Selective Synthesis of Some Aminosugars via Catalytic Aminohydroxylation of Protected 2,3-Unsaturated d -Gluco- And d -Galacto-2-hexenopyranosides

Article abstract of DOI:10.1021/acs.joc.0c01170

The aminohydroxylation of methyl 4,6-di-O-(tert-butyldimethylsilyl)-2,3-unsaturated α-d-glucopyranoside proceeds in the presence of chloramine-T, OsO4 (4 mol %), (DHQ)2PHAL (5 mol %), and triethylbenzylammonium chloride (TEBAC) in both a stereoselective a

Full text of DOI:10.1021/acs.joc.0c01170

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Article
Selective Synthesis of Some Aminosugars via Catalytic Aminohydroxylation
of Protected 2,3-Unsaturated D-Gluco- and D-Galacto-2-hexenopyranosides
Ippei Fukuhara, Ryosuke Matsubara, and Masahiko Hayashi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01170 • Publication Date (Web): 26 Jun 2020
Downloaded from pubs.acs.org on June 27, 2020
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Page 1 of 33
The Journal of Organic Chemistry
Selective Synthesis of Some Aminosugars via Catalytic
Aminohydroxylation of Protected 2,3-Unsaturated D-Gluco- and D-
Galacto-2-hexenopyranosides
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Ippei Fukuhara, Ryosuke Matsubara, and Masahiko Hayashi*
Department of Chemistry, Graduate School of Science, Kobe University, Kobe 657-8501, Japan
Supporting Information Placeholder
OTBS
O
OTBS
NHTs
O
aminohydroxylation
TBSO
RO
TBSO
HO
OMe
-D-glucal
OMe
71%
OMe
OR
O
RO
RO
OR
O
OR
O
aminohydroxylation
OMe
+
OMe
OH
NHTs
OH
TsHN
-D-galactal
51%
7%
19% (R = Me)
62% (R = Bz)
ABSTRACT: The aminohydroxylation of methyl 4,6-di-O-(tert-butyldimethylsilyl)-2,3-unsaturated -
D-glucopyranoside proceeds in the presence of chloramine-T, OsO4 (4 mol%), (DHQ)2PHAL (5 mol%),
and TEBAC (triethylbenzylammonium chloride) in both a stereo- and regioselective manner to produce
protected methyl -D-mannosamide as the sole product. In contrast, the reaction of methyl 2,3-unsaturated
-D-galactopyranoside under the same conditions produced a mixture of regioisomers, although the
stereochemistry was perfectly controlled. The regioisomeric ratio was dependent on the nature of the
protecting group and ligand used.
INTRODUCTION
Aminosugar moieties are often found in natural and unnatural compounds.1,2 For example, D-glucosamine
is a main constitutent of bacterial peptidoglycan, fungal and insect chithin, and mammalian glycoproteins.
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Furthermore, a few carbohydrates containing aminosugars, such as sialyl acids,3 anthracycline
antibiotics,4 kanamycin,5 and pyranmycins6 have been also reported. In contrast, rare sugars have been
recognized as functional biological compounds because of their application as low-calorie sweeteners,
antioxidants, inhibitors of various glycosidases, and so on.7,8 In 2016, we reported the selective synthesis
of D-talopyranosides and D-gulopyranosides using asymmetric dihydroxylation. In these reactions, a
complete reversal of the diastereoselectivity was observed in the reaction using protected 2,3-unsaturated
D-galactopyranoside due to the protecting group selected, which led to the selective formation of D-
talopyranoside and D-gulopyranoside.9 When O-benzoyl-protected 2,3-unsaturated D-galactopyranoside
was used as a substrate, D-talopyranoside was obtained as the predominant product. In contrast to the
dihydroxylation of 2,3-unsaturated sugars, aminohydroxylation requires control over not only the
stereoselectivity, but also the regioselectivity of the reaction.10 In 1977, Dyong and co-workers reported
reaction of 3,4,6-tri-O-acetyl-D-glucal (1,2-unsaturated) with chroramine-T, the sodium salt of N-chloro-
p-toluenesulfonamide in the presence of OsO4 to afford to mixture of four products, those were regio- and
stereoisomers of 1-amino-2-hydroxy and 1-hydroxy-2-amino sugars.11 In 1995, Matsumoto et al.
reported the aminohydroxylation of 3,4-unsaturated sugars to afford a regioisomeric mixture of 3-
amino-4-hydroxy and 3-hydroxy-4-amino sugars using OsO4 and chroramine-T.12 However, the authors
did not examine the reaction in the presence of a chiral ligand. In 2015, Cadona and Goti reported the
tethered aminohydroxylation of D-glycals. The reaction included the K2OsO2(OH)4 oxidation of
carbamate to give oxazolidinone, followed by hydrolysis using LiOH/H2O to afford the target 2- and 3-
aminosugars.13 This paper reports the synthesis of D-aminosugars including rare aminosugars using
asymmetric catalytic aminohydroxylation14-16 of 2,3-unsaturated D-gluco- and D-galacto-2-
hexenopyranosides (2,3-unsaturated D-glucopyranoside and 2,3-unsaturated D-galactopyranoside). Most
of the reported methods use 1,2-unsaturated D-glucopyranoside (D-glucal) as a substrate, whereas, in our
case, 2,3-unsaturated D-glucopyranoside and 2,3-unsaturated D-galactopyranoside were used those led
high regio- and stereoselective synthesis of aminosugars.
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The Journal of Organic Chemistry
RESULTS AND DISCUSSION
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8
9
Initially, we attempted the reaction of methyl 4,6-di-O-(tert-butyldimethylsilyl)-2,3-unsaturated D-
glucopyranoside (/ = 88:12) using chloramine-T (1.25 eq.), OsO4 (4 mol%), (DHQ)2PHAL (5 mol%),
and TEBAC (triethylbenzylammonium chloride), which serve as a phase transfer (PT) catalyst. The
results of our optimization study are summarized in Table 1.
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Table 1. Catalytic Aminohydroxylation of Methyl 4,6-di-O-(tert-Butyldimethylsilyl)-2,3-
Unsaturated D-Glucopyranoside
chloramine-T (1.25 eq.)
OsO4 (4 mol %)a
OTBS
OTBS
OTBS
O
OH
NHTs
(DHQ)2PHAL (5 mol %)
TEBAC (5 mol %)
O
O
TBSO
TBSO
HO
TBSO
HO
+
OMe
(/ = 88:12)
t-BuOH:H2O = 1:1
20°C (r.t.), 10 h
OMe
OMe
2
3
1
yield (%)b
variation from above
2
3
entry
__
1
2
3
4
5
6
7
72
43
56
30
73
71
11
24
5
at 58 C
°
at 0 C
°
.
31
11
6
K2OsO4 2H2O instead of OsO4
no TEBAC
1
Only  isomer of substrate was used.
1
Only  isomer of substrate was used.
(DHQD)2PHAL instead of (DHQ)2PHAL
67
33
11
60
8
1
Only  isomer of substrate was used.
quinuclidine instead of (DHQ)2PHAL
a 1% OsO4 in tert-butyl alcohol solution containing 0.35% of tert-butyl hydroperoxide.
b
1
2
3
Isolated yield. The ratio of and was determined by H NMR analysis.
H3C
H3C
H
H3C
H3C
H
H
H
H
N N
O
O
N N
N
N
N
N
N
O
O
H
H
H
H3CO
OCH3
H3CO
OCH3
N
N
N
(DHQ)2PHAL
(DHQD)2PHAL
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The reaction proceeds via an imidotorioxoosmium (VIII) species, followed by a [3+2] cylcoaddition
reaction and hydrolysis to afford the aminohydroxylated product.17,18 In most cases, protected methyl-D-
mannosamide 2 was predominantly accompanied by the formation of protected methyl -D-
mannopyranoside 3.The best result was obtained under the conditions shown in entry 6. In all cases, both
the stereoselectivity and regioselectivity were controlled perfectly in the aminohydroxylation reaction.19
As for the effect of reaction temperature, we found room temperature (20 ºC) was the best choice to
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obtain desired amino sugar 2 (entry 1__3). As an osmium source, the use of OsO4 solution (see
Experimental Section) afforded higher yield than the use of K2OsO4.2H2O (entry 4). The effect of the
addition of phase transfer catalyst (PTC) such as TEBAC was proved to suppress the formation of
undesired diol product (entery 5). Judging from the results from entries 6-8, the use of only -isomer as
a substrate gave higher yield. The use of (DHQ)2PHAL as a ligand afforded the best result, this may be
because of the matching effect of substrate control and catalyst control.
The obtained region- and stereoselectivity may be explained by considering the conformation of substrate
1. We calculated the difference in the stability of the two possible conformations of methyl 2,3-
0
unsaturated -D-glucopyranoside and its derivatives (Table 2). The H5 conformer of trimethylsilyl-
protected 2,3-unsaturated methyl-D-glucopyranoside was found to be 6 kcal/mol more stable than its
5
corresponding H0 conformer. In addition, for the compound possessing only a methoxy group at the
anomeric position, the 0H5 conformer was 2 kcal/mol more stable than the 5H0 conformer, whereas for the
compound possessing a methyl group at the anomeric position, the 0H5 conformer was 1.2 kcal/mol less
5
stable than its H0 conformer (See, Supporting Information). We notice that we should give cation to
discuss the relationship between the difference of calculated ground state energy and distribution of
products. However, the values shown in Table 2 would support the explanation of regio- and
stereoselectivity of the results in Table 1. It should be noted in the case of methyl group instead of methoxy
group at anomeric position, the stabilization by anomeric effect was not observed.
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Table 2. Conformations of 2,3-Unsaturated D-Glucopyranoside Derivatives
1
2
3
4
5
6
7
8
9
Me3SiO
OSiMe3
O
H
O
H
H
Me3SiO
H
H
Me3SiO
Me3SiO
OMe
OMe
OMe
O
OSiMe3
1A
H
OMe
1B
-D-glucal
H
O
O
H
O
OMe
1B'
OMe
Me
1A'
O
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11
12
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H
O
H
Me
O
Me
1B"
1A"
substrate
A
B
0.0
0.0
0.0
–6.0
-unsaturated--D-glucopyranoside (1A, 1B)
2--methoxy-3,4-dihydropyran (1A’, 1B’)
2--methyl-3,4-dihydropyran (1A”, 1B”)
–2.6
+1.2
kcal/mol
LC-BLYP/6-31G(d) (in gas phase)
Our conformational analysis showed that both “N (NTs)” and “O” approach from the less hindered top-
side of the double bond (Scheme 1). Concerning the perfect regioselectivity, it may be explained the
bulky “N (NTs)” favored less hindered C2-position.20 As for the generation of dihydroxylated diol 3,
another catalytic cycle (cycle AD) accompanies cycle AA, as shown in Scheme 2, which shows the
catalytic cycle for the reaction of methyl 4,6-di-O-protected-2,3-unsaturated -D-galactopyranoside
(Table 3).
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Scheme 1. Origin of the Regio- and Stereoselectivity of the Aminohydroxylation Reaction
1
2
3
4
5
6
7
8
O N
OTBS
O
TBSO
H
O
H
TBSO
H
H
H
TBSO
TBSO
OMe
OMe
OMe
O
TBSO
1
H
1A
1B
9
10
11
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OTBS
NHTs
O
TBSO
HO
OMe
Subsequently, we examined the reaction of methyl 4,6-di-O-(t-butyldimethylsilyl)-2,3-
unsaturated -D-galactopyranoside. However, the reactivity of -D-galactopyranoside in the
aminohydroxylation reaction was lower when compared with -D-glucopyranoside, and starting
material 4 remained unreacted even upon increasing the amounts of OsO4 and (DHQ)2PHAL
used in the reaction. In addition, the formation of the diol product was observed when using -
D-galactopyranoside derivatives in the reaction, particularly for the benzoyl protected substrates
(SI Table 1). Therefore, we changed the substrate from 4,6-protected -D-galactopyranoside to
-D-galactopyranoside.21 The results are summarized in Table 3.
Scheme 2. Catalytic Cycle for the Formation of the N-Tosyl Amino Alcohol (5a–5f and 6a–6f)
and Diol (7a–7f)
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OR
OR
OR
RO
RO
RO
+
O
O
O
1
2
3
4
5
6
7
8
H2O
OCH3
OCH3
OCH3
H2O
OH
OH
NTs
RO
OH
NTs
HO
OR
O
RO
RO
O
OR
O
OR
O
OCH3
OCH3
+
OCH3
O
O
TsN
O
O
Os
NTs
TsN
O
Os
Os
O
O
NTs
NTs
O
O
H2O
TsNH2
TsNH2
O
L*
RO
*L
NTs
Os
Na
L*
Na
Cl
Os
Cl
cycle AA
O
cycle AD
O
O
O
NHTs
O
O
TsN
RO
RO
H2O
OR
O
OR
O
9
OR
O
OCH3
OCH3
OCH3
O
10
11
12
13
14
15
16
17
18
19
L*
L*
NTs
Os
O
TsN
NTs
+
O
O
Os
O
Os
Os
O
O
O
O
O
O
Os
O
L*
O
L*
O
O
O
L*
L*
O
RO
L*: chiral ligand
OR
O OCH3
Table 3. Aminohydroxylation of Methyl 4,6-di-O-Protected 2,3-Unsaturated -D-
20
21
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50
51
52
53
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57
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59
60
Galactopyranosides
chloramine-T (1.25 eq.)
OsO4 (4 mol %)a
OR
OR
O
OR
OR
OR
O
OR
O
OR
OR
O OMe
ligand (5 mol %)
TEBAC (5 mol %)
OMe
OMe
OMe
+
+
OH
NHTs
NHTs
OH
t-BuOH:H2O = 1:1
OH
6 a-6 f
OH
7 a-7 f
4 a-4 f




5 a-5 f




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yieldb
6 a-6 f
1
2
3
4
5
6
7
8
5 a-5 f
7 a-7 f
 




entry
1
ligand (5 mol %)
none
R
time/h
6
4 a
Me (  )
14
22
4
15
19
14
16
25
41
16
19
20
31
25
22
19
24
28
42
23
41
27
31
62
56
25
26
2
4 b
Bn (  )
2
none
4
35
67
62
13
13
0
4 c
Bz (  )
3
none
24
24
3
4 d
Piv (  )
4
none
5
9
4 e
TBS (  )
5
none
30
16
21
30
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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27
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29
30
31
32
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58
59
60
4 f
TBDPS (  )
6
none
24
4
4 a
Me (  )
7
quinuclidine
quinuclidine
quinuclidine
quinuclidine
quinuclidine
quinuclidine
(DHQ)2PHAL
(DHQ)2PHAL
(DHQ)2PHAL
(DHQ)2PHAL
(DHQ)2PHAL
(DHQ)2PHAL
(DHQD)2PHAL
(DHQD)2PHAL
(DHQD)2PHAL
(DHQD)2PHAL
(DHQD)2PHAL
(DHQD)2PHAL
4 b
Bn (  )
8
6
17
43
37
16
11
0
4 c
Bz (  )
9
6
4 d
Piv (  )
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
9
12
35
7
4 e
TBS (  )
12
6
4 f
TBDPS (  )
4 a
Me (  )
4
51
47
37
34
52
16
20
29
7
4 b
Bn (  )
3
6
4 c
Bz (  )
6
19
11
4
4 d
Piv (  )
6
4 e
TBS (  )
24
48
7
4 f
TBDPS (  )
12
0
4 a
Me (  )
4 b
Bn (  )
5
5
4 c
Bz (  )
8
17
14
2
4 d
Piv (  )
5
7
4 e
TBS (  )
24
24
48
7
4 f
TBDPS (  )
4
a 1% OsO4 in tert-butyl alcohol solution containing 0.35% of tert-butyl hydroperoxide. b Yield was
determined by H NMR analysis for each product based on starting materials, then each product ( , , and
1
5 6
7
) was separated by silica-gel column chromatography.
The results show the nature of the protecting group R influences the regioselectivity of the reaction.19
The regioselectivity may be controlled by the synergistic effect between the stereo- and electronic
effects of the substrate19a and the nature of the ligand used in the reaction. The highest selectivity
observed for 3-N-tosyl-2-hydroxy product 5a was obtained in the case of the smallest protecting group
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(R = Me). The reaction may proceed via conformer of 4A,22 whereas the highest selectivity observed for
2-N-tosyl-3-hydroxy product 6f was obtained when R = Bz (Scheme 3). Upon comparing the reaction
performed in the presence and absence of the ligand, it is clear that the use of a ligand remarkably
increases the yield of the aminohydroxylated product obtained. Among the ligands studied
(quinuclidine, (DHQ)2PHAL, and (DHQD)2PHAL), the chiral (DHQ)2PHAL and (DHQD)2PHAL
ligands enhance both the reactivity and selectivity. For example, when methoxy-protected 2,3-
unsaturated -D-galactopyranoside 4a was used as the substrate, the use of quinuclidine afforded the
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
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17
18
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3-N-tosyl-2-hydroxy product 5a and 2-N-tosyl-3-hydroxy product 6a in 21 and 16% yield,
respectively. When (DHQ)2PHAL was used instead of quinuclidine, 5a and 6a were obtained in 51
and 19% yield, respectively (The ratio of 5a/6a was 73:27). The use of (DHQD)2PHAL gave 5a
and 6a in 7 and 62% yield, respectively for benzoyl-protected 2,3-unsaturated -D-galactopyranoside
6c (The ratio of 5a/6c was 10:90).
Scheme 3. Origin of the Stereo- and Regioselectivity in the Aminohydroxylation Reaction
BzO
MeO
H
OBz
H
O
OMe
H
O
OMe
OMe
OMe
H
OMe
H
H
BzO
H
MeO
H
BzO
H
MeO
H
O
H
O
H
N
O
O N
4 a

4 c

BzO
OMe
OBz
O
OMe
O
OMe
OMe
NHTs
OH
OH
NHTs
6 f

5 a

In summary, the aminohydroxylation of methyl 4,6-di-O-(tert-butyldimethylsilyl)-2,3-unsaturated -D-
glucopyranoside proceeded in both a stereo- and regioselective manner to afford protected methyl -D-
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mannopyranoside. In contrast, methyl 2,3-unsaturated -D-galactopyranoside was inert to the conditions
considered for the aminohydroxylation reaction. Therefore, by changing the stereochemistry of the
anomeric position from  to , the use of methyl 2,3-unsaturated -D-galactopyranoside gave a mixture
of regioisomers, although the stereochemistry was perfectly controlled. The regioisomer was dependent
on the nature of the protecting group and ligand used. The highest selectivity of the 3-N-tosyl-2-hydroxy
product (73:27) was obtained using a combination of the methyl protected substrate and (DHQ)2PHAL
ligand. In contrast, the highest selectivity of the 2-N-tosyl-3-hydroxy product (10:90) was obtained using
a combination of the benzoyl-protected substrate and (DHQD)2PHAL ligand. D-Glucosamine, D-
mannosamine, and D-galactosamine are common aminosugars. Thus, the aminosugars obtained from
methyl 2,3-unsaturated -D-galactopyranoside are classified as rare aminosugars. Further studies on the
synthesis of other aminosugars based on this strategy are ongoing in our laboratory.
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Experimental section
General Section. All reactions were carried out in well-cleaned and oven-dried glassware under magnetic
stirring. All starting materials were obtained from commercial sources or were synthesized using standard
procedures. Melting points were measured on a Yanaco MP-500D instrument and were not corrected. 1H
and 13C{1H} NMR spectra (400 and 100 MHz, respectively) were recorded on a Bruker Avance III HD
400 spectrometer; TMS (0 ppm) and CDCl3 (77.0 ppm) were used as internal standards, respectively. The
following abbreviations are used to describe NMR peak multiplicity: s = singlet, d = doublet, t = triplet,
q = quartet, and m = multiplet. Mass spectra were measured on a Thermo Auest LCQ DECA Plus
instrument with GL Sciences Inc. Inert Cap5 as a column (70–310 °C) or JEOL The AccuTOF LC-plus
JMS-T 100LP. Mass spectra were measured using a JEOL JMS-T100LP (DART method, ambient
ionization) or a LTQ Orbitrap Elite (Thermo Fisher Scientific, Brehmen, Germany) with an electrospray
ionization (ESI) ion source. Elemental analyses were performed using Yanaco CHN Corder MT-5.
Optical rotations were measured by HORIBA SEPA-500 Polarimeter using 10 cm cell. Preparative
column chromatography was performed with Fuji Silysia BW-4:10MH silica gel or YMC_GEL Silica (6
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nm I-40-63 µm). Thin layer chromatography (TLC) was carried out on Merck 25 TLC silica gel 60 F254
aluminum sheets.
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Preparation of OsO4 solution.23 Commercially available OsO4 (1 g) was solved in 39.8 mL of tert-butyl
alcohol and 0.20 mL of 70% (or 90%) tert-butyl peroxide. The mixture was stirred to provide 25 mg (ca.
0.1 mmol)/1 mL stock solution.
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Synthesis of Starting Materials
Methyl 2,3-dideoxy-4,6-di-O-(tert-butyldimethylsilyl)-α-D-erythro-hex-2-enopyranoside (1). In the
two-necked flask were added 3,4,6-tri-O-acetyl-D-glucal (6.0 g, 22 mmol), MeOH (1.8 mL, 44 mmol),
and ClCH2CH2Cl (80 mL). Then 1 M SnCl4 in CH2Cl2 (6.6 mL, 6.6 mmol) was dropped slowly at 0 ºC.
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After confirmation of the complete consumption of 3,4,6-tri-O-acetyl-D-glucall by H NMR, satd.
NaHCO3 was added for quenching of the reaction. Extraction with CH2Cl2, followed by washing with
brine and dried with anhydrous Na2SO4. After evaporation, the obtained residue was silica-gel column
chromatographed using hexane and ethyl acetate (4:1) as an eluent to give methyl 4,6-di-O-acetyl-2,3-
dideoxy--D-threo-hex-2-enopyranoside (4.4 g, 17.2 mmol, 78%). Then, NaOMe (378 mg, 7 mmol) and
MeOH (10 mL) were added to the CH2Cl2 (15 mL) solution of 4,6-di-O-acetyl-2,3-dideoxy--D-threo-
hex-2-enopyranoside (2.44 g, 10 mmol). After stirring for 2 h at room temperature, the mixture was
concentrated to remove solvent. To the residue, were added imidazole (5.4 g, 80 mmol) and tert-
butyldimethylsilyl chloride (7.5 g, 50 mmol) and DMF (20 mL). After stirring 20 h, methanol was added
for quenching. Extraction with diethyl ether, followed by washing with brine and dried with anhydrous
Na2SO4. After evaporation, the obtained residue was silica-gel column chromatographed using hexane
and ethyl acetate (50:1) as an eluent to give methyl 2,3-dideoxy-4,6-di-O-(tert-butyldimethylsilyl)-α-D-
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erythro-hex-2-enopyranoside (1) (3.4 g, 8.6 mmol, 86%). Colorless liquid; []D = +108.4 (c = 1.0,
CHCl3); IR (neat) 2954, 2928, 2885, 2857, 1472, 1463, 1390, 1361, 1312, 1252, 1187, 1126, 1094, 1070,
1015, 967, 884, 833, 812, 774, 671 cm-1; 1H NMR (400 MHz, CDCl3) δ = 5.68 (ddd, J = 10.2, 2.6, 2.0
Hz, 1H), 4.85 (s, 1H), 4.12 (dq, J = 8.9, 1.6 Hz, 1H) 3.87 (dd, J = 11.1, 1.7 Hz, 1H), 3.62–3.77 (m, 2H),
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3.43 (s, 3H), 0.91 (s, 9H), 0.88 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H), 0.07 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 134.6, 125.5, 95.3, 72.7, 64.3, 62.9, 55.6, 26.1, 25.8, 18.6, 18.0, -4.1, -4.7, -5.0, -5.2; HRMS
[ESI+]. m/z calcd for C19H40NaO4Si2: 411.2357 [M+Na]+, Found: 411.2353 [M+Na]+.
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Synthesis of Methyl 4,6-di-O-Acetyl-2,3-dideoxy--D-threo-hex-2-enopyranoside (S1).9 In the two-
necked flask were added 3,4,6-tri-O-acetyl-D-galactal (1.5 g, 5.5 mmol), MeOH (0.45 mL, 11 mmol), and
ClCH2CH2Cl (40 mL). Then 1 M SnCl4 in CH2Cl2 (1.65 mL, 1.65 mmol) was dropped slowly at 0 ºC.
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After confirmation of the complete consumption of 3,4,6-tri-O-acetyl-D-galactal by H NMR, satd.
NaHCO3 was added for quenching of the reaction. Extraction with CH2Cl2, followed by washing with
brine and dried with anhydrous Na2SO4. After evaporation, the obtained residue was silica-gel column
chromatographed using hexane and ethyl acetate (4:1) as an eluent to give methyl 4,6-di-O-acetyl-2,3-
dideoxy--D-threo-hex-2-enopyranoside (S1) (926 mg, 3.8 mmol, 69%). White solid; mp = 55.1__56.0
°C; []D27 = -159.7 (c = 0.43, CHCl3); IR (neat) 2957, 2897, 2825, 1730, 1437, 1365, 1220, 1183, 1103,
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1042, 959, 906, 750, 648, 600 cm-1; H NMR (400 MHz, CDCl3)  = 6.12 (ddd, J = 0.8, 5.2, 10.0 Hz,
1H), 6.04 (dd, J = 2.8, 10.0 Hz, 1H), 5.02 (dd, J = 2.8, 5.6 Hz, 1H), 4.97 (d, J = 2.8 Hz, 1H), 4.33 (dt, J =
13
2.8, 6.0 Hz,1H), 4.24 (d, J = 6.4 Hz, 2H), 3.45 (s, 3H), 2.09 (s, 3H), 2.08 (s, 3H); C{1H} NMR (100
MHz, CDCl3)  = 170.6, 170.3, 130.5, 125.2, 94.8, 66.7, 62.8, 55.6, 20.8; HRMS [DART+]. m/z calcd for
C10H13O5: 213.0763 [M-OMe]+, Found: 213.0769 [M-OMe]+.
Synthesis of Methyl 4,6-di-O-Benzoyl-2,3-dideoxy--D-threo-hex-2-enopyranoside (4c). In the two-
necked flask were added methyl 4,6-di-O-acetyl-2,3-dideoxy--D-threo- hex-2-enopyranoside (S1) (2.2
g, 9.0 mmol), NaOMe (194 mg, 3.6 mmol), MeOH (5 mL), and CH2Cl2 (7.5 mL). After stirring for 2 h at
room temperature, the mixture was concentrated to remove solvent. To the residue, were added pyridine
(13 mmol) and benzoyl chloride (5.2 mL, 45 mmol). After stirring 20 h, methanol was added for
quenching. Extraction with ethyl acetate, followed by washing with brine and dried with anhydrous
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Na2SO4. After evaporation, the obtained residue was silica-gel column chromatographed using hexane
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and ethyl acetate (10:1) as an eluent to give methyl 4,6-di-O-benzoyl-2,3-dideoxy--D-threo-hex-2-
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enopyranoside (4c) (3.3 g, 8.8 mmol, 98%). White solid; mp = 94.4__98.7 °C; []D26 = -197.6 (c =
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0.35, CHCl3); IR (neat) 2800__3000, 1712, 1601, 1584, 1490, 1449, 1417, 1331, 1312, 1290,
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1261, 1175, 1128, 1096, 1069, 1048, 1026, 964, 879, 859, 804, 754, 707, 686, 617 cm-1; H
NMR (400 MHz, CDCl3)  = 8.01__8.07 (m, 4H), 7.54__7.60 (m, 2H), 7.41__7.46 (m, 4H), 6.28
(ddd, J = 1.2, 5.6, 10.0 Hz, 1H), 6.10 (dd, J = 2.8, 10.0 Hz, 1H), 5.35 (dd, J = 2.4, 5.6 Hz, 1H),
5.05 (d, J = 2.4 Hz, 1H), 4.67 (dd, J = 7.6, 10.8 Hz), 4.60 (ddd, J = 1.6, 2.0, 10.4 Hz, 1H), 4.52(dd,
J = 4.4, 10.8 Hz, 1H), 3.48 (s, 3H); C{1H} NMR (100 MHz, CDCl3)  = 133.3, 130.7, 129.8,
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129.6, 128.4, 125.3, 95.0, 67.2, 63.5, 55.7; HRMS [DART+]. m/z calcd for C20H17O5: 337.1076
[M-OMe]+, Found:337.1055 [M-OMe]+
Synthesis of Methyl 4,6-di-O-(tert-Butyldimethylsilyl)-2,3-dideoxy--D-threo-hex-2-enopyranoside
(4e). In the two-necked flask were added methyl 4,6-di-O-acetyl-2,3-dideoxy--D-threo-hex-2-
enopyranoside (S1) (2.2 g, 9.0 mmol), NaOMe (194 mg, 3.6 mmol), MeOH (5 mL), and CH2Cl2 (7.5 mL).
After stirring for 2 h at room temperature, the mixture was concentrated to remove solvent. To the residue,
were added imidazole (4.9 g, 72 mmol) and tert-butyldimethylsilyl chloride (6.8 g, 45 mmol) and DMF
(20 mL). After stirring 20 h, methanol was added for quenching. Extraction with diethyl ether, followed
by washing with brine and dried with anhydrous Na2SO4. After evaporation, the obtained residue was
silica-gel column chromatographed using hexane and ethyl acetate (50:1) as an eluent to give methyl 4,6-
di-O-(tert-butyldimethylsiloxy)-2,3-dideoxy--D-threo-hex-2-enopyranoside (4e) (3.0 g, 7.6 mmol,
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85%). Colorless liquid; []D27 = -95.4 (c = 0.35, CHCl3); IR (neat) 2950, 2924, 2891, 2854, 1470, 1408,
1359, 1251, 1188, 1142, 1109, 1096, 1045, 1020, 1004, 959, 936, 872, 832, 772, 731, 687, 664 cm-1; 1H
NMR (400 MHz, CDCl3)  = 6.01 (ddd, J = 0.8, 5.2, 10.0 Hz, 1H), 5.87 (dd, J = 3.2, 12.5 Hz, 1H), 4.92
(d, J = 2.8 Hz, 1H), 3.93 (ddd, J = 2.4, 6.4, 7.2 Hz, 1H), 3.89 (dd, J = 2.4, 5.2 Hz, 1H), 3.82 (dd, J = 5.2,
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10.4 Hz, 1H), 3.76 (dd, J = 6.8, 10.8 Hz, 1H), 3.43 (s, 3H), 0.90 (s, 9H), 0.89 (s, 9H), 0.07__0.08 (m, 12H);
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13C{1H} NMR (100 MHz, CDCl3)  = 129.8, 127.7, 95.0, 71.8, 62.8, 62.0, 55.2, 25.9, 25.8, 18.3, 18.2, -
4.0, -4.7, -5.3, -5.4; HRMS [DART+]. m/z calcd for C18H37O3Si2:357.2281 [M-OMe]+, Found: 357.2253
[M-OMe]+.
Synthesis of 1,5-Anhydro-6-O-(tert-butyldimethylsilyl)-3,4-O-carbonate-2-deoxy-D-lyxo-hex-1-
enopyranose (S2).21 In the two-necked flask were added 3,4,6-tri-O-acetyl-D-galactal (0.27 g, 1 mmol),
CH2Cl2 (0.83 mL), MeOH (0.56 mL), and NaOMe (0.022 g, 0.4 mmol) and the mixture was stirred at 29
°C for 2 h. After removal of solvent under reduced pressure, CH2Cl2 (2.2 mL) and imidazole (0.15 g, 2.2
mmol) were added then tert-butylchlorodimethylsilane (0.17 g, 1.1 mmol) was added at 0 °C. After
stirring at room temperature, the mixture was quenched with MeOH. After usual work-up, the mixture of
imidazole (6.8 mg, 0.1 mmol) and 1,1’-carbonyldiimidazole (0.24 g, 1.5 mmol) in THF (0.45 mL) solution
was added to the above mixture at 0 °C. After stirring at room temperature for 20 h and usual work-up.
The obtained residue was purified by silica-gel column chromatography (benzene:CH2Cl2 = 2:1) to give
1,5-anhydro-6-O-(tert-butyldimethylsilyl)-3,4-O-carbonate-2-deoxy-D-lyxo-hex-1-enopyranose
(S2)
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(0.15 g, 0.51 mmol, 51%). White solid; mp = 52.0–54.0 °C; [α]D = -74.6 (c = 1.0, CHCl3); IR (neat)
2948, 2928, 2885, 2857, 1786, 1647, 1470, 1463, 1367, 1316, 1242, 1166, 1115, 1086, 1069, 1017, 995,
898, 833, 778, 768, 697, 668, 645 cm-1; 1H NMR (400 MHz, CDCl3) δ = 6.66 (d, J = 6.7 Hz, 1H), 5.18
(dd, J = 7.6, 3.2 Hz, 1H), 4.99–4.91 (m, 2H), 3.98–3.83 (m, 3H), 0.90 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ = 154.3, 149.3, 98.2, 74.1, 72.9, 69.0, 61.2, 25.9, 18.4, -5.3, -5.4;
HRMS [DART]. m/z calcd for C13H23O5Si1: 287.1315 [M-OMe]+, Found:287.1304 [M-OMe]+.
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Synthesis of Methyl 2,3-Dideoxy-6-O-(tert-butyldimethylsilyl)-β-D-threo-hex-2-enopyranoside (S3).21
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In the two-necked flask were added 1,5-anhydro-6-O-(tert-butyldimethylsilyl)-3,4-O-carbonate-2-
deoxy-D-lyxo-hex-1-enopyranose S2 (0.29 g, 1 mmol), THF (6 mL), MeOH (0.08 mL, 2 mmol), PPh3
(0.079 g, 0.3 mmol), and Pd(OAc)2 (0.022 g, 0.1 mmol), and the mixture was stirred at room temperature
for 17 h. After filtration, the residue was washed with ethyl acetate, and solvent was removed under
reduced pressure. The obtained crude product was purified by silica-gel column chromatography
(hexane:ethyl acetate = 4:1) to afford methyl 2,3-dideoxy-6-O-(tert-butyldimethylsilyl)-β-D-threo-hex-2-
enopyranoside (S3) (0.23 g, 0.84 mmol, 84%). Colorless liquid; [α]D21 = -120.3 (c = 1.0, CHCl3); IR(neat)
3426, 2948, 2928, 2883, 2855, 1471, 1389, 1252, 1206, 1121, 1091, 1049, 995, 953, 834, 776, 670 cm-1;
1H NMR (400 MHz, CDCl3) δ = 6.11–6.02 (m, 1H), 5.73 (d, J = 10.1 Hz, 1H), 4.90 (s, 1H), 3.91–3.80
(m, 2H), 3.74 (ddd, J = 10.5, 6.0, 2.3 Hz, 1H), 3.60 (tt, J = 6.1, 2.5 Hz, 1H), 3.47–3.40 (m, 3H), 2.5 (br s,
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1H), 0.88–0.82 (m, 9H), 0.03 (s, 6H); C{1H} NMR (100 MHz, CDCl3) δ = 131.1, 130.3, 98.7, 75.7,
62.7, 62.4, 55.8, 25.9, 18.3, -5.3, -5.4; HRMS [DART]. m/z calcd for C13H27O4Si1: 275.1679 [M-OMe]+,
Found:275.1659 [M-OMe]+.
Synthesis of Methyl 2,3-Dideoxy-β-D-threo-hex-2-enopyranoside (S4). In the two-necked flask were
added methyl 2,3-dideoxy-β-D-threo-hex-2-enopyranoside (S3) (2.7 g, 9.54 mmol) and THF (95 mL).
Tetrabutylammonium fluoride in THF 1 mol/L (19 mL, 19 mmol) was added to the mixture at 0 °C, and
the mixture was stirred at room temperature for 2 h. After removal of solvent, the obtained residue was
purified by silica-gel column chromatography (hexane:ethyl acetate = 4:1) to afford methyl 2,3-dideoxy-
β-D-threo-hex-2-enopyranoside (S4) (1.5 g, 9.32 mmol, 94%). White solid; mp: 73.5-74.0 °C; [α]D20 = -
183.0 (c = 1.0, CHCl3); IR(neat) 3252 br, 3047, 3001, 2969, 2927, 2838, 1395, 1339, 1203, 1147, 1117,
1051, 1037, 1002, 991, 953, 856, 785, 622, cm-1; 1H NMR (400 MHz, CDCl3) δ = 6.14 (ddd, J = 10.1,
4.8, 1.4 Hz, 1H), 5.85 (dt, J = 10.1, 1.1 Hz, 1H), 5.01 (q, J = 1.5 Hz, 1H), 4.08–4.01 (m, 1H), 3.96 (dt, J
= 12.2, 6.0 Hz, 1H), 3.87 (ddd, J = 12.0, 7.4, 4.5 Hz, 1H), 3.79 (ddd, J = 7.4, 4.4, 3.1 Hz, 1H), 3.55 (s,
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3H), 2.27 (br, 1H), 2.0 (br s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 130.9, 130.1, 98.4, 75.1, 62.8, 62.4,
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56.1; HRMS [DART]. m/z calcd for C6H9O3:129.0552 [M-OMe]+, Found:129.0555 [M-OMe]+.
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Synthesis of methyl 2,3-dideoxy-4,6-di-O-methyl-β-D-threo-hex-2-enopyranoside (4a). In the two-
necked flask were added methyl 2,3-dideoxy-β-D-threo-hex-2-enopyranoside (0.48 g, 3 mmol) and DMF
(7.2 mL). NaH (60%, dispersion in paraffin liquid, 0.48 g, 3 mmol) was added at 0 ºC, and the mixture
was stirred for 1 h at 0 ºC. Iodomethane (0.75 mL, 12 mmol) was added at this temperature, and the
reaction was stirred at room temperature for 21 h. After the confirmation of completion of the reaction,
the mixture was quenched with methanol. After usual work-up, the obtained crude product was purified
by silica-gel column chromatography (hexane:ethyl acetate = 2:1) to afford methyl 2,3-dideoxy-4,6-di-
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O-methyl-β-D-threo-hex-2-enopyranoside (4a) (0. 47g, 2.5 mmol, 83%). Colorless liquid; [α]D = -
223.6 (c = 0.40, CHCl3); IR(neat) 2897, 2824, 1446, 1394, 1324, 1202, 1118, 1097, 1056, 1000, 961, 881,
831, 795, 665, 622 cm-1; 1H NMR (400 MHz, CDCl3) δ = 6.18–6.09 (m, 1H), 5.91 (d, J = 10.3 Hz, 1H),
5.01 (s, 1H), 3.88 (tt, J = 5.7, 2.4 Hz, 1H), 3.71–3.62 (m, 3H), 3.53–3.48 (m, 3H), 3.45–3.41 (m, 3H),
3.41– 3.39 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 131.4, 127.9, 97.9, 73.9, 72.0, 70.2, 59.3, 56.6,
55.4; HRMS [DART]. m/z calcd for C8H13O3: 157.0865 [M-OMe]+, Found: 157.0890 [M-OMe]+.
Synthesis of Methyl 2,3-Dideoxy-4,6-di-O-benzyl-β-D-threo-hex-2-enopyranoside (4b). In the two-
necked flask were added methyl 2,3-dideoxy-β-D-threo-hex-2-enopyranoside (S4) (0.56 g, 3.5 mmol) and
DMF (17 mL). NaH (60%, dispersion in paraffin liquid, 0.56 g, 14 mmol) was added at 0 ºC, and the
mixture was stirred for 1 h at 0 ºC. Benzyl bromide (1.66 mL, 14 mmol) was added at this temperature,
and the reaction was stirred at room temperature for 21 h. After the confirmation of completion of the
reaction, the mixture was quenched with methanol. After usual work-up, the obtained crude product was
purified by silica-gel column chromatography (hexane:ethyl acetate = 5:1) to afford methyl 2,3-dideoxy-
20
4,6-di-O-benzyl-β-D-threo-hex-2-enopyranoside (4b) (1.2 g, 3.5 mmol, 100%). Colorless liquid; [α]D
= -146.2 (c = 1.0, CHCl3); IR (neat) 3028, 2862, 1496, 1453, 1206, 1109, 1096, 1055, 1027, 1002, 960,
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792, 733, 696, 608 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.38–7.23 (m, 10H) , 6.06 (ddd, J = 10.2, 4.4,
1.5 Hz, 1H), 5.88 (dt, J = 10.3, 1.0 Hz, 1H) , 5.01 (q, J = 1.5 Hz, 1H), 4.68–4.51 (m, 4H) , 4.00–3.92 (m,
1H), 3.92–3.86, (m, 1H), 3.80 (s, 1H), 3.51 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ = 138.5, 138.3,
131.1, 128.4, 128.3, 127.8, 127.6, 98.0, 74.1, 73.6, 70.8, 69.6, 68.5, 55.6; HRMS [DART]. m/z calcd for
C20H21O3: 309.1491 [M-OMe]+, Found: 309.1499 [M-OMe]+.
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Synthesis of Methyl 2,3-Dideoxy-4,6-di-O-benzoyl-β-D-threo-hex-2-enopyranoside (4c). In the two-
necked flask were added methyl 2,3-dideoxy-β-D-threo-hex-2-enopyranoside (1.44 g, 9.0 mmol), CH2Cl2
(20 mL), and pyridine (5.81 mL, 72 mmol). Benzoyl chloride (4.2 mL, 36 mmol) was added at 0 °C, and
the mixture was stirred at room temperature for 24 h. After the confirmation of completion of the reaction,
the mixture was quenched with methanol. After usual work-up, the obtained crude product was purified
by silica-gel column chromatography (hexane:ethyl acetate = 10:1→hexane:ethyl acetate = 5:1) to give
methyl 2,3-dideoxy-4,6-di-O-benzoyl-β-D-threo-hex-2-enopyranoside (4c) (3.3 g, 9 mmol, 100%).
White solid; mp: 70.0–70.5 ºC; [α]D20 = -223.1 (c = 1.0, CHCl3); IR(neat) 2926, 2382, 1718, 1450, 1251,
1
1176, 1106, 1057, 1028, 902, 706, 687, 676, 642 cm-1; H NMR (400 MHz, CDCl3) δ = 8.03–7.97 (m,
2H), 7.61–7.50 (m, 2H), 6.24 (ddd, J = 10.2, 4.7, 1.5 Hz, 1H), 6.07–5.99 (m, 1H), 5.54–5.48 (m, 1H),
5.15 (q, J = 1.5 Hz, 1H), 4.70 (dd, J = 11.4, 7.2 Hz, 1H), 4.54 (dd, J = 11.5, 5.7 Hz, 1H), 4.34 (ddd, J =
7.1, 5.7, 3.1 Hz, 1H), 3.55 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 133.4, 133.2, 132.5, 129.9, 129.8,
129.7, 129.6, 128.5, 126.8, 97.9, 71.3, 64.6, 63.4, 55.6; HRMS [DART]. m/z calcd for C20H17O5:
337.1076 [M-OMe]+, Found: 337.1087 [M-OMe]+.
Synthesis of methyl 2,3-dideoxy-4,6-di-O-pivaloyl-β-D-threo-hex-2-enopyranoside (4d). In the two-
necked flask were added methyl 2,3-dideoxy-β-D-threo-hex-2-enopyranoside (0.56 g, 3.5 mmol), CH2Cl2
(7.7 mL), pyridine (2.8 mL, 35 mmol), and N,N-dimethyl-4-aminopyridine (0.043 g, 0.35 mmol). Pivaloyl
chloride (2.13 mL, 17.5 mmol) was added at 0 ºC, and the mixture was stirred at room temperature for 21
h. After the confirmation of completion of the reaction, the mixture was quenched with methanol. After
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usual work-up, the obtained crude product was purified by silica-gel column chromatography
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(hexane:ethyl acetate = 6:1) to afford methyl 2,3-dideoxy-4,6-di-O-pivaloyl-β-D-threo-hex-2-
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enopyranoside (4d) (1.14 g, 3.5 mmol, 100%). Colorless liquid; [α]D = -167.5 (c = 1.0, CHCl3);
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IR(neat) 2971, 2936, 2907, 2869, 1727, 1480, 1462, 1397, 1280, 1209, 1142, 1056, 952, 768, 752, 533
cm-1; 1H NMR (400 MHz, CDCl3) δ = 6.10–6.04 (m, 1H), 5.94 (d, J = 10.1 Hz, 1H), 5.10–5.04 (m, 2H),
4.31 (dd, J = 11.1, 7.1 Hz, 1H), 4.19 (dd, J = 11.1, 6.4 Hz, 1H), 4.06 (td, J = 6.7, 2.8 Hz, 1H), 3.50 (s,
3H), 1.21 (s, 9H), 1.12 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ = 27.1, 27.1, 38.8, 39.0, 55.2, 62.3,
63.2, 71.2, 98.0, 126.8, 132.5, 177.7, 178.1; HRMS [DART]. m/z calcd for C16H25O5: 297.1702 [M-
OMe]+, Found: 297.1711[M-OMe]+.
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Synthesis of Methyl 2,3-Dideoxy-4,6-di-O-(tert-butyldimethylsilyl)-β-D-threo-hex-2-enopyranoside
(4e). In the two-necked flask were added methyl 2,3-dideoxy-6-O-[(1,1-dimethyl)silyl]-β-D-threo-hex-
2-enopyranoside (1.82 g, 6.6 mmol), CH2Cl2 (15 mL) and imidazole (1.08 g, 15.9 mmol). tert-
Butylchlorodimethylsilane (1.2 g, 7.9 mmol) was added at 0 °C, and the mixture was stirred at room
temperature for 17 h. After the confirmation of completion of the reaction, the mixture was quenched with
methanol. After usual work-up, the obtained crude product was purified by silica-gel column
chromatography (hexane:ethyl acetate = 1:30) to give methyl 2,3-dideoxy-4,6-di-O-(tert-
butyldimethylsilyl)-β-D-threo-hex-2-enopyranoside (4e) (2.36 g, 6.1 mmol, 92%). Colorless liquid;
[α]D20 = -99.2 (c = 1.0, CHCl3); IR(neat) 2954, 2928, 2883, 2856, 1471, 1389, 1252, 1095, 1059, 1005,
833, 773, 667, 538 cm-1; 1H NMR (400 MHz, CDCl3) δ = 5.97 (ddd, J = 10.2, 4.5, 1.5 Hz, 1H), 5.75 (dt,
J = 10.2, 1.0 Hz, 1H), 5.01 (q, J = 1.5 Hz, 1H), 4.10–4.05 (m, 1H), 3.83 (s, 1H), 3.81 (s, 1H), 3.63 (dt, J
= 6.2, 3.0 Hz, 1H), 3.47 (s, 3H), 0.90 (s, 9H) 0.88 (s, 9H), 0.07 (s, 12H); 13C{1H} NMR (100 MHz, CDCl3)
δ 131.5, 129.5, 97.7, 76.6, 63.0, 62.6, 55.0, 26.1, 26.0, 18.5, 18.3, -4.0, -4.6, -5.1; HRMS [DART]. m/z
calcd for C18H37O3Si2: 357.2281 [M-OMe]+, Found:357.2294 [M-OMe]+.
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Synthesis of methyl 2,3-dideoxy-4,6-di-O-( tert-butyldiphenylsilyl)-β-D-threo-hex-2-enopyranoside
(4f). In the two-necked flask were added methyl 2,3-dideoxy-β-D-threo-hex-2-enopyranoside (0.48 g, 3
mmol), CH2Cl2 (6.7 mL), and imidazole (0.98 g, 14.4 mmol) were added. tert-Butyldiphenylsilyl
chloride (1.85 mL, 7.2 mmol) was added at 0 ºC, and the mixture was stirred at room temperature for 21
h. After the confirmation of completion of the reaction, the mixture was quenched with methanol. After
usual work-up, the obtained crude product was purified by silica-gel column chromatography
(hexane:ethyl acetate = 12:1) to afford methyl 2,3-dideoxy-4,6-di-O-(tert-butyldiphenylsilyl)-β-D-threo-
hex-2-enopyranoside (4f) (1.61 g, 2.4 mmol, 84%). Colorless liquid; [α]D20 = -72.6 (c = 1.0, CHCl3); IR
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(neat) 2958, 2930, 2893, 2856, 1427, 1390, 1111, 1055, 998, 822, 738, 699, 610 cm-1; H NMR (400
MHz, CDCl3) δ = 7.68 (ddd, J = 12.8, 8.0, 1.5 Hz, 4H), 7.60 (ddd, J = 11.6, 8.0, 1.3 Hz, 4H),0.91 (s, 9H),
7.43–7.27 (m, 12H) , 5.65 – 5.55 (m, 2H), 4.89 (s, 1H), 4.10 (dd, J = 11.0, 7.7 Hz 1H) , 4.07–4.03 (m,
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1H), 3.94 (dd, J = 11.0, 4.2 Hz 1H), 3.64 (dt, J = 7.6, 4.1 Hz 1H), 3.52 (s, 3H), 1.07 (s, 9H); C{1H}
NMR (100 MHz, CDCl3) δ 136.2, 135.9, 135.8, 135.7, 134.1, 134.0, 133.9, 133.4, 131.2, 129.9, 129.7,
129.5, 127.8, 127.7, 127.5, 97.7, 76.6, 64.4, 64.0, 55.4, 27.1, 27.0,19.4; HRMS [DART]. m/z calcd for
C38H45O3Si2: 605.2907 [M-OMe]+, Found: 605.2935 [M-OMe]+.
General procedure for the catalytic asymmetric aminohydroxylation. In the Schlenk flask were
added protected 2,3-unsaturated D-gluco- or D-galacto-2-hexenopyranoside (0.5 mmol),
benzyltriethylammonium chloride (0.025 mmol), (DHQ)2PHAL (0.025 mmol), tert-BuOH (0.5 mL), H2O
(0.5 mL), chloramine T･3H2O (0.625 mmol), and OsO4 solution (0.2 mL, 0.02 mmol). The reaction
mixture was stirred at room temperature. After the confirmation of completion of the reaction, Na2SO3
(0.5 mmol) was added at room temperature for quenching. The mixture was stirred at room temperature
for 3 h. Extraction with CHCl3 followed by evaporation afforded crude product. The ratio was determined
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1
by H NMR analysis using an internal standard at this stage. For purification silica-gel column
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chromatography was used.
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Typical procedure for the catalytic asymmetric aminohydroxylation. In the Schlenk flask were
added 2,3-dideoxy-4,6-di-O-(tert-butyldimethylsilyl)-β-D-threo-hex-2-enopyranoside (0.19 g, 0.5
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mmol), benzyltriethylammonium chloride (5.7 mg, 0.025 mmol), (DHQ)2PHAL (0.019 g, 0.025 mmol),
tert-BuOH (0.5 mL), H2O (0.5 mL), chloramine T･3H2O (0.176 g, 0.625 mmol), and OsO4 solution (0.2
mL, 0.02 mmol). The reaction mixture was stirred at room temperature. After the confirmation of
completion of the reaction, Na2SO3 (0.071 g, 0.5 mmol) was added at room temperature for quenching.
The mixture was stirred at room temperature for 3 h. Extraction with CHCl3 followed by evaporation
afforded crude product. The ratio was determined by 1H NMR analysis using an internal standard at this
stage. For purification silica-gel column chromatography (hexane:ethyl acetate = 2:1) was used.
Methyl 4,6-di-O-(tert-Butyldimethylsilyl)-2-deoxy-2-(p-toluenesulfonamido)-α-D-mannopyranoside
20
(2). White solid; mp: 93.0–94.0°C; []D = +28.3 (c = 1.0, CHCl3); IR (neat) 3498, 3278, 2954, 2927,
2899, 2856, 1471, 1456, 1440, 1359, 1316, 1307, 1273, 1251, 1165, 1092, 1073, 1057, 1004, 965, 939,
835, 814, 803, 777, 662, 552 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.76 (d, J = 8.3 Hz, 2H), 7.33 (d, J =
8.0 Hz, 2H), 4.74 (d, J = 8.5 Hz, 1H), 4.30 (d, J = 1.6 Hz, 1H), 3.67–3.85 (m, 3H), 3.53 (dq, J = 2.7, 2.2
Hz, 1H), 3.48 (t, J = 9.1 Hz, 1H), 3.40 (ddd, J = 9.3, 4.8, 1.9 Hz, 1H), 3.22 (s, 3H), 2.44 (s, 3H), 2.13 (d,
J = 8.2 Hz, 1H), 0.91 (s, 9H), 0.87 (s, 9H), 0.11 (s, 3H), 0.08 (s, 6H), 0.07 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ = 144.0, 136.8, 129.9, 127.3, 99.2, 73.3, 69.7, 62.4, 56.9, 54.8, 26.0, 21.6, 18.3, -3.9, -
4.9, -5.0, -5.2; HRMS [DART]. m/z calcd for C25H46NO6SSi2: 544.2584 [M-OMe]+, Found: 544.2594[M-
OMe]+.
Methyl 4,6-di-O-(tert-Butyldimethylsilyl)-α-D-mannopyranoside (3). Colorless liquid; [α]D21 = +59.8 (c
= 1.0, CHCl3); IR(neat) 3445, 2952, 2928, 2895, 2856, 1472, 1463, 1388, 1360, 1251, 1100, 1071, 1057,
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968, 879, 833, 807, 776, 676 cm-1; 1H NMR (400 MHz, CDCl3) δ = 4.70 (d, J = 1.4 Hz, 1H), 3.82–3.90
(m, 2H), 3.63–3.79 (m, 3H), 3.50 (dt, J = 8.8, 6.3 Hz, 1H), 3.37 (s, 3H), 2.24 (br s, 1H), 2.14 (br s, 1H),
0.89 (s, 9H), 0.89 (s, 9H), 0.14 (s, 3H), 0.10 (s, 3H), 0.07 (s, 3H), 0.07 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 100.5, 73.3, 72.4, 71.3, 69.5, 62.7, 54.8, 26.0, 18.5, 18.4, -3.9, -4.7, -5.0, -5.2; HRMS [ESI+].
m/z calcd for C19H42NaO6Si2: 445.2412 [M+Na]+, Found: 445.2405 [M+Na]+.
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Methyl
4,6-di-O-(tert-butyldimethylsilyl)-3-deoxy-3-(p-toluenesulfonamido)-α-D-gulopyranoside
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(5e). White solid; mp: 99.0–99.9 °C; [α]D = + 19.5 (c = 0.18, CHCl3); IR (neat) 3509, 3274, 2953,
2929, 2856, 1462, 1427, 1355, 1328, 1254, 1164, 1110, 1096, 1088, 1056, 1021, 899, 833, 778, 666, 578
cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.77 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 5.82 (d, J = 9.0
Hz, 1H) , 4.67 (d, J = 3.5 Hz, 1H), 3.97 (dt, J = 10.4, 4.7 Hz, 1H), 3.84 (d, J = 3.4 Hz, 1H), 3.79 (t, J =
6.3 Hz, 1H), 3.56–3.68 (m, 2H), 3.50 (dt, J = 8.5, 3.9 Hz, 1H), 3.43 (s, 3H), 2.42 (s, 3H), 1.82 (d, J = 10.5
Hz, 1H) , 0.89 (s, 9H), 0.86 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H), 0.01 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 143.7, 137.6, 129.9, 127.3, 100.3, 70.3, 67.2, 63.4, 62.5, 56.7, 55.8, 26.0, 25.8, 21.7, 18.4,
18.0, -4.6, -5.1, -5.2, -5.3; HRMS [ESI+]. m/z calcd for C26H49NNaO7SSi2: 598.2660 [M+Na]+, Found:
598.2640.
Methyl
4,6-di-O-(tert-Butyldimethylsilyl)-2-deoxy-2-(p-toluenesulfonamido)-α-D-gulopyranoside
(6e). White solid; mp: 74.5–75.3 °C; [α]D20 = +41.7 (c = 0.33, CHCl3); IR (neat) 3506, 3435, 3274, 3144,
2950, 2928, 2884, 2855, 2360, 2341, 1598, 1470, 1462, 1416, 1356, 1321, 1253, 1152, 1113, 1092, 1053,
1021, 940, 859, 833, 813, 778, 666, 650 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.91 (d, J = 8.3 Hz, 2H),
7.42 (d, J = 8.1 Hz, 2H), 5.50 (d, J = 10.1 Hz, 1H), 4.77 (d, J = 3.2 Hz, 1H), 3.93 (t, J = 6.3 Hz, 1H), 3.87
(d, J = 3.8 Hz, 1H), 3.85–3.72 (m, 3H) 0.13 (s, 3H), 3.54–3.61 (m, 1H), 3.48 (s, 3H), 3.45 (s, 1H), 2.54
(s, 3H), 1.00 (s, 9H), 0.95 (s, 9H), 0.17 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ = 143.5, 137.9, 129.8,
127.1, 100.2, 71.7, 69.6, 66.6, 62.2, 55.8, 49.5, 25.8, 25.7, 21.5, 18.2, 17.9, -5.0, -5.2, -5.3, -5.4; HRMS
[ESI+]. m/z calcd for C26H49NNaO7SSi2: 598.2660 [M+Na]+, Found: 598.2645.
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Methyl 4,6-di-O-Methyl-3-deoxy-3-(p-toluenesulfonamido)-β-D-gulopyranoside (5a). Colorless
liquid; [α]D19 = -72.0 (c = 0.48, CHCl3); IR (neat) 3474, 3271, 2929, 2830, 1598, 1448, 1409, 1372, 1329,
1205, 1158, 1082, 1055, 998, 948, 911, 814, 752, 730, 673, 551 cm-1; 1H NMR (400 MHz, CDCl3) δ =
7.78 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 5.31 (br s, 1H), 4.38 (d, J = 8.1 Hz, 1H), 4.13 (t, J =
6.1 Hz, 1H), 3.73 (s, 1H), 3.72–3.65 (m, 1H), 3.55 (d, J = 6.2 Hz, 2H), 3.51–3.46 (m, 4H), 3.37 (t, J = 1.8
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Hz, 6H), 2.8 (br s, 1H), 2.44 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 144.0, 135.0, 129.9, 127.6,
101.0, 76.9, 71.8, 71.3, 66.6, 59.2, 58.7, 56.7, 52.7, 21.6; HRMS [DART]. m/z calcd for C16H26N1O7S:
376.1430 [M+H]+, Found: 376.1421 [M+H]+.
Methyl 4,6-di-O-Methyl-2-deoxy-2-(p-toluenesulfonamido)-β-D-gulopyranoside (6a). Colorless
liquid; [α]D19 = -94.6 (c = 0.22, CHCl3); IR (neat) 3458, 3282, 2929, 2824, 1598, 1446, 1404, 1324, 1200,
1152, 1078, 1038, 948, 908, 814, 752, 730, 671, 551 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.75 (d, J =
8.3 Hz, 2H), 5.1 (br s, 1H), 4.46 (d, J = 8.3 Hz, 1H), 4.43 (s, 1H), 4.04 (td, J = 7.3, 5.9, 0.8 Hz, 1H) ,
3.60–3.44 (m, 2H), 3.37 (s, 3H), 3.36 (s, 3H), 3.33–3.29 (m, 1H) 3.29–3.22 (m, 3H), 3.17–3.06 (m, 2H),
2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.7, 136.0, 129.6, 127.5, 99.3, 77.3, 71.9, 71.2, 66.5,
59.3, 58.5, 56.3, 55.0, 21.6; HRMS [DART]. m/z calcd for C16H26N1O7S: 376.1430 [M+H]+, Found:
376.1415 [M+H]+.
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Methyl 4,6-di-O-Methyl-β-D-gulopyranoside (7a). Colorless liquid; [α]D = -36.7 (c = 0.02, CHCl3);
IR (neat) 3426, 2918, 2848, 1726, 1448, 1201, 1100, 1072, 1030, 955, 911, 750, 672, 620, 593, 566, 536
cm-1; 1H NMR (400 MHz, CDCl3) δ = 4.51 (d, J = 7.9 Hz, 1H), 4.26 (t, J = 3.4 Hz, 1H), 4.08 (dt, J = 6.3,
1.4 Hz, 1H) 3.69–3.57 (m, 3H), 3.54 (s, 3H), 3.44 (s, 3H), 3.41 (s, 3H) 3.37 (dd, J = 3.4, 1.6 Hz, 1H) , 2.5
(br s, 1H), 2.4 (br s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 101.2, 78.0, 72.1, 69.5, 67.5, 59.3, 58.9,
56.7; HRMS [DART]. m/z calcd for C9H19O6: 223.1182 [M+H]+, Found: 223.1199 [M+H]+.
Methyl 4,6-di-O-Benzyl-3-deoxy-3-(p-toluenesulfonamido)-β-D-gulopyranoside (5b). Colorless liquid;
[α]D20 = -76.5 (c = 0.64, CHCl3); IR (neat) 3468, 3269, 2928, 2868, 1453, 1358, 1159, 1088, 1066, 942,
814, 698, 673, 596 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.63 (d, J = 8.3 Hz, 2H), 7.38–7.25 (m, 12H)
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, 5.1 (br s, 1H), 4.58–4.32 (m, 5H), 4.15 (t, J = 5.9 Hz, 1H), 4.04–3.98 (m, 1H), 3.77 (ddd, J = 7.5, 5.0,
1.7 Hz, 1H), 3.61 (dd, J = 10.0, 6.6 Hz, 1H), 3.48 (m, 5H) , 2.4 (br s, 1H), 2.39 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 143.9, 138.1, 137.8, 135.2, 129.8, 128.4, 128.3, 127.9, 127.7, 127.6, 127.5, 101.1,
74.5, 73.3, 72.9, 72.0, 69.0, 66.8, 56.8, 53.6, 21.6; HRMS [DART]. m/z calcd for C27H30N1O6S: 496.1794
[M-OMe]+, Found: 496.1799 [M-OMe]+.
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Methyl 4,6-di-O-Benzyl-2-deoxy-2-(p-toluenesulfonamido)-β-D-gulopyranoside (6b). Colorless liquid;
[α]D13 = -100.7 (c = 0.34, CHCl3); IR (neat) 3026, 2916, 2862, 1454, 1323, 1154, 1076, 1038, 747, 666,
1
551 cm-1; H NMR (400 MHz, CDCl3) δ = 7.70 (d, J = 8.3 Hz, 2H), 7.36–7.16 (m, 12H), 4.79 (s, 1H),
4.56–4.47 (m, 3H), 4.47–4.41 (m, 3H), 4.10 (td, J = 6.4, 1.4 Hz, 1H), 3.63–3.53 (m, 3H), 3.33 (s, 3H),
13
3.09 (dt, J = 8.1, 2.7 Hz, 1H), 2.6 (br s, 1H), 2.39 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 143.8,
138.0, 137.7, 135.4, 129.8, 128.4, 128.3, 128.0, 127.9, 127.7, 127.5, 99.2, 74.7, 73.4, 72.6, 72.2, 68.8,
66.6, 56.5, 55.4, 21.6; HRMS [DART]. m/z calcd for C27H30N1O6S: 496.1794 [M-OMe]+, Found:
496.1809 [M-OMe]+.
Methyl 4,6-di-O-Benzyl-β-D-gulopyranoside (7b). Colorless liquid; [α]D13 = -55.5 (c = 0.28, CHCl3); IR
(neat) 3393, 2914, 1716, 1586, 1453, 1314, 1268, 1205, 1071, 1026, 747, 697, 666 cm-1; 1H NMR (400
MHz, CDCl3) δ = 7.38–7.20 (m, 10H), 4.67–4.41 (m, 5H), 4.18 (t, J = 3.4 Hz, 1H), 4.13 (dt, J = 6.3, 1.3
Hz, 1H), 3.76–3.60 (m, 4H), 3.53 (s, 3H), 2.6 (br s, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.1, 137.9,
128.4, 128.0, 127.9, 127.7, 101.3, 75.7, 73.4, 72.9, 72.2, 69.5, 68.9, 68.3, 56.8; HRMS [DART]. m/z calcd
for C21H27O6: 375.1808 [M+H]+, Found: 375.1803 [M+H]+.
Methyl 4,6-di-O-Benzoyl-3-deoxy-3-(p-toluenesulfonamido)-β-D-gulopyranoside (5c). White solid;
mp: 82.0–84.0 ºC; [α]D13 = -120.7 (c = 0.30, CHCl3); IR (neat) 3462, 3272, 2292, 1721, 1600, 1451, 1317,
1265, 1159, 1092, 1026, 942, 814, 708, 669, 550 cm-1; 1H NMR (400 MHz, CDCl3) δ = 8.02 (d, J = 7.8
Hz, 4H) 7.88 (d, J = 7.0 Hz, 2H) 7.61–7.50 (m, 2H), 7.46–7.36 (m, 4H), 7.29 (dd, J = 8.2, 2.7 Hz, 2H) ,
5.92 (t, J = 3.8 Hz, 1H), 5.24 (d, J = 3.6 Hz, 1H), 4.70–4.56 (m, 3H), 4.37 (dd, J = 11.0, 5.6 Hz, 1H) ,
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3.88–3.79 (m, 1H), 3.58 (s, 3H), 3.57 (s, 1H), 2.57 (brs, 1H), 2.37 (s, 3H); C{1H} NMR (100 MHz,
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CDCl3) δ 133.5, 133.1, 129.9, 129.7, 129.6, 129.0, 128.5, 128.4, 127.9, 101.2, 70.2, 68.6, 67.4, 62.8, 57.2,
53.7, 21.6; HRMS [DART]. m/z calcd for C27H26N1O8S: 524.1379 [M-OMe]+, Found: 524.1394 [M+H]+.
Methyl 4,6-di-O-Benzoyl-2-deoxy-2-(p-toluenesulfonamido)-β-D-gulopyranoside (6c). White solid;
mp: 66.0–72.0 ºC; [α]D13 = -97.3 (c = 0.23, CHCl3); IR (neat) 3464, 3276, 2959, 1720, 1600, 1451, 1327,
1264, 1156, 1112, 1026, 814, 709, 670, 551 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.98 (dd, J = 8.4, 1.3
Hz, 4H), 7.67–7.59 (m, 3H), 7.57–7.51 (m, 1H), 7.49–7.37 (m, 4H), 7.04 (d, J = 7.9 Hz, 2H), 5.27 (dd, J
= 3.7, 1.2 Hz, 1H), 4.98 (d, J = 4.0 Hz, 1H), 4.64 (d, J = 8.2 Hz, 1H), 4.54 (dd, J = 10.7, 6.9 Hz, 1H),
4.51–4.43 (m, 1H), 4.40 (t, J = 3.2 Hz, 1H ), 4.34 (dd, J = 10.7, 5.5 Hz, 1H), 3.39 (s, 3H), 3.13–3.08 (m,
1H), 3.0 (br s, 1H), 2.26 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 166.0, 165.1, 143.8, 135.4, 133.6,
133.2, 129.9, 129.7, 129.6, 129.0, 128.5, 128.4, 127.3, 99.7, 70.1, 69.6, 62.5, 57.2, 56.9, 55.2, 21.4; HRMS
[DART]. m/z calcd for C28H30N1O9S: 556.1641 [M+H]+, Found: 556.1651 [M+H]+.
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Methyl 4,6-di-O-benzoyl-β-D-gulopyranoside (7c). White solid; mp: 50.0–52.0 ºC; [α]D20 = -65.5 (c =
1.0, CHCl3); IR (neat) 3445, 2913, 1716, 1601, 1451, 1263, 1110, 1070, 1024, 707, 685 cm-1; 1H NMR
(400 MHz, CDCl3) δ = 8.11–8.04 (m, 2H) , 8.04–7.97 (m, 2H) , 7.62–7.50 (m, 2H) , 7.48–7.37 (m, 4H) ,
5.38 (dd, J = 3.6, 1.3 Hz, 1H), 4.69 (d, J = 8.0 Hz, 1H), 4.61 (dd, J = 10.9, 6.9 Hz, 1H), 4.52 (td, J = 12.6,
1.2 Hz, 1H), 4.41 (dd, J = 10.9, 5.8 Hz, 1H), 4.30 (q, J = 3.3 Hz, 1H), 3.81–3.73 (m, 1H), 3.61 (s, 3H),
3.05 (s, 1H), 2.74 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 166.1, 165.4, 133.6, 133.1, 129.9, 129.7,
129.1, 128.5, 128.4, 101.6, 70.5, 70.2, 69.4, 68.8, 62.6, 57.2; HRMS [DART]. m/z calcd for C21H23O8:
403.1393 [M+H]+, Found: 403.1404 [M+H]+.
Methyl 4,6-di-O-Pivaloyl-3-deoxy-3-(p-toluenesulfonamido)-β-D-gulopyranoside
(5d). Colorless
liquid; [α]D20 = -64.9 (c = 0.53, CHCl3); IR (neat) 3473, 3280, 2972, 2866, 1732, 1480, 1281, 1155, 1136,
1091, 1043, 944, 752, 667, 551 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.34 (d, J = 7.9 Hz, 2H), 7.34 (d,
J = 7.9 Hz, 2H), 5.51 (dd, J = 3.4, 1.1 Hz, 1H), 5.20–5.10 (m, 1H), 4.53 (d, J = 8.0 Hz, 1H), 4.44 (td, J =
6.9, 1.2 Hz 1H), 4.25 (dd, J = 11.0, 7.1 Hz 1H), 4.03 (dd, J = 11.0, 6.9 Hz, 1H), 3.62 (dd, J = 7.6, 5.0 Hz,
1H), 3.54 (s, 3H), 3.33 (t, J = 3.6 Hz 1H), 2.6 (br s, 1H), 2.43 (s, 3H), 1.28 (s, 9H), 1.20 (s, 9H); 13C{1H}
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NMR (100 MHz, CDCl3) δ 177.9, 176.8, 144.1, 134.3, 129.8, 127.9, 101.0, 69.6, 67.5, 67.0, 61.4, 57.2,
53.7, 39.0, 38.7, 27.1, 21.6; HRMS [DART]. m/z calcd for C23H34N1O8S: 484.2005 [M-OMe]+, Found:
484.2010 [M-OMe]+.
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Methyl 4,6-di-O-Benzyl-2-deoxy-2-(p-toluenesulfonamido)-β-D-gulopyranoside (6d). Colorless liquid;
[α]D16 = -70.9 (c = 0.14, CHCl3); IR (neat) 3479, 3277, 2972, 1732, 1480, 1282, 1141, 1083, 1042, 754,
732, 667, 551 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.71 (d, J = 8.6 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H),
5.0 (br s, 1H), 4.89 (dd, J = 3.6, 1.4 Hz, 1H), 4.53 (d, J = 8.3 Hz, 1H), 4.30–4.22 (m, 1H), 4.21–4.10 (m,
2H), 4.02 (dd, J = 11.1, 6.4 Hz, 1H), 3.35 (s, 3H), 3.01 (dt, J = 7.8, 3.5 Hz, 1H), 2.92 (br, 1H), 2.42 (s,
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3H), 1.17 (s, 9H), 1.13 (s, 9H); C{1H} NMR (100 MHz, CDCl3) δ 178.0, 177.2, 143.8, 136.1, 129.7,
127.4, 99.6, 69.9, 68.8, 67.7, 61.7, 56.9, 55.0, 39.0, 38.7, 27.1, 26.9, 21.5; HRMS [DART]. m/z calcd for
C23H34N1O8S: 484.2005 [M-OMe]+, Found: 484.1996 [M-OMe]+.
Methyl 4,6-di-O-Pivaloyl-β-D-gulopyranoside (7d). Colorless crystal; mp = 116.0–117.0 ˚ C; [α]D21 = -
48.9 ˚(c = 0.11, CHCl3); IR (neat) 3495, 2975, 2907, 2845, 1716, 1480, 1284, 1164, 1122, 1061, 966, 768,
741, 666 cm-1; 1H NMR (400 MHz, CDCl3) δ = 5.0 (br s, 1H), 4.58 (d, J = 8.1 Hz, 1H), 4.30 (t, J = 6.9
Hz, 1H), 4.22 (dd, J = 10.9, 7.3 Hz, 1H), 4.14–4.05 (m, 2H), 3.61–3.55 (m, 1H), 3.57 (s, 3H), 3.0 (br s,
1H), 2.7 (br s, 1H), 1.22 (s, 9H), 1.19 (s, 9H)); 13C{1H} NMR (100 MHz, CDCl3) δ 178.1, 177.6, 101.4,
70.0, 69.9, 69.3, 68.7, 61.9, 57.2, 39.1, 38.8, 27.1; HRMS [DART]. m/z calcd for C17H31O8: 363.2019
[M+H]+, Found:363.2014 [M+H]+.
Methyl
4,6-di-O-(tert-Butyldimethylsilyl)-3-deoxy-3-(p-toluenesulfonamido)-β-D-gulopyranoside
(5e). Colorless crystal; mp: 119.0–121.0 ºC; [α]D17 = -73.2 (c = 0.38, CHCl3); IR (neat) 3496, 3214,
2961, 2927, 2855, 1462, 1254, 1161, 1117, 1078, 1052, 937, 833, 775, 674, 578 cm-1, 1H NMR (400 MHz,
CDCl3) δ = 7.75 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.3 Hz, 2H), 5.2 (br, 1H), 4.33 (d, J = 8.3 Hz, 1H), 4.18
(d, J = 2.7 Hz, 1H), 3.93 (t, J = 6.4 Hz, 1H), 3.79–3.60 (m, 3H), 3.50 (s, 3H), 3.31–3.25 (m, 1H), 2.42 (s,
3H), 0.90 (s, 9H), 0.82 (s, 9H), 0.08 (s, 3H), 0.06 (s, 3H), 0.05 (s, 3H), 0.03 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 144.0, 135.3, 129.9, 127.8, 101.4, 74.2, 68.5, 66.7, 62.3, 57.2, 56.8, 26.0, 25.9, 21.7, 18.4,
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18.1, -4.7, -4.8, -5.0, -5.2; HRMS [DART]. m/z calcd for C25H46N1O6SSi2: 544.2584 [M-OMe]+, Found:
544.2594 [M-OMe]+.
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4,6-di-O-(tert-Butyldimethylsilyl)-2-deoxy-2-(p-toluenesulfonamido)-β-D-gulopyranoside
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(6e). White solid; mp: 187.0–188.0 ºC; [α]D17 = -88.8 (c = 0.22 , CHCl3); IR (neat) 3525 br, 3270, 2952,
2928, 2886, 2855, 1470, 1407, 1331, 1249, 1159, 1118, 1075, 1048, 942, 881, 835, 780, 670, 532 cm-1;
1H NMR (400 MHz, CDCl3) δ = 7.29 (d, J = 8.0 Hz, 2H), 4.82 (d, J = 2.7 Hz, 1H), 4.47 (d, J = 8.2 Hz,
1H), 4.17 (q, J = 3.1 Hz, 1H), 3.85–3.79 (m, 1H), 3.76 (d, J = 3.6 Hz, 1H), 3.65 (s, 1H), 3.12 (dt, J = 8.2,
2.8 Hz, 1H) , 2.69 (d, J = 3.1 Hz, 1H) , 2.41 (s, 3H) , 3.63 (s, 1H), 3.36 (s, 3H) 0.87 (s, 9H), 0.80 (s, 9H),
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0.04 (s, 9H), 0.03 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 143.9, 135.8, 129.9, 127.6, 99.6, 74.5,
70.4, 68.7, 61.9, 56.7, 55.0, 26.0, 25.9, 21.7, 18.4, 18.1, -4.6, -4.9, -5.1, -5.2; HRMS [DART]. m/z calcd
for C25H46N1O6SSi2: 544.2584 [M-OMe]+, Found: 544.2611 [M-OMe]+.
Methyl 4,6-di-O-(tert-butyldimethylsilyl)-β-D-gulopyranoside (7e). Colorless liquid; [α]D19 = -42.6 ˚(c
= 0.17, CHCl3); IR (neat) 3439 br, 2950, 2928, 2881, 2856, 1472, 1389, 1361, 1253, 1076, 1046, 1022,
1005, 939, 833, 774, 731, 666 cm-1; 1H NMR (400 MHz, CDCl3) δ = 4.49 (d, J = 8.0 Hz, 1H), 4.02 (t, J
= 3.2 Hz, 1H), 3.89–3.82 (m, 2H), 3.75–3.68 (m, 3H), 2.5 (br s, 1H), 2.5 (br s, 1H), 0.90 (s, 9H), 0.89 (s,
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9H), 0.09 (s, 3H), 0.08 (s, 3H), 0.07 (s, 3H), 0.03 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 101.7,
74.5, 71.8, 69.5, 69.4, 61.9, 57.2, 26.1, 25.9, 18.4, 18.2, -4.6, -4.8, -5.1, -5.2; HRMS [DART]. m/z calcd
for C19H43O6Si2: 423.2598 [M+H]+, Found: 423.2623 [M+H]+.
Methyl
4,6-di-O-(tert-Butyldiphenylsilyl)-3-deoxy-3-(p-toluenesulfonamido)-β-D-gulopyranoside
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(5f). Colorless liquid; [α]D = -45.1 (c = 1.0, CHCl3); IR (neat) 3046, 2930, 2857, 1427, 1160, 1104,
1091, 1055, 936, 908, 755, 734, 700 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 7.9, 1.3 Hz, 2H),
7.54–7.29 (m, 16H), 7.25–7.11 (m, 6H), 4.9 (br s, 1H), 4.33 (d, J = 8.2 Hz, 1H), 4.20 (d, J = 3.3 Hz, 1H),
3.94–3.82 (m, 2H), 3.74 (dd, J = 10.8, 8.1 Hz, 1H), 3.55 (s, 3H), 3.44–3.39 (m, 1H), 3.10 (dd, J = 10.9,
3.2 Hz, 1H), 2.40 (s, 3H), 2.2 (br s, 1H), 0.98 (s, 9H), 0.89 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ
143.6, 136.1, 135.9, 135.6, 135.2, 133.8, 133.6, 133.0, 132.4, 129.9, 129.7, 129.6, 127.8, 127.7, 127.6,
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101.4, 75.1, 70.1, 66.8, 64.5, 56.9, 56.5, 27.1, 26.8, 21.7, 19.4, 19.2; Anal. Calcd for C45H57NO7SSi2: C,
67.04; H, 6.97; N, 1.70. Found: C, 66.77; H, 7.01; N, 1.90.
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(6f). Colorless liquid; [α]D = -41.4 (c = 1.0, CHCl3); IR (neat) 2950, 2940, 2893, 2857, 1427, 1324,
1111, 1053, 998, 821, 755, 736, 700, 607 cm-1; 1H NMR (400 MHz, CDCl3) δ = 7.73 (dd, J = 8.3, 1.8 Hz,
2H), 7.60–7.51 (m, 2H), 7.48–7.21 (m, 18H), 7.10 (t, J = 7.6 Hz, 2H), 5.34 (d, J = 4.8 Hz, 1H), 4.44 (d, J
= 8.3 Hz, 1H), 4.17 (q, J = 3.2 Hz, 1H), 3.84 (dd, J = 8.3, 2.2 Hz, 1H), 3.75 (dd, J = 10.8, 8.2 Hz, 1H),
3.58 (d, J = 3.5 Hz, 1H), 3.44 (ddd, J = 8.0, 4.7, 3.0 Hz, 1H), 3.36 (s, 3H), 3.13 (dd, J = 10.8, 2.8 Hz, 1H),
2.6 (br s, 1H), 2.40 (s, 3H) 0.94 (s, 9H), 0.89 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.5, 136.6,
136.1, 135.9, 135.7, 135.5, 133.8, 133.6, 132.7, 132.5, 130.0, 129.8, 129.7, 127.8, 127.6, 127.5, 99.9,
75.4, 70.8, 64.6, 56.5, 54.6, 27.0, 26.8, 21.7, 19.4.19.1; Anal. Calcd for C45H57NO7SSi2: C, 67.04; H, 6.97;
N, 1.70. Found: C, 66.67; H, 7.01; N, 1.70.
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Methyl 4,6-di-O-(tert-Butyldiphenylsilyl)-β-D-gulopyranoside (7f). Colorless liquid; [α]D16 = -12.1 (c =
0.44, CHCl3); IR (neat) 3417, 2952, 2930, 2893, 2857, 1427, 1104, 1069, 1046, 755, 735, 700, 614 cm-1;
1H NMR (400 MHz, CDCl3) δ = 7.64 (dd, J = 8.0, 1.4 Hz, 2H), 7.57–7.48 (m, 6H), 7.47–7.23 (m, 14H),
7.19 (t, J = 7.5 Hz, 2H), 4.46 (d, J = 8.0 Hz, 1H), 3.94–3.78 (m, 4H), 3.76 (d, J = 3.4 Hz, 1H), 3.58 (s,
3H), 3.50–3.40 (m, 1H), 2.28 (d, J = 2.7 Hz, 1H), 2.21 (d, J = 1.3 Hz, 1H), 1.00 (s, 9H), 0.96 (s, 9H);
13C{1H} NMR (100 MHz, CDCl3) δ 136.0, 135.8, 135.7, 133.9, 133.7, 133.3, 132.9, 130.0, 129.9, 129.6,
127.8, 127.7, 101.7, 75.4, 71.4, 71.3, 69.4, 64.4, 57.0, 27.1, 26.9, 19.5, 19.3; HRMS [DART]. m/z calcd
for C38H47O5Si2: 639.2962 [M-OMe]+, Found: 639.2962 [M-OMe]+.
DFT calculations
All calculations were performed with the Gaussian 09 package.24 The geometry was optimized by the LC-
BLYP25 DFT method with 6-31G* basis set in gas phase. Frequency analyses were also carried out to
identify the stationary points (no imaginary frequency) and to estimate thermodynamic properties at
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Page 28 of 33
298.15 K and 1 atm and Gibbs free energies. The molecular structures were depicted by using the
CYLview v1.0.561 .26
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Supporting Information
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The supporting information is available free of charge at
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Procedure for the synthesis of starting materials 1 and 4a-4f, typical procedure for
aminohydroxylation, characterization of products, 1H and 13C NMR spectral data for all compounds, and
DFT calculations.
AUTHOR INFORMATION
Corresponding Author
Masahiko Hayashi
*E-mail: mhayashi@kobe-u.ac.jp. Website: http://www2.kobe- u.ac.jp/~mhayashi/
ORCID
Masahiko Hayashi: 0000-0002-1716-6686
Ryosuke Matsubara: 0000-0001-8941-2391
Notes
The authors declare no competing financial interest.
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