C -Glycosylation of Substituted β-Naphthols with Trichloroacetimidate Glycosyl Donors

Article abstract of DOI:10.1055/s-0036-1591746

Several glycosyl donors have been systematically investigated for C-glycosylation of substituted β-naphthols to delineate the effect of the substituents. Whereas glycosylations of the parent 2-naphthol are smoothly achievable, those of differently substituted 2-naphthols are cumbersome. Efficiency of the glycosylation depends on the nature of both the glycosyl donors and the substituents of the arene ring. Among various glycosyl donors, trichloroacetimidate glycosyl donors are found to be superior for glycosylation with substituted 2-naphthols.

Full text of DOI:10.1055/s-0036-1591746

SYNTHESIS
0
0
3
9
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7
8
8
1
1
4
3
7
-
2
1
0
X
©
Georg Thieme Verlag Stuttgart · New York
2018, 50, A–I
paper
A
en
Synthesis
S. Chakraborty, D. Mal
Paper
C-Glycosylation of Substituted β-Naphthols with Trichloroacet-
imidate Glycosyl Donors
Soumen Chakraborty
OR
O
R1
RO
RO
AcO
R1
R1
R2
Dipakranjan Mal*
0
0
0
0
0-
0
0
1
6-
6
3
4
9-
9
3
2
R2
O
R2
RO
O
Department of Chemistry, Indian Institute of
Technology Kharagpur, Kharagpur 721302,
India
N3
CCl3
OAc
HN
RO
dmal@chem.iitkgp.ernet.in
SnCl4, DCM
TMSOTf, MeCN
0 °C to rt, 2 h
O
OH
–78 °C to –35° C
OR
OR
O
OH
OH
to rt, 12 h
RO
= H, Naph, etc
= H, F, OH, Me, OMe, etc
R = OMe, OBn
R
R
1
2
N3 OAc
R1 = H, Et, Pr, Br, CO2Me, Ph, CN, Ac, etc
R2 = H, CN, Me, OH, OMe, etc
O
R1 = R2
=
Received: 18.10.2017
Accepted after revision: 01.12.2017
Published online: 03.01.2018
tion of this study, we examined glycosylation reactions of
differently substituted β-naphthols with different glycosyl
donors. Herein, we report on the suitability of trichloroace-
timidate glycosyl donors for various β-naphthols.
DOI: 10.1055/s-0036-1591746; Art ID: ss-2017-z0676-op
Abstract Several glycosyl donors have been systematically investigat-
ed for C-glycosylation of substituted β-naphthols to delineate the effect
of the substituents. Whereas glycosylations of the parent 2-naphthol
are smoothly achievable, those of differently substituted 2-naphthols
are cumbersome. Efficiency of the glycosylation depends on the nature
of both the glycosyl donors and the substituents of the arene ring.
Among various glycosyl donors, trichloroacetimidate glycosyl donors
are found to be superior for glycosylation with substituted 2-naphthols.
Since our long-term objective was to achieve a total syn-
thesis of
a C-glycosylated natural product, namely,
12
mayamycin, by the application of glycosylation of a suit-
able 2-naphthol derivative at an early stage of the synthetic
route, we considered varying the substituents of ring A
of the naphthols. For that purpose, we prepared various
2
-naphthols with different substituents at the C6 or C7 po-
sition from commercially available naphthols. First, we in-
vestigated the effect of alkyl, aryl, ester, and bromo substit-
uents at the C6 position of 2-naphthols on glycosylation
with different glycosyl donors. To this end, 6-ethyl-2-naph-
thol (2)13 and 6-isopropyl-2-naphthol (4) were synthe-
sized from commercially available ketone 1 (Scheme 1) by
following reported methods.
Key words C-glycosylation, 2-naphthols, Lewis acids, trichloroacetimi-
date, glycosyl donors, substituent effects
C-Aryl glycosides are a class of compounds in which a
14
carbohydrate moiety is attached to an aromatic ring
1
through a C–C bond at the anomeric position. Many meth-
odologies have been developed over the last few decades for
2
the synthesis of C-aryl glycosides. Complex natural prod-
O
ucts have been synthesized by application of the methodol-
ogies. Depending upon the core structures of the aglycon
moieties in naturally occurring C-aryl glycosides, glycosyla-
tion of different arenes, phenols or naphthols are carried
out to achieve a total synthesis. Phenols and α-naphthols
6
PPh3
CH2
i) H2, Pd-C
MeOH
i) NaBH ,TFA
5
7
8
4
A
0 °C to rt
60%
A
t
KO Bu
4
3
78%
B
B
THF
2 h
65%
ii) BBr3, DCM
–78 °C to rt
80%
1
ii)
BBr3, DCM
78 °C to rt
2
–
3
OH
have been studied extensively for glycosylation. However,
O
O
OH
85%
studies on glycosylation of β-naphthols are scanty. Only the
parent β-naphthol has been studied for its glycosylation4
with different glycosyl donors, which include (i) anomeric
4
3
1
2
Scheme 1 Synthesis of 6-ethyl-2-naphthol (2) and 6-isopropyl-2-
naphthol (4)
5
6
OH/OMe as glycosyl donors; (ii) anomeric acetate; (iii)
7
8
anomeric fluoride; (iv) anomeric phosphates and (v) ano-
9
6-Phenyl-2-naphthol (6)15 and 6-naphthyl-2-naphthol
meric trichloroacetimidate as glycosyl donors. In connec-
tion with our studies on the synthesis of C-glycosylated
(7)16 were synthesized in a single step from commercially
available 6-bromo-2-naphthol (5) by using reported meth-
ods (Scheme 2).
10
natural product, we recently reported on the deleterious
effect of a C7 methyl group on the C-glycosylation of
11
β-naphthol with an acetate glycosyl donor. In a continua-
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

B
Synthesis
S. Chakraborty, D. Mal
Paper
B(OH)2
the glycosylation reactions of naphthols 2, 4, 5, 6, and 10
B(OH)2
Br
were carried out at –78 °C with SnCl . The results are sum-
4
marized in Table 1. However, the reactions of donor 21 with
naphthols 11, 12, and 14 were not successful under the
same reaction conditions (Scheme 5).
Ba(OH)2, Pd(PPh3)4
H2O–THF
Ba(OH)2, Pd(PPh3)4
H2O–dioxane
100 °C, 24 h
80 °C, 24 h
65%
OH
80%
OH
OH
7
5
6
O
O
O
O
CO2H
Scheme 2 Synthesis of 6-phenyl-2-naphthol (6) and 6-naphthyl-2-
naphthol (7)
Pd(OAc)2
CH2Br2
K2HPO4
H , Pd/C
MeOH
2
1
40 °C
36 h
90%
For 2-naphthols containing electron-withdrawing
groups at the C6 position, we chose methyl-6-hydroxy-2-
naphthoate (10) and 6-cyano-2-naphthol (8), which
5
6%
OBn
OH
OBn
15
DIBAL-H
–78 °C
16
17
17
18
toluene
were obtained as indicated in Scheme 3.
O
O
HO
Et3SiH
O
CO2H
2
CO Me
Br
CN
BF •OEt
H2, Pd/C
MeOH
3
2
MeOH
concd H2SO4
overnight reflux
CuCN
DMF
150 °C
TFA
8
8%
DCM
°C to rt
2 h
72%
0
60%
95%
OH
OBn
two steps
OBn
OH
OH
OH
OH
2
0
19
18
9
10
5
8
Scheme 4 Synthesis of 6,7-fused β-naphthols 17 and 20 having a
fused ring between C6 and C7
Scheme 3 Synthesis of methyl-6-hydroxy-2-naphthoate (10) and 6-cy-
ano-2-naphthol (8)
1
1
OBn
We also prepared 7-methyl-2-naphthol (11), 7-me-
AcO
1
9
thoxy-2-naphthol (12), 7-fluoro-2-naphthol (13), and
-hydroxy-2-naphthol (14), which have a substituent at the
C7 position (Figure 1).
O
O
BnO
BnO
7
BnO
O
CCl3
N3
OAc
NH
21
22
O
F
OH
O
OBn
O
O
O
BnO
BnO
O
O
CCl3
O
O
CCl3
OH
OH
OH
13
OH
NH
NH
11
12
14
23
24
Figure 1 2-Naphthols having C7 substituents
Figure 2 Glycosyl donors used in this study
Two 6,7-fused β-naphthols, namely 17 and 20, were
synthesized, as shown in Scheme 4. Naphthofuranone 17
was obtained by Yu lactonization of 15 followed by deben-
R1
20
R2
zylation of 16 (H , Pd/C) (Scheme 4). Naphthofuran 20 was
prepared by a sequence of (i) reduction of lactone 16 with
diisobutylaluminum hydride (DIBAL-H) to furnish alcohol
2
SnCl , DCM
O
4
starting naphthol
recovered
AcO
N3
+
–
78 °C to –35 °C to rt
OAc
12 h
21
1
8, (ii) reduction of lactol 18 with Et SiH and borontrifluo-
OH
3
1
2
ride diethyl etherate to 19, and (iii) debenzylation of naph-
thofuran 19.
Keeping in mind the structures of aryl C-glycoside natu-
ral products, we chose to experiment with glycosyl donor
8, R = CN, R = H
1
2
1
1
1
1, R = H, R = Me
1
2
2, R = H, R = OMe
1
2
4, R = H, R = OH
O
2
0, R1 = R2
=
2
1 for C-glycosylation of the 2-naphthols (Figure 2).
21
Azido acetate 21 was selected because of its higher re-
22
Scheme 5 Attempted glycosylation of 21 with naphthols 8, 11, 12, 14,
and 20
activity and because of our earlier success with C-glyco-
sylation of the parent 2-naphthol. With azido sugar 21,
10
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C
Synthesis
S. Chakraborty, D. Mal
Paper
Table 1 Summary of C-Glycosylations of 2-Naphthols with Glycosyl
Donor 21
From the glycosylation studies (Table 1), it is evident
that alkyl or aryl substituents at the C6 position do not pose
any problem in glycoside formation. Glycosylation of 6-eth-
yl-2-naphthol (2), and 6-isopropyl-2-naphthol (4), oc-
curred smoothly with glycosyl donor 21 (entries 1 and 2)
producing the desired C-glycosides 25 (a and b) and 26 (a
and b) in good yields. Similarly, bromonaphthol 5 gave 27a
and 27b in 42% and 35% yield, respectively (entry 3). How-
ever, in case of naphthol 10, in which an ester group is pres-
ent at the C6 position (entry 4), C-glycoside 28 was ob-
tained only in 59% yield. For naphthol 6, with a phenyl sub-
stituent at the C6 position, C-glycoside 29 was furnished in
63% isolated yield (entry 5). The reactions of donor 21 with
naphthols 8, 11, 12, 14, and 20 were not fruitful and did not
give any pure products. These results clearly show that C7
substituents of 2-naphthols have a deleterious effect on the
glycosylation with donor 21.
Entry Glycosyl acceptor
Product
Yield (%)a,b
2
2
5a 52
5b 29
1
O
OH
OH
N3 OAc
25a (N3 in equatorial),
2
25b (N3 in axial)
As a test case, we changed the glycosyl donor and used
glycosyl donor 22 for the substituted 2-naphthol 14 hav-
2
2
6a 44
6b 30
2
23
O
OH
ing a hydroxyl group at C7. Interestingly, the glycosylation
reaction proceeded smoothly in the presence of TMSOTf to
furnish glycoside 30 in 72% isolated yield (Scheme 6). Simi-
lar trichloroacetimidates have been used in the glycosyla-
OH
N3 OAc
4
2
2
6a (N3 in equatorial),
6b (N3 in axial)
9c
Br
tion of 7-hydroxy-2-naphthol (14) and 7-methoxy-2-
naphthol (12)9 in the presence of TMSOTf in DCM.
d
Br
OH
2
2
7a 42
7b 35
OH
OBn
O
3
TMSOTf
O
OH
BnO
BnO
MeCN
OH
18
+
BnO
OH
N3
OAc
BnO
O
CCl3 0 °C to rt
O
2
h
5
2
2
7a (N3 in equatorial),
7b (N3 in axial)
OBn
OBn
72 %
NH
OH
BnO
22
1
4
30
COOMe
COOMe
Scheme 6 Glycosylation of donor 22 with naphthol 14
4
59
The success of the glycosylation reaction (Scheme 6) en-
couraged us to further explore the reactivity of trichloro-
acetimidate glycosyl donors towards glycosylation with dif-
ferent 2-naphthols; the results are summarized in Table 2.
For 6-naphthyl-2-naphthol (7) we used 2323 as glycosyl
donor and TMSOTf as Lewis acid, and obtained glycoside 31
in 86% isolated yield (Table 2, entry 1). The high yield of the
glycosylation reaction using 23 as glycosyl donor prompted
us to carry out glycosylations with other naphthols. 7-Fluo-
ro-2-naphthol (13) and 7-methoxy-2-naphthol (12) in re-
action with glycosyl donor 23 resulted in glycosides 32 and
N3
O
OH
OH
10
28
OAc
5
63
N3
O
OH
OH
33 in 92% and 81% isolated yields, respectively (entries 2
6
29
OAc
and 3). Most interestingly, 7-methyl-2-naphthol (11),
which was inert to glycosylation with donor 21, also react-
ed with donor 23, giving C-glycoside 34 in 93% isolated
yield (entry 4). Naphthol 20 also reacted with donor 23 un-
der the standard conditions and glycoside 35 was obtained
in 67% isolated yield (entry 5). 2-Deoxytrichloroacetimidate
donor 2423 also furnished glycoside 36 in good yield on
a
4
Reaction conditions: SnCl , DCM, –78 to –35 °C to r.t., 12 h.
The ratio of the products was determined after column chromatographic
b
purification. In all cases anomeric configuration was β. Two isomers in en-
tries 1, 2 and 3 are due to different configuration at C3 of the sugar. For
entries 4 and 5 only one isomer was obtained.
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Synthesis
S. Chakraborty, D. Mal
Paper
treatment with naphthol 11 under the standard conditions
entry 6). Similar reactions of acetate donor 21 were carried
Entry Glycosyl acceptor
Product
Yield (%)
(
out with naphthols 8, 11, 12, 14, and 20. However, the cor-
responding glycosylated products were not obtained, and
only starting naphthols were recovered.
Attempts at glycosylation of 8 and 17 (Figure 3) with do-
nors 21, 22, and 23 failed to give any pure products. This is
probably due to deactivation of the naphthalene ring with
the electron-withdrawing substituents. Likewise, naphthols
4
O
93a
O
OH
O
OH
O
O
11
3
4
3
7 and 38 did not undergo glycosylation with glycosyl do-
O
O
nors 21, 22, or 23 under different conditions.
O
67a
5
Ac
CN
O
CN
O
O
OH
O
OH
O
O
20
35
OH
38
OH
37
OH
OH
8
17
Figure 3 Naphthols that did not undergo glycosylation with any glyco-
syl donors
6
68b
O
OH
OBn
OBn
OH
BnO
11
3
6
Table 2 Summary of C-Glycosylations of 2-Naphthols with Glycosyl
Donors 23 and 24
a
Reaction conditions: 23, TMSOTf, MeCN, 0 °C to r.t., 2 h.
Reaction conditions: 24, TMSOTf, MeCN, 0 °C to r.t., 2 h.
b
Entry Glycosyl acceptor
Product
Yield (%)
Finally, a comparative study of glycosylation of the
naphthols 11 was done with three different glycosyl do-
nors, namely, 23, 39, and 40. These donors differ only in the
nucleofuge at the anomeric carbon (Table 3). We have used
the same naphthol 11 in all the three cases. When trichlo-
roacetimidate group (entry 1) was present at the anomeric
position, the reaction was very smooth, giving the C-glyco-
side 34 in 93% isolated yield. For the other two donors, in
which the anomeric carbon has OH or OAc, the yields of gly-
cosylations were low, and significant amounts of starting
naphthol were recovered. For glycosyl donor 39, the yield of
glycoside 34 was only 15%. When acetate was present at the
anomeric position, only a trace amount of the product was
1
86a
O
O
OH
O
OH
O
O
7
3
1
F
F
1
92a
detected in the H NMR spectrum and the product could
2
O
O
not be purified. This may be due to facile formation of ox-
acarbenium ion at low temperature from 40, at which the
nucleophilicity of 11 was insufficient for the Friedel–Crafts
reaction. Thus, donor 40 was completely consumed but did
not take part in a productive pathway. Nevertheless, glyco-
syl donor 23 proved to be useful.
OH
O
OH
O
O
13
3
2
O
O
In conclusion, various substituted 2-naphthols were
synthesized and their C-glycosylation with different glyco-
syl donors was studied under Lewis acidic conditions. From
these studies it is evident that neither electron-donating
nor weak electron-withdrawing groups at the C6 position
pose any problem to glycosylation with different glycosyl
donors. However, strong electron-withdrawing groups at
81a
3
O
O
OH
OH
O
O
O
12
3
3
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S. Chakraborty, D. Mal
Paper
Table 3 Comparison of C-Glycosylations of Naphthol 11 with 23 and Two Glycosyl Donors
Entry
Glycosyl donor
Product
Conditions
Yield (%)
O
O
O
O
O
O
CCl3
1
O
TMSOTf, MeCN, 0 °C to r.t., 2 h
93
O
OH
NH
O
O
O
23
34
O
O
O
2
O
34
34
TMSOTf, MeCN, 0 °C to r.t., 2 h
TMSOTf, MeCN, 0 °C to r.t., 2 h
15
OH
O
3
9
O
O
O
3
O
≤1a
OAc
O
40
a
1
Only detected by H NMR spectroscopic analysis.
both the C6 and C7 position retard the reaction. Although
alkyl substituents at the C7 position can cause problems in
glycosylation with donors 21, 39, and 40, C7 substituted
naphthols undergo smooth glycosylation with donors 22,
Glycosylation of Donor 21 with 2-Naphthols (2, 4, 5, 6, and 10);
General Procedure
To a stirred solution of 2-naphthol derivative (0.5 mmol) and glycosyl
donor 21 (0.75 mmol) and 4 Å molecular sieves in DCM (15 mL) was
added tin(IV) chloride (2.48 mL, 1 M in DCM, 2.48 mmol) at –78 °C.
The reaction mixture was stirred at –78 °C for 10 min and then the
temperature was gradually increased to –35 °C and kept overnight.
The reaction was quenched with saturated sodium bicarbonate solu-
tion and the mixture was extracted with DCM. The organic phase was
dried and concentrated to give the crude product, which was purified
by flash column chromatography (EtOAc/hexane) to obtain the de-
sired C-glycosides.
23, and 24. It is concluded that trichloroacetimidate glyco-
syl donors are superior for glycosylation of substituted β-
naphthols. An extension of this study to the total synthesis
of mayamycin is underway.
All commercially available reagents were used without further purifi-
cation. Melting points were determined in open-end capillary tubes
and are uncorrected. Solvents were dried prior to use by following
standard procedures. TLC were carried out on precoated plates (Mer-
ck silica gel 60, GF254), and the spots were visualized with UV, fluo-
Glycosylation of Trichloroacetimidate Glycosyl Donors (22, 23, and
24) with 2-Naphthols (7, 11, 12, 13, 14, and 20); General Procedure
To a stirred solution of trichloroacetimidate glycosyl donor (0.6
mmol), and 2-naphthol derivative (0.5 mmol) in anhydrous MeCN (5
mL) was added trimethylsilyl trifluoromethanesulfonate (0.05 mL)
dropwise at 0 °C under argon atmosphere. The mixture was stirred at
r.t. for 2 h, then cooled 0 °C and the reaction was quenched with tri-
ethylamine and the mixture was concentrated under reduced pres-
sure and purified by flash column chromatography on silica gel (EtO-
Ac/hexane) to afford the desired glycosides.
rescent light, or by staining with 10% H SO4 in methanol. Flash col-
2
umn chromatography was performed on silica gel (230–400 mesh).
1
13
H and C NMR spectra for all the compounds were recorded at
00/400/600 and 50/100/150 MHz (Bruker Avance 200, Bruker
2
Avance II 400, Bruker Ascend 600), respectively; the chemical shifts
are reported in ppm downfield of tetramethylsilane and referenced to
residual solvent peak (CHCl ; δH = 7.26 and δ = 77.23). Multiplets are
3
C
reported with the following abbreviations: s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet, br = broad resonance. Mass
spectra were recorded with a MS-TOF mass spectrometer. The phrase
6
-(Benzyloxy)naphtho[2,3-c]furan-1(3H)-one (16)
A 30 mL reaction tube equipped with a magnetic stir bar was charged
with Pd(OAc) (11.2 mg, 0.05 mmol) followed by K HPO (261 mg, 1.5
‘
usual work-up’ or ‘worked up in the usual manner’ indicates washing
2
2
4
of the organic phase with water (2 × 1/4 the volume of organic phase)
and brine (1 × 1/4 the volume of organic phase), and drying (anhy-
drous Na SO ), filtration, and concentration under reduced pressure.
mmol) and 6-(benzyloxy)-2-naphthoic acid 15 (139 mg, 0.5 mmol),
and dibromomethane (10 mL). The reaction tube was sealed with a
Teflon cap and the reaction mixture was stirred at 140 °C for 36 h, af-
ter which it was filtered through a Celite pad, and the filtrate was con-
centrated in vacuum. The residue was purified by flash column chro-
matography (20% EtOAc/hexane) to give lactone 16 (81.2 mg, 56%) as
off-white solid; mp 167–169 °C.
2
4
In most of the cases, yields refer to isolated yields after purification.
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S. Chakraborty, D. Mal
Paper
1
13
H NMR (400 MHz, CDCl ): δ = 8.42 (s, 1 H), 7.95 (d, J = 9.1 Hz, 1 H),
C NMR (125 MHz, DMSO-d ): δ = 155.4, 138.9, 135.3, 134.7, 129.7,
3
6
7.75 (s, 1 H), 7.51–7.27 (m, 7 H), 5.45 (s, 2 H), 5.23 (s, 2 H).
128.7, 119.5, 118.7, 117.7, 109.3, 72.2, 72.1.
13
HRMS (ESI): m/z [M + H]+ calcd for C12H11O : 187.0759; found:
C NMR (100 MHz, CDCl ): δ = 171.4, 159.4, 141.3, 138.3, 136.4,
3
2
1
6
31.7, 129 (2C), 128.5, 127.8, 127, 121.6, 120.8, 119.5, 107.3, 70.5,
9.7.
187.0763.
HRMS (ESI): m/z [M + H]+ calcd for C19H15O : 291.1021; found:
(2R,3S,4R,6R)-4-Azido-6-(6-ethyl-2-hydroxynaphthalen-1-yl)-2-
methyltetrahydro-2H-pyran-3-yl Acetate (25a)
3
291.1006.
The general procedure for glycosylation of donor 21 with naphthol 2
was followed using azido acetate 21 (193 mg, 0.75 mmol) and naph-
thol 2 (86 mg, 0.5 mmol). The crude product was purified by flash col-
umn chromatography on silica gel (10% EtOAc/hexane) to afford 25a
6
-Hydroxynaphtho[2,3-c]furan-1(3H)-one (17)
To a stirred solution of 16 (1.0 g, 3.58 mmol) in MeOH (30 mL), 10%
Pd/C (100 mg) was added and the reaction mixture was hydrogenated
using hydrogen gas contained in a balloon for 6 h. The reaction mix-
ture was filtered through Celite, solvent was evaporated under re-
duced pressure and purified by column chromatography on silica gel
35
(96 mg, 52%) as a colorless semisolid; [α]
D
+64.5 (c 0.4, CHCl3).
1
H NMR (400 MHz, CDCl ): δ = 8.46 (s, 1 H), 7.65 (d, J = 8.9 Hz, 1 H),
3
7.59–7.53 (m, 2 H), 7.35 (dd, J = 8.7, 1.8 Hz, 1 H), 7.09 (d, J = 8.8 Hz,
1 H), 5.50 (dd, J = 11.8, 2.2 Hz, 1 H), 4.90 (t, J = 9.6 Hz, 1 H), 3.85–3.73
(m, 2 H), 2.77 (q, J = 7.6 Hz, 2 H), 2.46–2.38 (m, 1 H), 2.19 (s, 3 H),
2.11–2.00 (m, 1 H), 1.37 (d, J = 6.2 Hz, 3 H), 1.31 (t, J = 7.6 Hz, 3 H).
(25% EtOAc/hexane) to obtain 17 (551 mg, 90%) as a white solid; mp
145–147 °C.
1
H NMR (400 MHz, DMSO-d ): δ = 10.31 (s, 1 H), 8.42 (s, 1 H), 8.05 (d,
6
13
J = 8.9 Hz, 1 H), 7.87 (s, 1 H), 7.25 (d, J = 2.5 Hz, 1 H), 7.20 (dd, J = 8.9,
C NMR (100 MHz, CDCl ): δ = 170.2, 153.2, 139.1, 129.9, 129.3,
3
2
.4 Hz, 1 H), 5.49 (s, 2 H).
129.1, 128.3, 127.1, 120.5, 120.1, 113.9, 76.7, 76.3, 75.2, 61.2, 36.2,
28.7, 21.1, 18.2, 15.7.
13
C NMR (100 MHz, DMSO-d ): δ = 171.2, 158.5, 141.7, 138.5, 138.1,
6
132.1, 127.8, 126.6, 120.4, 119.3, 109.2, 70.0.
HRMS (ESI): m/z [M + Na]+ calcd for C20H23N O423Na: 392.1586;
3
HRMS (ESI): m/z [M + Na]+ calcd for C12H O323Na: 223.0371; found:
found: 392.1599.
8
223.0352.
(2R,3S,4S,6R)-4-Azido-6-(6-ethyl-2-hydroxynaphthalen-1-yl)-2-
methyltetrahydro-2H-pyran-3-yl Acetate (25b)
6-Hydroxynaphtho[2,3-c]furan-1(3H)-one (19)
Compound 25b was obtained along with compound 25a (53 mg, 29%)
Under nitrogen atmosphere, to a stirred solution of 16 (66.7 mg, 0.23
mmol) in anhydrous toluene (5 mL) at –78 °C was added DIBAL-H
35
as a colorless semisolid; [α]
D
+44.5 (c 0.4, CHCl3).
1
(0.26 mL, 1 M in cyclohexane, 0.26 mmol) over 5 min. MeOH (1 mL)
H NMR (400 MHz, CDCl ): δ = 8.62 (s, 1 H), 7.62 (dd, J = 11.3, 8.9 Hz,
3
was added and the mixture was allowed to warm to r.t. The solvent
was removed under reduced pressure. This crude alcohol 18 was di-
rectly used in the next step. To a stirred solution of crude 18 in DCM
2 H), 7.58–7.53 (m, 1 H), 7.36 (dd, J = 8.6, 2.0 Hz, 1 H), 7.07 (d,
J = 8.8 Hz, 1 H), 5.74 (dd, J = 8.6, 5.0 Hz, 1 H), 4.90 (dd, J = 10.0, 3.3 Hz,
1 H), 4.32–4.22 (m, 2 H), 2.77 (q, J = 7.6 Hz, 2 H), 2.18–2.21 (m, 5 H),
1.36 (d, J = 6.2 Hz, 3 H), 1.30 (t, J = 7.6 Hz, 3 H).
(
5 mL) was added BF ·OEt (5 drops) and Et SiH (0.1 mL) at 0 °C. The
3
2
3
reaction mixture was then allowed to warm r.t. and stirring was con-
tinued for 2 h. The reaction was quenched with saturated sodium bi-
carbonate solution and the mixture was extracted with DCM. The or-
ganic phase was dried and concentrated and purified by flash column
chromatography (10% EtOAc/hexane) to obtain 19 (45.7 mg, 72% over
two steps) as a yellow solid; mp 151–153 °C.
13
C NMR (150 MHz, CDCl ): δ = 170.2, 153.3, 139.1, 129.7, 129.2,
3
1
2
29.1, 128.3, 126.8, 120.8, 119.9, 114.2, 74.8, 73.2, 72.0, 58.6, 35.8,
8.7, 20.8, 18.3, 15.7.
HRMS (ESI): m/z [M + Na]+ calcd for C20H23N O423Na: 392.1586;
found: 392.1599.
3
1
H NMR (400 MHz, CDCl ): δ = 7.73 (d, J = 9.7 Hz, 1 H), 7.60 (s, 1 H),
3
(
2
2R,3S,4R,6R)-4-Azido-6-(2-hydroxy-6-isopropylnaphthalen-1-yl)-
-methyltetrahydro-2H-pyran-3-yl Acetate (26a)
7
.56 (s, 1 H), 7.51–7.35 (m, 5 H), 7.23–7.21 (m, 2 H), 5.20 (s, 4 H), 5.18
(s, 2 H).
The general procedure for glycosylation of donor 21 with naphthol 4
was followed using azido acetate 21 (193 mg, 0.75 mmol) and naph-
thol 4 (93 mg, 0.5 mmol). The crude product was purified by flash col-
umn chromatography on silica gel (10% EtOAc/hexane) to afford 26a
13
C NMR (100 MHz, CDCl ): δ = 157, 139, 137.1, 136.3, 134.5, 129.5,
3
128.9, 128.8, 128.3, 127.8, 119.3, 119.1, 118.3, 107.6, 73.1, 73.0, 70.3.
HRMS (ESI): m/z [M + H]+ calcd for C19H17O : 277.1229; found:
2
35
277.1225.
(84 mg, 44%) as a colorless semisolid; [α] +84.6 (c 0.4, CHCl3).
D
1
H NMR (400 MHz, CDCl ): δ = 8.46 (s, 1 H), 7.66 (d, J = 8.9 Hz, 1 H),
3
1,3-Dihydronaphtho[2,3-c]furan-6-ol (20)
7.58–7.56 (m, 2 H), 7.42–7.36 (m, 1 H), 7.09 (d, J = 8.9 Hz, 1 H), 5.50
To a stirred solution of 19 (247 mg, 0.9 mmol) in MeOH (15 mL), 10%
Pd/C (25 mg) was added and the reaction mixture was hydrogenated
using hydrogen gas in balloon for 6 h. The reaction mixture was fil-
tered through Celite, solvent was evaporated under reduced pressure
and purified by column chromatography on silica gel (20% EtOAc/hex-
ane) to obtain 20 (147 mg, 88%) as a white solid; mp 132–134 °C.
1
(dd, J = 11.6, 2.2 Hz, 1 H), 4.90 (td, J = 9.6, 1.7 Hz, 1 H), 3.87–3.74 (m,
2 H), 3.04 (p, J = 7.0 Hz, 1 H), 2.42 (ddd, J = 13.9, 4.9, 2.3 Hz, 1 H), 2.19
(s, 3 H), 2.08–2.05 (m, 1 H), 1.37 (d, J = 6.1 Hz, 3 H), 1.32 (d, J = 6.9 Hz,
6 H)
13
C NMR (150 MHz, CDCl ): δ = 170.2, 153.2, 143.7, 130.1, 129.2,
3
129.2, 126.9, 125.6, 120.6, 120.0, 113.9, 76.7, 76.3, 75.2, 61.2, 36.2,
H NMR (400 MHz, DMSO-d ): δ = 9.66 (s, 1 H), 7.71 (d, J = 8.8 Hz,
33.9, 24.2, 24.1, 21.1, 18.2.
6
1
5
H), 7.64 (s, 1 H), 7.56 (s, 1 H), 7.10 (s, 1 H), 7.03 (d, J = 8.7 Hz, 1 H),
.05 (s, 4 H).
HRMS (ESI): m/z [M + Na]+ calcd for C21H25N O 23Na: 406.1743;
found: 406.1730.
3
4
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

G
Synthesis
S. Chakraborty, D. Mal
Paper
1
(
2
2R,3S,4S,6R)-4-Azido-6-(2-hydroxy-6-isopropylnaphthalen-1-yl)-
-methyltetrahydro-2H-pyran-3-yl acetate (26b)
Compound 26b was obtained along with compound 26a (57 mg, 30%)
H NMR (600 MHz, CDCl ): δ = 8.94 (s, 1 H), 8.50 (d, J = 1.8 Hz, 1 H),
3
8.06 (dd, J = 8.9, 1.9 Hz, 1 H), 7.79 (d, J = 8.9 Hz, 1 H), 7.68 (d,
J = 8.9 Hz, 1 H), 7.15 (d, J = 8.9 Hz, 1 H), 5.75 (dd, J = 10.3, 3.5 Hz, 1 H),
4.91 (dd, J = 10.0, 3.3 Hz, 1 H), 4.33–4.26 (m, 2 H), 3.96 (s, 3 H), 2.20–
35
as a colorless semisolid; [α] +78.5 (c 0.4, CHCl3).
1
D
2
.18 (m, 5 H), 1.37 (d, J = 6.2 Hz, 3 H).
H NMR (400 MHz, CDCl ): δ = 8.63 (s, 1 H), 7.63 (t, J = 9.6 Hz, 2 H),
3
13
C NMR (100 MHz, CDCl ): δ = 170.2, 167.4, 156.2, 133.4, 132.1,
7
.56 (d, J = 1.9 Hz, 1 H), 7.40 (dd, J = 8.8, 2.0 Hz, 1 H), 7.07 (d,
J = 8.8 Hz, 1 H), 5.73 (t, J = 6.9 Hz, 1 H), 4.90 (dd, J = 9.9, 3.3 Hz, 1 H),
.33–4.22 (m, 2 H), 3.03 (p, J = 6.9 Hz, 1 H), 2.22–2.17 (m, 5 H), 1.36
3
1
5
31.7, 128.0, 126.7, 124.9, 121, 120.9, 114.6, 74.7, 73.2, 72.2, 58.4,
2.4, 35.8, 20.9, 18.3.
4
HRMS (ESI): m/z [M + H]+ calcd for C20H22N O : 400.1509; found:
(d, J = 6.2 Hz, 3 H), 1.32 (d, J = 6.9 Hz, 6 H).
3
6
13
400.1518.
C NMR (100 MHz, CDCl ): δ = 170.2, 153.3, 143.6, 129.8, 129.3,
3
1
3
29.1, 126.9, 125.4, 120.9, 119.9, 114.2, 74.8, 73.3, 72.0, 58.6, 35.8,
3.9, 24.2, 24.1, 20.8, 18.3.
(2R,3S,4S,6R)-4-Azido-6-(2-hydroxy-6-phenylnaphthalen-1-yl)-2-
methyltetrahydro-2H-pyran-3-yl Acetate (29)
HRMS (ESI): m/z [M + Na]+ calcd for C21H25N O423Na: 406.1743;
3
found: 406.1745.
The general procedure for glycosylation of donor 21 with naphthol 6
was followed using azido acetate 21 (193 mg, 0.75 mmol) and naph-
thol 6 (110 mg, 0.5 mmol). The crude product was purified by flash
column chromatography on silica gel (25% EtOAc/hexane) to afford 29
(2R,3S,4R,6R)-4-Azido-6-(6-bromo-2-hydroxynaphthalen-1-yl)-2-
methyltetrahydro-2H-pyran-3-yl Acetate (27a)
35
(
131 mg, 63%) as a yellow gum; [α] +58.3 (c 0.3, CHCl3).
D
The general procedure for glycosylation of donor 21 with naphthol 5
was followed using azido acetate 21 (193 mg, 0.75 mmol) and naph-
thol 5 (111 mg, 0.5 mmol). The crude product was purified by flash
column chromatography on silica gel (7% EtOAc/hexane) to afford 27a
1
H NMR (400 MHz, CDCl ): δ = 8.75 (s, 1 H), 7.97 (d, J = 1.8 Hz, 1 H),
3
7.76–7.75 (m, 4 H), 7.49–7.36 (m, 4 H), 7.13 (d, J = 8.9 Hz, 1 H), 5.78 (t,
J = 6.9 Hz, 1 H), 4.93–4.90 (m, 1 H), 4.34–4.27 (m, 2 H), 2.24–2.19 (m,
5 H), 1.38 (d, J = 6.1 Hz, 3 H).
35
(88 mg, 42%) as a white semisolid; [α] +66.6 (c 0.4, CHCl3).
D
13
1
C NMR (150 MHz, CDCl ): δ = 170.2, 154.1, 141.0, 136, 130.5, 130.1,
H NMR (400 MHz, CDCl ): δ = 8.58 (s, 1 H), 7.92 (d, J = 2.0 Hz, 1 H),
3
3
1
1
29.2, 129.1, 128.8, 128.5, 127.4, 127.3, 126.9, 126.7, 121.5, 120.5,
14.3, 74.8, 73.3, 72.1, 58.6, 35.9, 20.8, 18.3.
7.62 (d, J = 8.9 Hz, 1 H), 7.56–7.48 (m, 2 H), 7.13 (d, J = 9.0 Hz, 1 H),
5.46 (dd, J = 11.8, 2.2 Hz, 1 H), 4.90 (t, J = 9.7 Hz, 1 H), 3.84–3.72 (m,
2 H), 2.36 (ddd, J = 14.1, 4.9, 2.2 Hz, 1 H), 2.19 (s, 3 H), 2.09–2.02 (m,
1 H), 1.37 (d, J = 6.2 Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C24H23N O423Na: 440.1586;
3
found: 440.1583.
13
C NMR (100 MHz, CDCl ): δ = 170.2, 154.2, 131.2, 130.3, 130.2,
3
1
2
29.5, 129.3, 122.3, 121.4, 116.9, 114.3, 76.4, 75.5, 75.1, 57.6, 36.2,
1.1, 18.1.
1-((2S,3S,4R,5R,6R)-3,4,5-Tris(benzyloxy)-6-(benzyloxymethyl)tet-
rahydro-2H-pyran-2-yl)naphthalene-2,7-diol (30)
HRMS (ESI): m/z [M + Na]+ calcd for C18H18BrN O423Na: 442.0378;
found: 442.0383.
The general procedure for glycosylation of donor 22 with naphthol 14
was followed using donor 22 (409 mg, 0.6 mmol) and naphthol 14 (80
mg, 0.5 mmol). The crude product was purified by flash column chro-
matography on silica gel (30% EtOAc/hexane) to afford 30 (245 mg,
3
(2R,3S,4S,6R)-4-Azido-6-(6-bromo-2-hydroxynaphthalen-1-yl)-2-
35
72%) as a yellowish solid; mp 183–185 °C; [α]
D
+112.6 (c 0.5, CHCl3).
methyltetrahydro-2H-pyran-3-yl Acetate (27b)
1
H NMR (400 MHz, CDCl ): δ = 8.63 (s, 1 H), 7.68 (d, J = 8.7 Hz, 2 H),
Compound 27b was obtained along with compound 27a as a colorless
3
35
7.37–7.32 (m, 10 H), 7.31–7.28 (m, 6 H), 7.21–7.16 (m, 2 H), 7.09 (d,
J = 7.3 Hz, 1 H), 7.04–7.00 (m, 2 H), 6.95 (dd, J = 8.8, 2.3 Hz, 1 H), 6.40
semisolid (73 mg, 35%); [α] +62.3 (c 0.3, CHCl3).
D
1
H NMR (400 MHz, CDCl ): δ = 8.74 (s, 1 H), 7.90 (d, J = 1.3 Hz, 1 H),
3
(d, J = 7.5 Hz, 2 H), 5.22 (d, J = 9.6 Hz, 1 H), 4.98 (d, J = 11.0 Hz, 1 H),
7.59 (d, J = 8.9 Hz, 1 H), 7.53 (s, 2 H), 7.11 (d, J = 8.9 Hz, 1 H), 5.68 (dd,
4.91–4.86 (m, 2 H), 4.65–4.55 (m, 2 H), 4.47 (d, J = 12.0 Hz, 1 H), 4.22
J = 10.8, 2.8 Hz, 1 H), 4.90 (dd, J = 9.9, 3.3 Hz, 1 H), 4.33–4.23 (m, 2 H),
(d, J = 9.6 Hz, 1 H), 4.03–3.95 (m, 2 H), 3.86–3.78 (m, 2 H), 3.74–3.64
2.23–2.09 (m, 5 H), 1.37 (d, J = 6.2 Hz, 3 H).
(m, 2 H), 3.52–3.48 (m, 1 H).
13
C NMR (150 MHz, CDCl ): δ = 170.2, 154.2, 131.0, 130.3, 130.1,
3
13
C NMR (150 MHz, CDCl ): δ = 155.7, 154.6, 138.9, 138.3, 138.0,
3
1
2
29.4, 129.3, 122.6, 121.2, 116.9, 114.5, 74.7, 73.0, 72.1, 58.4, 35.8,
0.8, 18.2.
1
1
37.2, 134.3, 130.6, 130.5, 128.8, 128.7, 128.7, 128.6, 128.3, 128.2,
28.1, 128.0, 128.0, 127.8, 124.3, 117.6, 115.0, 113.6, 105.9, 86.4, 82.1,
HRMS (ESI): m/z [M + Na]+ calcd for C18H18BrN O423Na: 442.0378;
3
79.0, 77.4 (2C), 75.9, 75.6, 75.5, 73.7, 68.0.
found: 442.0383.
HRMS (ESI): m/z [M + Na] calcd for C44H42O723Na: 705.2828; found:
+
705.2826.
Methyl 5-((2R,4S,5S,6R)-5-Acetoxy-4-azido-6-methyltetrahydro-
2
H-pyran-2-yl)-6-hydroxy-2-naphthoate (28)
5
′-((2S,3S,4R,5R,6R)-3,4,5-Trimethoxy-6-(methoxymethyl)tetrahy-
The general procedure for glycosylation of donor 21 with naphthol 10
was followed using azido acetate 21 (193 mg, 0.75 mmol) and naph-
thol 10 (101 mg, 0.5 mmol). The crude product was purified by flash
column chromatography on silica gel (20% EtOAc/hexane) to afford 28
dro-2H-pyran-2-yl)-1,2′-binaphthyl-6′-ol (31)
The general procedure for glycosylation of donor 23 with naphthol 7
was followed using donor 23 (228 mg, 0.6 mmol) and naphthol 7 (135
mg, 0.5 mmol). The crude product was purified by flash column chro-
matography on silica gel (20% EtOAc/hexane) to afford 31 (210 mg,
35
(117 mg, 59%) as a yellow semisolid; [α] +44.6 (c 0.4, CHCl3).
D
35
86%) as a light-brown gum; [α] +69.3 (c 0.5, CHCl3).
D
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

H
Synthesis
S. Chakraborty, D. Mal
Paper
1
13
H NMR (400 MHz, CDCl ): δ = 8.56 (s, 1 H), 8.08 (d, J = 8.9 Hz, 1 H),
C NMR (150 MHz, CDCl ): δ = 163.7, 154.8, 136.2, 133, 130.2, 128.3,
3
3
7
.98–7.82 (m, 4 H), 7.78 (d, J = 8.8 Hz, 1 H), 7.61 (dt, J = 9.7, 3.0 Hz,
H), 7.57–7.46 (m, 3 H), 7.42 (t, J = 7.6 Hz, 1 H), 7.21 (d, J = 8.8 Hz,
H), 5.31 (d, J = 9.7 Hz, 1 H), 3.72–3.60 (m, 8 H), 3.58–3.41 (m, 7 H),
.84 (s, 3 H).
125.5, 121.9, 118.8, 114.5, 88.0, 84.2, 79.0 (2C), 76.8, 70.8, 61.1, 60.8,
60.3, 59.5, 22.5.
1
1
2
HRMS (ESI): m/z [M + H]+ calcd for C21H29O : 377.1964; found:
6
377.1962.
13
C NMR (100 MHz, CDCl ): δ = 154.9, 140.3, 135.5, 134.1, 132.0,
3
1
1
5
30.6, 129.3, 129.1, 128.5, 127.8, 127.4, 126.3, 126.2, 126, 125.7,
22.6, 120.3, 115.0, 88.1, 84.4, 79.1, 79.0, 77.0, 70.8, 61.3, 60.9, 60.6,
9.5.
5
-((2S,3S,4R,5R,6R)-3,4,5-Trimethoxy-6-(methoxymethyl)tetrahy-
dro-2H-pyran-2-yl)-1,3-dihydronaphtho[2,3-c]furan-6-ol (35)
The general procedure for glycosylation of donor 23 with naphthol 20
was followed using donor 23 (228 mg, 0.6 mmol) and naphthol 20 (93
mg, 0.5 mmol). The crude product was purified by flash column chro-
matography on silica gel (25% EtOAc/hexane) to afford 35 (135 mg,
HRMS (ESI): m/z [M + Na] calcd for C30H32O623Na: 511.2097; found:
+
511.2099.
35
7
-Fluoro-1-((2S,3S,4R,5R,6R)-3,4,5-trimethoxy-6-(methoxymeth-
67%) as a yellow semisolid; [α] +43.2 (c 0.3, CHCl ).
D
3
yl)tetrahydro-2H-pyran-2-yl)naphthalen-2-ol (32)
1
H NMR (400 MHz, CDCl ): δ = 8.66 (s, 1 H), 7.83 (s, 1 H), 7.69 (d,
3
The general procedure for glycosylation of donor 23 with naphthol 13
was followed using donor 23 (228 mg, 0.6 mmol) and naphthol 13 (81
mg, 0.5 mmol). The crude product was purified by flash column chro-
matography on silica gel (25% EtOAc/hexane) to afford 32 (175 mg,
J = 8.9 Hz, 1 H), 7.56 (s, 1 H), 7.12 (d, J = 8.8 Hz, 1 H), 5.24–5.16 (m,
5 H), 3.68 (s, 3 H), 3.66 (d, J = 2.9 Hz, 1 H), 3.62 (s, 3 H), 3.56–3.48 (m,
5 H), 3.41 (s, 3 H), 2.74 (s, 3 H).
13
C NMR (100 MHz, CDCl ): δ = 152.2, 139.0, 135.3, 132.6, 130.3,
3
35
92%) as a brown semisolid; [α]
D
+103.5 (c 0.4, CHCl3).
119.9, 119.7, 115.1, 114.2, 113.0, 88.0, 84.2, 78.9, 76.9, 73.3, 72.9,
61.2, 60.9, 60.4, 59.4.
1
H NMR (400 MHz, CDCl ): δ = 8.57 (s, 1 H), 7.70 (dt, J = 8.8, 3.0 Hz,
3
2
1
3
H), 7.60 (d, J = 12.2 Hz, 1 H), 7.12–7.02 (m, 2 H), 5.06 (d, J = 9.6 Hz,
H), 3.68 (s, 3 H), 3.66 (d, J = 2.7 Hz, 1 H), 3.65–3.59 (m, 4 H), 3.54–
.37 (m, 7 H), 2.75 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C22H29O : 405.1913; found:
7
405.1908.
1
3
C NMR (100 MHz, CDCl ): δ = 161.6 (d, J = 242.7 Hz), 155.6, 134
3
C–F
1-((2R,4R,5S,6R)-4,5-Bis(benzyloxy)-6-(benzyloxymethyl)tetrahy-
dro-2H-pyran-2-yl)-7-methylnaphthalen-2-ol (36)
(d, JC–F = 9.4 Hz), 130.7 (d, JC–F = 9.5 Hz), 130.4, 125.9, 119.2 (d, JC–F
=
=
2
2
.7 Hz), 114.7 (d, JC–F = 5.4 Hz), 113.3 (d, JC–F = 24.9 Hz), 107.0 (d, JC–F
3 Hz), 88.0, 84.3, 79.0, 78.9, 77.1, 70.8, 61.2, 60.9, 60.4, 59.5.
The general procedure for glycosylation of donor 24 with naphthol 11
was followed using donor 24 (346 mg, 0.6 mmol) and naphthol 11 (79
mg, 0.5 mmol). The crude product was purified by flash column chro-
matography on silica gel (30% EtOAc/hexane) to afford 36 (195 mg,
HRMS (ESI): m/z [M + H]+ calcd for C20H26FO : 381.1713; found:
3
6
81.1720.
35
6
8%) as an off-white semisolid; [α] +76.8 (c 0.2, CHCl3).
D
7
-Methoxy-1-((2S,3S,4R,5R,6R)-3,4,5-trimethoxy-6-(me-
1
H NMR (400 MHz, CDCl ): δ = 9.03 (s, 1 H), 7.67 (d, J = 7.7 Hz, 2 H),
3
thoxymethyl)tetrahydro-2H-pyran-2-yl)naphthalen-2-ol (33)
7
.40–7.24 (m, 16 H), 7.16 (d, J = 8.3 Hz, 1 H), 7.08 (d, J = 8.9 Hz, 1 H),
5.45 (dd, J = 11.8, 2.2 Hz, 1 H), 4.98 (d, J = 10.9 Hz, 1 H), 4.74–4.44 (m,
5 H), 3.87 (ddd, J = 26.6, 9.2, 3.0 Hz, 3 H), 3.77–3.64 (m, 2 H), 2.52 (s,
3 H), 2.49 (s, 1 H), 2.01 (ddd, J = 16.7, 12.5, 9.7 Hz, 1 H).
13
The general procedure for glycosylation of donor 23 with naphthol 12
was followed using donor 23 (228 mg, 0.6 mmol) and naphthol 12 (87
mg, 0.5 mmol). The crude product was purified by flash column chro-
matography on silica gel (15% EtOAc/hexane) to afford 33 (158 mg,
C NMR (100 MHz, CDCl ): δ = 154.3, 138.6, 138.5, 138.1, 136.6,
3
35
81%) as a yellowish semisolid; [α]
D
+92.5 (c 0.4, CHCl3).
131.1, 129.0, 128.7, 128.6, 128.3, 128.1, 127.9, 125.2, 119.9, 119.4,
114.7, 80.3, 79.1, 77.5, 75.7, 75.4, 73.6, 71.5, 68.2, 36.2, 22.5.
1
H NMR (400 MHz, CDCl ): δ = 7.62 (dd, J = 8.8, 3.5 Hz, 2 H), 7.27 (s,
3
1
3
H), 6.98 (dd, J = 8.8, 3.0 Hz, 2 H), 5.13 (d, J = 9.7 Hz, 1 H), 3.92 (s,
H), 3.68–3.61 (m, 8 H), 3.54–3.40 (m, 4 H), 3.41 (s, 3 H), 2.75 (s, 3 H).
HRMS (ESI): m/z [M+NH4]+ calcd for C38H42NO : 592.3063; found:
5
592.3043.
13
C NMR (150 MHz, CDCl ): δ = 158.3, 155.3, 134.1, 130.1, 129.9,
3
1
6
24.4, 117.4, 114.9, 114.1, 102.8, 87.9, 84.3, 78.9, 77.1, 70.7, 61.0,
0.7, 60.2, 59.4, 55.5.
Acknowledgment
HRMS (ESI): m/z [M + H]+ calcd for C21H29O : 393.1913; found:
7
We gratefully acknowledge the Council of Scientific and Industrial Re-
search (CSIR) for financial support (02(0183)/14/EMRII), and the
Department of Science and Technology for instrumental facilities.
S. C. thanks CSIR and IIT Kharagpur for his research fellowship. We are
also thankful to Dr. S. C. Pan (IIT Guwahati) for HRMS facility.
3
93.1910.
7
-Methyl-1-((2S,3S,4R,5R,6R)-3,4,5-trimethoxy-6-(methoxymeth-
yl)tetrahydro-2H-pyran-2-yl)naphthalen-2-ol (34)
The general procedure for glycosylation of donor 23 with naphthol 11
was followed using donor 23 (228 mg, 0.6 mmol) and naphthol 11 (79
mg, 0.5 mmol). The crude product was purified by flash column chro-
matography on silica gel (20% EtOAc/hexane) to afford 34 (174 mg,
Supporting Information
35
93%) as a white semisolid; [α] +56.2 (c 0.2, CHCl3).
Supporting information for this article is available online at
D
1
https://doi.org/10.1055/s-0036-1591746.
S
u
p
p
o
nrtogI
i
f
rm oaitn
S
u
p
p
ortioIgnfmr oaitn
H NMR (400 MHz, CDCl ): δ = 8.41 (s, 1 H), 7.73 (s, 1 H), 7.68–7.65
3
(m, 1 H), 7.63–7.61 (m, 1 H), 7.14 (d, J = 8.2 Hz, 1 H), 7.09–7.05 (m,
1
3
H), 5.22 (d, J = 9.8 Hz, 1 H), 3.69–3.41 (m, 15 H), 2.72 (s, 3 H), 2.50 (s,
H).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

I
Synthesis
S. Chakraborty, D. Mal
Paper
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I