ring opening-ring closure strategy for the synthesis of aryl-C-glycosides

Article abstract of DOI:10.1021/jo500730y

A new ring-opening-ring closure strategy for the synthesis of aryl-C-glycosides was described. This strategy exploited the nickel-catalyzed regioselective β-O elimination of glycals by reactions with various aryl boronic acids or potassium aryltrifluoroborates to yield the ring-opened products, which underwent the Lewis acid, protonic acid, PhSeCl, or NBS mediated ring closure reactions to afford diverse aryl-C-glycosides. After Lewis acids and protonic acids were screened, it was found that, starting from the ring-opened substrates, the Ph₃PHBr or Sc(OTf)₃ mediated ring closure reaction provided α- or β-preferred aryl-C- Δ^2,3-glycosides, respectively. Furthermore, β-d-phenyl-C-glycosides were successfully prepared via the PhSeCl-mediated cyclization reaction, whereas the α-d-phenyl-C-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by Bu₃SnH/AIBN, the synthesis of 2-deoxy-aryl-C- glycosides was ultimately realized in a stereoselective manner.

Full text of DOI:10.1021/jo500730y

Article
pubs.acs.org/joc
“Ring Opening−Ring Closure” Strategy for the Synthesis of
Aryl‑C‑glycosides
Chen-Fu Liu, De-Cai Xiong, and Xin-Shan Ye*
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No.
38, Beijing 100191, China
S
* Supporting Information
ABSTRACT: A new “ring-opening−ring closure” strategy for
the synthesis of aryl-C-glycosides was described. This strategy
exploited the nickel-catalyzed regioselective β-O elimination of
glycals by reactions with various aryl boronic acids or potassium
aryltrifluoroborates to yield the ring-opened products, which
underwent the Lewis acid, protonic acid, PhSeCl, or NBS
mediated ring closure reactions to afford diverse aryl-C-
glycosides. After Lewis acids and protonic acids were screened,
it was found that, starting from the ring-opened substrates, the
Ph3PHBr or Sc(OTf)3 mediated ring closure reaction provided α-
or β-preferred aryl-C-Δ2,3-glycosides, respectively. Furthermore,
β-D-phenyl-C-glycosides were successfully prepared via the
PhSeCl-mediated cyclization reaction, whereas the α-D-phenyl-
C-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by
Bu3SnH/AIBN, the synthesis of 2-deoxy-aryl-C-glycosides was ultimately realized in a stereoselective manner.
the Pd(OAc)2 catalyzed cross-coupling reaction of peracetylated
glycals with aryl boronic acids yielded the ring-opened
byproduct.12 We envisioned that, by screening proper reaction
conditions, the ring-opened byproduct could probably become
the dominant product. Then the ring-opened product would
stereoselectively cyclize to afford the corresponding aryl-C-
glycosides (Figure 1).
INTRODUCTION
■
As naturally occurring structural units, aryl-C-glycosides are
ubiquitous which exhibit significant biological activities and
pharmacological potentials.1 For example, pluramycin A, an
antitumor and antibacterial antibiotic produced by Streptomyces
pluncolorescens, inhibits protein and nucleic acid syntheses by
intact cells of E. coli B at the concentration innocuous to energy
generation.2 Therefore, considerable efforts have been devoted
to the development of more practical and efficient methods for
the preparation of these kinds of compounds.3 The currently
available methodologies for the synthesis of aryl-C-glycosides
mainly include the following: (1) the electrophilic substitutions
of glycosyl donors toward electron-rich aryl acceptors,4 (2) the
O−C migration of O-glycosides to C-glycosides,5 (3) the
transition-metal-mediated C-glycosylations,6 and (4) the de
novo synthesis of a sugar ring moiety.7 Among these approaches,
the transition-metal-mediated C-glycosylations have attracted
much attention since the reactions are usually completed under
mild conditions in regio- and/or stereospecific manners.8 For
instance, a new access to these compounds by the cross-coupling
reactions of glycosyl bromides with aryl zinc reagents or aryl
Grignard reagents using Ni (0)9 or Co10 as catalysts was reported
recently. Although progress has been made, more efficient
approaches to prepare this type of compounds are still needed.
Herein, we report a new “ring opening−ring closure” strategy for
the preparation of aryl-C-glycosides. This new strategy was
inspired by two aspects. One is the previously reported method
for the synthesis of alkyl-C-glycosides which employed the Wittig
reaction and cyclization sequence,11 and the other is the fact that
Based on our continuous work toward the development of
new methods for aryl-C-glycoside synthesis,13 the first step of the
transition-metal-catalyzed reaction between protected glycals
and aryl metal reagents may involve the insertion of the aryl
transition metal into the CC bond of the glycal affording the
reactive intermediate. As shown in Figure 2, the intermediate
would undergo β-eliminations probably by three routes.13b The
first route carries out 3-β-H elimination to afford the enol ether
type of aryl-C-glycosides; the second route undergoes 3-β-O
elimination to yield aryl-C-Δ2,3-glycosides; the third route
performs 5-β-O elimination to provide the alcohol products. In
fact, the 3-β-H elimination pathway was demonstrated by Liu
and co-workers.14 On the other hand, it was reported that the 5-
β-O elimination product could be avoided by screening solvents
and the 3-β-O elimination product was obtained exclusively.12
Here we want to explore the possibility of the microwave-assisted
nickel-catalyzed regioselective 5-β-O elimination reaction of
perbenzylated glycals with aryl boronic acids or potassium
aryltrifluoroborates, which would be subsequently followed by
Received: March 30, 2014
Published: April 29, 2014
© 2014 American Chemical Society
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Figure 1. Proposed strategy for aryl-C-glycoside synthesis.
a
Table 1. Screening of Optimal Conditions
temp
entry
1
catalyst
base/additive
solvent
(°C)
yield (%)
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
NiCl2
−
BAIB
toluene
MeCN
MeCN
MeCN
MeCN
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
110
100
100
100
100
110
110
110
110
110
110
110
110
110
110
110
110
110
110
170
0
b
Figure 2. Three possible routes for β-eliminations.
2
28% of 4
30% of 5
34% of 6
31% of 7
trace
b
3
BQ
b
4
b
DDQ
Na2S2O8
K3PO4
K3PO4
the Sc(OTf)3, Ph3PHBr, PhSeCl, or NBS mediated cyclization
reaction to yield various aryl-C-glycosides.
5
6
7
NiI2
trace
RESULTS AND DISCUSSION
■
8
Ni(PPh3)2Cl2 K3PO4
0
We began to investigate the reaction of perbenzylated glucal 1a
with phenyl boronic acid 2a. Perbenzylated glucal 1a was chosen
for several reasons. First, compared with the acetyl or benzoyl
protective group, benzyl is an electron-donating group, which
would facilitate the insertion of aryl transition metal species;
second, compared with other electron-donating groups such as
tert-butyldimethylsilyl (TBS) and methyl groups, the benzyl is
more common and the benzene ring might assist the reaction by
chelating with the transition metal center; last but not least, the
benzyl group could be compatible with other functional groups
of aryl units and could be easily removed from the sugar ring
under mild conditions in high yield.
9
Ni(dppe)Cl2
Ni(dppp)Cl2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
K3PO4
K3PO4
K3PO4
K2CO3
Na2CO3
Cs2CO3
NaOH
KOBut
Et3N
0
10
11
12
13
14
15
16
17
0
c
43 (33)
42
40
trace
trace
0
d
30 (0)
b
18
K2CO3/4 Å MS toluene
K2CO3/3 Å MS toluene
K2CO3/4 Å MS toluene
73
56
93
b
19
e
20
Initially, the palladium catalyst was used to check the reaction.
The reaction did not occur until the oxidants were employed
(Table 1, entries 1−5). The results demonstrated that the effect
of oxidants played an important role in the reaction. BAIB as the
oxidant afforded the ring-opened alcohol 4 in 28% yield, whereas
BQ, DDQ, and Na2S2O8 as oxidants provided α-C-glycoside 5 in
30% yield, enone type C-glycoside 6 in 34% yield, and β-C-
glycoside 7 in 31% yield, respectively. Subsequently, the nickel
catalysts were investigated, and fortunately, the ring-opened
product 3aa was obtained exclusively in 43% isolated yield (entry
11) in the presence of Ni(acac)2 and K3PO4 in toluene at 110 °C
under air. When other nickel catalysts were used, almost no
reactions occurred (entries 6−10). Further studies indicated that
the presence of any phosphorus or nitrogen ligands would
destroy the reaction. Bases were examined in order to improve
the reaction efficiency. Among these bases, inorganic bases such
as K2CO3 and Na2CO3 gave comparable results with K3PO4
a
Reaction conditions: 1a (0.05 mmol), 2a (0.1 mmol), catalyst (10%
mmol), base (0.1 mmol), MS (100 mg), and solvent (1.0 mL) for 24
b
c
d
h. Microwave heating for 1 h. Catalyst (1.0 equiv) was used. Et3N
(1.0 mL) was used. Microwave heating for 1.5 h.
e
(entries 12−13), whereas stronger bases such as Cs2CO3,
NaOH, and KOBut resulted in almost no products (entries 14−
16); the organic base such as Et3N gave a lower yield than K3PO4
(entry 17). When the microwave irradiation and molecular sieves
were used, it was observed that the reaction yield was greatly
increased (entries 18−19). The higher temperature led to the
better yield (in 93% yield, entry 20). Therefore, the optimized
reaction conditions are Ni(acac)2 as the catalyst, K2CO3 as the
base, and toluene as the solvent in the presence of 4 Å molecular
sieves under microwave heating for 1.5 h at 170 °C.
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a
Table 2. Reactions with Various Aryl Boronic Acids
a
Reaction conditions: 1a (0.05 mmol), 2 (0.1 mmol), Ni(acac)2 (10% mol), K2CO3 (0.1 mmol), 4 Å MS (100 mg), toluene (1.0 mL), under
b
microwave heating at 170 °C for 1.5 h. Isolated yield.
With the optimal conditions in hand, the scope of aryl boronic
acids was investigated (Table 2). The results showed that the
reaction could be applied to a wide variety of aryl boronic acids,
both electron-donating substituted groups (entries 5−9) and
electron-withdrawing substituted groups (entries 10−12) are
tolerated. Notably, reactions of fluoro-, chloro-, bromo-, and
iodo-substituted phenyl boronic acids with 1a proceeded very
well, providing the desired products 3an, 3ao, and 3ap (entries
13−15), which could be used for further transformations. The
more electron-rich α-naphthaleneboronic acid and β-naph-
thaleneboronic acid also performed smoothly in this trans-
formation, generating products 3ad and 3ae in 84% and 77%
yield, respectively (entries 3, 4). Furthermore, the steric
hindrance of boronic acids did not influence the reaction
efficiency (entries 1, 2).
This nickel catalyzed regioselective β-elimination reaction was
further expanded to a range of substituted glycals (Table 3). The
results indicated that reactions of perbenzylated glycals
proceeded smoothly in good yields. Perbenzylated galactal 1b,
like its glucose counterpart, reacted with phenyl boronic acid
(entry 1), boronic acid containing the electron-donating
substituent (entry 2), and boronic acid containing the
electron-withdrawing substituent (entry 3), affording the
corresponding products 3ba, 3bb, and 3bc in 85%, 70%, and
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a
Table 3. Reactions with Different Glycals
Scheme 1. Reactions of Potassium Aryltrifluoroborates with
Glucal 1a
outcome of the reaction (data not shown). Significantly
improved results were obtained when scandium(III) trifluoro-
methanesulfonate was used, affording aryl-C-Δ2,3-glycosides as a
mixture of α/β anomers with the β-isomer preferred (Table 4).
The α- and β-configurations of aryl-C-Δ2,3-glycosides were
determined on the basis of 1H and 13C NMR analyses.15 On the
other hand, the protonic acids were also examined. The PPh3HBr
gave the optimal results. The use of other protonic acids resulted
in either poor stereoselectivity or a low yield. With the optimal
conditions in hand, the scope of substrates was explored. As
shown in Table 4, it was found that the reaction could be applied
to a wide variety of ring-opened styrene-ol structures. The
electron-rich aryl substituent did not affect the reaction. The
halogen was also tolerated under the reaction conditions (entries
7−8). Catalyzed by Sc(OTf)3, the ring-opened alcohol was
converted smoothly into the Ferrier rearrangement type product
with the α/β ratio ranging from 1:1.1 to 1:5.6 (entries 1−5, 7−8).
Notably, the p-methoxy substituted substrate gave β-aryl-C-Δ2,3-
glycoside in low yield (entry 6). By contrast, the α-anomers were
prepared in a highly stereoselective manner by PPh3HBr
mediated cyclization.16 Exceptions were found when α- or β-
naphthalene was used as the substituent, which afforded a
mixture of α/β anomers (entries 4−5). In addition, the acid-
sensitive group was not compatible with this transformation
(entry 6).
a
Reaction conditions: glycal (0.05 mmol), aryl boronic acid (0.1
mmol), Ni(acac)2 (10% mol), K2CO3 (0.1 mmol), 4 Å MS (100 mg),
toluene (1.0 mL), under microwave heating at 170 °C for 1.5 h.
The formation of aryl-C-Δ2,3-glycoside products could be
attributed to the allyl cation induced by Lewis acids or protonic
acids. Since 2-deoxy-aryl-C-glycoside is a component of some
naturally occurring bioactive compounds, it is in demand to
develop an efficient approach to synthesize these kinds of
compounds. Therefore, following the reported protocol,17 the
PhSeCl-mediated cyclization was successfully applied to the ring-
opened substrates, leading to the formation of β-D-phenyl-C-
glycosides 9a and 9b. The extra phenylselenyl group was finally
removed by Bu3SnH/AIBN in high yield (Scheme 2).18
b
Isolated yield.
76% yield, respectively. Perbenzylated xylal 1c also reacted with
phenyl boronic acid to give the alcohol product 3ca in 76% yield
(entry 4). It is noteworthy that the reaction of 2-substituted
glucals provided different results. The benzyloxy substituted
glucal 1d underwent the reaction smoothly, producing the (Z)-
styrene derivative 3da in 71% yield (entry 5), whereas the
acetoxy substituted glucal 1e did not undergo this reaction (entry
6).
Other aryl metallic compounds such as benzeneboronic acid
pinacol ester, potassium phenyltrifluoroborate, and phenyl tri-n-
butyltin were also examined. It was found that only potassium
phenyltrifluoroborate was able to react with glucal 1a to afford
(E)-styrene derivative 3aa in 61% yield under the optimized
conditions (Scheme 1). Moreover, the reaction of 4-tert-butyl
substituted potassium phenyltrifluoroborate with 1a provided
3aq in 48% yield under the same conditions.
The disclosed method provides a convenient protocol for the
preparation of ω-alkenyl-1-alcohol derivatives from simple and
readily available starting materials by nickel-catalyzed regiose-
lective 5β-O elimination, which results in useful skeleton
structures for further transformations.
Next, the ring-opened products were “closed” to afford C-
glycosides. For this purpose, the Lewis acids were screened. The
use of different Lewis acids had a dramatic impact on the
By contrast, in virtue of the previous reports on NBS-mediated
cyclization, the preparation of α-D-aryl-C-glycoside 11a was also
realized, as exemplified in Scheme 3. Subsequently, the bromine
atom was also removed by Bu3SnH/AIBN in benzene to provide
C-glycoside 12 in high yield.19 Moreover, NIS was also applied to
the cyclization reaction, affording the corresponding α-phenyl-C-
glycoside 11b. It is noteworthy that compounds 11a and 11b are
1
conformationally flexible, which are more stable in the C4
conformation.20 Thus, a new and efficient protocol for the
stereoselective synthesis of 2-deoxy-aryl-C-glycosides was
developed.
CONCLUSION
■
In summary, we have developed an efficient and practical “ring
opening−ring closure” strategy for the preparation of 2-deoxy-
aryl-C-glycosides starting from glycals. The key step involved the
microwave-assisted nickel-catalyzed regioselective 5β-O elimi-
nation of glycals, producing the ring-opened intermediate
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a
Table 4. Sc(OTf)3 or PPh3HBr Mediated Cyclization Reactions
a
Reaction conditions: 3a (0.1 mmol, 1.0 equiv), Sc(OTf)3 (5% mmol) or PPh3HBr (0.5−1.0 equiv), dry CH2Cl2 or ClCH2CH2Cl (0.5 mL), 0 °C.
b
1
Isolated yield, α/β ratio was determined by H NMR analysis of the crude product.
products. These ring-opened products underwent the Lewis acid
or protonic acid mediated cyclization to yield aryl-C-Δ2,3-
glycosides. On the other hand, the ring-opened products were
treated with NBS or PhSeCl to yield the cyclized products α- or
β-2-deoxy-aryl-C-glycosides, respectively. The disclosed ap-
proach may find wide applications in the synthesis of various
aryl-C-glycosides with biological importance.
EXPERIMENTAL SECTION
■
General Methods. All chemicals were purchased as reagent grade
and used without further purification, unless otherwise noted. All
reaction solvents were purified before use. Dichloromethane (CH2Cl2)
was distilled over calcium hydride (CaH2). Toluene was distilled over
sodium. All reactions were carried out under anhydrous conditions with
freshly distilled solvents, unless otherwise noted. Reactions were
monitored by analytical thin-layer chromatography (TLC) on silica
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Scheme 2. Synthetic Approach to 2-Deoxy-β-D-phenyl-glycosides
Scheme 3. Synthetic Approach to 2-Deoxy-α-D-phenyl-C-glycoside
gel 60 F254 precoated on aluminum plates. Spots were detected under
UV (254 nm) and/or by staining with acidic ceric ammonium
molybdate. Solvents were evaporated under reduced pressure and
below 40 °C (bath temperature). Column chromatography was
performed on silica gel (200−300 mesh). 1H NMR spectra were
recorded on a spectrometer at 25 °C. Chemical shifts (in ppm) were
referenced to tetramethylsilane (δ = 0 ppm) in deuterated chloroform. 13
C NMR spectra were obtained by using the same NMR spectrometers
and were calibrated with CDCl3 (δ = 77.00 ppm). High-resolution mass
spectrometry was performed on a spectrometer. The microwave heating
was performed on a dynamic model (Discover SP, CEM; external sensor
type used for measuring reaction mixture temperatures).
70.6, 71.0, 73.4, 74.2, 79.8, 81.1, 125.8, 126.1, 127.68, 127.70, 127.82,
127.86, 127.9, 128.1, 128.3, 128.38, 128.43, 130.3, 131.5, 135.47, 135.54,
137.9, 138.0, 138.1; FT-HRMS (ESI) calcd for C34H36O4Na [M + Na]+:
531.2500, found 531.2515.
(2R,3R,4R,E)-6-((1,1′-Biphenyl)-2-yl)-1,3,4-tris(benzyloxy)-
hex-5-en-2-ol (3ac). Yield 80% (22.8 mg), colorless oil, Rf = 0.65
(petroleum ether/acetone = 2:1), [α]25D −6.4 (c 0.8, CHCl3); 1H NMR
(400 MHz, CDCl3): δ 2.83 (d, 1H, J = 5.2 Hz), 3.57 (d, 2H, J = 4.8 Hz),
3.62 (dd, 1H, J = 4.0, 6.8 Hz), 4.01−4.06 (m, 1H), 4.09 (dd, 1H, J = 3.6,
8.0 Hz), 4.30 (d, 1H, J = 12.0 Hz), 4.47 (s, 2H), 4.57 (d, 1H, J = 11.2
Hz), 4.60 (d, 1H, J = 12.0 Hz), 4.62 (d, 1H, J = 11.2 Hz), 6.25 (dd, 1H, J
= 8.0, 16.0 Hz), 6.60 (d, 1H, J = 16.0 Hz), 7.19−7.39 (m, 23H), 7.53−
7.55 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 70.4, 70.5, 70.9, 73.3,
74.0, 79.7, 80.8, 126.2, 127.1, 127.45, 127.51, 127.64, 127.69, 127.73,
127.8, 128.07, 128.09, 128.1, 128.29, 128.33, 128.4, 129.7, 130.1, 132.9,
134.5, 137.7, 138.0, 138.1, 140.8, 141.0; FT-HRMS (ESI) calcd for
C39H38O4Na [M + Na]+: 593.2662, found 593.2662.
The perbenzyl protected glucal,21 galactal,21 xylal,22 2-acetoxyper-
benzyl glucal,23 2-benzoxyperbenzyl glucal,24 and per tert-butyldime-
thylsilyl glucal13a were prepared according to the previous reports.
General Procedure for Nickel-Catalyzed Reaction of Perben-
zylated Glycals with Aryl Boronic Acids or Potassium
Aryltrifluoroborates. A mixture of perbenzylated glycals (0.05
mmol, 1.0 equiv), aryl boronic acid or potassium aryltrifluoroborate
(0.1 mmol, 2.0 equiv), Ni(acac)2 (0.1 equiv), K2CO3 (2.0 equiv), 4 Å
molecular sieves (100 mg), and dry toluene (1.0 mL) was heated to 170
°C for 1.5 h by microwave irradiation. The solvent was evaporated. Then
the mixture was diluted with CH2Cl2 and washed with distilled water,
and the organic layer was dried over anhydrous Na2SO4 and evaporated
under reduced pressure; the residue was subjected to column
chromatography to afford the pure product.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(naphthalen-1-yl)-hex-
5-en-2-ol (3ad). Yield 84% (22.8 mg), colorless oil, Rf = 0.62
1
(petroleum ether/acetone = 2:1), [α]25 +98.5 (c 0.1, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.85 (d, 1H, J = 5.2 Hz), 3.62−3.69 (m,
2H), 3.75 (dd, 1H, J = 3.6, 6.8 Hz), 4.10−4.15 (m, 1H), 4.40 (dd, 1H, J =
3.6, 7.6 Hz), 4.52−4.54 (m, 3H), 4.62 (d, 1H, J = 11.2 Hz), 4.69 (d, 1H, J
= 11.6 Hz), 4.78 (d, 1H, J = 12.0 Hz), 6.33 (dd, 1H, J = 7.6, 15.6 Hz),
7.21−7.56 (m, 20H), 7.80 (d, 1H, J = 8.0 Hz), 7.85−7.88 (m, 1H),
8.02−8.04 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 70.5, 70.9, 71.0,
73.4, 74.2, 79.9, 81.0, 123.7, 123.9, 125.6, 125.8, 126.1, 127.65, 127.68,
127.8, 127.9, 128.1, 128.2, 128.3, 128.4, 128.5, 129.8, 130.7, 131.1, 133.6,
134.2, 137.9, 138.0, 138.1; FT-HRMS (ESI) calcd for C37H40NO4 [M +
NH4]+: 562.2952, found 562.2960.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-phenyl-hex-5-en-2-ol
(3aa). Yield 93% (23.0 mg) from phenyl boronic acid, yield 61% (15.0
mg) from potassium phenyltrifluoroborate, colorless oil, Rf = 0.65
1
(petroleum ether/acetone = 2:1), [α]25 −13.4 (c 1.5, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.82 (d, 1H, J = 5.6 Hz), 3.60 (dd, 1H, J =
5.2, 10.0 Hz), 3.63 (dd, 1H, J = 4.0, 10.4 Hz), 3.68 (dd, 1H, J = 4.0, 6.8
Hz), 4.04−4.09 (m, 1H), 4.25 (dd, 1H, J = 3.2, 7.6 Hz), 4.40 (d, 1H, J =
11.6 Hz), 4.51 (s, 2H), 4.59 (d, 1H, J = 11.6 Hz), 4.64 (d, 1H, J = 12.0
Hz), 4.68 (d, 1H, J = 12.0 Hz), 6.30 (dd, 1H, J = 8.0, 16.0 Hz), 6.58 (d,
1H, J = 16.0 Hz), 7.24−7.38 (m, 20H); 13C NMR (100 MHz, CDCl3): δ
70.4, 70.6, 70.9, 73.3, 74.2, 79.7, 81.0, 126.6, 127.6, 127.7, 127.8, 127.9,
128.1, 128.1, 128.3, 128.3, 128.4, 128.6, 133.6, 136.4, 137.9, 138.0,
138.1; FT-HRMS (ESI) calcd for C33H34O4Na [M + Na]+: 517.2349,
found 517.2346.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(naphthalen-2-yl)-hex-
5-en-2-ol (3ae). Yield 77% (20.9 mg), colorless oil, Rf = 0.62
1
(petroleum ether/acetone = 2:1), [α]25 −30.0 (c 1.9, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.85 (d, 1H, J = 5.2 Hz), 3.63 (dd, 1H, J =
5.2, 9.6 Hz), 3.66 (dd, 1H, J = 4.0, 10.0 Hz), 3.72 (dd, 1H, J = 3.6, 6.8
Hz), 4.07−4.13 (m, 1H), 4.31 (dd, 1H, J = 4.0, 7.6 Hz), 4.44 (d, 1H, J =
11.6 Hz), 4.51 (s, 2H), 4.61 (d, 1H, J = 11.6 Hz), 4.66 (d, 1H, J = 11.6
Hz), 4.70 (d, 1H, J = 12.0 Hz), 6.41 (dd, 1H, J = 7.6, 16.0 Hz), 6.74 (d,
1H, J = 16.0 Hz), 7.21−7.34 (m, 15H), 7.42−7.48 (m, 2H), 7.56 (dd,
1H, J = 1.2, 4.4 Hz), 7.70 (s, 1H), 7.77−7.81 (m, 3H); 13C NMR (100
MHz, CDCl3): δ 70.5, 70.8, 71.0, 73.4, 74.2, 79.9, 81.1, 123.6, 126.0,
126.3, 126.6, 127.0, 127.6, 127.66, 127.68, 127.8, 128.0, 128.1, 128.15,
128.22, 128.3, 128.36, 128.4, 133.1, 133.5, 133.6, 133.9, 137.9, 138.0,
138.1; FT-HRMS (ESI) calcd for C37H36O4Na [M + Na]+: 567.2500,
found 567.2519.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(o-tolyl)-hex-5-en-2-ol
(3ab). Yield 88% (22.4 mg), colorless oil, Rf = 0.65 (petroleum ether/
1
acetone = 2:1), [α]25 −30.7 (c 0.7, CHCl3); H NMR (400 MHz,
D
CDCl3): δ 2.33 (s, 3H), 2.82 (d, 1H, J = 5.2 Hz), 3.59−3.66 (m, 2H),
3.69 (dd, 1H, J = 3.6, 6.8 Hz), 4.05−4.10 (m, 1H), 4.27 (dd, 1H, J = 3.2,
8.0 Hz), 4.43 (d, 1H, J = 12.0 Hz), 4.51 (s, 2H), 4.59 (d, 1H, J = 11.6
Hz), 4.66 (d, 1H, J = 11.6 Hz), 4.69 (d, 1H, J = 12.0 Hz), 6.18 (dd, 1H, J
= 8.0, 16.0 Hz), 6.80 (d, 1H, J = 16.0 Hz), 7.16−7.19 (m, 3H), 7.23−
7.34 (m, 15H), 7.40 (t, 1H); 13C NMR (100 MHz, CDCl3): δ 19.8, 70.4,
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(3-methoxyphenyl)-
hex-5-en-2-ol (3af). Yield 68% (17.8 mg), colorless oil, Rf = 0.60
1
(petroleum ether/acetone = 2:1), [α]25 +31.0 (c 0.1, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.81 (d, 1H, J = 5.2 Hz), 3.58−3.65 (m,
4681
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2H), 3.68 (dd, 1H, J = 4.0, 6.8 Hz), 3.82 (s, 3H), 4.04−4.09 (m, 1H),
4.25 (dd, 1H, J = 3.6, 7.6 Hz), 4.41 (d, 1H, J = 12.0 Hz), 4.50 (s, 2H),
4.58 (d, 1H, J = 11.6 Hz), 4.64 (d, 1H, J = 12.0 Hz), 4.67 (d, 1H, J = 12.0
Hz), 6.30 (dd, 1H, J = 8.0, 16.0 Hz), 6.56 (d, 1H, J = 16.0 Hz), 6.83 (dd,
1H, J = 2.0, 8.0 Hz), 6.91 (s, 1H), 6.97 (d, 1H, J = 7.6 Hz), 7.23−7.33 (m,
16H); 13C NMR (100 MHz, CDCl3): δ 55.2, 70.4, 70.7, 71.0, 73.4, 74.2,
79.7, 81.0, 111.8, 113.6, 119.3, 126.9, 127.7, 127.8, 127.9, 128.1, 128.3,
128.39, 128.43, 129.6, 133.5, 137.8, 137.9, 138.0, 138.1, 159.8; FT-
HRMS (ESI) calcd for C34H36O5Na [M + Na]+: 547.2450, found
547.2437.
1H, J = 11.6 Hz), 4.67 (d, 1H, J = 12.0 Hz), 6.38 (dd, 1H, J = 7.2, 16.0
Hz), 6.61 (d, 1H, J = 16.0 Hz), 7.22−7.36 (m, 15H), 7.48 (t, 1H, J = 8.0
Hz), 7.60 (d, 1H, J = 7.6 Hz), 8.09−8.11 (m, 1H), 8.16 (t, 1H, J = 2.0
Hz); 13C NMR (100 MHz, CDCl3): δ 70.4, 70.9, 71.3, 73.5, 74.2, 79.2,
80.5, 121.2, 122.3, 127.79, 127.83, 127.92, 128.1, 128.3, 128.4, 128.5,
129.5, 130.4, 130.7, 132.3, 137.6, 137.9, 138.2; FT-HRMS (ESI) calcd
for C33H33NO6Na [M + Na]+: 562.2194, found 562.2187.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(3-(trifluoromethyl)-
phenyl)-hex-5-en-2-ol (3al). Yield 72% (20.2 mg), colorless oil, Rf =
0.63 (petroleum ether/acetone = 2:1), [α]25D −13.2 (c 1.9, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 2.77 (brs, 1H), 3.61−3.64 (m, 2H), 3.68
(dd, 1H, J = 3.6, 7.2 Hz), 4.05 (brs, 1H), 4.27 (dd, 1H, J = 3.6, 7.2 Hz),
4.42 (d, 1H, J = 12.0 Hz), 4.52 (s, 2H), 4.58 (d, 1H, J = 11.6 Hz), 4.61 (d,
1H, J = 12.0 Hz), 4.66 (d, 1H, J = 12.0 Hz), 6.32 (dd, 1H, J = 8.0, 16.0
Hz), 6.58 (d, 1H, J = 16.0 Hz), 7.21−7.32 (m, 15H), 7.43 (t, 1H), 7.50
(t, 2H), 7.56 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 70.4, 70.9, 71.0,
73.4, 74.1, 79.4, 80.7, 124.04 (d, 1C, J = 270.8 Hz), 123.16, 123.19,
123.23, 123.26, 124.21, 124.25, 124.28, 124.32, 127.7, 127.74, 127.79,
127.85, 128.0, 128.2, 128.3, 128.35, 128.4, 128.9, 129.0, 129.6, 130.95 (d,
1C, J = 32.1 Hz), 131.7, 137.2, 137.7, 137.91, 137.93; FT-HRMS (ESI)
calcd for C34H33F3O4Na [M + Na]+: 585.2201, found 585.2204.
Methyl 4-((3R,4R,5R,E)-3,4,6-Tris(benzyloxy)-5-hydroxy-hex-
1-en-1-yl)benzoate (3am). Yield 71% (19.6 mg), colorless oil, Rf =
0.60 (petroleum ether/acetone = 2:1), [α]25D −22.8 (c 0.6, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 2.78 (d, 1H, J = 5.6 Hz), 3.63−3.65 (m,
2H), 3.68 (dd, 1H, J = 3.2, 7.2 Hz), 3.92 (s, 3H), 4.03−4.08 (m, 1H),
4.28 (dd, 1H, J = 3.2, 7.2 Hz), 4.42 (d, 1H, J = 12.0 Hz), 4.51(s, 2H), 4.59
(s, 2H), 4.67 (d, 1H, J = 12.0 Hz), 6.38 (dd, 1H, J = 7.2, 16.0 Hz), 6.61
(d, 1H, J = 16.0 Hz), 7.25−7.35 (m, 15H), 7.38 (d, 2H, J = 8.4 Hz), 7.99
(d, 2H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3): δ 52.1, 70.3, 70.9,
71.0, 73.4, 74.2, 79.4, 80.8, 126.4, 127.73, 127.76, 127.82, 127.87, 128.1,
128.2, 128.32, 128.38, 128.43, 129.2, 129.7, 129.9, 132.2, 137.7, 137.9,
140.8, 166.8; FT-HRMS (ESI) calcd for C35H36O6K [M + K]+:
591.2143, found 591.2139.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(3-chloro-4-fluoro-
phenyl)-hex-5-en-2-ol (3an). Yield 78% (21.3 mg), colorless oil, Rf =
0.65 (petroleum ether/acetone = 2:1), [α]25D −42.6 (c 3.5, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 2.77 (d, 1H, J = 5.2 Hz), 3.60−3.64 (m,
2H), 3.65 (dd, 1H, J = 3.2, 6.8 Hz), 4.01−4.06 (m, 1H), 4.23 (dd, 1H, J =
3.6 Hz, 7.6 Hz), 4.40 (d, 1H, J = 11.6 Hz), 4.52 (s, 2H), 4.57 (d, 1H, J =
11.6 Hz), 4.60 (d, 1H, J = 11.6 Hz), 4.65 (d, 1H, J = 12.0 Hz), 6.16 (dd,
1H, J = 7.6, 16.0 Hz), 6.45 (d, 1H, J = 16.0 Hz), 7.08 (t, 1H, J = 8.4 Hz),
7.14−7.17 (m, 1H), 7.25−7.33 (m, 16H); 13C NMR (100 MHz,
CDCl3): δ 70.4, 70.9, 71.0, 73.4, 74.2, 79.4, 80.7, 116.5, 116.7, 121.1,
121.3, 126.2, 126.3, 127.75, 127.82, 127.84, 127.9, 128.0, 128.1, 128.2,
128.35, 128.40, 128.44, 130.9, 133.0, 133.7, 133.8, 137.7, 138.0, 156.3,
158.8; FT-HRMS (ESI) calcd for C33H32ClFO4Na [M + Na]+:
569.1854, found 569.1848.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(4-methoxyphenyl)-
hex-5-en-2-ol (3ag). Yield 73% (19.1 mg), colorless oil, Rf = 0.60
1
(petroleum ether/acetone = 2:1), [α]25 −17.5 (c 5.8, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.85 (d, 1H, J = 5.2 Hz), 3.62−3.69 (m,
2H), 3.71 (dd, 1H, J = 4.0, 6.8 Hz), 3.86 (s, 3H), 4.08−4.12 (m, 1H),
4.26 (dd, 1H, J = 3.6, 8.0 Hz), 4.43 (d, 1H, J = 12.0 Hz), 4.54 (s, 2H),
4.63 (d, 1H, J = 11.6 Hz), 4.69 (d, 1H, J = 11.6 Hz), 4.71 (d, 1H, J = 12.0
Hz), 6.19 (dd, 1H, J = 8.0, 16.0 Hz), 6.56 (d, 1H, J = 16.0 Hz), 6.91 (d,
2H, J = 8.8 Hz), 7.28−7.38 (m, 17H); 13C NMR (100 MHz, CDCl3): δ
55.3, 70.5 (2 × C), 71.0, 73.4, 74.2, 80.0, 81.1, 114.0, 124.1, 127.65,
127.68, 127.81, 127.83, 128.08, 128.12, 128.3, 128.36, 128.38, 129.2,
133.3, 138.0, 138.1, 138.2, 159.5; FT-HRMS (ESI) calcd for
C34H36O5Na [M + Na]+: 547.2450, found 547.2446.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(2,6-dimethoxyphenyl)-
hex-5-en-2-ol (3ah). Yield 55% (15.2 mg), colorless oil, Rf = 0.58
1
(petroleum ether/acetone = 2:1), [α]25 +14.1 (c 0.3, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.89 (d, 1H, J = 5.2 Hz), 3.60 (dd, 1H, J =
5.6, 10.0 Hz), 3.64 (dd, 1H, J = 3.6, 10.0 Hz), 3.71 (dd, 1H, J = 4.0, 6.8
Hz), 3.82 (s, 6H), 4.07−4.12 (m, 1H), 4.20 (dd, 1H, J = 4.0, 8.4 Hz),
4.43 (d, 1H, J = 12.0 Hz), 4.49 (s, 2H), 4.60 (d, 1H, J = 11.6 Hz), 4.71 (d,
1H, J = 12.0 Hz), 4.78 (d, 1H, J = 11.6 Hz), 6.57 (d, 2H, J = 8.4 Hz), 6.72
(dd, 1H, J = 8.4, 16.0 Hz), 6.92 (d, 1H, J = 16.0 Hz), 7.17 (t, 1H, J = 8.4
Hz), 7.23−7.37 (m, 15H); 13C NMR (100 MHz, CDCl3): δ 55.7, 70.1,
70.6, 71.1, 73.3, 74.3, 81.7, 82.0, 103.9, 113.9, 124.8, 127.4, 127.52,
127.54, 127.8, 128.0, 128.17, 128.23, 128.29, 128.31, 128.4, 130.3, 138.3,
138.4, 138.6, 158.6; FT-HRMS (ESI) calcd for C35H38O6Na [M + Na]+:
577.2561, found 577.2554.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(2,4-dimethoxyphenyl)-
hex-5-en-2-ol (3ai). Yield 67% (18.5 mg), colorless oil, Rf = 0.58
1
(petroleum ether/acetone = 2:1), [α]25 +58.8 (c 0.3, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.88 (d, 1H, J = 5.2 Hz), 3.59 (dd, 1H, J =
5.2, 10.0 Hz), 3.63 (dd, 1H, J = 4.0, 10.0 Hz), 3.68 (dd, 1H, J = 4.0, 6.4
Hz), 3.82 (s, 6H), 4.06−4.09 (m, 1H), 4.22 (dd, 1H, J = 3.6, 8.4 Hz),
4.40 (d, 1H, J = 12.0 Hz), 4.50 (s, 2H), 4.59 (d, 1H, J = 11.2 Hz), 4.67 (d,
1H, J = 12.0 Hz), 4.68 (d, 1H, J = 11.6 Hz), 6.22 (dd, 1H, J = 8.0, 16.0
Hz), 6.45 (d, 1H, J = 2.0 Hz), 6.48 (dd, 1H, J = 2.4, 8.4 Hz), 6.83 (d, 1H,
J = 16.0 Hz), 7.24−7.33 (m, 16H); 13C NMR (100 MHz, CDCl3): δ
55.40, 55.42, 70.3, 70.6, 71.1, 73.3, 74.2, 80.7, 81.4, 98.5, 104.8, 118.6,
124.6, 127.56, 127.6, 127.8, 127.9, 128.1, 128.2, 128.3, 128.7, 138.2,
138.2, 138.4, 158.0, 160.7; FT-HRMS (ESI) calcd for C35H38O6Na [M +
Na]+: 577.2560, found 577.2559.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(4-bromophenyl)-hex-
5-en-2-ol (3ao). Yield 83% (23.7 mg), colorless oil, Rf = 0.65
1
(petroleum ether/acetone = 2:1), [α]25 −57.7 (c 3.6, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.79 (d, 1H, J = 5.2 Hz), 3.61−3.65 (m,
2H), 3.69 (dd, 1H, J = 3.6, 7.2 Hz), 4.04−4.09 (m, 1H), 4.27 (dd, 1H, J =
3.6, 7.6 Hz), 4.43 (d, 1H, J = 12.0 Hz), 4.53 (s, 2H), 4.62 (s, 2H), 4.68 (d,
1H, J = 12.0 Hz), 6.28 (dd, 1H, J = 7.6, 16.0 Hz), 6.53 (d, 1H, J = 16.0
Hz), 7.22 (d, 2H, J = 8.4 Hz), 7.27−7.37 (m, 15H),7.47 (d, 2H, J = 8.4
Hz); 13C NMR (100 MHz, CDCl3): δ 70.4, 70.89, 70.93, 73.4, 74.2,
79.5, 80.8, 127.6, 127.76, 127.82, 127.9, 128.1, 128.2, 128.3, 128.40,
128.44, 131.7, 132.2, 135.3, 137.8, 138.0; FT-HRMS (ESI) calcd for
C33H33BrO4Na [M + Na]+: 595.1449, found 595.1447.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(3-(methylthio)phenyl)-
hex-5-en-2-ol (3aj). Yield 73% (19.7 mg), colorless oil, Rf = 0.60
1
(petroleum ether/acetone = 2:1), [α]25 −11.5 (c 4.0, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 2.49 (s, 3H), 2.79 (d, 1H, J = 5.2 Hz),
3.61−3.63 (m, 2H), 3.67 (dd, 1H, J = 3.6, 6.8 Hz), 4.03−4.07 (m, 1H),
4.25 (dd, 1H, J = 3.6, 7.6 Hz), 4.40 (d, 1H, J = 12.0 Hz), 4.51 (s, 2H),
4.58 (d, 1H, J = 11.6 Hz), 4.62 (d, 1H, J = 11.6 Hz), 4.67 (d, 1H, J = 12.0
Hz), 6.28 (dd, 1H, J = 8.0, 16.0 Hz), 6.53 (d, 1H, J = 16.0 Hz), 7.12−7.17
(m, 2H), 7.24−7.32 (m, 17H); 13C NMR (100 MHz, CDCl3): δ 15.8,
70.4, 70.8, 71.0, 73.4, 74.2, 79.7, 81.0, 123.4, 124.7, 126.0, 127.4, 127.7,
127.8, 127.9, 128.1, 128.2, 128.3, 128.4, 128.43, 129.0, 133.0, 137.0,
137.9, 138.1, 138.9; FT-HRMS (ESI) calcd for C34H36O4SNa [M +
Na]+: 563.2227, found 563.2220.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(4-iodophenyl)-hex-5-
en-2-ol (3ap). Yield 86% (26.6 mg), colorless oil, Rf = 0.65 (petroleum
ether/acetone = 2:1), [α]25D −9.6 (c 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3): δ 2.77 (d, 1H, J = 5.2 Hz), 3.61−3.62 (m, 2H), 3.66 (dd, 1H, J =
3.6, 6.8 Hz), 4.01−4.07 (m, 1H), 4.24 (dd, 1H, J = 3.2, 7.2 Hz), 4.40 (d,
1H, J = 12.0 Hz), 4.51 (s, 2H), 4.59 (s, 2H), 4.65 (d, 1H, J = 12.0 Hz),
6.27 (dd, 1H, J = 7.6, 16.0 Hz), 6.48 (d, 1H, J = 16.0 Hz), 7.06 (d, 2H, J =
8.4 Hz), 7.25−7.34 (m, 15H), 7.64 (d, 2H, J = 8.4 Hz); 13C NMR (100
MHz, CDCl3): δ 70.4, 70.9, 70.93, 73.4, 74.2, 79.5, 80.9, 127.7, 127.8,
127.9, 128.1, 128.2, 128.3, 128.39, 128.43, 132.3, 135.9, 137.6, 137.8,
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(3-nitrophenyl)-hex-5-
en-2-ol (3ak). Yield 63% (16.9 mg), colorless oil, Rf = 0.55 (petroleum
1
ether/acetone = 2:1), [α]25 −28.6 (c 0.3, CHCl3); H NMR (400
D
MHz, CDCl3): δ 2.75 (d, 1H, J = 5.2 Hz), 3.64−3.65 (m, 2H), 3.68 (dd,
1H, J = 3.6, 7.2 Hz), 4.01−4.07 (m, 1H), 4.29 (dd, 1H, J = 3.2, 6.8 Hz),
4.43 (d, 1H, J = 12.0 Hz), 4.53 (s, 2H), 4.57 (d, 1H, J = 11.6 Hz), 4.61 (d,
4682
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137.99, 138.02; FT-HRMS (ESI) calcd for C33H33IO4Na [M + Na]+:
643.1316, found 643.1293.
(2R,3R,4R,E)-1,3,4-Tris(benzyloxy)-6-(4-(tert-butyl)phenyl)-
hex-5-en-2-ol (3aq). Yield 48% (13.2 mg) from potassium 4-tert-
CDCl3): δ 2.30 (d, 1H, J = 6.0 Hz), 3.52 (dd, 1H, J = 5.6, 9.6 Hz), 3.59
(dd, 1H, J = 3.2, 9.6 Hz), 3.81 (dd, 1H, J = 3.2, 7.2 Hz), 4.01−4.04 (m,
1H), 4.27 (d, 1H, J = 2.8 Hz), 4.39 (d, 1H, J = 11.6 Hz), 4.44 (s, 2H),
4.49 (d, 1H, J = 11.2 Hz), 4.68 (d, 1H, J = 11.2 Hz), 4.70 (d, 1H, J = 11.6
Hz), 4.85 (s, 2H), 6.20 (s, 1H), 7.17−7.35 (m, 23H), 7.62 (d, 2H, J = 7.2
Hz); 13C NMR (100 MHz, CDCl3): δ 70.0, 71.1, 71.9, 72.0, 73.3, 74.8,
77.91, 79.7, 113.5, 126.7, 127.6, 127.7, 127.8, 127.9, 128.0, 128.2, 128.3,
128.4, 128.5, 128.6, 128.8, 135.3, 137.3, 137.8, 138.0, 138.1, 152.3; FT-
HRMS (ESI) calcd for C40H44NO5 [M + NH4]+: 618.3214, found
618.3211.
General Procedure for Microwave-Assisted Pd(OAc)2-Cata-
lyzed Reaction of Benzyl Protected Glucal with Phenylboronic
Acid. A mixture of 1a (0.1 mmol), 2a (0.2 mmol), Pd(OAc)2 (0.01
mmol), oxidant (0.2 mmol), and MeCN (1.0 mL) was heated for 1 h at
100 °C under microwave irradiation. The solvent was evaporated. Then
the mixture was subjected to column chromatography to afford the
product.
butylphenyltrifluoroborate, colorless oil, Rf = 0.65 (petroleum ether/
1
acetone = 2:1), [α]25 +50.0 (c 0.1, CHCl3); H NMR (400 MHz,
D
CDCl3): δ 1.33 (s, 9H), 2.81 (d, 1H, J = 5.2 Hz), 3.59 (dd, 1H, J = 5.2,
10.0 Hz), 3.62 (dd, 1H, J = 4.0, 10.0 Hz), 3.67 (dd, 1H, J = 4.0, 6.8 Hz),
4.03−4.09 (m, 1H), 4.23 (dd, 1H, J = 4.0, 8.0 Hz), 4.39 (d, 1H, J = 12.0
Hz), 4.50 (s, 2H), 4.58 (d, 1H, J = 11.6 Hz), 4.66 (d, 1H, J = 11.6 Hz),
4.67 (d, 1H, J = 12.0 Hz), 6.27 (dd, 1H, J = 8.0, 16.0 Hz), 6.57 (d, 1H, J =
16.0 Hz), 7.25−7.38 (m, 19H); 13C NMR (100 MHz, CDCl3): δ 31.3,
34.6, 70.4, 70.5, 71.0, 73.4, 74.3, 79.9, 81.2, 125.5, 125.7, 126.4, 127.67,
127.72, 127.8, 128.1, 128.3, 128.38, 128.41, 133.6, 138.0, 138.1, 138.2,
151.1; FT-HRMS (ESI) calcd for C37H42O4Na [M + Na]+: 573.2975,
found 573.2970.
(2R,3S,4R,E)-1,3,4-Tris(benzyloxy)-6-phenyl-hex-5-en-2-ol
(3ba). Yield 85% (21.0 mg), colorless oil, Rf = 0.65 (petroleum ether/
(4R,5R)-4,6-Bis(benzyloxy)-5-hydroxy-1,1-diphenyl-hexan-3-
1
acetone = 2:1), [α]25 +23.3 (c 0.1, CHCl3); H NMR (400 MHz,
one (4). Yield 28% (13.4 mg), colorless oil, Rf = 0.62 (petroleum ether/
D
1
acetone = 2:1), [α]25 +40.6 (c 0.2, CHCl3); H NMR (400 MHz,
CDCl3): δ 2.84 (d, 1H, J = 6.0 Hz), 3.54 (d, 2H, J = 5.6 Hz), 3.68 (dd,
1H, J = 3.2, 6.0 Hz), 4.10−4.12 (m, 1H), 4.24 (t, 1H, J = 6.8 Hz), 4.42 (d,
1H, J = 11.6 Hz), 4.48 (d, 1H, J = 12.0 Hz), 4.50 (d, 1H, J = 10.4 Hz),
4.53 (d, 1H, J = 11.6 Hz), 4.67 (d, 1H, J = 11.6 Hz), 4.67 (d, 1H, J = 11.2
Hz), 6.22 (dd, 1H, J = 8.0, 16.0 Hz), 6.62 (d, 1H, J = 16.0 Hz), 7.22−7.40
(m, 20H); 13C NMR (100 MHz, CDCl3): δ 69.8, 70.7, 71.0, 73.4, 74.1,
80.2, 80.3, 126.6, 126.9, 127.7, 127.81, 127.84, 127.9, 128.0, 128.30,
128.33, 128.36, 128.41, 128.6, 134.4, 136.3, 137.9, 138.00, 138.03; FT-
HRMS (ESI) calcd for C33H34O4Na [M + Na]+: 517.2344, found
517.2340.
(2R,3S,4R,E)-1,3,4-Tris(benzyloxy)-6-(4-methoxyphenyl)-
hex-5-en-2-ol (3bb). Yield 70% (18.3 mg), colorless oil, Rf = 0.62
(petroleum ether/acetone = 2:1), [α]25D +2.4 (c 0.7, CHCl3); 1H NMR
(400 MHz, CDCl3): δ 2.86 (d, 1H, J = 6.0 Hz), 3.54 (d, 2H, J = 5.6 Hz),
3.67 (dd, 1H, J = 3.2, 6.0 Hz), 3.82 (s, 3H), 4.08−4.13 (m, 1H), 4.21 (t,
1H, J = 6.8 Hz), 4.41 (d, 1H, J = 11.6 Hz), 4.48 (d, 1H, J = 12.0 Hz), 4.50
(d, 1H, J = 9.6 Hz), 4.53 (d, 1H, J = 11.6 Hz), 4.66 (d, 1H, J = 12.0 Hz),
4.68 (d, 1H, J = 11.2 Hz), 6.07 (dd, 1H, J = 8.0, 16.0 Hz), 6.55 (d, 1H, J =
16.0 Hz), 6.87 (d, 2H, J = 8.8 Hz), 7.21−7.33 (m, 17H); 13C NMR (100
MHz, CDCl3): δ 55.3, 69.9, 70.5, 71.1, 73.4, 74.1, 80.37, 80.44, 114.0,
124.6, 127.6, 127.7, 127.77, 127.83, 127.9, 128.32, 128.36, 128.39, 128.4,
129.2, 133.9, 138.0, 138.10, 138.12, 159.5; FT-HRMS (ESI) calcd for
C34H36O5Na [M + Na]+: 547.2450, found 547.2442.
Methyl 4-((3R,4S,5R,E)-3,4,6-Tris(benzyloxy)-5-hydroxy-hex-
1-en-1-yl)benzoate (3bc). Yield 76% (21.0 mg), colorless oil, Rf =
0.60 (petroleum ether/acetone = 2:1), [α]25D +14.0 (c 0.1, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 2.77 (d, 1H, J = 6.4 Hz), 3.51−3.58 (m,
2H), 3.69 (dd, 1H, J = 2.8, 6.0 Hz), 3.92 (s, 3H), 4.07−4.12 (m, 1H),
4.26 (t, 1H, J = 6.8 Hz), 4.44 (d, 1H, J = 11.6 Hz), 4.49 (d, 1H, J = 12.0
Hz), 4.52 (d, 1H, J = 12.0 Hz), 4.53 (d, 1H, J = 12.0 Hz), 4.64 (d, 1H, J =
11.2 Hz), 4.66 (d, 1H, J = 11.6 Hz), 6.32 (dd, 1H, J = 7.6, 16.0 Hz), 6.65
(d, 1H, J = 16.0 Hz), 7.18−7.34 (m, 15H), 7.41 (d, 2H, J = 8.4 Hz), 8.00
(d, 2H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3): δ 52.1, 69.8, 71.1 (2
× C), 73.4, 74.2, 80.0, 80.3, 126.5, 127.73, 127.75, 127.82, 127.88,
127.92, 128.28, 128.37, 128.39, 128.45, 129.3, 129.96, 130.02, 133.00,
137.8, 137.9, 138.0, 140.8, 166.8; FT-HRMS (ESI) calcd for
C35H36O6Na [M + Na]+: 575.2399, found 575.2401.
(2R,3R,E)-2,3-Bis(benzyloxy)-5-phenyl-pent-4-en-1-ol (3ca).
Yield 76% (14.2 mg), colorless oil, Rf = 0.65 (petroleum ether/acetone
= 2:1), [α]25D −31.2 (c 0.4, CHCl3); 1H NMR (400 MHz, CDCl3): δ
2.07 (dd, 1H, J = 5.2, 5.6 Hz), 3.61−3.70 (m, 2H), 3.75−3.80 (m, 1H),
4.18 (t, 1H, J = 6.8 Hz), 4.46 (d, 1H, J = 12.0 Hz), 4.68 (d, 1H, J = 11.6
Hz), 4.70 (d, 1H, J = 12.0 Hz), 4.83 (d, 1H, J = 11.6 Hz), 6.21 (dd, 1H, J
= 8.0, 16.0 Hz), 6.62 (d, 1H, J = 16.0 Hz), 7.26−7.41 (m, 15H); 13C
NMR (100 MHz, CDCl3): δ 62.2, 70.7, 73.5, 81.0, 81.3, 126.0, 126.6,
127.7, 127.80, 127.84, 127.97, 128.0, 128.4, 128.5, 128.6, 134.0, 136.3,
138.2, 138.4; FT-HRMS (ESI) calcd for C25H26O3Na [M + Na]+:
397.1774, found 397.1772.
D
CDCl3): δ 2.42 (d, 1H, J = 6.0 Hz), 3.28 (dd, 1H, J = 7.2, 17.6 Hz), 3.45
(dd, 1H, J = 8.0, 17.6 Hz), 3.49 (d, 2H, J = 4.8 Hz), 3.81 (d, 1H, J = 6.8
Hz), 3.99−4.04 (m, 1H), 4.15 (d, 1H, J = 11.6 Hz), 4.32 (d, 1H, J = 11.6
Hz), 4.41 (d, 1H, J = 11.6 Hz), 4.46 (d, 1H, J = 11.6 Hz), 4.65 (t, 1H, J =
7.2 Hz), 7.15−7.35 (m, 20H); 13C NMR (100 MHz, CDCl3): δ 45.1,
45.3, 70.0, 70.8, 72.8, 73.4, 84.2, 126.4, 127.8, 127.9, 128.0, 128.4, 128.5,
137.1, 137.7, 144.0, 144.1, 208.8; FT-HRMS (ESI) calcd for C32H36NO4
[M+NH4]+: 498.2639, found 498.2636.
(2R,3R,6R)-3-Benzyloxy-2-benzyloxymethyl-6-phenyl-dihy-
dro-2H-pyran-4(3H)-one (7). Yield 31% (12.5 mg), colorless oil, Rf =
0.66 (petroleum ether/acetone = 2:1), [α]25D +87.1 (c 0.1, CHCl3); 1H
NMR (CDCl3, 400 MHz): δ 2.76 (d, 2H, J = 6.8 Hz), 3.83−3.85 (m,
3H), 4.28 (d, 1H, J = 9.6 Hz), 4.50 (d, 1H, J = 11.2 Hz), 4.58 (d, 1H, J =
12.4 Hz), 4.67 (d, 1H, J = 12.4 Hz), 4.68 (t, 1H, J = 7.2 Hz), 4.94 (d, 1H,
J = 11.2 Hz), 7.26−7.38 (m, 15H); 13C NMR (CDCl3, 100 MHz): δ
50.0, 69.2, 73.5, 73.6, 79.4, 79.7, 80.9, 125.7, 127.6, 127.7, 128.0, 128.2,
128.2, 128.4, 128.4, 128.6, 137.4, 138.2, 140.1, 205.7; FT-HRMS (ESI)
calcd for C26H26O4Na [M + Na]+: 425.1723, found 425.1727.
General Procedure for Sc(OTf)3-Catalyzed Cyclization Re-
action (Method A). At 0 °C, the ring-opened alcohol (0.1 mmol, 1.0
equiv) was dissolved in dry CH2Cl2 or ClCH2CH2Cl (0.5 mL). The
Sc(OTf)3 (0.05 equiv) was added as one portion. The mixture was
stirred until the alcohol was consumed which was monitored by TLC.
After the reaction was completed (usually the color of the reaction was
turned gray or dark), the mixture was washed by water and extracted by
CH2Cl2. The combined organic layers were dried, and the solvent was
evaporated. The residue was subjected to column chromatography to
afford the product.
General Procedure for PPh3HBr-Mediated Cyclization Re-
action (Method B). At 0 °C, the ring-opened alcohol (0.1 mmol, 1.0
equiv) was dissolved in dry CH2Cl2 or ClCH2CH2Cl (0.5 mL). The
PPh3HBr (0.5−1.0 equiv) was added as one portion. The mixture was
stirred until the alcohol was consumed which was monitored by TLC.
After the reaction was completed (usually the color of the reaction was
turned yellow), the mixture was washed by water and extracted by
CH2Cl2. The combined organic layers were dried, and the solvent was
evaporated. The residue was subjected to column chromatography to
yield the product.
(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)benzene (8aa). Yield 92% (35.5 mg) by Method A, α:β = 1:3; yield
94% (36.3 mg) by Method B, α only. For α-anomer: colorless oil, Rf =
0.70 (petroleum ether/acetone = 2:1); 1H NMR (400 MHz, CDCl3): δ
3.59−3.63 (m, 1H), 3.67−3.72 (m, 2H), 4.20 (d, 1H, J = 7.2 Hz), 4.46
(d, 1H, J = 12.4 Hz), 4.49 (d, 1H, J = 13.2 Hz), 4.59 (d, 1H, J = 12.8 Hz),
4.62 (d, 1H, J = 12.0 Hz), 5.31 (brs, 1H), 6.10 (brd, 1H, J = 10.4 Hz),
6.14 (brd, 1H, J = 10.4 Hz), 7.25−7.36 (m, 13H), 7.44 (d, 2H, J = 7.6
Hz); 13C NMR (100 MHz, CDCl3): δ 69.1, 70.1, 70.7, 71.1, 73.3, 74.1,
127.1, 127.5, 127.7, 127.8, 127.9, 128.0, 128.28, 128.33, 128.37, 129.6,
138.17, 138.20, 139.5; FT-HRMS (ESI) calcd for C52H52O6Na [2M +
Na]+: 795.3656, found 795.3668. For β-anomer: colorless oil, Rf = 0.71
(2R,3R,4S,Z)-1,3,4,5-Tetrakis(benzyloxy)-6-phenyl-hex-5-en-
2-ol (3da). Yield 71% (21.3 mg), colorless oil, Rf = 0.65 (petroleum
ether/acetone = 2:1), [α]25D +11.5 (c 0.3, CHCl3); 1H NMR (400 MHz,
4683
dx.doi.org/10.1021/jo500730y | J. Org. Chem. 2014, 79, 4676−4686

The Journal of Organic Chemistry
Article
1
(petroleum ether/acetone = 2:1); 1H NMR (400 MHz, CDCl3): δ 3.74
(dd, 1H, J = 5.6, 11.2 Hz), 3.80−3.85 (m, 2H), 4.16 (d, 1H, J = 8.8 Hz),
4.51 (d, 1H, J = 11.2 Hz), 4.60 (d, 2H, J = 10.8 Hz), 4.65 (d, 1H, J = 11.6
Hz), 5.19 (brs, 1H), 5.86 (d, 1H, J = 10.4 Hz), 6.00 (d, 1H, J = 10.4 Hz),
7.23−7.34 (m, 15H); 13C NMR (100 MHz, CDCl3): δ 69.9, 70.5, 71.2,
73.4, 77.4, 77.8, 126.0, 127.1, 127.5, 127.6, 127.8, 127.88, 127.91, 128.3,
128.38, 128.43, 131.7, 138.1, 138.4, 140.8; FT-HRMS (ESI) calcd for
C26H26O3Na [M + Na]+: 409.1769, found 409.1777. The spectroscopic
data of 8aa coincide with the previous reports.15,25
acetone = 2:1); [α]25 +46.7 (c 0.8, CHCl3); H NMR (400 MHz,
D
CDCl3): δ 3.79 (dd, 1H, J = 5.6, 10.8 Hz), 3.88 (dd, 1H, J = 2.0, 10.8
Hz), 4.02 (ddd, 1H, J = 2.0, 5.6, 8.8 Hz), 4.27 (dd, 1H, J = 3.2, 8.8 Hz),
4.56 (d, 1H, J = 11.6 Hz), 4.57 (d, 1H, J = 12.8 Hz), 4.63 (d, 1H, J = 12.4
Hz), 4.70 (d, 1H, J = 11.6 Hz), 5.89 (d, 1H, J = 3.2 Hz), 6.08 (s, 2H),
7.24−7.34 (m, 10H), 7.42−7.50 (m, 3H), 7.59 (d, 1H, J = 6.8 Hz), 7.79
(d, 1H, J = 8.0 Hz), 7.84−7.87 (m, 1H), 8.14−8.16 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ 70.0, 70.7, 71.3, 73.4, 75.0, 78.4, 123.8, 124.9,
125.4, 125.5, 126.0, 126.4, 127.4, 127.7, 127.8, 127.9, 128.3, 128.4, 128.6,
128.7, 130.9, 131.4, 133.9, 136.1, 138.1, 138.5; FT-HRMS (ESI) calcd
for C30H32NO3 [M + NH4]+: 454.2377, found 454.2377.
o-(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)toluene (8ab). Yield 89% (35.6 mg) by Method A, α:β = 1:2.4;
yield 78% (31.2 mg) by Method B, α only. For α-anomer: colorless oil,
2-(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)-naphthalene (8ae). Yield 86% (37.5 mg) by Method A, α:β = 1:3;
yield 76% (33.1 mg) by Method B, α:β = 2.5:1. For α-anomer: colorless
1
Rf = 0.69 (petroleum ether/acetone = 2:1); H NMR (400 MHz,
CDCl3): δ 2.47 (s, 3H), 3.52 (dd, 1H, J = 5.2, 13.6 Hz), 3.60−3.67 (m,
2H), 4.21−4.23 (m, 1H), 4.44 (d, 1H, J = 12.4 Hz), 4.52 (d, 1H, J = 11.6
Hz), 4.54 (d, 1H, J = 12.4 Hz), 4.64 (d, 1H, J = 11.6 Hz), 5.48 (dd, 1H, J
= 2.0, 4.8 Hz), 6.02 (ddd, 1H, J = 1.6, 3.2, 10.4 Hz), 6.20 (dt, 1H, J = 2.0,
10.4 Hz), 7.11−7.15 (m, 1H), 7.19−7.35 (m, 13H); 13C NMR (100
MHz, CDCl3): δ 19.2, 69.1, 70.39, 70.41, 71.2, 71.7, 73.2, 125.2, 127.5,
127.7, 127.8, 127.9, 128.3, 128.4, 128.7, 130.0, 130.7, 136.7, 138.2,
138.3; FT-HRMS (ESI) calcd for C27H32NO3 [M + NH4]+: 418.2377,
found 418.2380. The spectroscopic data coincide with the previous
oil, Rf = 0.69 (petroleum ether/acetone = 2:1); [α]25 −45.8 (c 0.4,
D
CHCl3); 1H NMR (400 MHz, CDCl3): δ 3.61 (dd, 1H, J = 2.4, 10.4 Hz),
3.70 (dd, 1H, J = 4.4, 10.0 Hz), 3.72−3.76 (m, 1H), 4.23 (dd, 1H, J = 2.0,
8.0 Hz), 4.46 (d, 1H, J = 12.0 Hz), 4.51 (d, 1H, J = 11.6 Hz), 4.59 (d, 1H,
J = 12.4 Hz), 4.64 (d, 1H, J = 11.6 Hz), 5.46 (brd, 1H), 6.21 (s, 2H),
7.26−7.31 (m, 10H), 7.45−7.48 (m, 2H), 7.59 (dd, 1H, J = 1.6, 8.4 Hz),
7.79−7.84 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 69.3, 70.3, 70.8,
71.3, 73.3, 74.2, 126.1, 126.3, 126.9, 127.55, 127.58, 127.8, 127.87,
127.94, 128.2, 128.3, 128.4, 129.5, 133.0, 133.1, 137.0, 138.20, 138.24;
FT-HRMS (ESI) calcd for C30H32NO3 [M + NH4]+: 454.2377, found
report.15 For β-anomer: colorless oil, Rf = 0.70 (petroleum ether/
1
acetone = 2:1); [α]25 +91.2 (c 1.6, CHCl3); H NMR (400 MHz,
D
CDCl3): δ 2.39 (s, 3H), 3.74 (dd, 1H, J = 5.6, 10.8 Hz), 3.81−3.88 (m,
2H), 4.17 (d, 1H, J = 8.4 Hz), 4.52 (d, 1H, J = 11.6 Hz), 4.59 (d, 1H, J =
12.0 Hz), 4.64 (d, 1H, J = 10.8 Hz), 4.70 (d, 1H, J = 11.6 Hz), 5.39 (brs,
1H), 5.88 (d, 1H, J = 10.4 Hz), 6.02 (d, 1H, J = 10.4 Hz), 7.13−7.19 (m,
3H), 7.25−7.33 (m, 11H); 13C NMR (100 MHz, CDCl3): δ 19.1, 70.0,
70.6, 71.2, 73.4, 75.0, 78.0, 126.1, 126.2, 127.3, 127.4, 127.66, 127.70,
127.75, 127.81, 127.9, 128.3, 128.4, 130.6, 131.0, 135.9, 138.1, 138.5;
FT-HRMS (ESI) calcd for C27H28NaO3 [M + Na]+: 423.1936, found
423.1925.
454.2373. For β-anomer: colorless oil, Rf = 0.70 (petroleum ether/
1
acetone = 2:1); [α]25 +26.0 (c 0.2, CHCl3); H NMR (400 MHz,
D
CDCl3): δ 3.78 (dd, 1H, J = 5.2, 10.8 Hz), 3.85 (dd, 1H, J = 1.6, 10.8
Hz), 3.90 (ddd, 1H, J = 1.6, 5.6, 8.4 Hz), 4.20−4.23 (m, 1H), 4.55 (d,
1H, J = 11.6 Hz), 4.58 (d, 1H, J = 12.4 Hz), 4.65 (d, 1H, J = 12.4 Hz),
4.69 (d, 1H, J = 11.6 Hz), 5.36 (brs, 1H), 5.93 (dt, 1H, J = 1.6, 10.4 Hz),
6.04 (dt, 1H, J = 3.6, 10.4 Hz), 7.26−7.36 (m, 10H), 7.45−7.47 (m, 3H),
7.81−7.83 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 70.0, 70.6, 71.3,
73.4, 77.6, 77.9, 125.1, 125.9, 126.0, 126.2, 127.5, 127.7, 127.8, 128.0,
128.3, 128.4, 131.6, 133.2, 133.3, 138.1, 138.2, 138.5; FT-HRMS (ESI)
calcd for C30H32NO3 [M + NH4]+: 454.2377, found 454.2375.
2-(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)-1,1′-biphenyl (8ac). Yield 74% (34.2 mg) by Method A, α:β =
1:5.6; yield 71% (32.8 mg) by Method B, α only. For α-anomer:
colorless oil, Rf = 0.69 (petroleum ether/acetone = 2:1); [α]25D −37.4 (c
0.5, CHCl3); 1H NMR (400 MHz, CDCl3): δ 3.57 (dd, 1H, J = 3.2, 10.4
Hz), 3.66 (dd, 1H, J = 4.8, 10.8 Hz), 3.97−4.00 (m, 1H), 4.07−4.09 (m,
1H), 4.48 (d, 1H, J = 12.4 Hz), 4.51 (d, 1H, J = 12.4 Hz), 4.59 (d, 1H, J =
11.6 Hz), 4.68 (d, 1H, J = 11.6 Hz), 5.28−5.29 (m, 1H), 5.83 (ddd, 1H, J
= 2.8, 4.4, 10.4 Hz), 6.10 (dt, 1H, J = 4.4, 10.4 Hz), 7.28−7.41 (m, 16H),
7.49−7.51 (m, 2H), 7.58−7.60 (m, 1H); 13C NMR (100 MHz, CDCl3):
δ 69.3, 70.0, 70.8, 70.9, 71.1, 73.2, 126.4, 127.0, 127.1, 127.5, 127.7,
128.0, 128.1, 128.3, 128.4, 128.9, 129.7, 130.5, 130.7, 135.9, 138.3, 140.8,
143.0; FT-HRMS (ESI) calcd for C32H34NO3 [M + NH4]+: 480.2533,
found 480.2537. For β-anomer: colorless oil, Rf = 0.70 (petroleum
ether/acetone = 2:1), [α]25D +6.8 (c 1.5, CHCl3); 1H NMR (400 MHz,
CDCl3): δ 3.65−3.81 (m, 3H), 4.15 (d, 1H, J = 6.4 Hz), 4.48 (d, 1H, J =
11.6 Hz), 4.54 (d, 1H, J = 12.0 Hz), 4.62 (d, 2H, J = 12.0 Hz), 5.21 (brs,
1H), 5.79 (d, 1H, J = 10.4 Hz), 5.97 (d, 1H, J = 10.4 Hz), 7.22−7.36 (m,
16H), 7.44−7.50 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 70.1, 70.6,
71.0, 73.3, 74.2, 77.8, 126.1, 127.1, 127.5, 127.66, 127.69, 127.74, 128.0,
128.3, 128.4, 129.6, 130.1, 131.9, 137.7, 138.1, 138.5, 140.5, 141.8; FT-
HRMS (ESI) calcd for C32H31O3 [M + H]+: 463.2268, found 463.2276.
1-(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)-naphthalene (8ad). Yield 82% (35.7 mg) by Method A, α:β = 1:2;
yield 76% (33.1 mg) by Method B, α:β = 2:1. For α-anomer: colorless
1-(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)-4-methoxybenzene (8af). Yield 40% (16.6 mg) by Method A. β-
1
Anomer: colorless oil, Rf = 0.68 (petroleum ether/acetone = 2:1); H
NMR (400 MHz, CDCl3): δ 3.72 (dd, 1H, J = 5.6, 11.2 Hz), 3.79−3.84
(m, 2H), 3.80 (s, 3H), 4.12−4.16 (m, 1H), 4.51 (d, 1H, J = 11.2 Hz),
4.56 (d, 1H, J = 12.4 Hz), 4.61 (d, 1H, J = 12.4 Hz), 4.66 (d, 1H, J = 11.6
Hz), 5.14 (brs, 1H), 5.84 (dt, 1H, J = 3.2, 10.0 Hz), 6.00 (dt, 1H, J = 4.0,
10.4 Hz), 6.87 (d, 2H, J = 8.8 Hz), 7.28−7.34 (m, 12H); 13C NMR (100
MHz, CDCl3): δ 55.3, 70.0, 70.6, 71.3, 73.4, 77.3, 77.9, 113.8, 126.0,
127.5, 127.8, 127.8, 127.9, 128.3, 128.4, 128.6, 131.8, 159.4; FT-HRMS
(ESI) calcd for C27H28O4Na [M + Na]+: 439.1874, found 439.1872. The
spectroscopic data coincide with the previous report.15
1-(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)-3-chloro-4-fluorobenzene (8ag). Yield 74% (32.4 mg) by
Method A, α:β = 1:1.1; yield 82% (35.9 mg) by Method B, α only. For α-
anomer: colorless oil, Rf = 0.69 (petroleum ether/acetone = 2:1); [α]25
D
−11.2 (c 0.8, CHCl3); 1H NMR (400 MHz, CDCl3): δ 3.59−3.70 (m,
3H), 4.16 (dd, 1H, J = 2.0, 7.6 Hz), 4.47 (d, 1H, J = 12.0 Hz), 4.49 (d,
1H, J = 11.6 Hz), 4.59 (d, 1H, J = 12.0 Hz), 4.62 (d, 1H, J = 11.6 Hz),
5.24 (brs, 1H), 6.04 (ddd, 1H, J = 1.6, 2.8, 10.4 Hz), 6.16 (dt, 1H, J = 2.0,
10.4 Hz), 7.10 (t, 1H, J = 8.8 Hz), 7.25−7.35 (m, 11H), 7.48 (dd, 1H, J =
2.0, 6.8 Hz); 13C NMR (100 MHz, CDCl3): δ 69.1, 70.0, 70.9, 71.3, 72.8,
73.4, 116.3, 116.5, 120.9, 121.0, 127.6, 127.7, 127.8, 128.0, 128.3, 128.4,
128.6, 130.2, 136.9, 138.0, 138.1, 156.5, 158.9; FT-HRMS (ESI) calcd
for C26H28ClFNO3 [M + NH4]+: 456.1742, found 456.1740. For β-
1
oil, Rf = 0.69 (petroleum ether/acetone = 2:1); H NMR (400 MHz,
CDCl3): δ 3.46−3.50 (m, 1H), 3.62−3.66 (m, 2H), 4.28−4.30 (m, 1H),
4.35 (d, 1H, J = 12.0 Hz), 4.49 (d, 1H, J = 12.0 Hz), 4.53 (d, 1H, J = 11.6
Hz), 4.66 (d, 1H, J = 11.6 Hz), 6.04 (d, 1H, J = 2.4 Hz), 6.17 (ddd, 1H, J
= 3.2, 4.8, 10.4 Hz), 6.28 (dt, 1H, J = 3.6, 10.4 Hz), 7.14−7.16 (m, 2H),
7.21−7.41 (m, 9H), 7.49−7.58 (m, 3H), 7.80−7.88 (m, 2H), 8.39 (d,
1H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3): δ 69.0, 70.5, 70.9, 71.27,
71.32, 73.1, 124.6, 124.8, 125.7, 126.3, 126.9, 127.4, 127.75, 127.79,
128.0, 128.2, 128.4, 128.5, 129.1, 129.7, 132.2, 134.1, 134.3, 138.21,
138.24; FT-HRMS (ESI) calcd for C30H28O3Na [M + Na]+: 459.1931,
found 459.1937. The spectroscopic data coincide with the previous
report.15 For β-anomer: colorless oil, Rf = 0.70 (petroleum ether/
anomer: colorless oil, Rf = 0.70 (petroleum ether/acetone = 2:1); [α]25
D
+7.0 (c 0.7, CHCl3); 1H NMR (400 MHz, CDCl3): δ 3.71 (dd, 1H, J =
5.6, 10.8 Hz), 3.78−3.82 (m, 2H), 4.11−4.14 (m, 1H), 4.50 (d, 1H, J =
11.6 Hz), 4.56 (d, 1H, J = 12.0 Hz), 4.62 (d, 1H, J = 12.0 Hz), 4.65 (d,
1H, J = 11.6 Hz), 5.13 (d, 1H, J = 1.2 Hz), 5.79 (dt, 1H, J = 1.6, 10.4 Hz),
6.02 (dt, 1H, J = 2.0, 10.0 Hz), 7.09 (t, 1H, J = 8.8 Hz), 7.18−7.22 (m,
1H), 7.27−7.34 (m, 10H), 7.40 (dd, 1H, J = 2.0, 7.2 Hz); 13C NMR (100
MHz, CDCl3): δ 69.7, 70.2, 71.4, 73.4, 76.2, 77.8, 116.3, 116.6, 126.8,
126.9, 127.0, 127.6, 127.8, 127.9, 128.0, 128.3, 128.4, 129.5, 130.7, 137.9,
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138.3; FT-HRMS (ESI) calcd for C26H24ClFO3Na [M + Na]+:
461.1281, found 461.1298.
10a (51.0 mg, 93% yield) as a colorless oil: Rf = 0.71 (petroleum ether/
acetone = 2:1); 1H NMR (400 MHz, CDCl3): δ 1.74 (dt, 1H, J = 11.6,
13.2 Hz), 2.39 (ddd, 1H, J = 2.0, 5.2, 13.2 Hz), 3.59 (ddd, 1H, J = 2.4, 4.0,
6.0 Hz), 3.65 (dd, 1H, J = 8.4 Hz, 9.6 Hz), 3.78−3.86 (m, 3H), 4.42 (dd,
1H, J = 1.6, 11.6 Hz), 4.58 (d, 1H, J = 12.4 Hz), 4.63 (d, 1H, J = 10.8 Hz),
4.65 (d, 1H, J = 11.6 Hz), 4.67 (d, 1H, J = 12.4 Hz), 4.72 (d, 1H, J = 11.6
Hz), 4.95 (d, 1H, J = 10.8 Hz), 7.24−7.39 (m, 20H); 13C NMR (100
MHz, CDCl3): δ 39.2, 69.6, 71.4, 73.4, 75.1, 77.5, 78.4, 79.5, 81.2, 125.9,
127.5, 127.6, 127.63, 127.7, 128.0, 128.31, 128.34, 128.4, 138.5, 138.6,
141.5; FT-HRMS (ESI) calcd for C33H34O4Na [M + Na]+: 517.2349,
found 517.2350. The spectroscopic data coincide with the previous
report.26
(2R,3S,4R,6R)-3,4-Bisbenzyloxy-2-benzyloxymethyl-6-
phenyltetrahydropyran (10b). Compound 10b was prepared from
compound 9b as described in the preparation of compound 10a,
yielding 10b (47.3 mg, 87% yield) as a colorless oil: Rf = 0.71 (petroleum
ether/acetone = 2:1); [α]25D +5.8 (c 0.8, CHCl3); 1H NMR (400 MHz,
CDCl3): δ 2.05−2.08 (m, 1H), 2.20−2.29 (m, 1H), 3.64−3.75 (m, 4H),
3.96 (brs, 1H), 4.40 (dd, 1H, J = 2.0, 11.2 Hz), 4.44 (d, 1H, J = 12.0 Hz),
4.49 (d, 1H, J = 11.6 Hz), 4.62 (s, 2H), 4.67 (d, 1H, J = 11.6 Hz), 4.98 (d,
1H, J = 12.0 Hz), 7.22−7.38 (m, 20H); 13C NMR (100 MHz, CDCl3): δ
34.3, 69.4, 70.0, 72.5, 73.5, 74.2, 77.8, 78.2, 78.9, 126.2, 127.2, 127.3,
127.5, 127.6, 127.7, 127.9, 128.1, 128.2, 128.3, 128.4, 138.1, 138.5, 139.2,
141.6; FT-HRMS (ESI) calcd for C33H34O4Na [M + Na]+: 517.2355,
found 517.2358.
1-(4,6-Di-O-benzyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
syl)-4-iodobenzene (8ah). Yield 86% (44.0 mg) by Method A, α:β =
1:4.6; yield 72% (36.9 mg) by Method B, α only. For α-anomer:
colorless oil, Rf = 0.69 (petroleum ether/acetone = 2:1); [α]25D −126.0
1
(c 0.2, CHCl3); H NMR (400 MHz, CDCl3): δ 3.58−3.69 (m, 3H),
4.16 (dd, 1H, J = 2.0, 7.6 Hz), 4.46 (d, 1H, J = 12.0 Hz), 4.48 (d, 1H, J =
11.6 Hz), 4.58 (d, 1H, J = 12.0 Hz), 4.61 (d, 1H, J = 11.6 Hz), 5.23 (brs,
1H), 6.04 (ddd, 1H, J = 1.6, 2.8, 10.4 Hz), 6.14 (dt, 1H, J = 2.0, 10.4 Hz),
7.18 (d, 2H, J = 8.4 Hz), 7.24−7.34 (m, 10H), 7.66 (d, 2H, J = 8.4 Hz);
13C NMR (100 MHz, CDCl3): δ 69.1, 70.0, 70.9, 71.2, 73.3, 73.5, 127.6,
127.79, 127.85, 127.93, 128.3, 128.4, 128.9, 129.95, 137.5, 138.06,
138.12, 139.3; FT-HRMS (ESI) calcd for C26H29NIO3 [M + NH4]+:
530.1187, found 530.1184. For β-anomer: colorless oil, Rf = 0.70
1
(petroleum ether/acetone = 2:1); [α]25 −29.0 (c 0.4, CHCl3); H
D
NMR (400 MHz, CDCl3): δ 3.72 (dd, 1H, J = 5.6, 10.8 Hz), 3.78−3.83
(m, 2H), 4.11−4.15 (m, 1H), 4.51 (d, 1H, J = 11.6 Hz), 4.56 (d, 1H, J =
12.4 Hz), 4.61 (d, 1H, J = 12.4 Hz), 4.65 (d, 1H, J = 11.6 Hz), 5.12 (d,
1H, J = 1.6 Hz), 5.79 (dt, 1H, J = 1.6, 10.4 Hz), 5.99 (dt, 1H, J = 2.0, 10.0
Hz), 7.09 (d, 2H, J = 8.4 Hz), 7.25−7.34 (m, 10H), 7.66 (d, 2H, J = 8.4
Hz); 13C NMR (100 MHz, CDCl3): δ 69.8, 70.3, 71.3, 73.4, 76.8, 77.8,
126.4, 127.5, 127.8, 127.9, 128.3, 128.4, 129.0, 131.0, 137.5, 138.0, 138.4,
140.5; FT-HRMS (ESI) calcd for C52H50I2O6Na [2M + Na]+:
1047.1589, found 1047.1604.
(2R,3R,4S,5S,6R)-3,4-Bis(benzyloxy)-2-(benzyloxymethyl)-5-
bromo-6-phenyltetrahydro-2H-pyran (11a). In a sealed tube, NBS
(0.32 mmol) was added to the solution of compound 3aa (0.31 mmol)
in dry CH2Cl2 (2.5 mL) at room temperature. Then the mixture was
heated to 80 °C for about 12 h (monitored by TLC). After the reaction
was completed, the mixture was washed by distilled water and extracted
by CH2Cl2. The solvent was evaporated, and the residue was subjected
to column chromatography to yield 11a (140.0 mg, 78% yield) as a
colorless oil: Rf = 0.67 (petroleum ether/acetone = 2:1); [α]25D +12.5 (c
0.8, CHCl3); 1H NMR (400 MHz, CDCl3): δ 3.76 (dd, 1H, J = 3.2, 6.4
Hz), 3.78−3.87 (m, 2H), 3.89−3.96 (m, 2H), 4.52 (d, 1H, J = 12.4 Hz),
4.54 (d, 1H, J = 11.2 Hz), 4.63 (d, 1H, J = 12.0 Hz), 4.67 (d, 1H, J = 12.0
Hz), 4.68 (d, 1H, J = 11.2 Hz), 4.71 (d, 1H, J = 12.0 Hz), 4.81 (dd, 1H, J
= 3.2, 5.6 Hz), 5.11 (d, 1H, J = 5.6 Hz), 7.20−7.35 (m, 20H); 13C NMR
(100 MHz, CDCl3): δ 53.6, 68.5, 72.9, 73.3, 73.6, 74.4, 75.0, 76.3, 77.4,
126.8, 127.5, 127.6, 127.7, 127.8, 127.9, 128.07, 128.08, 128.3, 128.4,
128.51, 128.54, 137.6, 137.90, 137.94, 138.3; FT-HRMS (ESI) calcd for
C33H37BrNO4 [M + NH4]+: 590.1901, found 590.1900.
(2R,3R,4S,5S,6R)-3,4-Bis(benzyloxy)-2-(benzyloxymethyl)-5-
iodo-6-phenyltetrahydro-2H-pyran (11b). Compound 11b was
prepared from compound 3aa and NIS at 50 °C as described in the
preparation of compound 11a, yielding 11b (138.4 mg, 72% yield) as a
colorless oil: Rf = 0.67 (petroleum ether/acetone = 2:1); [α]25D +23.6 (c
0.3, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 3.34 (dd, 1H, J = 3.2, 6.0
Hz), 3.77−3.88 (m, 3H), 3.97 (dd, 1H, J = 1.6, 10.4 Hz), 4.52 (d, 1H, J =
12.0 Hz), 4.55 (d, 1H, J = 12.0 Hz), 4.64 (d, 2H, J = 12.0 Hz), 4.68 (d,
1H, J = 11.2 Hz), 4.69 (d, 1H, J = 11.6 Hz), 4.97 (dd, 1H, J = 3.6, 6.0 Hz),
5.13 (d, 1H, J = 6.0 Hz), 7.20−7.40 (m, 20H); 13C NMR (CDCl3, 100
MHz): δ 35.0, 68.5, 72.6, 73.3, 73.5, 74.5, 75.3, 77.3, 77.7, 126.8, 127.5,
127.6, 127.7, 127.8, 127.9, 127.96, 128.03, 128.1, 128.25, 128.32, 128.39,
128.43, 128.49, 128.52, 137.4, 137.9, 138.3, 138.6; FT-HRMS (ESI)
calcd for C33H37NIO4 [M + NH4]+: 638.1762, found 638.1771.
(2R,3R,4R,6S)-3,4-Bisbenzyloxy-2-benzyloxymethyl-6-
phenyltetrahydropyran (12). In a sealed tube, Bu3SnH (0.14 mmol,
2.0 equiv) and a catalytic amount of AIBN (5%−20% equiv) were added
to the solution of compound 11a (40.0 mg, 0.07 mmol, 1.0 equiv) in dry
benzene (0.5 mL) at room temperature. Then the mixture was heated to
80 °C for about 12 h (monitored by TLC). After the reaction was
completed, the mixture was washed by distilled water and extracted by
CH2Cl2. The solvent was evaporated, and the residue was subjected to
column chromatography to give 12 (33.0 mg, 95% yield) as white
semisolids: Rf = 0.72 (petroleum ether/acetone = 2:1); 1H NMR (400
MHz, CDCl3): δ 2.05 (ddd, 1H, J = 4.8, 9.6, 14.4 Hz), 2.57 (dt, 1H, J =
4.0, 13.6 Hz), 3.61 (dd, 1H, J = 4.0, 8.0 Hz), 3.65 (t, 1H, J = 8.0 Hz), 3.71
(ddd, 1H, J = 2.8, 4.0, 9.2 Hz), 3.72 (dd, 1H, J = 2.8, 10.4 Hz), 3.78 (dd,
(2R,3R,4S,5S,6S)-3,4-Bis(benzyloxy)-2-(benzyloxymethyl)-6-
phenyl-5-(phenylselanyl)tetrahydro-2H-pyran (9a). At −78 °C,
compound 3aa (0.31 mmol) was dissolved in dry CH2Cl2 (2.5 mL),
PhSeCl (0.32 mmol) was added, and the mixture was stirred for 4 h.
After the reaction was completed, the mixture was washed by dilute
NaHCO3 (aq) and extracted by CH2Cl2. The solvent was evaporated,
and the residue was subjected to column chromatography to give 9a
(171.0 mg, 85% yield) as a colorless oil: Rf = 0.70 (petroleum ether/
1
acetone = 2:1); [α]25 +7.1 (c 0.8, CHCl3); H NMR (400 MHz,
D
CDCl3): δ 3.26 (t, 1H, J = 11.2 Hz), 3.57 (ddd, 1H, J = 2.0, 4.0, 9.6 Hz),
3.72 (dd, 1H, J = 8.8, 10.8 Hz), 3.72 (dd, 1H, J = 1.6, 11.2 Hz), 3.79 (dd,
1H, J = 4.0, 10.8 Hz), 3.82 (t, 1H, J = 8.8 Hz), 4.38 (d, 1H, J = 11.2 Hz),
4.49 (d, 1H, J = 12.0 Hz), 4.59 (d, 1H, J = 12.0 Hz), 4.67 (d, 1H, J = 10.4
Hz), 4.88 (d, 1H, J = 10.4 Hz), 4.95 (d, 1H, J = 10.4 Hz), 5.09 (d, 1H, J =
10.4 Hz), 6.98 (t, 2H, J = 7.2 Hz), 7.04−7.13 (m, 3H), 7.20−7.33 (m,
18H), 7.39−7.41 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 54.4, 69.1,
73.4, 75.0, 75.9, 79.5, 80.1, 83.8, 84.8, 127.3, 127.4, 127.6, 127.7, 127.89,
127.93, 128.0, 128.1, 128.26, 128.30, 128.4, 128.55, 128.64, 129.0, 134.9,
138.2, 138.3, 138.5, 139.0; FT-HRMS (ESI) calcd for C39H42NO4Se [M
+NH4]+: 668.2274, found 668.2273.
(2R,3S,4S,5S,6S)-3,4-Bis(benzyloxy)-2-(benzyloxymethyl)-6-
phenyl-5-(phenylselanyl)tetrahydro-2H-pyran (9b). Compound
9b was prepared from compound 3ba as described in the preparation of
compound 9a, yielding 9b (177.0 mg, 88% yield) as a colorless oil: Rf =
0.70 (petroleum ether/acetone = 2:1); [α]25D +15.4 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3): δ 3.53 (dd, 1H, J = 4.8, 8.0 Hz), 3.54 (dd, 1H,
J = 2.4, 11.2 Hz), 3.62 (dd, 1H, J = 4.8, 7.6 Hz), 3.66 (dd, 1H, J = 4.8, 7.6
Hz), 3.74 (t, 1H, J = 11.2 Hz), 4.08 (d, 1H, J = 2.4 Hz), 4.38 (d, 1H, J =
11.2 Hz), 4.38 (d, 1H, J = 11.2 Hz), 4.42 (d, 1H, J = 11.6 Hz), 4.61 (d,
1H, J = 11.6 Hz), 4.63 (d, 1H, J = 11.2 Hz), 4.79 (d, 1H, J = 11.6 Hz),
4.95 (d, 1H, J = 11.6 Hz), 7.04 (t, 2H, J = 7.6 Hz), 7.13−7.19 (m, 3H),
7.22−7.36 (m, 18H), 7.43 (d, 2H, J = 6.8 Hz); 13C NMR (100 MHz,
CDCl3): δ 49.9, 68.7, 72.0, 73.0, 73.4, 74.4, 77.1, 81.8, 83.7, 127.3, 127.4,
127.56, 127.65, 127.67, 127.74, 128.0, 128.1, 128.3, 128.4, 128.5, 135.4,
137.8, 138.1, 139.1, 139.5; FT-HRMS (ESI) calcd for C39H39SeO4 [M +
H]+: 651.2012, found 651.2006.
(2R,3R,4R,6R)-3,4-Bisbenzyloxy-2-benzyloxymethyl-6-
phenyltetrahydropyran (10a). In a sealed tube, Bu3SnH (0.22 mmol,
2.0 equiv) and a catalytic amount of AIBN (5%−20% equiv) were added
to the solution of compound 9a (74.0 mg, 0.11 mmol, 1.0 equiv) in dry
benzene (1.0 mL) at room temperature. Then the mixture was heated to
80 °C for about 12 h (monitored by TLC). After the reaction was
completed, the solvent was evaporated and the mixture was washed by
distilled water and extracted by CH2Cl2. After evaporation of the
solvent, the residue was subjected to column chromatography to give
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The Journal of Organic Chemistry
Article
1H, J = 4.4, 10.4 Hz), 4.52 (d, 1H, J = 11.2 Hz), 4.53 (d, 1H, J = 12.0 Hz),
4.65 (d, 1H, J = 12.0 Hz), 4.68 (d, 2H, J = 12.0 Hz), 4.79 (d, 1H, J = 11.2
Hz), 5.12 (t, 1H, J = 4.0 Hz), 7.16−7.36 (m, 20H); 13C NMR (100
MHz, CDCl3): δ 32.4, 69.1, 71.9, 72.0, 73.1, 73.4, 74.2, 77.2, 77.7, 126.4,
127.2, 127.6, 127.6, 127.7, 127.8, 127.9, 127.9, 128.3, 128.4, 128.5, 138.3,
138.4, 138.5, 139.9; FT-HRMS (ESI) calcd for C33H38NO4 [M +
NH4]+: 512.2795, found 512.2798. The spectroscopic data coincide
with the previous report.27
(11) Levy, D. E.; Tang, C. The Chemistry of C-Glycosides; Pergamon,
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ASSOCIATED CONTENT
* Supporting Information
NMR spectra for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
S
(16) Trace amount of β-anomer could be found at elevated reaction
temperature.
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Tetrahedron 2002, 58, 6069−6091.
AUTHOR INFORMATION
Corresponding Author
*E-mail: xinshan@bjmu.edu.cn.
Notes
■
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This work was financially supported by the grants
(2012CB822100, 2013CB910700, 2012ZX09502001-001)
from the Ministry of Science and Technology of China, the
National Natural Science Foundation of China (Grant No.
21232002), and Beijing Higher Education Young Elite Teacher
Project (YETP0063).
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