Catalytic C6 functionalization of 2,3-disubstituted indoles by scandium triflate

Article abstract of DOI:10.1021/jo402511b

We report herein an unprecedented direct catalytic C6 functionalization reaction of 2,3-disubstituted indoles with various N-Ts aziridines catalyzed by Sc(OTf)₃ under mild conditions. Mechanistic studies revealed that a kinetically favored but reversible formal [3 + 2] annulation occurs initially. The direct C6 functionalization, although having a relatively higher energetic barrier, delivers the thermodynamically favorable products.

Full text of DOI:10.1021/jo402511b

Article
pubs.acs.org/joc
Catalytic C6 Functionalization of 2,3-Disubstituted Indoles by
Scandium Triflate
Hua Liu, Chao Zheng,* and Shu-Li You*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Lu, Shanghai 200032, People’s Republic of China
S
* Supporting Information
ABSTRACT: We report herein an unprecedented direct
catalytic C6 functionalization reaction of 2,3-disubstituted
indoles with various N−Ts aziridines catalyzed by Sc(OTf)3
under mild conditions. Mechanistic studies revealed that a
kinetically favored but reversible formal [3 + 2] annulation
occurs initially. The direct C6 functionalization, although
having a relatively higher energetic barrier, delivers the thermodynamically favorable products.
Scheme 1. C6 Functionalization of 2,3-Disubstituted Indole
Catalyzed by Sc(OTf)3
INTRODUCTION
■
Indoles are among the most privileged structures that are
widely distributed in natural products as well as molecules of
pharmaceutical interest.1 Therefore, direct functionalization of
indoles has attracted tremendous attention and numerous
methods to achieve this goal have been reported in the past
several decades.2 Nonetheless, most of these reactions occur at
the more reactive pyrrole ring and the reactions involving the
fused benzene motif are relatively less developed. One strategy
for the functionalization at the benzene ring of indoles is to link
the other reaction partner and the indole core with a proper
tether to construct the peri-annulated products in an
intramolecular way.3 Other methods4 include taking advantage
of a directing group,4a−f using a preinstalled functionality4g−j or
carrying out enzyme-catalyzed reactions.4k−p Recently, Garg
and co-workers5 reported an elegant method to access various
C4-, C5-, C6-, or C7-substituted indoles via indolyne
intermediates. However, to the best of our knowledge, direct
catalytic C6 functionalization of indoles has not been reported
to date.6
The annulation of indoles with 1,3-dipolar equivalents has
been found to be an efficient method to deliver polycyclic
indole derivatives by diverse catalytic systems.7 As part of our
ongoing program on exploring the dearomatization of
substituted indoles,8 we envisaged that 2,3-disubstituted indoles
might undergo annulation with donor−acceptor aziridines,
affording pyrroloindoline products possessing two consecutive
quaternary chiral centers by a Lewis acid catalyst.9 To our
surprise, the C6 -functionalized indoles were obtained as the
major products in the presence of a catalytic amount of
Sc(OTf)3 for a series of substrates (Scheme 1). A plausible
mechanism involving a reversible [3 + 2] annulation prior to
the direct C6 functionalization was proposed for this
transformation on the basis of further experiments and DFT
calculations. Herein, we wish to report our results on this
subject.
RESULTS AND DISCUSSION
■
At the outset, the N−Ts aziridine 1a and 2,3-dimethylindole
(2a) were chosen as the model substrates. In the presence of 10
mol % of Ni(ClO4)2·6H2O and activated 4 Å molecular sieves
(MS), the annulation product 3aa was obtained in 60% yield,
along with 21% of the C6-functionalized product 4aa under
mild conditions. No reaction was observed without 4 Å MS
(Table 1, entries 1 and 2).10 With these results in hand, a series
of Lewis acids were screened. 3aa was afforded as the major or
the sole product when using Sn(OTf)2 or Fe(OTf)3 (Table 1,
entries 5 and 6), while employing Co(ClO4)2·6H2O, Zn-
(ClO4)2·6H2O, or Sc(OTf)3 led to 4aa predominantly (Table
1, entries 3, 4, and 8). The utilization of In(OTf)3 resulted in a
mixture of 3aa and 4aa (Table 1, entry 7). In some cases, a
small amount of C5-substituted indole derivative 5aa was also
isolated. The structures of 3aa, 4aa, and 5aa were confirmed
unambiguously by single crystal X-ray diffraction analyses.11
With Sc(OTf)3 as the optimal catalyst, various solvents such as
Received: November 12, 2013
Published: January 12, 2014
© 2014 American Chemical Society
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a
Table 1. Optimization of Reaction Conditions
b
c
entry
catalyst
dolvent
MS
time (h)
yield (%) of 3aa, 4aa
3aa:4aa:5aa
d
1
Ni(ClO4)2·6H2O
Ni(ClO4)2·6H2O
Co(ClO4)2·6H2O
Zn(ClO4)2·6H2O
Sn(OTf)2
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
DCM
DCE
none
4 Å
4 Å
4 Å
4 Å
4 Å
4 Å
4 Å
4 Å
4 Å
4 Å
4 Å
3 Å
5 Å
none
3 Å
3 Å
12
3
no reaction
60, 21
ND
2
30:10:<1
1:10:1
0:9:1
3
3
ND, 55
ND, 66
79, trace
76, ND
30, 29
4
2
5
3
>20:1:<1
1:0:0
6
Fe(OTf)3
3
7
In(OTf)3
3
10:10:<1
0:9.5:1
0:6.3:1
0:6.7:1
0:2.5:1
ND
8
Sc(OTf)3
1.5
0.5
0.5
0.5
24
0.5
24
0.25
3
ND, 75
ND, 76
ND, 75
ND, 14
no reaction
ND, 80
20, ND
ND, 50
ND, 70
ND, 77
9
Sc(OTf)3
10
11
12
13
14
15
Sc(OTf)3
Sc(OTf)3
MeCN
THF
Sc(OTf)3
Sc(OTf)3
PhMe
PhMe
PhMe
PhMe
PhMe
0:9:1
Sc(OTf)3
1:0:0
Sc(OTf)3
0:9:1
e
16
Sc(OTf)3
0:11.5:1
0:12:1
f
17
Sc(OTf)3
0.75
a
Conditions: 1a (0.2 mmol), 2a (0.3 mmol), catalyst (10 mol %), and activated MS (100 mg) in anhydrous solvent (2 mL) at room temperature.
b
c
d
e
Isolated yields. The ratio 3aa:4aa:5aa was determined by 1H NMR of the crude reaction mixture. ND = not determined. The loading of catalyst
f
was reduced to 5 mol %. 0.4 mmol of 2a was used.
Scheme 2. Control Experiments
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a
Table 2. Substrate Scope
a
Conditions: 1 (0.2 mmol), 2 (0.3 mmol), Sc(OTf)3 (10 mol %), and activated 3 Å MS (100 mg) in anhydrous toluene (2 mL) at room
b
temperature. The isolated yield of is 4 reported. The ratio 4:5 was determined by 1H NMR of the crude reaction mixture. The reaction was carried
at 80 °C for 24 h. Combined yield of 4ae and 5ae. Combined yield of the two diastereomers of 3af.
c
d
Scheme 3. Reactions of Monosubstituted Indoles
toluene, DCM, DCE, CH3CN, and THF were examined (Table
1, entries 8−12), and toluene was still found to be the optimal
solvent with a relatively higher regioselectivity favored for 4aa
(Table 1, entry 8). To further optimize the reaction conditions,
different types of MS and catalyst loadings were tested (Table
1, entries 13−16). The addition of 3 Å MS with 10 mol % of
Sc(OTf)3 gave the best results. In addition, increasing the
loading of 2a enhanced the regioselectivity without affecting the
yield of 4aa (Table 1, entry 17). Finally, the optimal reaction
conditions were identified as described in Table 1, entry 13.
TLC monitoring of the reaction suggested that the
annulation products 3aa were always generated initially during
the course of the C6 functionalization. The amount of 3aa
decreased gradually while those of 4aa and 5aa increased. Thus,
several control experiments were carried out to check whether
4aa and 5aa were transformed from 3aa (Scheme 2). In the
presence of 10 mol % of Sc(OTf)3, 3aa was converted
smoothly to 4aa in 70% yield and the ratio 4aa:5aa was 4.5:1.
When 1 equiv of 2a was added, the yield of 4aa was increased
to 85%, with the ratio 4aa:5aa was enhanced to 10:1.
Moreover, when 1 equiv of tetrahydrocarbazole 2d was added
instead of 2a, the crossover products 4ad and 5ad were
afforded along with 4aa and 5aa. The combined yield of 4aa
and 4ad was 79%, with a ratio of 4aa to 4ad of 1:1.2. These
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Figure 1. Calculated reaction pathways and optimized structures of the three key transition states. The ΔG values are in kcal/mol. The bond
distances are in Å. Most of the hydrogen atoms are omitted for the sake of clarity.
results implicated that the C6 functionalization products were
converted from the annulation products and the transformation
probably goes through an intermolecular path rather than
intramolecular rearrangement.
suitable substrate, because no desired product could be
obtained when 2h was subjected to the standard conditions.
DFT calculations were performed to shed light on the
reaction mechanism. As shown in Figure 1, the complex C-0
(0.0 kcal/mol) of Sc(OTf)3-coordinated N−Ts aziridine 1a and
2,3-dimethylindole (2a) was set as the starting point of the
calculations. A weak interaction between the indole N−H
moiety and one triflate anion of Sc(OTf)3 could be observed.12
The C−C bond of the aziridine ring is cleaved very easily
through TS-0 (9.1 kcal/mol) to yield the azomethine ylide
INT-0 (−2.7 kcal/mol). The following attack of the indole C3
position at the N−Ts iminium carbon is quite facile (TS-1a, 6.0
kcal/mol). The possibility of the direct attack of the indole C3
position at the aziridine ring via SN2 displacement or an
intimate ion pair was also considered. This kind of mechanism
was suggested by Johnson for the cycloaddition reactions of
donor−acceptor cyclopropanes.13 However, such a transition
state could not be located in the current system. The 3,3-
disubstituted indolenine intermediate INT-1a (−7.8 kcal/mol)
then undergoes a subsequent ring-closing process (TS-2a, −6.6
kcal/mol), leading to INT-2a (−9.0 kcal/mol), which is the
Sc(OTf)3-coordinated annulation product. The calculated low
energetic barrier for the formation of the annulation product is
in agreement with the fast formation of 3aa observed
experimentally. Notably, the energetic barrier between INT-
2a and TS-1a is not high (15.0 kcal/mol), indicating that the
Next, various N−Ts aziridines 1 and 2,3-disubstituted
indoles 2 were subjected to the optimized conditions to
evaluate the scope of the reaction (Table 2). In most cases, the
desired C6 alkylation products 4 could be generated smoothly
in good to excellent yields. Aziridines with different aryl
substituents or ester groups were well tolerated, with up to 93%
yield of 4aa−4ga and >20:1 regioselectivity. On the other hand,
different indoles led to different outcomes. The reaction of
indoles 2b−d worked well to afford the corresponding 4ab−
4ad with up to 78% yield and 17:1 ratio of 4:5. When N−Me
tetrahydrocarbazole 2e was employed, the ratio of 4ae and 5ae
decreased dramatically to 2.5:1. Notably, when
tetrahydrocyclopenta[b]indole 2f was used, only the annulation
product 3af could be obtained in 70% yield with 1.6:1 dr.
Prolonged reaction time or elevated temperature did not lead
to the formation of the desired C6 functionalization products.
In addition, monosubstituted indole substrates were also tested
(Scheme 3). Under the optimized conditions, 3-methylindole
2g was converted to the corresponding annulation product 3ag
(45% yield) and C6-functionalized product 4ag (50% yield), as
well as a trace amount of C5-functionalized product 5ag
(4ag:5ag = 9:1). However, 2-methylindole (2h) was not a
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1H), 7.54−7.47 (m, 1H), 7.38 (d, J = 8.0 Hz, 2H), 7.34−7.29 (m,
2H), 5.31 (s, 1H), 4.01 (s, 3H), 3.23 (s, 3H), 2.46 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 163.8, 162.8, 145.2, 135.5, 133.1, 131.1, 129.8,
129.2, 128.5, 128.0, 126.9, 126.3, 126.1, 125.01, 124.97, 123.0, 56.6,
54.1, 52.8, 48.2, 21.7; IR (thin film): νmax (cm−1) 3013, 2956, 2849,
1740, 1594, 1434, 1335, 1162, 1119, 910, 804, 735, 679; HRMS (ESI-
TOF) calcd for C23H25N2O6S [M + NH4]+ 457.1428, found 457.1442.
Dimethyl 3-cyclohexyl-1-tosylaziridine-2,2-dicarboxylate (1h):
annulation process could be reversible. Therefore, other
possible reaction pathways of INT-0 were investigated. The
transition state for the direct attack of the indole C6 position at
the N−Ts iminium carbon was located (TS-1b, 11.6 kcal/mol).
The proton at the indole C6 position is then abstracted by the
α carbanion intramolecularly (TS-3b, 6.0 kcal/mol) after a
minor conformational switch (INT-1b → INT-1b′), giving the
more stabilized final complex INT-3b (−14.1 kcal/mol). These
calculation results confirmed that the annulation reaction is
kinetically more favored but is reversible. The functionalization
at the C6 position, although with a higher energetic barrier, is a
thermodynamically favorable process.14 In addition, the
energetic barrier of TS-1b, the rate-determining step of the
C6 functionalization process, is 20.6 kcal/mol relative to INT-
2a, which is also in accord with the fact that most reactions
were complete within 0.5 h at room temperature.
The reaction pathway of the C5 functionalization was also
investigated computationally. The energetic barrier of the direct
attack of the indole C5 position at the N−Ts iminium carbon
(TS-1c) is higher than that of TS-1b by 3.5 kcal/mol. In order
to probe the origin of the high regioselectivity favoring C6 over
C5 functionalization, a molecular orbital analysis of 2a was
conducted. The contribution of the 2pz orbital of C6 to the
HOMO of 2a was estimated to be 12.5%, which is more
significant in comparison with the contribution of the 2pz
orbital of C5 (<1%). The sharp difference in the HOMO
distributions implies that the nucleophilicity at the C6 position
of 2a might be much stronger than that at the C5 position.
Further calculations on a series of model substrates revealed
that an electron-donating group at the C2 position of indoles
might play an important role in enhancing the nucleophilicity at
the C6 position.11
1
colorless oil, 1.01 g, 85% yield; H NMR (300 MHz, CDCl3) δ 7.79
(d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H), 3.76 (s, 3H), 3.69 (s,
3H), 3.39 (d, J = 9.2 Hz, 1H), 2.35 (s, 3H), 1.74−1.38 (m, 5H), 1.15−
0.85 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 164.1, 163.8, 144.6,
135.6, 129.4, 127.7, 55.0, 53.6, 53.1, 52.7, 36.8, 30.4, 28.7, 25.6, 24.9,
24.8, 21.4; IR (thin film): νmax (cm−1) 2929, 2853, 1750, 1436, 1337,
1224, 1163, 1120, 1090, 917, 815, 680; HRMS (ESI-TOF) calcd for
C19H26NO6S [M + H]+ 396.1475, found 396.1493.
Procedure for the Preparation of the Annulation Product
3aa. To a mixture of 2a (29 mg, 0.2 mmol), Fe(OTf)3 (10 mg, 0.02
mmol), and 4 Å MS (100 mg) in anhydrous DCM (0.8 mL) was
added 1a (117 mg, 0.3 mmol) in DCM (1.2 mL) with stirring. The
reaction mixture was stirred at room temperature and monitored by
TLC. After the reaction was complete, the mixture was directly
subjected to silica gel column chromatography purification (petroleum
ether/ethyl acetate 5/1) to afford the desired product 3aa.
(1S,3aR,8bR)-Dimethyl 3a,8b-dimethyl-1-phenyl-2-tosyl-
1,3a,4,8b-tetrahydropyrrolo[3,4-b]indole- 3,3(2H)-dicarboxylate
1
(3aa): white solid, 101 mg, 95% yield; mp 169−171 °C; H NMR
(400 MHz, CDCl3) δ 7.18 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 4.2 Hz,
2H), 6.90−6.85 (m, 1H), 6.80 (d, J = 8.6 Hz, 2H), 6.74 (td, J = 7.4, 0.8
Hz, 1H), 6.38−6.24 (m, 4H), 6.19 (d, J = 7.0 Hz, 1H), 5.40 (s, 1H),
3.99 (s, 6H), 3.73 (s, 1H), 2.21 (s, 3H), 1.74 (s, 3H), 1.48 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 169.5, 167.8, 146.7, 142.4, 137.7, 137.3,
132.2, 128.8, 128.3, 128.2, 127.7, 127.6, 127.2, 126.8, 126.7, 124.4,
118.9, 109.1, 84.7, 80.0, 77.5, 59.7, 52.9, 52.6, 22.6, 21.2, 20.1; IR (thin
film): νmax (cm−1) 3341, 2921, 1761, 1602, 1492, 1257, 1144, 1062,
871, 749, 702, 657; HRMS (ESI-TOF) calcd for C29H30N2NaO6S [M
+ Na]+ 557.1717, found 557.1708.
CONCLUSIONS
■
General Procedure for the Reaction of 2,3-Disubstituted
Indoles with Aziridines by Sc(OTf)3. To a mixture of 2 (0.3 mmol),
Sc(OTf)3 (10 mg, 0.02 mmol), and 3 Å MS (100 mg) in toluene (2
mL) was added 1 (0.2 mmol) with stirring. The reaction mixture was
stirred at room temperature and monitored by TLC. After the reaction
was complete, the crude reaction mixture was filtered through a pad of
silica gel and washed with ethyl acetate. The solvents were removed
under reduced pressure. The ratio 4:5 was determined by 1H NMR of
the crude reaction mixture. Then the residue was purified by silica gel
column chromatography (petroleum ether/ethyl acetate 4/1) to afford
the desired product 4 (and 3 or 5 in some cases).
In summary, we have disclosed an unprecedented direct C6
functionalization of 2,3-disubstituted indoles with N−Ts
aziridines catalyzed by Sc(OTf)3. Mechanistic investigations
suggested that the initial formation of the annulation products
is a kinetically favored but reversible process while direct C6
functionalization has a relatively higher energetic barrier but
leads to more stabilized products. Future studies will be focused
on expanding the substrate scope as well as developing
asymmetric variants of these novel transformations.
Dimethyl 2-(N-((2,3-dimethyl-1H-indol-6-yl)(phenyl)methyl)-4-
EXPERIMENTAL SECTION
methylphenylsulfonamido)malonate (4aa): white solid, 86 mg,
■
1
80% yield; mp 144−145 °C; H NMR (300 MHz, CDCl3) δ 7.85
General Methods. Unless stated otherwise, all reactions were
carried out in flame-dried glassware under a dry argon atmosphere. All
solvents were freshly distilled according to standard methods prior to
(d, J = 8.3 Hz, 2H), 7.70 (s, 1H), 7.33−7.22 (m, 4H), 7.22−7.15 (m,
3H), 7.12 (d, J = 8.2 Hz, 2H), 6.76 (d, J = 8.2 Hz, 1H), 6.30 (s, 1H),
4.86 (s, 1H), 3.66 (s, 3H), 3.38 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H),
2.17 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.3, 167.1, 143.3,
138.4, 136.8, 134.8, 132.0, 129.7, 128.9, 128.6, 127.9, 127.2, 120.4,
117.2, 111.9, 106.5, 64.9, 62.6, 53.0, 52.5, 21.4, 11.4, 8.4; IR (thin
film): νmax (cm−1) 3392, 2924, 2854, 1756, 1737, 1434, 1132, 1247,
1155, 1026, 808, 786, 665; HRMS (ESI-TOF) calcd for C29H34N3O6S
[M + NH4]+ 552.2163, found 552.2159.
1
use. H NMR spectra were obtained at 300, 400, or 600 MHz and
recorded relative to tetramethylsilane signal (0 ppm) or residual protio
solvent. 13C NMR spectra were obtained at 75, 100, or 150 MHz, and
chemical shifts were recorded relative to the solvent resonance
(CDCl3, 77.0 ppm; DMSO-d6, 39.5 ppm). Data for 1H NMR are
recorded as follows: chemical shift (δ, ppm) (multiplicity (s = singlet,
d = doublet, t = triplet, m = multiplet or unresolved, br = broad
singlet), coupling constant(s) in Hz, integration). Data for 13C NMR
are reported in terms of chemical shift (δ, ppm).
General Procedure for the Preparation of Aziridines 1. The
aziridines 1a−j were prepared according to the reported procedures.15
The characterization data of the two new compounds 1b,h are
summarized below.
Dimethyl 2-(N-((2,3-dimethyl-1H-indol-5-yl)(phenyl)methyl)-4-
methylphenylsulfonamido)malonate (5aa): white solid, 9 mg, 9%
1
yield; mp 125−127 °C; H NMR (400 MHz, CDCl3) δ 7.90 (d, J =
8.3 Hz, 2H), 7.76 (s, 1H), 7.35−7.31 (m, 2H), 7.25−7.18 (m, 4H),
7.14 (d, J = 8.6 Hz, 2H), 7.06 (d, J = 8.4 Hz, 1H), 6.81 (dd, J = 8.4, 1.5
Hz, 1H), 6.31 (s, 1H), 4.87 (s, 1H), 3.67 (s, 3H), 3.42 (s, 3H), 2.32 (s,
3H), 2.31 (s, 3H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
167.3, 167.1, 143.3, 138.5, 136.9, 134.6, 131.4, 129.1, 129.0, 128.80,
128.78, 128.0, 127.7, 127.4, 122.5, 119.2, 109.6, 107.2, 65.1, 62.6, 53.0,
52.5, 21.5, 11.5, 8.3; IR (thin film): νmax (cm−1) 3403, 2948, 1744,
Dimethyl 3-(naphthalen-1-yl)-1-tosylaziridine-2,2-dicarboxylate
(1b): white solid, 0.90 g, 68% yield; mp 130−132 °C; 1H NMR
(400 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.3 Hz,
2H), 7.83 (d, J = 8.1 Hz, 1H), 7.80−7.75 (m, 1H), 7.61−7.55 (m,
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1597, 1435, 1336, 1247, 1151, 1042, 909, 808, 730, 668; HRMS (ESI-
TOF) calcd for C29H34N3O6S [M + NH4]+ 552.2163, found 552.2155.
Dimethyl 2-(N-((2,3-dimethyl-1H-indol-6-yl)(naphthalen-1-yl)-
methyl)-4-methylphenylsulfonamido)malonate (4ba): white solid,
103 mg, 88% yield; mp 177−179 °C; 1H NMR (400 MHz, CDCl3) δ
7.97 (d, J = 7.2 Hz, 1H), 7.71 (d, J = 8.2 Hz, 2H), 7.69−7.58 (m, 4H),
7.33−7.16 (m, 4H), 7.11 (s, 1H), 7.04 (s, 1H), 6.84 (d, J = 8.2 Hz,
2H), 6.75 (d, J = 7.8 Hz, 1H), 4.92 (s, 1H), 3.73 (s, 3H), 3.19 (s, 3H),
2.25 (s, 3H), 2.14 (s, 3H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 167.5, 167.3, 143.0, 136.7, 134.9, 133.9, 133.5, 132.2, 130.4, 129.9,
129.4, 128.5, 128.33, 128.30, 127.8, 125.9, 125.1, 124.9, 123.9, 121.0,
117.7, 112.5, 106.7, 63.7, 63.1, 53.2, 52.1, 21.2, 11.5, 8.3; IR (thin
film): νmax (cm−1) 3395, 2959, 1753, 1736, 1469, 1338, 1249, 1155,
1016, 804, 760, 666; HRMS (ESI-TOF) calcd for C33H36N3O6S [M +
NH4]+ 602.2319, found 602.2309.
3H), 2.31 (s, 3H), 2.25 (s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.6, 167.3, 143.2, 138.3, 136.3, 134.9, 132.6, 132.4, 129.5,
128.7, 128.5, 128.4, 128.2, 128.0, 126.9, 123.0, 120.9, 117.6, 113.0,
106.8, 65.1, 63.6, 53.4, 52.1, 21.3, 11.5, 8.4; IR (thin film): νmax (cm−1)
3397, 3033, 2936, 1760, 1744, 1471, 1329, 1251, 1156, 1018, 786, 725,
666; HRMS (ESI-TOF) calcd for C29H33BrN3O6S [M + NH4]+
630.1268, found 630.1258.
Diethyl 2-(N-((2,3-dimethyl-1H-indol-6-yl)(phenyl)methyl)-4-
methylphenylsulfonamido)malonate (4ia): white solid, 88 mg, 78%
1
yield; mp 163−165 °C; H NMR (400 MHz, CDCl3) δ 7.87 (d, J =
8.3 Hz, 2H), 7.76 (s, 1H), 7.34−7.21 (m, 4H), 7.20−7.14 (m, 3H),
7.10 (d, J = 6.6 Hz, 2H), 6.76 (d, J = 8.1 Hz, 1H), 6.30 (s, 1H), 4.81
(s, 1H), 4.22−4.06 (m, 2H), 3.94−3.82 (m, 1H), 3.75−3.63 (m, 1H),
2.30 (two s, 6H), 2.16 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H), 0.99 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8, 166.7, 143.2, 138.6,
137.0, 134.8, 131.8, 130.0, 129.0, 128.9, 128.7, 128.6, 127.8, 127.2,
120.6, 117.3, 111.9, 106.7, 64.9, 62.9, 62.2, 61.7, 21.4, 13.8, 13.4, 11.5,
8.4; IR (thin film): νmax (cm−1) 3398, 1751, 1735, 1470, 1332, 1252,
1148, 1021, 808, 785, 665; HRMS (ESI-TOF) calcd for C31H38N3O6S
[M + NH4]+ 580.2476, found 580.2487.
Dimethyl 2-(N-((2,3-dimethyl-1H-indol-6-yl)(4-nitrophenyl)-
methyl)-4-methylphenylsulfonamido)malonate (4ca): Yellow solid,
1
93 mg, 80% yield; mp 165−167 °C; H NMR (400 MHz, CDCl3) δ
7.99 (d, J = 8.8 Hz, 2H), 7.89 (s, 1H), 7.77 (d, J = 8.3 Hz, 2H), 7.53
(d, J = 8.7 Hz, 2H), 7.28 (d, J = 8.2 Hz, 1H), 7.17 (s, 1H), 7.12 (d, J =
8.2 Hz, 2H), 6.63 (dd, J = 8.2, 1.2 Hz, 1H), 6.40 (s, 1H), 4.83 (s, 1H),
3.79 (s, 3H), 3.20 (s, 3H), 2.31 (two s, 6H), 2.17 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.3, 166.7, 146.9, 146.5, 143.9, 136.6, 134.8,
132.7, 129.6, 129.1, 128.9, 128.5, 128.4, 123.0, 120.7, 117.7, 112.6,
106.9, 64.7, 62.8, 53.4, 52.4, 21.5, 11.5, 8.4; IR (thin film): νmax (cm−1)
3399, 1758, 1746, 1512, 1326, 1152, 1032, 839, 727, 671; HRMS (ESI-
TOF) calcd for C29H33N4O8S [M + NH4]+ 597.2014, found 597.2004.
Dimethyl 2-(N-((4-chlorophenyl)(2,3-dimethyl-1H-indol-6-yl)-
methyl)-4-methylphenylsulfonamido)malonate (4da): white solid,
Diisopropyl 2-(N-((2,3-dimethyl-1H-indol-6-yl)(phenyl)methyl)-4-
methylphenylsulfonamido)malonate (4ja): white solid, 97 mg, 82%
1
yield; mp 173−174 °C; H NMR (400 MHz, CDCl3) δ 7.90 (d, J =
8.3 Hz, 2H), 7.74 (s, 1H), 7.32−7.26 (m, 2H), 7.25−7.20 (m, 2H),
7.17−7.11 (m, 3H), 7.07 (d, J = 8.0 Hz, 2H), 6.73 (dd, J = 8.2, 1.4 Hz,
1H), 6.27 (s, 1H), 5.02−4.92 (m, 1H), 4.72 (s, 1H), 4.66−4.57 (m,
1H), 2.29 (s, 3H), 2.26 (s, 3H), 2.13 (s, 3H), 1.26 (d, J = 6.2 Hz, 3H),
1.18 (d, J = 6.3 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H), 0.79 (d, J = 6.3 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 166.5, 166.2, 143.1, 138.7,
137.0, 134.8, 131.8, 130.1, 129.0, 128.9, 128.8, 128.5, 127.8, 127.1,
120.7, 117.4, 112.0, 106.7, 70.2, 69.6, 64.8, 63.1, 21.5, 21.4, 21.3, 20.9,
11.5, 8.3; IR (thin film): νmax (cm−1) 3388, 1751, 1728, 1469, 1324,
1248, 1151, 1022, 786, 703, 668, 640; HRMS (ESI-TOF) calcd for
C33H42N3O6S [M + NH4]+ 608.2789, found 608.2799.
1
87 mg, 76% yield; mp 122−124 °C; H NMR (400 MHz, CDCl3) δ
7.89 (s, 1H), 7.81 (d, J = 8.2 Hz, 2H), 7.30−7.21 (m, 4H), 7.15−7.09
(m, 4H), 6.70 (d, J = 7.8 Hz, 1H), 6.27 (s, 1H), 4.82 (s, 1H), 3.71 (s,
3H), 3.28 (s, 3H), 2.32 (s, 3H), 2.29 (s, 3H), 2.16 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.3, 166.9, 143.6, 137.1, 136.7, 134.8, 133.0,
132.2, 129.9, 129.19, 129.17, 129.0, 128.5, 128.0, 120.4, 117.4, 112.0,
106.7, 64.5, 62.6, 53.2, 52.5, 21.4, 11.5, 8.4; IR (thin film): νmax (cm−1)
3373, 2953, 1763, 1747, 1492, 1244, 1148, 1013, 810, 741, 726, 664;
HRMS (ESI-TOF) calcd for C29H33ClN3O6S [M + NH4]+ 586.1773,
found 586.1766.
Dimethyl 2-(N-((2-ethyl-3-methyl-1H-indol-6-yl)(phenyl)methyl)-
4-methylphenylsulfonamido)malonate (4ab): white solid, 81 mg,
74% yield; mp 148−150 °C; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J
= 8.3 Hz, 2H), 7.81 (s, 1H), 7.32−7.24 (m, 4H), 7.20−7.14 (m, 3H),
7.10 (d, J = 8.1 Hz, 2H), 6.75 (dd, J = 8.4, 1.3 Hz, 1H), 6.31 (s, 1H),
4.86 (s, 1H), 3.65 (s, 3H), 3.36 (s, 3H), 2.70 (q, J = 7.6 Hz, 2H), 2.29
(s, 3H), 2.18 (s, 3H), 1.22 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.3, 167.1, 143.3, 138.5, 137.7, 136.9, 134.8, 129.9, 129.0,
128.9, 128.7, 128.6, 127.9, 127.3, 120.6, 117.5, 111.9, 105.8, 65.0, 62.7,
53.0, 52.5, 21.4, 19.3, 13.9, 8.3; IR (thin film): νmax (cm−1) 3388, 2953,
1762, 1750, 1436, 1328, 1148, 1038, 815, 783, 664; HRMS (ESI-TOF)
calcd for C30H36N3O6S [M + NH4]+ 566.2319, found 566.2313.
Dimethyl 2-(N-((5,6,7,8,9,10-hexahydrocyclohepta[b]indol-3-yl)-
(phenyl)methyl)-4-methylphenylsulfonamido)malonate (4ac):
white solid, 90 mg, 78% yield; mp 135−137 °C; 1H NMR (400
MHz, CDCl3) δ 7.85 (d, J = 8.3 Hz, 2H), 7.74 (s, 1H), 7.30−7.23 (m,
4H), 7.19−7.14 (m, 3H), 7.11 (d, J = 8.1 Hz, 2H), 6.75 (dd, J = 8.3,
1.4 Hz, 1H), 6.30 (s, 1H), 4.85 (s, 1H), 3.65 (s, 3H), 3.37 (s, 3H),
2.80−2.70 (m, 4H), 2.30 (s, 3H), 1.91−1.81 (m, 2H), 1.79−1.68 (m,
4H); 13C NMR (100 MHz, CDCl3) δ 167.3, 167.2, 143.3, 138.6,
138.4, 136.8, 133.8, 129.5, 129.0, 128.8, 128.7, 128.6, 127.9, 127.3,
120.5, 117.1, 113.4, 111.9, 64.9, 62.6, 53.0, 52.6, 31.7, 29.5, 28.7, 27.4,
24.6, 21.4; IR (thin film): νmax (cm−1) 3390, 2923, 1759, 1740, 1434,
1322, 1245, 1149, 1023, 911, 800, 730, 701; HRMS (ESI-TOF) calcd
for C32H38N3O6S [M + NH4]+ 592.2476, found 592.2466.
Dimethyl 2-(N-((4-bromophenyl)(2,3-dimethyl-1H-indol-6-yl)-
methyl)-4-methylphenylsulfonamido)malonate (4ea): white solid,
105 mg, 86% yield; mp 133−135 °C; 1H NMR (400 MHz, CDCl3) δ
7.88 (s, 1H), 7.80 (d, J = 8.1 Hz, 2H), 7.29−7.21 (m, 4H), 7.18 (d, J =
8.3 Hz, 2H), 7.12 (d, J = 7.9 Hz, 2H), 6.70 (d, J = 8.1 Hz, 1H), 6.25 (s,
1H), 4.82 (s, 1H), 3.72 (s, 3H), 3.28 (s, 3H), 2.33 (s, 3H), 2.29 (s,
3H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 166.9,
143.6, 137.6, 136.7, 134.8, 132.3, 130.9, 130.2, 129.2, 129.1, 129.0,
128.5, 121.2, 120.4, 117.4, 112.1, 106.7, 64.5, 62.6, 53.2, 52.5, 21.5,
11.5, 8.4; IR (thin film): νmax (cm−1) 3373, 3033, 2953, 1762, 1746,
1433, 1317, 1245, 1148, 1027, 830, 749, 670; HRMS (ESI-TOF) calcd
for C29H33BrN3O6S [M + NH4]+ 630.1268, found 630.1258.
Dimethyl 2-(N-((3-bromophenyl)(2,3-dimethyl-1H-indol-6-yl)-
methyl)-4-methylphenylsulfonamido)malonate (4fa): white solid,
104 mg, 85% yield; mp 156−158 °C; 1H NMR (400 MHz, CDCl3) δ
7.86−7.77 (m, 3H), 7.45 (s, 1H), 7.29 (d, J = 8.1 Hz, 2H), 7.22−7.18
(m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.03 (t, J = 7.9 Hz, 1H), 6.73 (dd, J
= 8.2, 1.4 Hz, 1H), 6.28 (s, 1H), 4.80 (s, 1H), 3.77 (s, 3H), 3.28 (s,
3H), 2.33 (s, 3H), 2.32 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.2, 166.9, 143.6, 140.9, 136.6, 134.8, 132.2, 131.2, 130.2,
129.5, 129.3, 129.1, 128.5, 127.1, 122.2, 120.7, 117.6, 112.1, 106.9,
64.6, 62.6, 53.3, 52.5, 21.5, 11.6, 8.4; IR (thin film): νmax (cm−1) 3413,
1762, 1735, 1598, 1434, 1330, 1259, 1154, 1046, 787, 728, 669;
HRMS (ESI-TOF) calcd for C29H33BrN3O6S [M + NH4]+ 630.1268,
found 630.1259.
Dimethyl 2-(4-methyl-N-(phenyl(2,3,4,9-tetrahydro-1H-carbazol-
7-yl)methyl)phenylsulfonamido)malonate (4ad): white solid, 83 mg,
74% yield; mp 123−125 °C; 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J
= 8.3 Hz, 2H), 7.73 (s, 1H), 7.26−7.19 (m, 4H), 7.15−7.10 (m, 3H),
7.07 (d, J = 8.3 Hz, 2H), 6.71 (dd, J = 8.2, 1.4 Hz, 1H), 6.26 (s, 1H),
4.83 (s, 1H), 3.61 (s, 3H), 3.35 (s, 3H), 2.68−2.56 (m, 4H), 2.26 (s,
3H), 1.88−1.74 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 167.2,
167.1, 143.3, 138.5, 136.9, 135.34, 135.28, 129.9, 128.9, 128.7, 128.6,
127.9, 127.4, 127.3, 120.6, 117.1, 112.0, 109.7, 65.1, 62.6, 53.0, 52.6,
23.2, 23.1, 21.4, 20.8; IR (thin film): νmax (cm−1) 2952, 1743, 1435,
Dimethyl 2-(N-((2-bromophenyl)(2,3-dimethyl-1H-indol-6-yl)-
methyl)-4-methylphenylsulfonamido)malonate (4ga): white solid,
114 mg, 93% yield; mp 170−172 °C; 1H NMR (400 MHz, CDCl3) δ
7.89 (d, J = 7.7 Hz, 1H), 7.77 (s, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.33−
7.25 (m, 2H), 7.17 (td, J = 7.6, 1.1 Hz, 1H), 7.04−6.96 (m, 4H), 6.64
(d, J = 8.3 Hz, 1H), 6.59 (s, 1H), 4.81 (s, 1H), 3.82 (s, 3H), 3.21 (s,
1052
dx.doi.org/10.1021/jo402511b | J. Org. Chem. 2014, 79, 1047−1054

The Journal of Organic Chemistry
Article
1335, 1151, 1030, 907, 811, 730, 666; HRMS (ESI-TOF) calcd for
C31H36N3O6S [M + NH4]+ 578.2319, found 578.2310.
1455, 1287, 1145, 1051, 990, 737, 678; HRMS (ESI-TOF) calcd for
C28H29N2O6S [M + H]+ 521.1741, found 521.1738.
Dimethyl 2-(4-methyl-N-((3-methyl-1H-indol-6-yl)(phenyl)-
Dimethyl 2-(4-methyl-N-((9-methyl-2,3,4,9-tetrahydro-1H-carba-
zol-7-yl)(phenyl)methyl)phenylsulfonamido)malonate (4ae): white
solid, 48 mg, 42% yield; mp 167−169 °C; 1H NMR (400 MHz,
CDCl3) δ 7.92 (d, J = 8.3 Hz, 2H), 7.34−7.19 (m, 7H), 7.13 (d, J = 8.0
Hz, 2H), 6.68 (d, J = 8.2 Hz,1H), 6.34 (s, 1H), 4.86 (s, 1H), 3.58 (s,
3H), 3.52 (s, 3H), 3.51 (s, 3H), 2.71−2.63 (m, 4H), 2.30 (s, 3H),
1.97−1.77 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 167.12, 167.09,
143.3, 138.4, 136.9, 136.6, 136.4, 129.3, 129.1, 128.9, 128.7, 127.9,
127.6, 126.4, 119.8, 117.1, 109.3, 108.9, 65.0, 62.4, 52.80, 52.77, 28.8,
23.1, 22.0, 21.4, 21.0; IR (thin film): νmax (cm−1) 2916, 2840, 1764,
1745, 1469, 1334, 1289, 1156, 1030, 813, 666; HRMS (ESI-TOF)
calcd for C32H38N3O6S [M + NH4]+ 592.2476, found 592.2479.
Dimethyl 2-(4-methyl-N-((9-methyl-2,3,4,9-tetrahydro-1H-carba-
zol-6-yl)(phenyl)methyl)phenylsulfonamido)malonate (5ae): white
solid, 23 mg, 20% yield; mp 142−144 °C; 1H NMR (400 MHz,
CDCl3) δ 7.90 (d, J = 8.3 Hz, 2H), 7.35−7.29 (m, 2H), 7.24−7.18 (m,
4H), 7.14 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.5 Hz, 1H), 6.86 (dd, J =
8.4, 1.7 Hz, 1H), 6.31 (s, 1H), 4.86 (s, 1H), 3.67 (s, 3H), 3.57 (s, 3H),
3.45 (s, 3H), 2.68 (t, J = 5.9 Hz, 2H), 2.58 (t, J = 6.0 Hz, 2H), 2.32 (s,
3H), 1.96−1.88 (m, 2H), 1.84−1.78 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 167.3, 167.0, 143.3, 138.6, 137.0, 136.4, 136.2, 128.9,
128.83, 128.77, 127.9, 127.3, 127.2, 126.8, 122.0, 118.9, 109.4, 108.0,
65.1, 62.5, 53.0, 52.6, 29.0, 23.12, 23.07, 22.0, 21.4, 20.9; IR (thin
film): νmax (cm−1) 2925, 2851, 1744, 1434, 1337, 1245, 1152, 1042,
807, 701, 668; HRMS (ESI-TOF) calcd for C32H35N2O6S [M + H]+
575.2210, found 575.2214.
methyl)phenylsulfonamido)malonate (4ag): white solid; mp 144−
1
145 °C, 52 mg, 50% yield. H NMR (400 MHz, CDCl3) δ 9.45 (s,
1H), 7.57 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 7.8 Hz, 1H), 7.33−7.12 (m,
7H), 7.10−6.97 (m, 3H), 6.35 (s, 1H), 5.06 (s, 1H), 3.62 (s, 3H), 3.47
(s, 3H), 2.22 (s, 3H), 1.79 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
167.9, 166.8, 143.8, 136.4, 136.0, 135.6, 129.8, 129.01, 128.96, 128.9,
128.4, 128.2, 127.8, 122.0, 119.0, 118.3, 111.1, 109.8, 62.6, 58.7, 53.5,
52.9, 21.4, 8.7; IR (thin film): νmax (cm−1) 3392, 2943, 1766, 1737,
1493, 1339, 1265, 1143, 1047, 763, 663; HRMS (ESI-TOF) calcd for
C28H29N2O6S [M + H]+ 521.1741, found 521.1744.
Computational Methods. All calculations in this paper were
performed with the Gaussian09 package.16 The density functional
theory (DFT) method was employed using the M06 functional.17
SDD basis sets18 with the associated effective core potential was used
for Sc and the 6-31G(d) basis sets19 for other atoms. The key word
“5d” was specified to use five pure d functions in the calculations.
Optimizations were conducted without any constraint using the SMD
model20 in toluene (ε = 2.3741). Frequency analyses were carried out
to confirm each structure being a minimum (no imaginary frequency)
or a transition state (only one imaginary frequency). The energies
were further estimated by single-point calculations at the M06/SDD/
6-311++G(d,p) level of theory. The Gibbs free energies in toluene
(ΔG) were discussed throughout this paper. The orbital composition
analyses were conducted using Multiwfn.21 All figures of the calculated
3D structures were prepared using CYLview.22 Details of the
computational work can be found in the Supporting Information.
(3aR,8bR,9S)-Dimethyl 9-phenyl-10-tosyl-1,2,3,4-tetrahydro-
3a,8b-(methanoiminomethano)cyclopenta[b]indole-11,11-dicar-
boxylate (3af-1, minor diastereoisomer of 3af): white solid, 30 mg,
ASSOCIATED CONTENT
■
1
27% yield; mp 273−274 °C; H NMR (400 MHz, CDCl3) δ 7.26−
S
* Supporting Information
7.15 (m, 4H), 6.92 (tt, J = 7.3, 1.2 Hz, 1H), 6.83−6.74 (m, 3H), 6.36
(d, J = 7.8 Hz, 1H), 6.29 (t, J = 7.5 Hz, 1H), 6.22 (td, J = 7.5, 0.9 Hz,
1H), 6.10 (d, J = 7.9 Hz, 1H), 5.86 (d, J = 7.5 Hz, 1H), 5.68 (s, 1H),
4.00 (s, 3H), 3.99 (s, 3H), 3.96 (s, 1H), 2.66−2.56 (m, 1H), 2.37−
2.18 (m, 2H), 2.21 (s, 3H), 2.02−1.86 (m, 2H), 1.69−1.52 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 170.1, 167.7, 148.8, 142.5, 137.8,
Figures, tables, text, and CIF files giving H and 13C NMR
1
spectra of all new compounds, crystallographic data for 3aa,
4aa, and 5aa, complete citation of ref 16, computational details
(including the figures not presented in the text), 3D structures,
and Cartesian coordinates of all calculated stationary points.
This material is available free of charge via the Internet at
http://pubs.acs.org.
137.2, 131.5, 129.7, 129.0, 128.6, 127.8, 127.7, 127.1, 127.01, 127.00,
124.9, 119.2, 108.6, 88.1, 85.1, 75.7, 70.5, 53.1, 52.7, 40.64, 40.59, 28.6,
21.3; IR (thin film): νmax (cm−1) 3353, 2952, 1761, 1599, 1489, 1334,
1231, 1154, 1037, 750, 700; HRMS (ESI-TOF) calcd for
C30H31N2O6S [M + H]+ 547.1897, found 547.1907.
AUTHOR INFORMATION
Corresponding Author
■
(3aR,8bR,9R)-Dimethyl 9-phenyl-10-tosyl-1,2,3,4-tetrahydro-
3a,8b-(methanoiminomethano)cyclopenta[b]indole-11,11-dicar-
boxylate (3af-2, major diastereoisomer of 3af): white solid, 47 mg,
43% yield; mp 208−209 °C; 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J
= 7.5 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H),
7.21−7.16 (m, 1H), 7.10 (dd, J = 7.4, 0.7 Hz, 1H), 7.04 (td, J = 7.7,
1.2 Hz, 1H), 6.95 (d, J = 8.1 Hz, 2H), 6.82−6.76 (m, 3H), 6.53 (d, J =
7.6 Hz, 1H), 5.76 (s, 1H), 4.19 (br, 1H), 4.00 (s, 3H), 3.42 (s, 3H),
2.33 (s, 3H), 1.97 (dd, J = 12.7, 5.2 Hz, 1H), 1.80−1.70 (m, 2H),
1.60−1.42 (m, 2H), 1.20 (dd, J = 13.1, 6.7 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 168.6, 168.1, 149.1, 143.0, 137.8, 137.3, 130.6, 129.3,
128.9, 128.3, 128.1, 127.9, 127.5, 127.3, 122.9, 119.7, 108.1, 85.4, 84.0,
74.8, 66.9, 52.8, 51.6, 40.3, 40.1, 24.8, 21.4; IR (thin film): νmax (cm−1)
3378, 2949, 2870, 1752, 1599, 1484, 1340, 1249, 1154, 1052, 920, 746,
704, 667; HRMS (ESI-TOF) calcd for C30H31N2O6S [M + H]+
547.1897, found 547.1904.
(1S,3aR,8bS)-Dimethyl 8b-methyl-1-phenyl-2-tosyl-1,3a,4,8b-
tetrahydropyrrolo[3,4-b]indole-3,3(2H)-dicarboxylate (3ag): white
solid; mp 215−216 °C, 47 mg, 45% yield. 1H NMR (600 MHz,
DMSO-d6, 80 °C) δ 7.20 (d, J = 7.8 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H),
6.85 (t, J = 6.6 Hz, 1H), 6.68−6.86 (m, 5H), 6.36 (d, J = 7.2 Hz, 1H),
6.09 (t, J = 7.2 Hz, 1H), 5.95 (d, J = 7.8 Hz, 1H), 5.78 (br, 1H), 5.11
(s, 1H), 4.51 (d, J = 4.8 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 2.21 (s,
3H), 1.66 (s, 3H); 13C NMR (150 MHz, DMSO-d6, 80 °C) δ 168.6,
166.4, 149.1, 142.1, 137.3, 136.7, 131.9, 128.1, 127.8, 127.5, 126.9,
126.3, 126.2, 123.6, 117.1, 108.4, 81.5, 77.3, 76.8, 57.3, 52.3, 52.0, 26.7,
20.3; IR (thin film): νmax (cm−1) 3354, 3055, 2953, 1764, 1735, 1609,
*Fax: (+86) 21-5492-5087. Tel: (+86) 21-5492-5085. E-mail:
zhengchao@sioc.ac.cn (C.Z.); slyou@sioc.ac.cn (S.L.Y.). Web:
http://shuliyou.sioc.ac.cn/.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Basic Research Program of China
(2010CB833300) and the National Natural Science Founda-
tion of China (21025209, 21121062, 21332009, and 21302209)
for generous financial support.
REFERENCES
■
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