, 20.7, 20.5, 20.4; IR (film, cm−1): ν = 2934, 1747, 1644, 1494,
1369, 1315, 1227; HRMS (ESI): calcd for C27H29F3NO8S (M + H):
584.1566; found: 584.1567.
4-Fluorophenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-ben-
zylidene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-
glucopyranoside 22. Viscous oil: 23 mg, 58%, α:β =20:1; 1H NMR
(CDCl3, 400 MHz): δ = 8.44 (d, J = 2.0 Hz, 1 H), 8.21 (d, J = 7.2 Hz,
1 H), 7.62−7.50 (m, 5 H), 7.21−7.17 (m, 1 H), 7.10−7.02 (m, 4 H),
6.92 (d, J = 7.2 Hz, 2 H), 5.69 (d, J = 8.4 Hz, 1 H), 5.58 (t, J = 9.6 Hz,
1 H), 5.37 (d, J = 3.6 Hz, 1 H), 5.19 (s, 1 H), 5.11 (app t, J = 10.0 Hz,
1 H), 5.04−4.93 (m, 2 H), 4.64 (d, J = 12.0 Hz, 1 H), 4.36−4.18 (m,
4 H), 4.10−4.04 (m, 1 H), 3.77−3.59 (m, 4 H), 3.51 (td, J = 9.6, 4.8 Hz,
1 H), 2.13 (s, 3 H), 2.04 (s, 3 H), 1.84 (s, 3 H); 13C NMR (CDCl3,
100 MHz): δ = 170.7, 169.8, 169.7, 163.0 (d, JC−F = 248 Hz), 160.5,
153.7, 136.2, 135.7, 135.6, 133.1, 131.8, 130.8, 129.0, 128.2, 127.9, 125.5,
116.3, 116.1, 101.5, 99.0, 95.2, 87.0, 81.9, 77.2, 74.6, 72.3, 70.6, 70.0,
68.6, 68.4, 67.8, 62.1, 55.5, 20.8, 20.7, 20.3; IR (film, cm−1): ν = 3382,
2958, 1744, 1643, 1490, 1368, 1314, 1223; HRMS (ESI): calcd for
C42H41Cl3F4N2O13S (M + H): 995.1409; found: 995.1434.
4-Fluorophenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-1-thiol-α-D-glucopyranoside 29. Viscous
oil: 2 mg, 9%, α only; 1H NMR (CDCl3, 400 MHz):22 δ = 8.65 (d, J = 2.0
Hz, 1 H), 8.27 (d, J = 8.0 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.64−7.53
(m, 2 H), 7.50−7.45 (m, 2 H), 7.03−6.97 (m, 2 H), 5.64 (t, J = 10.0 Hz,
1 H), 5.60 (d, J = 5.6 Hz, 1 H), 5.14 (app t, J = 10.0 Hz, 1 H), 4.71−4.63
(m, 1 H), 4.30 (dd, J = 12.4, 5.2 Hz, 1 H), 4.03−3.94 (m, 2 H), 2.06 (s,
3 H), 2.02 (s, 3 H), 1.89 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ =
170.6, 169.9, 169.7, 161.2, 160.4, 134.5, 134.4, 133.1, 132.3, 131.0, 129.1,
129.0, 127.9, 125.5 (q, JC−F = 5.7 Hz), 116.3, 116.0, 86.8, 72.1, 71.6,
68.7, 68.3, 62.2, 20.72, 20.69, 20.4; IR (film, cm−1): ν = 2922, 1748,
1644, 1491, 1368, 1315, 1227; HRMS (ESI): calcd for C26H26F4NO7S
(M + H): 572.1366; found: 572.1368.
2965, 1743, 1642, 1474, 1368, 1314, 1224; HRMS (ESI): calcd for
C42H42Cl3F4N2O13S (M + H): 995.1409; found: 995.1409.
2-Fluorophenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-1-thiol-α-D-glucopyranoside 30. Viscous
oil: 1.3 mg, 4%, α only; 1H NMR (CDCl3, 400 MHz): δ = 8.67 (d, J =
2.0 Hz, 1 H), 8.29 (d, J = 8.0 Hz, 1 H), 7.74−7.53 (m, 5 H), 7.13−7.06
(m, 2 H), 5.76 (d, J = 6.0 Hz, 1 H), 5.70 (t, J = 9.6 Hz, 1 H), 5.18−5.02
(m, 2 H), 4.70−4.63 (m, 1 H), 4.27 (dd, J = 12.0, 4.8 Hz, 1 H), 4.03 (dd,
J = 9.6, 5.6 Hz, 1 H), 3.85 (dd, J = 12.0, 2.0 Hz, 1 H), 2.06 (s, 3 H), 1.97
(s, 3 H), 1.90 (s, 3 H); IR (film, cm−1): ν = 2925, 1749, 1644, 1474,
1370, 1315, 1228; HRMS (ESI): calcd for C26H26F4NO7S (M + H):
572.1366; found: 572.1368.
2-Trifluoromethylphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-tri-
fluoromethylbenzylideneamino-α-D-glucopyranosyl-(1→3)-
4,6-O-benzylidene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-
thiol-β-D-glucopyranoside 24. Viscous oil: 31 mg, 61%, α only;
[α]24D = 19.8 (c = 3.3, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.42
(d, J = 2.0 Hz, 1 H), 8.22 (d, J = 7.6 Hz, 1 H), 7.70 (d, J = 7.6 Hz, 1 H),
7.70 (d, J = 7.6 Hz, 1 H), 7.63 (d, J = 7.6 Hz, 1 H), 7.60−7.48 (m, 3 H),
7.46−7.40 (m, 1 H), 7.22−7.15 (m, 1 H), 7.10−7.03 (m, 2 H), 6.90 (d,
J = 7.6 Hz, 2 H), 5.65−5.53 (m, 2 H), 5.34 (d, J = 4.0 Hz, 1 H), 5.20 (s,
1 H), 5.14−4.94 (m, 3 H), 4.53 (d, J = 12.0 Hz, 1 H), 4.44−4.37 (m,
1 H), 4.33−4.22 (m, 3 H), 4.13−4.05 (m, 2 H), 3.85 (t, J = 4.8 Hz, 2 H),
3.77 (t, J = 6.4 Hz, 1 H), 3.61 (dd, J = 10.0, 3.6 Hz, 1 H), 3.50 (td, J = 9.6,
4.8 Hz, 1 H), 2.11 (s, 3 H), 2.02 (s, 3 H), 1.82 (s, 3 H); 13C NMR
(CDCl3, 100 MHz): δ = 170.7, 169.8, 169.6, 160.5, 154.0, 136.2, 135.5,
132.3, 131.9, 130.8, 128.9, 128.3, 128.0, 125.5, 101.6, 99.2, 95.0, 81.9,
77.2, 74.8, 72.3, 70.7, 70.0, 68.6, 68.4, 67.9, 62.5, 55.6, 20.77, 20.75, 20.4;
IR (film, cm−1): ν = 3382, 2987, 1748, 1642, 1521, 1441, 1369, 1313,
1226; HRMS (ESI): calcd for C43H42Cl3F6N2O13S (M + H): 1045.1377;
found: 1045.1379.
Phenyl 3,4,6-Tri-O-benzyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-benzylidene-
2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-glucopyra-
noside 39. Viscous oil: 36 mg, 64%, α:β = 6:1; 1H NMR (CDCl3, 400
MHz):23 δ = 8.53 (d, J = 2.0 Hz, 1 H), 8.33 (d, J = 7.6 Hz, 1 H), 7.62−
7.13 (m, 26 H), 6.92 (d, J = 7.6 Hz, 2 H), 5.82 (d, J = 9.2 Hz, 1 H), 5.22
(d, J = 4.0 Hz, 1 H), 5.18 (s, 1 H), 4.87−4.04 (m, 13 H), 3.81−3.36 (m, 8
H); 13C NMR (CDCl3, 100 MHz): δ = 159.8, 154.1, 138.1, 138.0, 136.3,
133.6, 132.2, 132.9, 132.0, 131.8, 130.4, 128.9, 128.4, 128.3, 128.23,
128.18, 128.14, 128.10, 127.92, 127.91, 127.89, 127.8, 127.7, 127.5,
126.1, 125.5 (q, JC−F = 5.6 Hz), 125.4, 123.8 (d, JC−F = 273 Hz), 101.4,
99.5, 95.3, 87.8, 81.9, 80.9, 77.8, 77.2, 75.7, 75.6, 75.0, 74.6, 73.7, 70.9,
70.0, 68.5, 55.2; IR (film, cm−1): ν = 3389, 2867, 1743, 1640, 1454, 1368,
1314; HRMS (ESI): calcd for C57H55Cl3F3N2O10S (M + H): 1121.2595;
found: 1121.2575.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-α-D-glucopyranosyl-(1→3)-4-O-benzyl-2-O-
benzoyl-6-O-tert-butyldimethylsilyl-1-thiol-β-D-galactopyrano-
side 40. Viscous oil: 25 mg, 55%, α only; [α]24 = 73.9 (c = 1.8,
D
CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.62 (s, 1 H), 8.08 (d, J =
7.6 Hz, 2 H), 7.95 (d, J = 7.6 Hz, 1 H), 7.63−7.54 (m, 2 H), 7.50−7.15
(m, 14 H), 5.87−5.76 (m, 1 H), 5.49 (t, J = 9.6 Hz, 1 H), 5.18 (d, J = 11.2
Hz, 1 H), 5.12 (d, J = 3.2 Hz, 1 H), 4.99 (t, J = 9.6 Hz, 1 H), 4.82−4.75
(m, 1 H), 4.47 (d, J = 11.2, Hz, 1 H), 4.18−4.02 (m, 3 H), 3.94−3.55 (m,
6 H), 2.01 (s, 3 H), 1.79 (s, 3 H), 1.74 (s, 3 H), 0.85 (s, 9 H), 0.01 (s,
3 H), −0.01 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.5, 168.7,
168.3, 164.9, 161.3, 138.8, 133.1, 132.9, 132.1, 131.3, 130.7, 130.1, 129.8,
128.7, 128.6, 128.4, 128.0, 127.6, 127.5, 127.1, 125.4 (q, JC−F = 5.7 Hz),
98.2, 86.6, 81.0, 79.3, 77.2, 74.7, 72.8, 72.7, 70.5, 68.1, 67.9, 61.5, 61,4,
25.8, 20.6, 20.5, 20.3, 18.2, −5.4, −5.5; IR (film, cm−1): ν = 2928, 1728,
1668, 1602, 1365, 1314, 1263; HRMS (ESI): calcd for
C52H61F3NO13SSi (M + H): 1024.3585; found: 1024.3585.
2-Fluorophenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-α-D-glucopyranosyl-(1→3)-4,6-O-ben-
zylidene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-
glucopyranoside 23. Viscous oil: 30 mg, 60%, α only; [α]24D = 21.9
(c = 1.5, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.41 (d, J = 2.0 Hz,
1 H), 8.21 (d, J = 7.6 Hz, 1 H), 7.63−7.33 (m, 5 H), 7.20−7.03 (m, 5 H),
6.89 (d, J = 7.6 Hz, 2 H), 5.69 (d, J = 8.4 Hz, 1 H), 5.57 (t, J = 10.0 Hz,
1 H), 5.35 (d, J = 3.6 Hz, 1 H), 5.17 (s, 1 H), 5.14−4.97 (m, 3 H), 4.59
(d, J = 12.0 Hz, 1 H), 4.42−4.24 (m, 4 H), 4.14−4.05 (m, 1 H), 3.82−
3.54 (m, 3 H), 3.63 (dd, J = 10.0, 3.6 Hz, 1 H), 3.52−3.44 (m, 1 H), 2.12
(s, 3 H), 2.03 (s, 3 H), 1.83 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ =
170.7, 169.8, 169.7, 162.0 (d, JC−F = 245 Hz), 160.5, 153.9, 136.2, 135.8,
131.9, 130.9, 130.8, 129.0, 128.35. 128.27, 127.9, 125.5, 124.8, 124.7,
116.2, 116.0, 101.6, 99.1, 95.1, 86.6, 82.0, 76.3, 74.7, 72.3, 70.7, 70.1,
68.6, 68.4, 67.9, 62.3, 55.9, 20.81, 20.76, 20.4; IR (film, cm−1): ν = 3332,
Phenyl 6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-α-D-glucopyranosyl-(1→3)-4-O-benzyl-
2-O-benzoyl-6-O-tert-butyldimethylsilyl-1-thiol-β-D-galacto-
pyranoside 41. Viscous oil: 33 mg, 61%, α only; [α]24D = 30.4 (c = 0.1,
CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.69 (d, J = 2.0 Hz, 1 H),
8.02 (d, J = 6.8 Hz, 2 H), 7.95 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 7.6 Hz,
1 H), 7.48−7.32 (m, 7 H), 7.26−7.17 (m, 8 H), 7.14−7.07 (m, 6 H),
6.99−6.93 (m, 4 H), 5.92−5.76 (m, 1 H), 5.14 (d, J = 7.2 Hz, 1 H), 5.05
7339
dx.doi.org/10.1021/jo301050q | J. Org. Chem. 2012, 77, 7330−7343

The Journal of Organic Chemistry
Article
(d, J = 3.2 Hz, 1 H), 4.80 (d, J = 9.6 Hz, 1 H), 4.62 (d, J = 11.6 Hz, 1 H),
4.48 (d, J = 11.2 Hz, 1 H), 4.40 (d, J = 10.8 Hz, 1 H), 4.33 (d, J = 11.6 Hz,
1 H), 4.27 (d, J = 10.8 Hz, 1 H), 4.02−3.97 (m, 3 H), 3.92−3.88 (m,
1 H), 3,81 (dd, J = 12.0, 3.2 Hz, 1 H), 3.77−3.63 (m, 2 H), 3.49 (m, 3 H),
3.46 (t, J = 9.6 Hz, 1 H), 1.98 (s, 3 H), 0.83 (s, 9 H), 0.03 (s, 3 H), −0.03
(s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.5, 165.1, 160.5, 138.9,
138.1, 137.8, 133.1, 132.1, 132.0, 130.3, 130.0, 129.7, 128.7, 128.5, 128.3,
128.2, 128.1, 128.0, 127.9, 127.60, 127.57, 127.52, 127.47, 127.4, 127.1,
97.3, 86.8, 80.1, 79.2, 79.0, 77.2, 75.5, 75.0, 74.6, 74.3, 71.9, 69.6, 62.4,
61.3, 25.8, 20.8, 18.1, −5.4, −5.6; IR (film, cm−1): ν = 2925, 1735, 1642,
1454, 1362, 1314; HRMS (ESI): calcd for C62H69F3NO11SSi (M + H):
1120.4313; found: 1120.4309.
132.1, 131.4, 130.6, 129.0, 128.5, 128.29, 128.27, 128.2, 128.0, 127.9,
127.6, 127.4, 125.7 (q, JC−F = 5.6 Hz), 109.4, 100.8, 83.8, 81.8, 80.8,
76.5, 76.0, 75.1, 69.2, 66.7, 62.7, 28.2, 26.5, 21.0, 16.8; IR (film, cm−1):
ν = 2926, 1739, 1638, 1455, 1381, 1314; HRMS (ESI): calcd for
C45H49F3NO9S (M + H): 836.3080; found: 836.3088.
2-Trifluorophenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoro-
methylbenzylideneamino-α-D-glucopyranosyl-(1→4)-2,3-di-O-
isopropylidene-1-thiol-α-L-rhamnopyranoside 45. Viscous oil: 40
mg, 98%, α only; [α]24D = −48.9 (c = 0.8, CH2Cl2); 1H NMR (CDCl3,
400 MHz): δ = 8.66 (d, J = 2.0 Hz, 1 H), 8.21 (d, J = 7.6 Hz, 1 H), 7.75
(d, J = 7.6 Hz, 1 H), 7.68 (d, J = 7.6 Hz, 2 H), 7.61−7.46 (m, 3 H), 7.37−
7.32 (m, 1 H), 5.79 (s, 1 H), 5.66 (t, J = 10.0 Hz, 1 H), 5.24 (t, J = 9.6 Hz,
1 H), 5.03 (d, J = 3.6 Hz, 1 H), 4.53−4.41 (m, 3 H), 4.24 (dd, J = 10.0,
6.0 Hz, 1 H), 4.28−4.20 (m, 1 H), 4.14 (dd, J = 10.0, 2.0 Hz, 1 H), 3.71
(dd, J = 10.0, 3.6 Hz, 1 H), 3.48 (dd, J = 10.0, 7.6 Hz, 1 H), 2.12 (s, 3 H),
2.04 (s, 3 H), 1.88 (s, 3 H), 1.55 (s, 3 H), 1.37 (s, 3 H), 1.17 (d, J = 6.4
Hz, 1 H); 13C NMR (CDCl3, 100 MHz): δ = 170.8, 170.0, 169.8, 161.1,
133.6, 133.3, 133.2, 132.2, 130.8, 129.4, 129.1, 128.4, 127.3, 126.8 (q,
JC−F = 5.6 Hz), 125.6 (q, JC−F = 5.6 Hz), 125.4, 123.6 (d, JC−F = 275 Hz),
109.5, 100.0, 84.4, 81.9, 76.7, 76.5, 72.6, 70.9, 68.4, 67.8, 67.0, 61.6, 28.2,
26.6, 20.8, 20.7, 20.4, 16.9; IR (film, cm−1): ν = 2937, 1749, 1642, 1577,
1381, 1312, 1222; HRMS (ESI): calcd for C36H40F6NO11S (M + H):
808.2226; found: 808.2228.
2-Trifluorophenyl 6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-
trifluoromethylbenzylideneamino-α-D-glucopyranosyl-(1→4)-
2,3-di-O-isopropylidene-1-thiol-α-L-rhamnopyranoside 46. Vis-
cous oil: 35 mg, 78%, α only; [α]24D = −7.6 (c = 1.0, CH2Cl2); 1H NMR
(CDCl3, 400 MHz): δ = 8.76 (d, J = 2.0 Hz, 1 H), 8.35 (d, J = 7.6 Hz,
1 H), 7.76−7.44 (m, 6 H), 7.37−7.26 (m, 6 H), 7.21−7.12 (m, 5 H),
5.80 (s, 1 H), 4.93−4.87 (m, 2 H), 4.72 (d, J = 10.4 Hz, 1 H), 4.63−4.57
(m, 2 H), 4.61 (dd, J = 10.4, 6.0 Hz, 1 H), 4.43−4.18 (m, 6 H), 3.77 (t,
J = 9.6 Hz, 1 H), 3.61 (dd, J = 10.0, 3.2 Hz, 1 H), 3.45 (dd, J = 10.0, 7.6 Hz,
1 H), 2.06 (s, 3 H), 1.55 (s, 3 H), 1.35 (s, 3 H), 1.12 (d, J = 6.4 Hz, 1 H);
13C NMR (CDCl3, 100 MHz): δ = 170.8, 160.4, 138.0, 137.9, 133.5, 133.3,
Phenyl 6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-1-thiol-α-D-glucopyranoside 49. Viscous
oil: 5 mg, 8%, α only; 1H NMR (CDCl3, 400 MHz): δ = 8.75 (d, J = 2.0
Hz, 1 H), 8.39 (d, J = 8.0 Hz, 1 H), 7.73−7.52 (m, 3 H), 7.48−7.44 (m,
2 H), 7.37−7.08 (m, 13 H), 5.55 (d, J = 5.2 Hz, 1 H), 4.88 (d, J =
10.8 Hz, 1 H), 4.69 (d, J = 10.4 Hz, 1 H), 4.63−4.52 (m, 3 H), 4.34−4.26
(m, 2 H), 4.17 (dd, J = 12.0, 2.0 Hz, 1 H), 3.95 (dd, J = 10.0, 5.6 Hz, 1 H),
3.65 (dd, J = 9.6, 8.8 Hz, 1 H), 3.35−3.26 (m, 1 H), 1.95 (s, 3 H); 13C
NMR (CDCl3, 100 MHz): δ = 170.7, 159.5, 137.81, 137.75, 133.7,
132.2, 131.8, 130.7, 128.91, 128.85, 128.5, 128.3, 128.1, 128.0, 127.7,
127.1, 125.6 (q, JC−F = 5.7 Hz), 87.0, 81.8, 77.5, 75.23, 75.18, 75.1, 70.0,
63.1, 20.8; IR (film, cm−1): ν = 2923, 1742, 1641, 1454, 1364, 1314; HRMS
(ESI): calcd for C36H35F3NO5S (M + H): 650.2188; found: 650.2195.
2-Trifluorophenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoro-
methylbenzylideneamino-α-D-glucopyranosyl-(1→3)-4-O-ben-
zyl-2-O-benzoyl-6-O-tert-butyldimethylsilyl-1-thiol-β-D-galac-
topyranoside 42. Viscous oil: 38 mg, 71%, α only; [α]24D = 30.4 (c =
1
0.1, CH2Cl2); H NMR (CDCl3, 400 MHz): δ = 8.62 (d, J = 2.0 Hz,
1 H), 8.04 (d, J = 7.2 Hz, 2 H), 7.98 (d, J = 7.6 Hz, 2 H), 7.94 (d, J = 7.6
Hz, 1 H), 7.62−7.52 (m, 3 H), 7.47−7.38 (m, 3 H), 7.32−7.10 (m, 8 H),
5.99−5.87 (m, 1 H), 5.48 (t, J = 9.6 Hz, 1 H), 5.22 (d, J = 10.8 Hz, 1 H),
5.13 (d, J = 3.2 Hz, 1 H), 4.82−4.74 (m, 1 H), 4.79 (d, J = 8.8 Hz, 1 H),
4.15−4.02 (m, 3 H), 3.89−3.71 (m, 4 H), 3.65 (dd, J = 10.0, 3.2 Hz,
1 H), 3.58 (t, J = 6.4 Hz, 1 H), 2.01 (s, 3 H), 1.78 (s, 3 H), 1.73 (s, 3 H),
0.85 (s, 9 H), 0.02 (s, 3 H), −0.01 (s, 3 H); 13C NMR (CDCl3, 100
MHz): δ = 170.5, 169.7, 169.2, 164.8, 161.4, 138.7, 134.0, 133.0, 132.1,
132.0, 130.7, 129.9, 129.8, 128.5, 128.3, 128.1, 128.0, 127.3, 127.1, 126.4
(q, JC−F = 5.6 Hz), 125.4 (q, JC−F = 5.8 Hz), 98.1, 86.3, 80.9, 79.3, 77.2,
74.8, 72.6, 70.4, 68.1, 67.8, 61.5, 61,3, 25.8, 20.7, 20.5, 20.4, 18.2, −5.4,
−5.5; IR (film, cm−1): ν = 2930, 1738, 1640, 1452, 1366, 1312, 1224;
HRMS (ESI): calcd for C53H60F6NO13SSi (M + H): 1092.3459; found:
1092.3451.
132.2, 132.1, 130.9, 130.6, 129.3, 128.5, 128.3, 128.2, 127.9, 127.8, 127.6,
127.1, 126.7 (q, JC−F = 5.8 Hz), 125.7 (q, JC−F = 5.5 Hz), 120.4, 109.5,
100.7, 84.5, 81.5, 80.8, 76.7, 76.5, 75.9, 75.1, 69.3, 67.2, 62.7, 28.1, 26.5,
20.9, 16.8; IR (film, cm−1): ν = 2935, 1740, 1641, 1454, 1381, 1312;
HRMS (ESI): calcd for C46H48F6NO9S (M + H): 904.2954; found:
904.2957.
2,6-Dimethylphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluor-
omethylbenzylideneamino-α-D-glucopyranosyl-(1→4)-2,3-di-
O-isopropylidene-1-thiol-α-L-rhamnopyranoside 47. Viscous oil:
1
28 mg, 74%, α only; [α]24 = −70.8 (c = 4.8, CH2Cl2); H NMR
D
(CDCl3, 400 MHz): δ = 8.66 (d, J = 2.0 Hz, 1 H), 8.21 (d, J = 8.0 Hz,
1 H), 7.69 (d, J = 7.6 Hz, 1 H), 7.63−7.53 (m, 2 H), 7.17−7.05 (m, 2 H),
5.67 (t, J = 10.0 Hz, 1 H), 5.40 (s, 1 H), 5.24 (app t, J = 9.6 Hz, 1 H), 5.02
(d, J = 3.6 Hz, 1 H), 4.55−4.42 (m, 3 H), 4.36 (dd, J = 7.2, 5.6 Hz, 1 H),
4.22−4.05 (m, 3 H), 3.72 (dd, J = 10.0, 3.6 Hz, 1 H), 3.43 (dd, J = 10.0,
7.6 Hz, 1 H), 2.53 (s, 6 H), 2.12 (s, 3 H), 2.05 (s, 3 H), 1.89 (s, 3 H), 1.53
(s, 3 H), 1.36 (s, 3 H), 1.15 (d, J = 6.4 Hz, 1 H); 13C NMR (CDCl3, 100
MHz): δ = 170.9, 170.0, 169.9, 161.2, 143.0, 133.2, 132.1, 131.5, 130.8,
128.8, 128.31, 128.28, 125.6 (q, JC−F = 5.6 Hz), 123.9 (d, JC−F = 263 Hz),
109.4, 99.9, 84.4, 81.9, 77.6, 76.5, 72.6, 70.8, 68.3, 67.72, 67.68, 61.6,
28.2, 26.6, 22.1, 20.8, 20.7, 20.4, 17.0; IR (film, cm−1): ν = 2936, 1746,
1641, 1459, 1378, 1314, 1220; HRMS (ESI): calcd for C37H45F3NO11S
(M + H): 768.2665; found: 768.2668.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-α-D-galactopyranosyl-(1→3)-4,6-O-benzyli-
dene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-D-gluco-
pyranoside 54. Viscous oil: 65 mg, 67%, α only; [α]24D = 15.1 (c = 4.6,
CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.47 (d, J = 2.0 Hz, 1 H),
8.17 (d, J = 7.2 Hz, 1 H), 7.63 (d, J = 7.2 Hz, 1 H), 7.57−7.46 (m, 4 H),
7.39−7.30 (m, 3 H), 7.23−7.18 (m, 1 H), 7.14−7.08 (m, 2 H), 6.97 (d,
J = 7.2 Hz, 2 H), 5.66 (d, J = 8.4 Hz, 1 H), 5.47−5.38 (m, 3 H), 5.19 (s,
1 H), 5.09−5.03 (m, 1 H), 5.00 (d, J = 12.0 Hz, 1 H), 4.63 (d, J = 12.0 Hz,
1 H), 4.54 (t, J = 6.4 Hz, 1 H), 4.31 (dd, J = 10.4, 4.8 Hz, 1 H), 4.38−4.24
(m, 1 H), 4.20−4.05 (m, 2 H), 3.85 (dd, J = 10.4, 3.6 Hz, 1 H), 3.77−
3.68 (m, 2 H), 3.57−3.48 (m, 1 H), 2.15 (s, 3 H), 2.09 (s, 3 H), 1.83 (s,
3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.5, 170.1, 169.7, 160.5, 153.9,
136.4, 132.4, 131.8, 130.6, 129.1, 128.9, 128.4, 128.2, 128.0, 125.5, 101.5,
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-α-D-glucopyranosyl-(1→4)-2,3-di-O-isopropyli-
dene-1-thiol-α-L-rhamnopyranoside 43. Viscous oil: 30 mg, 81%, α
only; 1H NMR (CDCl3, 400 MHz): δ = 8.66 (d, J = 2.0 Hz, 1 H), 8.20
(d, J = 7.6 Hz, 1 H), 7.69 (d, J = 7.6 Hz, 1 H), 7.63−7.52 (m, 2 H), 7.48−
7.44 (m, 2 H), 7.33−7.23 (m, 3 H), 5.76 (s, 1 H), 5.66 (t, J = 9.6 Hz, 1
H), 5.24 (app t, J = 9.6 Hz, 1 H), 5.02 (d, J = 3.6 Hz, 1 H), 4.53−4.44 (m,
2 H), 4.38−4.25 (m, 3 H), 4.15−4.06 (m, 2 H), 3.71 (dd, J = 10.0, 3.6
Hz, 1 H), 3.47 (dd, J = 10.0, 7.6 Hz, 1 H), 2.12 (s, 3 H), 2.04 (s, 3 H),
1.89 (s, 3 H), 1.55 (s, 3 H), 1.37 (s, 3 H), 1.17 (d, J = 6.0 Hz, 1 H); 13C
NMR (CDCl3, 100 MHz): δ = 170.9, 170.0, 169.8, 161.3, 133.6, 132.2,
131.7, 131.4, 130.8, 130.0, 128.3, 127.4, 125.6 (q, JC−F = 5.4 Hz), 109.4,
100.0, 83.7, 82.1, 76.7, 76.5, 72.7, 70.8, 68.3, 67.7, 66.5, 61.5, 28.2, 26.5,
20.8, 20.7, 20.4, 16.9; IR (film, cm−1): ν = 2932, 1747, 1641, 1578, 1379,
1314, 1220; HRMS (ESI): calcd for C35H41F3NO11S (M + H): 740.2352
; found: 740.2351.
Phenyl 6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-α-D-glucopyranosyl-(1→4)-2,3-di-O-
isopropylidene-1-thiol-α-L-rhamnopyranoside 44. Viscous oil: 30
mg, 72%, α only; 1H NMR (CDCl3, 400 MHz): δ = 8.78 (d, J = 2.0 Hz,
1 H), 8.36 (d, J = 7.6 Hz, 1 H), 7.30 (d, J = 7.6 Hz, 1 H), 7.67−7.53 (m,
2 H), 7.49−7.45 (m, 2 H), 7.38−7.13 (m, 13 H), 5.77 (s, 1 H), 4.94−
4.87 (m, 2 H), 4.73 (d, J = 10.4 Hz, 1 H), 4.65−4.57 (m, 2 H), 4.51 (dd,
J = 12.0, 2.0 Hz, 1 H), 4.40−4.25 (m, 6 H), 3.38 (dd, J = 10.0, 8.8 Hz,
1 H), 3.64 (dd, J = 10.0, 3.6 Hz, 1 H), 3.45 (dd, J = 10.0, 7.6 Hz, 1 H),
2.08 (s, 3 H), 1.56 (s, 3 H), 1.36 (s, 3 H), 1.13 (d, J = 6.4 Hz, 1 H); 13C
NMR (CDCl3, 100 MHz): δ = 170.9, 160.6, 138.0, 137.9, 133.7, 133.5,
7340
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Article
99.7, 95.3, 87.5, 82.2, 76.1, 74.6, 70.0, 68.5, 68.2, 67.3, 66.8, 66.7, 62.3,
55.8, 20.9, 20.7, 20.3; IR (film, cm−1): ν = 3340, 2937, 1745, 1644,
1528, 1374, 1314, 1220; HRMS (ESI): calcd for C42H43Cl3F3N2O13S
(M + H): 977.1504 ; found: 977.1509.
(t, J = 8.0 Hz, 1 H), 4.11−4.03 (m, 2 H), 3.94−3.85 (m, 2 H), 3.80−3.67
(m, 3 H), 3.62−3.57 (m, 1 H), 2.08 (s, 3 H), 1.96 (s, 3 H), 1.82 (s, 3 H),
0.86 (s, 9 H), 0.02 (s, 3 H), −0.01 (s, 3 H); 13C NMR (CDCl3, 100
MHz): δ = 170.1, 169.9, 169.2, 165.0, 161.3, 138.8, 133.1, 132.8, 132.5,
132.2, 132.1, 131.9, 130.5, 130.0, 129.7, 128.7, 128.5, 128.0, 127.5, 127.1,
125.4 (q, JC−F = 5.7 Hz), 98.8, 86.7, 80.9, 79.3, 77.2, 74.7, 73.0, 68.1, 67.9,
67.0, 66.7, 61.5, 61.0, 25.8, 20.7, 20.6, 20.3, 18.2, −5.4, −5.5; IR (film,
cm−1): ν = 2929, 1747, 1642, 1453, 1371, 1314, 1249; HRMS (ESI):
calcd for C52H61F3NO13SSi (M + H): 1024.3585; found: 1024.3581.
Phenyl 6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-α-D-galactopyranosyl-(1→3)-4-O-ben-
zyl-2-O-benzoyl-6-O-tert-butyldimethylsilyl-1-thiol-β-D-galac-
topyranoside 58. Viscous oil: 29 mg, 51%, α only; [α]24D = 116.3 (c =
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-1-thiol-α-D-galactopyranoside 60. Viscous oil:
10 mg, 16%, α only; 1H NMR (CDCl3, 400 MHz):22 δ = 8.69 (d, J =
2.0 Hz, 1 H), 8.30−8.26 (m, 1 H), 7.72−7.47 (m, 5 H), 7.33−7.22 (m,
3 H), 5.75 (d, J = 5.6 Hz, 1 H), 5.58−5.47 (m, 2 H), 4.84 (t, J = 6.4 Hz,
1 H), 4.19 (dd, J = 10.4, 5.6 Hz, 1 H), 4.13−4.04 (m, 2 H), 2.19 (s, 3 H),
1.92 (s, 3 H), 1.89 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.4,
170.1, 169.7, 160.3, 132.3, 131.9, 130.7, 129.2, 128.9, 127.2, 125.5, 86.8,
77.2, 69.6, 67.4, 66.9, 62.0, 20.7, 20.62, 20.55; IR (film, cm−1): ν = 2927,
1748, 1642, 1439, 1372, 1314, 1227; HRMS (ESI): calcd for C26H27
F3NO7S (M + H): 554.1460; found: 554.1460.
Phenyl 6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-α-D-galactopyranosyl-(1→3)-4,6-O-
benzylidene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-thiol-β-
D-glucopyranoside 55. Viscous oil: 30 mg, 56%, α:β = 14:1; 1H NMR
(CDCl3, 400 MHz):23 δ = 8.59 (d, J = 2.0 Hz, 1 H), 8.26 (d, J = 7.2 Hz,
1 H), 7.64−7.45 (m, 4 H), 7.36−7.17 (m, 14 H), 7.12−7.06 (m, 2 H),
6.95 (d, J = 7.6 Hz, 2 H), 5.60 (d, J = 8.8 Hz, 1 H), 5.36 (d, J = 3.6 Hz,
1 H), 5.20 (s, 1 H), 4.94 (t, J = 12.0 Hz, 2 H), 4.82 (d, J = 10.0 Hz, 1 H),
4.64−4.52 (m, 4 H), 4.33−4.25 (m,2 H), 4.20−3.96 (m, 6 H), 3.84−
3.72 (m, 3 H), 3.53−3.46 (m, 1 H), 2.05 (s, 3 H); 13C NMR (CDCl3,
100 MHz): δ = 170.4, 160.4, 154.2, 138.2, 138.0, 136.3, 134.0, 133.1,
132.1, 131.7, 130.3, 129.0, 128.9, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9,
127.5, 127.4, 125.6 (q, JC−F = 5.6 Hz), 125.5, 123.9 (d, JC−F = 273 Hz),
101.4, 100.1, 95.5, 81.9, 77.2, 76.1, 74.6, 73.2, 72.6, 70.3, 69.0, 68.5, 64.8,
55.5, 21.0; IR (film, cm−1): ν = 3350, 2924, 1741, 1640, 1524, 1370,
1313, 1234; HRMS (ESI): calcd for C52H51Cl3F3N2O11S (M + H):
1073.2231 ; found: 1073.2237.
1
0.3, CH2Cl2); H NMR (CDCl3, 400 MHz): δ = 8.73 (d, J = 2.0 Hz,
1 H), 8.03−7.94 (m, 3 H), 7.61−7.56 (m, 2 H), 7.46−7.05 (m, 24 H),
5.82 (t, J = 9.6 Hz, 1 H), 5.13−5.07 (m, 2 H), 4.83−4.74 (m, 2 H), 4.42−
4.34 (m, 3 H), 4.26 (d, J = 11.2 Hz, 1 H), 4.10−3.93 (m, 8 H), 3.75−3.66
(m, 2 H), 3.57 (t, J = 10.8 Hz, 1 H), 1.91 (s, 3 H), 0.84 (s, 9 H), 0.00 (s,
3 H), −0.02 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.1, 164.9,
160.9, 138.9, 138.1, 133.5, 133.2, 132.1, 131.9, 130.1, 130.0, 129.7, 128.7,
128.4, 128.29, 128.27, 128.2, 127.9, 127.7, 127.5, 127.4, 125.3 (q, JC−F
=
5.3 Hz), 97.6, 86.9, 79.3, 78.5, 77.2, 74.6, 74.4, 73.3, 72.7, 71.9, 70.4, 69.1,
63.0, 61.4, 25.8, 20.8, 18.2, −5.4, −5.6; IR (film, cm−1): ν = 2927, 1733,
1638, 1454, 1314, 1261; HRMS (ESI): calcd for C62H69F3NO11SSi (M +
H): 1120.4313; found: 1120.4311.
2-Trifluoromethylphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-tri-
fluoromethylbenzylideneamino-α-D-galactopyranosyl-(1→3)-
4-O-benzyl-2-O-benzoyl-6-O-tert-butyldimethylsilyl-1-thiol-β-
D-galactopyranoside 59. Viscous oil: 34 mg, 62%, α only; [α]24
=
D
85.5 (c = 1.6, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.64 (d, J = 2.0
Hz, 1 H), 8.07−7.92 (m, 4 H), 7.63−7.54 (m, 3 H), 7.46−7.38 (m, 3 H),
7.32−7.15 (m, 8 H), 5.90 (t, J = 9.6 Hz, 1 H), 5.38 (dd, J = 3.2, 10.8 Hz,
1 H), 5.16−5.10 (m, 2 H), 5.03 (d, J = 2.0 Hz, 1 H), 4.78 (d, J = 10.0 Hz,
1 H), 4.44 (d, J = 10.8 Hz, 1 H), 4.18 (t, J = 7.2 Hz, 1 H), 4.10−4.02 (m,
2 H), 3.88−3.67 (m, 5 H), 3.58 (t, J = 6.4 Hz, 1 H), 2.07 (s, 3 H), 1.95 (s,
3 H), 1.80 (s, 3 H), 0.85 (s, 9 H), 0.02 (s, 3 H), −0.01 (s, 3 H); 13C NMR
(CDCl3, 100 MHz): δ = 170.2, 170.0, 169.2, 165.0, 161.4, 138.6, 134.1,
133.1, 132.1, 132.0, 130.5, 130.3, 129.7, 129.6, 129.1, 128.7, 128.5, 128.3,
128.1, 127.8, 127.3, 127.1, 126.4 (q, JC−F = 5.8 Hz), 125.4 (q, JC−F = 5.8
Hz), 122.7, 122.3 (d, JC−F = 272 Hz), 98.7, 86.3, 80.7, 79.3, 77.2, 74.8, 72.7,
68.0, 67.8, 67.0, 66.6, 61.5, 61.1, 25.8, 20.68, 20.66, 20.3, 18.2, −5.4, −5.5;
IR (film, cm−1): ν = 2929, 1746, 1641, 1452, 1372, 1312, 1249; HRMS
(ESI): calcd for C53H60F6NO13SSi (M + H): 1092.3459; found: 1092.3456.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-azido-α-D-glucopyrano-
syl-(1→3)-4,6-O-benzylidene-2-deoxy-2-(2,2,2-trichloroethyl)-
amino-1-thiol-β-D-glucopyranoside 68. Viscous oil: 15 mg, 18%, α
only; [α]24D = 60.8 (c = 0.5, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ =
7.52−7.45 (m, 4 H), 7.37−7.32 (m, 6 H), 5.65−5.57 (m, 2 H), 5.45−
5.36 (m, 2 H), 5.13−5.01 (m, 2 H), 4.90 (d, J = 12.0 Hz, 1 H), 4.65 (d, J =
12.0 Hz, 1 H), 4.40 (dd, J = 10.4, 4.8 Hz, 1 H), 4.34−4.23 (m, 2 H), 4.16−
4.11 (m, 1 H), 4.01 (dd, J = 12.0, 3.2 Hz, 1 H), 3.85−3.77 (m, 2 H), 3.60−
3.47 (m, 2 H), 3.19 (dd, J = 10.8, 4.0 Hz, 1 H), 2.09 (s, 3 H), 2.07 (s, 3 H),
2.03 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.7, 170.0, 169.5, 153.7,
136.8, 132.5, 132.0, 129.2, 128.34, 128.32, 125.9, 101.4, 98.9, 95.1, 86.8,
74.6, 70.0, 69.7, 68.5, 68.4, 67.6, 62.0, 60.5, 55.9, 20.8, 20.7, 20.6; IR (film,
cm−1): ν = 2923, 2108, 1748, 1453, 1367, 1215; HRMS (ESI): calcd for
C34H37Cl3N4O13SK (M + K): 885.0781; found: 885.0792.
Phenyl 6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-o-trifluorome-
thylbenzylideneamino-1-thiol-α-D-galactopyranoside 61. Vis-
cous oil: 2 mg, 6%, α only; 1H NMR (CDCl3, 400 MHz): δ = 8.54 (d, J =
2.0 Hz, 1 H), 8.20 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 7.6 Hz, 1 H), 7.63−
7.45 (m, 4 H), 7.35−7.15 (m, 13 H), 4.95−4.99 (m, 2 H), 4.60 (d, J =
11.6 Hz, 1 H), 4.54 (d, J = 12.0 Hz, 1 H), 4.49 (d, J = 12.0 Hz, 1 H), 4.33
(dd, J = 11.2, 6.8 Hz, 1 H), 4.17 (dd, J = 11.2, 5.2 Hz, 1 H), 3.87−3.83
(m, 2 H), 3.77−3.72 (m, 2 H), 2.02 (s, 3 H); 13C NMR (CDCl3, 100
MHz): δ = 170.6, 160.6, 138.3, 137.7, 132.8, 132.2, 130.3, 129.7, 129.4,
129.1, 128.64, 128.59, 128.2, 128.0, 127.7, 127.6, 127.3, 125.6 (q, JC−F
=
5.6 Hz), 124.0 (d, JC−F = 273 Hz), 86.3, 81.6, 76.4, 74.2, 72.4, 71.7, 70.4,
63.8, 20.8; IR (film, cm−1): ν = 2924, 1740, 1642, 1439, 1314, 1234;
HRMS (ESI): calcd for C36H35F3NO5S (M + H): 650.2188 ; found:
650.2181.
2-Trifluoromethylphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-tri-
fluoromethylbenzylideneamino-α-D-galactopyranosyl-(1→3)-
4,6-O-benzylidene-2-deoxy-2-(2,2,2-trichloroethyl)amino-1-
thiol-β-D-glucopyranoside 56. Viscous oil: 38 mg, 73%, α only;
[α]24D = 12.3 (c = 1.7, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.46
(d, J = 2.0 Hz, 1 H), 8.18 (d, J = 7.2 Hz, 1 H), 7.78 (d, J = 7.6 Hz, 1 H),
7.71 (d, J = 7.2 Hz, 1 H), 7.64 (d, J = 7.2 Hz, 1 H), 7.59−7.34 (m, 4 H),
7.23−7.18 (m, 1 H), 7.13−7.07 (m, 2 H), 6.94 (d, J = 7.2 Hz, 2 H), 5.64
(d, J = 8.8 Hz, 1 H), 5.48−5.36 (m, 3 H), 5.20 (s, 1 H), 5.08 (d, J = 12.0
Hz, 1 H), 4.92−4.83 (m, 1 H), 4.64−4.60 (m, 1 H), 4.56 (d, J = 12.0 Hz,
1 H), 4.28 (dd, J = 10.4, 4.8 Hz, 1 H), 4.21−4.03 (m, 3 H), 3.95−3.73
(m, 4 H), 3.52−3.44 (m, 1 H), 2.15 (s, 3 H), 2.12 (s, 3 H), 1.83 (s, 3 H);
13C NMR (CDCl3, 100 MHz): δ = 170.5, 170.1, 169.7, 160.6, 154.1,
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-azido-1-thiol-α-D-gluco-
pyranoside 69. Viscous oil: 16 mg, 40%, α only; 1H NMR (CDCl3, 400
MHz): δ = 7.53−7.46 (m, 2 H), 7.38−7.29 (m, 3 H), 5.64 (d, J = 5.6 Hz,
1 H), 5.34 (dd, J = 10.4, 9.2 Hz, 1 H), 5.04 (dd, J = 10.4, 9.6 Hz, 1 H),
4.67−4.56 (m, 1 H), 4.30 (dd, J = 12.4, 4.8 Hz, 1 H), 4.09 (dd, J = 10.4,
5.6 Hz, 1 H), 4.03 (dd, J = 12.4, 2.0 Hz, 1 H), 2.11 (s, 3 H), 2.06 (s, 3 H),
2.04 (s, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.5, 169.8, 134.1,
132.2, 129.2, 128.1, 86.4, 72.0, 68.6, 68.4, 61.9, 61.6, 20.7, 20.6; IR (film,
cm−1): ν = 2918, 2109, 1748, 1367, 1227; HRMS (ESI): calcd for
C18H21N3O7NaS (M + Na): 446.0998; found: 446.0997.
136.3, 132.2, 131.8, 130.6, 129.0, 128.45, 128.36, 128.0, 126.9 (q, JC−F
=
5.6 Hz), 125.5, 101.6, 99.8, 95.1, 82.0, 77.2, 76.1, 74.7, 70.0, 68.4, 68.2,
67.2, 67.0, 66.9, 60.4, 55.5, 21.0, 20.8, 20.4; IR (film, cm−1): ν = 3339,
2927, 1745, 1644, 1526, 1374, 1312, 1225; HRMS (ESI): calcd for
C43H42Cl3F6N2O13S (M + H): 1045.1377; found: 1045.1367.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylben-
zylideneamino-α-D-galactopyranosyl-(1→3)-4-O-benzyl-2-O-
benzoyl-6-O-tert-butyldimethylsilyl-1-thiol-β-D-galactopyrano-
1
side 57. Viscous oil: 46 mg, 52%, α:β = 8:1; H NMR (CDCl3, 400
2-Trifluoromethylphenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-azido-
MHz):23 δ = 8.66 (d, J = 2.0 Hz, 1 H), 8.12−8.07 (m, 2 H), 7.95 (d, J =
7.6 Hz,1 H), 7.66−7.18 (m, 18 H), 5.79 (t, J = 9.6 Hz, 1 H), 5.41 (dd, J =
3.2, 10.8 Hz, 1 H), 4.83−4.77 (m, 1 H), 4.44 (d, J = 11.6 Hz, 1 H), 4.20
α-D-glucopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-
(2,2,2-trichloroethyl)amino-1-thiol-β-D-glucopyranoside 70.
1
Viscous oil: 6 mg, 13%, α only; [α]24 = 28.0 (c = 0.1, CH2Cl2); H
D
7341
dx.doi.org/10.1021/jo301050q | J. Org. Chem. 2012, 77, 7330−7343

The Journal of Organic Chemistry
Article
NMR (CDCl3, 400 MHz): δ = 7.79 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 7.6
Hz, 1 H), 7.55−7.35 (m, 7 H), 5.65−5.60 (m, 2 H), 5.44−5.36 (m, 2 H),
5.01 (app t, J = 10.0 Hz, 1 H), 4.93 (d, J = 12.0 Hz, 1 H), 4.57 (d, J = 12.0
Hz, 1 H), 4.39 (dd, J = 10.8, 4.8 Hz, 1 H), 4.28−4.17 (m, 2 H), 4.07−
4.03 (m, 1 H), 3.93−3.81 (m, 3 H), 3.70−3.52 (m, 3 H), 317 (dd, J =
10.8, 3.6 Hz, 1 H), 2.09 (s, 3 H), 2.07 (s, 3 H), 2.03 (s, 3 H); 13C NMR
(CDCl3, 100 MHz): δ = 170.5, 170.0, 169.5, 154.0, 136.7, 132.3, 129.2,
128.5, 128.3, 125.9, 101.5, 99.0, 94.9, 81.3, 77.2, 74.8, 69.7, 68.4, 67.7,
62.2, 60.4, 20.74, 20.68, 20.65; IR (film, cm−1): ν = 3346, 2923, 2108,
1745, 1536, 1371, 1314, 1260; HRMS (ESI): calcd for
C35H36Cl3F3N4O13NaS (M + Na): 937.0915; found: 937.0922.
Phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-azido-α-D-glucopyrano-
syl-(1→4)-2,3-di-O-isopropylidene-1-thiol-α-L-rhamnopyrano-
side 71. Viscous oil: 17 mg, 49%, α only; 1H NMR (CDCl3, 400 MHz):
δ = 7.52−7.43 (m, 2 H), 7.36−7.27 (m, 3 H), 5.75 (s, 1 H), 5.50 (t, J =
9.6 Hz, 1 H), 5.15 (app t, J = 10.0 Hz, 1H), 5.08 (d, J = 4.0 Hz, 1 H),
4.47−4.31 (m, 3 H), 4.26−4.17 (m, 2 H), 4.05 (dd, J = 2.0, 10.0 Hz,
1 H), 3.52−3.38 (m, 2 H), 2.104 (s, 3 H), 2.096 (s, 3 H), 2.05 (s, 3 H),
1.53 (s, 3 H), 1.35 (s, 3 H), 1.28 (d, J = 6.0 Hz, 3 H); 13C NMR (CDCl3,
100 MHz): δ = 170.7, 170.0, 169.7, 133.1, 131.9, 129.1, 127.7, 109.5,
98.5, 83.5, 82.2, 76.6, 76.3, 70.6, 67.9, 67.5, 66.0, 61.3, 61.1, 28.2, 26.5,
20.8, 20.7, 20.6, 17.2; IR (film, cm−1): ν = 2982, 2108, 1749, 1380, 1221;
HRMS (ESI): calcd for C27H35N3O11NaS (M + Na): 632.1890; found:
632.1888.
3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylbenzylide-
neamino-α-D-glucopyranosyl-(1→4)-2,3-di-O-isopropylidene-
L-rhamnopyranosyl-(1→6)-1,2,3,4-bis-(di-O-isopropylidene)-α-
D-galactopyranoside 64. After the solution of disaccharide thioglyco-
side 45 (16 mg, 0.02 mmol), galactosyl acceptor 63 (10 mg, 0.04 mmol)
and 4 Å MS (100 mg) in 2.0 mL of dry CH2Cl2 under argon was stirred
at room temperature for 1 h and then cooled to −78 °C, NIS (14 mg,
0.06 mmol) was added. The reaction was allowed to warm to room
temperature and stirred for 20 min and was then cooled to −78 °C.
AgOTf (3 mg, 0.01 mg) was added to the reaction, and the resulting
mixture was warmed to 0 °C for 1 h and then slowly to room
temperature overnight. TLC showed that the reaction was not complete,
an additional amount of NIS (10 mg, 0.04 mmol) and AgOTf (3 mg,
0.01 mg) were added. The solution was stirred at 35 °C for 3 h. The
reaction mixture was filtered through a Celite pad, evaporated, and
purified by flash chromatography on silica gel (hexane/ethyl acetate = 3/
1 →2/1 → 3/2) to afford trisaccharide 64 (15 mg, 85%, α:β = 3:2). α,α-
64: [α]24D = 29.8 (c = 0.5, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ =
8.65 (d, J = 2.0 Hz, 1 H), 8.18−8.15 (m, 1 H), 7.72−7.67 (m, 1 H),
7.58−7.51 (m, 2 H), 5.64 (t, J = 9.6 Hz, 1 H), 5.54 (d, J = 4.8 Hz, 1 H),
5.23 (app t, J = 9.6 Hz, 1 H), 5.02−4.98 (m, 2 H), 4.63 (dd, J = 8.0, 2.4
Hz, 1 H), 4.53−4.42 (m, 2 H), 4.32 (dd, J = 10.0, 2.8 Hz, 1 H), 4.26−
4.20 (m, 3 H), 4.14−4.08 (m, 1 H), 3.87−3.80 (m, 2 H), 3.70 (dd, J =
10.0, 3.2 Hz, 1 H), 3.57 (dd, J = 10.0, 6.8 Hz, 1 H), 3.37 (dd, J = 10.0, 7.6
Hz, 1 H), 2.12 (s, 3 H), 2.03 (s, 3 H), 1.88 (s, 3 H), 1.57 (s, 3 H), 1.53 (s,
3 H), 1.41 (s, 3 H), 1.34 (s, 6 H), 1.32 (s, 3 H), 1.20 (d, J = 6.4 Hz, 3 H);
13C NMR (CDCl3, 100 MHz): δ = 170.9, 170.0, 169.9, 161.2, 133.3,
1456, 1381, 1315, 1223; HRMS (ESI): calcd for C41H55F3NO17 (M +
H): 890.3422; found: 890.3428.
3,4,6-Tri-O-acetyl-2-deoxy-2-o-trifluoromethylbenzylide-
neamino-α-D-glucopyranosyl-(1→3)-4,6-O-benzylidene-2-
deoxy-2-(2,2,2-trichloroethyl)amino-β-D-glucopyranosyl-(1→6)-
1,2,3,4-bis-(di-O-isopropylidene)-α-D-galactopyranoside 65.
Viscous oil: 5 mg, 81%, β only; α,β-65: [α]24D = −5.9 (c = 1.6, CH2Cl2);
1H NMR (CDCl3, 400 MHz): δ = 8.44 (d, J = 2.0 Hz, 1 H), 8.24 (d, J =
7.2 Hz, 1 H), 7.64−7.52 (m, 3 H), 7.21−7.16 (m, 1 H), 7.09 (t, J = 7.6
Hz, 1 H), 6.93 (d, J = 7.6 Hz, 2 H), 5.64 (d, J = 4.8 Hz, 1 H), 5.60 (t, J =
9.6 Hz, 1 H), 5.53 (d, J = 4.8 Hz, 1 H), 5.36 (d, J = 4.0 Hz, 1 H), 5.18 (s,
1 H), 5.12(d, J = 7.2Hz, 1 H), 5.09 (d, J = 9.6 Hz, 1 H), 4.82 (d, J = 8.4 Hz,
1 H), 4.61 (dd, J = 8.0, 2.4 Hz, 1 H), 4.53−4.14 (m, 7 H), 4.07−3.95 (m,
2 H), 3.82−3.40 (m, 7 H), 2.14 (s, 3 H), 2.03 (s, 3 H), 1.84 (s, 3 H), 1.58
(s, 3 H), 1.46 (s, 3 H), 1.35 (s, 3 H), 1.34 (s, 3 H);13C NMR (CDCl3,
100 MHz): δ = 170.7, 169.9, 169.6, 160.3, 136.4, 133.2, 131.9, 130.7,
129.0, 128.9, 128.3, 127.9, 125.5, 109.4, 108.6, 102.1, 101.5, 99.1, 96.2,
95.4, 83.3, 77.2, 75.5, 74.6, 72.3, 71.1, 70.8, 70.6, 70.3, 68.9, 68.6, 67.8,
65.8, 62.3, 59.3, 56.5, 26.2, 26.0, 24.3, 22.7, 20.9, 20.8, 20.4; IR (film,
cm−1): ν = 3468, 2926, 1747, 1634, 1586, 1455, 1375, 1314; HRMS
(ESI): calcd for C48H57Cl3F3N2O19 (M + H): 1127.2573; found:
1127.2569.
3,4,6-Tri-O-acetyl-2-deoxy-2-N-acetyl-α-D-glucopyranosyl-
(1→3)-4,6-di-O-acetyl-2 Deoxy-2-(2,2,2-trichloroethyl)amino-
β-D-glucopyranosyl-(1→6)-1,2,3,4-bis-(di-O-isopropylidene)-α-
D-galactopyranoside 66. A 25 mL RBF was charged with 65 (5 mg,
0.0044 mmol, 1.0 equiv), 6N HCl (4.5 μL, 0.027 mmol, 6.0 equiv) and
acetone (1.0 mL). The solution was stirred under reflux for 5 min,
concentrated in vacuo. The crude amine salt was used directly without
further purification. To another A 25 mL RBF was charged with this
crude amine intermediate, acetic anhydrate (0.5 mL), and pyridine (1.0
mL). After the reaction mixture had been stirring at room temperature
overnight, it was azeotroped with toluene for three times. The resulting
residue was purified by silica gel flash chromatography (hexane/ethyl
acetate = 1/2 → 1/3) to afford trisaccharide 66 (5 mg, 99%) as a viscous
oil. 66: [α]24D = 12.3 (c = 0.6, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ
= 5.75 (d, J = 8.4 Hz, 1 H), 5.66 (d, J = 9.6 Hz, 1 H), 5.20−4.99 (m, 5 H),
4.66 (d, J = 8.4 Hz, 1 H), 4.60 (dd, J = 8.0, 2.4 Hz, 1 H), 4.51 (d, J = 12.0
Hz, 1 H), 4.39 (dt, J = 10.0, 4.0 Hz, 1 H), 4.32 (dd, J = 5.2, 2.4 Hz, 1 H),
4.23−4.16 (m, 4 H), 4.09−3.94 (m, 4 H), 3.76−3.52 (m, 3 H), 2.14
(s, 3 H), 2.11 (s, 3 H), 2.04 (s, 3 H), 2.014 (s, 3 H), 2.009 (s, 3 H), 1.97
(s, 3 H), 1.56 (s, 3 H), 1.44 (s, 3 H), 1.34 (s, 3 H), 1.33 (s, 3 H);
13C NMR (CDCl3, 100 MHz): δ = 171.0, 170.8, 170.6, 109.4, 108.7,
98.4, 96.2, 95.3, 77.2, 74.7, 71.6, 71.2, 71.1, 70.9, 70.6, 70.2, 69.2,
68.1, 68.0, 67.7, 61.9, 56.4, 51.2, 26.2, 25.0, 24.3, 23.0, 22.7, 20.84,
20.82, 20.74, 20.69, 20.6; IR (film, cm−1): ν = 3347, 2924, 1747, 1669,
1539, 1455, 1374, 1231; HRMS (ESI): calcd for C39H55Cl3N2O22Na
(M + Na): 1031.2210; found: 1031.2197.
ASSOCIATED CONTENT
■
S
* Supporting Information
132.0, 130.8, 129.3, 128.2, 125.6 (q, JC−F = 5.6 Hz), 124.0 (d, JC−F = 275
Hz), 109.3, 109.1, 108.7, 99.9, 96.9, 96.2, 81.7, 77.2, 76.0, 75.6, 72.7,
71.1, 70.9, 70.6, 70.4, 68.3, 67.6, 66.5, 65.7, 64.9, 61.6, 28.2, 26.4, 26.2,
26.0, 24.9, 24.5, 20.8, 20.7, 20.5, 16.9; IR (film, cm−1): ν = 2934, 1752,
1640, 1455, 1381, 1314, 1242; HRMS (ESI): calcd for C41H55F3NO17
Detailed experimental procedures and characterization data,
including 1H NMR and 13C NMR spectra for all new
compounds, are provided. This material is available free of
charge via the Internet at http://pubs.acs.org.
(M + H): 890.3422; found: 890.3420. α,β-64: [α]24 = 25.5 (c = 0.2,
D
CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 8.65 (d, J = 2.0 Hz, 1 H),
8.16 (d, J = 7.2 Hz, 1 H), 7.60 (d, J = 7.2 Hz, 1 H), 7.62−7.51 (m, 2 H),
5.63 (t, J = 10.0 Hz, 1 H), 5.49 (d, J = 4.8 Hz, 1 H), 5.22 (t, J = 9.6 Hz,
1 H), 5.02 (d, J = 3.6 Hz, 1 H), 4.82 (d, J = 2.0 Hz, 1 H), 4.61 (dd, J =
10.0, 2.0 Hz, 1 H), 4.49−4.43 (m, 2 H), 4.35−4.22 (m, 4 H), 4.12−3.98
(m, 3 H), 3.77 (dd, J = 9.6, 8.8 Hz, 1 H), 3.71 (dd, J = 12.0, 3.2 Hz, 1 H),
3.57−3.44 (m, 2 H), 2.12 (s, 3 H), 2.03 (s, 3 H), 1.88 (s, 3 H), 1.57 (s,
3 H), 1.51 (s, 3 H), 1.44 (s, 3 H), 1.38 (s, 3 H), 1.35 (s, 3 H), 1.31 (s,
3 H), 1.25 (d, J = 6.0 Hz, 3 H); 13C NMR (CDCl3, 100 MHz): δ = 170.9,
170.0, 161.3, 130.8, 128.3, 110.7, 109.1, 108.6, 99.9, 98.8, 96.2, 81.5, 77.2,
74.6, 72.5, 70.7, 70.6, 70.5, 68.4, 67.8, 67.7, 65.5, 61.6, 28.0, 26.5, 26.1, 26.0,
24.8, 24.5, 20.8, 20.7, 20.5, 17.6; IR (film, cm−1): ν = 2927, 1752, 1644,
AUTHOR INFORMATION
■
Corresponding Author
*hien-nguyen@uiowa.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the University of Iowa and National Institutes of
Health (R01 GM098285) for their financial support.
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dx.doi.org/10.1021/jo301050q | J. Org. Chem. 2012, 77, 7330−7343

The Journal of Organic Chemistry
Article
benzylidene group is acid-sensitive, activation of 2-trifluorophenyl
thioglycoside donors were explored with NIS/AgOTf.
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