Diastereoselective Synthesis of Tetrahydrospiro[carbazole-1,3′-indolines] via an InBr3-Catalyzed Domino Diels-Alder Reaction

DOI: 10.1021/acs.joc.1c00103

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Journal of Organic Chemistry p. 5616 - 5629 (2021)

Update date:2022-09-26

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Authors:

Wang, Daqian

Sun, Jing

Liu, Ru-Zhang

Wang, Yang

Yan, Chao-Guo

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Article abstract of DOI:10.1021/acs.joc.1c00103

A simple InBr3-catalyzed domino reaction of indoles, phenylacetylenes, and various 3-methyleneoxindolines in toluene is described. This reaction not only provided a convenient synthetic protocol for polysubstituted tetrahydrospiro[carbazole-1,3′-indolines] in good yields but also gave completely different diastereoisomers of the tetrahydrospiro[carbazole-1,3′-indolines] to that of the previously reported TfOH-catalyzed one-pot reaction of indoles, acetophenones, and 3-methyleneoxindolines. Additionally, the InBr3-catalyzed reaction of the initially prepared 1,1′-bis(indolyl)phenylethanes with 3-phenacylideneoxindolines also gave the corresponding tetrahydrospiro[carbazole-1,3′-indolines] in good yields and with excellent diastereoselectivity. The reaction mechanism involved the sequential in situ generation of reactive dienophilic 3-alkenylindole, the Diels-Alder reaction, and the Lewis acid controlled diastereoisomerization process.

Full text of DOI:10.1021/acs.joc.1c00103

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Diastereoselective Synthesis of Tetrahydrospiro[carbazole-1,3′-

indolines] via an InBr₃‑Catalyzed Domino Diels−Alder Reaction

Daqian Wang, Jing Sun, Ru-Zhang Liu,* Yang Wang, and Chao-Guo Yan*

Cite This: J. Org. Chem. 2021, 86, 5616 −5629

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ABSTRACT: A simple InBr₃-catalyzed domino reaction of

indoles, phenylacetylenes, and various 3-methyleneoxindolines in

toluene is described. This reaction not only provided a convenient

synthetic protocol for polysubstituted tetrahydrospiro[carbazole-

1,3′-indolines] in good yields but also gave completely diﬀerent

diastereoisomers of the tetrahydrospiro[carbazole-1,3′-indolines]

to that of the previously reported TfOH-catalyzed one-pot reaction

of indoles, acetophenones, and 3-methyleneoxindolines. Addition-

ally, the InBr₃-catalyzed reaction of the initially prepared 1,1′-

bis(indolyl)phenylethanes with 3-phenacylideneoxindolines also

gave the corresponding tetrahydrospiro[carbazole-1,3′-indolines] in good yields and with excellent diastereoselectivity. The reaction

mechanism involved the sequential in situ generation of reactive dienophilic 3-alkenylindole, the Diels−Alder reaction, and the Lewis

acid controlled diastereoisomerization process.

dienophiles has been proven to be the most eﬃcient strategy

for the synthesis of many tetrahydrocarbazole derivatives.^9,10In

this respect, the domino reaction of the in situ generated 3-

vinylindoles and its sequential Diels−Alder reaction showed

many advantages such as avoiding time-consuming isolation of

the intermediates, minimal waste generation, molecular

diversity, and atom-economy. In recent years, many elegant

synthetic methodologies with deﬁnite regio-, diastereo-, and

enantio-control strategies based on the domino Diels−Alder

reaction have been successfully developed.^11,12

INTRODUCTION

■

Tetrahydrocarbazole and spirooxindoles scaﬀolds appear

broadly in many biologically active compounds and functional

materials.^1,2Many tetrahydrocarbazole-containing molecules

possess a wide range of biological activities such as DNA

biosynthesis, Inhibitors in bacteria,^3atreating potency cigarette

smoke-induced acute lung injury in patients^3band anxiolytic

activity (Figure 1).^3cThe tetrahydrocarbazole derivatives also

For the construction of diverse spiro-carbazole-oxindole

systems, the Diels−Alder reaction of vinylindoles with reactive

dienophilic 3-methyleneoxindoles has attracted great atten-

tion.¹³⁻¹⁵For example, Barbas and co-workers successfully

developed C2-symmetric bisthiourea catalyzed Diels−Alder

reaction of 3-vinylindolines with 3-methyleneindolinones for

enantioselective construction of spiro[carbazole-1,3′-oxindo-

lines] (eq 1 in Scheme 1).^13aRecently, we found that TfOH

catalyzed a one-pot reaction of indoles, acetophenones and 3-

methyleneoxindolines in toluene aﬀorded polysubstituted

tetrahydrospiro[carbazole-1,3′-indolines] in satisfactory yields

with high diastereoselectivity (eq 2 in Scheme 1).¹⁶For

developing the synthetic applications of this eﬃcient synthetic

Figure 1. Representative natural products containing tetrahydrocar-

bazole or spirooxindole scaﬀolds

show signiﬁcant inhibitory activity against Mycobacterium

tuberculosis and are thus of interest as potential new lead

compounds for anti-TB active drugs.^3d,fNowadays, various

synthetic strategies for the preparation of tetrahydrocarbazole

derivatives have been exploited.⁴⁻⁸Among these sophisticated

synthetic methodologies for tetrahydrocarbazoles, the Diels−

Alder reaction of 3-vinyl- or 2-vinylindoles with diverse

Received: January 13, 2021

Published: April 5, 2021

https://doi.org/10.1021/acs.joc.1c00103

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With the feasible reaction conditions, the scope of the

domino reaction was explored. Various (E)-3-phenacylide-

neoxindoles were employed in the one-pot two-step reaction.

The results were summarized in Table 1. All reactions

Scheme 1. Diastereoselective Synthesis of Polysubstituted

Tetrahydrospiro[carbazole-1,3′-indolines]

Table 1. Synthesis of Spiro[carbazole-1,3′-indolines] 1a−

yield

entry comp

R¹

R²

R³

R⁴

(%)

p-CH₃OC₆H₄

p-CH₃C₆H₄

p-ClC₆H₄

n-Bu p-CH₃C₆H₄

n-Bu p-CH₃OC₆H₄

p-CH₃C₆H₄

p-CH₃OC₆H₄

C₆H₅

protocol, we noticed that the desired 3-alkenylindoles can also

be easily obtained by indium nonaﬂuorobutanesulfonate^17aor

indium tribromide^17bcatalyzed hydroarylation reaction of

alkynes with indoles. Thus, the domino reaction of indoles,

phenylacetylenes, and (E)-3-phenacylideneoxindoles was

carried out in toluene in the presence of the readily available

Lewis acid InBr₃. We found that polysubstituted

tetrahydrospiro[carbazole-1,3′-indolines] with the deﬁnite

conﬁguration could be conveniently prepared in good yields

(eq 3 in Scheme 1). This InBr₃-catalyzed domino reaction of

indoles, phenylacetylenes, and various 3-methyleneoxindolines

in toluene not only provided a convenient synthetic protocol

for polysubstituted tetrahydrospiro[carbazole-1,3′-indolines]

in good yields but also gave the completely diﬀerent

diastereoisomer of the tetrahydrospiro[carbazole-1,3′-indo-

lines] to that of the corresponding TfOH catalyzed one-pot

reaction of indoles, acetophenones, and 3-methyleneoxindo-

lines. Herein we wish to reveal this very unprecedented result

and the related reactions.

C₆H₅

p-ClC₆H₄

p-CH₃C₆H₄

p-CH₃OC₆H₄

p-CH₃C₆H₄

C₆H₅

p-CH₃C₆H₄

p-Cl

p-Me

m-Me

p-OEt

o-OMe

p-Ph

p-Br

p-F

o-F

Reaction conditions: indole (0.7 mmol), phenylacetylene (0.5

mmol), InBr₃(5 mol %), toluene (2.0 mL), 110 °C, 15 min; 3-

phenacylideneoxindole (0.5 mmol), 80 °C, 14 h. Isolated yields.

RESULTS AND DISCUSSION

■

It has been reported that InBr₃catalyzed hydroarylation of

alkynes with indoles leading to the synthesis of 3-vinylindoles

in good to excellent yields.^17bTherefore, a one-pot two-step

reaction procedure was ﬁrst employed. After the ﬁnishing of

the reaction of phenylacetylene and N-methylindole in toluene

in the presence of InBr₃at 110 °C for 15 min, (E)-1-benzyl-5-

methyl-3-(2-oxo-2-(4-methoxyphenylethylidene)indolin-2-one

was introduced. The second-step reaction was carried out in

110 °C. After workup, the expected polysubstituted spiro-

[carbazole-1,3′-indoline] 1a was obtained in a moderate yield.

Then, the amount of acid catalyst, molar ratio of the three

substrates, reaction temperature, and reaction time of the one-

pot two-step reaction procedure were carefully screened. At

last, we were pleased to ﬁnd product 1a can be obtained in

76% yield by carrying out the second-step reaction at 80 °C for

14 h. The TLC analysis showed that only one product was

predominately formed in the reaction system.

proceeded smoothly to give the expected tetrahydrospiro-

[carbazole-1,3′-indolines] 1a−1i in moderate to good yields

(entries 1−9). Besides 1-methylindole, indole itself also

resulted in the spiro products 1j−1p in good yields (entries

10−16). Additionally, the substituted phenylacetylenes also

gave the spiro compounds 1q−1y in satisfactory yields (entries

17−25). It should be pointed out that the known 1,1′-

bis(indolyl)phenylethanes were also produced as a byproduct

in very lower yields in some cases.¹⁸The structures of the

obtained products 1a−1y were fully characterized by various

spectroscopies. Because there are three chiral centers in the

newly formed cyclohexenyl ring, several diastereoisomers

might be formed in the reaction. H and ¹³C NMR spectra

clearly showed that there is only one diastereoisomer in the

obtained products. The single-crystal structures of the

compounds 1g (Figure 2), 1h, 1i, and 1m (Figure S1 −S4)

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Table 2. Synthesis of Spiro[carbazole-1,3′-indolines] 2a−

entry

compd

R¹

R²

OR³

yield (%)

OMe

OEt

Figure 2. ORTEP drawing (30%) of the crystal structure of the

compound 1g.

were determined by the X-ray diﬀraction method, in which the

4-aryl group exists on the trans-position of the 2-benzoyl group

and the 1-phenyl group of the oxindole moiety. It was well-

known that the benzoyl group and the phenyl group of the

oxindole moiety exist on the cis-position in the starting (E-)-3-

phenacylideneoxindoles.¹⁹Thus, the relative conﬁguration of

these two groups was inversed in the reaction, which means

that this reaction must have a diastereoisomerization process.

Therefore, based on NMR spectra and single-crystal structures,

the spiro compounds 1a−1y were assigned as relative (1,2)-cis-

(2,4)-trans-conﬁguration. Comparing the relative conﬁguration

of tetrahydrospiro[carbazole-1,3′-indolines] 1a−1y with that

of our previously prepared similar spiro compounds (eq 2 in

Scheme 1) by the TfOH-catalyzed a one-pot reaction of

indoles, acetophenones, and 3-methyleneoxindolines in

toluene,^16ait is very interesting to ﬁnd that only the

conﬁguration of the 4-aryl group is opposite, while the

conﬁgurations of the 2-benzoyl group and the 1-phenyl group

of the oxindole moiety are the same. Thus, these two reactions

successfully provided eﬃcient methods for the diastereose-

lective synthesis of polysubstituted tetrahydrospiro[carbazole-

1,3′-indolines]. These two reactions complemented each other

for the synthesis of the spiro compounds with a deﬁnite

conﬁguration.

Reaction conditions: indole (0.7 mmol), phenylacetylene (0.5

mmol), alkyl (E)-2-(2-oxoindolin-3-ylidene)acetate (0.5 mmol),

toluene (2.0 mL), InBr₃(5 mol %), 80 °C, 10 h. Isolated yields.

Figure 3. ORTEP drawing (30%) of the crystal structure of the

compound 2f.

With success in the reactions of 3-phenacylideneoxindoles,

we turned our attention to another commonly used 3-

methyleneoxindole. A couple of alkyl (E)-2-(2-oxoindolin-3-

ylidene)acetates were employed in the one-pot reaction. The

results are summarized in Table 2. The reactions usually

resulted in the expected spiro compounds 2a−2g in moderate

yields. In each case, the byproducts 1,1′-bis(indolyl)-

phenylethanes were also observed. All of the spiro products

hydroarylation of phenylacetylene with N-methylindole in

toluene gave 1-methyl-3-(1-phenylvinyl)indole in a high yield.

However, we could not isolate the desired 3-vinylindole in the

reaction. From the InBr₃-catalyzed reaction of 1-methylindole

with phenylacetylene in toluene, 1,1′-bis(indolyl)phenylethane

can be isolated in 74% yield. We envisioned that 1,1′-

bis(indolyl)phenylethane might be involved in the formation

of spiro compounds. Thus, the reaction of the initially

prepared 1,1′-bis(indolyl)phenylethanes with 3-phenacylide-

neoxindoles was investigated under similar reaction conditions.

The results are summarized in Table 3. It can be seen that the

same spiro compounds 1c, 1e, and 1r were obtained in slightly

higher yields (entries 1−3). Then, 1,1′-bis(indolyl)-

phenylethanes 3a−3e derived from p-MeO-, p-Et-, p-n-Pro-,

p-n-Bu-, and p-NO₂-substituted phenylacetylenes were also

employed in the reaction. The expected spiro compounds 4a−

2a−2g were characterized by IR, HRMS, and H and ¹³C

NMR spectroscopies. The single-crystal structure of com-

pound 2f (Figure 3) indicated that it has the same relative

conﬁguration as that of the spiro compounds 1g, 1h, 1i, and

1m, in which the 2-ethoxycarbonyl group stands on the trans-

position of the 4-aryl group and the 1-phenyl group of the

oxindole moiety. This result showed that this reaction has the

same outcome as the stereochemistry.

In order to study the reaction mechanism, we tried to

separate the expected key intermediate 3-vinylindole in the

reaction. According to the previous report,^17bInBr₃-catalyzed

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indole to give the isolated 1,1′-bis(indolyl)phenylethane 3. On

the other hand, 1,1′-bis(indolyl)phenylethane 3 might lose an

indolyl scaﬀold under the circumstance of InBr₃to give 2-

Table 3. Synthesis of Spiro[carbazole-1,3′-indoline]s 4a−

alkenylindole (A).^19b,19In fact, they were in the interchange

equilibrium in the reaction system. Then, a Diels−Alder

reaction of the intermediate (A) with 3-phenacylideneoxindole

through the endo-transition state gave the cyclized intermediate

(B), which in turn converted to the intermediate (C) by the

antarafacial 1,3-H shift under the catalysis of InBr₃. At last, in

the catalysis of InBr₃, the intermediate (C) converted to the

more stable diastereoisomer 1 by the epimerization process of

the intermediate (D). In this reaction process, the Lewis acid

InBr₃plays a crucial eﬀect on the diastereoselectivity, which

dynamically controlled the formation of the relatively unstable

diastereoisomer (Ar on a-bond and ArCO on e-bonds).

Alternatively, the strong Brønsted acid TfOH-catalyzed

reaction of indole, acetophenone, and 3-methyleneoxindole

to give the most thermodynamically stable diastereoisomer

(both Ar and ArCO on e-bonds).^16aDFT calculations showed

that the free energy diﬀerence of the two diastereoisomers is

4.3 kcal/mol (Supporting Information).

entry comp

Ar¹

C₆H₅

R¹

R²

Ar²

yield (%)

p-ClC₆H₄

p-MeOC₆H₄

p-MeC₆H₄

p-ClC₆H₄

p-MeC₆H₄

p-ClC₆H₄

p-MeOC₆H₄

p-ClC₆H₄

C₆H₅

n-Bu

p-MeC₆H₄

p-MeOC₆H₄

p-EtC₆H₄

p-n-PrC₆H₄

p-n-BuC₆H₄

p-NO₂C₆H₄

Reaction conditions: 1,1′-bis(indolyl)phenylethane (0.35 mmol), 3-

phenacylideneoxindoline (0.35 mmol), toluene (2.0 mL), InBr₃(5

mol %), 80 °C, 10 h. Isolated yields.

To support the reaction mechanism, some control experi-

ments were carried out. At ﬁrst, 3-(1-phenylvinyl)indole was

initially prepared from the reaction of 3-acetylindole with

phenylmagnesium bromide according to the published

method.²⁰The further reaction with 3-phenacylideneoxindole

carried out in the presence of InBr₃gave the spiro compound

1k in 85% yield (Scheme 3). Second, Diels−Alder reaction of

3-(1-phenylvinyl)indole with 3-phenacylideneoxindole in

toluene at 80 °C for 15 h gave the expected intermediate B1

in 86% yield, which was in turn converted to the spiro

compound 1n in 80% yield by heating in toluene in the

presence of InBr₃. These results not only clearly showed that 3-

alkenylindole token part in the reaction process, but also

suggested that InBr₃actually controlled the outcome of the

stereochemistry. When the above-obtained tetrahydrospiro-

[carbazole-1,3′-indolines] 1b and 1c were treated with HOTf

in toluene at 80 °C for 30 min. Instead of the formation of the

spiro compounds with the conversion of the relative

conﬁguration, it was surprised to ﬁnd that the spiro skeleton

was decomposed to give the oxindole-substituted carbazole

derivatives 5a and 5b in 78% and 81% yields, respectively

(Scheme 3). The chemical structures of the carbazoles were

conﬁrmed by determining the single-crystal structure 5a

(Figure S6).^16bIt should be pointed out that the spiro

compound 5a, which was previously prepared from the TfOH-

catalyzed one-pot reaction of N-methylindole, acetophenone,

and 3-methyleneoxindoline in toluene, and a plausible

formation mechanism was also rationally proposed in our

recent work.^16bOn the other hand, it could not be converted

to the spiro compound 1n in toluene in the presence of InBr₃.

These results indicated that the two diastereoisomers could

not be interchanged in the reaction system. Additionally, we

tried to dehydrogenated tetrahydrospiro[carbazole-1,3′-indo-

lines] by oxidation with 2,3-dicyano-5,6-dichlorobenzoquinone

(DDQ) in EtOH or MeCN; complicated mixtures were

obtained. These results showed that the obtained spiro

compounds were sensitive to the reaction conditions. At last,

for industrial applications, the gram-scale reactions were

conducted. The spiro compound 1j could be successfully

prepared in 54% yield. It was a little lower than the previous

yields in the microscale reactions.

4g were produced in satisfactory yields (entries 4−10). The

structures of the obtained products 4a−4g were all established

by IR, HRMS, ¹H and ¹³C NMR spectroscopies. These results

not only showed that this reaction has a wide variety but also

indicated that 1,1′-bis(indolyl)phenylethane was the key

intermediate of the domino reaction.

For explaining the formation of the spiro compounds, a

plausible reaction mechanism was brought forward in Scheme

2 on the basis of the obtained results and the previous

reports.¹⁶⁻¹⁹At ﬁrst, the InBr₃-catalyzed reaction of indole

with phenylacetylene in toluene gave a InBr₃-coordinated 2-

alkenylindole (A), which could react further with an excess

Scheme 2. Plausible Reaction Mechanism

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Scheme 3. Control and Gram-Scale Experiments

100 MHz. High-resolution mass spectra (HRMS) were recorded in

ESI mode using a MicroTOF mass spectrometer. Single-crystal X-ray

data were collected with a Bruker Smart APEX-2 CCD diﬀractometer.

All reactions were monitored by thin-layer chromatography (TLC)

using silica gel plates (silica gel 60 F254 0.25 mm), and components

were monitored by observation under UV light (254 and 365 nm).

1. General Procedure for the Preparation of

Tetrahydrospiro[carbazole-1,3′-indolines] 1a−1y. In a 10 mL

Shleck tube were added indole (0.7 mmol, 1.4 equiv), phenyl-

acetylene (0.5 mmol, 1.0 equiv), indium bromide (0.025 mmol, 0.05

equiv), and toluene (2.0 mL). The mixture was heated at 110 °C by

an oil bath for 15 min. Then, (E)-3-phenacylideneoxindole (0.5

mmol, 1.0 equiv) was added, and the solution was heated at 80 °C by

an oil bath for 14 h. After removing the solvent, the residue was

subjected to column chromatography on silica gel with ethyl acetate

and petroleum ether (v/v = 1:20) to aﬀord the desired products 1a−

1y.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-methoxybenzoyl)-9-methyl-4-phe-

nyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1a):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, yellow

solid, 242 mg, 76%, mp 140−142 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.60−7.58 (m, 2H), 7.46−7.35 (m, 7H), 7.32−7.30 (m, 1H), 7.26−

7.25 (m, 1H), 7.19−7.14 (m, 2H), 7.14−7.08 (m, 2H), 7.00−6.95

(m, 2H), 6.81 (s, 1H), 6.76−6.74 (m, 1H), 6.57−6.55 (m, 2H), 5.33

(d, J = 15.6 Hz, 1H), 4.90 (d, J = 14.8 Hz, 1H), 4.76 (d, J = 4.4 Hz,

1H), 4.36 (d, J = 12.4 Hz, 1H), 3.75 (s, 3H), 3.67−3.59 (m, 1H),

2.83 (s, 3H), 2.22−2.19 (m, 1H), 2.17 (s, 3H); ¹³C{¹H} NMR (100

MHz, CDCl₃) δ 196.7, 176.9, 163.3, 144.4, 142.3, 138.3, 136.6, 134.7,

CONCLUSIONS

■

In summary, we have investigated the InBr₃-catalyzed domino

reaction of indoles, phenylacetylenes, and 3-methyleneoxindo-

lines. This one-pot two-step reaction successfully provided an

eﬃcient synthetic protocol for functionalized tetrahydrospiro-

[carbazole-1,3′-indolines] in good yields and with high

diastereoselectivity. More importantly, this reaction selectively

aﬀorded tetrahydrospiro[carbazole-1,3′-indolines] with a dif-

ferent conﬁguration to that of the known reaction. The relative

conﬁguration of the spiro compounds was conﬁrmed by the

determination of several single-crystal structures. The stereo-

chemistry of the reaction was clearly elucidated. The

advantages of this reaction including easily available starting

materials, relatively mild conditions, excellent diastereoselec-

tivity, and wide functional group tolerance, which enabled this

reaction, might ﬁnd potential applications in synthetic and

medicinal chemistry.

EXPERIMENTAL SECTION

■

Unless noted, the commercial reagents and solvents were used

without further puriﬁcation. 1,1′-Bis(indolyl)phenylethanes^18aand

(E)-3-methyleneoxindoles^18b,cwere prepared by the published

methods. Melting points were recorded with a micromelting point

apparatus and are uncorrected. IR spectra were recorded using a

Bruker Tensor 27 spectrometer (KBr disc). The H and ¹³C{¹H}

NMR spectra were recorded with a Varian 400 spectrometer at 400 or

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132.2, 131.1, 130.6, 129.2, 128.7, 128.6, 128.5, 128.4, 128.1, 127.8,

126.6, 126.0, 123.4, 122.1, 119.2, 113.9, 113.5, 109.0, 108.8, 55.4,

49.9, 49.5, 45.1, 37.7, 33.0, 29.5, 21.1; IR (KBr) υ 3697, 3325, 3056,

3024, 1714, 1678, 1599, 1574, 1494, 1467, 1363, 1337, 1262, 1229,

1180, 1165, 1120, 1078, 1026, 986, 930, 876, 840, 810, 775 cm⁻¹; MS

119.2, 113.9, 113.4, 108.7, 108.2, 55.3, 49.8, 49.4, 40.6, 37.7, 32.9,

29.4, 29.3, 21.1, 20.6, 13.8; IR (KBr) υ 3695, 3055, 1710, 1680, 1599,

1495, 1465, 1366, 1342, 1308, 1262, 1228, 1192, 1163, 1115, 1031,

984, 929, 838, 816, 772 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

C₃₉H₃₈N₂NaO₃([M + Na]⁺) 605.2775, found 605.2760.

(m/z) HRMS (ESI) calcd for C₄₂H₃₆N₂NaO₃([M + Na]⁺)

rel-(1S,2R,4S)-1′-Benzyl-5′-chloro-9-methyl-2-(4-methylbenzo-

yl)-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one

(1f): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

639.2618, found 639.2610.

rel-(1S,2R,4S)-1′-Benzyl-5′,9-dimethyl-2-(4-methylbenzoyl)-4-

phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1b):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 233 mg, 75%, mp 224−226 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.60−7.58 (m, 2H), 7.46−7.42 (m, 2H), 7.39−7.34 (m, 5H), 7.31−

7.30 (m, 1H), 7.26−7.25 (m, 1H), 7.18−7.12 (m, 2H), 7.03−7.01

(m, 2H), 6.98−6.95 (m, 2H), 6.90−6.88 (m, 2H), 6.81 (s, 1H),

6.76−6.74 (m, 1H), 5.33 (d, J = 15.2 Hz, 1H), 4.90 (d, J = 15.6 Hz,

1H), 4.76 (d, J = 11.2 Hz, 1H), 3.62 (td, J₁= 13.2 Hz, J₂= 5.6 Hz,

1H), 2.84 (s, 3H), 2.27 (s, 3H), 2.24−2.21 (m, 1H), 2.16 (s, 3H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.8, 176.9, 144.3, 143.8,

white solid, 282 mg, 88%, mp 223−225 °C; H NMR (400 MHz,

CDCl₃) δ 7.58−7.57 (m, 2H), 7.47−7.43 (m, 2H), 7.40−7.30 (m,

6H), 7.25−7.25 (m, 1H), 7.21−7.14 (m, 3H), 7.01−6.99 (m, 4H),

6.92−6.90 (m, 2H), 6.80−6.78 (m, 1H), 5.35 (d, J = 15.2 Hz, 1H),

4.90 (d, J = 15.2 Hz, 1H), 4.77 (d, J = 4.4 Hz, 1H), 4.36 (d, J = 12.0

Hz, 1H), 3.60 (td, J₁= 13.2 Hz, J₂= 5.6 Hz, 1H), 2.88 (s, 3H), 2.28

(s, 3H), 2.28−2.23 (m, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

197.6, 176.5, 144.1, 144.0, 143.3, 138.3, 136.0, 133.6, 132.9, 132.2,

129.2, 129.0, 128.9, 128.7, 128.5, 128.4, 128.3, 127.9, 126.8, 125.9,

123.1, 122.5, 119.4, 119.3, 114.5, 110.2, 108.9, 50.4, 49.5, 45.3, 37.6,

32.8, 29.6, 21.5; IR (KBr) υ 3696, 3029, 1721, 1681, 1605, 1484,

1429, 1364, 1332, 1269, 1230, 1212, 1188, 1168, 1122, 1077, 1027,

985, 926, 874, 847, 818 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

142.3, 138.3, 136.6, 134.7, 132.5, 132.2, 131.1, 129.3, 129.3, 129.1,

128.8, 128.7, 128.6, 128.5, 127.7, 126.7, 126.0, 123.5, 122.2, 119.3,

114.0, 109.1, 108.9, 50.1, 49.5, 45.2, 37.7, 32.9, 29.5, 21.5, 21.1; IR

(KBr) υ 3699, 3056, 3026, 1715, 1683, 1602, 1495, 1468, 1436, 1364,

1336, 1290, 1232, 1184, 1127, 1076, 1028, 985, 934, 851, 816, 791

C₄₁H₃₃ClN₂NaO₂([M + Na]⁺) 643.2123, found 643.2129.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-methoxybenzoyl)-9-methyl-4-phe-

nyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1g):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 237 mg, 76%, mp 183−185 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.61−7.59 (m, 2H), 7.44−7.31 (m, 8H), 7.29−7.26 (m, 1H), 7.19−

7.12 (m, 3H), 7.09−7.04 (m, 3H), 7.01−6.97 (m, 1H), 6.92−6.86

(m, 2H), 6.56−6.54 (m, 2H), 6.36 (d, J = 15.6 Hz, 1H), 4.91 (d, J =

15.2 Hz, 1H), 4.77 (d, J = 4.8 Hz, 1H), 4.40 (d, J = 12.0 Hz, 1H),

3.75 (s, 3H), 3.62 (td, J_.= 12.4 Hz, J₂= 4.8 Hz, 1H), 2.84 (s, 3H),

2.20 (d, J = 13.2 Hz, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

196.8, 176.9, 163.3, 144.6, 144.4, 138.3, 136.5, 134.5, 131.1, 130.5,

128.9, 128.8, 128.6, 128.4, 128.1, 127.8, 126.6, 126.0, 122.7, 122.6,

122.2, 119.2, 114.1, 113.5, 109.3, 108.9, 55.4, 50.00, 49.4, 45.2, 37.7,

33.0, 29.5; IR (KBr) υ 3690, 3054, 3026, 1724, 1677, 1600, 1571,

1510, 1487, 1466, 1420, 1359, 1337, 1294, 1267, 1225, 1184, 1167,

1111, 1076, 1031, 985, 907, 876, 840, 804, 776, 753 cm⁻¹; MS (m/z)

cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₄₂H₃₆N₂NaO₂([M +

Na]⁺) 623.2669, found 623.2672.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-chlorobenzoyl)-5′,9-dimethyl-4-

phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1c):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 218 mg, 68%, mp 139−141 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.60−7.58 (m, 2H), 7.47−7.43 (m, 2H), 7.39−7.35 (m, 5H), 7.32−

7.30 (m, 1H), 7.28−7.27 (m, 1H), 7.19−7.12 (m, 2H), 7.07−7.05

(m, 2H), 7.02−6.97 (m, 4H), 6.80−6.75 (m, 2H), 5.30 (d, J = 15.2

Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.77 (d, J = 4.4 Hz, 1H), 4.34 (d,

J = 12.4 Hz, 1H), 3.63 (td, J₁= 13.2 Hz, J₂= 5.6 Hz, 1H), 2.84 (s,

3H), 2.17−2.16 (m, 4H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.0,

176.5, 144.3, 142.2, 139.4, 138.3, 136.4, 134.4, 133.3, 132.3, 130.8,

129.7, 129.4, 128.8, 128.7, 128.6, 128.5, 128.4, 127.7, 126.7, 125.9,

123.3, 122.2, 119.3, 119.2, 113.8, 109.1, 108.8, 50.0, 49.4, 45.1, 37.7,

32.7, 29.5, 21.1; IR (KBr) υ 3702, 3059, 1707, 1688, 1589, 1494,

1469, 1434, 1401, 1367, 1336, 1292, 1201, 1183, 1092, 1013, 987,

929, 875, 842, 814, 763 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

HRMS (ESI) calcd for C₄₁H₃₄N₂NaO₃([M + Na]⁺) 625.2462,

found 625.2450.

rel-(1S,2R,4S)-2-Benzoyl-1′-benzyl-5′-ﬂuoro-9-methyl-4-phenyl-

2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1h): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, yellow

solid, 272 mg, 89%, mp 143−145 °C; ¹H NMR (600 MHz, CDCl₃) δ

7.58−7.58 (m, 2H), 7.43−7.33 (m, 9H), 7.27−7.26 (m, 1H), 7.19−

7.10 (m, 6H), 7.00−7.00 (m, 1H), 6.87−6.86 (m, 1H), 6.79−6.79

(m, 2H), 5.35 (d, J = 15.0 Hz, 1H), 4.91 (d, J = 15.0 Hz, 1H), 4.78 (s,

1H), 4.39 (d, J = 12.0 Hz, 1H), 3.62−3.58 (m, 1H), 2.90 (s, 3H),

2.24 (d, J = 13.8 Hz, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

198.0, 176.5, 159.1 (d, J = 240.8 Hz), 144.0, 140.7, 138.4, 136.1,

134.8, 133.6, 133.1, 132.7 (d, J = 7.3 Hz), 128.8, 128.7, 128.5, 128.4,

128.3, 128.2, 127.9, 126.7, 125.9, 122.5, 119.4, 119.3, 115.3 (d, J =

20.0 Hz), 114.2, 110.8 (d, J = 24.6 Hz), 109.9 (d, J = 7.8 Hz), 108.9,

50.3, 49.8, 45.3, 37.6, 32.6, 29.5; IR (KBr) υ 3697, 3058, 1718, 1687,

1597, 1490, 1470, 1447, 1368, 1332, 1267, 1225, 1201, 1165, 1077,

1025, 986, 969, 937, 873, 847, 815, 791 cm⁻¹; MS (m/z) HRMS

C₄₁H₃₃ClN₂NaO₂([M + Na]⁺) 643.2123, found 643.2124.

rel-(1S,2R,4S)-1′-Butyl-5′,9-dimethyl-2-(4-methylbenzoyl)-4-phe-

nyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1d):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 159 mg, 54%, mp 138−140 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.45−7.42 (m, 2H), 7.39−7.35 (m, 3H), 7.25−7.24 (m, 1H), 7.17−

7.16 (m, 2H), 7.05−7.03 (m, 1H), 7.00−6.96 (m, 3H), 6.88−6.86

(m, 2H), 6.81−6.78 (m, 2H), 4.74 (d, J = 4.8 Hz, 1H), 4.35 (d, J = 12

Hz, 1H), 3.97−3.82 (m, 2H), 3.57 (td, J₁= 13.2 Hz, J₂= 5.2 Hz, 1H),

3.00 (s, 3H), 2.26 (s, 3H), 2.20 (s, 3H), 1.93−1.82 (m, 2H), 1.53−

1.51 (m, 1H), 1.04 (t, J = 7.6 Hz, 3H), 0.89−0.83 (m, 2H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 197.6, 176.4, 144.4, 143.6, 142.6, 138.3,

134.8, 132.6, 131.8, 131.2, 129.2, 129.0, 128.6, 128.5, 128.4, 126.6,

126.0, 123.5, 122.1, 119.2, 113.9, 108.8, 108.2, 49.9, 49.4, 40.6, 37.7,

32.8, 29.4, 29.3, 21.5, 21.1, 20.7, 13.9; IR (KBr) υ 3693, 3025, 1711,

1687. 1604, 1495, 1467, 1366, 1341, 1294, 1229, 1192, 1168, 1115,

1013, 982, 929, 849, 814, 771 cm⁻¹; MS (m/z) HRMS (ESI) calcd

(ESI) calcd for C₄₀H₃₁FN₂NaO₂([M + Na]⁺) 613.2262, found

613.2253.

for C₃₉H₃₈N₂NaO₂([M + Na]⁺) 589.2825, found 589.2813.

rel-(1S,2R,4S)-2-Benzoyl-1′-benzyl-9-methyl-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1i): ethyl acetate

and petroleum ether (v/v = 1:20) as the eluent, white solid, 193

rel-(1S,2R,4S)-1′-Butyl-2-(4-methoxybenzoyl)-5′,9-dimethyl-4-

phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1e):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 145 mg, 48%, mp 147−149 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.43−7.37 (m, 5H), 7.25−7.16 (m, 3H), 7.08−7.03 (m, 3H), 6.99−

6.98 (m, 1H), 6.81−6.78 (m, 2H), 6.55−6.54 (m, 2H), 4.74 (s, 1H),

4.34−4.31 (m, 1H), 3.93−3.88 (m, 2H), 3.75 (s, 3H), 3.62−3.56 (m,

1H), 3.01 (s, 3H), 2.21 (s, 3H), 2.21−2.16 (m, 1H), 1.89−1.85 (m,

2H), 1.06−1.02 (m, 3H), 0.86−0.84 (m, 2H); ¹³C{¹H} NMR (100

MHz, CDCl₃) δ 196.6, 176.4, 163.1, 144.4, 142.6, 138.3, 134.8, 131.8,

131.2, 130.5, 129.2, 128.6, 128.5, 128.2, 126.5, 126.0, 123.5, 122.1,

mg, 65%, mp 217−219 °C; H NMR (400 MHz, CDCl₃) δ 7.61−

7.60 (m, 2H), 7.44−7.25 (m, 10H), 7.19−7.14 (m, 3H), 7.12−7.05

(m, 5H), 7.01−6.97 (m, 1H), 6.92−6.89 (m, 2H), 5.35 (d, J = 15.2

Hz, 1H), 4.93 (d, J = 15.2 Hz, 1H), 4.78 (d, J = 4.8 Hz, 1H), 4.46 (d,

J = 12.0 Hz, 1H), 3.60 (td, J₁= 12.8 Hz, J₂= 5.2 Hz, 1H), 2.85 (s,

3H), 2.27 (d, J = 13.6 Hz, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

198.2, 176.8, 144.6, 144.3, 138.4, 136.5, 135.0, 134.4, 133.0, 131.0,

129.0, 128.8, 128.6, 128.4, 128.3, 128.2, 127.8, 126.7, 126.0, 122.7,

122.3, 119.2, 119.1, 114.1, 109.3, 108.9, 50.2, 49.4, 45.2, 37.7, 32.7,

5621

https://doi.org/10.1021/acs.joc.1c00103

J. Org. Chem. 2021, 86, 5616−5629

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

29.5.; IR (KBr) υ 3056, 3027, 1718, 1682, 1608, 1484, 1465, 1369,

1340, 1296, 1267, 1217, 1187, 1169, 1105, 1078, 1028, 984, 952, 924,

907, 869, 834, 790 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

rel-(1S,2R,4S)-1′-Benzyl-5′-chloro-2-(4-methylbenzoyl)-4-phenyl-

2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1n): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, yellow

solid, 242 mg, 77%, mp 168−170 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.54−7.52 (m, 2H), 7.48−7.44 (m, 2H), 7.41−7.37 (m, 3H), 7.35−

7.28 (m, 4H), 7.20−7.15 (m, 4H), 7.11−7.09 (m, 2H), 7.03−6.99

(m, 1H), 6.97−6.95 (m, 3H), 6.80−6.78 (m, 1H), 5.29 (d, J = 15.2

Hz, 1H), 4.89 (d, J = 15.6 Hz, 1H), 4.75 (d, J = 4.8 Hz, 1H), 4.37 (d,

J = 11.6 Hz, 1H), 3.80 (td, J₁= 12.8 Hz, J₂= 5.2 Hz, 1H), 2.38 (d, J =

13.6 Hz, 1H), 2.30 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

197.9, 176.9, 144.2, 144.0, 142.6, 136.8, 136.1, 133.2, 132.7, 131.9,

129.2, 129.0, 128.9, 128.7, 128.6, 128.4, 127.9, 127.8, 126.8, 123.1,

122.8, 120.0, 119.5, 113.6, 111.0, 110.6, 49.2, 48.5, 44.5, 37.4, 33.5,

21.6, 21.5; IR (KBr) υ 3623, 3437, 3269, 3059, 1703, 1681, 1606,

1486, 1454, 1430, 1342, 1290, 1229, 1210, 1175, 1118, 1076, 1027,

994, 916, 869, 841, 812 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

C₄₀H₃₂N₂NaO₂([M + Na]⁺) 595.2356, found 595.2349.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-chlorobenzoyl)-5′-methyl-4-phenyl-

2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1j): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, yellow

solid, 213 mg, 68%, mp 152−154 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.55−7.53 (m, 2H), 7.48−7.44 (m, 2H), 7.40−7.36 (m, 5H), 7.33−

7.26 (m, 2H), 7.17−7.15 (m, 3H), 7.12−7.12 (m, 4H), 7.02−6.99

(m, 2H), 6.77−6.75 (m, 2H), 5.25 (d, J = 15.6 Hz, 1H), 4.91 (d, J =

15.2 Hz, 1H), 4.76 (d, J = 5.2 Hz, 1H), 4.35 (d, J = 11.6 Hz, 1H),

3.84 (td, J₁= 12.8 Hz, J₂= 5.6 Hz, 1H), 2.31 (d, J = 13.6 Hz, 1H),

2.18 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.2, 197.1,

177.1, 177.0, 144.1, 141.5, 139.5, 136.7, 136.6, 134.1, 133.0, 132.3,

130.6, 129.9, 129.5, 128.7, 128.5, 128.4, 127.9, 127.8, 126.9, 123.3,

122.6, 119.8, 119.4, 113.1, 110.9, 109.4, 48.9, 48.2, 44.5, 37.4, 33.3,

21.1; IR (KBr) υ 3698, 3439, 3323, 3058, 3026, 1713, 1589, 1495,

1454, 1400, 1342, 1288, 1210, 1185, 1092, 1027, 1011, 991, 928, 873,

840, 809, 779 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

C₄₀H₃₁ClN₂NaO₂([M + Na]⁺) 629.1966, found 629.1974.

rel-(1S,2R,4S)-1′-Benzyl-5′-methyl-2-(4-methylbenzoyl)-4-phe-

nyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1o):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, yellow

solid, 231 mg, 76%, mp 262−264 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.55−7.53 (m, 2H), 7.47−7.43 (m, 2H), 7.39−7.36 (m, 4H), 7.32−

7.30 (m, 1H), 7.29−7.27 (m, 1H), 7.17−7.11 (m, 5H), 7.01−6.93

(m, 4H), 6.78−6.74 (m, 2H), 5.29 (d, J = 15.6 Hz, 1H), 4.89 (d, J =

15.6 Hz, 1H), 4.75 (d, J = 4.2 Hz, 1H), 4.40 (d, J = 12.4 Hz, 1H),

3.83 (td, J₁= 13.2 Hz, J₂= 5.6 Hz, 1H), 2.38−2.35 (m, 1H), 2.29 (s,

3H), 2.17 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 198.0, 177.3,

144.3, 143.9, 141.6, 136.8, 136.7, 134.3, 132.2, 132.1, 130.8, 129.4,

129.1, 128.8, 128.6, 128.5, 127.6, 127.5, 127.0, 126.7, 123.3, 122.5,

119.8, 119.4, 113.2, 110.9, 109.4, 49.1, 48.2, 44.5, 37.5, 33.5, 21.6,

21.1; IR (KBr) υ 3695, 3310, 3026, 1693, 1604, 1497, 1453, 1347,

1291, 1232, 1212, 1187, 1174, 1078, 1028, 993, 931, 875, 846, 827,

C₄₀H₃₁ClN₂NaO₂([M + Na]⁺) 629.1966, found 629.1977.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-methylbenzoyl)-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1k): ethyl acetate

and petroleum ether (v/v = 1:20) as the eluent, yellow solid, 226 mg,

76%, mp 165−167 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.56−7.55 (m,

2H), 7.45−7.27 (m, 8H), 7.24−7.09 (m, 7H), 7.03−6.98 (m, 2H),

6.94−6.86 (m, 4H), 5.32 (d, J = 15.6 Hz, 1H), 4.90 (d, J = 15.6 Hz,

1H), 4.76 (d, J = 4.8 Hz, 1H), 4.44 (d, J = 12.0 Hz, 1H), 3.80 (td, J₁=

13.2 Hz, J₂= 5.6 Hz, 1H), 2.36 (d, J = 13.6 Hz, 1H), 2.29 (s, 3H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 198.0, 177.4, 144.2, 144.0,

143.9, 136.8, 136.6, 134.1, 132.2, 130.8, 129.1, 129.0, 128.9, 128.6,

128.5, 128.4, 127.9, 127.7, 127.0, 126.7, 122.7, 122.5, 119.8, 119.4,

113.4, 110.9, 109.6, 49.0, 48.23, 44.5, 37.5, 33.4, 21.5; IR (KBr) υ

3697, 3459, 3323, 3056, 3028, 1710, 1684, 1607, 1489, 1455, 1346,

1290, 1229, 1210, 1176, 1116, 1078, 1030, 994, 900, 869, 825 cm⁻¹;

809, 770 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₄₁H₃₄N₂NaO₂

([M + Na]⁺) 609.2512, found 609.2517.

rel-(1S,2R,4S)-2-Benzoyl-1′-benzyl-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1p): ethyl acetate

and petroleum ether (v/v = 1:20) as the eluent, yellow solid, 197 mg,

68%, mp 157−159 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.57−7.55 (m,

2H), 7.45−7.28 (m, 9H), 7.21−7.10 (m, 8H), 7.05−6.98 (m, 2H),

6.94−6.87 (m, 2H), 5.31 (d, J = 15.2 Hz, 1H), 4.91 (d, J = 15.2 Hz,

1H), 4.76 (d, J = 4.8 Hz, 1H), 4.46 (d, J = 12.4 Hz, 1H), 3.80 (td, J₁=

13.6 Hz, J₂= 5.6 Hz, 1H), 2.36 (d, J = 13.2 Hz, 1H); ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ 198.4, 177.2, 144.2, 144.0, 136.8, 136.6, 134.7,

133.9, 133.1, 130.8, 129.0, 128.9, 128.6, 128.4, 128.3, 127.9, 127.7,

126.9, 126.7, 122.7, 122.6, 122.5, 119.8, 119.4, 113.4, 110.9, 109.6,

49.0, 48.3, 44.5, 37.4, 33.3; IR (KBr) υ 3077, 3020, 1710, 1678, 1600,

1468, 1465, 1369, 1338, 1299, 1266, 1221, 1177, 1109, 1104, 1069,

1022, 988, 985, 920, 906, 867, 839, 791 cm⁻¹; MS (m/z) HRMS

MS (m/z) HRMS (ESI) calcd for C₄₀H₃₂N₂NaO₂([M + Na]⁺)

595.2356, found 595.2362.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-methoxybenzoyl)-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1l): ethyl acetate

and petroleum ether (v/v = 1:20) as the eluent, yellow solid, 210

mg, 69%, mp 158−160 °C; H NMR (400 MHz, CDCl₃) δ 7.56−

7.55 (m, 2H), 7.45−7.27 (m, 9H), 7.21−7.10 (m, 6H), 7.04−6.98

(m, 2H), 6.93−6.86 (m, 2H), 6.61−6.59 (m, 2H), 5.32 (d, J = 15.6

Hz, 1H), 4.91 (d, J = 15.6 Hz, 1H), 4.76 (d, J = 4.8 Hz, 1H), 4.42 (d,

J = 12.4 Hz, 1H), 3.82 (d, J = 4.8 Hz, 1H), 3.77 (s, 3H), 2.35 (d, J =

13.2 Hz, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.0, 177.4,

163.3, 144.3, 144.0, 136.8, 136.6, 134.1, 130.9, 130.7, 129.0, 128.8,

128.6, 128.4, 127.9, 127.7, 127.6, 127.0, 126.7, 122.6, 122.5, 119.7,

119.4, 113.5, 113.3, 110.9, 109.5, 55.4, 49.0, 48.1, 44.4, 37.5, 33.6; IR

(KBr) υ 3618, 3256, 3058, 1696, 1678, 1602, 1573, 1510, 1490, 1456,

1359, 1291, 1262, 1230, 1170, 1115, 1078, 1029, 991, 955, 902, 869,

(ESI) calcd for C₃₉H₃₀N₂NaO₂([M + Na]⁺) 581.2199, found

581.2205.

rel-(1S,2R,4S)-1′-Benzyl-4-(4-chlorophenyl)-5′,9-dimethyl-2-(4-

methylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-

one (1q): ethyl acetate and petroleum ether (v/v = 1:20) as the

840, 808 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₄₀H₃₂N₂NaO₃

([M + Na]⁺) 611.2305, found 611.2314.

eluent, white solid, 229 mg, 70%, mp 176−178 °C; H NMR (400

rel-(1S,2R,4S)-1′-Benzyl-5′-chloro-2-(4-methoxybenzoyl)-4-phe-

nyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1m):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 280 mg, 87%, mp 270−272 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.53−7.51 (m, 2H), 7.47−7.43 (m, 2H), 7.40−7.30 (m, 6H), 7.25 (s,

1H), 7.19−7.11 (m, 6H), 7.02−6.99 (m, 1H), 6.96 (s, 1H), 6.78−

6.76 (m, 1H), 6.63−6.61 (m, 2H), 5.27 (d, J = 15.2 Hz, 1H), 4.89 (d,

J = 15.6 Hz, 1H), 4.75 (d, J = 4.8 Hz, 1H), 4.35 (d, J = 12.0 Hz, 1H),

3.86−3.81 (m, 1H), 3.78 (s, 3H), 2.37 (d, J = 13.6 Hz, 1H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 196.8, 176.9, 163.5, 144.0, 142.6, 136.8,

136.1, 133.3, 132.7, 130.8, 129.0, 128.9, 128.7, 128.4, 127.9, 127.8,

127.7, 127.5, 126.9, 126.8, 123.1, 122.8, 119.9, 119.5, 113.7, 111.0,

110.6, 55.4, 49.2, 48.4, 44.5, 37.4, 33.6; IR (KBr) υ 3695, 3300, 3063,

1703, 1677, 1599, 1511, 1485, 1454, 1349, 1310, 1264, 1229, 1168,

1117, 1076, 1025, 991, 922, 840, 817 cm⁻¹; MS (m/z) HRMS (ESI)

calcd for C₄₀H₃₁ClN₂NaO₃⁺([M + Na]⁺) 645.1915, found 645.1899.

MHz, CDCl₃) δ 7.59−7.57 (m, 2H), 7.42−7.40 (m, 2H), 7.38−7.29

(m, 5H), 7.22−7.12 (m, 3H), 7.07−7.05 (m, 2H), 7.01−6.93 (m,

4H), 6.77−6.74 (m, 2H), 5.32 (d, J = 15.2 Hz, 1H), 4.89 (d, J = 15.2

Hz, 1H), 4.72 (d, J = 4.8 Hz, 1H), 4.32 (d, J = 12.0 Hz, 1H), 3.62 (td,

J₁= 13.2 Hz, J₂= 5.2 Hz, 1H), 2.83 (s, 3H), 2.29 (s, 3H), 2.19−2.17

(m, 1H), 2.17 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.6,

176.6, 144.0, 142.9, 142.2, 138.3, 136.5, 134.7, 132.5, 132.4, 132.3,

130.8, 130.0, 129.3, 129.1, 128.7, 128.6, 128.4, 128.3, 127.7, 125.8,

123.3, 122.2, 119.4, 119.0, 113.4, 109.1, 108.9, 49.9, 49.4, 45.1, 37.1,

32.5, 29.5, 21.5, 21.1; IR(KBr)υ: 3699, 3028, 1712, 1686, 1603, 1497,

1468, 1437, 1363, 1335, 1289, 1231, 1184, 1128, 1081, 1031, 1012,

988, 934, 838, 818, 793 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

C₄₂H₃₅ClN₂NaO₂([M + Na]⁺) 657.2279, found 657.2287.

rel-(1S,2R,4S)-1′-Benzyl-9-methyl-2-(4-methylbenzoyl)-4-(p-

tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1r):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

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solid, 214 mg, 69%, mp 205−207 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.61−7.59 (m, 2H), 7.38−7.35 (m, 2H), 7.32−7.23 (m, 5H), 7.17−

7.10 (m, 4H), 7.07−6.96 (m, 4H), 6.89−6.85 (m, 4H), 5.36 (d, J =

15.2 Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.73 (d, J = 4.0 Hz, 1H),

4.43 (d, J = 12.4 Hz, 1H), 3.57 (td, J₁= 13.2 Hz, J₂= 5.2 Hz, 1H),

2.84 (s, 3H), 2.43 (s, 3H), 2.34−2.18 (m, 1H), 2.26 (s, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 197.9, 176.9, 144.6, 143.8, 141.2, 138.3,

136.5, 136.1, 134.3, 132.5, 131.1, 129.2, 129.0, 128.9, 128.8, 128.5,

128.4, 128.2, 127.7, 126.0, 122.7, 122.6, 122.2, 119.3, 119.2, 114.3,

109.3, 108.8, 50.2, 49.4, 45.1, 37.3, 32.9, 29.4, 21.5, 21.1; IR (KBr) υ

3700, 3029, 1716, 1683, 1605, 1488, 1466, 1362, 1338, 1293, 1266,

1230, 1209, 1186, 1169, 1110, 1078, 1015, 987, 903, 882, 843, 805,

(m, 4H), 7.40−7.36 (m, 3H), 7.33−7.30 (m, 2H), 7.20−7.13 (m,

3H), 7.08−7.00 (m, 4H), 6.92−6.84 (m, 4H), 5.37 (d, J = 15.2 Hz,

1H), 4.92 (d, J = 15.2 Hz, 1H), 4.81 (d, J = 4.4 Hz, 1H), 4.47 (d, J =

12.4 Hz, 1H), 3.67−3.60 (m, 1H), 2.86 (s, 3H), 2.26−2.23 (m, 1H),

2.23 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.8, 176.9,

144.7, 143.9, 143.5, 141.0, 139.7, 138.4, 136.5, 134.5, 132.6, 131.1,

129.1, 129.0, 128.9, 128.8, 128.5, 128.4, 127.8, 127.3, 127.2, 127.1,

126.0, 122.8, 122.7, 122.3, 119.4, 119.3, 114.1, 109.4, 108.9, 50.2,

49.4, 45.2, 37.5, 32.8, 29.5, 21.5; IR (KBr) υ 3453, 3026, 1711, 1682,

1605, 1482, 1464, 1339, 1225, 1161, 1077, 873, 841 cm⁻¹; MS (m/z)

HRMS (ESI) calcd for C₄₇H₃₈N₂NaO₂([M + Na]⁺) 685.2825,

found 685.2815.

773, 753 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₄₂H₃₆N₂NaO₂

rel-(1S,2R,4S)-1′-Benzyl-4-(4-bromophenyl)-9-methyl-2-(4-meth-

ylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one

(1w): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

([M + Na]⁺) 623.2669, found 623.2672.

rel-(1S,2R,4S)-1′-Benzyl-9-methyl-2-(4-methylbenzoyl)-4-(m-

tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1s):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 221 mg, 71%, mp 182−183 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.61−7.59 (m, 2H), 7.39−7.35 (m, 2H), 7.32−7.28 (m, 2H), 7.27−

7.23 (m, 2H), 7.19−7.11 (m, 5H), 7.04−6.97 (m, 4H), 6.91−6.86

(m, 4H), 5.36 (d, J = 15.2 Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.73

(d, J = 4.4 Hz, 1H), 4.45 (d, J = 16.0 Hz, 1H), 3.57 (td, J₁= 12.0 Hz,

J₂= 5.6 Hz, 1H), 2.84 (s, 3H), 2.40 (s, 3H), 2.32 (s, 3H), 2.22−2.19

(m, 1H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.9, 176.9, 144.6,

144.2, 143.8, 138.3, 138.1, 136.5, 134.3, 132.5, 131.1, 129.4, 129.3,

129.0, 128.9, 128.8, 128.4, 127.7, 127.6, 127.4, 126.0, 125.6, 122.7,

122.6, 122.1, 119.3, 119.2, 114.2, 109.3, 108.8, 50.2, 49.34, 45.1, 37.7,

37.6, 32.9, 29.4, 21.6; IR (KBr) υ 3699, 3028, 1717, 1684, 1606, 1487,

1466, 1361, 1338, 1292, 1230, 1210, 1182, 1108, 1077, 1013, 987,

905, 886, 843, 830, 794, 770, 754 cm⁻¹; MS (m/z) HRMS (ESI)

white solid, 305 mg, 89%, mp 191−193 °C; H NMR (400 MHz,

CDCl₃) δ 7.60−7.54 (m, 4H), 7.39−7.35 (m, 2H), 7.32−7.28 (m,

1H), 7.24−7.12 (m, 6H), 7.05−6.98 (m, 4H), 6.94−6.85 (m, 4H),

5.35 (d, J = 15.6 Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.71 (d, J = 4.4

Hz, 1H), 4.35 (d, J = 12.4 Hz, 1H), 3.60 (td, J₁= 13.2 Hz, J₂= 5.6 Hz,

1H), 2.84 (s, 3H), 2.29 (s, 3H), 2.16 (d, J = 13.6 Hz, 1H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 197.6, 176.7, 144.6, 144.1, 143.5, 138.4,

136.5, 134.5, 132.6, 131.7, 130.9, 130.4, 129.2, 128.8, 128.5, 128.3,

127.8, 125.8, 122.8, 122.4, 120.5, 119.5, 119.1, 113.5, 109.4, 109.0,

50.0, 49.4, 45.2, 37.3, 32.5, 29.6, 21.6; IR (KBr) υ 3453, 3027, 1712,

1684, 1605, 1485, 1464, 1360, 1336, 1289, 1229, 1185, 1167, 1106,

1073, 1008, 985, 903, 880, 838, 792 cm⁻¹; MS (m/z) HRMS (ESI)

calcd for C₄₁H₃₃BrN₂NaO₂⁺([M + Na]⁺) 687.1618, found 687.1613.

rel-(1S,2R,4S)-1′-Benzyl-4-(4-ﬂuorophenyl)-9-methyl-2-(4-meth-

ylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one

(1x): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

calcd for C₄₂H₃₆N₂NaO₂([M + Na]⁺) 623.2669, found 623.2672.

white solid, 225 mg, 72%, mp 256−258 °C; H NMR (400 MHz,

rel-(1S,2R,4S)-1′-Benzyl-4-(4-ethoxyphenyl)-9-methyl-2-(4-meth-

ylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one

(1t): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

CDCl₃) δ 7.60−7.59 (m, 2H), 7.39−7.29 (m, 5H), 7.25−7.21 (m,

1H), 7.19−7.10 (m, 5H), 7.06−6.98 (m, 4H), 6.94−6.86 (m, 4H),

5.36 (d, J = 15.2 Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.74 (d, J = 4.4

Hz, 1H), 4.39 (d, J = 12.4 Hz, 1H), 3.60 (td, J₁= 12.8 Hz, J₂= 5.2 Hz,

1H), 2.84 (s, 3H), 2.28 (s, 3H), 2.17 (d, J = 13.6 Hz, 1H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 197.7, 176.7, 161.8 (d, J = 243.0 Hz),

144.6, 144.0, 140.1, 140.0, 138.4, 136.5, 134.4, 132.6, 130.1, 130.0,

129.1, 129.0, 128.8, 128.4, 128.3, 127.8, 125.9, 122.7, 122.6, 122.4,

119.2 (d, J = 27.3 Hz), 115.4 (d, J = 21.1 Hz), 113.9, 109.4, 109.0,

50.0, 49.3, 45.1, 37.0, 32.7, 29.5, 21.5; IR (KBr) υ 3440, 3029, 1714,

1682, 1604 1490, 1463, 1360, 1337, 1290, 1215, 1185, 1166, 1109,

1075, 1013, 985, 903, 879, 841 cm⁻¹; MS (m/z) HRMS (ESI) calcd

white solid, 163 mg, 50%, mp 215−217 °C; H NMR (400 MHz,

CDCl₃) δ 7.61−7.59 (m, 2H), 7.39−7.35 (m, 2H), 7.32−7.27 (m,

3H), 7.18−7.01 (m, 6H), 7.04−6.98 (m, 2H), 6.96−6.85 (m, 6H),

5.36 (d, J = 15.2 Hz, 1H), 4.91 (d, J = 15.6 Hz, 1H), 4.71 (d, J = 4.0

Hz, 1H), 4.43 (d, J = 11.6 Hz, 1H),, 4.14−4.06 (m, 2H), 3.55 (td, J₁=

13.2 Hz, J₂= 5.6 Hz, 1H), 2.84 (s, 3H), 2.27 (s, 3H), 2.20 (d, J = 13.6

Hz, 1H), 1.46 (t, J = 6.8 Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃)

δ 198.0, 176.9, 157.8, 144.6, 143.8, 138.3, 136.5, 136.2, 134.2, 132.6,

131.1, 129.6, 129.1, 128.9, 128.8, 128.4, 127.8, 127.7, 126.0, 122.7,

122.6, 122.2, 119.3, 119.2, 114.5, 109.3, 108.8, 63.6, 50.2, 49.4, 45.2,

36.8, 32.9, 29.5, 21.5, 15.0; IR (KBr) υ 3056, 3030, 1713, 1680, 1608,

1509, 1483, 1362, 1336, 1297, 1247, 1185, 1168, 1115, 1079, 1046,

1013, 987, 922, 906, 873, 838, 810 cm⁻¹; MS (m/z) HRMS (ESI)

for C₄₁H₃₃FN₂NaO₂([M + Na]⁺) 627.2418, found 627.2410.

rel-(1S,2R,4R)-1′-Benzyl-4-(2-ﬂuorophenyl)-9-methyl-2-(4-meth-

ylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one

(1y): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

calcd for C₄₃H₃₈N₂NaO₃([M + Na]⁺) 653.2775, found 653.2781.

white solid, 219 mg, 71%, mp 194−196 °C; H NMR (400 MHz,

rel-(1S,2R,4R)-1′-Benzyl-4-(2-methoxyphenyl)-9-methyl-2-(4-

methylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-

one (1u): ethyl acetate and petroleum ether (v/v = 1:20) as the

CDCl₃) δ 7.61−7.59 (m, 2H), 7.39−7.35 (m, 3H), 7.33−7.27 (m,

1H), 7.24−7.23 (m, 1H), 7.20−7.12 (m, 6H), 7.05−6.98 (m, 4H),

6.91−6.86 (m, 4H), 5.37 (d, J = 15.2 Hz, 1H), 5.03 (d, J = 4.8 Hz,

1H), 4.91 (d, J = 15.2 Hz, 1H), 4.39 (d, J = 11.2 Hz, 1H), 3.55 (td, J₁

= 13.6 Hz, J₂= 5.6 Hz, 1H), 2.84 (s, 3H), 2.29−2.27 (m, 4H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.6, 176.7, 161.2 (d, J = 245

Hz), 144.6, 143.9, 138.3, 136.4, 134.9, 132.6, 131.2 (d, J = 14.4 Hz),

131.0, 130.1 (d, J = 4.2 Hz), 129.1, 129.0, 128.8, 128.5 (d, J = 8.0

Hz), 128.4, 128.2, 127.7, 125.7, 124.0 (d, J = 3.2 Hz), 122.6, 122.3,

119.4, 119.2 (d, J = 3.7 Hz), 119.0, 115.5 (d, J = 21.5 Hz), 113.0,

109.3, 108.9, 50.5, 49.3, 45.2, 31.7, 30.2, 29.5, 21.5; IR (KBr) υ 3429,

3029, 1724, 1684, 1606, 1485, 1465 1360, 1337, 1293, 1266, 1228,

1184, 1110, 1078, 1031 987, 905, 879, 838, 798 cm⁻¹; MS (m/z)

eluent, yellow solid, 198 mg, 62%, mp 128−130 °C; H NMR (400

MHz, CDCl₃) δ 7.62−7.60 (m, 2H), 7.39−7.35 (m, 3H), 7.32−7.27

(m, 2H), 7.17−7.12 (m, 3H), 7.10−6.85 (m, 11H), 5.38 (d, J = 15.2

Hz, 1H), 5.04 (d, J = 4.8 Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.38 (d,

J = 12.4 Hz, 1H), 3.86 (s, 3H), 3.43 (td, J₁= 12.4 Hz, J₂= 5.2 Hz,

1H), 2.84 (s, 3H), 2.33 (d, J = 13.6 Hz, 1H), 2.26 (s, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 198.0, 177.0, 157.5, 144.7, 143.7, 138.4,

136.6, 134.8, 132.7, 132.0, 131.4, 129.5, 129.0, 128.8, 128.5, 128.0,

127.8, 126.0, 122.8, 122.6, 122.2, 120.3, 119.3, 119.2, 114.6, 110.4,

109.2, 108.8, 55.5, 51.1, 49.5, 45.2, 32.3, 29.5, 27.0, 21.5; IR (KBr) υ

3432, 3056, 1716, 1682, 1606, 1486, 1463, 1363, 1338, 1290, 1238,

1170, 1111, 1077, 1029, 990, 901, 873, 842 cm⁻¹; MS (m/z) HRMS

HRMS (ESI) calcd for C₄₁H₃₃FN₂NaO₂([M + Na]⁺) 627.2418,

found 627.2404.

(ESI) calcd for C₄₂H₃₆N₂NaO₃([M + Na]⁺) 639.2618, found

2. General Procedure for the Preparation of

Tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate 2a−

2g. To a 10 mL Schlenk tube were added indole (0.6 mmol, 1.2

equiv), phenylacetylene (0.6 mmol, 1.2 equiv), alkyl (E)-2-(2-

oxoindolin-3-ylidene) acetate (0.5 mmol, 1.0 equiv), indium bromide

(0.025 mmol, 0.05 equiv), and toluene (2.0 mL). The mixture was

heated at 80 °C by an oil bath for 10 h. After removing the solvent,

639.2605.

rel-(1S,2R,4S)-4-([1,1′-Biphenyl]-4-yl)-1′-benzyl-9-methyl-2-(4-

methylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-

one (1v). ethyl acetate and petroleum ether (v/v = 1:20) as the

eluent, yellow solid, 157 mg, 46%, mp 230−232 °C; H NMR (400

MHz, CDCl₃) δ 7.69−7.65 (m, 4H), 7.62−7.60 (m, 2H), 7.53−7.44

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the residue was subjected to column chromatography on silica gel

with ethyl acetate and petroleum ether (v/v = 1:20) to aﬀord the

desired products 2a−2g.

129 mg, 46%, mp 230−232 °C; H NMR (400 MHz, CDCl₃) δ

7.44−7.43 (m, 2H), 7.36−7.29 (m, 7H), 7.19−7.04 (m, 6H), 6.98−

6.94 (m, 1H), 6.85 (s, 1H), 6.79−6.77 (m, 1H), 5.15 (d, J = 15.2 Hz,

1H), 4.76 (d, J = 15.6 Hz, 1H), 4.69 (d, J = 6.0 Hz, 1H), 3.97−3.89

(m, 1H), 3.86−3.80 (m, 1H), 3.66 (td, J₁= 12.8 Hz, J₂= 5.6 Hz, 1H),

3.40 (d, J = 13.6 Hz, 1H), 2.42 (d, J = 13.6 Hz, 1H), 2.25 (s, 3H),

0.95 (t, J = 7.2 Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 176.4,

172.0, 144.6, 141.2, 136.8, 136.5, 133.2, 132.5, 131.3, 129.3, 128.8,

128.5, 128.3, 127.9, 127.8, 127.0, 126.4, 123.9, 122.5, 119.7, 119.5,

113.6, 110.8, 109.2, 60.8, 49.6, 44.7, 44.3, 36.7, 32.2, 21.1, 13.8; IR

(KBr) υ 3538, 3343, 1730, 1606, 1453, 1433, 1329, 1268, 1169, 1109,

1066, 1019, 869, 825 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

rel-Methyl(1S,2R,4S)-1′-benzyl-5′-chloro-2′-oxo-4-phenyl-

2,3,4,9-tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate

(2a): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

white solid, 139 mg, 49%, mp 209−211 °C; H NMR (400 MHz,

CDCl₃) δ 7.42−7.33 (m, 7H), 7.25−7.10 (m, 8H), 7.00−6.97 (m,

2H), 6.80−6.78 (m, 1H), 5.10 (d, J = 15.6 Hz, 1H), 4.81 (d, J = 15.2

Hz, 1H), 4.68−4.48 (m, 1H), 3.65−3.59 (m, 1H), 3.45 (s, 3H),

3.39−3.39 (m, 1H), 2.45 (d, J = 13.2 Hz, 1H); ¹³C{¹H} NMR (100

MHz, CDCl₃) δ 176.1, 172.3, 144.1, 142.3, 136.8, 135.9, 133.0, 132.0,

129.1, 128.9, 128.6, 128.3, 128.2, 128.0, 127.8, 126.8, 126.5, 123.5,

122.9, 120.0, 119.6, 114.0, 110.9, 110.5, 52.1, 49.6, 44.7, 44.5, 36.6,

32.3; IR (KBr) υ 3354, 3035, 1742, 1614, 1449, 1339, 1283, 1266,

1169, 1063, 923, 850, 810, 756 cm⁻¹; MS (m/z) HRMS (ESI) calcd

C₃₆H₃₂N₂NaO₃([M + Na]⁺) 563.2305, found 563.2298.

rel-Ethyl(1S,2R,4S)-1′-benzyl-5′,9-dimethyl-2′-oxo-4-phenyl-

2,3,4,9-tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate (2f):

ethyl acetate and petroleum ether (v/v = 1:20) as the eluent, white

solid, 129 mg, 45%, mp 163−165 °C; ¹H NMR (400 MHz, CDCl₃) δ

7.50−7.48 (m, 2H), 7.34−7.30 (m, 7H), 7.23−7.10 (m, 4H), 7.06−

7.04 (m, 1H), 6.97−6.94 (m, 1H), 6.88 (s, 1H), 6.80−6.78 (m, 1H),

5.10 (d, J = 15.2 Hz, 1H), 4.80 (d, J = 15.2 Hz, 1H), 4.70 (d, J = 5.2

Hz, 1H), 3.80−3.76 (m, 2H), 3.50 (td, J₁= 13.2 Hz, J₂= 6.4 Hz, 1H),

3.29 (d, J = 13.2 Hz, 1H), 2.83 (s, 3H), 2.26 (s, 3H), 2.26−2.23 (m,

1H), 0.85 (t, J = 6.8 Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

175.4, 171.7, 144.5, 141.5, 138.3, 136.2, 133.4, 132.6, 131.2, 129.2,

128.7, 128.5, 128.4, 128.4, 127.8, 126.3, 126.0, 124.2, 122.2, 119.4,

119.2, 114.3, 108.9, 108.8, 60.5, 50.1, 47.5, 44.8, 36.9, 31.6, 29.6, 21.1,

13.8; IR (KBr) υ 3333, 3058, 1727, 1614, 1491, 1450, 1340, 1293,

1267, 1168, 1077, 1027, 931, 864, 812 cm⁻¹; MS (m/z) HRMS (ESI)

for C₃₄H₂₇ClN₂NaO₃([M + Na]⁺) 569.1602, found 569.1599.

rel-Ethyl(1S,2R,4S)-1′-benzyl-2′-oxo-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate (2b): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, white solid,

131 mg, 48%, mp 118−120 °C; H NMR (400 MHz, CDCl₃) δ

7.45−7.43 (m, 2H), 7.36−7.27 (m, 6H), 7.25−7.23 (m, 2H), 7.14−

7.07 (m, 4H), 7.04−7.00 (m, 1H), 6.97−6.94 (m, 1H), 6.91−6.89

(m, 1H), 5.15 (d, J = 15.2 Hz, 1H), 4.78 (d, J = 15.2 Hz, 1H), 4.69

(d, J = 5.6 Hz, 1H), 3.94−3.86 (m, 1H), 3.85−3.77 (m, 1H), 3.65 (td,

J₁= 12.8 Hz, J₂= 5.6 Hz, 1H), 3.42 (d, J = 13.2 Hz, 1H), 2.42 (d, J =

13.2 Hz, 1H), 0.91 (t, J = 7.2 Hz, 3H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 176.4, 172.0, 144.5, 143.7, 136.8, 136.4, 132.9, 131.3, 129.0,

128.9, 128.5, 128.3, 128.0, 127.8, 127.0, 126.4, 123.2, 123.0, 122.6,

119.8, 119.5, 113.8, 110.9, 109.5, 60.8, 49.7, 44.8, 44.3, 36.8, 32.2,

13.8; IR (KBr) υ 3343, 3068, 1754, 1634, 1465, 1460, 1334, 1256,

1242, 1156, 1027, 922, 865, 845 cm⁻¹; MS (m/z) HRMS (ESI) calcd

calcd for C₃₇H₃₄N₂NaO₃([M + Na]⁺) 577.2462, found 577.2461.

rel-Ethyl(1S,2R,4S)-1′-benzyl-9-methyl-2′-oxo-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate (2g): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, white solid,

for C₃₅H₃₀N₂NaO₃([M + Na]⁺) 549.2149, found 549.2146.

112 mg, 40%, mp 109−111 °C; H NMR (400 MHz, CDCl₃) δ

rel-Ethyl(1S,2R,4S)-1′-benzyl-5′-ﬂuoro-2′-oxo-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate (2c): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, yellow solid,

7.51−7.49 (m, 2H), 7.34−7.29 (m, 7H), 7.25−7.25 (m, 2H), 7.19−

7.10 (m, 4H), 7.05−7.01 (m, 1H), 6.97−6.90 (m, 2H), 5.13 (d, J =

15.2 Hz, 1H), 4.83 (d, J = 15.2 Hz, 1H), 4.71−4.70 (m, 1H), 3.78−

3.75 (m, 2H), 3.53−3.49 (m, 1H), 3.32 (d, J = 12.4 Hz, 1H), 2.83 (s,

3H), 2.24 (d, J = 12.8 Hz, 1H), 0.82 (t, J = 7.2 Hz, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 175.4, 171.7, 144.4, 143.9, 138.3, 136.1,

133.5, 131.2, 129.0, 128.8, 128.4, 128.4, 128.3, 127.9, 126.3, 126.0,

123.5, 123.0, 122.2, 119.4, 119.2, 114.4, 109.1, 108.8, 60.5, 50.1, 47.6,

44.8, 36.9, 31.5, 29.5, 13.7; IR (KBr) υ 3438, 3293, 1777, 1605, 1460,

1444, 1320, 1270, 1177, 1109, 1056, 1020, 871, 830 cm⁻¹; MS (m/z)

147 mg, 52%, mp 125−127 °C; H NMR (400 MHz, CDCl₃) δ

7.44−7.42 (m, 2H), 7.38−7.31 (m, 5H), 7.25−7.23 (m, 3H), 7.20−

7.10 (m, 4H), 6.99−6.94 (m, 2H), 6.83−6.81 (m, 2H), 5.14 (d, J =

15.6 Hz, 1H), 4.77 (d, J = 15.6 Hz, 1H), 4.69 (d, J = 5.6 Hz, 1H),

3.98−3.90 (m, 1H), 3.88−3.80 (m, 1H), 3.62 (td, J₁= 13.2 Hz, J₂=

6.4 Hz, 1H), 3.36 (td, J₁= 13.2 Hz, J₂= 2.4 Hz, 1H), 2.45 (d, J = 13.2

Hz, 1H), 0.96 (t, J = 7.2 Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃)

δ 176.2, 171.8, 159.3 (d, J = 240.8 Hz,), 144.2, 139.6, 139.5, 136.4 (d,

J = 77.5 Hz), 133.1 (d, J = 77.0 Hz), 132.1, 128.9, 128.6, 128.2, 127.9,

126.8, 126.5, 122.8, 119.9, 119.6, 115.3 (d, J = 23.4 Hz), 114.0, 111.2

(d, J = 24.5 Hz), 110.9, 110.0 (d, J = 7.5 Hz), 61.0, 50.0, 44.7, 44.5,

36.6, 32.1, 29.7, 13.8; IR (KBr) υ 3340, 3066, 1730, 1617, 1488, 1449,

1340, 1266, 1243, 1176, 1065, 1030, 931, 865, 813 cm⁻¹; MS (m/z)

HRMS (ESI) calcd for C₃₆H₃₂N₂NaO₃([M + Na]⁺) 563.2305,

found 563.2308.

3. General Procedure for the Preparations of 1,1′-Bis-

(indolyl)phenylethanes. To a 10 mL Schlenk tube were added

indole (1.5 mmol, 3.0 equiv), phenylacetylene (0.5 mmol, 1.0 equiv),

indium bromide (0.025 mmol, 0.05 equiv), and toluene (2.0 mL).

The mixture was heated at 90 °C by an oil bath for 3 h. After the

solvent was removed, the residue was subjected to column

chromatography on silica gel with ethyl acetate and petroleum ether

(v/v = 1:60) as an eluent to aﬀord compounds 3a−3e.

HRMS (ESI) calcd for C₃₅H₂₉FN₂NaO₃([M + Na]⁺) 567.2054,

found 567.2054.

rel-Ethyl(1S,2R,4S)-1′-benzyl-5′-chloro-2′-oxo-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate (2d): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, white solid,

3,3′-(1-(4-Ethylphenyl)ethane-1,1-diyl)bis(1-methyl-1H-indole)

(3a): ethyl acetate and petroleum ether (v/v = 1:60) as the eluent,

145 mg, 50%, mp 123−125 °C; H NMR (400 MHz, CDCl₃) δ

white solid, 170 mg, 82%, mp 204−206 °C; H NMR (400 MHz,

7.43−7.41 (m, 2H), 7.37−7.28 (m, 6H), 7.24−7.10 (m, 7H), 7.02−

6.96 (m, 2H), 6.82−6.80 (m, 1H), 5.15 (d, J = 15.2 Hz, 1H), 4.77 (d,

J = 15.2 Hz, 1H), 4.68 (d, J = 5.2 Hz, 1H), 3.99−3.91 (m, 1H), 3.88−

3.80 (m, 1H), 3.62 (td, J₁= 13.2 Hz, J₂= 6.0 Hz, 1H), 3.40−3.36 (m,

1H), 2.45 (d, J = 13.6 Hz, 1H), 0.96 (t, J = 7.2 Hz, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 176.0, 171.8, 144.2, 142.2, 136.8, 135.9,

133.1, 132.0, 129.0, 128.9, 128.6, 128.3, 128.2, 128.0, 127.8, 126.8,

126.5, 123.6, 122.8, 119.9, 119.6, 114.1, 110.9, 110.4, 61.0, 49.7, 44.8,

44.4, 36.6, 32.1, 13.8; IR (KBr) υ 3628, 3333, 1728, 1607, 1485, 1453,

1430, 1337, 1294, 1174, 1108, 1076, 1050, 1026, 873, 812 cm⁻¹; MS

CDCl₃) δ 7.32−7.26 (m, 5H), 7.26−7.24 (m, 1H), 7.17−7.13 (m,

2H), 7.07−7.05 (m, 2H), 6.93−6.89 (m, 2H), 6.48 (s, 2H), 3.66 (s,

6H), 2.62 (q, J = 7.6 Hz, 2H), 2.33 (s, 3H), 1.22 (t, J = 7.6 Hz, 3H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 145.6, 141.3, 137.8, 128.0,

127.9, 127.2, 126.9, 123.5, 122.2, 121.0, 118.3, 109.1, 43.4, 32.6, 29.2,

28.3, 15.4; IR (KBr) υ 3427, 3060, 1925, 1694, 1594, 1510, 1468,

1335, 1246, 1207, 1142, 1081, 1002, 857, 805 cm⁻¹; MS (m/z)

HRMS (ESI) calcd for C₂₈H₂₈N₂Na⁺([M + Na]⁺) 415.2145, found

415.2146.

(m/z) HRMS (ESI) calcd for C₃₅H₂₉ClN₂NaO₃([M + Na]⁺)

3,3′-(1-(4-Nitrophenyl)ethane-1,1-diyl)bis(1-methyl-1H-indole)

(3b): ethyl acetate and petroleum ether (v/v = 1:60) as the eluent,

583.1759, found 583.1753.

white solid, 108 mg, 50%, mp 242−243 °C; H NMR (400 MHz,

CDCl₃) δ 8.09−8.07 (m, 2H), 7.58−7.56 (m, 2H), 7.32−7.30 (m,

1H), 7.24−7.17 (m, 5H), 6.96−6.92 (m, 2H), 6.53 (s, 2H), 3.69 (s,

rel-Ethyl(1S,2R,4S)-1′-benzyl-5′-methyl-2′-oxo-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indoline]-2-carboxylate (2e): ethyl

acetate and petroleum ether (v/v = 1:20) as the eluent, white solid,

5624

https://doi.org/10.1021/acs.joc.1c00103

J. Org. Chem. 2021, 86, 5616−5629

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

6H), 2.36 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 156.1, 146.0,

137.8, 129.0, 128.0, 126.4, 123.1, 121.7, 121.4, 118.7, 109.4, 44.1,

32.7, 29.1; IR (KBr) υ 3688, 3053, 1909, 1736, 1614, 1539, 1468,

1364, 1325, 1244, 1204, 1128, 1084, 1049, 1013, 977, 920, 846, 805

MHz, CDCl₃) δ 7.60−7.58 (m, 2H), 7.38−7.35 (m, 2H), 7.32−7.28

(m, 5H), 7.25 (s, 1H), 7.19−7.12 (m, 2H), 7.05−6.96 (m, 6H), 6.80

(s, 1H), 6.77−6.75 (m, 1H), 5.30 (d, J = 15.2 Hz, 1H), 4.91 (d, J =

15.2 Hz, 1H), 4.74 (d, J = 4.0 Hz, 1H), 4.35 (d, J = 12.0 Hz, 1H),

3.61 (td, J₁= 12.8 Hz, J₂= 5.2 Hz, 1H), 2.84 (s, 3H), 2.75 (dd, J₁=

15.2 Hz, J₂= 7.6 Hz, 2H), 2.18 (s, 3H), 2.14 (s, 1H), 1.34 (t, J = 7.6

Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.0, 176.6, 142.8,

142.3, 141.4, 139.3, 138.3, 136.5, 134.4, 133.4, 132.3, 130.9, 129.8,

129.4, 128.8, 128.6, 128.5, 128.4, 128.1, 127.7, 126.0, 123.4, 122.2,

119.3, 119.2, 114.2, 109.1, 108.8, 50.2, 49.4, 45.2, 37.4, 32.9, 29.5,

28.6, 21.1, 16.1; IR (KBr) υ: 3410, 3025, 1901, 1713, 1684, 1584,

1495, 1467, 1398, 1364, 1334, 1290, 1246, 1223, 1200, 1179, 1086,

1013, 988, 930, 873, 845, 809 cm⁻¹; MS (m/z) HRMS (ESI) calcd

cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₂₆H₂₃N₃NaO₂([M +

Na]⁺) 432.1682, found 432.1682.

3,3′-(1-(4-Butylphenyl)ethane-1,1-diyl)bis(1-methyl-1H-indole)

(3c): ethyl acetate and petroleum ether (v/v = 1:60) as the eluent,

white solid, 174 mg, 79%, mp 159−160 °C; H NMR (400 MHz,

CDCl₃) δ 7.31−7.26 (m, 5H), 7.26−7.23 (m, 1H), 7.17−7.13 (m,

2H), 7.05−7.03 (m, 2H), 6.93−6.89 (m, 2H), 6.48 (s, 2H), 3.65 (s,

6H), 2.59−2.55 (m, 2H), 2.33 (s, 3H), 1.62−1.55 (m, 2H), 1.39−

1.30 (m, 2H), 0.91 (t, J = 7.6 Hz, 3H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 145.8, 140.2, 138.0, 128.2, 128.1, 127.9, 127.1, 123.7, 122.4,

121.2, 118.5, 109.3, 43.6, 35.4, 33.8, 32.7, 29.5, 22.7, 14.3; IR (KBr) υ

3434, 3064, 1955, 1696, 1569, 1510, 1445, 1336, 1220, 1203, 1114,

1003, 856, 803 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₃₀H₃₂N₂Na⁺

([M + Na]⁺) 443.2458, found 443.2459.

for C₄₃H₃₇ClN₂NaO₂([M + Na]⁺) 671.2436, found 671.2419.

rel-(1S,2R,4S)-1′-Benzyl-5′-chloro-4-(4-ethylphenyl)-9-methyl-2-

(4-methylbenzoyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-

2′-one (4c): ethyl acetate and petroleum ether (v/v = 1:20) as the

eluent, yellow solid, 105 mg, 45%, mp 264−266 °C; H NMR (400

3,3′-(1-(4-Propylphenyl)ethane-1,1-diyl)bis(1-methyl-1H-indole)

MHz, CDCl₃) δ 7.59−7.57 (m, 2H), 7.39−7.36 (m, 2H), 7.33−7.32

(m, 1H), 7.29−7.27 (m, 4H), 7.26−7.25 (m, 1H), 7.18−7.13 (m,

3H), 7.02−6.99 (m, 4H), 6.90−6.88 (m, 2H), 6.79−6.77 (m, 1H),

5.34 (d, J = 15.2 Hz, 1H), 4.90 (d, J = 15.6 Hz, 1H), 4.74−4.73 (m,

1H), 4.36 (d, J = 12.4 Hz, 1H), 3.61−3.53 (m, 1H), 2.88 (s, 3H),

3.75 (dd, J₁= 15.2 Hz, J₂= 7.6 Hz, 2H), 2.28 (s, 3H), 2.23 (d, J =

12.0 Hz, 1H), 1.34 (t, J = 7.6 Hz, 3H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 197.7, 176.5, 144.0, 143.3, 142.8, 141.1, 138.3, 136.0, 133.6,

133.0, 132.2, 129.1, 128.9, 128.8, 128.5, 128.4, 128.1, 127.9, 127.8,

125.9, 123.1, 122.4, 119.4, 114.6, 110.2, 108.9, 50.4, 49.5, 45.3, 37.3,

32.9, 29.6, 28.6, 21.6, 16.0; IR (KBr) υ 3428, 3058, 1721, 1675, 1603,

1481, 1429, 1360, 1322, 1228, 1186, 1160, 1119, 1075, 1016, 983,

918, 869, 843, 813 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

(3d): ethyl acetate and petroleum ether (v/v = 1:60) as the eluent,

white solid, 173 mg, 81%, mp 156−158 °C; H NMR (400 MHz,

CDCl₃) δ 7.31−7.27 (m, 5H), 7.26−7.24 (m, 1H), 7.17−7.13 (m,

2H), 7.05−7.03 (m, 2H), 6.93−6.89 (m, 2H), 6.48 (s, 2H), 3.66 (s,

6H), 2.55 (t, J = 7.6 Hz, 2H), 2.33 (s, 3H), 1.65−1.60 (m, 2H),

0.94−0.91 (m, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 145.6,

139.8, 137.8, 128.1, 127.9, 127.8, 126.9, 123.6, 122.3, 121.0, 118.3,

109.1, 43.4, 37.6, 32.6, 29.2, 24.5, 14.0; IR (KBr) υ 3455, 3056, 1924,

1665, 1575, 1510, 1494, 1383, 1274, 1224, 1142, 1043, 1032, 852,

832 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₂₉H₃₀N₂Na⁺([M +

Na]⁺) 429.2301, found 429.2303.

3,3′-(1-(4-Methoxyphenyl)ethane-1,1-diyl)bis(1-methyl-1H-in-

dole) (3e): ethyl acetate and petroleum ether (v/v = 1:60) as the

C₄₃H₃₇ClN₂NaO₂([M + Na]⁺) 671.2436, found 671.2421.

eluent, white solid, 116 mg, 56%, mp 186−188 °C; H NMR (400

rel-(1S,2R,4S)-1′-Benzyl-2-(4-chlorbenzoyl)-5′,9-dimethyl-4-(4-

propylphenyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-

one (4d): ethyl acetate and petroleum ether (v/v = 1:20) as the

MHz, CDCl₃) δ 7.32−7.26 (m, 5H), 7.24 (s, 1H), 7.18−7.14 (m,

2H), 6.94−6.90 (m, 2H), 6.79−6.77 (m, 2H), 6.47 (s, 2H), 3.78 (s,

3H), 3.66 (s, 6H), 2.32 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

157.4, 140.7, 137.8, 129.0, 128.0, 126.8, 123.6, 122.2, 121.0, 118.3,

113.0, 109.1, 55.1, 43.0, 32.6, 29.2; IR(KBr)υ: 3050, 2042, 1887,

1736, 1606, 1504, 1467, 1366, 1328, 1241, 1174, 1083, 1021, 835,

809 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₂₇H₂₆N₂NaO⁺([M +

Na]⁺) 417.1937, found 417.1941.

eluent, yellow solid, 184 mg, 77%, mp 208−210 °C; H NMR (400

MHz, CDCl₃) δ 7.60−7.58 (m, 2H), 7.38−7.35 (m, 2H), 7.32−7.27

(m, 4H), 7.26−7.25 (m, 2H), 7.18−7.12 (m, 2H), 7.04 (s, 4H),

7.00−6.97 (m, 2H), 6.80 (s, 1H), 6.77−6.75 (m, 1H), 5.30 (d, J =

15.2 Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.74 (d, J = 4.8 Hz, 1H),

4.36 (d, J = 12.4 Hz, 1H), 3.61 (td, J₁= 12.4 Hz, J₂= 5.2 Hz, 1H),

2.84 (s, 3H), 2.68 (t, J = 7.6 Hz, 2H), 2.18 (s, 3H), 2.14 (s, 1H), 1.74

(td, J₁= 14.8 Hz, J₂= 7.6 Hz, 2H), 1.02 (t, J = 7.2 Hz, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 197.0, 176.6, 142.2, 141.4, 141.2, 139.3,

138.3, 136.5, 134.4, 133.4, 132.3, 130.9, 129.8, 129.4, 128.8, 128.7,

128.6, 128.5, 128.4, 127.7, 126.0, 123.4, 122.2, 119.3, 119.2, 114.2,

109.1, 108.8, 50.2, 49.4, 45.2, 37.7, 37.4, 32.8, 29.5, 24.9, 21.1, 14.0;

IR (KBr) υ 3419, 3025, 1903, 1718, 1683, 1585, 1494, 1468, 1431,

1398, 1367, 1334, 1291, 1248, 1222, 1200, 1177, 1087, 1013, 987,

929, 873, 844, 809 cm⁻¹; MS (m/z) HRMS (ESI) calcd for

4. General Procedure for the Preparation of

Tetrahydrospiro[carbazole-1,3′-indolines] 4a−4g. To a 10 mL

ﬂask were added 1,1′-bis(indolyl)phenylethane (0.35 mmol, 1.0

equiv), (E)-3-phenacylideneoxindole (0.35 mmol, 1.0 equiv), indium

bromide (0.018 mmol, 0.05 equiv), and toluene (3.0 mL). The

mixture was heated at 80 °C by an oil bath for 10 h. After removing

the solvent, the residue was subjected to column chromatography on

silica gel with ethyl acetate and petroleum ether (v/v = 1:20) as an

eluent to aﬀord the desired products 1c, 1e, 1r, and 4a−4g.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-chlorobenzoyl)-4-(4-methoxyphen-

yl)-5′,9-dimethyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-

2′-one (4a): ethyl acetate and petroleum ether (v/v = 1:20) as the

C₄₄H₃₉ClN₂NaO₂([M + Na]⁺) 685.2592, found 685.2573.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-methoxybenzoyl)-9-methyl-4-(4-

propylphenyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-

one (4e): ethyl acetate and petroleum ether (v/v = 1:20) as the

eluent, yellow solid, 181 mg, 77%, mp 213-215 °C; H NMR (400

MHz, CDCl₃) δ 7.60−7.58 (m, 2H), 7.38−7.35 (m, 2H), 7.32−7.27

(m, 4H), 7.19−7.17 (m, 2H), 7.09 (s, 4H), 7.01−6.97 (m, 4H),

6.79−6.75 (m, 2H), 5.29 (d, J = 15.2 Hz, 1H), 4.91 (d, J = 15.2 Hz,

1H), 4.73−4.72 (m, H), 4.34 (d, J = 12.0 Hz, 1H), 3.88 (s, 3H), 3.59

(td, J₁= 12.8 Hz, J₂= 5.2 Hz, 1H), 2.83 (s, 3H), 2.17 (s, 3H), 2.14 (s,

1H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 197.1, 176.6, 158.6, 142.3,

139.4, 138.3, 136.5, 136.2, 134.3, 133.4, 132.3, 130.9, 129.8, 129.6,

129.4, 128.8, 128.7, 128.4, 127.8, 126.0, 123.4, 122.3, 119.3, 119.2,

114.3, 114.0, 109.2, 108.9, 55.5, 50.2, 49.4, 45.2, 36.9, 32.9, 29.5, 21.1;

IR (KBr) υ 3409, 3062, 1887, 1710, 1680, 1584, 1493, 1466, 1434,

1396, 1331, 1290, 1245, 1204, 1173, 1084, 1027, 982, 926, 873, 844,

807 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₄₂H₃₅ClN₂NaO₃⁺([M

+ Na]⁺) 673.2228, found 673.2212.

eluent, yellow solid, 184 mg, 79%, mp 121−123 °C; H NMR (400

MHz, CDCl₃) δ 7.61−7.59 (m, 2H), 7.39−7.35 (m, 2H), 7.32−7.28

(m, 2H), 7.25−7.21 (m, 4H), 7.18−7.13 (m, 3H), 7.10−7.04 (m,

3H), 7.00−6.96 (m, 1H), 6.91−6.85 (m, 2H), 6.55−6.53 (m, 2H),

5.36 (d, J = 15.2 Hz, 1H), 4.91 (d, J = 15.2 Hz, 1H), 4.74 (d, J = 4.4

Hz, 1H), 4.41 (d, J = 12.0 Hz, 1H), 3.74 (s, 3H), 3.59 (td, J₁= 12.8

Hz, J₂= 5.2 Hz, 1H), 2.84 (s, 3H), 2.68−2.64 (m, 2H), 2.18 (d, J =

13.2 Hz, 1H), 1.78−1.69 (m, 2H), 1.01 (t, J = 7.2 Hz, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 196.9, 177.0, 163.3, 144.7, 141.6, 141.0,

138.4, 136.6, 134.4, 131.2, 130.6, 128.9, 128.8, 128.7, 128.5, 128.4,

128.1, 127.8, 126.1, 122.8, 122.7, 122.2, 119.3, 119.2, 114.3, 113.5,

109.3, 108.9, 55.3, 50.1, 49.5, 45.2, 37.8, 37.4, 33.1, 29.5, 24.9, 14.0;

IR (KBr) υ 3424, 3053, 1908, 1718, 1677, 1600, 1508, 1486, 1464,

1338, 1307, 1261, 1225, 1163, 1113, 1078, 1025, 986, 902, 873, 841,

802 cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₄₄H₄₀N₂NaO₃⁺([M +

Na]⁺) 667.2931, found 667.2922.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-chlorobenzoyl)-5′,9-dimethyl-4-(4-

propylphenyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-

one (4b): ethyl acetate and petroleum ether (v/v = 1:20) as the

eluent, yellow solid, 169 mg, 72%, mp 239−241 °C; H NMR (400

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Article

rel-(1S,2R,4S)-1′-Benzyl-4-(4-butylphenyl)-2-(4-chlorobenzoyl)-

5′,9-dimethyl-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-

one (4f): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

yellow solid, 181 mg, 74%, mp 120−122 °C; H NMR (400 MHz,

108.6, 48.8, 43.8, 32.4, 21.0; IR (KBr) υ 3691, 3055, 3029, 1917,

1806, 1699, 1598, 1556, 1490, 1467, 1438, 1378, 1359, 1322, 1219,

1179, 1124, 1083, 1016, 1001, 984, 918, 866, 842, 829, 812, 764

cm⁻¹; MS (m/z) HRMS (ESI) calcd for C₄₁H₃₁ClN₂NaO⁺([M +

Na]⁺) 625.2017, found 625.2007.

CDCl₃) δ 7.60−7.58 (m, 2H), 7.38−7.35 (m, 2H), 7.32−7.27 (m,

4H), 7.25−7.24 (m, 2H), 7.19−7.12 (m, 2H), 7.04 (s, 4H), 7.01−

6.99 (m, 2H), 6.80 (s, 1H), 6.77−6.75 (m, 1H), 5.30 (d, J = 15.2 Hz,

1H), 4.91 (d, J = 15.6 Hz, 1H), 4.74 (d, J = 4.4 Hz, 1H), 4.36 (d, J =

12.0 Hz, 1H), 3.61 (td, J₁= 13.2 Hz, J₂= 5.6 Hz, 1H), 2.83 (s, 3H),

2.72−2.68 (m, 2H), 2.18 (s, 3H), 2.14 (s, 1H), 1.73−1.66 (m, 2H),

1.46−1.41 (m, 2H), 0.99 (t, J = 7.6 Hz, 3H); ¹³C{¹H} NMR (100

MHz, CDCl₃) δ 197.0, 176.6, 142.2, 141.4, 141.3, 139.3, 138.3 136.5,

134.4, 133.3, 132.3, 130.9, 129.7, 129.3, 128.7, 128.6, 128.5, 128.4,

128.3, 127.7, 126.0, 123.4, 122.2, 119.3, 119.2, 114.1, 109.1, 108.8,

50.1, 49.4, 45.1, 37.4, 35.4, 34.0, 32.8, 29.5, 22.5, 21.1, 14.0; IR (KBr)

υ 3415, 3023, 1909, 1716, 1688, 1588, 1495, 1466, 1400, 1362, 1334,

1181, 1089, 1012, 987, 929, 877, 845, 810 cm⁻¹; MS (m/z) HRMS

6. Synthesis of 3-(1-Phenylvinyl)-1H-indole and Its Diels−

Alder Reaction. According to the reported method, under N₂, to a

solution of phenylmagnesium bromide (25 mmol, 2.5 equiv) in dry

Et₂O (40 mL) at 0 °C (ice bath) was added the Et₂O solution of 1-

(1H-indol-3-yl)ethan-1-one (10 mmol, 1.0 equiv) dropwise. Then,

the reaction mixture was warmed to 50 °C by an oil bath and stirred

at the same temperature for 12 h. Upon completion, the reaction

mixture was cooled to 0 °C by an ice bath. A saturated aqueous

NH₄Cl solution (40 mL) was added dropwise. The organic layer was

separated. The aqueous layer was extracted with ethyl acetate (3 × 50

mL). The combined organic layers were dried over anhydrous

Na₂SO₄, ﬁltered, and concentrated. The residue was dissolved in

CH₂Cl₂(50 mL), to which was added anhydrous MgSO₄(0.5 g per

mmol of the substrate) followed by silica gel (200−300 mesh particle

size, 0.5 g per mmol of the substrate). The mixture was then stirred at

room temperature for 5 h, and the reaction progress was monitored

by thin-layer chromatography. Upon completion, the reaction mixture

was ﬁltered and washed with ethyl acetate. The ﬁltrate was

concentrated, and the residue was puriﬁed by silica gel chromatog-

raphy to aﬀord the desired 3-(1-phenylvinyl)-1H-indole.

To a 50 mL ﬂask were added 3-(1-phenylvinyl)-1H-indole (0.35

mmol, 1.0 equiv), (E)-1-benzyl-3-(2-oxo-2-(p-tolyl)ethylidene)-

indolin-2-one (0.35 mmol, 1.0 equiv), InBr₃(0.018 mmol, 0.05

equiv), and toluene (3 mL). The mixture was heated to 80 °C by an

oil bath for 14 h. Upon completion, the solvent was removed. Then,

the residue was puriﬁed by column chromatography on silica gel with

ethyl acetate and petroleum ether (v/v = 1:20) as an eluent to aﬀord

the product rel-(1S,2R,4S)-1′-benzyl-2-(4-methylbenzoyl)-4-phenyl-

2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1k).

(ESI) calcd for C₄₅H₄₁ClN₂NaO₂([M + Na]⁺) 699.2749, found

699.2737.

rel-(1S,2R,4S)-1′-Benzyl-2-(4-chlorobenzoyl)-5′,9-dimethyl-4-(4-

nitrophenyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3′-indolin]-2′-one

(4g): ethyl acetate and petroleum ether (v/v = 1:20) as the eluent,

yellow solid, 120 mg, 50%, mp 252−254 °C; H NMR (400 MHz,

CDCl₃) δ 8.32−8.30 (m, 2H), 7.57−7.55 (m, 4H), 7.39−7.29 (m,

3H), 7.22−7.10 (m, 4H), 7.08−7.06 (m, 3H), 7.03−6.98 (m, 2H),

6.78−6.75 (m, 2H), 5.26 (d, J = 15.6 Hz, 1H), 4.90 (d, J = 15.2 Hz,

1H), 4.84 (d, J = 5.2 Hz, 1H), 4.22 (d, J = 11.2 Hz, 1H), 3.72 (td, J₁=

13.6 Hz, J₂= 6.0 Hz, 1H), 2.86 (s, 3H), 2.19 (s, 3H), 2.16 (s, 1H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 196.6, 176.0, 152.2, 146.9,

142.1, 139.8, 138.4, 136.2, 134.5, 133.4, 132.6, 130.3, 129.7, 129.4,

129.3, 128.7, 128.3, 127.8, 125.5, 123.9, 123.2, 122.6, 119.7, 118.8,

112.4, 109.4, 109.1, 49.7, 49.4, 45.1, 37.6, 31.8, 29.6, 21.1; IR (KBr) υ

3445, 3027, 1712, 1689, 1591, 1518, 1495, 1470, 1399, 1343, 1184,

1091, 1012, 989, 931, 880, 854, 810 cm⁻¹; MS (m/z) HRMS (ESI)

calcd for C₄₁H₃₂ClN₃NaO₄⁺([M + Na]⁺) 688.1974, found 688.1973.

5. General Procedure for the Reactions of 3(9H-Carbazol-2-

yl)indolin-2-ones 5a and 5b. To a 10 mL ﬂask were added

tetrahydrospiro[carbazole-1,3′-indolines] (0.35 mmol), toluene (3.0

mL), and TfOH (0.053 g), and the system was heated to 80 °C by an

oil bath for 30 min. Upon completion, the solvent was removed at

reduced pressure by rotatory evaporation, and the residue was

subjected to column chromatography on silica gel with ethyl acetate

and petroleum ether (v/v = 1:20) as an eluent to aﬀord the desired

products 5a−5b.

7. Procedure for the Gram-Scale Reaction of (1S,2R,4S)-1′-

Benzyl-2-(4-clorobenzoyl)-5′-methyl-4-phenyl-2,3,4,9-

tetrahydrospiro[carbazole-1,3′-indolin]-2′-one (1j). To a 40 mL

Schlenk tube were added indole (7.0 mmol), phenylacetylene (5.0

mmol), indium bromide (0.125 mmol), and toluene (10.0 mL). The

mixture was stirred at 110 °C by an oil bath for 15 min. Then, (E)-3-

phenacylideneoxindoles (4.0 mmol) was added, and the solution was

stirred at 80 °C by an oil bath for 16 h. After removing the solvent,

the residue was subjected to column chromatography on silica gel

with ethyl acetate and petroleum ether (v/v = 1:20) as an eluent to

aﬀord the desired product 1j (1.30 g, 54%).

1-Benzyl-5-methyl-3-(9-methyl-4-phenyl-1-(p-tolyl)-9H-carba-

zol-2-yl)-1,3-dihydro-2H-inden-2-one (5a): ethyl acetate and petro-

leum ether (v/v = 1:20) as the eluent, white solid, 165 mg, 78%, mp

ASSOCIATED CONTENT

* Supporting Information

■

sı

159−161 °C; H NMR (400 MHz, CDCl₃) δ 7.81−7.80 (m, 1H),

7.51−7.44 (m, 6H), 7.37−7.35 (m, 4H), 7.29−7.23 (m, 6H), 6.94−

6.89 (m, 2H), 6.85 (s, 1H), 6.59−6.58 (m, 1H), 6.44 (s, 1H), 5.02−

4.99 (m, 1H), 4.80−4.77 (m, 2H), 3.29 (s, 3H), 2.47 (s, 3H), 2.20 (s,

3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 177.1, 142.4, 141.1, 141.0,

139.3, 137.7, 137.2, 136.3, 135.0, 134.3, 132.2, 132.1, 131.3, 130.8,

129.4, 129.2, 128.9, 128.7, 128.3, 128.1, 127.5, 127.4, 125.7, 125.5,

125.4, 122.2, 122.1, 119.7, 118.7, 108.6, 108.5, 48.9, 43.8, 32.2, 21.4,

21.0; IR (KBr) υ 3674, 3026, 1893, 1807, 1700, 1598, 1555, 1519,

1490, 1467, 1435, 1378, 1321, 1218, 1179, 1123, 1078, 1022, 1001,

982, 918, 892, 866, 826, 809, 788, 763 cm⁻¹; MS (m/z) HRMS (ESI)

calcd for C₄₂H₃₄N₂NaO⁺([M + Na]⁺) 605.2563, found 605.2562.

1-Benzyl-3-(1-(4-chlorophenyl)-9-methyl-4-phenyl-9H-carbazol-

2-yl)-5-methyl-1,3-dihydro-2H-inden-2-one (5b): ethyl acetate and

petroleum ether (v/v = 1:20) as the eluent, white solid, 81%, mp

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.1c00103.

Experiment procedures and H, ¹³C NMR, and HRMS

spectra (PDF)

Accession Codes

The crystallographic data of compounds 1g (CCDC 2036202),

1h (CCDC 2036203), 1i (CCDC 2036204), 1m (CCDC

2036205), 2f (CCDC 2036206), and 5a (CCDC 2036207)

have been deposited at the Cambridge Crystallographic

Database Center (http//www.ccdc.cam.ac.uk)

AUTHOR INFORMATION

Corresponding Authors

■

173−175 °C; H NMR (400 MHz, CDCl₃) δ 7.94−7.92 (m, 1H),

7.74−7.46 (m, 8H), 7.37−7.28 (m, 5H), 7.25−7.25 (m, 2H), 6.96−

6.91 (m, 2H), 6.84 (s, 1H), 6.61−6.60 (m, 1H), 6.44−6.30 (m, 2H),

5.00 (d, J = 14.8 Hz, 1H), 4.79 (d, J = 15.6 Hz, 1H), 4.69 (s, 1H),

3.30−3.07 (m, 3H), 2.21 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃)

δ 176.7, 142.4, 141.1, 140.9, 139.1, 137.6, 136.7, 136.1, 134.2, 134.0,

133.9, 132.3, 132.2, 130.9, 129.3, 128.9, 128.8, 128.7, 128.3, 128.2,

127.6, 127.5, 127.3, 125.6, 125.4, 124.2, 122.2, 119.7, 118.9, 108.8,

Ru-Zhang Liu − College of Chemistry and Chemical

Engineering, Yangzhou University, Yangzhou 225002,

China; orcid.org/0000-0002-9569-2622;

Email: liurzh@yzu.edu.cn

Chao-Guo Yan − College of Chemistry and Chemical

Engineering, Yangzhou University, Yangzhou 225002,

5626

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J. Org. Chem. 2021, 86, 5616−5629

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

Enantioselective synthesis of tetrahydrocarbazoles via trienamine

catalysis and their anxiolytic-like activity. Bioorg. Med. Chem. Lett.

2020, 30, 127063. (d) Choi, T. A.; Czerwonka, R.; Frohner, W.;

Krahl, M. P.; Reddy, K. R.; Franzblau, S. G.; Knolker, H.-J. Synthesis

and activity of carbazole derivatives against Mycobacterium tuber-

culosis. ChemMedChem 2006, 1, 812−815. (e) Choi, T. A.;

Czerwonka, R.; Forke, R.; Jaeger, A.; Knoell, J.; Krahl, M. P.;

Krause, T.; Reddy, K. R.; Franzblau, S. G.; Knoelker, H.-J. Transition

metals in organic synthesis - Part 83: Synthesis and pharmacological

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G.; Knolker, H.-J. Anti-tuberculosis activity and structure-activity

relationships of oxygenated tricyclic carbazole alkaloids and synthetic

derivatives. Bioorg. Med. Chem. 2017, 25, 6167−6174.

China; orcid.org/0000-0002-2777-9582;

Email: cgyan@yzu.edu.cn

Authors

Daqian Wang − College of Chemistry and Chemical

Engineering, Yangzhou University, Yangzhou 225002, China

Jing Sun − College of Chemistry and Chemical Engineering,

Yangzhou University, Yangzhou 225002, China

Yang Wang − College of Chemistry and Chemical Engineering,

Yangzhou University, Yangzhou 225002, China;

orcid.org/0000-0003-2540-2199

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.1c00103

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Petrini, M. Synthetic Approaches to 3-(2-Nitroalkyl) Indoles and

Their Use to Access Tryptamines and Related Bioactive Compounds.

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Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

This work was ﬁnancially supported by the National Natural

Science Foundation of China (21572196 and 21871227) and

the Priority Academic Program Development of Jiangsu

Higher Education Institutions (BK2013016).

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