Glycosylations of Glycals using N-Iodosuccinimide (NIS) and Phosphorus Compounds for Syntheses of 2-Iodo- and 2-Deoxyglycosides

Article abstract of DOI:10.1021/acs.joc.5b01542

The glycosylations of glycals and alcohols using N-iodosuccinimide (NIS) and a catalytic amount of PPh₃ effectively proceeded under mild conditions to provide the corresponding 2-deoxy-2-iodoglycosides in high yields. The reactivity of the iodo

Full text of DOI:10.1021/acs.joc.5b01542

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Article
Glycosylations of Glycals Using N-Iodosuccinimide (NIS) and
Phosphorus Compounds for Syntheses of 2-Iodo- and 2-Deoxyglycosides
Tomoya Kimura, Daisuke Takahashi, and Kazunobu Toshima
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01542 • Publication Date (Web): 16 Sep 2015
Downloaded from http://pubs.acs.org on September 17, 2015
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Glycosylations of Glycals Using N-Iodosuccinimide (NIS) and
Phosphorus Compounds for Syntheses of 2-Iodo- and
2-Deoxyglycosides
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Tomoya Kimura, Daisuke Takahashi, and Kazunobu Toshima*
Department of Applied Chemistry, Faculty of Science and Technology, Keio University,
3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
*E-mail: toshima@applc.keio.ac.jp
ABSTRACT: The glycosylations of glycals and alcohols using N-iodosuccinimide (NIS) and a catalytic
amount of PPh3 effectively proceeded under mild conditions to provide the corresponding
2-deoxy-2-iodoglycosides in high yields. The reactivity of the iodoglycosylations with PPh3 significantly
increased compared to that using NIS alone as an activator. In addition, the glycosylations of glycals and
alcohols using catalytic amounts of NIS and P(OPh)3 were effectively realized to give the corresponding
2-deoxyglycosides in high yields.
Introduction
Many kinds of natural products including mono- and oligosaccharides, such as proteoglycans,
glycoproteins, glycolipids, and antibiotics, are now recognized as important biological substances. A large
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number of recent biological studies on these glycomolecules at the molecular level have shed light on the
biological significance of their carbohydrate parts (glycons) in molecular recognition for the transmission
of biological information,1 and it was found that carbohydrates play very important roles in many
biological events. Additionally, some glycomolecules are being used as new functional materials.2 For
example, there is great hope that certain alkyl glycosides can be employed as biodegradable surfactants.
Therefore, glycomolecules are worth developing in chemistry, biology, and material science. With this
stimulating background, the efficient synthesis of not only the carbohydrate itself, but also
carbohydrate-containing products, is of particular interest both in academia and in industry. In this context,
glycosylation, which is a crucial organic synthetic method to attach a sugar to other sugar moieties or other
molecules (aglycons), is becoming more and more important in synthetic organic chemistry and
carbohydrate chemistry, and considerable attention has been directed towards the development and
efficiency of glycosylation methods.3 In this study, we focused on the iodoglycosylation4 of glycals5 using
N-iodosuccinimide (NIS). 2-Iodoglycosides produced by iodoglycosylation can be converted to
2-deoxysugars, and thus this method widely applies to natural product6 or oligosaccharide synthesis.7
Additionally, 2-iodoglycosides can be used to label glycosides in biology.8 Although iodoglycosylation is
known as an efficient glycosylation methodology, it sometimes needs a reaction accelerator such as TfOH,
which is a strong acid,9 to improve the efficiency of the glycosylation reaction (Figure 1, path a).
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Consequently, it cannot be applied to acid-sensitive substrates. Herein, we report an efficient
iodoglycosylation utilizing PPh3 as a novel and neutral reaction accelerator. Along with this reaction, we
disclose a novel glycosylation of glycals using NIS and P(OPh)3 as a combined activator to directly give
2-deoxyglycosides.10 To realize such an efficient iodoglycosylation, we built upon Ishihara’s
iodocyclization reaction,11 in which NIS could be activated by a phosphorus compound as a nucleophilic
promoter. In this study, the high reactivity of a phosphonium iodide cation intermediate generated from
NIS and a phosphorus compound was well demonstrated (Figure 1, path b). In this context, we expected
that use of a phosphorus compound combined with NIS would realize an effective iodoglycosylation of
glycals under mild and neutral conditions.
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Figure 1. Activation of NIS by a protic acid (a) and a phosphorus compound (b).
Results and discussion
To investigate our hypothesis, we first selected tri-O-benzyl-D-glucal (1) and NIS as the glycosyl donor
and activator, respectively. We then investigated the iodoglycosylation reaction of 1 with alcohol 2a using
NIS and several phosphorus compounds under several conditions. These results are summarized in Table 1.
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It was found that the use of PBu3, P(OMe)3 or P(OPh)3 as an additive gave the corresponding glycoside 3a
in moderate yields to a similar degree as the reaction with no phosphorus compound (entries 1-4). In
addition, when P(OMe)3 and P(OPh)3 were employed as the reaction additive, non-negligible amounts of
the Ferrier-type12 rearranged by-products 5a and 613 were produced (entries 3 and 4). In contrast, when
PPh3 was used as the reaction additive, the reactivity of the reaction and the yield of 3a were dramatically
increased. Thus, we found that the use of PPh3 significantly promoted the iodoglycosylation using NIS just
as well as the use of TfOH, and the corresponding 2-deoxy-2-iodoglycosides were obtained in excellent
yields (82%, / = 75/25) (entries 5 and 6). It was also confirmed that the /-stereoselectivity of the
glycosylation using NIS and PPh3 was quite similar to that using NIS and TfOH. Based on these results, we
next examined the amounts of PPh3. When 0.1 equiv. PPh3 was employed as the reaction accelerator, the
yield of 3a was only moderate (entry 7). It was found that the use of 0.2 or 0.4 equiv. PPh3 gave the best
results (entries 5 and 8). Surprisingly, when 0.1 equiv. NIS and 0.2 equiv. P(OPh)3 were employed as an
activator and an additive, respectively, 2-deoxyglycoside 4a14 was directly produced in 39% yield (entry 9).
Although the reaction mechanism is different from the present glycosylation, the glycosylation using
PPh3-HBr to give 2-deoxyglycoside was reported by Mioskowski et al. 15 In the reaction using 0.1 equiv.
NIS and 0.2 equiv. PPh3, the glycosylation did not proceed at all (entry 10). Moreover, the glycosylation of
1 and 2a using 0.1 equiv. NIS and 0.2 equiv. P(OPh)3 at warmer reaction temperatures afforded 4a in
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excellent yields (entries 11-13). Interestingly, 2-deoxyglycoside 4a was not obtained by the glycosylation
reaction using 0.15 equiv. NIS and 0.15 equiv. P(OPh)3 or by using 0.2 equiv. NIS and 0.1 equiv. P(OPh)3,
and only the rearranged by-products 5a and 6 were produced as principal products in those cases (entries 14
and 15).
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Table 1. Glycosylations of 1 and 2a using NIS and several phosphorus compounds under several
conditions.
Yields(%)a
Entr
Temp. (ºC)
Time (h)
Conditions
3a
4a
5a
-
6
-
1
1
-40
-40
-40
-40
-40
-40
-40
-40
-40
-40
-20
0
12
12
12
12
12
12
12
12
12
12
12
12
3
NIS (2.0 eq.)
-
37
40
25
20
-
45 (/ = 48/52)
2
NIS (2.0 eq.), PBu3 (0.2 eq.)
NIS (2.0 eq.), P(OMe)3 (0.2 eq.)
NIS (2.0 eq.), P(OPh)3 (0.2 eq.)
NIS (2.0 eq.), PPh3 (0.2 eq.)
NIS (2.0 eq.), TfOH (0.2 eq.)
NIS (2.0 eq.), PPh3 (0.1 eq.)
NIS (2.0 eq.), PPh3 (0.4 eq.)
NIS (0.1 eq.), P(OPh)3 (0.2 eq.)
NIS (0.1 eq.), PPh3 (0.2 eq.)
NIS (0.1 eq.), P(OPh)3 (0.2 eq.)
NIS (0.1 eq.), P(OPh)3 (0.2 eq.)
NIS (0.1 eq.), P(OPh)3 (0.2 eq.)
-
-
-
53 (/ = 71/29)
3
-
8
10
-
8
8
-
42 (/ = 70/30)
4
-
49 (/ = 65/35)
5
-
82 (/ = 75/25)
6
-
-
-
-
86 (/ = 72/28)
7
-
-
-
31
-
58 (/ = 68/32)
8
-
-
-
83 (/ = 72/28)
9
-
-
-
-
-
-
-
52
89
-
39 (/ = 39/61)
-
10
11
12
13
-
-
-
-
84 (/ = 45/55)
88 (/ = 48/52)
89 (/ = 65/35)
-
-
-
rt
-
-
-
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rt
rt
3
3
NIS (0.15 eq.), P(OPh)3 (0.15 eq.)
NIS (0.2 eq.), P(OPh)3 (0.1 eq.)
-
-
-
-
58
54
31
30
-
-
9
a/ Ratios were determined by 1H NMR analysis.
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With these interesting and favorable results in hand, we propose the reaction mechanism of the present
iodoglycosylation reaction using NIS and PPh3 as shown in Figure 2. First, a reactive phosphonium iodide
cation is generated from NIS and PPh3 by nucleophilic activation of PPh3, which then continuously reacts
with glycal, the glycosyl donor. As a result, a glycosyl iodonium cation intermediate is generated. Finally,
the corresponding 2-deoxy-2-iodoglycoside is produced by nucleophilic addition of the alcohol to the
cation intermediate. Additionally, PPh3 behaves catalytically and is recycled during the reaction.
Figure 2. Proposed mechanism of the iodoglycosylation of glycal using NIS and PPh3.
Accordingly, we next examined the generality of the present iodoglycosylation method using primary
alcohols 2b and 2c, secondary chain alcohols 2d and 2e, and cyclic secondary alcohols 2f and 2g as
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glycosyl acceptors. These results are summarized in Table 2. In all cases, we found that the corresponding
glycosides 3b-3g as well as 3a were obtained in high yields with -stereoselectivities by the glycosylations
using NIS and PPh3 as a reaction accelerator at low temperature, -40 C.
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Table 2. Iodoglycosylations of 1 and several alcohols using NIS and PPh3.
a/ Ratios were determined by 1H NMR analysis.
Furthermore, we investigated the iodoglycosylation of 1 with acid-sensitive alcohols, 2h-l, by utilizing
TfOH or PPh3 as a reaction accelerator, and compared these results (Table 3). Although iodoglycosylation
of 2h, 2i and 2k with TfOH gave only a complex mixture, it was found that the use of PPh3 promoted
iodoglycosylations effectively to give the corresponding 2-deoxy-2-iodoglycosides 3h, 3i and 3k in good
yields (entries 1-4, 7 and 8). Similarly, when 2j and 2l were employed as glycosyl acceptors, the product
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yields significantly increased by using PPh3 as a reaction accelerator compared with the additive of TfOH
(entries 5, 6, 9 and 10). These results clearly indicated that the iodoglycosylation using PPh3 effectively
proceeded under mild conditions, and demonstrated the usefulness of PPh3 as a reaction accelerator for
iodoglycosylation using NIS.
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Table 3. Iodoglycosylations of 1 and acid-sensitive alcohols using NIS and TfOH or PPh3.
a/ Ratios were determined by 1H NMR analysis.
We performed a mechanistic study on the glycosylation reaction using NIS and P(OPh)3, which directly
produced 2-deoxyglycoside in Table 1 (Figure 3a). When deuterated alcohol 7 was employed as a glycosyl
acceptor, 2-deoxyglycosides 8, 9, 11 and 12, which were deuterated at the C-2 position, were produced in
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high yields. These results clearly indicated that glycosyl donor 1 was protonated by the glycosyl acceptor,
alcohol 7, at the C-2 position. Based on these experimental results, we propose the reaction mechanism for
the glycosylation as shown in Figure 3b. First, a phosphonium iodide cation is generated from NIS and
P(OPh)3 by nucleophilic addition of P(OPh)3. The unoccupied electron orbital of the phosphorus atom is
activated by the electron withdrawing effect of the phenoxy groups to accept two electrons from the alcohol,
the glycosyl acceptor. After the coordination of the glycosyl acceptor to the phosphorus atom, the proton of
the glycosyl acceptor activates the glycosyl donor. As a result of the reaction, an oxonium cation
intermediate is generated. Finally, a glycosidic bond is formed due to the nucleophilic addition of the
aglycon portion to the oxonium cation intermediate. Additionally, the phosphonium iodide cation
intermediate behaves catalytically and is recycled during the reaction. Furthermore, an excess amount of
P(OPh)3 to NIS decreases the Lewis acidity of the phosphonium iodide cation intermediate to prevent the
production of the rearranged by-products 5a and 6.
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Figure 3. Mechanistic study (a) and proposed mechanism (b) of the glycosylation using NIS and
P(OPh)3.
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Next, we examined the generality of the glycosylation method by catalytic amounts of NIS and P(OPh)3
using several alcohols. These results are summarized in Table 4. It was found that all glycosylations of
2b-h, j and l as well as 2a with 1 using NIS and P(OPh)3 proceeded smoothly to give the corresponding
2-deoxyglycosides 4b-d,14 e, f,14 g-h, j and l directly in high yields with -stereoselectivities.
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Table 4. Glycosylation reaction of 1 and several alcohols using NIS and P(OPh)3.
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1
b
c
a/ Ratios were determined by H NMR analysis. This reaction was performed at 40 ºC. 0.5 equiv. of
alcohol was used.
Finally, we examined the generality of the glycosylation method using 2a and other glycals,
tri-O-benzyl-D-galactal (14) and di-O-benzyl-6-deoxy-D-glucal (15) (Table 5). In condition A, which
employs NIS and PPh3, the corresponding 2-deoxy-2-iodoglycosides 16a and 17a were obtained from 14
and 15, respectively, in high yields (entries 1 and 2). In addition, it was found that the iodoglycosylation
reaction of 2a and acceptor 14 gave only the  isomer of 16a with complete -stereoselectivity. In contrast,
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under condition B, which uses NIS and P(OPh)3, the corresponding 2-deoxyglycosides 18a and 19a were
obtained from 14 and 15, respectively, in high yields (entries 3 and 4).
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Table 5. Glycosylations using 2a and 14 or 15 under conditions A and B.
Entry
Donor
Condition
Product
Yield (%)a
1
2
3
4
14
15
14
15
A
A
B
B
16a
17a
18a
19a
88 ( only)
89 (/ = 72/28)
91 (/ = 71/29)
86 (/ = 59/41)
a/ Ratios were determined by 1H NMR analysis.
Conclusion
In conclusion, we have developed novel glycosylation reactions using NIS and PPh3 or P(OPh)3. We
found that the use of NIS and PPh3 as a reaction accelerator realized effective iodoglycosylations under
mild conditions to provide 2-deoxy-2-iodoglycosides in high yields. On the other hand, the use of NIS and
P(OPh)3 was proven to be effective for the glycosylation to directly afford 2-deoxysugars in high yields.
These reactions, which can produce both 2-iodo- and 2-deoxyglycosides individually by changing the
phosphorus compound additive, are very attractive and provide new insights into the glycosylation reaction.
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Furthermore, although the present glycosylation methods could not simply be applied to glycals bearing
acetate protecting groups, they should find wide application in the synthesis of 2-iodo- and
2-deoxyglycosides, which frequently appear as biologically important glycons.
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Experimental Section
General procedure for iodoglycosylations of glucal 1 and alcohols 2 using NIS and PPh3
To a solution of glycosyl donor 1 (25.0 mg, 60.0 mol) in dry CH2Cl2 (0.600 mL) were added glycosyl
acceptor 2 (2.0 eq., 120 mol) and PPh3 (0.2 eq., 12.0 mol) at room temperature under Ar atmosphere.
After stirring at the same temperature for 20 min, the reaction mixture was cooled to −40 C, and then NIS
(2.0 eq., 120 mol) was added to the reaction mixture. After the reaction mixture was stirred for 12 h, the
reaction was quenched by addition of a mixture of 50 wt% Na2S2O3 and sat. NaHCO3 aq. (1/1, 2 ml) at −40
C. The resulting mixture was extracted with CHCl3 (2 mL × 3). The combined organic layer was washed
with brine (2 mL), dried over Na2SO4, and concentrated in vacuo. Purification of the residue by flash
column chromatography (10 g) gave the corresponding glycosides as a / mixture.
General procedure for glycosylations of glucal 1 and alcohols 2 using NIS and P(OPh)3
To a solution of glycosyl acceptor 2 (2.0 eq., 120 mol) in dry CH2Cl2 (0.600 mL) were added NIS (0.1
eq., 6.0 mol) and P(OPh)3 (0.2 eq., 12.0 mol) at room temperature under Ar atmosphere. After stirring at
the same temperature for 20 min, glycosyl donor 1 (25.0 mg, 60.0 mol) was added to the reaction mixture.
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After the reaction mixture was stirred for 3 h, the reaction was quenched by addition of a mixture of 50
wt% Na2S2O3 aq. and sat. NaHCO3 aq. (1/1, 2 ml). The resulting mixture was extracted with CHCl3 (2 mL
× 3). The combined organic layer was washed with brine (2 mL), dried over Na2SO4, and concentrated in
vacuo. Purification of the residue by flash column chromatography (10 g) gave the corresponding
glycosides as a / mixture.
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Cyclohexylmethyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3a): The anomeric
mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3a
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(23.5 mg, 60%). Colorless syrup; Rf 0.48 (8/1 n-hexane/EtOAc); []25 +14.8º (c 0.91, CHCl3); H NMR
D
(500 MHz, CDCl3)  7.42-7.24 (13H, m), 7.17-7.15 (2H, m), 5.17 (1H, br s), 4.85 and 4.49 (2H, ABq, J =
10.6 Hz), 4.71 and 4.53 (2H, ABq, J = 12.4 Hz), 4.70 and 4.53 (2H, ABq, J = 12.4 Hz), 4.48 (1H, dd, J =
1.2 and 4.3 Hz), 3.90 (1H, dd, J = 8.6 and 9.8 Hz), 3.84 (1H, ddd, J = 1.5, 4.3 and 9.8 Hz), 3.78 (1H, dd, J
= 4.3 and 10.9 Hz), 3.69 (1H, dd, J = 1.5 and 10.9 Hz), 3.45 (1H, dd, J = 6.6 and 9.5 Hz), 3.31 (1H, dd, J =
4.3 and 8.6 Hz), 3.18 (1H, dd, J = 6.1 and 9.2 Hz), 1.71-1.65 (6H, m), 1.26-1.10 (3H, m), 0.93-0.84 (2H,
m); 13C NMR (125 MHz, CDCl3)  138.4, 138.2, 137.7, 128.4, 128.3×2, 128.1×2, 127.8, 127.7, 127.6,
127.4, 101.5, 76.0, 75.3, 73.6, 73.3, 72.1, 71.0, 68.9, 37.8, 33.8, 30.0, 29.8, 26.5, 25.8, 25.7, 22.6, 14.1;
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C34H41IO5Na 679.1896; found 679.1900.
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Cyclohexylmethyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3a): The anomeric
mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3a
(9.2 mg, 23%). White solid; Rf 0.42 (8/1 n-hexane/EtOAc); []25D +25.4º (c 1.33, CHCl3); mp 66-67 C; 1H
NMR (500 MHz, CDCl3)  7.43-7.41 (2H, m), 7.34-7.27 (11H, m), 7.20-7.17 (2H, m), 4.98 and 4.85 (2H,
ABq, J = 10.1 Hz), 4.79 and 4.57 (2H, ABq, J = 10.9 Hz), 4.61 and 4.55 (2H, ABq, J = 12.0 Hz), 4.50 (1H,
d, J = 8.9 Hz), 3.92 (1H, dd, J = 8.9 and 10.9 Hz), 3.76-3.68 (4H, m), 3.60 (1H, dd, J = 8.6 and 9.7 Hz),
3.49 (1H, ddd, J = 2.3, 4.6 and 9.7 Hz), 3.29 (1H, dd, J = 7.2 and 9.2 Hz), 1.92-1.61 (6H, m), 1.29-1.13 (3H,
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m), 1.02-0.93 (2H, m); C NMR (125 MHz, CDCl3)  138.1, 137.7, 128.5, 128.4×2, 128.1, 127.9, 127.7,
127.6, 103.3, 85.9, 79.7, 76.0, 75.5, 75.2, 74.9, 73.5, 68.6, 37.8, 33.1, 30.1, 29.8, 26.6, 25.8×2; HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C34H41IO5Na 679.1896; found 679.1888.
n-Octyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3b): The anomeric mixture was
purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3b (24.4 mg,
61%). Colorless syrup; Rf 0.43 (8/1 n-hexane/EtOAc); []28D +11.6º (c 1.84, CHCl3); 1H NMR (500 MHz,
CDCl3)  7.42-7.24 (13H, m), 7.17-7.14 (2H, m), 5.21 (1H, br s), 4.85 and 4.48 (2H, ABq, J = 10.6 Hz),
4.72 and 4.53 (2H, ABq, J = 12.0 Hz), 4.70 and 4.52 (2H, ABq, J = 11.5 Hz), 4.49 (1H, dd, J = 1.4 and 4.0
Hz), 3.90 (1H, dd, J = 8.6 and 9.8 Hz), 3.85 (1H, ddd, J = 1.8, 4.6 and 9.8 Hz), 3.79 (1H, dd, J = 4.6 and
10.9 Hz), 3.70 (1H, dd, J = 1.8 and 10.9 Hz), 3.64 (1H, dt, J = 6.9 and 9.4 Hz), 3.38 (1H, dt, J = 6.6 and 9.8
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Hz), 3.32 (1H, dd, J = 4.0 and 8.6 Hz), 1.53-1.50 (2H, m), 1.30-1.24 (10H, m), 0.88 (3H, t, J = 7.2 Hz); 13C
NMR (125 MHz, CDCl3)  138.4, 138.2, 137.8, 128.4, 128.3×2, 128.1, 128.0, 127.8, 127.7, 127.6, 127.4,
101.3, 75.9, 75.3, 73.3, 72.1, 70.9, 68.9, 68.1, 33.8, 31.8, 29.4, 29.3, 29.2, 26.1, 22.6, 14.1; HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C35H45IO5Na 695.2209; found 695.2206.
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n-Octyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3b): The anomeric mixture was
purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3b (11.5 mg,
28%). White solid; Rf 0.38 (8/1 n-hexane/EtOAc); []29 +26.4º (c 1.38, CHCl3); mp 60-61 C; 1H NMR
D
(500 MHz, CDCl3)  7.43-7.42 (2H, m), 7.36-7.26 (11H, m), 7.19-7.17 (2H, m), 4.98 and 4.85 (2H, ABq, J
= 10.3 Hz), 4.80 and 4.56 (2H, ABq, J = 10.9 Hz), 4.61 and 4.55 (2H, ABq, J = 12.3 Hz), 4.52 (1H, d, J =
8.9 Hz), 3.92 (1H, dd, J = 8.9 and 10.9 Hz), 3.89 (1H, dt, J = 6.6 and 9.5 Hz), 3.76-3.68 (3H, m), 3.60 (1H,
dd, J = 8.6 and 9.8 Hz), 3.55-3.48 (2H, m), 1.69-1.59 (2H, m), 1.33-1.25 (10H, m), 0.88 (3H, t, J = 7.2 Hz);
13C NMR (125 MHz, CDCl3)  138.0, 137.7, 128.5, 128.4×2, 128.1, 127.9, 127.8, 127.6, 103.2, 85.9, 79.7,
75.5, 75.2, 74.9, 73.5, 70.4, 68.6, 33.2, 31.8, 29.4, 29.3, 29.2, 26.0, 22.7, 14.1; HRMS (ESI-TOF) m/z: [M
+ Na]+ calcd for C35H45IO5Na 695.2209; found 695.2216.
Methyl 2,3,4-tri-O-benzyl-6-O-(3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranosyl)--D-
glucopyranoside (3c): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 3/1) to give compound 3c (44.5 mg, 74%). Colorless syrup; Rf 0.41 (3/1
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n-hexane/EtOAc); []27 +36.4º (c 2.13, CHCl3); H NMR (500 MHz, CDCl3)  7.39-7.18 (28H, m),
D
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7.13-7.11 (2H, m), 5.27 (1H, br s), 4.99 and 4.80 (2H, ABq, J = 10.6 Hz), 4.87 and 4.45 (2H, ABq, J = 10.9
Hz), 4.85 and 4.47 (2H, ABq, J = 10.6 Hz), 4.79 and 4.69 (2H, ABq, J = 12.3 Hz), 4.69 and 4.49 (2H, ABq,
J = 12.3 Hz), 4.64 and 4.41 (2H, ABq, J = 12.0 Hz), 4.59 (1H, d, J = 3.4 Hz), 4.49 (1H, dd, J = 1.2 and 4.3
Hz), 3.98 (1H, dd, J = 9.2 and 9.2 Hz), 3.89 (1H, dd, J = 9.2 and 9.5 Hz), 3.83 (1H, dd, J = 4.3 and 11.5
Hz), 3.75 (1H, ddd, J = 1.5, 4.3 and 9.5 Hz), 3.69 (1H, ddd, J = 1.8, 4.3 and 9.8 Hz), 3.64 (1H, dd, J = 4.3
and 10.9 Hz), 3.58 (1H, dd, J = 1.5 and 11.5 Hz), 3.54 (1H, dd, J = 1.8 and 10.9 Hz), 3.50 (1H, dd, J = 3.4
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and 9.2 Hz), 3.41 (1H, dd, J = 9.2 and 9.8 Hz), 3.32 (3H, s), 3.24 (1H, dd, J = 4.3 and 9.2 Hz); C NMR
(125 MHz, CDCl3)  138.6, 138.4, 138.3, 138.1, 138.0, 137.4, 128.5, 128.4×2, 128.3, 128.2, 128.1,
128.0×2, 127.9×2, 127.8, 127.6×3, 127.5, 127.4×2, 101.7, 97.9, 82.1, 79.9, 77.4, 76.2, 75.8, 75.1, 74.9,
73.3, 73.2, 72.2, 70.7, 69.6, 68.6, 66.1, 55.1, 33.1; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C55H59IO10Na 1029.3051; found 1029.3060.
Methyl 2,3,4-tri-O-benzyl-6-O-(3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranosyl)--D-
glucopyranoside (3c): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 3/1) to give compound 3c (4.4 mg, 7%). White solid; Rf 0.38 (3/1 n-hexane/EtOAc);
[]25D +46.3º (c 0.84, CHCl3); mp 121-122 C; 1H NMR (500 MHz, CDCl3)  7.42-7.40 (2H, m), 7.37-7.22
(26H, m), 7.20-7.17 (2H, m), 4.99 and 4.82 (2H, ABq, J = 10.6 Hz), 4.96 and 4.82 (2H, ABq, J = 10.6 Hz),
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4.96 and 4.89 (2H, ABq, J = 10.9 Hz), 4.78 and 4.56 (2H, ABq, J = 11.2 Hz), 4.64 (1H, d, J = 3.5 Hz), 4.57
and 4.52 (2H, ABq, J = 12.1 Hz), 4.53 (1H, d, J = 8.9 Hz), 4.12-4.10 (1H, m), 4.02-3.99 (1H, m), 3.96 (1H,
dd, J = 8.9 and 10.6 Hz), 3.78-3.65 (6H, m), 3.58 (1H, dd, J = 3.5 and 9.2 Hz), 3.49 (1H, ddd, J = 1.5, 4.3
and 9.8 Hz), 3.39 (3H, s); 13C NMR (125 MHz, CDCl3)  138.7, 138.6, 138.2, 138.0, 137.6, 128.5, 128.4×2,
128.3, 128.1×3, 127.9×2, 127.7, 127.6, 103.0, 98.2, 85.7, 82.3, 79.7, 79.6, 75.8, 75.5, 75.4, 75.1, 74.9,
73.4×2, 69.5, 68.6, 68.0, 55.3, 32.5; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C55H59IO10Na 1029.3051;
found 1029.3045.
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Isopropyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3d): The anomeric mixture was
purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3d (22.1 mg,
61%). Colorless syrup; Rf 0.49 (8/1 n-hexane/EtOAc); []25D +13.5º (c 1.50, CHCl3); 1H NMR (500 MHz,
CDCl3)  7.42-7.41 (2H, m), 7.38-7.26 (11H, m), 7.16-7.14 (2H, m), 5.32 (1H, br s), 4.84 and 4.47 (2H,
ABq, J = 10.6 Hz), 4.72 and 4.52 (2H, ABq, J = 12.0 Hz), 4.70 and 4.52 (2H, ABq, J = 10.6 Hz), 4.48 (1H,
dd, J = 1.4 and 4.0 Hz), 3.93-3.88 (4H, m), 3.80 (1H, dd, J = 4.9 and 10.9 Hz), 3.69 (1H, dd, J = 2.0 and
10.9 Hz), 3.34 (1H, m), 1.17 (3H, d, J = 6.3 Hz), 1.12 (3H, d, J = 6.3 Hz); 13C NMR (125 MHz, CDCl3) 
138.4, 138.2, 137.8, 128.4, 128.3, 128.2, 128.1, 127.9, 127.7×2, 127.6, 127.4, 99.5, 76.0, 75.3, 73.3, 72.1,
70.8, 69.9, 68.9, 34.5, 23.2, 21.5; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C30H35IO5Na 625.1427;
found 625.1439.
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Isopropyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3d): The anomeric mixture was
purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3d (10.4 mg,
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29%). White solid; Rf 0.46 (8/1 n-hexane/EtOAc); []26 +32.1º (c 1.06, CHCl3); mp 91-92 C; 1H NMR
D
(500 MHz, CDCl3)  7.44-7.42 (2H, m), 7.36-7.26 (11H, m), 7.20-7.18 (2H, m), 4.98 and 4.85 (2H, ABq, J
= 10.3 Hz), 4.80 and 4.60 (2H, ABq, J = 10.6 Hz), 4.61 and 4.55 (2H, ABq, J = 12.3 Hz), 4.59 (1H, d, J =
8.9 Hz), 3.98 (1H, m), 3.90 (1H, dd, J = 8.9 and 10.9 Hz), 3.75-3.71 (2H, m), 3.68 (1H, dd, J = 4.9 and 10.9
Hz), 3.58 (1H, dd, J = 8.6 and 9.7 Hz), 3.50 (1H, ddd, J = 2.1, 4.9 and 9.7 Hz), 1.28 (3H, d, J = 6.3 Hz),
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1.26 (3H, d, J = 6.3 Hz); C NMR (125 MHz, CDCl3)  138.1, 137.7, 128.5, 128.4, 128.3, 128.1, 127.9,
127.7, 127.6, 102.0, 86.1, 79.7, 75.4, 75.2, 74.9, 73.4, 72.9, 68.7, 34.1, 23.4, 21.7; HRMS (ESI-TOF) m/z:
[M + Na]+ calcd for C30H35IO5Na 625.1427; found 625.1435.
1-((tert-Butyldiphenylsilyl)oxy)-(2R)-2-propyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo
--D-glucopyranoside (3e): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 8/1) to give compound 3e (35.5 mg, 69%). Colorless syrup; Rf 0.40 (8/1
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n-hexane/EtOAc); []25 +23.7º (c 1.12, CHCl3); H NMR (500 MHz, CDCl3)  7.68-7.64 (4H, m),
D
7.45-7.27 (19H, m), 7.17-7.14 (2H, m), 5.53 (1H, br s), 4.85 and 4.48 (2H, ABq, J = 10.6 Hz), 4.73 and
4.53 (2H, ABq, J = 12.0 Hz), 4.65 and 4.46 (2H, ABq, J = 11.5 Hz), 4.46 (1H, dd, J = 1.1 and 4.3 Hz), 3.98
(1H, ddd, J = 1.7, 4.6 and 10.0 Hz), 3.95-3.90 (2H, m), 3.81 (1H, dd, J = 4.6 and 10.9 Hz), 3.71 (1H, dd, J
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= 1.7 and 10.9 Hz), 3.57 (1H, dd, J = 6.9 and 10.9 Hz), 3.53 (1H, dd, J = 4.0 and 10.9 Hz), 3.32 (1H, dd, J
= 4.3 and 8.6 Hz), 1.10 (3H, d, J = 6.6 Hz), 1.06 (9H, s); 13C NMR (125 MHz, CDCl3)  138.4, 138.2,
137.8, 135.5, 133.4, 133.3, 129.7, 128.4, 128.3×2, 128.1, 127.9, 127.7×3, 127.6, 127.4, 101.9, 76.1, 75.4,
75.3, 73.4, 72.3, 70.7, 68.9, 67.9, 33.9, 26.8, 19.2, 17.8; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C46H53IO6SiNa 879.2552; found 879.2546.
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1-((tert-Butyldiphenylsilyl)oxy)-(2R)-2-propyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo -
-D-glucopyranoside (3e): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 8/1) to give compound 3e (11.2 mg, 22%). Colorless syrup; Rf 0.38 (8/1
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n-hexane/EtOAc); []26 +24.1º (c 1.32, CHCl3); H NMR (500 MHz, CDCl3)  7.69-7.66 (5H, m),
D
7.42-7.22 (18H, m), 7.18-7.16 (2H, m), 4.96 and 4.85 (2H, ABq, J = 10.3 Hz), 4.77 and 4.56 (2H, ABq, J =
10.6 Hz), 4.54 (1H, d, J = 8.9 Hz), 4.50 and 4.39 (2H, ABq, J = 12.3 Hz), 3.93-3.87 (2H, m), 3.84 (1H, dd,
J = 8.9 and 10.6 Hz), 3.68 (1H, dd, J = 8.6 and 10.6 Hz), 3.64 (1H, dd, J = 4.3 and 10.9 Hz), 3.60-3.55 (2H,
m), 3.53 (1H, dd, J = 1.8 and 10.9 Hz), 3.38 (1H, ddd, J = 1.8, 4.3 and 11.5 Hz), 1.32 (3H, d, J = 6.0 Hz),
1.05 (9H, s); 13C NMR (125 MHz, CDCl3)  138.1, 137.8×2, 135.7, 135.6, 133.8, 133.6, 129.6, 128.4×2,
128.3, 128.1, 127.9, 127.7×2, 127.6, 127.5, 102.0, 86.0, 79.5, 76.5, 75.5, 75.1, 74.9, 73.5, 68.5, 67.3, 33.8,
26.9, 19.3, 16.8; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C46H53IO6SiNa 879.2552; found 879.2549.
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Cyclohexyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3f): The anomeric mixture was
purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3f (25.7 mg,
67%). Colorless syrup; Rf 0.47 (8/1 n-hexane/EtOAc); []25D +20.3º (c 1.95, CHCl3); 1H NMR (500 MHz,
CDCl3)  7.43-7.41 (2H, m), 7.38-7.24 (11H, m), 7.18-7.15 (2H, m), 5.35 (1H, br s), 4.85 and 4.47 (2H,
ABq, J = 10.6 Hz), 4.72 and 4.52 (2H, ABq, J = 11.7 Hz), 4.70 and 4.52 (2H, ABq, J = 10.4 Hz), 4.47 (1H,
dd, J = 1.7 and 4.3 Hz), 3.96 (1H, ddd, J = 1.7, 4.3 and 10.0 Hz), 3.91 (1H, dd, J = 8.3 and 10.0 Hz), 3.80
(1H, dd, J = 4.3 and 10.9 Hz), 3.70 (1H, dd, J = 1.7 and 10.9 Hz), 3.59 (1H, m), 3.35 (1H, dd, J = 4.3 and
8.3 Hz), 1.82 (2H, br s), 1.68 (2H, br s), 1.50 (1H, br s), 1.37-1.17 (5H, m); 13C NMR (125 MHz, CDCl3) 
138.4, 138.2, 137.8, 128.4, 128.3, 128.2, 128.1, 128.0, 127.7×2, 127.6, 127.4, 99.4, 76.1, 75.7, 75.3, 73.3,
72.1, 70.9, 69.0, 34.7, 33.2, 31.5, 25.5. 24.0, 23.8, 76.1, 75.7, 75.3, 73.3, 72.1, 70.9, 69.0, 34.7, 33.2, 31.5,
25.5, 24.0, 23.8; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C33H39IO5Na 665.1740; found 665.1730.
Cyclohexyl 3,4,6-tri-O-benzyl-2-deoxy-2-iodo--D-glucopyranoside (3f): The anomeric mixture was
purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give compound 3f (9.0 mg,
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23%). White solid; Rf 0.43 (8/1 n-hexane/EtOAc); []27 +15.2º (c 1.15, CHCl3); mp 83-85 C; 1H NMR
D
(500 MHz, CDCl3)  7.44-7.42 (2H, m), 7.36-7.25 (11H, m), 7.21-7.19 (2H, m), 4.98 and 4.85 (2H, ABq, J
= 10.0 Hz), 4.80 and 4.58 (2H, ABq, J = 10.6 Hz), 4.64 (1H, d, J = 8.9 Hz), 4.61 and 4.56 (2H, ABq, J =
12.3 Hz), 3.92 (1H, dd, J = 8.9 and 10.6 Hz), 3.75-3.65 (4H, m), 3.58 (1H, dd, J = 8.9 and 9.8 Hz), 3.50
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(1H, ddd, J = 2.0, 4.9 and 9.8 Hz), 1.95 (2H, br s), 1.83-1.76 (2H, m), 1.53-1.21 (6H, m); C NMR (125
MHz, CDCl3)  138.1, 137.8×2, 128.5, 128.4, 128.3, 128.1, 127.9, 127.7, 127.6, 101.7, 86.1, 79.7, 78.1,
75.4, 75.2, 74.9, 73.4, 68.7, 34.1, 33.4, 31.4, 25.6, 24.0, 23.8; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C33H39IO5Na 665.1740; found 665.1737.
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(1R, 2S, 5R)-2-Isopropyl-5-methylcyclohexyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-
glucopyranoside (3g): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 8/1) to give compound 3g (27.1 mg, 65%). Colorless syrup; Rf 0.42 (8/1
n-hexane/EtOAc); []27 +15.2º (c 1.15, CHCl3); H NMR (500 MHz, CDCl3)  7.42-7.22 (13H, m),
1
D
7.18-7.16 (2H, m), 5.26 (1H, br s), 4.86 and 4.48 (2H, ABq, J = 10.6 Hz), 4.71 and 4.51 (2H, ABq, J = 12.1
Hz), 4.70 and 4.57 (2H, ABq, J = 11.5 Hz), 4.40 (1H, dd, J = 1.5 and 4.1 Hz), 4.03 (1H, ddd, J = 2.0, 4.9
and 9.7 Hz), 3.89 (1H, dd, J = 8.9 and 9.7 Hz), 3.79 (1H, dd, J = 4.9 and 10.9 Hz), 3.68 (1H, dd, J = 2.0
and 10.9 Hz), 3.30 (2H, m), 2.17 (1H, br d), 1.95-1.89 (1H, m), 1.36-1.26 (2H, m), 1.19-1.12 (1H, m), 0.88
(3H, d, J = 7.2 Hz), 0.82 (3H, d, J = 6.6 Hz), 0.72 (3H, d, J = 6.9 Hz); 13C NMR (125 MHz, CDCl3) 
138.2, 137.9, 137.8, 128.5, 128.4, 128.0×2, 127.9, 127.8, 127.7, 127.6, 100.4, 86.2, 79.7, 77.9, 75.3, 75.1,
75.0, 47.7, 40.3, 34.3, 34.1, 31.5, 25.0, 23.1, 22.3, 21.0, 15.8; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C37H47IO5Na 721.2366; found 721.2365.
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(1R, 2S, 5R)-2-Isopropyl-5-methylcyclohexyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-
glucopyranoside (3g): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 8/1) to give compound 3g (7.7 mg, 18%). White solid; Rf 0.39 (8/1 n-hexane/EtOAc);
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[]25 +15.2º (c 1.15, CHCl3); mp 98-99 C; 1H NMR (500 MHz, CDCl3)  7.44-7.42 (2H, m), 7.36-7.26
D
(11H, m), 7.22-7.20 (2H, m), 4.98 and 4.86 (2H, ABq, J = 10.4 Hz), 4.80 and 4.61 (2H, ABq, J = 10.9 Hz),
4.60 and 4.53 (2H, ABq, J = 12.0 Hz), 4.61 (1H, d, J = 8.9 Hz), 3.88 (1H, dd, J = 8.9 and 10.9 Hz),
3.75-3.71 (2H, m), 3.69 (1H, dd, J = 1.7 and 10.9 Hz), 3.62 (1H, dd, J = 8.9 and 9.7 Hz), 3.52-3.45 (2H, m),
2.32-2.27 (1H, m), 2.15 (1H, br d), 1.65 (2H, br d), 0.95 (3H, d, J = 6.6 Hz), 0.89 (3H, d, J = 6.9 Hz), 0.79
(3H, d, J = 6.9 Hz); 13C NMR (125 MHz, CDCl3)  138.4, 138.2, 137.7, 128.4, 128.3, 128.2, 128.1×2,
127.8, 127.7, 127.6, 127.4, 103.1, 81.9, 76.2, 75.3, 73.3, 72.2, 71.1, 69.0, 48.4, 42.5, 34.5, 34.2, 31.5, 25.8,
23.2, 22.2×2, 21.0, 16.3; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C37H47IO5Na 721.2366; found
721.2374.
(3S)-2,2-Dimethyl-1,3-dioxolane-4-methyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--
D-glucopyranoside (3h): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 3/1) to give compound 3h (24.4 mg, 60%). Colorless syrup; Rf 0.40 (3/1
1
n-hexane/EtOAc); []27 +13.4º (c 1.81, CHCl3); H NMR (500 MHz, CDCl3)  7.42-7.24 (13H, m),
D
7.16-7.14 (2H, m), 5.28 (1H, br s), 4.85 and 4.48 (2H, ABq, J = 10.6 Hz), 4.70 and 4.50 (2H, ABq, J = 12.1
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Hz), 4.69 and 4.53 (2H, ABq, J = 12.3 Hz), 4.58 (1H, dd, J = 1.4 and 4.3 Hz), 4.24 (1H, m), 4.01 (1H, dd, J
= 6.6 and 8.3 Hz), 3.89 (1H, dd, J = 8.3 and 9.8 Hz), 3.85 (1H, ddd, J = 1.7, 4.6 and 9.8 Hz), 3.77 (1H, dd,
J = 4.6 and 10.9 Hz), 3.70 (1H, dd, J = 1.7 and 10.9 Hz), 3.66 (1H, dd, J = 4.6 and 10.9 Hz), 3.62 (1H, dd,
J = 6.6 and 8.3 Hz), 3.49 (1H, dd, J = 6.3 and 10.3 Hz), 3.31 (1H, dd, J = 4.3 and 8.3 Hz), 1.39 (3H, s),
1.35 (3H, s); 13C NMR (125 MHz, CDCl3)  138.3, 138.2, 137.7, 128.4, 128.3×2, 128.0, 127.9, 127.8,
127.7, 127.6, 127.5, 109.7, 101.8, 75.8, 75.2, 74.5, 73.4, 72.3, 70.9, 68.9, 68.8, 66.4, 33.0, 26.7, 25.4;
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C33H39IO7Na 697.1638; found 697.1642.
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(3S)-2,2-Dimethyl-1,3-dioxolane-4-methyl 3’,4’,6’-tri-O-benzyl-2-deoxy-2-iodo--
D-glucopyranoside (3h): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 3/1) to give compound 3h (10.4 mg, 26%). Colorless syrup; Rf 0.40 (3/1
1
n-hexane/EtOAc); []26 +32.5º (c 0.86, CHCl3); H NMR (500 MHz, CDCl3)  7.43-7.41 (2H, m),
D
7.37-7.27 (11H, m), 7.19-7.17 (2H, m), 4.97 and 4.85 (2H, ABq, J = 10.1 Hz), 4.80 and 4.56 (2H, ABq, J =
10.6 Hz), 4.61 and 4.53 (2H, ABq, J = 12.0 Hz), 4.57 (1H, d, J = 8.9 Hz), 4.32 (1H, m), 4.10 (1H, dd, J =
6.3 and 8.3 Hz), 3.97 (2H, m), 3.90 (1H, dd, J = 8.9 and 10.9 Hz), 3.71 (3H, m), 3.62 (1H, dd, J = 8.6 and
9.8 Hz), 3.53 (1H, dd, J = 7.2 and 9.8 Hz), 3.50 (1H, ddd, J = 2.3, 4.0 and 9.8 Hz), 1.44 (3H, s), 1.36 (3H,
s); 13C NMR (125 MHz, CDCl3)  137.9, 137.7, 128.5, 128.4×2, 128.1, 127.9×2, 127.8×2, 127.7, 109.4,
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103.4, 85.7, 79.5, 75.6, 75.2, 75.0, 74.0, 73.5, 70.6, 68.4, 67.1, 32.5, 27.0, 25.3; HRMS (ESI-TOF) m/z: [M
+ Na]+ calcd for C33H39IO7Na 697.1638; found 697.1632.
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1-((Triethylsilyl)oxy)-4-buthyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranoside
(3i): The anomeric mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1)
to give compound 3i (22.0 mg, 49%). Colorless syrup; Rf 0.39 (8/1 n-hexane/EtOAc); []25 +9.27º (c
D
1.02, CHCl3); 1H NMR (500 MHz, CDCl3)  7.42-7.24 (13H, m), 7.16-7.14 (2H, m), 5.21 (1H, br s), 4.84
and 4.48 (2H, ABq, J = 10.6 Hz), 4.72 and 4.52 (2H, ABq, J = 11.9 Hz), 4.69 and 4.51 (2H, ABq, J = 11.6
Hz), 4.50 (1H, dd, J = 1.2 and 4.3 Hz), 3.90 (1H, dd, J = 8.6 and 9.8 Hz), 3.84 (1H, ddd, J = 1.8, 4.6 and
9.8 Hz), 3.79 (1H, dd, J = 4.6 and 10.9 Hz), 3.70-3.65 (2H, m), 3.60 (2H, t, J = 6.0 Hz), 3.41 (1H, dt, J =
6.6 and 9.5 Hz), 3.32 (1H, dd, J = 4.3 and 8.6 Hz), 1.62-1.51 (4H, m), 0.95 (9H, t, J = 7.8 Hz), 0.59 (6H, q,
J = 7.8 Hz); 13C NMR (125 MHz, CDCl3)  138.4, 138.2, 137.4, 128.4, 128.3×2, 128.1, 128.0, 127.8,
127.6×2, 127.4, 101.4, 75.9, 75.2, 73.4, 72.1, 70.9, 68.9, 67.9, 62.4, 33.7, 29.5, 26.0, 6.79, 4.37; HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C37H51IO6SiNa 769.2397; found 769.2374.
1-((Triethylsilyl)oxy)-4-buthyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranoside
(3i): The anomeric mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to
give compound 3i (12.4 mg, 28%). Colorless syrup; Rf 0.35 (8/1 n-hexane/EtOAc); []25D +24.5º (c 0.88,
CHCl3); 1H NMR (500 MHz, CDCl3)  7.44-7.42 (2H, m), 7.37-7.25 (11H, m), 7.19-7.17 (2H, m), 4.98 and
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4.86 (2H, ABq, J = 10.3 Hz), 4.80 and 4.56 (2H, ABq, J = 10.9 Hz), 4.61 and 4.54 (2H, ABq, J = 12.3 Hz),
4.53 (1H, d, J = 8.9 Hz), 3.95-3.89 (2H, m), 3.75-3.65 (5H, m), 3.61 (1H, dd, J = 8.6 and 9.8 Hz), 3.55 (1H,
dt, J = 6.6 and 9.8 Hz), 3.49 (1H, ddd, J = 2.3, 4.3 and 9.8 Hz), 1.71-1.60 (4H, m), 0.96 (9H, t, J = 7.8 Hz),
0.60 (6H, q, J = 7.8 Hz); 13C NMR (125 MHz, CDCl3)  138.0, 137.7, 128.5, 128.4×2, 128.3, 127.9×3,
127.8, 127.6, 103.1, 85.9, 79.6, 75.5, 75.2, 74.9, 73.5, 70.1, 68.6, 62.5, 33.1, 29.4, 25.9, 6.83, 4.41; HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C37H51IO6SiNa 769.2397; found 769.2377.
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1-((tert-Butyldimethylsilyl)oxy)-4-buthyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranoside
(3j): The anomeric mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1)
to give compound 3j (24.0 mg, 54%). Colorless syrup; Rf 0.42 (8/1 n-hexane/EtOAc); []25 +8.80º (c
D
1.90, CHCl3); 1H NMR (500 MHz, CDCl3)  7.42-7.25 (13H, m), 7.16-7.14 (2H, m), 5.21 (1H, br s), 4.85
and 4.48 (2H, ABq, J = 10.6 Hz), 4.72 and 4.52 (2H, ABq, J = 12.0 Hz), 4.70 and 4.51 (2H, ABq, J = 11.2
Hz), 4.49 (1H, dd, J = 1.2 and 4.0 Hz), 3.91 (1H, dd, J = 8.6 and 9.8 Hz), 3.84 (1H, ddd, J = 1.8, 4.6 and
9.8 Hz), 3.79 (1H, dd, J = 4.6 and 10.9 Hz), 3.70-3.65 (2H, m), 3.60 (2H, t, J = 6.3 Hz), 3.41 (1H, dt, J =
6.6 and 9.8 Hz), 3.32 (1H, dd, J = 4.0 and 8.6 Hz), 1.62-1.50 (4H, m), 0.89 (9H, s), 0.04 (6H, s); 13C NMR
(125 MHz, CDCl3)  138.4, 138.2, 137.7, 128.4, 128.3×2, 128.1, 128.0, 127.8, 127.7, 127.6, 127.4, 101.4,
75.9, 75.3, 73.4, 72.1, 70.9, 68.9, 67.9, 62.8, 33.7, 29.4, 26.0, 18.3, -5.30; HRMS (ESI-TOF) m/z: [M +
Na]+ calcd for C37H51IO6SiNa 769.2397; found 769.2385.
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1-((tert-Butyldimethylsilyl)oxy)-4-buthyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranoside
(3j): The anomeric mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1)
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to give compound 3j (14.1 mg, 31%). White solid; Rf 0.38 (8/1 n-hexane/EtOAc); []25 +23.3º (c 1.15,
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CHCl3); mp 38-39 C; 1H NMR (500 MHz, CDCl3)  7.44-7.42 (2H, m), 7.36-7.26 (11H, m), 7.19-7.17
(2H, m), 4.98 and 4.86 (2H, ABq, J = 10.3 Hz), 4.80 and 4.56 (2H, ABq, J = 10.9 Hz), 4.61 and 4.54 (2H,
ABq, J = 12.3 Hz), 4.53 (1H, d, J = 8.9 Hz), 3.95-3.90 (2H, m), 3.75-3.64 (5H, m), 3.61 (1H, dd, J = 8.6
and 9.8 Hz), 3.55 (1H, dt, J = 6.6 and 9.8 Hz), 3.49 (1H, ddd, J = 2.3, 4.3 and 9.8 Hz), 1.73-1.62 (4H, m),
0.89 (9H, s), 0.05 (6H, s); 13C NMR (125 MHz, CDCl3)  138.0, 137.7, 128.5, 128.4×2, 128.1, 127.9×2,
127.8×2, 127.6, 103.1, 85.9, 79.6, 75.5, 75.2, 74.9, 70.1, 68.5, 62.8, 33.2, 29.3, 25.9, 18.3, -5.25; HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C37H51IO6SiNa 769.2397; found 769.2401.
1-((Triethylsilyl)oxy)-(2R)-2-propyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranoside (3k)
: The anomeric mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give
compound 3k (21.6 mg, 49%). Colorless syrup; Rf 0.47 (8/1 n-hexane/EtOAc); []25 +12.5º (c 1.58,
D
1
CHCl3); H NMR (500 MHz, CDCl3)  7.42-7.25 (13H, m), 7.16-7.15 (2H, m), 5.52 (1H, br s), 4.85 and
4.48 (2H, ABq, J = 10.6 Hz), 4.73 and 4.50 (2H, ABq, J = 12.0 Hz), 4.70 and 4.53 (2H, ABq, J = 11.5 Hz),
4.58 (1H, br d, J = 4.0 Hz), 3.97 (1H, ddd, J = 1.5, 4.0 and 9.8 Hz), 3.93 (1H, dd, J = 8.6 and 9.8 Hz), 3.85
(1H, m), 3.81 (1H, dd, J = 4.0 and 10.6 Hz), 3.70 (1H, br d, J = 10.6 Hz), 3.50 (1H, br d, J = 5.5 Hz), 3.33
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(1H, dd, J = 4.0 and 8.6 Hz), 1.10 (3H, d, J = 6.6 Hz), 0.96 (9H, t, J = 8.1 Hz), 0.60 (6H, q, J = 8.1 Hz); 13C
NMR (125 MHz, CDCl3)  138.4, 138.2, 137.9, 128.4, 128.3, 128.2, 128.1, 127.9, 127.7×3, 127.4, 101.9,
76.1, 75.4, 75.3, 73.3, 72.2, 70.7, 68.9, 67.1, 34.0, 17.7, 6.83, 4.36; HRMS (ESI-TOF) m/z: [M + Na]+ calcd
for C36H49IO6SiNa 755.2241; found 755.2227.
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1-((Triethylsilyl)oxy)-(2R)-2-propyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-glucopyranoside (3k):
The anomeric mixture was purified by flash column chromatography (10g, n-hexane/EtOAc = 8/1) to give
compound 3k (8.8 mg, 20%). Colorless syrup; Rf 0.42 (8/1 n-hexane/EtOAc); []26 +27.9º (c 0.74,
D
CHCl3); 1H NMR (500 MHz, CDCl3)  7.43-7.42 (2H, m), 7.37-7.25 (11H, m), 7.20-7.17 (2H, m), 4.97 and
4.86 (2H, ABq, J = 10.3 Hz), 4.80 and 4.59 (2H, ABq, J = 10.6 Hz), 4.63 (1H, d, J = 9.2 Hz), 4.61 and 4.53
(2H, ABq, J = 10.9 Hz), 3.90-3.82 (3H, m), 3.74-3.69 (3H, m), 3.62 (1H, dd, J = 8.9 and 9.8 Hz), 3.50-3.46
(2H, m), 1.27 (3H, d, J = 6.0 Hz), 0.95 (9H, t, J = 8.0 Hz), 0.60 (6H, q, J = 8.0 Hz); 13C NMR (125 MHz,
CDCl3)  138.0, 137.8, 137.7, 128.5, 128.4×2, 128.1, 127.9×2, 127.7, 127.6, 102.1, 86.0, 79.6, 75.5, 75.2,
74.9, 73.6, 68.6, 66.5, 33.8, 16.8, 6.77, 4.39; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C36H49IO6SiNa
755.2241; found 755.2251.
1-((tert-Butyldimethylsilyl)oxy)-(2R)-2-propyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-
glucopyranoside (3l): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 8/1) to give compound 3l (22.1 mg, 50%). Colorless syrup; Rf 0.46 (8/1
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The Journal of Organic Chemistry
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n-hexane/EtOAc); []25 +12.8º (c 1.57, CHCl3); H NMR (500 MHz, CDCl3)  7.42-7.25 (13H, m),
D
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7.16-7.14 (2H, m), 5.51 (1H, br s), 4.85 and 4.48 (2H, ABq, J = 10.6 Hz), 4.73 and 4.51 (2H, ABq, J = 12.4
Hz), 4.70 and 4.53 (2H, ABq, J = 11.5 Hz), 4.54 (1H, dd, J = 1.1 and 4.3 Hz), 3.97 (1H, ddd, J = 1.7, 4.3
and 10.1 Hz), 3.92 (1H, dd, J = 8.6 and 10.1 Hz), 3.85 (1H, m), 3.81 (1H, dd, J = 4.3 and 10.9 Hz), 3.70
(1H, dd, J = 1.7 and 10.9 Hz), 3.49 (1H, br d, J = 5.8 Hz), 3.32 (1H, dd, J = 4.3 and 8.6 Hz), 1.09 (3H, d, J
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= 6.6 Hz), 0.90 (9H, s), 0.05×2 (6H, s); C NMR (125 MHz, CDCl3)  138.4, 138.2, 137.9, 128.4, 128.3,
128.2, 128.1, 127.9, 127.7×2, 127.6, 127.4, 101.8, 76.1, 75.3×2, 73.3, 72.2, 70.8, 68.9, 67.4, 34.0, 25.9,
18.2, 17.7, -5.35, -5.41; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C36H49IO6SiNa 755.2241; found
755.2261.
1-((tert-Butyldimethylsilyl)oxy)-(2R)-2-propyl 3’,4’,6’-tri-O-benzyl-2’-deoxy-2’-iodo--D-
glucopyranoside (3l): The anomeric mixture was purified by flash column chromatography (10g,
n-hexane/EtOAc = 8/1) to give compound 3l (10.4 mg, 24%). White solid; Rf 0.40 (8/1 n-hexane/EtOAc);
[]25D +26.8º (c 0.77, CHCl3); mp 54-55 C; 1H NMR (500 MHz, CDCl3)  7.44-7.25 (13H, m), 7.20-7.18
(2H, m), 4.97 and 4.86 (2H, ABq, J = 10.3 Hz), 4.80 and 4.60 (2H, ABq, J = 10.6 Hz), 4.63 (1H, d, J = 8.9
Hz), 4.56 and 4.54 (2H, ABq, J = 10.9 Hz), 3.90-3.81 (3H, m), 3.74-3.70 (3H, m), 3.61 (1H, dd, J = 8.9 and
9.8 Hz), 3.50-3.45 (2H, m), 1.26 (3H, d, J = 6.6 Hz), 0.89 (9H, s), 0.06 (3H, s), 0.04 (3H, s); 13C NMR (125
MHz, CDCl3)  138.0, 137.8, 137.7, 128.5, 128.4×2, 128.1, 127.9×2, 127.7, 127.6, 101.9, 86.0, 79.6, 76.6,
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