Glycosylation reaction of thioglycosides by using hypervalent iodine(III) reagent as an excellent promoter

Article abstract of DOI:10.1248/cpb.c16-00203

Thioglycosides are available donors in glycosylation due to the stability of the anomeric C-S bond under general reaction conditions of protection and deprotection, and offer orthogonality in their activation. We report now that the hypervalent iodine eff

Full text of DOI:10.1248/cpb.c16-00203

8
38
Chem. Pharm. Bull. 64, 838–844 (2016)
Vol. 64, No. 7
Special Collection of Papers
This article is dedicated to Professor Satoshi Ōmura in celebration of his 2015 Nobel Prize.
Regular Article
Glycosylation Reaction of Thioglycosides by Using Hypervalent Iodine(III)
Reagent as an Excellent Promoter
,
a
a
b
b
,a,b
Tetsuya Kajimoto,* Koji Morimoto, Ryosuke Ogawa, Toshifumi Dohi, and Yasuyuki Kita*
a
Research Organization of Science and Technology, Ritsumeikan University; 1–1–1 Nojihigashi,
b
Kusatsu, Shiga 525–8577, Japan: and College of Pharmaceutical Sciences, Ritsumeikan University;
1–1–1 Nojihigashi, Kusatsu, Shiga 525–8577, Japan.
Received February 29, 2016; accepted April 12, 2016
Thioglycosides are available donors in glycosylation due to the stability of the anomeric C–S bond under
general reaction conditions of protection and deprotection, and offer orthogonality in their activation. We
report now that the hypervalent iodine effectively induced glycosylation reaction of thioglycosides with vari-
ous alcohols. This method features a high efficiency, completion in a short time, and proceeding under very
mild conditions.
Key words glycosylation; hypervalent iodine reagent; thioglycoside
18–30)
Thioglycosides are the most widely used glycosyl donors organic chemistry.
We have been engaged in the develop-
for glycoside synthesis. Since the first report in 1909, the ment of the oxidation of the sulfur atom utilizing hypervalent
31,32)
chemistry of thioglycosides has been significantly investigated iodine reagents to form an active iodonium intermediate.
and numerous methodologies have been reported on their Thus, we have recently developed novel methods of hyperva-
1–5)
33)
preparation and activation in the past three decades.
Thio- lent iodine-induced glycosylation of thioglycoside. Besides
glycoside donors are relatively easy to prepare, stable under our study, a few methods have been reported as for the activa-
3
4–36)
various reaction conditions of protection and deprotection, and tion of thioglycosides with hypervalent iodines to date
;
6
)
offer orthogonality in their activation. An important feature however, activation of disarmed thioglycosides with hyper-
of thioglycosides is their ability to serve not only as glycosyl valent iodines still remains impractical and unavailable in
donors, but also acceptors. This feature, as the tunable reac- the synthesis of biologically active oligosaccharides. Herein,
tivity of thioglycosides, has often been used for the synthesis we now would like to report a new organosulfur participat-
7
)
of various oligosaccharides.
ing promoter system in which both the armed and disarmed
In general, the activation of thioglycosides was performed thioglycoside donors can be activated by using the hypervalent
using a mercury salt, such as HgSO , HgCl , Hg(OBz) , or iodine reagent (Chart 1).
4
2
2
8
–11)
33)
Hg(NO ) .
The use of copper(II) trifluoromethanesulfonate
Based on our previous investigation of the glycosylation,
3
2
Cu(OTf)2 (Mukaiyama) or CuBr –Bu NBr–AgOTf (Ogawa we examined the glycosylation reaction of methyl 2-deoxy-
2
4
12,13)
and Ito) as an activator was further investigated.
Recently, 2-phthalimido-3,4,6-tri-O-acetyl-1-thio-D-glucopyranoside 1a
In(OTf)3 was reported to become an effective activator by with 1-O-methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside 2
14)
ball milling under a solvent-free condition. However, these using the combination of phenyliodine(III) bis(trifluoroacetate)
reported systems for the glycosylation of thioglycosides have (PIFA) with various acids. As a result, the reaction with
relied on a toxic heavy metal oxidant for product formation. PIFA and trifluoromethanesulfonic acid (TfOH) afforded the
On the other hand, iodonium species generated from haloni- best yield (77%). The use of the 4-fluoro, 4-trifluoromethyl,
um-based reagents, such as N-iodosuccinimide (NIS), in con- 4-methyl and pentafluoro-substituted phenyliodine(III) re-
junction with a catalytic amount of a Brønsted or Lewis acid, agents did not increase the yield of the coupling product 3a
1
5)
were first reported in 1990 by van Boom and colleagues.
(Chart 2). The use of trimethylsilyl trifluoromethanesulfonate
bis[cyclohexyl]-trifluoromethanesulfonylborane,
Although these methods have been effective in carrying out (TMSOTf),
a range of glycosylations, most of these still have a limited and methanesulfonic acid produced poor results. Thus, the
scope. Generally, these methods often require low tempera-
tures (<20°C) for generating the reactive intermediates. In
recent several years, other unique methods such as thioper-
oxide promotor and photochemical activation using blue light
emitting diode (LED) have also been successfully explored for
16,17)
thioglycoside based-glycosidation.
Nowadays, the environmentally-benign hypervalent iodine
oxidation has witnessed significant progress in the field of Chart 1. The Hypervalent Iodine Induced Metal-Free Glycosylation
*
To whom correspondence should be addressed. e-mail: kajimoto@fc.ritsumei.ac.jp; kita@ph.ritsumei.ac.jp
©
2016 The Pharmaceutical Society of Japan

Vol. 64, No. 7 (2016)
Chem. Pharm. Bull.
839
Chart 2. Glycosylation Reactions of 1a and 2 Using PIFA with Various Acids
combination of PIFA (1.0eq.) and TfOH (2.0eq.) was em- 1-adamantananol 7 (−)- and (+)-borneols 8, 12, (+)-fenchyl
ployed as the activator of the thioglycoside donor in the glyco- alcohol 13 and ent-17-nor-kauranol 14 were glycosylated with
sylation reactions. It is noted that this reaction did not proceed 1c in good yields.
in the absence of TfOH. On the basis of the above finding, it
The synthesis of disaccharides by the described glycosyl-
could be suggested that TfOH coordinated with the carbonyl ation was also performed using 1c and 1-O-methyl 2,3,4-tri-
oxygen of trifluoroacetate in PIFA and assisted lowering the O-benzyl-α-D-glucopyanoside 2 as the donor and the acceptor
electron density of the iodine, of which the function played an substrates, respectively. Since the former was “disarmed” and
4
0,41)
important role to activate the thioglycosides.
the latter was “armed,”
the combination seemed to be one
The scope of the glycosylation donors 1a and b with vari- of the most undesired ones; however, the reaction occurred to
ous acceptors was investigated under the optimal conditions provide the desired disaccharide 3a in 87% yield (Chart 3).
(
Table 1). The reactions of 1a with a secondary alcohol 4 or Similarly, in the case of donor 1d and acceptor 2, the reaction
gave the corresponding glycosides 3b and c in moderate smoothly proceeded and gave the disaccharides 3n in good
yields (entries 1, 2). It was also found that cholestanol 6 could yield.
5
be employed as a glycosyl acceptor and gave the glycosylated
In conclusion, we found that the hypervalent iodine, PIFA,
product 3d in 60% yield (entry 3). The tertiary alcohol 7 was is an excellent promoter of thioglycosides in the presence of
glycosylated in 58% under the same reaction condition in spite TfOH in the glycosylation reaction and the reaction afforded
of the steric hindrance caused by the adamantane skeleton satisfactory results especially using the thioglycosides bear-
(
entry 4). In addition, a more hindered alcohol, such as the ing a phthalimido group at the C-2 position. In addition, our
−)-borneol 8, was glycosylated with 1a in a good yield (entry method could allow the glycosylation of the undesirable com-
).
bination of substrates, i.e., the combination of the “disarmed”
Encouraged by these results, we further evaluated the re- donor and “armed” acceptor, in excellent yields.
(
5
action for the synthesis of disaccharides. The glycosylations
of the glycosyl donor 1a with the benzoylated glycosyl ac- Experimental
1
13
ceptor 9 having a free hydroxyl group at the C-6 position,
General Remarks The H-NMR and C-NMR spectra
proceeded with a excellent yield (entry 6). The reaction of 1b were recorded by a JEOL JMN-400 spectrometer operating
with acceptor 9 afforded the desired disaccharide 3h in a good at 400MHz in CDCl at 25°C with tetramethylsilane as the
3
yield (entry 7). The glycosylations of the donor with the ga- internal standard. Data are reported as follows: chemical shift
lactosyl acceptor 10, having a free hydroxyl group at the C-4 in ppm (δ), integration, multiplicity (s=singlet, d=doublet,
position, also proceeded in a satisfactory yield (entry 8). The t=triplet, q=quartet, brs=broad singlet, m=multiplet), cou-
more stereocongested acceptor 11 was condensed with 1a with pling constant (Hz). The infrared spectra (IR) were obtained
an equal efficiency (entry 9).
On the other hand, odorless p-octyloxylbenzenthiol
using a Hitachi 270-50 spectrometer, absorptions are reported
in reciprocal centimeters. The mass spectra were obtained
33,37–39)
was chosen as the source of the aglycon moiety of the 1-thio- using a Shimadzu GCMS-QP 5000 instrument with ioniza-
glycosides to avoid tedious handling of odoriferous organosul- tion voltages of 70eV. The high resolution mass spectra were
fur compounds like methanethiol or benzenethiol, generated performed by the Elemental Analysis Section of Osaka Uni-
during the conventional glycosylation reaction using methyl versity. Column chromatography and TLC were carried out
or phenyl 1-thioglycosides. Based on this information, p-oc- on Merck Silica gel 60 (230–400 mesh) and Merck Silica gel
tyloxyphenyl 2-deoxy-2-phthalimido-3,4,6-tri-O-acetyl-1-thio- F254 plates (0.25mm), respectively. The spots and bands were
β-D-glucopyranoside 1c was adopted as the donor glycoside detected by UV irradiation (254, 365nm).
37–39)
and synthesized by a method reported in the literature.
Materials PhI(OCOCF3)2 (PIFA), methyl 2-deoxy-2-
In addition, p-octyloxyphenyl 2-deoxy-2-phthalimido-3,4,6- phthalimido-3,4,6-tri-O-acetyl-1-thio-β-D-glucopyranoside 1a,
tri-O-acetyl-1-thio-β-D-galactopyranoside 1d was prepared methyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside 1b,
37)
from 2-deoxy-2-phthalimino-D-galactose tetraacetate
and 1-O-methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside 2, (l)-
p-octyloxybenzenethiol in 83% yield using the same protocol. menthol 4, cholestanol 6, 2- and 1-adamanntanols 5, 7,
As shown in Table 2, the reaction of the thioglycoside 1c with (−)- and (+)-borneol 8, 12, and (+)-fenchyl alcohol 13 are
alkanols smoothly proceeded and the yield was improved in commercially available and used as received. All other start-
comparison with the use of the glycosyl donor 1a. Secondary ing materials are commercially available. They were used
alcohols 4–6 gave the desired products in good yields. In ad- without further purification. p-Octyloxyphenyl 2-deoxy-2-
dition, the substrates carrying a hindered alcohol, such as the phthalimido-3,4,6-tri-O-acetyl-1-thio-β-D-glucopyranoside 1c

8
40
Chem. Pharm. Bull.
Vol. 64, No. 7 (2016)
a), b)
Table 1. Reaction of Glycosyl Donors and Acceptors
Entry
1
Donor
Acceptor
Product
Yield (%)
57
2
3
〃
〃
58
60
4
5
〃
〃
58
63
6
〃
87
7
8
〃
40
56
9
〃
59
a) Reactions were carried out by adding PIFA (0.2mmol) to a stirred solution of the starting glycosyl donar (0.2mmol) and glycosyl acceptors 4–11 (0.3mmol) in CH Cl
2
2
(4mL) in the presence of TfOH (0.4mmol) at 0°C. b) Yield of isolated product.

Vol. 64, No. 7 (2016)
Chem. Pharm. Bull.
841
a), b)
Table 2. Glycosylation Reaction of Glycosyl Donor 1c
a) Reactions were carried out by adding PIFA (0.20mmol) to a stirred solution of the starting glycosyl donar 1c (0.20mmol) and glycosyl acceptors 4–8, 12–14 (0.30mmol)
in CH Cl (4mL) in the presence of TfOH (0.40mmol) at 0°C. b) Yield of isolated product.
2
2
Chart 3. Synthesis of Disaccharides 3a and n Using Thioglycoside Activation with PIFA
3
1)
was synthesized by the method in the literature,
i.e., J=10.0Hz), 5.09 (1H, t, J=10.0Hz), 5.56 (1H, d, J=10.0 Hz),
BF ·Et O (268mL, 2.12mmol) was added to a solution of 5.76 (1H, t, J=10.0Hz), 6.78, 7.33 (2H, each d, J=8.8Hz),
3
2
2
(
-deoxy-2-phthalimido-1,3,4,6-tetra-O-acetyl-D-glucopyranose 7.76 (2H, dd, J=5.3, 3.0Hz), 7.88 (2H, dd, J=5.3, 3.0Hz)
13
676mg, 1.41mmol), and p-octyloxybenzenethiol (506mg, ppm; C-NMR (100MHz, C D N) δ: 13.6, 19.5, 19.7, 20.0,
5
5
2
.12mmol) in dichloromethane (5mL) at 0°C and the mix- 22.2, 25.8, 28.7, 28.76, 28.85, 31.3, 53.8, 61.9, 67.6, 68.6, 71.6,
ture was stirred for 20h at room temperature (r.t.). After the 75.9, 83.2, 114.9 (2C), 120.5, 122.3 (2C), 130.9, 131.3, 134.2,
reaction, the reaction mixture was poured into ice water and 134.3, 135.8 (2C), 159.7, 166.9, 167.8, 169.0, 169.7, 169.8ppm;
−1
extracted with ethyl acetate. The organic layer was washed IR: 2930, 2856, 1778, 1747, 1719, 1593, 1495, 1470cm ; high
+
with a saturated aqueous solution of sodium chloride, dried resolution (HR)-MS: Calcd for C H NNaO S [M+Na] :
3
4
41
10
over magnesium sulfate, and evaporated. The residue was 678.2349. Found: 678.2343.
purified by silica gel column chromatography (n-hexane–
p-Octyloxyphenyl 2-deoxy-2-phthalimido-3,4,6-tri-O-acetyl-
ethyl acetate=2:1) to afford p-octyloxyphenyl 2-deoxy-2- 1-thio-β-D-galactopyranoside 1d was also prepared from
phthalimido-3,4,6-tri-O-acetyl-1-thio-β-D-glucopyranoside 1c 2-deoxy-2-phthalimino-D-galactose tetraacetate and p-octyl-
(
829mg, 89%) as a colorless syrup.
oxybenzenethiol with good yield (83%) in the same way as
1
H-NMR (300MHz, CDCl ) δ: 0.89 (3H, t, J=7.0Hz), 1.78 the synthesis of 1c, i.e., 1d was obtained by the reaction of
3
(2H, quint, J=7.0Hz), 1.83, 2.01, 2.10 (3H, each s), 3.86 (1H, 2-deoxy-2-phthalimino-D-galactose tetraacetate with p-octyl-
dq, J=10.0, 2.4Hz), 3.93 (2H, t, J=6.6Hz), 4.20 (1H, dd, oxybenzenethiol in the presence of BF ·Et O in CH Cl .
3
2
2
2
J=12.3, 2.4Hz), 4.26 (1H, dd, J=12.3, 5.0Hz), 4.28 (1H, t,

8
42
Chem. Pharm. Bull.
Vol. 64, No. 7 (2016)
+
p-Octyloxyphenyl 2-Deoxy-2-phthalimido-3,4,6-tri-O-ace- Calcd for C H NNaO [M+Na] 596.2472. Found 596.2466.
3
0
39
10
tyl-1-thio-β-D-galactopyranoside (1d)
2-Adamantyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-β-D-
1
H-NMR (400MHz, CDCl ) δ: 0.85–0.86 (3H, m), 1.26–1.29 glucopyranoside (3c)
3
1
(
2
(
8H, m), 1.41 (2H, m), 1.74 (2H, q, J=6.8Hz), 1.81 (3H, s),
.02 (3H, s), 2.14 (3H, s), 3.89 (2H, t, J=6.4Hz), 4.03–4.05 δ: 1.22–1.35 (4H, m), 1.46–1.76 (10H, m), 1.81 (3H, s), 2.00
1H, m), 4.09–4.14 (1H, m), 4.18–4.20 (1H, m), 4.56 (1H, t, (3H, s), 2.09 (3H, s), 3.74 (1H, brs), 3.84 (1H, dq, J=7.8,
White solid, mp 187–190°C; H-NMR (400MHz, CDCl )
3
J=10.8Hz), 5.45 (1H, s), 5.54 (1H, d, J=9.3Hz), 5.77 (1H, d, 2.4Hz), 4.12 (1H, dd, J=12.0, 2.4Hz), 4.31–4.39 (2H, m),
J=10.8Hz), 6.75–6.77 (2H, m), 7.31–7.34 (2H, m), 7.75–7.76 5.16 (1H, t, J=9.3Hz), 5.40 (1H, d, J=8.2Hz), 5.82 (1H, dd,
1
3
(
1
2H, m), 7.86 (2H, brs) ppm; C-NMR (100MHz, CDCl ) δ: J=10.7, 9.2Hz), 7.70–7.72 (2H, m), 7.82–7.84 (2H, m) ppm;
3
13
4.1, 20.5, 20.7, 22.6, 26.0, 29.1, 29.2, 29.3, 31.8, 50.1, 61.6,
C-NMR (100MHz, CDCl ) δ: 20.5, 20.7, 20.8, 26.9, 27.0,
3
6
1
6.8, 68.0, 68.9, 74.4, 77.2, 84.6, 114.8 (2C), 121.3, 123.6, 30.9, 31.2, 31.3, 33.2, 36.1, 36.5, 37.2, 54.8, 62.1, 69.2, 70.7,
23.7, 131.3, 131.5, 134.3, 134.4, 135.8 (2C), 159.8, 167.3, 168.0, 71.6, 81.4, 96.3, 123.5 (2C), 131.3 (2C), 134.3 (2C), 169.5,
1
69.8, 170.3, 170.4ppm; IR (KBr): 3052, 2930, 2857, 2253, 170.3, 170.8ppm; IR (KBr): 2911, 2852, 1761, 1716, 1387, 1226,
−1
1748, 1716, 1594, 1569, 1494, 1470, 1384, 1245, 1174, 1118, 1043, 903, 817, 791, 746, 722, 684cm ; HR-FAB-MS: Calcd
−1
+
1
088, 1045, 912, 831, 741, 672cm ; HR-FAB-MS: Calcd for for C H NNaO [M+Na] 592.2159. Found 592.2153.
30 35 10
+
C H NNaO S [M+Na] 678.2349. Found 678.2343.
Cholestan-3β-yl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-
General Procedure To a stirred solution of 2-deoxy- β-D-glucopyranoside (3d)
-phthalimido-3,4,6-tri-O-acetyl-1-thio-D-glucopyranoside 1a White solid, mp 167–170°C; H-NMR (400MHz, CDCl ) δ:
3
4
41
10
1
2
3
and 1-O-methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside 2 (1 0.57 (3H, s), 0.62 (3H, s), 0.81–1.83 (40H, m), 1.88 (3H, s), 2.00
equiv) in the presence of MS 4A in CH Cl (0.2 M), TfOH (2 (3H, s), 2.08 (3H, s), 3.47–3.52 (1H, m), 3.80–3.86 (1H, m),
2
2
equiv) was added at −78°C. Then, PIFA (1 equiv) was subse- 3.99–4.14 (1H, m), 4.24–4.32 (2H, m), 5.13 (1H, t, J=9.2Hz),
quently added to the reaction mixture with stirring and stirred 5.43 (1H, d, J=8.8Hz), 5.75 (1H, t, J=9.2Hz), 7.71–7.73 (2H,
13
for an additional 3h under the same conditions, while the m), 7.83–7.85 (2H, m) ppm; C-NMR (100MHz, CDCl ) δ:
3
reaction was monitored by TLC. A saturated aqueous solution 11.9, 12.2, 18.6, 20.5, 20.6, 20.8, 21.1, 22.5, 22.8, 23.8, 24.1,
of sodium hydrogen carbonate was added to the mixture when 28.0, 28.2, 28.6, 29.1, 32.0, 34.3, 35.36, 35.4, 35.7, 36.1, 36.9,
the reaction completed. The aqueous phase was extracted with 39.5, 39.9, 42.5, 44.5, 54.2, 54.9, 56.2, 56.4, 62.2, 69.1, 70.9,
CH Cl . The extract was dried over anhydrous Na SO and 71.6, 79.5, 96.9, 123.6 (2C), 131.4 (2C), 134.2 (2C), 169.5,
2
2
2
4
then evaporated to dryness. The crude residue was purified 170.2, 170.8ppm; IR (KBr): 2927, 2867, 1748, 1716, 1387,
−1
by column chromatography on silica gel (eluent: n-hexane– 1229, 1074, 1040, 833, 803, 749, 721, 678cm ; HR-FAB-MS:
+
CH Cl ) to give the pure glycosylation product 3a in 77% Calcd for C H NNaO [M+Na] 828.4663. Found 828.4568.
2
2
47 67
10
yield.
1-Adamantyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-β-D-
Methyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-D-gluco- glucopyranoside (3e)
pyranosyl-β(1→6)-2,3,4-tri-O-benzyl-α-D-glucopyranoside (3a) White solid, mp 185–189°C; H-NMR (400MHz, CDCl ) δ:
1
3
1
White solid, mp 150–151°C; H-NMR (400MHz, CDCl ) δ: 1.22–1.25 (4H, m), 1.45–1.57 (7H, m), 1.67–1.70 (4H, m), 1.83
3
1
.78 (3H, s), 1.96 (3H, s), 2.02 (3H, s), 3.10 (3H, s), 3.16 (1H, (3H, s), 2.00 (3H, s), 2.06 (3H, s), 3.83–3.88 (1H, m), 4.08–4.12
t, J=9.2Hz), 3.31 (1H, dd, J=10.0, 3.6Hz), 3.57–3.60 (2H, (1H, m), 4.25–4.31 (2H, m), 5.09 (1H, t, J=9.6Hz), 5.54 (1H,
m), 3,75–3.82 (2H, m), 4.01–4.12 (3H, m), 4.23–4.35 (4H, m), d, J=8.0Hz), 5.82 (1H, dd, J=10.7, 9.2Hz), 7.71–7.74 (2H, m),
13
4
.50 (1H, d, J=12.0Hz), 4.58 (1H, d, J=11.2Hz), 4.65 (1H, d, 7.83–7.85 (2H, m) ppm; C-NMR (100MHz, CDCl ) δ: 20.5,
3
J=11.6Hz), 4.78 (1H, d, J=11.8Hz), 5.11 (1H, t, J=11.2Hz), 20.7, 20.8, 29.7, 30.5 (2C), 35.9 (2C), 42.1 (2C), 55.0, 62.5,
5
.36 (1H, d, J=8.4Hz), 5.72 (1H, dd, J=11.4, 8.8Hz), 69.4, 70.8, 71.3, 75.8, 91.6, 123.6 (2C), 131.4 (2C), 134.2 (2C),
6.94–6.96 (2H, m), 7.14–7,24 (15H, m), 7.48 (2H, brs) ppm; 169.6, 170.2, 170.7ppm; IR (KBr): 2911, 2854, 1749, 1718,
13
−1
C-NMR (100MHz, CDCl ) δ: 20.4, 20.6, 20.8, 54.4, 55.0, 1386, 1275, 1262, 1226, 1068, 1031, 971, 789, 750, 724cm ;
3
6
2.0, 68.7, 68.9, 69.1, 70.7, 71.9, 73.4, 74.7, 75.7, 77.5, 79.6, HR-FAB-MS: Calcd for C H NNaO [M+Na]+ 592.2159.
3
0
35
10
81.8, 97.8, 98.3, 123.5, 127.5, 127.6, 127.7, 127.9, 127.93, 128.1, Found 592.2153.
1
28.3 (2C), 128.4, 131.1, 134.1, 137.7, 138.1, 138.6, 169.4, 170.2,
(−)-Bornyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-β-D-
170.8ppm; IR (KBr): 2930, 1752, 1719, 1455, 1386, 1366, 1234, glucopyranoside (3f)
−1
1
1071, 1043, 913, 745, 700, 647cm ; HR-FAB-MS: Calcd for
White solid, mp 130–134°C; H-NMR (400MHz, CDCl )
3
+
C H NNaO [M+Na] 904.3156. Found 904.3151.
δ: 0.45–0.58 (2H, m), 0.72 (3H, s), 0.74 (3H, s), 0.79 (3H, s),
4
8
51
15
(−)-Menthyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-β-D- 0.96–1.02 (1H, m), 1.22–1.41 (3H, m), 1.58–1.64 (1H, m), 2.82
glucopyranoside (3b) (3H, s), 2.00 (3H, s), 2.08 (3H, s), 3.79–3.83 (1H, m), 3.89–3.93
1
White solid, mp 130–131°C; H-NMR (400MHz, CDCl ) δ: (1H, m), 4.13 (1H, dd, J=12.0, 2.4Hz), 4.28–4.33 (2H, m), 5.15
3
0
.68 (6H, d, J=3.4Hz), 0.78 (3H, d, J=7.3Hz), 0.85–1.22 (4H, (1H, t, J=9.6Hz), 5.25 (1H, d, J=8.0Hz), 5.82 (1H, dd, J=10.8,
13
m), 1.50–1.70 (5H, m), 1.84 (3H, s), 2.01 (3H, s), 2.06 (3H, s), 8.8Hz), 7.70–7.73 (2H, m), 7.83–7.85 (2H, m) ppm; C-NMR
3
.37 (1H, td, J=10.8, 4.0Hz), 3.80–3.85 (1H, m), 4.12–4.29 (100MHz, CDCl ) δ: 13.2, 18.8, 19.6, 20.5, 20.7, 20.8,
3
(
3H, m), 5.11 (1H, t, J=9.2Hz), 5.37 (1H, d, J=8.4Hz), 5.79 26.3, 27.9, 35.8, 44.6, 47.7, 49.1, 54.9, 62.2, 69.4, 70.6, 71.6,
(dd, 1H, J=10.7, 8.8Hz), 7.70–7.74 (2H, m), 7.83–7.85 (2H, m) 83.6, 96.9, 123.5 (2C), 131.3 (2C), 134.3 (2C), 169.5, 170.2,
13
ppm; C-NMR (100MHz, CDCl ) δ: 15.4, 20.5, 20.66, 20.7, 170.8ppm; IR (KBr): 2955, 2874, 1749, 1718, 1386, 1368,
3
−1
2
7
0.8, 22.0, 22.9, 25.0, 31.2, 34.0, 40.3, 47.3, 54.9, 62.5, 69.5, 1226, 1076, 1033, 752, 722, 675cm ; HR-FAB-MS: Calcd for
0.9, 71.4, 78.4, 95.7, 123.5 (2C), 134.2 (2C), 169.6, 170.2, C H NNaO [M+Na] 594.2315. Found 594.2310.
+
3
0
37
10
170.7ppm; IR (KBr): 2954, 2923, 2870, 1751, 1719, 1387, 1260,
−1
1231, 1102, 1079, 1035, 806, 748, 721cm ; HR-FAB-MS:

Vol. 64, No. 7 (2016)
Chem. Pharm. Bull.
843
Methyl (3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-D-gluco- (2C), 134.3 (2C), 169.5, 170.2, 170.7ppm; IR (KBr): 2949,
pyranosyl)-β-(1→6)-2,3,4-tri-O-benzoyl-α-D-glucopyranoside 1779, 1749, 1718, 1388, 1368, 1229, 1079, 1047, 1035, 780, 747,
4
2)
−1
+
(
3g)
719 cm ; HR-FAB-MS: Calcd for C H NNaO [M+Na]
30 37 10
1
H-NMR (400MHz, CHCl ) δ: 1.84 (3H, s), 2.00 (3H, s), 594.2315. Found 594.2310.
3
2
.03 (3H, s), 3.05 (3H, s), 3.59 (1H, dd, J=7.3, 3.4Hz), 3.86
(+)-Fenchyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-β-D-
(
4
4
1H, d, J=7.5Hz), 4.05 (1H, d, J=10.5Hz), 4.10–4.13 (m, 2H), glucopyranoside (3l)
.31 (dd, 1H, J=12.5, 4.5Hz), 4.36 (t, 1H, J=10.0, 9.0, Hz),
1
White solid, mp 117–119°C; H-NMR (400MHz, CDCl ) δ:
3
.70 (1H, d, J=3.4Hz), 5.05 (1H, dd, J=3.9, 2.4Hz), 5.14 (1H, 0.59 (3H, s), 0.80 (3H, s), 0.94 (3H, s), 1.22–1.32 (4H, m), 1.58
t, J=9.3Hz), 5.25 (1H, t, J=9.8Hz), 5.40 (1H, d, J=8.8Hz), (3H, s), 1.85 (3H, s), 2.02 (3H, s), 2.06 (3H, s), 3.00 (1H, d,
.80 (1H, t, J=9.8Hz), 5.99 (1H, t, J=9.8Hz), 7.19–7.49 (7H, J=1.6Hz), 3.81–3.85 (1H, m), 4.19 (2H, d, J=4.0Hz), 4.33 (1H,
m), 7.71–7.90 (12H, m) ppm. dd, J=10.8, 8.0Hz), 5.07–5.16 (2H, m), 5.83 (1H, dd, J=10.8,
Methyl (2,3,4,6-Tetra-O-acetyl-D-glucopyranosyl)-β-(1→6)- 9.2Hz), 7.70–7.73 (2H, m), 7.82–7.84 (2H, m) ppm: C-NMR
5
13
4
3)
2
,3,4-tri-O-benzoyl-α-D-glucopyranoside (3h)
(100MHz, CDCl ) δ: 19.1, 20.5, 20.68, 20.7, 21.5, 25.4,
3
1
H-NMR (400MHz, CDCl ) δ: 1.99 (9H, s), 2.07 (3H, s), 25.9, 29.5, 39.1, 40.9, 48.0, 48.6, 54.8, 62.6, 69.5, 70.6, 71.4,
3
3.43 (3H, s), 3.66–3.70 (2H, m), 4.01–4.06 (2H, m), 4.19–4.25 94.6, 99.5, 123.5 (2C), 134.3 (2C), 131.0 (2C), 169.6, 170.2,
(
2H, m), 4.56 (1H, d, J=8.3Hz), 5.00–5.07 (2H, m), 5.17–5.22 170.7ppm; IR (KBr): 2949, 2874, 1749, 1718, 1387, 1367, 1275,
−1
(
3H, m), 5.39 (1H, t, J=9.8Hz), 6.10 (1H, t, J=9.8Hz), 1258, 1228, 1110, 1081, 1051, 971, 749, 721cm ; HR-FAB-MS:
+
7
.24–7.52 (9H, m), 7.81–7.83 (2H, m), 7.90–7.95 (4H, m) ppm.
Methyl 4-O-[3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-D-
glucopyranosyl]-β-(1→6)-2,3,6-tri-O-benzoyl-α-D-galactopyra- phthalimido-β-D-glucopyranoside (3m)
Calcd for C H NNaO [M+Na] 594.2315. Found 594.2310.
3
0
37
10
Ent-17-nor-kauran-16α-yl 3,4,6-Tri-O-acetyl-2-deoxy-2-
1
noside (3i)
White solid, mp 209–211°C; H-NMR (400MHz, CDCl3)
1
White solid, mp 87–89°C; H-NMR (400MHz, CDCl3) δ: 0.57–0.69 (3H, m), 0.71 (3H, s), 0.78 (3H, s), 0.83 (3H, s),
δ: 1.81 (3H, s), 1.94 (3H, s), 2.04 (3H, s), 3.33 (3H, s), 1.04–1.81 (18H, m), 1.84 (3H, s), 2.00 (3H, s), 2.09 (3H, s),
3
.61–3.65 (1H, m), 3.95–3.99 (1H, m), 4.07–4.12 (1H, m), 3.82 (1H, dq, J=7.8, 2.4Hz), 4.08–4.20 (2H, m), 4.29–4.34
4.30 (1H, t, J=6.4Hz), 4.37–4.49 (2H, m), 4.58–4.62 (1H, (2H, m), 5.13 (1H, d, J=9.6Hz), 5.25 (1H, t, J=8.8Hz), 5.86
m), 4.70–4.71 (1H, m), 4.96 (1H, d, J=3.4Hz), 5.10 (1H, t, (1H, dd, J=10.8, 9.2Hz), 7.70–7.73 (2H, m), 7.82–7.84 (2H, m)
1
3
J=9.3Hz), 5.21–5.25 (1H, m), 5.46–5.50 (2H, m), 5.77 (1H, ppm; C-NMR (100MHz, CDCl ): δ: 17.5, 18.0, 19.9, 20.5,
3
dd, J=8.8, 2.0Hz) 7.34–7.33 (6H, m), 7.42 (3H, t, J=7.3Hz), 20.6, 20.8, 21.0, 21.5, 25.6, 33.2, 33.5, 37.4, 37.9, 39.1, 40.1,
7
.50–7.56 (2H, m), 7.70–7.74 (6H, m), 8.03 (2H, d, J=6.8Hz) 41.6, 42.0, 43.2, 48.0, 54.9, 56.1, 56.7, 62.2, 69.4, 70.6, 71.6,
13
ppm; C-NMR (100MHz, CDCl ) δ: 20.3, 20.4, 20.5, 54.7, 79.4, 97.7, 123.5 (2C), 131.4 (2C), 134.3 (2C), 169.5, 170.2,
3
5
5.2, 61.4, 63.9, 67.9, 68.0, 68.7, 70.1, 71.5, 73.3, 77.4, 97.4 170.7ppm; IR (KBr): 2930, 2857, 1752, 1719, 1467, 1386, 1227,
−1
(2C), 123.7 (2C), 128.1 (2C), 128. 3 (4C), 129.0, 129.1, 129.5 1170, 1082, 1032, 764, 748, 722cm ; HR-FAB-MS: Calcd for
+
(
1
5C), 129.9 (3C), 131.3, 133.0 (2C), 133.2, 133.8 (2C), 165.0, C H NNaO [M+Na] 716.3411. Found 716.3405.
39 51 10
65.9, 166.7, 169.3, 169.9, 170.7ppm; IR (KBr): 3055, 2987,
Methyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-D-galacto-
−1
2
685, 2358, 2306, 1718, 1387, 1259, 1044, 896, 765cm ; MS pyranosyl-β-(1→6)-2,3,4-tri-O-benzyl-α-D-glucopyranoside
(
[
MALDI-TOF): m/z (%): Calcd for C H NNaO : 946.25; (3n)
48 45 18
+
1
M+Na] ; Found: 946.17 (100), 947.15 (50), 948.15 (26).
-Deoxy-2-phthalimido-3,4,6-tri-O-acetyl-D-glucopy- 1.77 (3H, s), 1.98 (3H, s), 2.10 (3H, s), 3.10 (3H, s), 3.16 (1H,
ranosyl-β-(1→6)-1,2:3,4-di-O-isopropylidene-α-D-galactopyra- t, J=9.2Hz), 3.31 (1H, dd, J=9.6, 3.6Hz), 3.55–3.60 (2H, m),
White solid, mp 58–67°C; H-NMR (400MHz, CDCl ) δ:
3
2
4
4)
noside (3j)
3.77 (1H, t, J=9.2Hz), 4.00–4.15 (5H, m), 4.30–4.33 (2H,
1
White solid, mp 207–210°C; H-NMR (400MHz, CDCl ) m), 4.50–4.66 (4H, m), 4.78 (1H, d, J=11.8Hz), 5.28 (1H,
3
δ: 0.98 (6H, s), 1.19 (3H, s), 1.35 (3H, s), 1.82 (3H, s), 1.98 d, J=8.4Hz), 5.40 (1H, d, J=3.4Hz), 5.73 (1H, dd, J=11.2,
(3H, s), 2.07 (3H, s), 3.64–3.66 (2H, m), 3.83–3.96 (3H, m), 3.2Hz), 6.96–6.98 (2H, m), 7.14–7.24 (15H, m), 7.45 (2H,
13
4
.04–4.14 (2H, m), 4.25–4.37 (3H, m), 5.06 (1H, d, J=5.4Hz), brs) ppm; C-NMR (100MHz, CDCl ) δ: 20.5, 20.7, 20.72,
3
5.14 (1H, dd, J=10.0, 9.5Hz), 5.40 (1H, d, J=8.3Hz), 5.80 (1H, 51.2, 54.9, 61.3, 66.6, 68.0, 68.7, 69.1, 70.8, 73.3, 74.7, 75.6,
dd, J=10.7, 9.1Hz), 7.66–7.68 (2H, m), 7.78–7.79 (2H, m) ppm; 77.6, 79.7, 81.8, 97.8, 98.7, 123.4 (2C), 127.6, 127.7, 127.86,
13
C-NMR (100MHz, CDCl ) δ: 20.4, 20.6, 20.7, 24.1, 24.6, 127.9 (3C), 128.0 (3C), 128.2 (3C), 128.4 (3C), 131.0 (2C),
3
25.3, 25.8, 54.5, 62.0, 67.4, 69.0, 70.1, 70.5, 70.6, 70.8, 71.5, 134.1 (2C), 137.7, 138.1, 138.6, 169.8, 170.3, 170.4ppm; IR
7
6.7, 77.0, 77.3, 95.9, 99.3, 107.9, 109.3, 123.4, 133.7, 169.5, (KBr): 3029, 2926, 1752, 1717, 1454, 1389, 1368, 1235, 1131,
−1
170.1, 170.7 ppm.
1070, 1052, 950, 798, 750, 724cm ; HR-FAB-MS: Calcd for
+
(
+)-Bornyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-β-D- C H NNaO [M+Na] 904.3156. Found 904.3151.
48 51 15
glucopyranoside (3k)
1
White solid, mp 114–116°C; H-NMR (400MHz, CDCl3)
δ: 0.33 (3H, s), 0.68 (3H, s), 0.73 (3H, s), 0.96–0.99 (2H, m), Grants-in-Aid for Scientific Research (A) from the Japan So-
.16–1.26 (4H, m), 1.52–1.61 (1H, m), 1.85 (3H, s), 2.00 (3H, s), ciety for the Promotion of Science (JSPS), a Grant-in-Aid for
.08 (3H, s), 3.62–3.68 (1H, m), 3.80–3.84 (1H, m), 4.06–4.13 Scientific Research on Innovative Areas “Advanced Molecular
1H, m), 4.28–4.35 (2H, m), 5.13 (1H, t, J=10.0Hz), 5.27 (1H, Transformation by Organocatalysts” from the Ministry of
d, J=8.4Hz), 5.80 (1H, dd, J=10.8, 8.8Hz), 7.70–7.73 (2H, m), Education, Culture, Sports, Science and Technology (MEXT)
Acknowledgments This work was partially supported by
1
2
(
13
7
.82–7.84 (2H, m) ppm; C-NMR (100MHz, CDCl ) δ: 13.1, of Japan. T.K. acknowledges support from the Grant-in-Aid
3
14.2, 18.7, 19.4, 20.5, 20.7, 20.8, 26.4, 27.8, 37.0, 44.9, 47.2, for Scientific Research (C). K.M. also acknowledges support
49.0, 54.8, 62.2, 69.3, 70.7, 71.6, 87.8, 99.8, 123.5 (2C), 131.4 from the Grant-in-Aid for Young Scientists (B) from the JSPS.

8
44
Chem. Pharm. Bull.
Vol. 64, No. 7 (2016)
2
2
2
2
1) Tohma H., Kita Y., Top. Curr. Chem., 224, 209–248 (2003).
2) Tohma H., Kita Y., Adv. Synth. Catal., 346, 111–124 (2004).
3) Zhdankin V. V., Stang P. J., Chem. Rev., 108, 5299–5358 (2008).
4) Merritt E. A., Olofsson B., Angew. Chem. Int. Ed., 48, 9052–9070
Conflict of Interest The authors declare no conflict of
interest.
References
(2009).
1
)
Codée J. D. C., Litjens R. E. J. N., van den Bos L. J., Overkleeft H.
S., van der Marel G. A., Chem. Soc. Rev., 34, 769–782 (2005).
Lian G., Zhang X., Yu B., Carbohydr. Res., 403, 13–22 (2015).
Boltje T. J., Buskas T., Boons G.-J., Nat. Chem., 1, 611–622 (2009).
Hanessian S., Bacquet C., Lehong N., Carbohydr. Res., 80, C17–
C22 (1980).
2
2
5) Dohi T., Kita Y., Chem. Commun., 2009, 2073–2085 (2009).
6) Duschek A., Kirsch S. F., Angew. Chem. Int. Ed., 50, 1524–1552
2
3
4
)
)
)
(2011).
27) Merritt E. A., Olofsson B., Synthesis, 2011, 517–538 (2011).
2
8) Fernández Gonzalez D., Benfatti F., Waser J., ChemCatChem, 4,
9
55–958 (2012).
9) Yusubov M. S., Zhdankin V. V., Curr. Org. Synth., 9, 247–272
2012), and references therein.
0) Kita Y., Dohi T., Chem. Rec., 15, 886–906 (2015).
1) Kita Y., Egi M., Ohtsubo M., Saiki T., Takada T., Tohma H., Chem.
5
6
7
)
)
)
Zhang Z., Ollmann I. R., Ye X.-S., Wischnat R., Baasov T., Wong
C.-H., J. Am. Chem. Soc., 121, 734–753 (1999).
Nicolaou K. C., Pavia M. R., Seitz S. P., J. Am. Chem. Soc., 104,
2
(
3
3
2
027–2029 (1982).
Codée J. D. C., Litjens R. E. J. N., van den Bos L. J., Overkleeft H.
S., van der Marel G. A., Chem. Soc. Rev., 34, 769–782 (2005).
Ferrier R. J., Hay R. W., Vethaviyaear N., Carbohydr. Res., 27,
Commun., 1999, 2225–2226 (1999).
32) Kita Y., Egi M., Tohma H., Chem. Commun., 1999, 143–144 (1999).
8
)
33) Kajimoto T., Morimoto K., Ogawa R., Dohi T., Kita Y., Eur. J. Org.
6
5–70 (1973).
Tsai T. Y. R., Jin H., Wiesner K., Can. J. Chem., 62, 1403–1405
1984).
0) Garegg P. J., Henrichson C., Norberg T., Carbohydr. Res., 116,
62–165 (1983).
1) Van Cleve J. W., Carbohydr. Res., 70, 161–164 (1979).
2) Mukaiyama T., Nakatsuka T., Shoda S., Chem. Lett., 1979, 487–490
1979).
3) Sato S., Mori M., Ito Y., Ogawa T., Carbohydr. Res., 155, C6–C10
1986).
4) Kumar V., Taxak N., Jangir R., Bharatam P. V., Kartha K. P. R., J.
Org. Chem., 79, 3427–3439 (2014).
Chem., 2015, 2138–2142 (2015).
4) Chu A. H., Minciunescu A., Bennett C. S., Org. Lett., 17, 6262–
9
)
3
(
6265 (2015).
1
35) Fukase K., Hasuoka A., Kinoshita I., Kusumoto S., Tetrahedron
1
Lett., 33, 7165–7168 (1992).
1
1
3
3
3
3
4
6) Fukase K., Kinoshita I., Kanoh T., Nakai Y., Hasuoka A., Kusumoto
S., Tetrahedron, 52, 3897–3904 (1996).
(
7) Kajimoto T., Ishioka Y., Katoh T., Node M., Bioorg. Med. Chem.
Lett., 16, 5736–5739 (2006).
8) Kajimoto T., Ishioka Y., Katoh T., Node M., J. Carbohydr. Chem.,
6, 469–495 (2007).
9) Kajimoto T., Arimitsu K., Ozeki M., Node M., Chem. Pharm. Bull.,
8, 758–764 (2010).
1
(
1
2
1
5) Veeneman G. H., van Leeuwen S. H., van Boom J. H., Tetrahedron
5
Lett., 31, 1331–1334 (1990).
0) Mootoo D. R., Konradsson P., Udodong U., Fraser-Reid B., J. Am.
Chem. Soc., 110, 5583–5584 (1988).
1
6) Wever W. J., Cinelli M. A., Bowers A. A., Org. Lett., 16, 30–33
2013).
7) He H., Zhu X., Org. Lett., 16, 3102–3105 (2014).
8) For recent reviews and publications, see: Stang P. J., Zhdankin V.
V., Chem. Rev., 96, 1123–1178 (1996).
9) Kita Y., Takada T., Tohma H., Pure Appl. Chem., 68, 627–637
1996).
(
41) Konradsson P., Mootoo D. R., McDevitt R. E., Fraser-Reid B. R., J.
1
1
Chem. Soc., Chem. Commun., 1990, 270–272 (1990).
42) Maity S. K., Basu N., Ghosh R., Carbohydr. Res., 354, 40–48
(
2012).
3) Lucas-Lopez C., Murphy N., Zhu X., Eur. J. Org. Chem., 2008,
401–4404 (2008).
4) Li Y., Yang Y., Yu B., Tetrahedron Lett., 49, 3604–3608 (2008).
1
4
4
(
4
2
0) Varvoglis A., “Hypervalent Iodine in Organic Synthesis,” Academic
Press, San Diego, CA, 1997.