Construction of dispirocyclopentanebisoxindoles via self-domino michael-aldol reactions of 3-phenacylideneoxindoles

Article abstract of DOI:10.1021/jo4010603

A simple protocol for the construction of novel dispirocyclopentanebisoxindoles is accomplished by the base promoted domino reactions between two molecules of 3-phenacylideneoxindoles with the participation of solvents, alcohol, or other added nucleophiles such as amines or thiophenols. Significantly, this domino reaction results in the complex dispiro compounds with high yields and diastereoselectivity, which would allow construction of dispirocyclopentanebisoxindole with four and five diastereoisomeric centers using simple materials.

Full text of DOI:10.1021/jo4010603

Article
pubs.acs.org/joc
Construction of Dispirocyclopentanebisoxindoles via Self-Domino
Michael-Aldol Reactions of 3‑Phenacylideneoxindoles
Jing Sun, Ya-Jing Xie, and Chao-Guo Yan*
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
S
* Supporting Information
ABSTRACT: A simple protocol for the construction of novel
dispirocyclopentanebisoxindoles is accomplished by the base promoted
domino reactions between two molecules of 3-phenacylideneoxindoles
with the participation of solvents, alcohol, or other added nucleophiles
such as amines or thiophenols. Significantly, this domino reaction results
in the complex dispiro compounds with high yields and diastereose-
lectivity, which would allow construction of dispirocyclopentanebisox-
indole with four and five diastereoisomeric centers using simple
materials.
allenoates in the presence of phosphines.12 The three-
INTRODUCTION
■
component [2+2+1]-cycloaddition reactions of isocyanides,
activated alkynes, and isatylidene malononitriles provided a new
approach to spirocyclopentaneoxindole.13 Several efficient
metal or organocatalyzed enantioselective syntheses of
spirocyclopentaneoxindoles were also successfully explored by
Marinetti,14 Trost,15 Barbas III,16 Shao,17 and Chen.18
Encouraged by these achievements and with the aim of
expanding our previous studies on the synthesis of spiroox-
indoles,19,20 here we report the facile construction of novel bis-
spirocyclopentenebisoxindoles by domino reaction between
two molecules of 3-phenacylideneoxindoles in basic solution.
The spirooxindole framework represents an important
structural motif that is embodied in a number of bioactive
natural products.1,2 The unique structural array and the highly
pronounced pharmacological activity displayed by this class of
spirooxindoles have made them attractive synthetic targets.3,4
The intense investigations on the isatin chemistry have led to
the successful design and synthesis of diverse types of
heterocyclic and carbocyclic spirooxindoles.5 Although the
synthetic approaches to heterocyclic spirooxindoles have been
widely investigated, the biological properties and syntheses of
the carbocyclic oxindoles are now attracting more and more
attention.6,7 Spirocyclopentaneoxindole moieties are found in
natural alkaloids such as cirinalins, notoamides, citrinadins, and
cyclopiamines (Scheme 1).8 Spirocyclopentaneoxindoles have
also been recognized as compounds with a wide spectrum of
biological activity, such as insecticidal, cytotoxic, anthelmintic,
and antibacterial. Therefore, substantial effort has focused on
both the synthetic and the biosynthetic aspects of this unique
ring system.9 As a consequence, a number of methods have
been developed for the efficient preparation of spirocyclopen-
taneoxindole derivatives. A TiCl4-mediated reaction of 1,1-
diarylethylenes and isatins gave spiroindeneoxindoles through
the tandem Prins and intramolecular Friedel−Crafts reac-
tions.10a An In(III)-catalyzed reductive cyclization of isatylidene
malononitriles by using the Hantzsch ester afforded the novel
bis-spirocyclopentenebisoxindoles.10b The intramolecular Wit-
tig reaction of isatin-derived phosphorus ylide also led to a
facile synthesis of spirocyclopenteneoxindoles.11 Shi and co-
workers have reported the diastereoselective synthesis of
spirocyclopenteneoxindoles via annulations of isatylidene
malononitrile with the Morita−Baylis−Hillman (MBH) carbo-
nates and isatin-derived electron-deficient alkenes with
RESULTS AND DISCUSSION
■
In the synthesis of the dispirooxindole-fused heterocycles via
domino reactions of in situ generated Huisgen 1,4-dipoles with
3-phenacylideneoxindole,19 we found that 3-phenacylideneox-
indole could produce an unexpected dispirocyclopentanebisox-
indole (2q) in 42% yield in the presence of 4-dimethylamino-
pyridine (DMAP). This surprising result is of value to us
because we were unable to find a published method for such a
convenient synthesis of this kind of product. A literature survey
showed that 3-phenacylideneoxindoles have long been used as
active electron-deficient alkenes in many synthetic procedures
such as 1,3-dipolar cycloaddition, Diels−Alder reaction,
Michael addition, and versatile multicomponent reactions for
the design of the fused cyclic and spirocyclic frameworks.8,21,22
However, there are no reports of effective 1,3-dipoles
cycloaddition or dimerization with those reagents. On the
other hand, there are very few examples of the synthesis of a
Received: May 15, 2013
© XXXX American Chemical Society
A
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Scheme 1. Typical Natural Products Containing Spirocyclopentaneoxindole Scaffold
complex dispirocyclopentanebisoxindole system.10,11b Barbas
Table 1. Synthesis of Dispirocyclopentanebisoxindoles 2a−
a
III reported the efficient synthesis of dispirocyclopentanebisox-
indoles with four chiral centers by organocatalyzed domino
asymmetric reactions of 3-substituted oxindoles with methyl-
enindolinones.16b Encouraged by this interesting result, we
decided to optimize the reaction conditions, which included the
choice of a base, solvent, temperature, and molar ratio of the
substrates (SPI, Table s1, Supporting Information). The best
result was obtained by stirring the methanolic solution of 3-
phenacylideneoxindole in the presence of piperidine at room
temperature for 5 h, which gave the desired dispirocyclopenta-
nebisoxindole 2q in 80% yield. Upon optimization of reaction
conditions, various 3-phenacylideneoxindoles with different
kinds of substituents in the oxindole and phenacyl moieties
were introduced into the transformation. We were satisfied to
find that the corresponding methoxy-substituted dispirocyclo-
pentanebisoxindoles 2a−2r were obtained in 80−98% yields
(Table 1, entries 1−18). Similarly, the reactions in ethanol
afforded the ethoxy-substituted dispirocyclopentanebisoxin-
doles 2s−2w in satisfactory yields (Table 1, entries 19−23).
These results showed that a base promoted unprecedented
domino reaction for the facile synthesis of dispirocyclopenta-
nebisoxindoles had been successfully established.
The methoxy and ethoxy groups in the above-obtained
dispirocyclopentanebisoxindoles obviously arise from the
nucleophilic substitution of methanol and ethanol. We
envisioned that if some stronger nucleophiles existed in the
reaction system, other nucleophilic-substituted products would
be formed. Thus, stronger nucleophiles such as aniline, p-
toluidine, p-chloroaniline, n-butylamine, or benzylamine were
added to acetonitrile solution of 3-phenacylideneoxindoles with
piperidine as a catalyst. To our delight, the reactions proceeded
smoothly to afford the expected amino-substituted dispirocy-
clopentanebisoxindoles (3a−3g) in satisfactory yields (Table 2,
entries 1−7). Furthermore, if no other nucleophile was added
to the reaction system, the acetonitrile solution of 3-
phenacylideneoxindoles in the presence of piperidine yielded
piperidino-substituted dispirocyclopentanebisoxindoles (3h−
3i) in good yields (Table 2, entries 8 and 9). Clearly,
piperidine acted as both base catalyst and nucleophile in the
reaction. We used morpholine and dimethylamine to replace
piperdine in similar reactions, and the corresponding
morpholino- and dimethylamine-substituted dispiro com-
pounds (3j and 3k) were also obtained in 85% and 50%
yields, respectively. These results not only provided a
convenient procedure for the preparation of versatile
dispirocyclopentanebisoxindoles but also shed more light on
the reaction mechanism of this domino reaction.
2w
b,c
entry compound
R
R′
Bn
Ar
R″ yield (%)
1
2a
2b
2c
2d
2e
2f
H
p-CH3OC6H4
p-ClC6H4
C6H5
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
85
2
H
Bn
83
3
CH3
CH3
F
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
Bn
96 (14:1)
4
p-CH3C6H4
C6H5
80
5
96
6
F
p-CH3C6H4
p-CH3OC6H4
C6H5
98
7
2g
2h
2i
F
97
8
F
82 (5:1)
9
F
Bn
p-CH3C6H4
p-CH3OC6H4
m-CH3OC6H4
C6H5
83
10
11
12
13
14
15
16
17
18
19
20
21
22
23
2j
F
Bn
89
2k
2l
F
Bn
90
Cl
Cl
Cl
Cl
Cl
Cl
Cl
F
H
93
2m
2n
2o
2p
2q
2r
H
p-CH3C6H4
p- CH3C6H4
p-ClC6H4
C6H5
92
n-Bu
n-Bu
Bn
87
90 (1:1)
87 (7:1)
80
Bn
p-CH3C6H4
p-ClC6H4
p-CH3C6H4
p-ClC6H4
p-CH3OC6H4
p-CH3C6H4
p-ClC6H4
Bn
96
2s
2t
n-Bu
n-Bu
n-Bu
Bn
83
F
Et
78 (12:1)
97
2u
2v
2w
Cl
Cl
Cl
Et
Et
85
Bn
Et
80 (7:1)
a
Reaction conditions: 3-phenacylideneoxindole (1.0 mmol) and
piperidine (0.5 mmol) in methanol or ethanol (10 mL) at rt for 4-5
b
c
hours. Isolated yield. Ratio of diastereoisomers.
The structures of the prepared dispirocyclopentanebisox-
indoles 2a−2w and 3a−3k were fully characterized by the
spectroscopic methods. Because there are five diastereoisomeric
carbon atoms in the newly formed cyclopentyl moiety in the
prepared dispirocyclopentanebisoxindoles 2a−2w and 3a−3k,
many diastereoisomers could exist for each product. To
determine the diastereochemistry of these complex dispiro
compounds, six crystal structures were successfully determined
by single-crystal X-ray diffraction studies performed on
compounds 2j, 2l, 2q, 2s, 3a, and 3j (SPI, Figures s1−s6,
B
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a
Table 2. Synthesis of Dispirocyclopentanebisoxindoles 3a−3j
b
entry
compound
R
R′
Ar
R″
yield (%)
1
3a
3b
3c
3d
3e
3f
Cl
Cl
F
n-Bu
n-Bu
Bn
p-CH3C6H4
p-ClC6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
C6H5
80
83
78
76
86
80
74
84
70
2
3
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
4
Cl
Cl
Cl
Cl
Cl
F
Bn
5
Bn
p-ClC6H5
CH2C6H5
n-C4H9
6
Bn
7
3g
3h
3i
Bn
c
8
Bn
(CH2)5
c
9
Bn
(CH2)5
d
e
10
11
3j
Cl
Cl
Bn
(CH2CH2)2O
85 (5:1)
d
3k
Bn
(CH3)2
50
a
Reaction conditions: 3-phenacylideneoxindole (1.0 mmol), amine (2.0 mmol), and piperidine (0.5 mmol) in CH3CN (10 mL) at rt for 12 h.
b
c
d
Isolated yield. Piperidine (2.0 mmol), no other amine was added. Morpholine or dimethylamine (2.0 mmol) to replace piperidine and no other
e
amine was added. Ratio of diastereoisomers.
1
Supporting Information). H and 13C NMR spectra clearly
carbon atom of one molecular 3-phenacylideneoxindole 1 gives
an adduct intermediate (A). Second, Michael addition of the
carbanion in intermediate (A) to another molecular 3-
phenacylideneoxindole 1 yields a new intermediate (B).
Third, the intramolecular aldol condensation of carbanion
with carbonyl group yields the cyclized intermediate (C).
Finally, the nucleophilic substitution of alcohol or amine to the
ammonium cation produces the final dispirocyclopentanebisox-
indoles 2 or 3. If no other of nucleophile was added, the excess
secondary amine in the solution acted as the nucleophile to
finish substitution reaction and to afford the dispirocyclopenta-
nebisoxindoles 3.
showed that one diastereoisomer usually existed in most of the
prepared samples. In a few cases, another minor diaster-
eoisomer could be observed (Table 1, entries 3, 8, 15, 16, 20,
and 23; Table 2, entry 10) with the ratio of diastereoisomer in
2c being 14:1 and the ratio of diastereoisomers in 2h being 5:1.
Only in the spiro compound 2o was the ratio of two
diastereoisomers equal. In the amino-substituted dispiro
compounds 3a−3k, two diastereoisomer with a ratio of 5:1
could be observed only in compound 3j. The molecular
structures of all six single crystals indicated that the following
major diastereoisomer occurs (Scheme 2) in which the two
To probe the credibility of our proposed mechanistic scheme
and shed more light on the formation of dispirocyclopentane-
bisoxindole, further experiments were carried out. First, the
stronger nucleophilic thiophenols were used as nucleophiles in
the base promoted self-domino reactions of 3-phenacylideneox-
indoles. A solution of equivalent molar 3-phenacylideneox-
indole and thiophenol in acetonitrile in the presence of
piperidine was stirred at room temperature. The reactions
could be finished in about 3−4 h, which is much faster than the
reactions in alcohol and in the presence of amine. After workup,
it is very surprising to find that the reactions afforded
dispirocyclopentanebisoxindoles without a phenylsulfanyl
group (4a−4n) in moderate to good yields. The results were
summarized in Table 3. The reactions of 3-phenacylideneox-
indoles without N-substituents and 3-acetonylideneoxindole
also proceeded smoothly to give the expected spiro compounds
in moderate yields (Table 3, entries 10−14). The structures of
prepared dispirocyclopentanebisoxindoles 4a−4n were fully
characterized by 1H and 13C NMR, HRMS, and IR spectra, and
their structures were confirmed by single-crystal X-ray
diffraction studies of 4a, 4g, 4i, 4k, and 4m (SPI, Figures
Scheme 2. Illustration of the Obtained Diastereoisomer of
Dispiro Compounds 2 and 3
oxindole moieties at 1,3-positions are in trans orientation, while
the 2-benzoyl group and the 5-aryl group are in cis orientation.
It is known that the benzoyl group and the aryl group of the
oxindole moiety exist in the cis position in the starting 3-
phenacylideneoxindoles.23 This fact displayed that a multistep
reaction process was involved in this reaction, and the most
thermodynamically stable diastereoisomer was preferentially
formed in this domino reaction.
1
s7−s11, Supporting Information). H NMR spectra and the
single crystal structure clearly indicated that the dispirocyclo-
pentanebisoxindoles 4a−4n existed in a diastereoisomer similar
To explain the formation of dispirocyclopentanebisoxindoles,
a plausible reaction mechanism is proposed in Scheme 3. First,
a 1,4-conjugated addition of secondary amine to the exocyclic
C
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Scheme 3. Proposed Formation Mechanism of Dispirocyclopentanebisoxindoles 2 and 3
a
Table 3. Synthesis of Dispirocyclopentanebisoxindoles 4a−4n
b
entry
compound
R
R′
Bn
Ar (R″)
yield (%)
1
4a
4b
4c
4d
4e
4f
H
p-CH3C6H4
p-ClC6H4
p-CH3C6H4
p-ClC6H4
p-CH3OC6H4
C6H5
75
68
88
66
79
82
80
76
2
H
Bn
Bn
Bn
Bn
Bn
Bn
n-Bu
n-Bu
H
3
CH3
F
4
5
Cl
Cl
Cl
F
6
7
4g
4h
4i
p-ClC6H4
p-CH3C6H4
p-CH3C6H4
C6H5
8
c
9
Cl
Cl
Cl
Cl
CH3
F
91
c
10
11
12
13
14
4j
73
c
4k
4l
H
p-CH3C6H4
p-CH3OC6H4
CH3
55
c
H
48
c
4m
4n
H
55
c
H
CH3
62
a
Reaction conditions: 3-phenacyloxindole (0.5 mmol), thiophenol (0.5 mmol), and piperidine (0.5 mmol) in acetonitrile (10.0 mL) at rt for 3−4 h.
b
c
Isolated yield. p-Chlorothiophenol was used as reactant.
to that of the above dispirocyclopentanebisoxindoles 2 and 3, in
which the two oxindole moieties at the 1,3-positions are in
trans orientation, while the 2-benzoyl group and the 5-aryl
group are in cis orientation. Thus this reaction is also a highly
diastereoselective reaction.
The most unusual feature of compounds 4a−4n is that no
expected phenylsulfanyl group or other nucleophilic substitu-
ents were introduced into the newly formed cyclopentyl ring.
There is one CH2 unit in the newly formed cyclopentane
moiety. This kind of dispirocyclopentanebisoxindole with
different substituents has recently been prepared by the
organocatalytic domino reaction between 3-substituted oxin-
dole and methyleneindolinones.16b Their results were very
helpful for us to understand the reaction mechanism of this self-
domino reaction. Thus, one molecule of 3-phenacylideneox-
indole was reduced by thiophenol to give the 3-phenacylox-
indole in the reaction. There are several reports about the
reduction of 3-phenacylideneoxindoles to give the 3-phenacy-
loxindoles by reducing reagents such as Zn, PMe3, Na2S2O4,
and NaHSO3.24 Thus, in the presence of thiophenol, the above
proposed reaction mechanism (Scheme 3) is slightly adjusted
to Scheme 4. At first, the nucleophilic 1,4-addition of
thiophenol to 3-phenacylideneoxindole afforded a phenyl-
sulfanyl-substituted adduct (D), which in turn transformed to
D
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domino reaction has high diastereoselectivity, which would
allow the construction of dispirocyclopentanebisoxindole with
four and five stereogenic centers. The reaction mechanism is
believed to involve domino Michael addition, aldol condensa-
tion, and nucleophilic substitution as well as the reduction
reaction. The advantages of the reactions are using readily
available starting materials, mild reaction conditions, opera-
tional simplicity, and a wide variety of substrates. This reaction
provides a convenient synthetic procedure for the preparation
of the complex dispirooxindole system. The potential uses of
the reaction in synthetic and medicinal chemistry may be
significant.
Scheme 4. Proposed Formation Mechanism of
Dispirocyclopentanebisoxindoles 4
EXPERIMENTAL SECTION
■
1. General Procedure for the Preparation of Methoxy- and
Ethoxy-Substituted Dispirocyclopentanebisoxindoles (2a−
2w). A solution of 3-phenacylideneoxindoles (1.0 mmol) and
piperidine (0.5 mmol, 0.042 g) in 10.0 mL of methanol or ethanol
was stirred at room temperature for about 4−5 h. Then, the resulting
precipitates were collected by filtration and washed with a little cold
ethanol to give the pure products 2a−2w for analysis.
1
3-phenacylindolinone (E). Then, Michael addition of the
carbanion of 3-phenacylindolinone (E) to another molecular 3-
phenacylideneoxindole 1 yielded a new intermediate (F).
Finally, the intramolecular aldol condensation of carbanion with
carbonyl group in intermediate (F) produced the finally
product 4. Thus, this reaction provided an efficient procedure
for in situ generation of 3-phenacylindolinones and its
sequential reactions.
To support the proposed mechanism, separation of the
reaction intermediates were attempted. (Scheme 5). In the
absence of piperidine, the reactions of 3-phenacylideneox-
indoles with thiophenol or p-chlorothiophenol in acetonitrile at
room temperature gave the phenylsulfanyl or 4-chlorophenyl-
sulfanyl adducts D1 and D2 in 77% and 84% yields,
respectively. On the other hand, the reaction of 3-
phenacylideneoxindole with 2-mercaptoethanol in the presence
of piperidine resulted in the 3-phenacyloxindole (E) in 91%
yield. The mechanism proposed in Scheme 4 is strongly
supported by the isolation of these two key intermediates. Now
we can conclude that the 3-phenacyloxindole is generated in
situ by the reduction of 3-phenacylideneoxindole with
thiophenol (E), which in turn undergo further sequential
reactions similar to the reaction described by Barbas III and co-
workers.16b
2a: white solid, 0.326 g, 85%, mp 236−238 °C; H NMR (600
MHz, CDCl3) δ 8.16 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.2 Hz, 1H),
7.40 (d, J = 7.8 Hz, 2H), 7.32−7.30 (m, 2H), 7.27−7.26 (m, 2H), 7.24
(s, 1H), 7.17−7.09 (m, 6H), 7.07−7.05 (m, 1H), 7.02−7.00 (m, 1H),
6.97−6.95 (m, 1H), 6.81 (s, 1H), 6.66 (d, J = 8.4 Hz, 2H), 6.54 (d, J =
8.4 Hz, 4H), 6.39 (d, J = 7.8 Hz, 1H), 6.37 (d, J = 7.8 Hz, 1H), 6.12 (s,
1H), 5.43 (d, J = 15.2 Hz, 1H), 5.35 (s, 1H), 5.27 (d, J = 16.1 Hz, 1H),
4.46 (d, J = 16.1 Hz, 1H), 4.25 (d, J = 15.2 Hz, 1H), 3.74 (s, 3H), 3.73
(s, 3H), 3.02 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 194.3, 180.2,
177.3, 163.0, 159.1, 143.8, 142.0, 135.6, 135.2, 130.6, 129.9, 129.6,
128.8, 128.7, 128.4, 128.3, 128.0, 127.9, 127.0, 126.8, 126.5, 126.0,
124.1, 122.0, 113.1, 113.0, 108.7, 108.4, 89.9, 84.5, 64.5, 62.0, 60.6,
58.9, 55.5, 55.0, 44.6, 43.8; IR (KBr) υ 3668, 3288, 3057, 2932, 2835,
1697, 1676, 1610, 1599, 1514, 1490, 1467, 1440, 1386, 1367, 1346,
1304, 1257, 1216, 1170, 1153, 1114, 1096, 1028, 982, 963, 922, 842,
805, 753 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C49H42N2NaO7 ([M + Na]+) 793.2884, found 793.2882.
1
2b: white solid, 0.322 g, 83%, mp 224−226 °C; H NMR (600
MHz, CDCl3) δ 8.15−8.14 (m, 1H), 7.97 (d, J = 7.2 Hz, 1H), 7.41 (d,
J = 7.2 Hz, 2H), 7.35−7.32 (m, 2H), 7.31−7.29 (m, 1H), 7.23−7.20
(m, 3H), 7.17 (d, J = 9.0 Hz, 2H), 7.13−7.08 (m, 6H), 7.03−7.00 (m,
2H), 6.96 (d, J = 8.4 Hz, 2H), 6.87 (s, 1H), 6.61 (d, J = 6.6 Hz, 2H),
6.44−6.41 (m, 2H), 6.08 (s, 1H), 5.35 (d, J = 15.0 Hz, 1H), 5.31 (s,
1H), 5.20 (d, J = 16.2 Hz, 1H), 4.49 (d, J = 16.2 Hz, 1H), 4.30 (d, J =
15.0 Hz, 1H), 3.00 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 194.9,
179.8, 176.8, 143.6, 142.0, 138.8, 135.8, 135.4, 135.2, 134.8, 133.8,
130.1, 129.0, 128.9, 128.7, 128.6, 128.5, 128.2, 128.1, 127.8, 127.2,
126.4, 126.1, 126.0, 124.2, 122.2, 108.9, 108.6, 89.7, 84.2, 64.3, 62.3,
60.6, 58.4, 44.7, 43.9; IR (KBr) υ 3676, 3341, 3063, 2933, 1700, 1610,
1592, 1491, 1468, 1434, 1386, 1370, 1300, 1240, 1215, 1181, 1157,
1092, 1005, 986, 963, 849, 809, 790, 756 cm−1; MS (m/z) HRMS
(ESI-TOF) calcd for C47H36Cl2N2NaO5 ([M + Na]+) 801.1893, found
801.1887.
CONCLUSION
■
In summary, we have developed a highly efficient protocol for
the synthesis of a novel dispirocyclopentanebisoxindole system
from the base catalyzed domino reaction between two
molecules of 3-phenacylideneoxindoles. Significantly, this
Scheme 5. Preparation of the Reaction Intermediates D and E
E
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1
2c: white solid, 0.322 g, 96%, mp 234−236 °C; H NMR (600
MHz, CDCl3) δ major 7.98 (s, 1H), 7.72 (s, 1H), 7.23 (t, J = 7.2 Hz,
1H), 7.15 (d, J = 7.8 Hz, 2H), 7.12−7.09 (m, 4H), 7.07−7.04 (m,
4H), 6.85 (s, 1H), 6.81 (d, J = 7.8 Hz, 1H), 6.51 (d, J = 7.8 Hz, 1H),
6.24 (d, J = 7.8 Hz, 1H), 6.09 (s, 1H), 5.24 (s, 1H), 3.96−3.91 (m,
1H), 3.82−3.78 (m, 1H), 3.27−3.22 (m, 1H), 3.20−3.16 (m, 1H),
3.09 (s, 3H), 2.40 (s, 3H), 2.33 (s, 3H), 1.65−1.62 (m, 1H), 1.59−
1.56 (m, 1H), 1.45−1.39 (m, 2H), 1.11−1.05 (m, 1H), 1.00−0.95 (m,
5H), 0.91−0.86 (m, 1H), 0.79 (t, J = 7.2 Hz, 3H), δ minor 8.00 (s,
1H), 7.69 (s, 1H), 6.54 (d, J = 7.8 Hz, 1H), 5.22 (s, 1H); 13C NMR
(150 MHz, CDCl3) δ 196.3, 179.7, 176.5, 141.7, 140.0, 137.4, 133.5,
132.0, 131.0, 130.8, 129.0, 128.6, 127.7, 127.4, 127.2, 127.1, 126.8,
126.4, 107.5, 107.3, 89.1, 84.7, 64.2, 61.7, 60.1, 58.5, 40.4, 39.8, 29.5,
29.0, 21.3, 20.1, 13.9, 13.7; IR (KBr) υ 3285, 3059, 2955, 2929, 2867,
1698, 1618, 1599, 1495, 1446, 1382, 1355, 1287, 1259, 1206, 1175,
1154, 1114, 1072, 1039, 991, 944, 900, 846, 805, 774, 756 cm−1; MS
(m/z) HRMS (ESI-TOF) calcd for C43H46N2NaO5 ([M + Na]+)
693.3299, found 693.3298.
MS (m/z) HRMS (ESI-TOF) calcd for C43H44F2N2NaO5 ([M +
Na]+) 729.3111, found 729.3111.
1
2g: white solid, 0.358 g, 97%, mp 204−206 °C; H NMR (600
MHz, CDCl3) δ 8.03 (dd, J = 8.4, 2.6 Hz, 1H), 7.65 (dd, J = 8.4, 2.6
Hz, 1H), 7.23 (d, J = 9.0 Hz, 2H), 7.06 (d, J = 9.0 Hz, 2H), 6.94 (td, J
= 8.8, 2.6 Hz, 1H), 6.76 (td, J = 8.6, 2.6 Hz, 1H), 6.63 (d, J = 9.0 Hz,
2H), 6.60 (d, J = 5.4 Hz, 2H), 6.58 (s, 1H), 6.53 (dd, J = 8.5, 4.1 Hz,
1H), 6.37 (dd, J = 8.5, 4.1 Hz, 1H), 6.00 (s, 1H), 5.14 (s, 1H), 3.97−
3.94 (m, 1H), 3.83−3.78 (m, 1H), 3.74 (s, 3H), 3.70 (s, 3H), 3.34−
3.30 (m, 1H), 3.26−3.21 (m, 1H), 3.09 (s, 3H), 1.67−1.60 (m, 2H),
1.46−1.41 (m, 2H), 1.21−1.15 (m, 1H), 1.07−1.01 (m, 3H), 0.98 (t, J
= 7.2 Hz, 3H), 0.82 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 193.9, 179.4, 176.6, 163.1, 159.9 (d, J = 182.0 Hz), 159.1, 158.3 (d, J
= 178.7 Hz), 140.0, 138.4, 132.4 (d, J = 8.7 Hz), 129.7, 129.5, 129.0,
128.4, 127.5, 114.8, 114.7, 114.1, 113.9, 113.2, 112.6, 108.3 (d, J = 8.3
Hz), 108.0 (d, J = 8.0 Hz), 107.9, 89.3, 84.3, 64.7, 61.3, 60.2, 59.0,
55.4, 55.0, 40.6, 40.0, 29.4, 29.1, 20.1, 13.8, 13.7; IR (KBr) υ 3679,
3362, 3067, 2959, 2935, 2872, 2838, 1695, 1676, 1602, 1574, 1514,
1491, 1454, 1377, 1359, 1270, 1248, 1176, 1151, 1117, 1094, 1035,
1011, 983, 945, 910, 845, 815, 751 cm−1; MS (m/z) HRMS (ESI-
TOF) calcd for C43H44F2N2NaO7 ([M + Na]+) 761.3009, found
761.3007.
1
2d: white solid, 0.278 g, 80%, mp 246−248 °C; H NMR (600
MHz, CDCl3) δ 7.97 (s, 1H), 7.70 (s, 1H), 7.07 (d, J = 8.4 Hz, 2H),
7.03 (d, J = 7.8 Hz, 1H), 6.96 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 7.8 Hz,
2H), 6.85 (d, J = 7.8 Hz, 2H), 6.82 (d, J = 7.8 Hz, 1H), 6.76 (s, 1H),
6.50 (d, J = 7.8 Hz, 1H), 6.27 (d, J = 7.8 Hz, 1H), 6.06 (s, 1H), 5.21
(s, 1H), 3.93−3.88 (m, 1H), 3.87−3.82 (m, 1H), 3.33−3.29 (m, 1H),
3.18−3.14 (m, 1H), 3.08 (s, 3H), 2.38 (s, 3H), 2.33 (s, 3H), 2.22 (s,
3H), 2.20 (s, 3H), 1.64−1.61 (m, 1H), 1.57−1.55 (m, 1H), 1.45−1.39
(m, 2H), 1.08−1.03 (m, 1H), 1.00−0.96 (m, 5H), 0.87−0.83 (m, 1H),
0.79 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 195.8, 179.8,
176.6, 142.7, 141.7, 140.0, 136.8, 134.8, 134.3, 133.4, 130.9, 128.8,
128.5, 128.4, 127.9, 127.3, 127.2, 126.9, 126.8, 126.3, 107.4, 107.2,
89.2, 84.6, 64.3, 61.5, 60.1, 58.6, 40.5, 39.8, 29.5, 29.1, 21.4, 21.3, 21.0,
20.2, 20.1, 14.0, 13.8; IR (KBr) υ 3679, 3654, 3342, 3035, 2958, 2928,
2809, 2348, 1696, 1604, 1496, 1440, 1361, 1288, 1260, 1201, 1146,
1113, 999, 934, 902, 809 cm−1; MS (m/z) HRMS (ESI-TOF) calcd
for C45H50N2NaO5 ([M + Na]+) 721.3612, found 721.3613.
1
2h: white solid, 0.306 g, 82%, mp 218−220 °C; H NMR (600
MHz, CDCl3) δ major 8.07 (dd, J = 8.7, 2.4 Hz, 1H), 7.77 (dd, J = 8.4,
2.4 Hz, 1H), 7.36−7.34 (m, 2H), 7.33−7.31 (m, 2H), 7.30−7.27 (m,
5H), 7.26 (br, 1H), 7.22−7.14 (m, 5H), 7.13−7.10 (m, 3H), 6.81 (td,
J = 8.7, 3.0 Hz, 1H), 6.78 (s, 1H), 6.68−6.64 (m, 1H), 6.55 (d, J = 7.2
Hz, 2H), 6.25 (dd, J = 8.4, 4.2 Hz, 1H), 6.22 (dd, J = 8.4, 4.2 Hz, 1H),
6.10 (s, 1H), 5.45 (d, J = 15.0 Hz, 1H), 5.34 (s, 1H), 5.16−5.12 (m,
1H), 4.50 (d, J = 16.2 Hz, 1H), 4.08 (d, J = 15.0 Hz, 1H), 3.04 (s, 3H),
δ minor 8.58 (s, 1H), 7.63 (dd, J = 7.8, 2.4 Hz, 1H), 7.53 (d, J = 7.2
Hz, 2H), 7.46 (dd, J = 8.4, 2.4 Hz, 1H), 7.23−7.21 (m, 3H), 7.00 (t, J
= 7.8 Hz, 2H), 6.92 (td, J = 8.4, 2.4 Hz, 1H), 6.59−6.56 (m, 1H), 6.50
(d, J = 7.2 Hz, 2H), 5.98 (dd, J = 9.0, 4.2 Hz, 1H), 5.53 (d, J = 15.6
Hz, 1H), 5.38 (s, 1H), 4.88 (d, J = 16.2 Hz, 1H), 4.72 (d, J = 16.2 Hz,
1H), 3.76 (d, J = 15.6 Hz, 1H), 3.10 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 195.9, 179.7, 176.8, 160.2 (d, J = 170.1 Hz), 158.6 (d, J =
167.2 Hz), 139.7, 138.1, 136.9, 135.2, 134.7, 132.7, 132.1 (d, J = 8.8
Hz), 128.9, 128.6, 128.2, 128.0, 127.9, 127.8, 127.7, 127.6, 127.4,
127.3, 127.1, 126.6, 126.5, 126.4, 115.2, 115.0, 114.9, 114.7, 114.5,
114.2, 114.0, 109.3 (d, J = 7.9 Hz), 109.1 (d, J = 8.4 Hz), 89.6, 84.6,
64.9, 62.6, 60.7, 59.0, 44.8, 44.0; IR (KBr) υ 3340, 3068, 3036, 2984,
2932, 2834, 1958, 1707, 1618, 1492, 1452, 1368, 1344, 1265, 1218,
1179, 1146, 1129, 1111, 1076, 1029, 1003, 981, 944, 897, 853, 808,
777 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C47H36F2N2NaO5
([M + Na]+) 769.2484, found 769.2484.
1
2e: white solid, 0.326 g, 96%, mp 206−208 °C; H NMR (600
MHz, CDCl3) δ 8.06 (dd, J = 8.4, 2.6 Hz, 1H), 7.68 (dd, J = 8.4, 2.6
Hz, 1H), 7.29 (d, J = 7.2 Hz, 1H), 7.21 (d, J = 7.2 Hz, 2H), 7.16−7.13
(m, 3H), 7.12−7.09 (m, 4H), 6.95 (td, J = 8.8, 2.6 Hz, 1H), 6.74 (td, J
= 8.6, 2.6 Hz, 1H), 6.70 (s, 1H), 6.52 (dd, J = 8.5, 4.1 Hz, 1H), 6.30
(dd, J = 8.5, 4.1 Hz, 1H), 6.03 (s, 1H), 5.20 (s, 1H), 3.98 (m, 1H),
3.78−3.74 (m, 1H), 3.25−3.21 (m, 2H), 3.09 (s, 3H), 1.64−1.61 (m,
1H), 1.58−1.53 (m, 1H), 1.45−1.39 (m, 2H), 1.18−1.14 (m, 1H),
1.04−1.00 (m, 3H), 0.96 (t, J = 7.2 Hz, 3H), 0.82 (t, J = 7.2 Hz, 3H);
13C NMR (150 MHz, CDCl3) δ 195.8, 179.3, 176.3, 160.0 (d, J =
181.2 Hz), 158.4 (d, J = 178.2 Hz), 140.0, 138.4, 136.9, 136.6, 132.5,
132.3 (d, J = 8.9 Hz), 128.2, 128.0, 127.7, 127.4, 127.2, 126.3, 115.0,
114.9, 114.8, 114.7, 114.6, 114.1, 114.0, 108.3 (d, J = 8.0 Hz), 108.0
(d, J = 8.0 Hz), 89.1, 84.6, 64.6, 61.8, 60.2, 58.7, 40.6, 40.0, 29.4, 28.9,
20.0, 13.9, 13.7; IR (KBr) υ 3271, 3068, 2961, 2935, 2872, 1691, 1620,
1580, 1490, 1452, 1377, 1348, 1271, 1219, 1197, 1150, 1123, 1074,
1003, 983, 944, 904, 855, 817, 775, 757 cm−1; MS (m/z) HRMS (ESI-
TOF) calcd for C41H40F2N2NaO5 ([M + Na]+) 701.2797, found
701.2795.
1
2i: white solid, 0.320 g, 83%, mp 214−216 °C; H NMR (600
MHz, CDCl3) δ 8.05 (dd, J = 8.5, 2.5 Hz, 1H), 7.75 (dd, J = 8.5, 2.5
Hz, 1H), 7.37 (d, J = 7.2 Hz, 2H), 7.33−7.29 (m, 3H), 7.17 (t, J = 7.8
Hz, 5H), 7.12 (t, J = 7.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 6.87 (d, J =
7.8 Hz, 2H), 6.79 (td, J = 8.8, 2.6 Hz, 1H), 6.68 (s, 1H), 6.67−6.65
(m, 1H), 6.56 (d, J = 7.2 Hz, 2H), 6.26 (td, J = 8.3, 4.1 Hz, 2H), 6.06
(s, 1H), 5.40 (d, J = 15.6 Hz, 1H), 5.30 (s, 1H), 5.23 (d, J = 16.2 Hz,
1H), 4.45 (d, J = 16.2 Hz, 1H), 4.17 (d, J = 15.6 Hz, 1H), 3.04 (s, 3H),
2.33 (s, 3H), 2.27 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 195.4,
179.7, 177.0, 160.1 (d, J = 168.3 Hz), 158.5 (d, J = 165.6 Hz), 143.6,
139.8, 138.1, 137.4, 135.3, 134.8, 134.2, 134.1, 132.2 (d, J = 9.0 Hz),
128.9, 128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 127.9, 127.5, 127.4,
127.1, 126.6, 126.5, 115.0, 114.9, 114.8, 114.6, 114.2, 114.0, 109.2 (d, J
= 8.0 Hz), 109.0 (d, J = 8.1 Hz), 89.9, 84.5, 64.9, 62.4, 60.7, 59.1, 44.8,
44.1, 21.6, 21.3; IR (KBr) υ 3653, 3306, 3065, 2920, 2834, 1689, 1607,
1490, 1454, 1372, 1347, 1268, 1224, 1178, 1145, 1112, 1095, 1031,
1006, 980, 942, 903, 860, 842, 809, 762 cm−1; MS (m/z) HRMS (ESI-
TOF) calcd for C49H40F2N2NaO5 ([M + Na]+) 797.2797, found
797.2796.
1
2f: white solid, 0.346 g, 98%, mp 216−218 °C; H NMR (600
MHz, CDCl3) δ 8.05 (dd, J = 8.4, 2.6 Hz, 1H), 7.66 (dd, J = 8.4, 2.6
Hz, 1H), 7.12 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.95−6.89
(m, 5H), 6.75 (td, J = 8.6, 2.6 Hz, 1H), 6.60 (s, 1H), 6.52 (dd, J = 8.5,
4.1 Hz, 1H), 6.32 (dd, J = 8.5, 4.1 Hz, 1H), 6.00 (s, 1H), 5.17 (s, 1H),
3.95−3.90 (m, 1H), 3.83−3.79 (m, 1H), 3.32−3.27 (m, 1H), 3.23−
3.18 (m, 1H), 3.08 (s, 3H), 2.24 (s, 3H), 2.21 (s, 3H), 1.65−1.61 (m,
1H), 1.57−1.53 (m, 1H), 1.45−1.39 (m, 2H), 1.16−1.10 (m, 1H),
1.02−0.95 (m, 6H), 0.81 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 195.3, 179.4, 176.5, 159.9 (d, J = 180.3 Hz), 158.3 (d, J =
177.5 Hz), 143.3, 140.1, 138.4, 137.2, 134.3, 133.7, 132.4 (d, J = 8.7
Hz), 128.7, 128.4, 128.0, 127.3, 126.2, 114.9, 114.8, 114.7, 114.1,
113.9, 108.2 (d, J = 8.1 Hz), 107.9 (d, J = 8.0 Hz), 89.3, 84.5, 64.6,
61.6, 60.2, 58.9, 40.6, 40.0, 29.4, 29.0, 21.5, 20.9, 20.1, 13.9, 13.7; IR
(KBr) υ 3844, 3679, 3655, 3328, 3072, 2957, 2932, 2872, 2349, 1696,
1608, 1489, 1453, 1352, 1268, 1193, 1120, 987, 910, 839, 811 cm−1;
1
2j: white solid, 0.358 g, 89%, mp 218−220 °C; H NMR (600
MHz, CDCl3) δ 8.03 (dd, J = 8.5, 2.5 Hz, 1H), 7.74 (dd, J = 8.4, 2.5
Hz, 1H), 7.38 (d, J = 7.2 Hz, 2H), 7.33−7.31 (m, 2H), 7.30−7.27 (m,
3H), 7.19−7.16 (m, 3H), 7.14−7.12 (m, 2H), 6.80 (td, J = 8.8, 2.6 Hz,
1H), 6.70 (s, 1H), 6.68−6.66 (m, 3H), 6.58 (d, J = 8.4 Hz, 2H), 6.53
F
dx.doi.org/10.1021/jo4010603 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(d, J = 7.2 Hz, 2H), 6.32 (dd, J = 8.6, 4.1 Hz, 1H), 6.27 (dd, J = 8.6,
4.2 Hz, 1H), 6.06 (s, 1H), 5.43 (d, J = 15.6 Hz, 1H), 5.27−5.24 (m,
2H), 4.45 (d, J = 16.2 Hz, 1H), 4.22 (d, J = 15.0 Hz, 1H), 3.77 (s, 3H),
3.76 (s, 3H), 3.04 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 194.0,
179.8, 177.1, 163.3, 160.1 (d, J = 170.7 Hz), 159.3, 158.5 (d, J = 168.0
Hz), 139.8, 138.1, 135.3, 134.8, 132.3 (d, J = 9.0 Hz), 129.6, 129.2,
128.9, 128.5, 128.4, 127.9, 127.1, 126.5, 115.1, 114.9, 114.8, 114.7,
114.6, 114.2, 114.0, 113.3, 113.1, 109.2, 109.1, 89.8, 84.4, 65.0, 60.7,
59.2, 55.5, 55.1, 44.8, 44.0; IR (KBr) υ 3356, 3069, 2938, 2836, 1712,
1690, 1603, 1577, 1513, 1490, 1453, 1374, 1349, 1295, 1250, 1180,
1144, 1114, 1031, 981, 945, 902, 866, 845, 808, 765 cm−1; MS (m/z)
HRMS (ESI-TOF) calcd for C49H40F2N2NaO7 ([M + Na]+)
829.2696, found 829.2695.
1430, 1355, 1268, 1230, 1202, 1156, 1113, 984, 886, 839, 811 cm−1;
MS (m/z) HRMS (ESI-TOF) calcd for C43H44Cl2N2NaO5 ([M +
Na]+) 761.2519, found 761.2516.
1
2o: white solid, 0.350 g, 90%, mp 208−210 °C; H NMR (600
MHz, CDCl3) δ major 8.17 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 8.4 Hz,
1H), 7.23 (dd, J = 8.1, 2.4 Hz, 1H), 7.14−7.10 (m, 4H), 7.08 (dd, J =
7.8, 1.8 Hz, 2H), 7.04−7.02 (m, 2H), 7.01−6.99 (m, 1H), 6.60 (s,
1H), 6.56 (d, J = 8.4 Hz, 1H), 6.38 (d, J = 8.4 Hz, 1H), 5.95 (s, 1H),
5.11 (s, 1H), 3.97−3.92 (m, 1H), 3.82−3.77 (m, 1H), 3.33−3.28 (m,
1H), 3.26−3.23 (m, 1H), 3.07 (s, 3H), 1.65−1.59 (m, 2H), 1.54−1.49
(m, 2H), 1.23−1.18 (m, 1H), 1.08−1.03 (m, 3H), 1.02−0.97 (m, 3H),
0.88−0.83 (m, 3H), δ minor 8.48 (br, 1H), 7.78 (d, J = 7.8 Hz, 1H),
7.51 (d, J = 7.8 Hz, 1H), 7.33 (dd, J = 8.4, 2.4 Hz, 1H), 6.87 (d, J = 8.4
Hz, 1H), 6.23 (d, J = 7.8 Hz, 1H), 5.22 (s, 1H), 4.89 (s, 1H), 4.07−
4.02 (m, 1H), 3.88−3.83 (m, 1H), 3.46−3.41 (m, 1H), 3.09 (s, 3H),
2.81−2.77 (m, 1H), 1.89−1.84 (m, 1H), 1.83−1.78 (m, 1H), 1.45−
1.39 (m, 3H), 0.80−0.76 (m, 1H); 13C NMR (150 MHz, CDCl3) δ
194.6, 194.4, 179.0, 178.8, 178.1, 176.0, 142.6, 142.1, 141.7, 141.0,
139.0, 138.8, 137.5, 135.4, 135.2, 133.9, 131.9, 129.4, 129.3, 129.2,
129.0, 128.8, 128.6, 128.5, 128.3, 128.2, 127.9, 127.8, 127.6, 127.5,
127.2, 126.8, 126.7, 126.2, 122.6, 110.1, 108.9, 108.8, 108.3, 89.1, 87.9,
85.7, 84.1, 65.8, 64.4, 61.8, 61.6, 60.4, 59.3, 58.4, 40.9, 40.7, 40.1, 29.4,
29.2, 29.1, 29.0, 20.1, 20.0, 13.9, 13.8, 13.7; IR (KBr) υ 3679, 3069,
2959, 2932, 2872, 1701, 1608, 1591, 1484, 1431, 1400, 1350, 1263,
1195, 1159, 1113, 1094, 1011, 984, 891, 848, 810 cm−1; MS (m/z)
HRMS (ESI-TOF) calcd for C41H38Cl4N2NaO5 ([M + Na]+)
801.1427, found 801.1422.
1
2k: white solid, 0.362 g, 90%, mp 220−222 °C; H NMR (600
MHz, CDCl3) δ 8.07 (dd, J = 8.5, 2.6 Hz, 1H), 7.78 (dd, J = 8.4, 2.6
Hz, 1H), 7.35 (d, J = 7.2 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 7.28 (d, J =
7.2 Hz, 1H), 7.19−7.15 (m, 3H), 7.11 (t, J = 7.8 Hz, 1H), 7.02 (t, J =
7.8 Hz, 1H), 6.93−6.91 (m, 2H), 6.87 (dd, J = 8.2, 2.5 Hz, 1H), 6.84−
6.81 (m, 3H), 6.72 (s, 1H), 6.69−6.66 (m, 2H), 6.60 (d, J = 7.2 Hz,
2H), 6.28−6.24 (m, 2H), 6.04 (s, 1H), 5.48 (d, J = 15.3 Hz, 1H), 5.30
(s, 1H), 5.16 (d, J = 16.2 Hz, 1H), 4.50 (d, J = 16.2 Hz, 1H), 4.06 (d, J
= 15.3 Hz, 1H), 3.67 (s, 3H), 3.48 (s, 3H), 3.05 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 196.0, 179.7, 176.7, 160.2 (d, J = 171.6 Hz),
159.5, 159.3, 158.6 (d, J = 169.1 Hz), 139.9, 138.4, 138.3, 138.2, 135.3,
134.8, 132.2 (d, J = 8.9 Hz), 128.9, 128.8, 128.7, 128.6, 128.3, 128.2,
127.8, 127.2, 126.4, 120.0, 119.5, 118.5, 115.1, 115.0, 114.9, 114.8,
114.7, 114.6, 114.1, 113.9, 111.7, 110.9, 109.3 (d, J = 7.8 Hz), 109.2
(d, J = 8.1 Hz), 89.5, 84.6, 64.9, 62.8, 60.7, 59.0, 55.3, 55.1, 44.7, 44.1;
IR (KBr) υ 3330, 3068, 2939, 2835, 1694, 1606, 1583, 1489, 1453,
1373, 1346, 1293, 1266, 1181, 1146, 1104, 1052, 994, 958, 897, 837,
808, 783 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C49H40F2N2NaO7 ([M + Na]+) 829.2696, found 829.2696.
1
2p: white solid, 0.338 g, 87%, mp 222−224 °C; H NMR (600
MHz, CDCl3) δ major 8.23 (d, J = 2.4 Hz, 1H), 7.99 (d, J = 2.4 Hz,
1H), 7.35−7.34 (m, 2H), 7.33−7.28 (m, 7H), 7.25−7.23 (m, 2H),
7.20−7.19 (m, 2H), 7.17 (d, J = 9.6 Hz, 1H), 7.10−7.14 (m, 1H),
7.12−7.09 (m, 3H), 7.08 (dd, J = 8.4, 2.4 Hz, 1H), 6.93 (dd, J = 8.4,
1.8 Hz, 1H), 6.69 (s, 1H), 6.51−6.50 (m, 2H), 6.26 (d, J = 8.4 Hz,
1H), 6.22 (d, J = 8.4 Hz, 1H), 6.09 (s, 1H), 5.44 (d, J = 15.6 Hz, 1H),
5.32 (s, 1H), 5.19 (d, J = 16.2 Hz, 1H), 4.47 (d, J = 16.2 Hz, 1H), 4.08
(d, J = 15.6 Hz, 1H), 3.04 (s, 3H), δ minor 8.51 (br, 1H), 7.85 (d, J =
1.8 Hz, 1H), 7.60 (d, J = 1.8 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 6.99 (t,
J = 7.8 Hz, 2H), 6.84 (dd, J = 8.4, 1.8 Hz, 1H), 6.67 (d, J = 8.4 Hz,
1H), 5.98 (d, J = 8.4 Hz, 1H), 5.55 (d, J = 15.6 Hz, 1H), 5.39 (s, 1H),
5.11 (s, 1H), 4.87 (d, J = 15.6 Hz, 1H), 4.69 (d, J = 15.6 Hz, 1H), 3.79
(d, J = 15.6 Hz, 1H), 3.10 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
196.0, 179.5, 176.6, 142.4, 140.6, 136.9, 136.8, 135.1, 134.6, 132.6,
132.1, 129.5, 128.9, 128.8, 128.7, 128.6, 128.2, 128.0, 127.9, 127.8,
127.4, 127.3, 127.1, 126.7, 126.6, 126.3, 109.8, 109.4, 89.6, 84.5, 64.8,
62.6, 60.7, 58.8, 44.7, 44.0; IR (KBr) υ 3678, 3286, 3065, 2934, 1707,
1690, 1608, 1484, 1452, 1431, 1347, 1262, 1238, 1211, 1177, 1159,
1106, 1078, 1029, 972, 944, 879, 813, 753 cm−1; MS (m/z) HRMS
(ESI-TOF) calcd for C47H36Cl2N2NaO5 ([M + Na]+) 801.1893, found
801.1893.
1
2l: white solid, 0.278 g, 93%, mp 242−244 °C; H NMR (600
MHz, CDCl3) δ 8.26 (br, 1H), 8.16 (s, 1H), 7.89 (s, 1H), 7.45 (br,
1H), 7.32 (d, J = 7.2 Hz, 3H), 7.24 (d, J = 7.8 Hz, 2H), 7.21−7.15 (m,
6H), 6.99 (d, J = 8.4 Hz, 1H), 6.60 (d, J = 8.4 Hz, 1H), 6.37 (d, J = 8.4
Hz, 1H), 6.33 (br, 1H), 5.97 (s, 1H), 5.26 (s, 1H), 3.15 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 197.0, 181.0, 178.3, 142.2, 140.9, 137.5,
136.9, 133.7, 133.2, 129.4, 128.8, 128.6, 127.9, 127.6, 127.5, 127.1,
126.8, 126.6, 125.9, 125.2, 111.3, 110.2, 89.1, 84.3, 65.2, 61.4, 59.9,
58.8; IR (KBr) υ 3478, 3360, 3058, 2935, 2839, 1722, 1703, 1621,
1476, 1444, 1347, 1303, 1249, 1219, 1190, 1158, 1106, 1076, 1037,
1006, 976, 956, 897, 814, 754 cm−1; MS (m/z) HRMS (ESI-TOF)
calcd for C33H24Cl2N2NaO5 ([M + Na]+) 621.0954, found 621.0953.
1
2m: white solid, 0.288 g, 92%, mp 216−218 °C; H NMR (600
MHz, CDCl3) δ 8.15 (s, 1H), 7.96 (s, 1H), 7.87 (s, 1H), 7.28 (br,
1H), 7.24 (d, J = 7.8 Hz, 2H), 7.17 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 7.8
Hz, 2H), 6.98 (d, J = 7.8 Hz, 3H), 6.95 (d, J = 8.4 Hz, 2H), 6.58 (d, J
= 8.4 Hz, 1H), 6.35 (d, J = 7.8 Hz, 1H), 6.22 (s, 1H), 5.92 (s, 1H),
5.22 (s, 1H), 3.14 (s, 3H), 2.25 (s, 6H); 13C NMR (150 MHz, CDCl3)
δ 196.2, 181.1, 178.3, 143.5, 142.2, 140.9, 136.9, 134.7, 134.4, 133.7,
129.6, 129.1, 128.8, 128.2, 127.6, 127.0, 126.6, 126.5, 126.0, 125.1,
111.2, 110.2, 89.3, 84.2, 65.2, 61.3, 59.9, 58.9, 21.5, 21.0; IR (KBr) υ
3426, 2929, 2025, 1707, 1618, 1515, 1475, 1438, 1340, 1302, 1249,
1186, 1158, 1109, 1046, 1008, 976, 953, 899, 812, 779 cm−1; MS (m/
z) HRMS (ESI-TOF) calcd for C35H28Cl2N2NaO5 ([M + Na]+)
649.1267, found 649.1267.
1
2q: white solid, 0.322 g, 80%, mp 216−218 °C; H NMR (600
MHz, CDCl3) δ 8.21 (s, 1H), 7.97 (s, 1H), 7.37 (d, J = 7.2 Hz, 2H),
7.33−7.29 (m, 3H), 7.17−7.14 (m, 5H), 7.12−7.10 (m, 2H), 7.06 (dd,
J = 8.2, 1.6 Hz, 1H), 6.98 (d, J = 7.8 Hz, 2H), 6.94 (dd, J = 8.2, 1.6 Hz,
1H), 6.86 (d, J = 7.8 Hz, 2H), 6.60 (s, 1H), 6.53 (d, J = 7.8 Hz, 2H),
6.26 (d, J = 9.0 Hz, 1H), 6.25 (d, J = 8.4 Hz, 1H), 6.05 (s, 1H), 5.40
(d, J = 15.0 Hz, 1H), 5.28−5.26 (m, 2H), 4.43 (d, J = 15.0 Hz, 1H),
4.17 (d, J = 15.0 Hz, 1H), 3.04 (s, 3H), 2.34 (s, 3H), 2.26 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 195.4, 179.5, 176.8, 143.5, 142.4, 140.6,
137.4, 135.1, 134.6, 134.2, 134.0, 132.2, 129.5, 128.9, 128.7, 128.5,
128.4, 127.9, 127.4, 127.3, 127.0, 126.7, 126.5, 126.3, 109.7, 109.3,
89.8, 84.4, 64.8, 62.5, 60.7, 58.9, 44.7, 44.1, 21.6, 21.3; IR (KBr) υ
3678, 3299, 3034, 2927, 1707, 1683, 1608, 1484, 1454, 1431, 1345,
1262, 1236, 1204, 1180, 1160, 1113, 1080, 1130, 994, 971, 940, 877,
840, 811, 787 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C49H40Cl2N2NaO5 ([M + Na]+) 829.2206, found 829.2202.
1
2n: white solid, 0.320 g, 87%, mp 228−230 °C; H NMR (600
MHz, CDCl3) δ 8.02 (s, 1H), 7.87 (s, 1H), 7.21 (d, J = 8.4 Hz, 1H),
7.10 (d, J = 7.8 Hz, 2H), 7.04−7.01 (m, 3H), 6.91 (d, J = 7.8 Hz, 3H),
6.90 (s, 1H), 6.52 (d, J = 6.0 Hz, 2H), 6.31 (d, J = 8.4 Hz, 1H), 5.98
(s, 1H), 5.16 (s, 1H), 3.95−3.90 (m, 1H), 3.86−3.81 (m, 1H), 3.31−
3.26 (m, 1H), 3.21−3.16 (m, 1H), 3.08 (s, 3H), 2.24 (s, 3H), 2.22 (s,
3H), 1.64−1.60 (m, 1H), 1.54−1.52 (m, 1H), 1.43−1.40 (m, 2H),
1.11−1.08 (m, 1H), 1.02−0.96 (m, 5H), 0.95−0.91 (m, 1H), 0.80 (t, J
= 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 195.4, 179.3, 176.3,
143.3, 142.7, 141.0, 137.3, 134.4, 133.7, 132.4, 129.2, 128.7, 128.6,
128.5, 128.1, 127.3, 126.9, 126.8, 126.2, 108.6, 108.5, 89.1, 84.4, 64.5,
61.6, 60.3, 58.7, 40.6, 40.0, 29.4, 29.0, 21.5, 21.0, 20.1, 14.0, 13.7; IR
(KBr) υ 3680, 3318, 3069, 2958, 2930, 2870, 2351, 1702, 1608, 1484,
1
2r: white solid, 0.405 g, 96%, mp 234−236 °C; H NMR (600
MHz, CDCl3) δ 8.17 (d, J = 1.8 Hz, 1H), 7.94 (d, J = 1.8 Hz, 1H),
7.38 (d, J = 7.2 Hz, 2H), 7.36 (d, J = 6.6 Hz, 2H), 7.34−7.32 (m, 1H),
7.23−7.22 (m, 5H), 7.16−7.14 (m, 4H), 7.10 (dd, J = 8.3, 2.1 Hz,
1H), 7.02−6.99 (m, 3H), 6.66 (s, 1H), 6.58−6.57 (m, 2H), 6.36 (d, J
G
dx.doi.org/10.1021/jo4010603 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1
= 8.4 Hz, 1H), 6.32 (d, J = 8.4 Hz, 1H), 6.00 (s, 1H), 5.33 (d, J = 15.0
Hz, 1H), 5.24−5.22 (m, 2H), 4.47 (d, J = 16.2 Hz, 1H), 4.28 (d, J =
15.0 Hz, 1H), 3.02 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 194.6,
179.2, 176.4, 142.3, 140.6, 139.1, 135.4, 135.0, 134.8, 134.3, 134.1,
131.7, 129.7, 129.0, 128.8, 128.7, 128.6, 128.3, 128.1, 128.0, 127.7,
127.6, 127.4, 126.7, 126.3, 109.9, 109.6, 89.7, 84.0, 64.6, 62.4, 60.7,
58.6, 44.8, 44.1; IR (KBr) υ 3319, 3068, 2932, 2834, 1705, 1691, 1609,
1591, 1484, 1454, 1430, 1401, 1367, 1342, 1264, 1236, 1211, 1180,
1160, 1094, 1031, 1003, 968, 939, 889, 848, 812, 794, 775 cm−1; MS
(m/z) HRMS (ESI-TOF) calcd for C47H34Cl4N2NaO5 ([M + Na]+)
869.1114, found 869.1111.
2v: white solid, 0.348 g, 85%, mp 234−236 °C; H NMR (600
MHz, CDCl3) δ 8.24 (d, J = 1.8 Hz, 1H), 7.97 (d, J = 1.8 Hz, 1H),
7.36−7.35 (m, 2H), 7.33−7.29 (m, 3H), 7.19−7.16 (m, 3H), 7.14−
7.10 (m, 4H), 7.05 (dd, J = 8.3, 1.9 Hz, 1H), 6.97 (d, J = 7.8 Hz, 2H),
6.94 (dd, J = 8.3, 1.9 Hz, 1H), 6.86 (d, J = 7.8 Hz, 2H), 6.54 (d, J = 7.2
Hz, 2H), 6.48 (s, 1H), 6.23 (d, J = 8.4 Hz, 2H), 6.12 (s, 1H), 5.32 (d, J
= 15.0 Hz, 1H), 5.28−5.25 (m, 2H), 4.44 (d, J = 16.2 Hz, 1H), 4.16
(d, J = 15.0 Hz, 1H), 3.32−3.27 (m, 1H), 3.11−3.06 (m, 1H), 2.33 (s,
3H), 2.26 (s, 3H), 0.80 (t, J = 6.6 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 195.6, 179.6, 176.9, 143.4, 142.4, 140.9, 137.3, 135.2, 134.7,
134.4, 134.3, 132.1, 129.3, 128.9, 128.7, 128.5, 128.4, 128.1, 127.9,
127.4, 127.3, 127.1, 126.8, 126.6, 126.5, 126.3, 109.7, 109.2, 88.3, 84.3,
68.3, 65.0, 62.7, 59.1, 44.8, 44.1, 21.6, 21.3, 15.3; IR (KBr) υ 3291,
3074, 3029, 2977, 2924, 1704, 1682, 1609, 1514, 1482, 1454, 1431,
1379, 1359, 1341, 1265, 1238, 1205, 1178, 1159, 1097, 1080, 1027,
976, 940, 898, 875, 839, 809, 786 cm−1; MS (m/z) HRMS (ESI-TOF)
calcd for C50H42Cl2N2NaO5 ([M + Na]+) 843.2363, found 843.2357.
1
2s: white solid, 0.298 g, 83%, mp 214−216 °C; H NMR (600
MHz, CDCl3) δ 8.05 (dd, J = 8.7, 2.3 Hz, 1H), 7.67 (dd, J = 8.4, 2.3
Hz, 1H), 7.12 (d, J = 7.8 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 6.93 (dd, J
= 8.8, 2.3 Hz, 1H), 6.90 (d, J = 7.8 Hz, 4H), 6.74 (td, J = 8.6, 2.3 Hz,
1H), 6.54 (s, 1H), 6.51 (dd, J = 8.4, 4.1 Hz, 1H), 6.31 (dd, J = 8.4, 4.0
Hz, 1H), 6.07 (s, 1H), 5.18 (s, 1H), 3.91−3.86 (m, 1H), 3.83−3.78
(m, 1H), 3.35−3.30 (m, 1H), 3.29−3.24 (m, 1H), 3.23−3.19 (m, 1H),
3.13−3.08 (m, 1H), 2.24 (s, 3H), 2.21 (s, 3H), 1.64−1.62 (m, 1H),
1.58−1.53 (m, 1H), 1.45−1.40 (m, 2H), 1.15−1.11 (m, 1H), 1.03−
0.96 (m, 6H), 0.84−0.80 (m, 6H); 13C NMR (150 MHz, CDCl3) δ
195.5, 179.4, 176.5, 159.9 (d, J = 173.9 Hz), 158.3 (d, J = 170.7 Hz),
143.2, 140.0, 138.6, 137.1, 134.4, 133.9, 132.3 (d, J = 8.7 Hz), 128.6,
128.5, 127.9, 127.4, 126.2, 114.9, 114.8, 114.7, 114.6, 114.1, 114.0,
108.0 (d, J = 8.3 Hz), 107.9 (d, J = 7.8 Hz), 87.8, 84.5, 68.1, 64.7, 61.6,
59.1, 40.7, 40.0, 29.5, 29.0, 21.5, 21.0, 20.6, 20.2, 20.1, 15.2, 13.9, 13.7;
IR (KBr) υ 3317, 3066, 2959, 2932, 2870, 1697, 1608, 1573, 1488,
1454, 1357, 1269, 1223, 1183, 1146, 1122, 1022, 987, 936, 900, 837,
814, 792 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C44H46F2N2NaO5 ([M + Na]+) 743.3267, found 743.3270.
1
2w: white solid, 0.344 g, 80%, mp 230−232 °C; H NMR (600
MHz, CDCl3) δ major 8.19 (d, J = 1.8 Hz, 1H), 7.94 (d, J = 1.2 Hz,
1H), 7.38−7.31 (m, 5H), 7.26−7.22 (m, 7H), 7.13 (dd, J = 8.4, 2.4
Hz, 4H), 6.99 (d, J = 8.4 Hz, 2H), 6.59−6.58 (m, 2H), 6.53 (s, 1H),
6.34 (d, J = 8.4 Hz, 1H), 6.31 (d, J = 8.4 Hz, 1H), 6.07 (s, 1H), 5.27
(d, J = 15.0 Hz, 1H), 5.34−5.21 (m, 2H), 4.48 (d, J = 16.2 Hz, 1H),
4.26 (d, J = 15.0 Hz, 1H), 3.27−3.23 (m, 1H), 3.09−3.04 (m, 1H),
0.80 (t, J = 7.2 Hz, 3H), δ minor 8.10 (br, 1H), 7.92 (br, 1H), 7.47 (d,
J = 7.2 Hz, 3H), 7.42−7.41 (m, 3H), 6.82 (d, J = 8.4 Hz, 2H), 6.44 (d,
J = 7.8 Hz, 1H), 6.27 (d, J = 8.4 Hz, 1H), 5.69 (s, 1H), 5.14 (s, 1H),
4.95 (d, J = 15.0 Hz, 1H), 4.62 (d, J = 15.0 Hz, 1H), 2.71 (br, 1H),
1.98 (br, 1H), 1.15−1.04 (m, 3H); 13C NMR (150 MHz, CDCl3) δ
194.8, 179.2, 176.5, 142.3, 140.8, 139.0, 135.7, 135.1, 134.9, 134.4,
133.9, 131.7, 129.5, 129.0, 128.8, 128.7, 128.6, 128.3, 128.2, 128.0,
127.9, 127.8, 127.5, 127.3, 126.7, 126.3, 109.9, 109.4, 88.2, 83.9, 68.5,
64.8, 62.6, 58.8, 44.1, 15.2; IR (KBr) υ 3326, 3068, 2931, 2351, 1706,
1691, 1609, 1591, 1483, 1454, 1430, 1400, 1348, 1264, 1234, 1206,
1178, 1157, 1093, 1031, 970, 881, 847, 810, 794, 771 cm−1; MS (m/z)
HRMS (ESI-TOF) calcd for C48H36Cl4N2NaO5 ([M + Na]+)
883.1271, found 883.1262.
1
2t: white solid, 0.296 g, 78%, mp 218−220 °C; H NMR (600
MHz, CDCl3) δ major 8.03 (dd, J = 8.4, 2.5 Hz, 1H), 7.65 (dd, J = 8.3,
2.5 Hz, 1H), 7.15−7.08 (m, 8H), 6.95 (td, J = 8.7, 2.5 Hz, 1H), 6.80
(td, J = 8.6, 2.5 Hz, 1H), 6.60 (s, 1H), 6.55 (dd, J = 8.5, 4.1 Hz, 1H),
6.37 (dd, J = 8.5, 4.0 Hz, 1H), 6.03 (s, 1H), 5.13 (s, 1H), 3.94−3.89
(m, 1H), 3.79−3.74 (m, 1H), 3.31−3.25 (m, 3H), 3.12−3.07 (m, 1H),
1.66−1.62 (m, 1H), 1.59−1.53 (m, 1H), 1.48−1.39 (m, 2H), 1.26−
1.21 (m, 1H), 1.11−1.05 (m, 3H), 0.98 (t, J = 7.2 Hz, 3H), 0.87 (t, J =
7.2 Hz, 3H), 0.84 (t, J = 7.2 Hz, 3H), δ minor 7.96 (d, J = 8.2 Hz, 1H),
7.62 (d, J = 2.4 Hz, 1H), 6.76 (dd, J = 8.8, 2.3 Hz, 1H), 6.51 (dd, J =
8.5, 4.1 Hz, 1H), 6.35−6.34 (m, 1H), 5.59 (s, 1H), 5.06 (s, 1H), 3.37−
3.35 (m, 1H), 2.65−2.64 (m, 2H), 1.97−1.96 (m, 2H); 13C NMR
(150 MHz, CDCl3) δ 194.7, 179.2, 176.2, 160.0 (d, J = 173.6 Hz),
158.4 (d, J = 171.2 Hz), 139.9, 138.9, 138.5, 135.4, 135.2, 133.7, 131.9
(d, J = 8.9 Hz), 128.6, 128.5, 128.2, 127.9, 127.8, 127.7, 127.5, 127.1,
115.2, 115.1, 115.0, 114.8, 114.6, 114.2, 114.0, 108.4 (d, J = 8.1 Hz),
108.2 (d, J = 8.1 Hz), 87.7, 84.1, 68.2, 64.6, 61.8, 58.9, 40.7, 40.1, 29.5,
29.1, 21.2, 15.2, 13.9, 13.7; IR (KBr) υ 3332, 3068, 2958, 2933, 2873,
1698, 1681, 1619, 1591, 1490, 1457, 1363, 1270, 1218, 1194, 1144,
1113, 1091, 1048, 1013, 985, 937, 907, 837, 814, 778, 752 cm−1; MS
(m/z) HRMS (ESI-TOF) calcd for C42H40Cl2F2N2NaO5 ([M + Na]+)
783.2175, found 783.2172.
2. General Procedure for the Preparation of the Amino-
Substituted Dispirocyclopentanebisoxindoles (3a−3k). A sol-
ution of 3-phenacylideneoxindoles (1.0 mmol), amine (2.0 mmol),
and piperidine (0.5 mmol, 0.042 g) in 10.0 mL of acetonitrile was
stirred at room temperature for about 12 h. Then, the resulting
precipitates were collected by filtration and washed with a little cold
ethanol to give the pure products 3a−3k for analysis.
1
3a: white solid, 0.324 g, 80%, mp 228−230 °C; H NMR (600
MHz, CDCl3) δ 8.12 (br, 1H), 7.98 (br, 1H), 7.34 (dd, J = 8.3, 1.7 Hz,
1H), 7.13 (d, J = 7.8 Hz, 2H), 7.08 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 8.4
Hz, 2H), 6.87 (d, J = 8.4 Hz, 1H), 6.81 (d, J = 7.8 Hz, 2H), 6.60 (d, J
= 7.8 Hz, 2H), 6.57−6.55 (m, 3H), 6.47 (d, J = 8.4 Hz, 1H), 6.16 (d, J
= 9.6 Hz, 1H), 6.09 (d, J = 8.4 Hz, 2H), 5.40 (s, 1H), 5.32 (d, J = 9.6
Hz, 1H), 3.69−3.64 (m, 1H), 3.62−3.58 (m, 1H), 3.25−3.19 (m, 2H),
2.19 (s, 3H), 2.11 (s, 3H), 1.99 (s, 3H), 1.25−1.15 (m, 2H), 1.07−
1.01 (m, 2H), 0.90−0.85 (m, 3H), 0.74−0.70 (m, 6H), 0.67−0.63 (m,
1H); 13C NMR (150 MHz, CDCl3) δ 195.1, 180.5, 176.0, 143.4,
143.3, 142.8, 141.3, 137.6, 134.3, 132.7, 132.1, 129.3, 128.7, 128.6,
128.2, 128.1, 127.3, 126.9, 126.6, 126.5, 126.3, 125.8, 113.2, 109.0,
108.7, 86.2, 65.6, 64.1, 61.2, 60.0, 40.7, 40.0, 29.2, 28.9, 21.5, 21.0,
20.2, 20.1, 14.0, 13.7; IR (KBr) υ 3454, 3034, 2979, 2948, 2025, 1739,
1709, 1651, 1609, 1480, 1459, 1433, 1369, 1346, 1313, 1284, 1234,
1183, 1139, 1117, 1024, 952, 918, 900, 875, 845, 812, 775 cm−1; MS
(m/z) HRMS (ESI-TOF) calcd for C49H49Cl2N3NaO4 ([M + Na]+)
836.2992, found 836.2986.
1
2u: white solid, 0.380 g, 97%, mp 204−206 °C; H NMR (600
MHz, CDCl3) δ 8.18 (d, J = 1.8 Hz, 1H), 7.87 (d, J = 1.8 Hz, 1H),
7.22−7.19 (m, 3H), 7.07 (d, J = 9.0 Hz, 2H), 7.02 (dd, J = 8.3, 2.1 Hz,
1H), 6.63 (d, J = 9.0 Hz, 2H), 6.59 (d, J = 9.0 Hz, 2H), 6.53 (d, J = 7.8
Hz, 1H), 6.45 (s, 1H), 6.35 (d, J = 8.4 Hz, 1H), 6.04 (s, 1H), 5.13 (s,
1H), 3.95−3.90 (m, 1H), 3.84−3.80 (m, 1H), 3.74 (s, 3H), 3.70(s,
3H), 3.36−3.32 (m, 1H), 3.31−3.26 (m, 1H), 3.24−3.19 (m, 1H),
3.14−3.09 (m, 1H), 1.66−1.63 (m, 1H), 1.57−1.55 (m, 1H), 1.46−
1.41 (m, 2H), 1.19−1.13 (m, 1H), 1.07−1.02 (m, 3H), 0.98 (t, J = 7.2
Hz, 3H), 0.85−0.80 (m, 6H); 13C NMR (150 MHz, CDCl3) δ 194.1,
179.4, 176.5, 163.0, 159.0, 142.7, 141.1, 132.3, 129.8, 129.5, 129.1,
128.6, 128.5, 128.4, 127.6, 126.8, 126.3, 113.2, 112.6, 108.5, 87.8, 84.2,
68.1, 64.7, 61.5, 58.0, 55.4, 55.0, 40.6, 40.0, 29.5, 29.1, 20.2, 15.3, 13.8,
13.7; IR (KBr) υ 3679, 3270, 3068, 2961, 2933, 2873, 2378, 2348,
2313, 1691, 1604, 1576, 1513, 1485, 1432, 1355, 1256, 1178, 1159,
1114, 1031, 982, 848, 808 cm−1; MS (m/z) HRMS (ESI-TOF) calcd
for C44H46Cl2N2NaO7 ([M + Na]+) 807.2574, found 807.2574.
1
3b: white solid, 0.354 g, 83%, mp 248−250 °C; H NMR (600
MHz, CDCl3) δ 8.19 (d, J = 1.8 Hz, 1H), 7.82 (d, J = 1.2 Hz, 1H),
7.28 (dd, J = 8.3, 1.7 Hz, 1H), 7.15 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4
Hz, 3H), 7.03 (dd, J = 8.3, 1.7 Hz, 1H), 6.98 (d, J = 8.4 Hz, 2H),
6.83−6.81 (m, 3H), 6.64−6.60 (m, 3H), 6.33 (s, 1H), 6.21 (d, J = 8.4
Hz, 1H), 6.03 (d, J = 8.4 Hz, 2H), 5.07 (s, 1H), 3.84−3.79 (m, 1H),
3.69−3.64 (m, 1H), 3.26−3.21 (m, 2H), 2.07 (s, 3H), 1.32−1.26 (m,
2H), 1.18−1.11 (m, 3H), 1.05−1.01 (m, 2H), 0.92−0.90 (m, 1H),
H
dx.doi.org/10.1021/jo4010603 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
0.85−0.80 (m, 6H); 13C NMR (150 MHz, CDCl3) δ 194.3, 180.3,
175.7, 143.0, 142.7, 141.2, 139.0, 135.2, 134.1, 131.7, 129.5, 129.1,
128.6, 128.5, 128.4, 128.0, 127.9, 127.6, 127.2, 127.1, 126.4, 125.8,
113.2, 109.4, 109.0, 85.9, 65.7, 64.0, 61.3, 59.6, 40.8, 40.1, 29.2, 29.0,
20.2, 20.1, 20.0, 13.9, 13.7; IR (KBr) υ 3425, 2959, 2930, 2870, 2025,
1702, 1680, 1611, 1520, 1484, 1431, 1379, 1356, 1294, 1231, 1186,
1115, 976, 813 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C47H43Cl4N3NaO4 ([M + Na]+) 876.1900, found 876.1899.
3450, 3368, 3280, 3065, 3028, 2918, 2848, 2025, 1712, 1671, 1608,
1483, 1451, 1431, 1376, 1348, 1233, 1176, 1117, 1079, 1030, 952, 839,
811, 788 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C55H45Cl2N3NaO4 ([M + Na]+) 904.2679, found 904.2666.
1
3g: white solid, 0.314 g, 74%, mp 242−246 °C; H NMR (600
MHz, CDCl3) δ 8.18 (s, 1H), 7.90 (s, 1H), 7.38−7.37 (m, 2H), 7.33−
7.32 (m, 3H), 7.18−7.16 (m, 1H), 7.13−7.10 (m, 6H), 7.05 (d, J = 8.4
Hz, 1H), 6.98 (d, J = 7.8 Hz, 2H), 6.93 (d, J = 8.4 Hz, 1H), 6.78 (d, J
= 7.8 Hz, 2H), 6.71 (s, 1H), 6.53 (d, J = 7.2 Hz, 2H), 6.24 (t, J = 8.4
Hz, 2H), 5.62 (s, 1H), 5.25 (d, J = 16.2 Hz, 1H), 5.20 (d, J = 15.6 Hz,
1H), 5.15 (s, 1H), 4.43 (d, J = 16.2 Hz, 1H), 4.33 (d, J = 15.6 Hz, 1H),
2.40−2.37 (m, 1H), 2.34 (s, 3H), 2.23 (s, 3H), 2.14−2.10 (m, 1H),
1.03−0.99 (m, 2H), 0.94−0.88 (m, 2H), 0.60 (t, J = 7.8 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 195.6, 181.6, 176.7, 143.2, 142.3, 140.9,
137.4, 135.2, 134.5, 134.3, 133.7, 129.4, 128.8, 128.7, 128.6, 128.5,
128.4, 128.0, 127.3, 127.1, 127.0, 126.9, 126.5, 126.4, 126.0, 109.7,
109.2, 85.9, 72.2, 65.1, 62.8, 60.6, 49.5, 44.9, 44.0, 32.3, 21.5, 21.3,
19.8, 13.7; IR (KBr) υ 3451, 3292, 3069, 2925, 2861, 2025, 1706,
1683, 1609, 1485, 1403, 1377, 1354, 1264, 1236, 1181, 1124, 1081,
1034, 977, 816, 789 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C52H47N3Cl2O4 ([M + H]+) 848.3016, found 848.3017.
1
3c: white solid, 0.330 g, 78%, mp 249−251 °C; H NMR (600
MHz, CDCl3) δ 8.12 (dd, J = 8.4, 2.4 Hz, 1H), 7.71 (dd, J = 8.3, 2.3
Hz, 1H), 7.19−7.14 (m, 4H), 7.10 (t, J = 7.8 Hz, 2H), 7.01 (t, J = 7.8
Hz, 2H), 6.88−6.84 (m, 10H), 6.69 (d, J = 7.8 Hz, 2H), 6.61 (td, J =
8.6, 2.4 Hz, 1H), 6.52 (d, J = 7.2 Hz, 2H), 6.48 (s, 1H), 6.33 (dd, J =
8.5, 4.1 Hz, 1H), 6.09 (d, J = 8.4 Hz, 2H), 5.96 (dd, J = 8.5, 4.2 Hz,
1H), 5.27−5.24 (m, 2H), 5.18 (d, J = 16.2 Hz, 1H), 4.42 (d, J = 16.2
Hz, 1H), 4.20 (d, J = 16.2 Hz, 1H), 2.28 (s, 3H), 2.24 (s, 3H), 2.11 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 195.1, 181.2, 176.8, 160.2 (d, J =
185.6 Hz), 158.6 (d, J = 183.0 Hz), 143.6, 143.5, 139.9, 138.4, 137.6,
135.3, 134.1, 133.7, 133.0, 131.8 (d, J = 8.8 Hz), 128.8, 128.7, 128.6,
128.5, 127.6, 127.4, 127.0, 126.8, 126.7, 126.6, 126.5, 115.2, 115.1,
114.9, 114.7, 114.6, 114.4, 113.7, 113.6, 113.2, 109.8 (d, J = 8.2 Hz),
109.4 (d, J = 8.0 Hz), 86.3, 66.4, 64.4, 62.4, 60.5, 44.4, 21.4, 20.3; IR
(KBr) υ 3424, 3071, 2956, 2931, 2868, 2026, 1711, 1675, 1611, 1520,
1483, 1431, 1379, 1354, 1294, 1251, 1224, 1190, 1095, 1013, 968, 847,
808 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C55H45F2N3NaO4
([M + Na]+) 872.3270, found 872.3270.
1
3h: white solid, 0.360 g, 84%, mp 224−226 °C; H NMR (600
MHz, CDCl3) δ 8.14 (s, 1H), 7.95 (s, 1H), 7.45 (d, J = 7.2 Hz, 2H),
7.38−7.34 (m, 4H), 7.18−7.16 (m, 1H), 7.14−7.11 (m, 4H), 7.08 (d, J
= 7.8 Hz, 2H), 7.03 (d, J = 7.8 Hz, 1H), 6.96−6.95 (m, 3H), 6.73 (d, J
= 7.2 Hz, 2H), 6.55 (d, J = 7.8 Hz, 2H), 6.32 (d, J = 8.4 Hz, 1H), 6.20
(d, J = 8.4 Hz, 1H), 5.73 (s, 1H), 5.23−5.21 (m, 2H), 5.01 (d, J = 15.0
Hz, 1H), 4.52 (d, J = 14.4 Hz, 1H), 4.43 (d, J = 16.2 Hz, 1H), 2.78 (s,
2H), 2.34 (s, 3H), 2.21 (s, 3H), 1.98 (br, 2H), 1.13−1.04 (m, 6H);
13C NMR (150 MHz, CDCl3) δ 193.8, 180.4, 174.9, 141.3, 140.5,
139.3, 135.1, 133.4, 133.3, 132.8, 132.5, 131.0, 127.3, 127.0, 126.0,
126.8, 126.7, 126.5, 126.3, 126.2, 125.3, 125.1, 124.6, 124.5, 107.7,
107.2, 83.8, 64.1, 60.9, 58.3, 51.7, 43.4, 42.2, 24.9, 22.2, 19.6, 19.4; IR
(KBr) υ 3449, 3065, 3033, 2931, 2851, 2815, 2763, 2026, 1708, 1678,
1606, 1516, 1483, 1432, 1377, 1342, 1271, 1239, 1177, 1118, 1081,
1033, 1004, 970, 898, 843, 810, 789 cm−1; MS (m/z) HRMS (ESI-
TOF) calcd for C53H47Cl2N3NaO4 ([M + Na]+) 882.2836, found
882.2833.
1
3d: white solid, 0.330 g, 76%, mp 264−266 °C; H NMR (600
MHz, CDCl3) δ 8.29 (s, 1H), 7.93 (s, 1H), 7.17−7.11 (m, 5H), 7.09
(t, J = 7.8 Hz, 2H), 7.02 (t, J = 7.2 Hz, 2H), 6.91−6.88 (m, 9H), 6.84−
6.82 (m, 3H), 6.55 (t, J = 7.2 Hz, 1H), 6.51 (s, 1H), 6.48 (d, J = 7.8
Hz, 2H), 6.34 (d, J = 8.4 Hz, 1H), 6.20 (d, J = 8.4 Hz, 2H), 5.96 (d, J
= 8.4 Hz, 1H), 5.31 (d, J = 16.2 Hz, 1H), 5.26 (s, 1H), 5.16 (d, J =
15.6 Hz, 1H), 4.42 (d, J = 16.2 Hz, 1H), 4.21 (d, J = 16.2 Hz, 1H),
2.28 (s, 3H), 2.23 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 195.0,
181.1, 176.6, 145.7, 143.6, 142.6, 140.9, 137.8, 135.1, 134.2, 133.5,
132.9, 131.7, 129.7, 129.2, 128.9, 128.8, 128.6, 128.5, 127.7, 127.4,
127.1, 126.8, 126.6, 126.5, 125.8, 117.9, 113.2, 110.1, 86.2, 66.1, 64.2,
62.5, 60.2, 44.6, 44.2, 21.6, 21.3; IR (KBr) υ 3396, 3279, 3072, 2918,
1806, 1712, 1682, 1607, 1513, 1486, 1432, 1378, 1356, 1312, 1255,
1235, 1181, 1144, 1078, 1034, 971, 896, 873, 836, 812, 787 cm−1; MS
(m/z) HRMS (ESI-TOF) calcd for C54H43Cl2N3NaO4 ([M + Na]+)
890.2523, found 890.2519.
1
3i: white solid, 0.290 g, 70%, mp 226−228 °C; H NMR (600
MHz, CDCl3) δ 7.98 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H),
7.44 (d, J = 7.2 Hz, 2H), 7.36−7.33 (m, 4H), 7.17−7.10 (m, 7H), 6.94
(d, J = 7.8 Hz, 2H), 6.77−6.74 (m, 3H), 6.67 (t, J = 8.4 Hz, 1H), 6.60
(d, J = 7.2 Hz, 2H), 6.31 (dd, J = 8.4, 3.6 Hz, 1H), 6.19 (dd, J = 8.4,
4.2 Hz, 1H), 5.75 (s, 1H), 5.22 (s, 1H), 5.16 (d, J = 16.2 Hz, 1H), 5.01
(d, J = 15.0 Hz, 1H), 4.52 (d, J = 15.0 Hz, 1H), 4.45 (d, J = 16.2 Hz,
1H), 2.78 (br, 2H), 2.33 (s, 3H), 2.22 (s, 3H), 1.98 (br, 2H), 1.13−
1.03 (m, 6H); 13C NMR (150 MHz, CDCl3) δ 195.7, 182.4, 177.0,
160.0 (d, J = 181.6 Hz), 158.4 (d, J = 178.4 Hz), 143.3, 139.7, 138.7,
137.0, 135.5, 135.4, 134.9, 134.4, 133.0 (d, J = 8.7 Hz), 128.9, 128.7,
128.6, 128.5, 128.1, 127.3, 127.0, 126.6, 126.4, 114.8, 114.6, 114.5,
114.4, 114.3, 114.2, 109.0 (d, J = 7.4 Hz), 108.8 (d, J = 8.1 Hz), 85.5,
66.2, 62.7, 60.5, 53.6, 45.4, 44.2, 26.9, 24.2, 21.6, 21.3; IR (KBr) υ
3449, 3279, 3087, 3033, 2929, 2850, 2807, 2764, 1679, 1606, 1487,
1448, 1380, 1344, 1264, 1225, 1170, 1137, 1081, 1011, 977, 903, 863,
813, 793, 760 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C53H47F2N3NaO4 ([M + Na]+) 850.3427, found 850.3424.
1
3e: white solid, 0.388 g, 86%, mp 257−259 °C; H NMR (600
MHz, CDCl3) δ 8.27 (s, 1H), 7.92 (s, 1H), 7.19−7.15 (m, 4H), 7.13
(d, J = 7.8 Hz, 1H), 7.11−7.05 (m, 4H), 6.92−6.83 (m, 11H), 6.78 (s,
1H), 6.48 (d, J = 7.2 Hz, 2H), 6.44 (d, J = 8.4 Hz, 1H), 6.34 (d, J = 7.8
Hz, 1H), 6.11 (d, J = 8.4 Hz, 2H), 6.00 (d, J = 8.4 Hz, 1H), 5.30 (d, J
= 16.2 Hz, 1H), 5.24 (s, 1H), 5.20 (d, J = 16.2 Hz, 1H), 4.63 (d, J =
8.4 Hz, 1H), 4.42 (d, J = 15.6 Hz, 1H), 4.19 (d, J = 16.2 Hz, 1H), 2.30
(s, 3H), 2.24 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 194.9, 180.9,
176.5, 144.4, 143.7, 142.5, 140.8, 137.9, 135.0, 134.1, 133.4, 132.7,
131.5, 129.8, 129.0, 128.9, 128.8, 128.7, 128.4, 128.3, 127.8, 127.4,
127.3, 127.1, 126.7, 126.5, 126.4, 125.8, 122.4, 114.2, 110.2, 110.0,
86.1, 66.0, 64.1, 62.4, 60.0, 44.6, 44.2, 21.6, 21.2; IR (KBr) υ 3448,
3071, 2921, 2026, 1710, 1683, 1608, 1486, 1431, 1376, 1348, 1234,
1180, 1095, 1034, 973, 813, 788 cm−1; MS (m/z) HRMS (ESI-TOF)
calcd for C54H42Cl3N3NaO4 ([M + Na]+) 924.2133, found 924.2123.
1
3j: white solid, 0.362 g, 85%, mp 224−226 °C; H NMR (600
1
3f: white solid, 0.352 g, 80%, mp 242−246 °C; H NMR (600
MHz, CDCl3) δ major 8.18 (s, 1H), 7.92 (s, 1H), 7.45−7.44 (m, 2H),
7.40−7.36 (m, 3H), 7.30 (s, 1H), 7.20−7.11 (m, 6H), 7.07 (d, J = 7.8
Hz, 2H), 7.03 (d, J = 8.4 Hz, 1H), 6.99−6.95 (m, 3H), 6.77−6.74 (m,
2H), 6.58 (d, J = 7.2 Hz, 2H), 6.33 (d, J = 8.4 Hz, 1H), 6.20 (d, J = 8.4
Hz, 1H), 5.68 (s, 1H), 5.20 (s, 1H), 5.05 (d, J = 15.0 Hz, 1H), 4.46 (d,
J = 3.6 Hz, 1H), 4.44 (br, 1H), 3.23−3.20 (m, 2H), 3.12−3.09 (m,
2H), 2.81−2.78 (m, 2H), 2.33 (s, 3H), 2.23 (s, 3H), 1.98 (t, J = 8.4
Hz, 2H), δ minor 8.90 (s, 1H), 7.82 (s, 1H), 7.60 (d, J = 7.2 Hz, 2H),
7.52 (s, 1H), 6.83 (d, J = 7.8 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 5.97
(d, J = 7.8 Hz, 1H), 5.25 (d, J = 15.6 Hz, 1H), 5.17−5.14 (m, 3H),
4.87 (s, 1H), 4.61 (d, J = 15.6 Hz, 1H), 3.86 (d, J = 15.6 Hz, 1H), 2.31
(s, 3H), 2.16 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 195.5, 182.0,
176.7, 143.3, 142.4, 141.1, 137.3, 135.2, 134.9, 134.7, 134.4, 132.8,
MHz, CDCl3) δ 8.04 (d, J = 1.8 Hz, 1H), 7.90 (d, J = 1.2 Hz, 1H),
7.36 (d, J = 7.8 Hz, 2H), 7.29−7.27 (m, 1H), 7.25−7.23 (m, 2H),
7.17−7.15 (m, 1H), 7.11−7.03 (m, 10H), 6.96 (d, J = 8.4 Hz, 2H),
6.92 (dd, J = 7.8, 1.8 Hz, 1H), 6.78−6.74 (m, 5H), 6.50 (d, J = 7.8 Hz,
2H), 6.22 (d, J = 3.0 Hz, 1H), 6.20 (d, J = 3.0 Hz, 1H), 5.62 (s, 1H),
5.22 (d, J = 16.2 Hz, 1H), 5.17−5.14 (m, 2H), 4.40 (d, J = 16.2 Hz,
1H), 4.32 (d, J = 15.0 Hz, 1H), 3.45 (d, J = 13.8 Hz, 1H), 3.37 (d, J =
13.2 Hz, 1H), 2.35 (s, 3H), 2.23 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 195.5, 181.6, 176.6, 143.2, 142.4, 140.9, 139.3, 137.5, 135.2,
134.5, 134.4, 133.6, 132.4, 129.5, 129.0, 128.7, 128.6, 128.5, 128.4,
128.1, 128.0, 127.3, 127.1, 127.0, 126.8, 126.4, 126.0, 109.7, 109.3,
85.9, 70.8, 65.2, 63.0, 60.6, 52.8, 45.1, 44.0, 21.6, 21.3; IR (KBr) υ
I
dx.doi.org/10.1021/jo4010603 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
129.5, 129.1, 129.0, 128.7, 128.6, 128.5, 128.4, 128.3, 128.0, 127.4,
127.2, 127.1, 126.6, 126.5, 126.4, 126.3, 109.7, 109.2, 85.5, 76.0, 67.3,
66.1, 63.0, 60.2, 52.9, 45.3, 44.1, 21.6, 21.3; IR (KBr) υ 3449, 3066,
3033, 2954, 2915, 2850, 2026, 1705, 1680, 1608, 1483, 1452, 1431,
1347, 1264, 1234, 1179, 1118, 1080, 1029, 976, 868, 815, 789 cm−1;
MS (m/z) HRMS (ESI-TOF) calcd for C52H45Cl2N3NaO5 ([M +
Na]+) 884.2628, found 884.2626.
2.29 (s, 3H), 2.22 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 196.1,
183.9, 177.0, 142.9, 141.6, 139.3, 137.2, 136.0, 135.8, 135.1, 134.7,
133.9, 131.2, 130.6, 129.0, 128.5, 128.3, 128.0, 127.9, 127.6, 127.2,
127.0, 126.8, 126.6, 126.5, 126.1, 108.4, 108.2, 84.4, 66.7, 65.3, 54.5,
47.2, 44.7, 44.0, 21.6, 21.4; IR (KBr) υ 3450, 3031, 2908, 2025, 1705,
1681, 1608, 1495, 1431, 1370, 1349, 1292, 1258, 1236, 1199, 1157,
1101, 1032, 1006, 933, 909, 812, 772 cm−1; MS (m/z) HRMS (ESI-
TOF) calcd for C50H44N2NaO4 ([M + Na]+) 759.3193, found
759.3202.
1
3k: white solid, 0.304 g, 50%, mp 228−230 °C; H NMR (600
MHz, CDCl3) δ 8.03 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 7.2 Hz, 3H),
7.35 (d, J = 4.8 Hz, 3H), 7.29 (br, 2H), 7.20−7.18 (m, 1H), 7.17−7.16
(m, 1H), 7.15 (br, 1H), 7.12 (d, J = 7.2 Hz, 2H), 7.08 (d, J = 8.4 Hz,
1H), 7.00 (d, J = 7.8 Hz, 2H), 6.96−6.93 (m, 3H), 6.71 (d, J = 7.2 Hz,
2H), 6.56 (d, J = 8.4 Hz, 1H), 6.39 (d, J = 8.4 Hz, 1H), 5.52 (s, 1H),
5.36 (s, 1H), 5.25 (d, J = 15.6 Hz, 1H), 4.94 (d, J = 16.2 Hz, 1H), 4.55
(d, J = 16.2 Hz, 1H), 4.46 (d, J = 15.7 Hz, 1H), 2.27 (s, 3H), 2.24 (s,
3H), 1.96 (s, 6H); 13C NMR (150 MHz, CDCl3) δ 195.7, 181.0,
176.3, 143.2, 142.2, 141.2, 136.6, 135.4, 135.0, 134.9, 133.8, 132.8,
128.7, 128.5, 128.2, 128.1, 127.8, 127.7, 127.6, 127.5, 127.2, 127.0,
126.9, 126.6, 126.5, 125.9, 125.6, 110.2, 109.5, 85.2, 75.8, 65.7, 61.9,
59.3, 44.6, 43.8, 43.2, 21.0, 20.7; IR (KBr) υ 3453, 3065, 3030, 2955,
2906, 2841, 2797, 2372, 2025, 1704, 1688, 1608, 1482, 1454, 1430,
1345, 1268, 1236, 1178, 1114, 1081, 1037, 975, 936, 906, 878, 843,
813, 791 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C50H44Cl2N3O4 ([M + H]+) 820.2703, found 820.2717.
1
4d: white solid, 0.129 g, 66%, mp 206−208 °C; H NMR (600
MHz, CDCl3) δ 8.02 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 7.8 Hz, 1H),
7.41−7.37 (m, 3H), 7.33 (d, J = 7.8 Hz, 2H), 7.23−7.22 (m, 3H), 7.13
(s, 4H), 7.10 (d, J = 7.8 Hz, 2H), 6.95 (s, 1H), 6.88−6.83 (m, 3H),
6.73 (t, J = 8.4 Hz, 1H), 6.56 (d, J = 7.2 Hz, 2H), 6.39 (dd, J = 8.4, 3.6
Hz, 1H), 6.35 (dd, J = 8.4, 3.6 Hz, 1H), 5.23−5.19 (m, 2H), 5.08 (d, J
= 15.2 Hz, 1H), 4.49 (d, J = 15.2 Hz, 1H), 4.44 (d, J = 16.0 Hz, 1H),
4.38 (d, J = 14.0 Hz, 1H), 2.53 (d, J = 14.0 Hz, 1H); 13C NMR (150
MHz, CDCl3) δ 194.8, 183.3, 176.4, 160.2 (J = 199.2 Hz), 158.6 (J =
197.2 Hz), 139.7, 139.1, 137.6, 136.4, 135.1, 135.0, 134.4, 134.1, 131.7
(J = 8.7 Hz), 129.3, 128.7, 128.5, 128.4, 128.3, 128.1, 128.0, 127.6,
127.3, 126.4, 115.4, 115.3, 115.2, 114.0, 113.8, 109.4 (J = 8.0 Hz), 84.0,
67.0, 65.1, 54.4, 46.7, 45.0, 44.1; IR (KBr) υ 3449, 2025, 1681, 1624,
1488, 1451, 1381, 1346, 1260, 1181, 1093, 1005, 929, 904, 830, 809,
758 cm− 1
; MS (m/z) HRMS (ESI-TOF) calcd for
C46H32Cl2F2N2NaO4 ([M + Na]+) 807.1599, found 807.1604.
3. General Procedure for the Preparation of Dispirocyclo-
pentanebisoxindoles (4a−4n) from the Domino Reaction of 3-
Phenacylideneoxindoles. A solution of 3-phenacylideneoxindoles
(0.5 mmol), thiophenol (0.5 mmol) and piperidine (0.5 mmol, 0.042
g) in 10.0 mL of acetonitrile was stirred at room temperature for about
3−4 h. Then, the resulting precipitates were collected by filtration and
washed with a little cold ethanol to give the pure products 4a−4n for
analysis.
1
4e: white solid, 0.160 g, 79%, mp 204−206 °C; H NMR (600
MHz, CDCl3) δ 8.20 (s, 1H), 7.92 (s, 1H), 7.37−7.32 (m, 3H), 7.29
(d, J = 7.8 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 7.17−7.15 (m, 1H),
7.12−7.09 (m, 5H), 6.94 (d, J = 8.4 Hz, 1H), 6.84 (s, 1H), 6.69 (d, J =
7.8 Hz, 2H), 6.50 (d, J = 8.4 Hz, 2H), 6.46 (d, J = 7.8 Hz, 2H), 6.32 (t,
J = 7.2 Hz, 2H), 5.32 (d, J = 16.2 Hz, 1H), 5.23−5.19 (m, 2H), 4.43−
4.41 (m, 2H), 4.38 (d, J = 6.9 Hz, 1H), 3.76 (s, 3H), 3.73 (s, 3H), 2.53
(d, J = 14.0 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 183.3, 175.8,
167.7, 142.3, 141.1, 137.5, 135.0, 134.6, 133.6, 129.7, 128.9, 128.7,
128.6, 128.5, 128.4, 128.3, 128.1, 127.4, 127.2, 127.0, 126.8, 126.4,
125.9, 110.0, 109.7, 84.6, 67.0, 61.3, 61.0, 54.3, 46.4, 44.6, 43.8, 21.2,
13.1; IR (KBr) υ 3450, 2934, 2839, 2021, 1704, 1680, 1606, 1513,
1481, 1429, 1376, 1345, 1253, 1176, 1106, 1080, 1030, 998, 929, 840,
813 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C48H38Cl2N2NaO6
([M + Na]+) 831.1999, found 831.1998.
1
4a: white solid, 0.133 g, 75%, mp 227−229 °C; H NMR (600
MHz, CDCl3) δ 8.20 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 7.2 Hz, 1H),
7.35−7.30 (m, 5H), 7.16−7.14 (m, 1H), 7.11−7.01 (m, 9H), 6.97−
6.93 (m, 4H), 6.75 (d, J = 7.8 Hz, 2H), 6.56 (d, J = 7.8 Hz, 2H), 6.40
(d, J = 7.2 Hz, 1H), 6.35 (d, J = 7.8 Hz, 1H), 5.35 (s, 1H), 5.25 (d, J =
16.0 Hz, 1H), 5.17 (d, J = 15.3 Hz, 1H), 4.48 (d, J = 13.9 Hz, 1H),
4.43 (d, J = 16.1 Hz, 1H), 4.38 (d, J = 15.3 Hz, 1H), 2.53 (d, J = 13.9
Hz, 1H), 2.32 (s, 3H), 2.22 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
196.0, 184.0, 177.1, 143.9, 143.1, 141.7, 137.2, 135.9, 135.6, 135.0,
134.5, 130.6, 129.0, 128.6, 128.5, 128.4, 128.3, 128.1, 127.9, 27.3,
127.1, 126.9, 126.6, 126.1, 125.8, 124.2, 121.9, 108.8, 108.5, 84.5, 66.7,
65.2, 54.4, 47.1, 44.7, 43.9, 21.6, 21.4; IR (KBr) υ 3449, 3281, 3059,
3028, 2916, 2858, 1707, 1680, 1611, 1518, 1491, 1467, 1435, 1390,
1350, 1303, 1265, 1233, 1180, 1102, 1077, 1015, 930, 837, 818, 768
cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C48H40N2NaO4 ([M +
Na]+) 731.2880, found 731.2865.
1
4f: white solid, 0.153 g, 82%, mp 221−223 °C; H NMR (600
MHz, CDCl3) δ 8.24 (s, 1H), 7.95 (s, 1H), 7.36−7.29 (m, 6H), 7.21−
7.14 (m, 8H), 7.11 (t, J = 7.8 Hz, 3H), 7.04 (t, J = 7.8 Hz, 2H), 6.94−
6.91 (m, 2H), 6.46 (d, J = 7.2 Hz, 2H), 6.30 (d, J = 7.8 Hz, 1H), 6.22
(d, J = 8.4 Hz, 1H), 5.28 (s, 1H), 5.25−5.21 (m, 2H), 4.46−4.42 (m,
2H), 4.24 (d, J = 15.3 Hz, 1H), 2.56 (d, J = 14.0 Hz, 1H); 13C NMR
(150 MHz, CDCl3) δ 196.1, 183.3, 176.3, 142.4, 140.1, 137.7, 136.9,
135.1, 134.3, 132.5, 131.9, 129.8, 129.1, 128.7, 128.6, 128.4, 128.2,
128.0, 127.9, 127.6, 127.2, 127.0, 126.3, 126.0, 109.8, 109.5, 84.4, 66.8,
65.5, 54.3, 46.5, 44.6, 43.9; IR (KBr) υ 3443, 3069, 2936, 2025, 1691,
1611, 1481, 1429, 1368, 1344, 1273, 1232, 1204, 1181, 1079, 989, 914,
814 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C46H34Cl2N2NaO4
([M + Na]+) 771.1788, found 771.1785.
1
4b: white solid, 0.127 g, 68%, mp 235−237 °C; H NMR (600
MHz, CDCl3) δ 8.15 (d, J = 6.6 Hz, 1H), 7.93 (d, J = 7.2 Hz, 1H),
7.38−7.33 (m, 5H), 7.22−7.20 (m, 3H), 7.16−7.13 (m, 1H), 7.11−
7.07 (m, 5H), 7.05−7.02 (m, 5H), 6.84 (d, J = 7.8 Hz, 2H), 6.58 (d, J
= 6.6 Hz, 2H), 6.45 (d, J = 7.2 Hz, 2H), 5.27 (s, 1H), 5.22 (d, J = 16.0
Hz, 1H), 5.09 (d, J = 15.2 Hz, 1H), 4.50 (d, J = 15.2 Hz, 1H), 4.47−
4.42 (m, 2H), 2.54 (d, J = 13.8 Hz, 1H); 13C NMR (150 MHz,
CDCl3) δ 195.2, 183.7, 176.7, 143.8, 141.6, 138.8, 136.9, 135.5, 135.3,
134.8, 133.9, 130.1, 129.2, 129.0, 128.7, 128.6, 128.4, 128.3, 128.2,
127.9, 127.8, 127.2, 127.0, 126.4, 126.2, 125.8, 124.4, 122.1, 108.9,
108.7, 84.1, 66.7, 65.1, 54.2, 46.8, 44.8, 43.9; IR (KBr) υ 3449, 3286,
3065, 3028, 2913, 1708, 1686, 1613, 1591, 1491, 1467, 1435, 1391,
1352, 1300, 1263, 1206, 1181, 1094, 1013, 959, 930, 909, 845, 827,
781 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C46H34Cl2N2NaO4
([M + Na]+) 771.1788, found 771.1773.
1
4g: white solid, 0.163 g, 80%, mp 228−230 °C; H NMR (600
MHz, CDCl3) δ 8.18 (d, J = 1.8 Hz, 1H), 7.90 (d, J = 1.8 Hz, 1H),
7.42−7.37 (m, 3H), 7.33 (d, J = 7.2 Hz, 2H), 7.22−7.21 (m, 3H),
7.13−7.11 (m, 5H), 7.08 (d, J = 8.4 Hz, 2H), 7.01 (dd, J = 8.3, 1.8 Hz,
1H), 6.90 (s, 1H), 6.86 (d, J = 8.4 Hz, 2H), 6.55−6.54 (m, 2H), 6.39
(d, J = 8.4 Hz, 1H), 6.36 (d, J = 8.4 Hz, 1H), 5.24 (d, J = 16.1 Hz,
1H), 5.17 (s, 1H), 5.06 (d, J = 15.2 Hz, 1H), 4.50 (d, J = 15.2 Hz, 1H),
4.43 (d, J = 16.1 Hz, 1H), 4.37 (d, J = 14.0 Hz, 1H), 2.52 (d, J = 14.0
Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 194.8, 183.2, 176.2, 142.4,
140.2, 139.1, 136.3, 135.0, 134.2, 134.1, 131.7, 129.9, 129.3, 129.0,
128.8, 128.7, 128.5, 128.3, 128.1, 128.0, 127.8, 127.7, 127.4, 127.3,
126.3, 126.1, 109.9, 109.7, 84.0, 66.8, 65.2, 54.2, 46.7, 45.0, 44.0, 29.7;
IR (KBr) υ 3449, 2919, 2025, 1711, 1687, 1640, 1481, 1428, 1350,
1235, 1180, 1091, 998, 933, 811 cm−1; MS (m/z) HRMS (ESI-TOF)
calcd for C46H32Cl4N2NaO4 ([M + Na]+) 839.1008, found 839.1002.
1
4c: white solid, 0.162 g, 88%, mp 233−235 °C; H NMR (600
MHz, CDCl3) δ 8.00 (s, 1H), 7.76 (s, 1H), 7.34−7.30 (m, 5H), 7.15−
7.12 (m, 1H), 7.09−7.05 (m, 6H), 7.00 (s, 1H), 6.96 (d, J = 7.8 Hz,
2H), 6.91 (d, J = 7.8 Hz, 1H), 6.75 (d, J = 7.8 Hz, 3H), 6.49 (d, J = 7.2
Hz, 2H), 6.29 (d, J = 7.8 Hz, 1H), 6.22 (d, J = 7.8 Hz, 1H), 5.34−5.30
(m, 2H), 5.17 (d, J = 15.3 Hz, 1H), 4.48 (d, J = 13.9 Hz, 1H), 4.39−
4.33 (m, 2H), 2.52 (d, J = 13.9 Hz, 1H), 2.36 (s, 3H), 2.33 (s, 3H),
1
4h: white solid, 0.128 g, 76%, mp 191−193 °C; H NMR (600
MHz, CDCl3) δ 8.05 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H),
J
dx.doi.org/10.1021/jo4010603 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
7.09 (d, J = 7.2 Hz, 2H), 6.97−6.94 (m, 3H), 6.91−6.89 (m, 4H), 6.81
(s, 1H), 6.74 (t, J = 8.4 Hz, 1H), 6.55 (dd, J = 8.2, 3.5 Hz, 1H), 6.30
(dd, J = 8.2, 3.5 Hz, 1H), 5.15 (s, 1H), 4.33 (d, J = 14.0 Hz, 1H),
3.84−3.77 (m, 2H), 3.37−3.33 (m, 1H), 3.21−3.16 (m, 1H), 2.41 (d, J
= 14.0 Hz, 1H), 2.25 (s, 3H), 2.22 (s, 3H), 1.63−1.58 (m, 1H), 1.55−
1.49 (m, 1H), 1.43−1.34 (m, 2H), 1.11−1.04 (m, 1H), 0.98 (t, J = 7.2
Hz, 5H), 0.91−0.86 (m, 1H), 0.78 (t, J = 7.2 Hz, 3H) ; 13C NMR (150
MHz, CDCl3) δ 195.6, 183.2, 176.2, 160.0 (J = 211.4 Hz), 158.4 (J =
208.1 Hz), 143.3, 132.3 (J = 8.7 Hz), 128.7, 128.5, 128.1, 127.2, 125.7,
115.4, 115.2, 114.8, 114.7, 114.6, 113.9, 113.7, 108.4 (J = 8.2 Hz),
107.9 (J = 8.0 Hz), 84.4, 66.8, 64.2, 54.5, 46.3, 40.7, 40.0, 29.4, 29.0,
21.5, 21.0, 20.2, 20.1, 14.0, 13.8; IR (KBr) υ 3449, 3072, 2957, 2870,
2025, 1704, 1684, 1615, 1489, 1453, 1358, 1261, 1193, 1162, 1133,
1010, 931, 902, 866, 813, 775 cm−1; MS (m/z) HRMS (ESI-TOF)
calcd for C42H42F2N2NaO4 ([M + Na]+) 699.3005, found 699.3000.
816, 779 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C34H26Cl2N2NaO6 ([M + Na]+) 651.1060, found 651.1051.
1
4m: white solid, 0.056 g, 55%, mp 220−222 °C; H NMR (600
MHz, CDCl3) δ 11.23 (br, 1H), 10.34 (s, 1H), 7.74 (s, 1H), 7.16 (s,
1H), 7.06 (d, J = 7.8 Hz, 1H), 6.97 (d, J = 7.8 Hz, 1H), 6.85 (d, J = 7.8
Hz, 1H), 6.72 (d, J = 7.8 Hz, 1H), 5.96 (s, 1H), 4.24 (s, 1H), 3.13 (d, J
= 13.8 Hz, 1H), 2.25 (s, 3H), 2.24 (s, 3H), 2.13 (d, J = 13.8 Hz, 1H),
1.24 (s, 3H), 0.85 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 201.9,
184.9, 179.0, 140.4, 139.1, 132.0, 131.7, 128.9, 128.8, 128.6, 128.1,
127.9, 126.7, 126.4, 109.8, 108.2, 81.3, 68.6, 64.7, 53.9, 48.8, 28.0, 21.0,
20.8, 19.7; IR (KBr) υ 3670, 3543, 3406, 3186, 3059, 2919, 2852,
1729, 1709, 1678, 1623, 1490, 1421, 1394, 1351, 1307, 1234, 1216,
1173, 1124, 1096, 1074, 1043, 998, 944, 872, 806 cm−1; MS (m/z)
HRMS (ESI-TOF) calcd for C24H24N2NaO4 ([M + Na]+) 427.1628,
found 427.1628.
1
1
4n: white solid, 0.064 g, 62%, mp 222−224 °C; H NMR (600
4i: white solid, 0.162 g, 91%, mp 217−219 °C; H NMR (600
MHz, CDCl3) δ 11.32 (br, 1H), 10.58 (s, 1H), 7.80 (d, J = 8.4 Hz,
1H), 7.20 (d, J = 7.2 Hz, 1H), 7.13−7.10 (m, 1H), 7.04−7.01 (m,
1H), 6.99−6.96 (m, 1H), 6.85−6.83 (m, 1H), 5.90 (s, 1H), 4.42 (s,
1H), 3.10 (d, J = 13.8 Hz, 1H), 2.24 (d, J = 13.8 Hz, 1H), 1.32 (s, 3H),
0.88 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 200.9, 183.3, 178.0,
157.5 (J = 207.3 Hz), 155.9 (J = 204.9 Hz), 137.8, 136.8, 132.5 (J =
8.8 Hz), 128.4, 128.3, 128.1, 114.1, 114.0, 113.1, 113.0, 112.6, 112.4,
112.3, 109.9 (J = 8.3 Hz), 108.0 (J = 8.1 Hz), 80.3, 67.1, 64.1, 53.1,
47.5, 26.8, 18.6; IR (KBr) υ 3398, 3313, 3218, 3079, 2991, 2935, 2890,
1721, 1697, 1632, 1605, 1483, 1433, 1337, 1311, 1258, 1237, 1199,
1177, 1131, 1089, 1038, 1011, 944, 901, 882, 866, 820, 790, 760 cm−1;
MS (m/z) HRMS (ESI-TOF) calcd for C22H18F2N2NaO4 ([M +
Na]+) 435.1127, found 435.1117.
MHz, CDCl3) δ 8.20 (s, 1H), 7.84 (s, 1H), 7.23 (d, J = 8.4 Hz, 1H),
7.07 (d, J = 7.8 Hz, 2H), 7.02 (d, J = 8.4 Hz, 1H), 6.94−6.90 (m, 6H),
6.80 (s, 1H), 6.57 (d, J = 8.4 Hz, 1H), 6.30 (d, J = 7.8 Hz, 1H), 5.13
(s, 1H), 4.32 (d, J = 14.0 Hz, 1H), 3.88−3.78 (m, 2H), 3.36−3.32 (m,
1H), 3.19−3.14 (m, 1H), 2.41 (d, J = 14.0 Hz, 1H), 2.25 (s, 3H), 2.22
(s, 3H), 1.62−1.59 (m, 1H), 1.54−1.50 (m, 1H), 1.41−1.35 (m, 2H),
1.03−1.02 (m, 1H), 0.99−0.96 (m, 5H), 0.82−0.81 (m, 1H), 0.77 (t, J
= 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 195.6, 183.1, 176.0,
143.2, 142.8, 140.5, 137.4, 134.7, 134.5, 132.2, 129.4, 129.3, 128.7,
128.6, 128.5, 128.4, 128.2, 127.4, 127.2, 126.7, 126.0, 125.7, 108.8,
108.5, 84.4, 66.7, 64.4, 54.3, 46.2, 40.7, 39.9, 29.3, 29.0, 21.5, 21.0,
20.2, 20.1, 14.0, 13.7; IR (KBr) υ 3447, 3070, 2957, 2930, 2869, 2025,
1705, 1684, 1608, 1514, 1482, 1429, 1355, 1272, 1233, 1190, 1115,
1009, 929, 907, 840, 813, 778 cm‑1; MS (m/z) HRMS (ESI-TOF)
calcd for C42H42Cl2N2NaO4 ([M + Na]+) 731.2414, found 731.2410.
4. General Procedure for the Reaction of 3-Phenacylide-
neoxindoles with Thiophenol. A solution of 1-benzyl-5-chloro-3-
(2-oxo-2-p-tolylethylidene)-1,3-dihydroindol-2-one (0.5 mmol) and
thiophenol or p-chlorothiophenol (0.5 mmol) in 10.0 mL of
acetonitrile was stirred at room temperature for about 3−4 h. Then,
solvent was evaporated under reduced pressure. The residue was
triturated with ethanol to give the pure product D1 and D2 for
analysis.
1
4j: white solid, 0.104 g, 73%, mp 240−242 °C; H NMR (600
MHz, CDCl3) δ 11.14 (br, 1H), 10.23 (s, 1H), 8.00 (s, 1H), 7.89 (s,
1H), 7.40 (t, J = 7.2 Hz, 1H), 7.28−7.27 (m, 2H), 7.23−7.21 (m, 3H),
7.18−7.16 (m, 1H), 7.13−7.11 (m, 2H), 7.01 (d, J = 7.8 Hz, 3H), 6.76
(s, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.38 (d, J = 7.8 Hz, 1H), 5.31 (s,
1H), 4.03 (d, J = 13.8 Hz, 1H), 2.44 (d, J = 13.8 Hz, 1H); 13C NMR
(150 MHz, CDCl3) δ 195.8, 182.9, 176.5, 140.6, 139.0, 137.2, 135.4,
132.0, 131.5, 128.1, 127.1, 126.9, 126.4, 126.0, 125.8, 125.4, 125.1,
124.9, 124.6, 123.5, 109.6, 108.6, 82.4, 65.7, 62.6, 54.9, 52.9, 44.5, 17.4;
IR (KBr) υ 3651, 3355, 3207, 3059, 2848, 1721, 1682, 1621, 1596,
1474, 1445, 1345, 1304, 1250, 1213, 1185, 1127, 1076, 1010, 975, 944,
897, 851, 814, 758 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for
C32H22Cl2N2NaO4 ([M + Na]+) 591.0849, found 591.0850.
1
D1: white solid, 0.191 g, 77%, mp 106−108 °C; H NMR (600
MHz, CDCl3) δ 7.71 (s, 1H), 7.68 (d, J = 7.8 Hz, 2H), 7.36 (d, J = 6.6
Hz, 2H), 7.24−7.22 (m, 4H), 7.15−7.14 (m, 3H), 7.12 (d, J = 7.8 Hz,
4H), 6.62 (d, J = 7.8 Hz, 1H), 5.40 (s, 1H), 5.15 (d, J = 15.9 Hz, 1H),
4.84 (d, J = 15.9 Hz, 1H), 4.30 (s, 1H), 2.38 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 195.4, 176.1, 144.3, 142.9, 135.1, 133.2, 133.1, 132.6,
129.3, 129.2, 129.1, 128.8, 128.5, 128.4, 128.2, 127.7, 127.5, 127.1,
109.9, 54.3, 48.0, 44.2, 21.7; IR (KBr) υ 3670, 3052, 2939, 1709, 1672,
1606, 1479, 1454, 1431, 1354, 1318, 1296, 1262, 1221, 1206, 1181,
1167, 1121, 1071, 1023, 978, 926, 908, 847, 818, 789 cm−1; MS (m/z)
HRMS (ESI-TOF) calcd for C30H25ClNO2S ([M + H]+) 498.1295,
found 498.1316.
1
4k: white solid, 0.082 g, 55%, mp 230−232 °C; H NMR (600
MHz, CDCl3) δ 11.16 (s, 1H), 10.25 (s, 1H), 7.98 (s, 1H), 7.86 (s,
1H), 7.22−7.18 (m, 3H), 7.04−7.02 (m, 3H), 6.92−6.91 (m, 2H),
6.88−6.87 (m, 2H), 6.69 (s, 1H), 6.62 (d, J = 7.8 Hz, 1H), 6.42 (d, J =
8.4 Hz, 1H), 5.26 (s, 1H), 4.00 (d, J = 13.8 Hz, 1H), 2.40 (d, J = 13.8
Hz, 1H), 2.23 (s, 3H), 2.19 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
196.7, 184.6, 178.1, 143.5, 142.2, 140.6, 137.0, 135.9, 134.4, 133.7,
129.9, 129.1, 128.6, 128.5, 128.2, 127.6, 126.9, 126.6, 126.5, 126.1,
125.0, 111.1, 110.2, 83.9, 67.3, 64.1, 56.5, 54.6, 46.3, 21.5, 21.0, 19.0;
IR (KBr) υ 3656, 3354, 2925, 1695, 1673, 1619, 1517, 1474, 1438,
1344, 1307, 1252, 1207, 1187, 1124, 1086, 1015, 975, 937, 903, 811,
774 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C34H26Cl2N2NaO4
([M + Na]+) 619.1162, found 619.1153.
1
D2: white solid, 0.223 g, 84%, mp 102−104 °C; H NMR (600
MHz, CDCl3) δ 7.71 (d, J = 7.8 Hz, 2H), 7.67 (s, 1H), 7.36 (d, J = 7.2
Hz, 2H), 7.28−7.27 (m, 1H), 7.24−7.23 (m, 2H), 7.17 (t, J = 7.8 Hz,
3H), 7.09 (d, J = 7.8 Hz, 2H), 6.98 (d, J = 7.8 Hz, 2H), 6.63 (d, J = 8.4
Hz, 1H), 5.36 (s, 1H), 5.15 (d, J = 15.8 Hz, 1H), 4.83 (d, J = 15.8 Hz,
1H), 4.28 (s, 1H), 2.41 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
195.2, 176.0, 144.6, 142.8, 135.1, 134.8, 134.7, 132.6, 131.4, 129.3,
129.2, 128.8, 128.5, 128.3, 128.2, 127.8, 127.2, 109.9, 54.3, 473.9, 44.2,
21.7; IR (KBr) υ 3669, 3061, 1708, 1674, 1607, 1479, 1453, 1430,
1355, 1318, 1296, 1261, 1222, 1207, 1181, 1167, 1121, 1096, 1076,
1012, 980, 926, 908, 837, 818, 788 cm−1; MS (m/z) HRMS (ESI-
TOF) calcd for C30H23Cl2NNaO2S ([M + Na]+) 554.0719, found
554.0713.
1
4l: white solid, 0.075 g, 48%, mp 174−176 °C; H NMR (600
MHz, CDCl3) δ 11.16 (br, 1H), 10.22 (s, 1H), 7.98 (s, 1H), 7.84 (s,
1H), 7.28 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.4
Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 6.76 (d, J = 8.4 Hz, 2H), 6.67−6.66
(m, 3H), 6.63 (d, J = 7.8 Hz, 1H), 6.47 (d, J = 8.4 Hz, 1H), 5.22 (s,
1H), 3.99 (d, J = 13.8 Hz, 1H), 3.73 (s, 3H), 3.66 (s, 3H), 2.40 (d, J =
13.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 195.2, 184.6, 178.2,
163.2, 158.9, 142.3, 140.6, 133.7, 131.1, 130.0, 129.8, 129.7, 128.6,
128.5, 127.5, 126.9, 126.6, 126.5, 125.0, 113.9, 112.9, 111.1, 110.2,
83.8, 67.3, 64.0, 56.5, 56.0, 55.4, 54.7, 46.4, 19.0; IR (KBr) υ 3680,
3353, 3111, 2918, 2848, 1724, 1680, 1598, 1572, 1514, 1473, 1440,
1349, 1305, 1254, 1213, 1183, 1132, 1090, 1018, 974, 934, 900, 836,
5. General Procedure for the Reaction of 3-Phenacylide-
neoxindoles with 2-Mercaptoethanol. A solution of 1-benzyl-5-
chloro-3-(2-oxo-2-p-tolylethylidene)-1,3-dihydroindol-2-one (0.5
mmol) and 2-mercaptoethanol (0.5 mmol) in 10.0 mL of acetonitrile
was stirred at room temperature for about 1 h. Then solvent was
evaporated under reduced pressure. The residue was triturated with
ethanol to give the pure product E: white solid, 0.177 g, 91%, mp
176−178 °C; 1H NMR (600 MHz, CDCl3) δ 7.90 (d, J = 7.8 Hz, 2H),
K
dx.doi.org/10.1021/jo4010603 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
7.36−7.33 (m, 4H), 7.28 (d, J = 7.2 Hz, 3H), 7.24 (s, 1H), 7.11 (d, J =
8.4 Hz, 1H), 6.63 (d, J = 8.4 Hz, 1H), 4.96 (s, 2H), 4.13 (d, J = 8.4 Hz,
1H), 3.88 (d, J = 18.2 Hz, 1H), 3.50−3.45 (m, 1H), 2.43 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 196.1, 177.4, 144.6, 142.0, 135.5, 133.6,
130.8, 129.4, 128.9, 128.3, 127.9, 127.8, 127.3, 124.9, 109.9, 44.1, 41.3,
39.8, 21.7; IR (KBr) υ 3670, 3062, 2913, 1712, 1685, 1608, 1488,
1453, 1432, 1399, 1355, 1291, 1227, 1209, 1183, 1077, 1023, 974, 908,
851, 812 cm−1; MS (m/z) HRMS (ESI-TOF) calcd for C24H21ClNO2
([M + H]+) 390.1255, found 390.1269.
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ASSOCIATED CONTENT
* Supporting Information
■
S
1H NMR and 13C NMR spectra for all compounds, molecular
structures, experimental conditions, and cif file. This material is
available free of charge via the Internet at http://pubs.acs.org.
Crystallographic data for compounds 2j (CCDC 905184), 2l
(CCDC 906362), 2q (CCDC 905183), 2s (CCDC 905185),
3a (CCDC 905186), 3j (CCDC 905187), 4a (CCDC 933927),
4g (CCDC 933928), 4i (CCDC 933929), 4k (CCDC
933930), and 4m (CCDC 933931) can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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AUTHOR INFORMATION
Corresponding Author
*Chao-Guo Yan. E-mail: cgyan@yzu.edu.cn.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by the National Natural
Science Foundation of China (Grant No. 21272200) and the
Priority Academic Program Development of Jiangsu Higher
Education Institutions. We also thank the Analysis and Test
Center of Yangzhou University for providing necessary
instruments for analysis.
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