Selective synthesis of fullerenol derivatives with terminal alkyne and crown ether addends

Article abstract of DOI:10.1021/jo300118h

A series of isomerically pure alkynyl-substituted fullerenol derivatives such as C₆₀(OH)₆(O(CH₂)₃CCH) ₂ were synthesized through Lewis acid catalyzed epoxy ring opening and/or S_N1 replaceme

Full text of DOI:10.1021/jo300118h

Article
pubs.acs.org/joc
Selective Synthesis of Fullerenol Derivatives with Terminal Alkyne
and Crown Ether Addends
Huan Huang,† Gang Zhang,† Sisi Liang,† Nana Xin,† and Liangbing Gan*,†,‡
†Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the
Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, People's Republic of
China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Lu, Shanghai 200032, People's Republic of China
S
* Supporting Information
ABSTRACT: A series of isomerically pure alkynyl-substituted full-
erenol derivatives such as C60(OH)6(O(CH2)3CCH)2 were synthesized
through Lewis acid catalyzed epoxy ring opening and/or SN1
replacement reactions starting from the fullerene−mixed peroxide
C60(O)(t-BuOO)4. Copper-catalyzed azide−alkyne cycloaddition read-
ily converted the terminal alkynyl groups into triazole groups.
Intramolecular oxidative alkyne coupling afforded a fullerenyl crown
ether derivative.
a facile functional group is an alternative method to attach
another functional partner onto the fullerenol cage. To prepare
such a mixed-fullerenol derivative, we have chosen alkynyl
groups as the reactive functional group. Fullerene derivatives
with terminal alkynyl addend(s) have been shown to be very
useful for further functionalization by Click chemistry.11 Here
we report the synthesis of fullerenol derivatives with various
numbers of hydroxyl groups together with one or two terminal
alkynyl groups and further reactions of the alkynyl group.
INTRODUCTION
■
Fullerenols have been a subject of intensive research in
medicine and materials chemistry because of their unique
properties such as free-radical scavenging,1 antioxidizing,2
photosensitizing,3 and electrochemical properties.4 Thus, its
synthesis has attracted much attention and a number of
methods have been developed, including both acidic5 and basic
hydroxylation methods.6 However, all these fullerenols are a
mixture of fullerene derivatives with different number of
hydroxyl groups and different chemical structures. To develop
practical functional materials, in particular for fullerene-based
medicine, the purity and identity of fullerenols are of crucial
importance. Meier and co-workers prepared the simplest
fullerene diols, C60(OH)2 and C70(OH)2, by the reaction of
C60 and C70 with RuO4 followed by acid hydrolysis.7 A mild
and facile process for the preparation of 1,4-fullerenols
C60ArOH was achieved by Wang and co-workers.8 Through
peroxide-mediated fullerene reactions, we have obtained a
variety of closed-cage and open-cage fullerenols with at least
one hydroxyl group and/or hemiketal moiety.9 Recently, we
reported the preparation of the first isomerically pure
multihydroxylated fullerene, C60(OH)8.10
The combination of fullerenol with other functional moieties
could expand possible applications for fullerenols. In the study
of photophysical properties, connecting the fullerene cage to
other chromophores has been proven to be a very successful
strategy to enhance the device performance.11 However,
hydroxyl groups directly bound on the fullerene cage show
reactivity quite different from those in classical organic
molecules, and it is difficult to attach other functional
components onto the fullerenol cage through the fullerenol
OH group. The preparation of fullerenol derivatives containing
RESULTS AND DISCUSSION
■
Synthesis of Fullerenol Derivatives with Alkynyl
Addends. Compound 1 was prepared from C60, as we have
reported previously.12 In the presence of boron trifluoride, the
epoxy group of 1 was opened with terminal alkynyl alcohols to
form compound 2 (Scheme 1). The yields of 2 decreased as the
length of the alcohol increased from 2a to 2c. Other Lewis
acids such as FeCl3 could also catalyze the reaction, but with
lower yields.
To convert the tert-butylperoxo groups in 2 into hydroxyl
groups, we heated it at 110 °C for 12 h (Scheme 1). Addition
of iodine improved the yield in this thermolysis reaction. Iodine
probably reacted with radical species, preventing them from
adding to the fullerene cage. Only two tert-butylperoxo groups
were converted into epoxy groups. The other two remained
unchanged even after prolonged heating. Raising the temper-
ature resulted in slow conversion into a complex mixture of
products. Compounds 3 and 4 are isomers, differing in the
relative locations of the two epoxy groups. Treatment of 3 with
Received: January 15, 2012
Published: February 13, 2012
© 2012 American Chemical Society
2456
dx.doi.org/10.1021/jo300118h | J. Org. Chem. 2012, 77, 2456−2462

The Journal of Organic Chemistry
Article
Scheme 1. Formation of Polyhydroxyl Derivatives
Containing One Alkynyl Substituent
Scheme 2. Silver Perchlorate Mediated Addition of Terminal
Alkynyl Alcohols
Scheme 3. Formation of Polyhydroxyl Derivatives
Containing Two Alkynyl Substituents
CF3SO3H/H2O opened the epoxy groups to form compounds
5 and 6. Compound 6 with one epoxy group remaining is an
intermediate to 5. Further treatment of 6 with CF3SO3H/H2O
could convert 6 into 5. Under the same hydrolysis conditions,
compound 4 gave very low yields of fullerenol derivatives,
indicating that the epoxy group next to the OH group was less
reactive because of steric effects.
Another way of making compound 5 is the silver perchlorate
mediated SN1 reaction of the fullerenol derivative 7 with the
corresponding alcohol (Scheme 2). Compound 7 was prepared
from 1 in four steps as reported before.10 Efforts to reduce the
two tert-butylperoxo groups in 5 were unsuccessful. The silver
perchlorate mediated SN1 reaction could also be applied to the
Cs-symmetric dichloro fullerenol derivative 8 (Scheme 3),
which was prepared from 1 in three steps.10 The resulting
product 9 could be further reduced into compound 10 with six
hydroxyl groups.
Scheme 4. Hydration of Terminal Alkynyl Groups
Hydration, Click Reaction, and Hay Coupling of
Alkynyl Groups in Fullerenols. The fullerenol derivatives
were very stable and could be stored for months with little
change. A sample of 10b was stored for about 1 year with
almost no noticeable decomposition. In an effort to test their
reactivity toward further derivatization, compounds 2b and 9a
were treated with a solution of mercury sulfate (Scheme 4).
The alkynyl group was converted into an acetyl group rapidly
to give 11 and 12, respectively. The result is the same as that
for classical organic alkyne hydration, yielding a ketone not an
aldehyde. Under the hydration conditions, the tert-butylperoxo
and the hydroxyl groups remained unchanged.
2457
dx.doi.org/10.1021/jo300118h | J. Org. Chem. 2012, 77, 2456−2462

The Journal of Organic Chemistry
Article
Copper-catalyzed azide−alkyne cycloaddition (CuAAC) is
the most widely used click reaction to prepare functional
compounds for materials and biological studies. The reaction
has also been successfully employed in the preparation of
functional fullerene derivatives by the groups of Schuster,
Nierengarten, Martin, and others.11 To test the reactivity of the
present alkyne fullerenol derivatives toward click reactions, we
treated 10b with (azidomethyl)benzene (Scheme 5). The bis-
signals in the range 136−150 ppm instead of the expected 25
for Cs symmetry for the 52 sp2 fullerene skeleton carbons, 21 of
which are twice the intensity of the other 10 signals. These
NMR data indicate that rotation of the crown ether moiety is
hindered at room temperature.
Spectroscopic data of compounds 3, 5, and 6 indicate that
they are C1 symmetric. It is not difficult to determine what
functional groups are present in these molecules through the
NMR and HRMS data. However, these data cannot determine
the exact locations of the addends. The structures shown in
Scheme 1 are mainly induced on the basis of correlations with
analogous reaction products reported previously. Mechanistic
considerations support the proposed structures with the alkoxy
group on the outside in compounds 2 and 9.14
Scheme 5. Click and Hay Coupling Reactions
To obtain more conclusive evidence about the structure
assignments, we tried to grow crystals under various conditions.
The long alkyl and glycol chains present in the above
compounds appear to not be suitable for single-crystal
formation. We then prepared the methoxyl derivatives 15−17
from 2d14a through essentially the same reaction sequence as
above (Scheme 6). In the synthesis of 15, the isomer 15a with
a
Scheme 6. Synthesis and X-ray Structure of 17
triazole derivative 13 was obtained in good yield. The addition
should be a stepwise process, but the mono-triazole compound
was not detected.
Another typical reaction for terminal alkyne is the oxidative
coupling of two terminal alkyne groups: i.e. Glaser coupling and
Hay coupling. Various conditions have been developed recently
for cross coupling of terminal alkynes.13 To prepare a crown
ether type product, we tried the intramolecular coupling of 10b
under Hay coupling conditions and obtained compound 14
with a crown size comparable to that of 24-crown-8 (Scheme
5). To avoid intermolecular coupling, the concentration of 10b
was kept at around 1 mg/3 mL in CHCl3, which is relatively
dilute compared to the case for other reactions in the present
work.
Characterization of Alkynyl Fullerenol Derivatives.
Spectroscopic data are in agreement with the structures
depicted in the schemes. Compounds 2, 4, and 9−13 are Cs
symmetric. Their 1H and 13C NMR spectra showed the
expected number of signals. For example, compound 9a
showed three signals at 6.07, 5.64, and 5.55 ppm in a ratio of
1:1:2 corresponding to the four OH groups. Its 13C NMR
spectrum showed 25 signals and 2 signals with half intensity in
the range from 136 to 149 ppm, assignable to the 52 sp2
fullerene skeleton carbons. For compounds 11 and 12, the
a
For clarity hydrogen atoms on the methyl groups are not shown.
the epoxy groups next to each other was also obtained, as in the
thermolysis reaction of compound 2b. Yields of the methoxyl
derivatives were higher than for the corresponding alkynyl
derivatives. Single crystals of 17 were obtained by slow
evaporation of its solution in CS2/hexane/toluene. The X-ray
structure showed that the three methoxyl groups are on the
outside of the central pentagon. Previously we have reported
the single-crystal X-ray structure of an isopropyl analogue of
compound 9.10 It is unlikely that the methyl and isopropyl
carbonyl carbon appears at δ 207.95 and 208.20 ppm in the 13
C
NMR spectra, respectively. Their carbonyl stretching bands
appear at 1718 and 1730 cm−1 as two intense signals on the IR
spectrum.
1H NMR spectrum of the crown ether derivative 14 is broad
at room temperature. Heating the NMR solution to 50 °C
improved the resolution. The six hydroxyl groups appear at
6.41, 5.89, and 5.52 ppm in a ratio of 2:1:2, in agreement with
its Cs symmetry. Its 13C NMR at room temperature showed 31
2458
dx.doi.org/10.1021/jo300118h | J. Org. Chem. 2012, 77, 2456−2462

The Journal of Organic Chemistry
Article
1.47 (s, 18H), 1.44 (s, 18H). 13C NMR (100 MHz, CDCl3; all signals
represent 2C, except as noted): δ 155.39, 150.10, 149.12, 149.00,
148.57, 148.56, 148.43 (1C), 148.39, 148.36, 148.27, 147.67, 147.51
(1C), 147.45, 147.34, 146.96, 145.86, 145.40, 144.96, 144.91, 144.37,
144.35, 143.91, 143.83, 143.33, 142.99, 142.71, 141.33, 138.63, 82.67,
82.43, 82.10 (C(CH3)3), 81.84 (C(CH3)3), 81.04 (1C), 80.91 (1C),
79.65 (1C), 74.56 (1C), 70.65 (1C), 70.56 (1C), 70.50, 69.45 (1C),
69.14 (1C), 58.42 (1C), 26.76 (8C), 26.72 (8C). FT-IR (microscope):
3517, 3305, 2979, 2929, 2871, 1457, 1388, 1364, 1243, 1193, 1099,
derivatives follow a different mechanism from the alkynyl
derivatives. Therefore, structures of all the new compounds
prepared in the present work can be assigned as shown in the
schemes.
In summary, fullerenols containing up to six hydroxyl groups
and one or two terminal alkynyl groups can be effectively
synthesized through Lewis acid catalyzed epoxy ring opening or
SN1 replacement reactions. Terminal alkyne groups in these
fullerenol derivatives exhibit reactivity comparable with that of
classical organic alkynes such as Click reactions and Hay
coupling. Further work will be directed toward attaching
specific designed functional groups to the fullerenol moiety and
exploring their possible applications.
+
1049, 1022, 872, 733 cm−1. ESI-HRMS: C85H56NO13 (M + NH4 )
calcd 1298.3746, found 1298.3766.
Compounds 3 and 4. To a solution of compound 2b (545 mg,
0.463 mmol) in 136 mL of toluene was added I2 (330 mg, 1.30 mmol).
After the mixture was stirred overnight at 110 °C, toluene was
removed under reduced pressure at 40 °C, and the residue was
purified by silica gel column chromatography, giving compound 3
(115 mg, 0.112 mmol, 35%) and compound 4 (161 mg, 0.156 mmol,
25%), both as red solids.
EXPERIMENTAL SECTION
■
All reagents were used as received. Toluene used for the reactions was
distilled from potassium under nitrogen. Dichloromethane (DCM)
was distilled from phosphorus pentoxide. Chloroform was treated with
concentrated H2SO4, washed with water to remove ethanol, and dried
with anhydrous K2CO3. Other solvents were used as received. The
reactions were carried out in air. The NMR spectra were obtained at
25 °C unless noted.
1
Characterization Data of Compound 3. H NMR (400 MHz,
CDCl3): δ 5.34 (s, 1H), 4.35 (q, J = 6.7 Hz, 1H), 4.05 (q, J = 7.0 Hz,
1H), 2.40 (m, 2H), 2.03 (t, J = 6.4 Hz, 2H), 1.96 (s, 1H), 1.52 (s, 9H),
1.50 (s, 9H). 13C NMR (100 MHz, CDCl3; all signals represent 1C,
except as noted): δ 150.56, 149.74, 149.57, 149.52, 148.84, 148.80,
148.77, 148.71, 148.60, 148.50, 148.32, 147.87, 147.83, 147.74, 147.64,
147.61, 147.55, 147.40, 147.25, 147.22, 147.15, 146.99 (2C), 146.67,
146.19, 145.93, 145.60, 145.58, 145.26, 145.14, 144.95, 144.83 (2C),
144.65, 144.58, 144.13, 144.05, 143.92, 143.86 (2C), 143.76, 143.59,
143.33, 143.09, 143.04, 142.84, 142.53, 141.60, 141.39, 140.76, 139.50,
139.25, 84.14, 83.42, 83.37 (C(CH3)3), 82.98, 82.35 (C(CH3)3),
80.21, 78.04, 71.71, 70.51, 69.41, 68.98, 67.69, 66.85, 29.05, 26.79
(3C), 26.65 (3C), 15.36. FT-IR (microscope): 3495, 3308, 2956,
2850, 1464, 1364, 1152, 1057, 853 cm−1. ESI-HRMS: C73H26NaO8 (M
+ Na+) calcd 1053.1520, found 1053.1499.
Caution: A large amount of peroxides is involved in some of the
reactions. Care must be taken to avoid possible explosion.
Compounds 2a−c. To a solution of the alcohol and compound 1
in DCM was added BF3·Et2O at 30 °C in the dark. The reaction was
monitored by TLC, and quenched by water. The organic layer was
dried over anhydrous sodium sulfate, and concentrated in vacuo to
give a crude residue that was purified by silica gel column
chromatography using a gradient of toluene and petroleum ether
(60−90 °C) to yield the desired compounds 2a−c (Table 1).
1
Characterization Data of Compound 4. H NMR (400 MHz,
CDCl3): δ 4.69 (s, 1H), 4.19 (t, J = 6.0, 2H), 2.42 (m, 2H), 2.02 (m,
3H), 1.44 (s, 18H). 13C NMR (100 MHz, CDCl3; all signals represent
2C, except as noted): δ 149.93, 149.64, 148.51, 148.25, 148.21 (1C),
148.01, 147.95, 147.78, 147.64 (1C), 147.34, 147.29, 146.68 (4C),
146.06, 145.98, 145.72, 145.25, 145.24, 144.66, 144.24, 144.12, 144.07,
143.96, 143.52, 142.51, 138.94, 138.32, 87.02 (1C), 83.39, 83.11, 82.09
(C(CH3)3), 78.67 (1C), 74.64 (1C), 69.57 (1C), 69.28 (1C), 65.37,
28.77 (1C), 26.68 (6C), 15.46 (1C). FT-IR (microscope): 3476, 3304,
2976, 2921, 2850, 1725, 1464, 1421, 1387, 1364, 1285, 1262, 1243,
1192, 1175, 1125, 1106, 1061, 1012, 927, 906, 872, 757, 639, 631
cm−1. ESI-HRMS: C73H26NaO8 (M + Na+) calcd 1053.1520, found
1053.1489.
Synthesis of Compounds 5a and 6. A 7.6 μL amount of TfOH
and 7.6 μL of water were added to a solution of compound 3 (76 mg,
0.074 mmol) in 19 mL of CHCl3 at room temperature. After the
mixture was stirred for 20 min, the solution was washed with water and
the organic layer was dried over anhydrous sodium sulfate. Then
CHCl3 was removed under reduced pressure at 35 °C. The residue
was purified by silica gel column chromatography, with toluene/
petroleum ether/ethyl acetate 10/5/2) as eluent, giving compound 5a
(25 mg, 0.023 mmol, 32%) and 6 (44 mg, 0.042 mmol, 56%), both as
red solids.
Table 1
product
1, mg
alcohol, equiv
time
yield, mg (%)
2a
2b
2b
585
1055
158
2
50
2
15 min
30 h
364 (57)
545 (41)
41 (24)
120 h
1
Characterization Data of Compound 2a. H NMR (400 MHz,
CDCl3): δ 4.93 (d, J = 2.4 Hz, 2H), 4.75 (s, 1H), 2.49 (t, J = 2.5 Hz,
1H), 1.48 (s, 18H), 1.46 (s, 18H). 13C NMR (100 MHz, CDCl3; all
signals represent 2C, except as noted): δ 155.83, 149.65, 149.12,
149.02, 148.67, 148.59, 148.46 (1C), 148.39, 148.37, 147.92, 147.68,
147.49 (1C), 147.45, 147.32, 146.95, 145.81, 145.30, 144.94, 144.75,
144.37, 144.33, 144.03, 143.90, 143.33, 142.87, 142.83, 141.21, 138.80,
82.50 (4C-(CH3)3), 82.25, 81.88, 81.19(1C), 80.91 (1C), 80.05 (1C),
75.09 (1C), 58.26 (1C), 26.73 (12C). FT-IR (microscope): 3520,
3292, 2979, 2931, 2868, 2130, 1474, 1456, 1387, 1364, 1243, 1192,
1120, 1099, 1089, 1069, 1059, 1050, 1020, 869 cm−1. ESI-HRMS:
+
C79H44NO10 (M + NH4 ) calcd 1166.2960, found 1166.2939.
Characterization Data of Compound 2b. H NMR (400 MHz,
1
CDCl3): δ 4.68 (s, 1H), 4.31 (t, J = 6.0 Hz, 2H), 2.38 (m, 2H), 2.01 (t,
J = 6.4 Hz, 2 H), 2.01 (t, J = 6.4 Hz, 2 H), 1.99 (s, 1H), 1.48 (s, 9H),
1.44 (s, 9H). 13C NMR (100 MHz, CDCl3; all signals represent 2C,
except as noted): δ 155.52, 150.04, 149.13, 149.00, 148.59 (4C),
148.44 (1C), 148.40, 148.36, 148.34, 147.67, 147.52 (1C), 147.47,
147.35, 146.97, 145.86, 145.32, 144.99, 144.90, 144.38, 144.36, 144.02,
143.87, 143.35, 142.98, 142.71, 141.32, 138.57, 83.53 (1C), 82.66,
82.41, 82.14 (C(CH3)3), 81.85 (C(CH3)3), 81.04 (1C), 80.92 (1C),
68.90 (1C), 68.82 (1C), 29.33 (1C), 26.76 (6C), 26.74 (6C), 15.36
(1C). FT-IR (microscope): 3522, 3307, 2979, 2931, 1473, 1387, 1364,
1243, 1193, 1094, 1070, 1049, 1021, 872, 755, 730 cm−1. ESI-HRMS:
Compound 5a. Another method for the synthesis of 5a was the
same as described for 9a (see below) starting from 4-pentyn-1-ol (92
μL, 1.1 mmol) and 7 (40 mg, 0.039 mmol). Yield of compound 5a: 29
mg (0.027 mmol, 69%, red solid).
1
Characterization Data of Compound 5a. H NMR (400 MHz,
CDCl3): δ 6.50 (s, 1H), 6.12 (s, 1H), 5.74 (s, 1H), 5.56 (s, 2H), 4.13
(t, J = 4.8 Hz, 2H), 2.42 (t, J = 4.8 Hz, 2H), 2.08 (s, 1H), 2.02 (t, J =
6.4 Hz, 2H), 1.41 (s, 9H), 1.40 (s, 9H). 13C NMR (100 MHz, CDCl3;
all signals represent 1C, except as noted): δ 151.19, 148.97, 148.90,
148.86, 148.71, 148.68, 148.65, 148.53 (2C), 148.47, 148.46, 148.33,
148.21, 148.17, 148.12 (4C), 148.09 (4C), 147.77, 147.69, 146.15,
145.87, 145.15, 145.14, 144.54 (2C), 144.47, 144.45, 144.41, 143.87,
143.83, 143.79, 143.66, 143.62, 143.51, 143.24 (2C), 143.00 (2C),
142.76, 142.69, 142.48, 142.40, 142.36, 139.12, 138.84, 137.14, 135.74,
+
C81H48NO10 (M + NH4 ) calcd 1194.3273, found 1194.3260.
Characterization Data of Compound 2c. H NMR (400 MHz,
CDCl3): δ 4.83 (s, 1H), 4.39 (t, J = 6.0 Hz, 2H), 4.22 (d, J = 4.0 Hz,
2H), 3.84 (t, J = 4.0 Hz, 2H), 3.69 (m, 8H), 2.44 (t, J = 4.0 Hz, 1H),
1
2459
dx.doi.org/10.1021/jo300118h | J. Org. Chem. 2012, 77, 2456−2462

The Journal of Organic Chemistry
Article
83.40, 83.22, 82.30 (C-(CH3)3), 82.24 (C-(CH3)3), 82.06, 81.35,
80.80, 80.73, 80.57, 76.05, 74.30, 69.47, 67.83, 28.67, 26.71 (6C),
15.55. FT-IR (microscope): 3403, 3307, 2975, 2926, 1387, 1364, 1192,
143.49, 143.33, 142.93, 142.42, 142.10, 139.55, 136.69, 82.84, 82.10,
81.62 (C(CH3)3), 81.10, 80.59 (1C), 79.72, 74.65, 74.12 (1C), 70.68,
70.67, 70.45, 70.17, 69.06, 68.88, 58.39, 26.69 (6C). FT-IR
(microscope): 3388, 3301, 2973, 2925, 2871, 1458, 1364, 1192,
1091, 1065, 1102, 943, 870, 757, 667 cm−1. ESI-HRMS: C86H52NaO16
(M + Na+) calcd 1363.3148, found 1363.3128.
+
1053, 757 cm−1. ESI-HRMS: C73H34NO10 (M + NH4 ) calcd
1084.2177, found 1084.2158.
Characterization Data of Compound 6. 1H NMR (400 MHz,
CDCl3): δ 6.16 (s, 1H), 5.39 (s, 1H), 5.26 (s, 1H), 4.11 (m, 1H), 3.98
(m, 1H)), 2.38 (m, 2H), 2.02 (s, 1H), 1.98 (t, J = 6.4 Hz, 2H), 1.45 (s,
9H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3; all signals represent
1C, except as noted): δ 150.99, 149.45, 149.42, 149.37, 149.27, 148.82,
148.59, 148.54 (2C), 148.32, 148.28, 148.01, 147.74, 147.61, 147.42,
147.36, 147.15, 147.01, 146.95, 146.91, 146.85, 146.60, 146.31, 146.25,
146.10, 145.71, 145.53, 145.26, 145.09, 144.58, 144.49, 144.18, 143.90,
143.75, 143.47, 143.32, 143.20, 143.04, 142.93, 142.55, 142.04, 141.92,
141.69, 141.64, 142.29, 140.88, 139.87, 139.06, 138.64, 138.38, 136.82,
132.28, 83.28, 83.02, 82.47, 82.05 (C(CH3)3), 81.93 (C(CH3)3),
80.73, 80.31, 75.76, 72.55, 71.42, 69.41, 69.20, 67.86, 28.89, 26.78
(3C), 26.71 (3C), 15.46. FT-IR (microscope): 3373, 3309, 2922,
2851, 1731, 1463, 1388, 1192, 1090, 1056, 912, 871 cm−1. ESI-HRMS:
Compound 9c. The synthesis was carried out as described for 9a,
starting from 8 (150 mg, 0.145 mmol) and 3,6,9,12-tetraoxapentadec-
14-yn-1-ol (2.01 mL, 6.81 mmol) in the presence of anhydrous silver
perchlorate (180 mg, 0.867 mmol). Yield of compound 9c: 25 mg
(0.18 mmol, 12%, red solid).
1
Characterization Data of Compound 9c. H NMR (400 MHz,
CDCl3): δ 6.11 (s, 1H), 5.88 (s, 2H), 5.72 (s, 1H), 3.98 (m, 36H),
2.46 (t, J = 2.4 Hz, 2H), 1.39 (s, 18H). 13C NMR (100 MHz, CDCl3;
all signals represent 2C, except as noted): δ 148.98, 148.91, 148.73
(3C), 148.69, 148.58 (4C), 148.42, 148.24, 148.20, 148.15, 148.09,
147.86 (1C), 146.36, 145.08, 144.77, 144.68, 144.46, 143.71, 143.65,
143.55, 143.38, 142.99, 142.48, 142.18, 139.60, 136.75, 82.94, 82.18,
81.72 (C(CH3)3), 81.18, 80.67 (1C), 79.72 (1C), 74.62, 74.19, 70.76,
70.73, 70.70, 70.66, 70.46, 70.27, 69.16, 68.95, 58.44, 26.75 (6C). FT-
IR (microscope): 3403, 3300, 2975, 2925, 2872, 2114, 1457, 1364,
1216,1192, 1093, 1065, 1037, 944, 870, 756 cm−1. ESI-HRMS:
C90H60NaO18 (M + Na+) calcd 1451.3672, found 1451.3656.
Compound 10a. To a solution of compound 9a (75 mg, 0.066
mmol) and AcOH (398 μL, 6.6 mmol) in CHCl3 (50 mL) was added
SnCl2 (1.285 g, 6.6 mmol) at 50 °C, and the mixture was stirred for 1
h. The solution was washed with water (3 × 150 mL), HCl (1 moL/L,
3 × 150 mL), and then water (3 × 150 mL). Then the organic layer
was dried over anhydrous sodium sulfate and concentrated in vacuo
and the residue was purified by silica gel column chromatography with
CHCl3/CH3OH (100/1) as eluent. Yield of compound 10a: 21 mg
(32%, red solid).
+
C73H32NO9 (M + NH4 ) calcd 1066.2072, found 1066.2046.
Compound 5b. The synthesis was carried out as described for 9a
(see below) starting from 2-[2-(2-propargyloxyethoxy)ethoxy]ethanol
(1124 mg, 5.98 mmol) and 7 (162 mg, 0.159 mmol). Yield of
compound 5b: 131 mg (0.112 mmol, 70%, red solid).
1
Characterization Data of Compound 5b. H NMR (400 MHz,
CDCl3): δ 4.32 (q, J = 16 Hz, 2H), 3.88 (m, 12H), 2.45 (s, 1H), 1.33
(s, 9H), 1.32 (s, 9H). 13C NMR (100 MHz, CDCl3; all signals
represent 1C, except as noted): δ 151.31, 148.95, 148.86, 148.85,
148.71, 148.66, 148.59, 148.55 (4C), 148.54, 148.37, 148.35, 148.26,
148.19, 148.16, 148.14, 148.13, 148.09 (2C), 148.06 (2C), 147.79,
146.22, 146.94, 145.45, 145.11, 144.81, 144.62, 144.48, 144.42, 144.35,
143.79, 143.76 (2C), 143.64, 143.52 (2C), 143.47, 143.40, 143.12,
143.04, 142.83, 142.71, 142.70, 142.23, 141.95, 139.17, 138.95, 137.31,
135.42, 82.87, 82.18 (C(CH3)3), 82.04 (C(CH3)3), 81.69, 81.08,
80.80, 80.49, 79.65, 76.15, 74.98, 70.61, 70.58, 70.16, 69.87, 69.01,
68.70, 58.21, 26.77 (6C). FT-IR (microscope): 3381, 3305, 2976,
2925, 2871, 2855, 1364, 1192, 1111, 1088, 1065, 1055, 756 cm−1. ESI-
HRMS: C77H38NaO13 (M + Na+) calcd 1193.2205, found 1193.2180.
Compound 9a. To a solution of 4-pentyn-1-ol (600 μL, 7.52
mmol) and compound 8 (78 mg, 0.075 mmol) in DCM (16 mL) was
added anhydrous silver perchlorate (94 mg, 0.45 mmol) at 30 °C in
the dark. The mixture was stirred for 1 h. The solution was washed
with water (3 × 50 mL), and the organic layer was dried over
anhydrous sodium sulfate. Then the solution was concentrated in
vacuo and the residue was purified by silica gel column
chromatography with toluene/petroleum ether/ethyl acetate (5/5/1)
as eluent, giving compound 9a (50 mg, 62%) as a red solid.
1
Characterization Data of Compound 10a. H NMR (400 MHz,
(CD3)2SO): δ 3.99 (t, J = 6.0 Hz, 2H), 2.72 (t, J = 2.5 Hz, 1H), 2.31
(m, 2H), 1.88 (m, 2H). 13C NMR (100 MHz, (CD3)2SO; all signals
represent 2C, except as noted): δ 150.93, 149.31, 148.31, 148.26,
148.21, 148.10 (4C), 148.06, 147.85 (4C), 147.80, 147.59, 147.33
(1C), 146.78, 145.12, 144.44, 144.10, 143.71, 143.51, 143.32, 143.30,
142.86, 142.65, 142.55, 142.26, 142.21 (1C), 138.51, 84.22, 83.95
(1C), 82,92, 81.55, 73.86 (1C), 71.69, 71.56, 67.85, 28.90, 14,86. FT-
IR (microscope): 3389, 3301, 2953, 2923, 2851, 1721, 1467, 1377,
+
1130, 1101, 1072, 994 cm−1. ESI-HRMS: C70H24NO8 (M + NH4 )
calcd 1006.1496, found 1006.1474.
Compound 10b. The synthesis was carried out as described for
10a, starting from SnCl2 (2.0 g, 10.5 mmol) and 9b (146 mg, 0.109
mmol). Yield of compound 10b: 57 mg (0.048 mmol, 45%, red solid).
1
Characterization Data of Compound 10b. H NMR (400 MHz,
1
Characterization Data of Compound 9a. H NMR (400 MHz,
CDCl3): δ 4.31 (d, J = 2.4 Hz, 4H), 3.99 (m, 24H), 2.52 (t, J = 2.4 Hz,
2H). 13C NMR (100 MHz, CDCl3; all signals represent 2C, except as
noted): δ 149.71, 148.91, 148.84 (1C), 148.80, 148.65, 148.62, 148.51
(4C), 148.24, 148.22, 148.10, 148.06, 147.73 (1C), 146.87, 144.78,
144.76, 144.70, 144.47, 144.11, 143.88, 143.39, 143.24, 142.44, 142.33,
142.22, 141.26, 136.36, 83.60, 82.87, 81.37, 79.79, 74.86 (1C), 74.82
(1C), 74.74 (1C), 72.36, 70.83, 70.58, 70.51, 70.07, 69.15, 68.95,
58.50. FT-IR (microscope): 3383, 3298, 2924, 2872, 1458, 1362, 1088,
CDCl3): δ 6.07 (s, 1H), 5.64 (s, 1H), 5.55 (s, 2H), 4.09 (q, J = 4.0 Hz,
4H), 2.42 (m, J = 2.4 Hz, 4H), 2.05 (s, 2H), 2.02 (m, J = 2.5 Hz, 4H),
1.41 (s, 18H). 13C NMR (100 MHz, CDCl3; all signals represent 2C,
except as noted): δ 148.92, 148.83, 148.72, 148.70 (1C), 148.60,
148.59, 148.52, 148.22, 148.15 (4C), 148.10, 147.99, 147.79 (1C),
146.18, 145.03, 144.61, 144.57, 144.46, 143.81, 143.74, 143.43, 143.24,
142.81, 142.53, 142.24, 139.23, 136.58, 83.49, 83.33, 82.16 (C-
(CH3)3), 81.99, 81.08, 80.64 (1C), 74.09 (1C), 69.20, 67.78, 28.81,
26.66 (6C), 15.52. FT-IR (microscope): 3423, 3304, 2976, 2928,
1387, 1364, 1243, 1217, 1192, 1160, 1059, 756 cm−1. ESI-HRMS:
+
1068, 940, 923, 667 cm−1. ESI-HRMS: C78H40NO14 (M + NH4 )
calcd 1214.2443, found 1214.2461.
Compound 11. To a solution of compound 2b (255 mg, 0.217
mmol) and HgSO4 (95 mg, 0.32 mmol) in toluene (26 mL) was
added 10% H2SO4 (26 mL, 0.65 mmol) at 50 °C, and the mixture was
stirred for 4 h. The solution was washed with water (3 × 150 mL).
Then the organic layer was dried over anhydrous sodium sulfate and
concentrated in vacuo and the residue was purified by silica gel column
chromatography with toluene/petrol oil/ethyl acetate (20/10/1) as
eluent. Yield of compound 11: 183 mg (0.153 mmol, 71%, red solid).
+
C78H40NO10 (M + NH4 ) calcd 1150.2647, found 1150.2620.
Compound 9b. The synthesis was carried out as described for 9a,
starting from
8 (191 mg, 0.184 mmol) and 2-[2-(2-
propargyloxyethoxy)ethoxy]ethanol (1.98 mL, 11.1 mmol) in the
presence of anhydrous silver perchlorate (229 mg, 1.10 mmol). Yield
of compound 9b: 191 mg (0.143 mmol, 77%, red solid).
1
Characterization Data of Compound 9b. H NMR (400 MHz,
1
CDCl3): δ 6.13 (s, 1H), 5.87 (s, 2H), 5.72 (s, 1H), 4.02 (m, 28H),
2.49 (t, J = 2.4 Hz, 2H), 1.39 (s, 18H). 13C NMR (100 MHz, CDCl3;
all signals represent 2C, except as noted): δ 148.95, 148.84, 148.66
(3C), 148.62, 148.51 (4C), 148.38, 148.17, 148.13, 148.08, 148.02,
147.80 (1C), 146.31, 145.02, 144.72, 144.62, 144.39, 143.64, 143.58,
Characterization Data of Compound 11. H NMR (400 MHz,
CDCl3): δ 4.66 (s, 1H), 4.21 (t, J = 6.4 Hz, 2H), 2.63 (t, J = 7.2 Hz,
2H), 2.16 (s, 3H), 2.05 (m, 2H), 1.48 (s, 18H), 1.44 (s, 18H). 13C
NMR (100 MHz, CDCl3; all signals represent 2C, except as noted): δ
207.95 (CO, 1C), 155.39, 149.95, 149.07, 148.94, 148.52, 148.50,
2460
dx.doi.org/10.1021/jo300118h | J. Org. Chem. 2012, 77, 2456−2462

The Journal of Organic Chemistry
Article
148.37 (1C), 148.34, 148.29, 148.18, 147.60, 147.44 (1C), 147.39,
147.28, 146.91, 145.79, 145.17,144.92, 144.82, 144.33, 144.27, 143.98,
143.81, 143.30, 142.92, 142.66, 141.24, 138.48, 82.58, 82.35, 82.08
(C(CH3)3), 81.81 (C(CH3)3), 80.87 (1C), 80.85 (1C), 69.28 (1C),
40.07 (1C), 30.06 (1C), 26.72 (6C), 26.70 (6C), 24.24 (1C). FT-IR
(microscope): 3520, 2978, 2930, 1718, 1473, 1364, 1242, 1193, 1146,
1098, 1071, 1049, 1021, 871, 755 cm−1. ESI-HRMS: C81H46NaO11 (M
+ Na+) calcd 1217.2932, found 1217.2926.
995, 908, 731 cm−1. ESI-HRMS: C78H34NaO14 (M + Na+) calcd
1217.1841, found 1217.1813.
Compound 15. The synthesis was carried out as described for 3
and 4, starting from 2d (C60(OH)(OCH3)(OOtBu)4; 574 mg, 0.511
mmol) and I2 (366 mg, 1.44 mmol). Yields: compound 15a, 197 mg
(0.202 mmol, 44%); unconverted starting material 2d, 57 mg; 15, 140
mg (0.143 mmol, 31%).
Characterization Data of Compound 15a. The structure of 15a is
1
Compound 12. The synthesis was carried out as described for 11
,starting from HgSO4 (95 mg, 0.32 mmol) and 9a (121 mg, 0.107
mmol) in the presence of 10% H2SO4 (12 mL, 0.64 mmol). Yield of
compound 12: 81 mg (0.069 mmol, 65%).
analogous to that of compound 3. H NMR (400 MHz, CDCl3): δ
5.35 (s, 1H), 3.91 (s, 3H), 1.52 (s, 9H), 1.49 (s, 9H). 13C NMR (100
MHz, CDCl3; all signals represent 1C, except as noted): δ 150.52,
149.75, 149.61, 149.57, 148.86, 148.81, 148.60, 148.53, 148.34, 148.24
(2C), 147.89, 147.85, 147.75, 147.65, 147.63, 147.55, 147.41, 147.29,
147.24, 147.17, 147.02 (2C), 146.67, 146.20, 145.95, 145.68, 145.59,
145.28, 145.17, 144.94 (2C), 144.85, 144.61, 144.56, 144.17, 144.00,
143.97, 143.88 (2C), 143.73, 143.61, 143.38, 143.06, 143.00, 142.86,
142.54, 141.62, 141.42, 140.80, 139.86, 139.48, 84.83, 83.26, 82.99,
82.37, 80.28, 78.03, 71.75, 70.53, 67.69, 66.88, 57.99, 26.72 (3C),
26.65 (3C). FT-IR (microscope): 3498, 2980, 2930, 2829, 1456, 1388,
1364, 1191, 1083, 1058, 1019, 950, 928, 853, 755 cm−1. ESI-HRMS:
C69H23O8 (M + H+) calcd 979.1387, found 979.1388.
1
Characterization Data of Compound 12. H NMR (400 MHz,
CDCl3): δ 6.02 (s, 1H), 5.62 (s, 1H), 5.48 (s, 2H), 4.01 (m, 4H), 2.66
(m, 4H), 2.20 (s, 6H), 2.07 (m, 4H), 1.41 (s, 18H). 13C NMR (100
MHz, CDCl3; all signals represent 2C, except as noted): δ 208.20,
148.88, 148.71, 148.68 (3C), 148.56 (4C), 148.48, 148.18, 148.11
(4C), 148.05, 147.94, 147.74 (1C), 146.11, 144.93, 144.57, 144.53,
144.42, 143.78, 143.73, 143.30, 143.20, 142.77, 142.49, 142.19, 139.20,
136.55, 83.29, 82.14 (C(CH3)3), 81.91, 81.01, 80.60 (1C), 74.04 (1C),
68.24, 40.09, 30.10, 26.64 (6C), 23.93. FT-IR (microscope): 3420,
2976, 2928, 1715, 1471, 1364, 1242, 1191, 1163, 1106, 1059, 1021,
925, 866, 754 cm−1. ESI-HRMS: C78H40NaO12 (M + Na+) calcd
1191.2412, found 1191.2378.
1
Characterization Data of Compound 15. H NMR (400 MHz,
CDCl3): δ 4.73 (s, 1H), 3.89 (s, 3H), 1.44 (s, 18H). 13C NMR (100
MHz, CDCl3; all signals represent 2C, except as noted): δ 149.68,
149.45, 148.53, 148.29, 148.25 (1C), 148.05, 147.98, 147.83, 147.68
(1C), 147.38, 147.31, 146.71 (4C), 146.08, 146.00, 145.79, 145.27,
144.70, 144.32, 144.28, 144.15 (4C), 143.92, 143.56, 142.53, 138.94,
138.62, 87.28, 83.15, 82.15, 78.64 (1C), 74.64 (1C), 65.40, 58.14
(1C), 26.68 (6C). FT-IR (microscope): 3483, 2979, 2930, 2829, 1457,
1420, 1387, 1364, 1192, 1124, 1083, 1062, 1012, 982, 923, 903, 872,
756 cm−1. ESI-HRMS: C69H22NaO8 (M + Na+) calcd 1001.1207,
found 1001.1209.
Compound 13. Copper sulfate (23 mg, 0.096 mmol) and sodium
ascorbate (38 mg, 0.19 mmol) were added to a solution of compound
10b (57 mg, 0.048 mmol) and 63 mg of benzyl azide (63 mg, 0.48
mmol) in a mixture of CHCl3 and water (1/1) at 60 °C. After the
mixture was stirred for 3 h, the organic layer was abstracted and dried
over anhydrous sodium sulfate. CHCl3 was removed under reduced
pressure at 35 °C, and the residue was purified by silica gel column
chromatography with CHCl3/CH3OH (40/1) as eluent. Yield of
compound 13: 43 mg (0.029 mmol, 62%, red solid).
Compound 16. Aluminum chloride (202 mg, 1.52 mmol) was
added to a solution of compound 15 (186 mg, 0.190 mmol) and 1.8
mL of MeOH in 60 mL of CHCl3 and 6 mL of THF at 30 °C. After
the mixture was stirred for 24 h, the solution was quenched with 2 mL
of HCl and washed with water. Then the organic layer was dried over
anhydrous sodium sulfate. CHCl3 was removed under reduced
pressure at 35 °C, and the residue was purified by silica gel column
chromatography with toluene/petroleum ether/ethyl acetate (8/4/1)
as eluent. Yield of compound 16: 135 mg (0.128 mmol, 65%, red
solid). Another minor product was isolated as 16a (28 mg, 0.027
mmol, 14%).
1
Characterization Data of Compound 13. H NMR (500 MHz,
CDCl3): δ 7.64 (s, 1H), 7.32 (m, 6H), 7.28 (m, 4H), 6.30 (s, 2H),
6.15 (s, 1H), 5.82 (s, 2H), 5.79 (s, 1H), 5.52 (s, 4H), 4.74 (q, J = 10
Hz, 4H), 4.13 (m, 2H), 4.04 (t, J = 10 Hz, 2H), 3.88 (t, J = 10 Hz,
2H), 3.77 (m, 10H), 3.74 (s, 8H). 13C NMR (125 MHz, CDCl3; all
signals represent 2C, except as noted): δ 150.02, 148.84, 148.75 (4C),
148.61, 148.57, 148.49, 148.28, 148.20, 148.15, 148.09, 148.04, 147.71
(1C), 146.77, 145.39 (1C), 144.81, 144.79, 144.62, 144.41, 144.02,
143.82, 143.30, 143.28, 142.49, 142.38, 142.26, 141.70, 136.58, 134.60,
129.03 (4C), 128.66, 128.15 (4C), 123.01, 83.41, 82.87 (1C), 81.29,
74.60 (1C), 72.15, 70.77, 70.52, 70.37, 69.99, 69.74, 68.80, 64.51,
54.15. FT-IR (microscope): 3379, 2923, 2871, 1456, 1353, 1292, 1210,
1087, 939, 757, 721 cm−1. ESI-HRMS: C92H49N6O14 (M − H+) calcd
1461.3312, found 1461.3292.
1
Characterization Data of Compound 16. H NMR (400 MHz,
CDCl3): δ 5.93 (s, 1H), 5.69 (s, 2H), 3.85 (s, 3H), 1.45 (s, 18H). 13
C
NMR (100 MHz, CDCl3; all signals represent 2C, except as noted): δ
150.65, 148.96, 148.82 (1C), 148.80, 148.74, 148.62, 148.58, 148.44,
148.27, 148.24, 148.18, 147.75 (1C), 147.65, 145.18, 144.40, 144.31,
144.00, 143.96, 143.77, 143.62, 143.00, 142.86, 141.52, 140.88, 140.69,
140.29, 137.91, 86.42, 83.26, 81.48, 80.58 (1C), 80.43 (1C), 70.13,
58.46 (1C), 26.70 (6C). FT-IR (microscope): 3375, 2978, 2930, 2826,
1388, 1365, 1190, 1116, 1081, 1006, 965, 855, 756 cm−1. ESI-HRMS:
C69H24Cl2NaO8 (M + Na+) calcd 1073.0740, found 1073.0770.
Characterization Data of Compound 16a. The structure of 16a is
similar to that of compound 16, except that one Cl was replaced by
Compound 14. Cuprous iodide (735 mg, 3.47 mmol) and
TMEDA (446 mg, 3.47 mmol) were added to a solution of compound
10b (23 mg, 0.019 mmol) in CHCl3 (70 mL) at 25 °C. After the
mixture was stirred for 3 h in the dark, the solution was washed with 2
M HCl (aq) (3 × 100 mL), followed by water (3 × 100 mL). Then
the organic layer was dried over anhydrous sodium sulfate. CHCl3 was
removed under reduced pressure at 35 °C, and the residue was
purified by silica gel column chromatography with CHCl3/CH3OH
(100/1) as eluent. Yield of compound 14: 15 mg (0.013 mmol, 65%,
red solid).
1
one OMe group. H NMR (400 MHz, CDCl3): δ 5.72 (s, 1H), 5.65
(s, 1H), 5.49 (s, 1H), 3.88 (s, 3H), 3.87 (s, 3H), 1.44 (s, 9H), 1.39 (s,
9H). 13C NMR (100 MHz, CDCl3; all signals represent 1C, except as
noted): δ 150.74, 148.96, 148.95, 148.83, 148.76, 148.68 (3C), 148.67,
148.65, 148.60, 148.56, 148.50, 148.43, 148.34, 148.26, 148.20 (4C),
148.15, 147.77, 147.39, 147.31, 146.21, 145.13, 144.75, 144.57, 144.49,
144.43, 144.40, 144.36, 144.08, 143.91 (2C), 143.79, 143.74, 143.59,
143.02, 142.99, 142.96, 142.86, 142.83, 142.61, 141.96, 141.72, 141.59,
140.90, 139.77 (2C), 138.63, 136.79, 85.52, 82.97, 82.85, 81.96, 81.42,
80.83, 80.78, 80.75, 80.45, 70.64, 58.50, 56.27, 26.70 (3C), 26.68 (3C).
FT-IR (microscope): 3406, 2978, 2929, 2829, 1455, 1387, 1364, 1191,
1114, 1080, 974, 864, 756 cm−1. ESI-HRMS: C70H31ClNO9 (M +
1
Characterization Data of Compound 14. H NMR (500 MHz,
CDCl3): δ 6.41 (s, 2H), 5.89 (s, 1H), 5.52 (s, 1H), 4.57 (s, 2H), 4.43
(s, 2H), 4.28 (s, 2H), 4.15 (m, 2H), 4.06 (t, J = 5 Hz, 2H), 3.95 (m,
2H), 3.85 (m, 20H). 13C NMR (126 MHz, CDCl3; all signals
represent 2C, except as noted): δ 149.85 (1C), 149.83 (1C), 149.02,
148.95 (1C), 148.91, 148.77, 148.73, 148.63, 148.58, 148.36, 148.32,
148.22, 148.18, 147.84 (1C), 147.00 (1C), 146.99 (1C), 144.88,
144.86 (4C), 144.58, 144.23, 143.99, 143.48, 143.35, 142.55 (1C),
142.54 (1C), 142.51, 142.36, 141.44 (1C), 141.43 (1C), 136.47, 90.94
(1C), 83.72, 82.98 (1C), 81.64, 81.51, 74.89 (1C), 72.54 (1C), 71.04
(1C), 70.99 (1C), 70.93 (1C), 70.75 (1C), 70.68, 70.62, 70.26 (1C),
70.21 (1C), 69.61 (1C), 69.50, 69.07, 60.20 (1C), 60.18 (1C). FT-IR
(microscope): 3384, 2924, 2872, 1456, 1351, 1291, 1271, 1209, 1087,
+
NH4 ) calcd 1064.1682, found 1064.1689.
Compound 17. Anhydrous silver perchlorate (179 mg, 0.865
mmol) was added to a solution of MeOH (9 mL) and compound 16
2461
dx.doi.org/10.1021/jo300118h | J. Org. Chem. 2012, 77, 2456−2462

The Journal of Organic Chemistry
Article
(227 mg, 0.216 mmol) in toluene (36 mL) at 30 °C in the dark, and
the mixture was stirred for 2 h. The solution was washed with water (3
× 50 mL), and the organic layer was dried over anhydrous sodium
sulfate. Then the solution was concentrated in vacuo and the residue
was purified by silica gel column chromatography with toluene/
petroleum ether/ethyl acetate (10/5/2) as eluent. Yield of compound
17: 175 mg (0.168 mmol, 77%, red solid).
Am. Chem. Soc. 1993, 115, 5453. (c) Chiang, L. Y.; Upasani, R. B.;
Swirczewski, J. W. J. Am. Chem. Soc. 1992, 114, 10154. (d) Kokubo, K.;
Matsubayashi, K.; Tategaki, H.; Takada, H.; Oshima, T. ACS Nano
2008, 2, 327.
(6) (a) Gonzalez, K. A.; Wilson, L. J.; Wu, W. J.; Nancollas, G. H.
Bioorg. Med. Chem. 2002, 10, 1991. (b) Li, J.; Takeuchi, A.; Ozawa, M.;
Li, X.; Saigo, K.; Kitazawa, K. J. Chem. Soc., Chem. Commun. 1993,
1784. (c) Wang, S.; He, P.; Zhang, J. M.; Jiang, H.; Zhu, S. Z. Synth.
Commun. 2005, 35, 1803.
1
Characterization Data of Compound 17. H NMR (400 MHz,
CDCl3): δ 5.31 (s, 2H), 5.28 (s, 1H), 3.91 (s, 6H), 3.80 (s, 3H), 1.38
(s, 18H). 13C NMR (100 MHz, CDCl3; all signals represent 2C,
except as noted): δ 148.95, 148.86 (1C), 148.71, 148.69, 148.64,
148.50, 148.36, 148.33, 148.25, 148.18, 148.14, 147.80 (1C), 147.47,
146.44, 144.75, 144.45 (4C), 143.88, 143.74, 143.28, 143.03, 142.93,
142.91, 142.82, 142.06, 140.68, 138.27, 85.08, 83.05, 81.71, 81.11,
80.88 (1C), 58.26 (1C), 56.24, 26.69 (6C). FT-IR (microscope):
3450, 2977, 2930, 2828, 1456, 1387, 1364, 1192, 1112, 1083, 1009,
(7) Meier, M. S.; Kiegiel, J. Org. Lett. 2001, 3, 1717.
(8) Wang, G. W.; Lu, Y. M.; Chen, Z. X. Org. Lett. 2009, 11, 1507.
(9) (a) Huang, S. H; Xiao, Z.; Wang, F. D.; Gan, L. B.; Zhang, X.;
Hu, X. Q.; Zhang, S. W.; Lu, M. J.; Pan, Q. Q.; Xu, L. J. Org. Chem.
2004, 69, 2442. (b) Xiao, Z.; Yao, J. Y.; Yang, D. Z.; Wang, F. D.;
Huang, S. H; Gan, L. B.; Jia, Z. S.; Jiang, Z. P.; Yang, X. B.; Zheng, B.;
Yuan, G.; Zhang, S. W.; Wang, Z. M. J. Am. Chem. Soc. 2007, 129,
16149. (c) Yao, J. Y.; Xiao, Z.; Gan, L. B.; Yang, D. Z.; Wang, Z. Org.
Lett. 2008, 10, 2003. (d) Wang, F. D.; Xiao, Z.; Yao, Z. P.; Jia, Z. S.;
Huang, S. H.; Gan, L. B.; Zhou, J.; Yuan, G.; Zhang, S. W. J. Org.
Chem. 2006, 71, 4374.
+
975, 868, 756 cm−1. ESI-HRMS: C71H34NO10 (M + NH4 ) calcd
1060.2177, found 1060.2180.
Crystal Data for Compound 17: C299H136O40S2, T = 173(2) K,
triclinic, space group P1, unit cell dimensions a = 14.809(2) Å, b =
̅
17.264(3) Å, c = 19.650(4) Å, V = 4780.0 (14) Å3. Z = 1, ρcalcd = 1.540
Mg/m3, 49 375/16 833 collected/unique reflections (R(int) =
0.0442). Final R indices (I > 2σ(I)): R1 = 0.1298, wR2 = 0.3344.
CCDC file: No. 818563.
(10) Zhang, G; Liu, Y; Liang, D. H.; Gan, L. B.; Li, Y. L. Angew.
Chem., Int. Ed. 2010, 49, 5293.
(11) For example: (a) Fazio, M. A.; Lee, O. P.; Schuster, D. I. Org.
Lett. 2008, 10, 4979. (b) Iehl, J.; Nierengarten, J. F. Chem. Eur. J. 2009,
15, 7306. (c) Nierengarten, J. F.; Iehl, J.; Oerthel, V.; Holler, M.;
Illescas, B. M.; Munoz, A.; Martin, N.; Rojo, J.; Sanchez-Navarro, M.;
Cecioni, S.; Vidal, S.; Buffet, K.; Durka, M.; Vincent, S. P. Chem.
Commun. 2010, 46, 3860. (d) Wu, J. C.; Wang, D. X.; Huang, Z. T.;
Wang, M. X. J. Org. Chem. 2010, 75, 8604. (e) Liu, J. Y.; El-Khouly, M.
E.; Fukuzumi, S.; Ng, D. K. P. Chem. Eur. J. 2011, 17, 1605. (f) Miguel,
G. D.; Wielopolski, M.; Schuster, D. I.; Fazio, M. A.; Lee, O. P.; Haley,
C. K.; Ortiz, A. L.; Echegoyen, L.; Clark, T.; Guldi, D. M. J. Am. Chem.
Soc. 2011, 133, 13036. (g) Munoz, A.; Illescas, B. M.; Sanchez-
Navarro, M.; Rojo, J.; Martin, N. J. Am. Chem. Soc. 2011, 133, 16758.
(12) Gan, L. B.; Huang, S. H.; Zhang, X.; Zhang, A. X.; Cheng, B. C.;
Cheng, H.; Li, X. L.; Shang, G. J. Am. Chem. Soc. 2002, 124, 13384.
(13) (a) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem.,
Int. Ed. 2000, 39, 2632. (b) Yin, W. Y.; He, C.; Chen, M.; Zhang, H.;
Lei, A. W. Org. Lett. 2009, 11, 709. (c) Shao, Z. H.; Peng, F. Z. Angew.
Chem., Int. Ed. 2010, 49, 9566.
ASSOCIATED CONTENT
* Supporting Information
■
S
Figures giving selected spectroscopic data for all new
compounds and a CIF file giving crystallographic data for 17.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gan@pku.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(14) (a) Huang, S. H.; Xiao, Z.; Wang, F. D.; Zhou, J.; Yuan, G.;
Zhang, S. W.; Chen, Z. F.; Thiel, W.; Schleyer, P. R.; Zhang, X.; Hu, X.
Q.; Chen, B. C.; Gan, L. B. Chem. Eur. J. 2005, 11, 5449. (b) Huang, S.
H.; Yang, X. B.; Zhang, X.; Hu, X. Q.; Gan, L. B.; Zhang, S. W. Synlett
2006, 8, 1266.
■
This work was supported by the NSFC (Nos. 20972003,
21132007) and the Major State Basic Research Development
Program (No. 2011CB808401).
REFERENCES
■
(1) (a) Johnson-Lyles, D. N.; Peifley, K.; Lockett, S.; Neun, B. W.;
Hansen, M.; Clogston, J.; Stern, S. T.; McNeil, S. E. Toxicol. Appl.
Pharmacol. 2010, 248, 249. (b) Jiao, F.; Liu, Y.; Qu, Y.; Li, W.; Zhou,
G. Q.; Ge, C. C.; Li, Y. F.; Sun, B. Y.; Chen, C. Y. Carbon 2010, 48,
2231.
(2) (a) Kato, S.; Aoshima, H.; Saitoh, Y.; Miwa, N. Bioorg. Med.
Chem. Lett. 2009, 19, 5293. (b) Xu, J. Y.; Su, Y. Y.; Cheng, J. S.; Li, S.
X.; Liu, R. L.; Li, W. X.; Xu, G. T.; Li, Q. N. Carbon 2010, 48, 1388.
(c) Injac, R.; Perse, M.; Cerne, M.; Potocnik, N.; Radic, N.;
Govedarica, B.; Djordjevic, A.; Cerar, A.; Strukelj, B. Biomaterials
2009, 30, 1184. (d) Xu, J. Y.; Han, K. Y.; Li, S. X.; Cheng, J. S.; Xu, G.
T.; Li, W. X.; Li, Q. N. J. Appl. Toxicol. 2009, 29, 578. (e) Kondo, H.;
Ohtake, Y. J. Appl. Polym. Sci. 2010, 118, 3625.
(3) Park, Y.; Singh, N. J.; Kim, K. S.; Tachikawa, T.; Majima, T.;
Choi, W. Chem. Eur. J. 2009, 15, 10843.
(4) (a) Wang, F. F.; Li, N.; Tian, D.; Xia, G. F.; Xiao, N. ACS Nano
2010, 4, 5565. (b) Li, J.; Vadahanambi, S.; Kee, C. D.; Oh, I. K.
Biomacromolecules 2011, 12, 2048. (c) Sardenberg, R. B.; Teixeira, C.
E.; Pinheiro, M.; Figueiredo, J. M. ACS Nano 2011, 5, 2681.
(d) Rajagopalan, M.; Oh, I. K. ACS Nano 2011, 5, 2248.
(5) (a) Chiang, L. Y.; Swirczewski, J. W.; Hsu, C. S.; Chowdhury, S.
K.; Cameron, S.; Creegan, K. J. Chem. Soc., Chem. Commun. 1992,
1791. (b) Chiang, L. Y.; Upasani, R. B.; Swirczewski, J. W.; Soled, S. J.
2462
dx.doi.org/10.1021/jo300118h | J. Org. Chem. 2012, 77, 2456−2462