TfOH-Catalyzed One-Pot Domino Reaction for Diastereoselective Synthesis of Polysubstituted Tetrahydrospiro[carbazole-1,3′-indoline]s

Article abstract of DOI:10.1021/acs.joc.7b02397

TfOH-catalyzed one-pot sequential reaction of indoles, acetophenones (cyclic ketones), and various 3-methyleneoxindolines in toluene afforded polysubstituted tetrahydrospiro[carbazole-1,3′-indoline]s in satisfactory yields. ¹H NMR spectra and s

Full text of DOI:10.1021/acs.joc.7b02397

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Article
TfOH catalyzed one-pot domino reaction for diastereoselective
synthesis of poly substituted tetrahydrospiro[carbazole-1,3'-indolines]
Ren-Yin Yang, Jing Sun, Yao Tao, Qiu Sun, and Chao-Guo Yan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02397 • Publication Date (Web): 13 Nov 2017
Downloaded from http://pubs.acs.org on November 18, 2017
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TfOH Catalyzed One-pot Domino Reaction for Diastereoselective Synthesis of
Polysubstituted Tetrahydrospiro[carbazole-1,3'-indolines]
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Ren-Yin Yang, Jing Sun*, Yao Tao, Qiu Sun, Chao-Guo Yan*
College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225002,
China. E-mail: sunjing@yzu.edu.cn; cgyan@yzu.edu.cn
Abstract: TfOH catalyzed one-pot sequential reaction of indoles, acetophenones (cyclic ketones)
and
various
3-methyleneoxindolines
in
toluene
afforded
polysubstituted
tetrahydrospiro[carbazole-1,3'-indolines] in satisfactory yields. 1H NMR spectra and single crystal
structures indicated that the obtained tetrahydrospiro[carbazole-1,3'-indolines] existing in unusual
trans-configuration. The reaction mechanism was believed to proceed with domino acid catalyzed
3-alkenylation of indoles with acetophenones, Diels-Alder reaction of 3-alkyenylindoles with
3-methyleneoxindolines and acid catalyzed diastereoisomerization process.
Keywords: carbazole; 3-methyleneoxindoline; spiro[carbazole-1,3'-indoline]; Diels-Alder
reaction; isomerization.
Introduction
The tetrahydrocarbazole architecture is a privileged heterocyclic ring system. It not
only widely exists in various naturally occurring alkaloids and pharmacologically active
compounds,1 but also is featured in a large family of synthetic analogues exhibiting a wide
spectrum of important bioactivities, such as anti-tumor activity, anti-protein kinase C
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activity.2 Additionally, the saturated carbazole derivatives are found potential applications
in organic light-emitting diodes and other functional materials.3 Therefore, many elegant
methods for the preparation of various tetrahydrocarbazole derivatives have been
developed in the past years,4-6 Among the many efficient synthetic methodologies for
tetrahydrocarbazoles, the [4+2] reaction of 3-vinylindolines or 2-vinylindolines with
diverse dienophiles has proven to be the most attractive strategy for the synthesis of many
carbazole derivatives.7-10 Practically, as one of mostly common used dipolarophiles and
dienophiles, 3-methyleneoxindolines were also employed in various cycloaddition reaction
to construct potential bioactive spiro-carbazole-oxindoline skeleton.11 Barbas and
coworkers successfully developed an C2-symmetric bisthiourea organocatalytic reaction
between 3-vinylindolines and methyleneindolinones for the direct construction of
spiro-carbazole-oxindoline containing three or four stereocenters (eq. 1 in Scheme 1).12
Melchiorre and coworkers also established a chiral amine-catalyzed asymmetric reaction of
methyleneindolinones with indole-2,3-quinodimethanes generated from α,β-unsaturated
aldehydes, which constructed a chiral spiro[tetrahydrocarbazole-3,3’-oxindoline] scaffold
in a highly stereoselective fashion.13 Feng’s group also achieved a highly efficient catalytic
asymmetric reaction between 3-vinylindoles and methyleneindolinones by using chiral
N,N’-dioxide-Ni(II) complexes as the catalysts.14 Shi and Tu reported chiral phosphoric
acid catalyzed asymmetric reactions of 2-vinylindolines with methyleneindolinones to
efficiently construct the spiro[tetrahydrocarbazole-3,3’-oxindoline] architecture with one
quaternary and three contiguous stereogenic centers in high yields and excellent
stereoselectivities (eq.
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Scheme 1 Synthetic strategies for spiro-carbazole-oxindolines
2 in Scheme 1).15 A similar cinchona-derived squaramide catalyzed asymmetric reaction of
2-vinylindoles with methyleneindolinones has also been disclosed.16 Very recently, a
AgOTf
catalyzed
alkyne-annulation/Diels–Alder
cascade
for
the
construction
of
tetrahydrospiro[carbazole-4,3’-indoline] derivatives has been established from
N-tosyl-2-(but-3-en-1-yn-1-yl)aniline with methyleneindolinones.17 Against this
background and in continuation of our aim to develop multicomponent reaction for
construction of diverse spirooxindoline systems,18 herein we wish to present TfOH
catalyzed one-pot domino reaction of indoles, acetophenones (cyclic ketones) and various
3-methyleneoxindolines
for
the
efficient
synthesis
of
tetrahydrospiro[carbazole-1,3'-indolines] in good yields and with unexpected
diastereoselectivity. The reaction process involved domino acid catalyzed 3-alkenylation of
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indoles with acetophenones, Diels-Alder reaction of 3-alkyenylindoles with
3-methyleneoxindoles and acid mediated diastereoisomerization process.
Results and Discussions
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Initially, the reaction conditions were examined by using 1-methylindole, acetophenone
and ethyl (E)-2-(1-benzyl-5-chloro-2-oxoindolin-3-ylidene)acetate as standard.9e When the
three-component reaction was carried out in the presence of TsOH and TfOH,
1-methylindole quickly added to 3-methyleneoxindoline to give the known Michael
addition product in high yield.19 In order to prevent the formation of this Michael addition
product, 1-methylindole firstly reacted with acetophenone in toluene in the presence of
TfOH. After TLC monitoring indicated that 1-methylindole has been completely consumed,
ethyl (E)-2-(1-benzyl-5-chloro-2-oxoindolin-3-ylidene)acetate was introduced in the
reaction mixture. After workup, the expected tetrahydrospiro[carbazole-1,3'-indoline] 1a
was successfully obtained in 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 the product 1a
can be obtained in 92% yield by carrying out the first-step reaction of 1-methylindole (0.5
mmol) and acetophenone (1.5 mmol) with TfOH (5 mol %) at 60 oC for half an hour, and
the second-step reaction with ethyl (E)-2-(2-oxoindolin-3-ylidene)acetate (0.5 mmol)
without further adding TfOH at 80 oC for twelve hours.
With the optimal reaction conditions in hand, we proceeded to explore the substrate
scope of the reaction. Various ethyl or methyl (E)-2-(2-oxoindolin-3-ylidene)acetates and
substituted acetophenones were employed in the one-pot two-step reaction. We were
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pleased to find that the reaction proceeded smoothly to give the expected functionalized
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tetrahydrospiro[carbazole-1,3'-indolines] 1a-1j in high yields. The results are summarized
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Table 1. Synthesis of tetrahydrospiro[carbazole-1,3'-indolines] 1a-1l via domino reactiona
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a Reaction conditions: indole (0.5 mmol), acetophenone (1.5 mmol), TfOH (5 mol%), toluene (2.0 mL), 60 oC, 1.5 hrs;
3-methyleneoxindoline (0.5 mmol), 80 oC, 12 hrs; bIsolated yields. c TfOH (10 mol%) was used.
in Table 1. The substituted acetophenones with both electron-donating group and
electron-withdrawing groups can be successfully employed in the reaction. The oxindoline
scaffold with various substituents have marginal effect on the products. Besides
1-methylindole, indole itself also resulted in the products 1k and 1l in good yields. The
structures of the obtained products 1a-1l were established by the various spectroscopy.
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Because there are three chiral carbon atoms in the newly-formed cyclohexenyl ring, several
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diastereoisomers might be formed in the reaction. H and 13C NMR spectra clearly
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indicated that there is only one diastereoisomer in the obtained products. The single crystal
structures of the compounds 1a (Fig. 1), 1f and 1k (Fig. s1-s2) were determined by X-ray
diffraction method. It was pleased to find that they have same relative configuration, in
which the aryl group, ethoxycarboxyl group exist in cis-position and the phenyl group of
the oxindoline moiety stands at trans-configuration. It should be pointed out that the
ethoxycarbonyl group and the phenyl group of the oxindoline moiety usually exist at
cis-position in the starting ethyl (E)-2-(2-oxoindolin-3-ylidene)acetates.19 Thus, the
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formation of
a
trans-configuration for these two groups in the obtained
tetrahydrospiro[carbazole-1,3'-indolines] 1a-1l suggested that the reaction contained a
more complicated cyclization process rather than the expected concerted Diels-Alder
reaction, which would afford the tetrahydrospiro[carbazole-1,3'-indolines] 1a-1l with
cis-configuration.20
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Fig. 1 ORTEP-drawing (30%) of the crystal structure of 1a
With the success in the reactions of ethyl (E)-2-(2-oxoindolin-3-ylidene)acetates, we turned
our
attention
to
another
commonly
used
3-methyleneoxindolines.
Various
3-phenacylideneoxindolines were employed in the one-pot two-step reaction. The results are
summarized in Table 2. Acetophenones with both electron-donating p-methyl group and
electron-withdrawing p-chloro, p-nitro groups reacted smoothly to give the corresponding
products 2a-2i in good yields. It should be pointed out that indoles both with N-methyl group and
without N-methyl group reacted well to afford the expected products. These results showed that
this reaction has a wide variety of substrate scope. Besides characterizing the obtained products
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2a-2i with IR, HRMS, H and 13C spectroscopy, the structure of compounds 2a, 2c and 2d were
unambiguously confirmed by single crystal X-ray diffraction analysis. From the single crystal
structure of 2a, 2c and 2d (Fig. s3-s5), we have found that they have same relative configuration
to that of the above obtained products 1a, 1f and 1k, which indicated that the reaction has same
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outcome of stereochemistry. It has been known that the phenacyl group or ethoxycarbonyl group
usually exists at cis-position to the phenyl group of the oxindoline moiety in the starting
3-phenacylideneoxindoline or ethyl (E)-2-(2-oxoindolin-3-ylidene)acetates.20 The previously
reported [4+2] reactions of 2-vinyl and 3-vinylindolines with various 3-methyleneoxindolines also
gave the spiro compounds with phenacyl group or ethoxycarbonyl group existing at cis-position to
the phenyl group of the oxindoline.12-17 If the in situ generated 3-alkenylindoles reacted with these
two kinds of 3-methyleneoxindolines according to concerted Diels-Alder reaction process, the
obtained tetrahydrospiro[carbazole-1,3'-indolines] 1 and 2 would have the cis-configuration for
the phenacyl group or ethoxycarbonyl group to the phenyl group of the oxindoline (Scheme 2).
Our obtained results clearly indicated that tetrahydrospiro[carbazole-1,3'-indolines] 1 and 2 have
the trans-configuration for the phenacyl (ethoxycarbonyl) group and the phenyl group of the
oxindoline. Thus, an unusual inversion of configuration was observed in the above reactions. A
literature survey showed that some Lewis acid catalyzed [4+2] reactions of 2-alkenyl and
3-alkenylindoles with activated dienophiles might proceed with pure Diels–Alder mechanism or
by asynchronous or stepwise mechanisms.21 Herein, our experiments provided a new example of
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unusual cycloaddition reaction of 3-alkenylindolines with the cyclic dienophiles.
Table 2. Synthesis of tetrahydrospiro[carbazole-1,3'-indolines] 2a-2i via domino reactiona
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aReaction conditions: indole (0.5 mmol), acetophenone (1.5 mmol), TfOH (5 mol%), toluene (2.0 mL), 60 oC, 1.5 hrs;
3-methyleneoxindoline (0.5 mmol), 80 oC, 12 hrs; bIsolated yields.
Scheme 2 stereochemistry of the domino reaction
For elucidating the stereochemistry of the reaction, various cyclic ketones were also
employed in this one-pot two-step reaction procedure. The results are summarized in Table
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3. Cyclopentanone, cyclohexanone, 4-tert-butylcyclohexane and cyclooctanone reacted
smoothly to give the expected carbocyclic fused tetrahydrospiro[carbazole-1,3'-indolines]
3a-3g in moderate to good yields. These results also showed that this reaction has a wide
variety of substrate scope. The structures of the spiro compounds 3a-3g were fully
characterized by the spectroscopy. The single crystal structures of the compound 3c (Fig.
2), 3e (Fig. s6) and 3g (Fig. s7) were also determined by X-ray diffraction method. They
showed different configurations. From Fig. 2, it can be seen that the fused cyclohexyl ring
has a trans-configuration and the benzoyl group and phenyl group of the oxindoline moiety
exist on cis-position, which was different to that of the above spiro compounds 1 and 2. In
the single crystal structure of the compound 3e, the fused cyclopentyl ring exists in
cis-configuration. The benzoyl group and phenyl group of the oxindoline moiety also exist
on cis-position. On the other hand, in the single crystal structure of the compound 3g (Fig.
s7), the fused cyclooctyl ring has a cis-configuration, while the ester group existing to the
trans-position of phenyl group of the oxindoline moiety. It might be duo to the steric effect
of the fused carbocyclic ring in the molecules, the most thermodynamically stable
diastereoisomer would be predominately produced in the domino process. The unusual
stereochemistry for the above obtained tetrahydrospiro[carbazole-1,3'-indolines] and the
corresponding cyclic fused derivatives ambiguously showed that an acid catalyzed
diastereoisomerization process was involved in the reaction.
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Fig. 2 ORTEP-drawing (30%) of the crystal structure of 3c
On the basis of above results and the previously reported reactions,7,21-23 a plausible
domino reaction mechanism was relationally proposed in Scheme 3 by using
3-phenacylideneoxindoline as the substrate. At first, a 3-alkenylindole (A) was generated
by the Friedel-Crafts reaction of indole and acetophenone with dehydration in the presence
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of triflic acid. Secondly, A Diels-Alder reaction of 3-alkenylindole (A) with
3-phenacylideneoxindolines directly afforded a 2,3,9,9a-tetrahydrocarbazole intermediate
(B),22 in which the benzoyl group and the phenyl group of oxindoline remained in
cis-configuration. Thirdly, The intermediate (B) in turn converted to
2,3,4,9-tetrahydrocarbazole intermediate (C) by 1,3-H shift process. In the intermediate (B)
and (C), the benzoyl group and phenyl group of oxindoline scaffold retained in the
cis-configuration. Then, the final separated spiro compound 2 was formed by HOTf
catalyzed keto-enol tautomerism through the intermediate (D), in which the configuration
of benzoyl group was inverted to the trans-position of the phenyl group of oxindoline
scaffold. In both 1,3-H shift and keto-enol tautomerism process, the configuration of the
substituents can be changed. It might be due to the larger steric effect of the substituents in
the newly-formed cyclohexenyl ring, the most thermodynamically stable
trans-diastereoisomer was predominately formed in the acid-catalyzed heating reaction
conditions.
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Scheme 3 Plausible reaction mechanism for domino three-component reaction
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In order to shed more light on the proposed reaction mechanism, further control
experiments were carried out. The Diels-Alder reaction of 3-methyleneoxindolines with
3-(1-phenylvinyl)indole, which was previously prepared from the reaction of
3-acetylindole with phenylmagnesium bromide according to the published method,24
actually resulted in the intermediates (B1)-(B4) in very high yields (Table 4). The
molecular structures (B1)-(B4) were established on the spectroscopy and determination of
the single crystal structures of (B2) (Fig. s8) and (B3) (Fig. 3), in which the
ethoxycarbonyl group or benzoyl group actually existing to the cis-position of the phenyl
group of oxindoline scaffold. An exo-cyclic C=C double bond of the dihydroindoline was
also observed in the molecule. When intermediates (B3) and (B4) were stirred in toluene in
the presence of TfOH at room
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Table 4. Acid catalyzed isomerization of tetrahydrospiro[carbazole-1,3'-indolines]a-d
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a Reaction conditions: 3-(1-phenylvinyl)indole (0.5 mmol), 3-methyleneoxindoline (0.5 mmol), toluene (2.0 mL), 80 oC, 15 hrs; b
TfOH (5 mol %), toluene (2.0 mL), rt, 5 hrs; c TfOH (5 mol%), toluene (2.0 mL), 50oC 30 hrs; d TfOH (5 mol %), toluene (2.0 mL),
rt, 5 hrs; d Isolated yields.
temperature for five hours, they completely converted to the above prepared spiro
compounds 2c and 2f in good yields. If the product B2 was were stirred in toluene in the
presence of TfOH at room temperature for five hours, the intermediate C2 was obtained in
96% yield, which was clearly formed by the 1,3-H shift, and the sequential
diastereoisomerization of ethoxycarbonyl group has no finished. The single crystal
structure of the intermediate C2 was successfully determined by X-Ray diffraction method
(Fig. s9). On the other hand, the products B1 and B2 in toluene in the presences of TfOH
was heated to 50 oC for longer time, the expected isomerized products 1l and 1m could be
formed in moderate yields. The single crystal structure of the compound 1m (Fig. s10) also
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showed that the ethoxycarbonyl group exists on the trans-position of phenyl group of the
oxindoline scaffold. These experiments clearly indicated that the initially formed
cis-isomer of tetrahydrospiro[carbazole-1,3'-indolines] actually isomerized to the more
sable trans-isomer in acidic solution. Thus, only the trans-isomers were successfully
synthesized in our acid catalyzed one-pot two-step reactions. These experiments not only
provided stronger evidence to our proposed reaction mechanism, but also developed an
efficient method for diastereoselective synthesis of the polysubstituted
tetrahydrospiro[carbazole-1,3'-indolines].
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Fig. 3 ORTEP-drawing (30%) of the crystal structure of B3
Conclusion
In summary, we have successfully developed an acid catalyzed domino reaction of
indole, acetophenones and 3-methyleneoxindolines for selective synthesis of biologically
important carbazole derivatives. Importantly, the one-pot two-step reaction protocol
afforded the functionalized tetrahydrospiro[carbazole-1,3'-indolines] with high
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diastereoselectivity Furthermore, the unusual trans-configuration of the obtained
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tetrahydrospiro[carbazole-1,3'-indolines]
clearly
revealed
a
domino
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9
alkenylation/Diels-Alder reaction/isomerization process. Additionally, the advantages of
this domino reaction included, readily available starting materials, simple reaction
conditions, broad scope of substrates, satisfactory yields and high diastereoselectivity,
which would be found potential applications in synthetic and medicinal chemistry.
Experimental section
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Experimental section
1. General procedure for the synthesis of tetrahydrospiro[carbazole-1,3'-indoline]
derivatives 1a-1l: In the nitrogen atmosphere, to a 10 mL Schlenk tube was added indole (0.5
mmol), substituted acetophenone (1.5 mmol), and TfOH (5% mol) and toluene (2.0 mL). The
mixture was heated at 60oC for 1.5 hours. Then, ethyl (E)-2-(2-oxoindolin-3-ylidene)acetate (0.5
mmol) was added. The solution was heated at 80oC for about 12 hours. The solvent was removed
at reduced pressure by rotator evaporation, the residue was subjected to preparative column
chromatography with a mixture of light petroleum and ethyl acetate (V/V = 5:1) as eluent to give
the pure product for analysis.
Ethyl
1'-benzyl-5'-chloro-9-methyl-2'-oxo-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline
]-2-carboxylate (1a): white solid, 92%, 0.264 g, m.p. 224-226℃; 1H NMR (400 MHz, CDCl3) δ:
7.49-7.44 (m, 4H), 7.37-7.30 (m, 5H), 7.25-7.23 (m, 2H), 7.10-7.08 (m, 3H), 6.83-6.80 (m, 2H),
6.70 (d, J = 8.0 Hz, 1H), 5.23 (d, J = 15.2 Hz, 1H), 4.77 (d, J = 15.6 Hz, 1H), 4.41 (dd, J1 = 11.6
Hz, J2 = 5.6 Hz, 1H), 3.97-3.84 (m, 2H), 3.45 (d, J = 12.8 Hz, 1H), 3.18-3.08 (m, 1H), 2.83 (s,
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3H), 2.44 (dd, J1 = 13.2 Hz, J2 = 5.6 Hz, 1H), 1.01 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 175.2, 171.2, 144.8, 142.7, 138.0, 135.7, 132.8, 131.9, 129.0, 128.8, 128.5, 128.4, 128.3,
128.2, 128.0, 126.6, 125.5, 124.0, 122.1, 120.3, 119.1, 116.5, 110.1, 108.7, 60.9, 52.8, 49.8, 45.0,
41.5, 33.1, 29.9, 13.9; IR (KBr) υ: 1720 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for
C36H32ClN2O3 ([M+H]+): 575.2101. Found: 575.2107.
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Ethyl
1'-benzyl-5',9-dimethyl-2'-oxo-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-c
arboxylate (1b): white solid, 90%, 0.100 g, m.p. 248-250℃; 1H NMR (400 MHz, CDCl3) δ: 7.60
(d, J = 6.4 Hz, 2H), 7.37-7.33 (m, 7H), 7.25 (brs, 1H), 7.17 (d, J = 8.0 Hz, 1H), 7.08-7.04 (m, 1H),
7.00-6.97 (m, 2H), 6.90 (d, J = 7.6 Hz, 1H), 6.69-6.65 (m, 1H), 6.56 (d, J = 7.6 Hz, 1H), 5.23 (d, J
= 15.2 Hz, 1H), 4.82 (d, J = 14.8 Hz, 1H), 4.45-4.43 (m, 1H), 3.65-3.55 (m, 3H), 3.41 (s, 3H),
2.95-2.87 (m, 1H), 2.49 (d, J = 13.6 Hz, 1H), 2.15 (s, 3H), 0.67 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 178.3, 170.7, 140.5, 139.7, 136.4, 136.2, 135.2, 131.0, 130.4, 128.0, 127.8, 127.6,
127.6, 127.5, 126.8, 125.9, 124.4, 123.4, 120.5, 118.3, 117.6, 107.8, 107.2, 59.3, 49.9, 44.0, 42.4,
36.6, 31.0, 28.2, 20.0, 12.5; IR (KBr) υ: 1719 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd.
for C37H35N2O3 ([M+H]+): 555.2648. Found: 555.2643.
Ethyl
1'-benzyl-9-methyl-2'-oxo-4-(p-tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-carb
oxylate (1c): white solid, 89%, 0.247 g, m.p. 232-234℃; 1H NMR (400 MHz, CDCl3) δ: 7.50 (d,
J = 7.2 Hz, 2H), 7.36-7.33 (m, 4H), 7.31-7.26 (m, 2H), 7.14-7.10 (m, 3H), 7.06-7.01 (m, 3H), 6.90
(d, J = 8.0 Hz, 1H), 6.82-6.79 (m, 1H), 6.74 (d, J = 8.0 Hz, 1H), 5.24 (d, J = 15.2 Hz, 1H), 4.79 (d,
J = 15.6 Hz, 1H), 4.38 (dd, J1 = 11.6 Hz, J2 = 5.6 Hz, 1H), 3.92-3.82 (m, 2H), 3.48 (d, J = 12.8 Hz,
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1H), 3.19-3.10 (m, 1H), 2.79 (s, 3H), 2.40-2.35 (m, 4H), 0.95 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 175.6, 171.4, 144.0, 142.0, 137.9, 136.2, 135.9, 132.5, 130.9, 129.2, 129.0, 128.7,
128.3, 128.2, 127.8, 125.6, 123.6, 122.9, 121.8, 120.3, 118.9, 116.3, 109.2, 108.6, 60.6, 53.0, 49.7,
44.8, 41.2, 33.2, 29.8, 21.2, 13.8; IR (KBr) υ: 1722 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF)
Calcd. for C37H35N2O3 ([M+H]+): 555.2648. Found: 555.2675.
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Ethyl 1'-butyl-4-(4-chlorophenyl)-5'-fluoro-9-methyl-2'-oxo-2,3,4,9-tetrahydrospiro
1
[carbazole-1,3'-indoline]-2-carboxylate (1d): white solid, 79%, 0.220 g, m.p. 239-241℃; H
NMR (400 MHz, CDCl3) δ: 7.37 (d, J = 7.6 Hz, 2H), 7.27 (d, J = 7.6 Hz, 2H), 7.11-7.06 (m, 3H),
6.90-6.86 (m, 2H), 6.84-6.82 (m, 1H), 6.70 (d, J = 8.0 Hz, 1H), 4.38 (dd, J1 = 11.2 Hz, J2 = 5.6 Hz,
1H), 3.93-3.83 (m, 3H), 3.76-3.71 (m, 1H), 3.39 (d, J = 12.8 Hz, 1H), 3.10-3.00 (m, 1H), 2.96 (s,
3H), 2.36 (dd, J1 = 13.6 Hz, J2 = 5.6 Hz, 1H), 1.79-1.70 (m, 2H), 1.52-1.43 (m, 2H), 1.03-0.98 (m,
6H); 13C NMR (100 MHz, CDCl3) δ: 174.9, 170.9, 159.2 (d, J = 240.8 Hz), 143.6, 140.3, 140.2,
138.0, 132.6 (d, J = 7.6 Hz), 132.2, 132.1, 129.7, 128.6, 125.3, 122.1, 120.1, 119.1, 115.7, 115.5
(d, J = 23.2 Hz), 111.8 (d, J = 24.7 Hz), 109.0, 108.9, 108.8, 60.8, 52.6, 49.9, 40.7, 40.6, 32.8,
29.7, 29.3, 20.5, 13.9, 13.8; IR (KBr) υ: 1724 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd.
for C33H33ClFN2O3 ([M+H]+): 559.2164. Found: 559.2186.
Ethyl
1'-butyl-5',9-dimethyl-2'-oxo-4-(p-tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-ca
1
rboxylate (1e): white solid, 83%, 0.222 g, m.p. 228-230℃; H NMR (400 MHz, CDCl3) δ: 7.32
(d, J = 7.2 Hz, 2H), 7.15-7.00 (m, 3H), 7.07-7.04 (m, 2H), 6.94 (s, 1H), 6.83-6.78 (m, 2H), 6.73 (d,
J = 8.0 Hz, 1H), 4.35 (dd, J1 = 11.2 Hz, J2 = 5.6 Hz, 1H), 3.94-3.83 (m, 3H), 3.75-3.67 (m, 1H),
3.43 (d, J = 12.8 Hz, 1H), 3.14-3.04 (m, 1H), 2.92 (s, 3H), 2.37-2.34 (m, 4H), 2.29 (s, 3H),
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1.79-1.71 (m, 2H), 1.52-1.43 (m, 2H), 1.01-0.97 (m, 6H); 13C NMR (100 MHz, CDCl3) δ: 175.3,
171.3, 142.0, 141.8, 137.9, 135.9, 132.8, 132.2, 131.0, 129.3, 129.1, 128.3, 125.6, 124.4, 121.7,
120.3, 118.8, 116.2, 108.5, 108.1, 60.5, 52.9, 49.7, 41.2, 40.5, 33.2, 29.6, 29.4, 21.2, 21.1, 20.5,
13.9, 13.8; IR (KBr) υ: 1724 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C35H39N2O3
([M+H]+): 535.2961. Found: 535.2979.
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Ethyl
9-methyl-2'-oxo-4-(p-tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-carboxylate
(1f): white solid, 93%, 0.216 g, m.p. 219-221℃; 1H NMR (400 MHz, CDCl3) δ: 8.47 (s, 1H), 7.33
(d, J = 7.2 Hz, 2H), 7.28 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 7.6 Hz, 2H), 7.10-7.02 (m, 4H), 6.94 (d,
J = 7.6 Hz, 1H), 6.83-6.80 (m, 1H), 6.74 (d, J = 8.0 Hz, 1H), 4.37 (dd, J1 = 10.8 Hz, J2 = 5.2 Hz,
1H), 3.97-3.88 (m, 2H), 3.47 (d, J = 13.2 Hz, 1H), 3.12-3.00 (m, 4H), 2.40-2.36 (m, 4H), 1.00 (t, J
= 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 177.8, 171.5, 141.9, 141.8, 138.0, 135.9, 132.4,
131.4, 129.1, 129.1, 128.2, 125.5, 123.7, 122.8, 121.7, 120.3, 118.8, 116.1, 110.2, 108.7, 60.8,
53.0, 50.2, 41.1, 33.2, 29.6, 21.2, 13.7; IR (KBr) υ: 1728 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF)
Calcd. for C30H29N2O3 ([M+H]+): 465.2178. Found: 465.2197.
Ethyl 1'-benzyl-5'-chloro-4-(4-methoxyphenyl)-9-methyl-2'-oxo-2,3,4,9-tetrahydrospiro
1
[carbazole-1,3'-indoline]-2-carboxylate (1g): white solid, 88%, 0.266 g, m.p. 207-209℃; H
NMR (400 MHz, CDCl3) δ: 7.47 (d, J = 7.2 Hz, 2H), 7.37-7.28 (m, 5H), 7.24 d, J = 8.0 Hz, 1H),
7.11-7.08 (m, 3H), 6.86 (d, J = 6.8 Hz, 2H), 6.84-6.80 (m, 2H), 6.75 (d, J = 7.6 Hz, 1H), 5.23 (d, J
= 15.2 Hz, 1H), 4.77 (d, J = 14.8 Hz, 1H), 4.36 (dd, J1 = 11.6 Hz, J2 = 5.6 Hz, 1H), 3.98-3.83 (m,
2H), 3.81 (s, 3H), 3.44 (d, J = 12.8 Hz, 1H), 3.14-3.05 (m, 1H), 2.82 (s, 3H), 2.43-2.38 (m, 1H),
1.01 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.2, 171.2, 158.2, 142.6, 138.0, 137.0,
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135.7, 132.8, 131.7, 129.3, 129.0, 128.8, 128.3, 128.2, 128.0, 125.5, 124.0, 122.0, 120.4, 119.0,
116.8, 113.8, 110.1, 108.7, 60.8, 55.2, 52.9, 49.8, 44.9, 40.7, 33.2, 29.9, 13.9; IR (KBr) υ: 1726
(C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C37H34ClN2O4 ([M+H]+): 605.2207. Found:
605.2222.
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Ethyl 1'-benzyl-5'-chloro-9-methyl-4-(4-nitrophenyl)-2'-oxo-2,3,4,9-tetrahydrospiro
1
[carbazole-1,3'-indoline]-2-carboxylate (1h): yellow solid, 89%, 0.276 g, m.p. 190-192℃; H
NMR (400 MHz, CDCl3) δ: 8.18 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 7.2 Hz,
2H), 7.38-7.26 (m, 4H), 7.15-7.12 (m, 3H), 6.84 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 7.6 Hz, 1H), 5.11
(d, J = 15.2 Hz, 1H), 4.79 (d, J = 15.2 Hz, 1H), 4.58-4.54 (m, 1H), 3.96-3.86 (m, 2H), 3.47 (d, J =
12.0 Hz, 1H), 3.15-3.06 (m, 1H), 2.86 (m, 3H), 2.45 (dd, J1 = 13.2 Hz, J2 = 4.4 Hz, 1H), 1.00 (t, J
= 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.0, 170.7, 152.9, 146.9, 142.6, 138.1, 135.5,
132.4, 132.3, 129.3, 129.2, 128.9, 128.5, 128.1, 128.1, 124.9, 124.0, 123.9, 122.4, 119.6, 119.5,
114.7, 110.3, 109.1, 61.0, 52.4, 49.7, 45.0, 41.1, 32.5, 30.0, 13.8; IR (KBr) υ: 1725(C=O) cm-1;
MS (m/z): HRMS (ESI-TOF) Calcd. for C36H31ClN3O5 ([M+H]+): 620.1952. Found: 620.1950.
Methyl
6'-chloro-9-methyl-2'-oxo-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-carbo
1
xylate (1i): white solid, 89%, 0.209 g, m.p. 278-280℃; H NMR (400 MHz, CDCl3) δ: 8.97 (s,
1H), 7.43 (d, J = 7.2 Hz, 2H), 7.33 (t, J = 7.2 Hz, 2H), 7.28 (d, J = 6.8 Hz, 1H), 7.13-7.07 (m, 2H),
7.04-6.99 (m, 3H), 6.81 (t, J = 7.2 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 4.40 (dd, J1 = 11.2 Hz, J2 =
5.6 Hz, 1H), 3.52-3.47 (m, 4H), 3.12-3.03 (m, 4H), 2.46-2.41 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ: 178.0, 172.0, 144.7, 143.1, 138.1, 134.8, 131.8, 129.8, 128.5, 128.4, 126.7, 125.4, 124.5,
122.9, 122.1, 120.3, 119.0, 116.2, 111.1, 108.8, 52.8, 52.2, 49.9, 41.5, 33.3, 29.8; IR (KBr) υ:
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1739 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C28H24ClN2O3 ([M+H]+): 471.1475.
Found: 471.1493.
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6'-chloro-9-methyl-2'-oxo-4-(p-tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-carb
oxylate (1j): white solid, 86%, 0.208 g, m.p. over 300℃; 1H NMR (400 MHz, CDCl3) δ: 8.74 (s,
1H), 7.30 (d, J = 7.6 Hz, 2H), 7.14-7.07 (m, 4H), 7.04-6.99 (m, 3H), 6.84-6.80 (m, 1H), 6.73 (d, J
= 8.0 Hz, 1H), 4.36 (dd, J1 = 10.8 Hz, J2 = 5.6 Hz, 1H), 3.51 (s, 3H), 3.46 (d, J = 13.6 Hz, 1H),
3.09-2.99 (m, 4H), 2.40 (dd, J1 = 13.2 Hz, J2 = 5.6 Hz, 1H), 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ: 177.9, 171.9, 143.1, 141.6, 138.0, 136.1, 134.8, 131.7, 129.9, 129.2, 128.1, 125.4, 124.5,
122.8, 122.0, 120.4, 119.0, 116.4, 111.0, 108.8, 52.9, 52.1, 49.9, 41.1, 33.3, 29.7, 21.2; IR (KBr) υ:
1735(C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C29H26ClN2O3 ([M+H]+): 485.1632.
Found: 485.1645.
Ethyl
1'-butyl-5'-chloro-2'-oxo-4-(p-tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-carbo
xylate (1k): white solid, 80%, 0.216 g, m.p. 238-240℃; 1H NMR (400 MHz, CDCl3) δ: 7.37-7.33
(m, 3H), 7.14-7.13 (m, 4H), 7.08 (s, 1H), 7.04 (t, J = 8.0 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 6.82 (t,
J = 7.6 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 4.37-4.33 (m, 1H), 4.04-3.90 (m, 2H), 3.78-3.74 (m, 2H),
3.47 (d, J = 13.2 Hz, 1H), 3.26-3.16 (m, 1H), 2.58-2.53 (m, 1H), 2.35 (s, 3H), 1.76-1.70 (m, 2H),
1.47-1.42 (m, 2H), 1.08 (t, J = 7.2 Hz, 3H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ: 175.6, 171.3, 143.0, 141.5, 136.3, 136.0, 132.5, 131.2, 129.2, 129.1, 128.2, 127.7, 126.5, 124.0,
122.2, 120.2, 119.4, 115.8, 110.7, 109.4, 60.9, 50.3, 49.3, 40.5, 40.4, 33.3, 29.1, 21.1, 20.3, 13.9,
13.8; IR (KBr) υ: 1726 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C33H34ClN2O3
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([M+H]+): 541.2258. Found: 541.2264.
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Ethyl
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1'-butyl-5'-methyl-2'-oxo-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-indoline]-2-carbox
ylate (1l): white solid, 87%, 0.220 g, m.p. 227-229℃; 1H NMR (400 MHz, CDCl3) δ: 7.48 (d, J =
7.2 Hz, 2H), 7.35-7.31 (m, 2H), 7.27-7.24 (m, 1H), 7.19-7.17 (m, 2H), 7.11 (d, J = 8.4 Hz, 1H),
7.04-7.00 (m, 1H), 6.92 (brs, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.82-6.79 (m, 1H), 6.71 (d, J = 7.6 Hz,
1H), 4.41-4.37 (m, 1H), 4.02-3.88 (m, 2H), 3.79-3.73 (m, 2H), 3.51 (d, J = 12.8 Hz, 1H),
3.32-3.23 (m, 1H), 2.58-2.54 (m, 1H), 2.30 (s, 3H), 1.77-1.72 (m, 2H), 1.49-1.40 (m, 2H), 1.05 (t,
J = 7.2 Hz, 3H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.9, 171.4, 144.8,
141.9, 136.3, 132.4, 132.0, 130.6, 129.4, 128.4, 126.6, 126.5, 124.3, 122.1, 120.0, 119.3, 115.2,
110.7, 108.2, 60.7, 50.3, 49.2, 41.0, 40.3, 33.3, 29.3, 21.1, 20.3, 13.9, 13.8; IR (KBr) υ: 1725
(C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C33H34N2NaO3 ([M+Na]+): 529.2467. Found:
529.2475.
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2. General procedure for the synthesis of tetrahydrospiro[carbazole-1,3'-indoline]
derivatives 2a-2i and 3a-3g: In the nitrogen atmosphere, to a 10 mL Schlenk tube was added
indole (0.5 mmol), substituted acetophenones or cyclohexanone (1.5 mmol), and TfOH (5% mol)
and toluene (2.0 mL). The mixture was heated at 60oC for 1.5 hours. Then,
3-phenacylideneoxindoline (0.5 mmol) was added. The solution was heated at 80oC for about 12
hours. The solvent was removed at reduced pressure by rotator evaporation, the residue was
subjected to preparative column chromatography with a mixture of light petroleum and ethyl
acetate (V/V = 5:1) as eluent to give the pure product for analysis.
1'-Benzyl-9-methyl-2-(4-methylbenzoyl)-4-(4-nitrophenyl)-2,3,4,9-etrahydrospiro[carbazole-
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1,3'-indolin]-2'-one (2a): yellow solid, 73%, 0.230 g, m.p. 220-222℃; H NMR (600 MHz,
CDCl3) δ: 8.15 (d, J = 9.0 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.56 (d, J =
7.2 Hz, 2H), 7.39-7.37 (m, 2H), 7.33-7.30 (m, 1H), 7.20-7.16 (m, 4H), 7.14-7.11 (m, 3H),
6.94-6.91 (m, 1H), 6.85-6.84 (m, 1H), 6.68 (d, J = 7.8 Hz, 1H), 5.34 (d, J = 15.6 Hz, 1H), 4.91 (d,
J = 15.6 Hz, 1H), 4.70-4.67 (m, 1H), 4.59 (dd, J = 7.6 Hz, 1H), 4.41-4.37 (m, 1H), 4.02-3.88 (m,
2H), 3.79-3.73 (m, 2H), 3.51 (d, J1 = 12.6 Hz, J2 = 1.2 Hz, 1H), 3.21-3.14 (m, 1H), 2.84 (s, 3H),
2.37 (s, 3H), 2.36-2.33 (m, 1H); 13C NMR (150 MHz, CDCl3) δ: 197.9, 176.3, 153.3, 146.8, 144.4,
138.2, 136.3, 134.0, 133.4, 130.4, 129.4, 129.3, 129.2, 128.8, 128.2, 128.1, 127.8, 125.2, 123.8,
123.0, 122.8, 122.2, 119.5, 119.4, 114.3, 109.6, 109.1, 54.3, 49.5, 45.1, 41.6, 32.9, 30.0, 21.6; IR
(KBr) υ: 1716 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C41H34N3O4 ([M+H]+):
632.2549. Found: 632.2539.
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1'-Benzyl-4-(4-chlorophenyl)-9-methyl-2-(4-methylbenzoyl)-2,3,4,9-tetrahydrospiro
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[carbazole-1,3'-indolin]-2'-one (2b): white solid, 66%, 0.205 g, m.p. 234-236℃; H NMR (600
MHz, CDCl3) δ: 7.61 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H),
7.38-7.36 (m, 2H), 7.32-7.29 (m, 2H), 7.24 (s, 1H), 7.19 (d, J = 9.0 Hz, 2H), 7.17-7.14 (m, 1H),
7.12-7.09 (m, 3H), 6.92-6.90 (m, 1H), 6.86-6.82 (m, 2H), 6.76 (d, J = 7.8 Hz, 1H), 5.35 (d, J =
15.6 Hz, 1H), 4.90 (d, J = 15.6 Hz, 1H), 4.56 (dd, J1 = 12.0 Hz, J1 = 1.2 Hz, 1H), 4.54-4.51 (m,
1H), 3.17-3.11 (m, 1H), 2.82 (s, 3H), 2.36 (s, 3H), 2.32-2.30 (m, 1H); 13C NMR (150 MHz,
CDCl3) δ: 198.1, 176.4, 144.4, 144.1, 143.7, 138.1, 136.4, 133.6, 133.5, 132.1, 130.8, 129.8, 129.4,
129.0, 128.7, 128.6, 128.2, 128.1, 127.7, 125.5, 122.9, 122.6, 121.9, 119.9, 119.1, 115.4, 109.4,
108.8, 54.8, 49.5, 45.1, 41.3, 33.4, 29.8, 21.6; IR (KBr) υ: 1716 (C=O) cm-1; MS (m/z): HRMS
(ESI-TOF) Calcd. for C41H34ClN2O2 ([M+H]+): 621.2309. Found: 621.2309.
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1'-Benzyl-5'-chloro-2-(4-methylbenzoyl)-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-ind
olin]-2'-one (2c): white solid, 75%, 0.227 g, m.p. 262-264℃; 1H NMR (400 MHz, CDCl3) δ: 7.78
(d, J = 7.6 Hz, 2H), 7.52-7.48 (m, 4H), 7.42-7.36 (m, 3H), 7.33-7.29 (m, 3H), 7.26-7.23 (m, 3H),
7.16-7.14 (m, 2H), 6.87-6.83 (m, 1H), 6.79-6.74 (m, 2H), 5.28 (d, J = 15.6 Hz, 1H), 4.90 (d, J =
15.6 Hz, 1H), 4.58-4.54 (m, 2H), 3.41-3.12 (m, 1H), 2.58-2.53 (m, 1H), 2.40 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 198.0, 176.7, 144.5, 142.8, 136.5, 136.0, 132.7, 132.2, 132.1, 129.5, 129.0,
128.9, 128.5, 128.4, 128.4, 127.8, 127.7, 127.7, 126.7, 126.6, 123.4, 122.3, 120.1, 119.6, 115.5,
110.9, 110.5, 53.8, 49.2, 44.5, 41.5, 34.0, 21.6; IR (KBr) υ: 1718 (C=O) cm-1; MS (m/z): HRMS
(ESI-TOF) Calcd. for C40H31ClN2NaO2 ([M+Na]+): 629.1972. Found: 629.1925.
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1'-Butyl-5'-chloro-2-(4-methoxybenzoyl)-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-ind
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olin]-2'-one (2d): white solid, 80%, 0.235 g, m.p. 204-206℃; H NMR (600 MHz, CDCl3) δ:
7.83 (d, J = 9.0 Hz, 2H), 7.47-7.46 (m, 2H), 7.30-7.27 (m, 3H), 7.23-7.20 (m, 2H), 7.13 (d, J = 7.8
Hz, 1H), 7.08 (brs, 1H), 7.04 (t, J = 7.8 Hz, 1H), 6.91-6.90 (m, 3H), 6.83 (t, J = 7.2 Hz, 1H),
6.77-6.76 (m, 1H), 4.53-4.50 (m, 1H), 4.48 (d, J = 12.0 Hz, 1H), 3.87-3.82 (m, 5H), 3.37-3.30 (m,
1H), 2.51-2.48 (m, 1H), 1.90-1.79 (m, 2H), 1.54-1.47 (m, 2H), 1.02 (t, J = 7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ: 196.7, 176.4, 163.7, 144.6, 143.5, 136.4, 132.3, 132.2, 130.6, 129.1, 128.5,
128.4, 128.3, 127.4, 126.7, 126.6, 123.6, 122.2, 120.0, 119.5, 115.5, 114.0, 110.8, 109.5, 55.5,
53.7, 49.1, 41.5, 40.6, 33.9, 29.1, 20.4, 13.9; IR (KBr) υ: 1717 (C=O) cm-1; MS (m/z): HRMS
(ESI-TOF) Calcd. for C37H34ClN2O3 ([M+H]+): 589.2258. Found: 589.2268.
1'-Benzyl-5'-fluoro-2-(4-methylbenzoyl)-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-ind
olin]-2'-one (2e): white solid, 73%, 0.215 g, m.p. 260-262℃; 1H NMR (600 MHz, CDCl3) δ: 7.77
(d, J = 7.8 Hz, 2H), 7.52 (d, J = 7.2 Hz, 2H), 7.50 (d, J = 7.2 Hz, 2H), 7.39-7.37 (m, 2H),
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7.32-7.29 (m, 3H), 7.24-7.21 (m, 3H), 7.17 (brs, 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.07-7.04 (m, 1H),
6.91-6.87 (m, 1H), 6.86-6.83 (m, 2H), 6.78 (d, J = 7.8 Hz, 1H), 6.75-6.73 (m, 1H), 5.26 (d, J =
15.6 Hz, 1H), 4.92 (d, J = 15.6 Hz, 1H), 4.57-4.54 (m, 2H), 3.42-3.36 (m, 1H), 2.56-2.53 (m, 1H),
2.39 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 197.9, 176.8, 159.1 (J = 240.2 Hz), 144.4, 140.3,
136.5, 136.2, 132.9, 132.3, 131.9 (J = 7.8 Hz), 129.5, 128.9, 128.9, 128.5, 128.4, 128.4, 127.7,
126.7, 126.7, 122.3, 120.1, 119.6, 115.6, 115.5 (J = 23.4 Hz), 111.1, 111.0, 110.8, 110.2, 110.1,
53.7, 49.5, 44.6, 41.6, 33.9, 21.6; IR (KBr) υ: 1713 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF)
Calcd. for C40H32FN2O2 ([M+H]+): 591.2448. Found: 591.2456.
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dolin]-2'-one (2f): white solid, 81%, 0.252 g, m.p. 255-257℃; H NMR (600 MHz, CDCl3) δ:
7.87-7.86 (m, 2H), 7.50 (d, J = 7.8 Hz, 4H), 7.38-7.36 (m, 2H), 7.31-7.29 (m, 3H), 7.24-7.22 (m,
1H), 7.20 (brs, 1H), 7.16-7.13 (m, 2H), 7.07-7.04 (m, 2H), 6.93-6.91 (m, 2H), 6.86-6.83 (m, 1H),
6.78 (d, J = 7.8 Hz, 1H), 6.73 (d, J = 9.0 Hz, 1H), 5.25 (d, J = 15.6 Hz, 1H), 4.91 (d, J = 15.6 Hz,
1H), 4.56-4.53 (m, 2H), 3.85 (s, 3H), 3.43-3.37 (m, 1H), 2.57-2.54 (m, 1H); 13C NMR (150 MHz,
CDCl3) δ: 196.7, 176.7, 163.8, 144.5, 142.9, 136.5, 136.0, 132.3, 132.1, 130.7, 129.1, 128.9, 128.5,
128.4, 128.2, 127.8, 127.7, 127.7, 126.7, 126.7, 123.4, 122.3, 120.1, 119.6, 115.6, 114.0, 110.8,
110.5, 55.5, 53.6, 49.3, 44.6, 41.6, 34.1; IR (KBr) υ: 1718 (C=O) cm-1; MS (m/z): HRMS
(ESI-TOF) Calcd. for C40H32ClN2O3 ([M+H]+): 623.2101. Found: 623.2103.
1'-Benzyl-5'-chloro-2-(4-chlorobenzoyl)-4-phenyl-2,3,4,9-tetrahydrospiro[carbazole-1,3'-ind
olin]-2'-one (2g): white solid, 78%, 0.244 g, m.p. 297-299℃; 1H NMR (400 MHz, CDCl3) δ: 7.81
(d, J = 8.4 Hz, 2H), 7.51-7.48 (m, 4H), 7.43 (d, J = 8.4 Hz, 2H), 7.40-7.37 (m, 2H), 7.34-7.29 (m,
3H), 7.24-7.22 (m, 1H), 7.19-7.15 (m, 3H), 7.09-7.05 (m, 2H), 6.87-6.84 (m, 1H), 6.79-6.75 (m,
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2H), 5.23 (d, J = 15.6 Hz, 1H), 4.94 (d, J = 15.6 Hz, 1H), 4.57-4.50 (m, 2H), 3.43-3.33 (m, 1H),
2.54-2.49 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 197.2, 176.3, 144.2, 142.8, 140.0, 136.4, 135.8,
133.5, 131.8, 131.8, 129.7, 129.2, 129.1, 128.9, 128.5, 128.3, 128.0, 127.8, 127.6, 126.8, 126.6,
123.3, 122.4, 120.1, 119.7, 115.5, 110.8, 110.6, 53.7, 49.1, 44.5, 41.4, 33.7; IR (KBr) υ: 1723
(C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C39H29Cl2N2O2 ([M+H]+): 627.1606. Found:
627.1593.
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1'-Benzyl-5'-chloro-2-(4-methylbenzoyl)-4-(p-tolyl)-2,3,4,9-tetrahydrospiro[carbazole-1,3'-in
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dolin]-2'-one (2h): white solid, 69%, 0.214 g, m.p. 259-261℃; H NMR (600 MHz, CDCl3) δ:
7.77 (d, J = 7.8 Hz, 2H), 7.50 (d, J = 7.2 Hz, 2H), 7.39-7.36 (m, 4H), 7.32-7.30 (m, 1H), 7.26-7.25
(m, 1H), 7.24 (brs, 1H), 7.17-7.13 (m, 3H), 7.10 (d, J = 7.8 Hz, 2H), 7.07-7.05 (m, 2H), 6.87-6.84
(m, 1H), 6.82-6.81 (m, 1H), 6.73 (d, J = 9.0 Hz, 1H), 5.25 (d, J = 15.6 Hz, 1H), 4.92 (d, J = 16.2
Hz, 1H), 4.55-4.50 (m, 2H), 3.38-3.31 (m, 1H), 2.54-2.50 (m, 1H), 2.39 (s, 3H), 2.32 (s, 3H); 13
C
NMR (150 MHz, CDCl3) δ: 198.0, 176.6, 144.4, 142.9, 141.3, 136.5, 136.1, 136.0, 132.8, 132.1,
132.1, 129.5, 129.2, 129.1, 128.9, 128.4, 128.2, 127.9, 127.7, 127.7, 126.8, 123.4, 122.3, 120.2,
119.6, 115.8, 110.8, 110.5, 53.9, 49.2, 44.6, 41.1, 34.0, 26.9, 21.6; IR (KBr) υ: 1719 (C=O) cm-1;
MS (m/z): HRMS (ESI-TOF) Calcd. for C41H34ClN2O2 ([M+H]+): 621.2309. Found: 621.2308.
1'-Benzyl-5'-chloro-4-(4-chlorophenyl)-2-(4-methylbenzoyl)-2,3,4,9-tetrahydrospiro
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[carbazole-1,3'-indolin]-2'-one (2i): white solid, 73%, 0.234 g, m.p. 247-249℃; H NMR (600
MHz, CDCl3) δ: 7.77 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 7.2 Hz, 2H), 7.43 (d, J = 7.2 Hz, 2H),
7.39-7.37 (m, 2H), 7.33-7.31 (m, 1H), 7.28-7.26 (m, 4H), 7.20 (brs, 1H), 7.17-7.15 (m, 2H),
7.09-7.07 (m, 2H), 6.88 (t, J = 7.2 Hz, 1H), 6.79-6.77 (m, 1H), 6.75 (d, J = 8.4 Hz, 1H), 5.24 (d, J
= 15.6 Hz, 1H), 4.92 (d, J = 15.6 Hz, 1H), 4.56-4.52 (m, 2H), 3.35-3.29 (m, 1H), 2.54-2.50 (m,
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1H), 2.40 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 197.7, 176.5, 144.5, 143.1, 142.8, 136.4, 135.9,
132.7, 132.3, 131.8, 129.7, 129.5, 129.2, 128.9, 128.7, 128.4, 127.9, 127.8, 127.6, 126.5, 123.4,
122.5, 119.9, 119.8, 115.0, 110.9, 110.6, 53.6, 49.2, 44.6, 40.8, 33.7, 21.6; IR (KBr) υ: 1718 (C=O)
cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for C40H31Cl2N2O2 ([M+H]+): 641.1763. Found:
641.1752.
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1'-Benzyl-4-(4-methylbenzoyl)-2,3,3a,4,6,10c-hexahydro-1H-spiro[cyclopenta[c]carbazole-5,
3'-indolin]-2'-one (3a): white solid, 70%, 0.187 g, m.p. 286-288℃; 1H NMR (400 MHz, CDCl3)
δ: 7.77 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 6.8 Hz, 1H), 7.51 (d, J = 7.2 Hz, 2H), 7.37-7.33 (m, 2H),
7.29 (d, J = 6.8 Hz, 1H), 7.25-7.23 (m, 2H), 7.16-7.10 (m, 4H), 7.03 (d, J = 7.2 Hz, 1H), 7.00 (s,
1H), 6.90-6.86 (m, 1H), 6.77 (d, J = 7.6 Hz, 1H), 5.27 (d, J = 15.2 Hz, 1H), 4.87 (d, J = 15.6 Hz,
1H), 4.72-4.71 (m, 1H), 3.86-3.81 (m, 1H), 3.08-3.00 (m, 1H), 2.68-2.61 (m, 1H), 2.39 (s, 3H),
2.08-2.01 (m, 1H), 1.92-1.90 (m, 1H), 1.48-1.39 (m, 2H), 1.26 (brs, 1H); 13C NMR (100 MHz,
CDCl3) δ: 198.7, 177.0, 143.9, 143.9, 136.7, 136.6, 133.9, 131.4, 130.9, 129.4, 128.9, 128.7, 128.2,
127.7, 127.5, 127.0, 122.8, 122.3, 122.2, 119.3, 119.2, 116.3, 110.9, 109.3, 49.6, 44.4, 41.2, 35.7,
34.1, 29.6, 28.1, 26.3, 21.6; IR (KBr) υ: 1716 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd.
for C37H33N2O2 ([M+H]+): 537.2542. Found: 537.2533.
1'-Benzyl-5'-chloro-5-(4-methylbenzoyl)-1,2,3,4,4a,5,6a,7,11b,11c-decahydrospiro
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[benzo[c]carbazole-6,3'-indolin]-2'-one (3b): white solid, 62%, 0.181 g, m.p. 259-261℃; H
NMR (600 MHz, CDCl3) δ: 7.79-7.64 (m, 3H), 7.58 (d, J = 7.8 Hz, 2H), 7.40 (t, J = 7.2 Hz, 2H),
7.35-7.33 (m, 1H), 7.28 (d, J = 7.8 Hz, 2H), 7.13-7.06 (m, 5H), 6.91 (d, J = 1.8 Hz, 1H), 6.73 (d, J
= 8.4 Hz, 1H), 5.31 (d, J = 15.0 Hz, 1H), 4.89 (d, J = 15.0 Hz, 1H), 4.48 (d, J = 1.8 Hz, 1H), 3.74
(brs, 1H), 3.04 (d, J = 13.8 Hz, 1H), 2.68-2.64 (m, 2H), 2.43 (s, 3H), 1.66 (d, J = 12.0 Hz, 1H),
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1.51 (d, J = 12.0 Hz, 1H), 1.29 (m, 3H), 1.11-1.05 (m, 1H); 13C NMR (150 MHz, CDCl3) δ: 198.2,
176.8, 144.1, 141.6, 137.0, 136.5, 135.1, 133.4, 131.9, 129.5, 128.9, 128.7, 128.4, 128.0, 127.9,
127.7, 126.5, 123.5, 122.1, 120.4, 119.6, 112.8, 111.0, 110.2, 60.5, 50.1, 44.7, 41.8, 36.8, 30.0,
26.3, 23.9, 21.6, 21.2; IR (KBr) υ: 1719 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for
C38H33ClN2NaO2 ([M+Na]+): 607.2128. Found: 607.2114.
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1'-Benzyl-5'-chloro-7-methyl-5-(4-methylbenzoyl)-1,2,3,4,4a,5,7,11c-octahydrospiro[benzo
[c]carbazole-6,3'-indolin]-2'-one (3c): white solid, 48%, 0.143 g, m.p. 281-283℃; 1H NMR (400
MHz, CDCl3) δ: 7.82 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.25-7.22 (m, 3H), 7.19-7.15
(m, 4H), 7.12-7.09 (m, 3H), 6.98 (d, J = 7.6 Hz, 2H), 6.67 (d, J = 7.6 Hz, 1H), 4.57 (d, J = 15.2 Hz,
1H), 4.49-4.41 (m, 2H), 3.07-2.98 (m, 2H), 2.90 (s, 3H), 2.39 (s, 3H), 2.33-2.25 (m, 1H),
1.97-1.94 (m, 1H), 1.77-1.74 (m, 1H), 1.65-1.59 (m, 2H), 1.54-1.47 (m, 2H), 1.15-1.06 (m, 1H);
13C NMR (100 MHz, CDCl3) δ: 198.4, 177.1, 144.3, 140.2, 137.9, 135.9, 134.7, 132.1, 130.2,
129.3, 128.6, 128.5, 128.4, 127.7, 127.6, 126.5, 125.5, 121.7, 120.6, 118.9, 116.3, 110.0, 108.9,
54.5, 53.7, 44.3, 42.1, 41.2, 32.0, 29.9, 29.1, 26.4, 26.2, 21.6; IR (KBr) υ: 1712 (C=O) cm-1; MS
(m/z): HRMS (ESI-TOF) Calcd. for C39H35ClN2NaO2 ([M+Na]+): 621.2285. Found: 621.2272.
5-Benzoyl-1'-benzyl-3-(tert-butyl)-5'-chloro-1,2,3,4,4a,5,7,11c-octahydrospiro[benzo
[c]carbazole-6,3'-indolin]-2'-one (3d): white solid, 72%, 0.225 g, m.p. 249-251℃; 1H NMR (400
MHz, CDCl3) δ: 7.84-7.80 (m, 3H), 7.58-7.56 (m, 3H), 7.50-7.47 (m, 2H), 7.42-7.38 (m, 2H),
7.34-7.31 (m, 1H), 7.13-7.05 (m, 5H,), 6.91 (s, 1H), 6.67 (d, J = 8.0 Hz, 1H), 5.27 (d, J = 15.2 Hz,
1H), 4.97 (d, J = 15.6 Hz, 1H), 4.53 (s, 1H), 3.69 (s, 1H), 3.10 (d, J = 13.2 Hz, 1H), 2.69 (d, J =
11.2 Hz, 1H), 2.51-2.42 (m, 1H), 1.84-1.77 (m, 1H), 1.62-1.59 (m, 1H), 1.31-1.28 (m, 1H),
1.06-0.96 (m, 1H), 0.88-0.82 (m, 1H), 0.73 (s, 9H, 3CH); 13C NMR (100 MHz, CDCl3) δ: 199.1,
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176.3, 141.7, 137.0, 136.4, 136.3, 135.0, 132.9, 132.0, 128.9, 128.7, 128.6, 128.0, 127.8, 127.7,
127.6, 126.5, 123.3, 122.0, 120.3, 119.5, 112.7, 111.1, 110.3, 60.5, 50.0, 48.9, 44.7, 42.0, 36.2,
32.5, 30.0, 27.5, 25.5, 22.4; IR (KBr) υ: 1719 (C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd.
for C41H40ClN2O2 ([M+H]+): 627.2778. Found: 627.2769.
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Ethyl 1'-benzyl-5'-chloro-6-methyl-2'-oxo-2,3,3a,4,6,10c-hexahydro-1H-spiro[cyclopenta[c]
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carbazole-5,3'-indoline]-4-carboxylate (3e): white solid, 71%, 0.191 g, m.p. 248-250℃; H
NMR (400 MHz, CDCl3) δ: 7.60 (d, J = 7.6 Hz, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.38-7.32 (m, 3H),
7.21-7.17 (m, 2H), 7.12-7.08 (m, 2H), 7.05 (s, 1H), 6.84 (d, J = 8.4 Hz, 1H), 4.99 (d, J = 15.2 Hz,
1H), 4.92 (d, J = 15.2 Hz, 1H), 3.81-3.77 (m, 1H), 3.72-3.68 (m, 1H), 3.50-3.41 (m, 2H),
3.06-2.99 (m, 1H), 2.95 (s, 3H), 2.52-2.45 (m, 2H), 2.17-2.09 (m, 1H), 1.98-1.92 (m, 1H),
1.85-1.77 (m, 1H), 1.71-1.63 (m, 1H), 1.47-1.39 (m, 1H), 0.89 (t, J = 6.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 176.8, 170.7, 140.7, 137.9, 135.1, 130.8, 129.6, 128.8, 128.7, 128.4, 128.3, 128.1,
126.3, 126.1, 122.2, 119.0, 119.0, 116.0, 109.9, 108.9, 60.5, 54.0, 52.3, 45.0, 37.2, 36.9, 32.7, 30.5,
29.4, 24.9, 13.8; IR (KBr) υ: 1720(C=O) cm-1; MS (m/z): HRMS (ESI-TOF) Calcd. for
C33H32ClN2O3 ([M+H]+): 539.2101. Found: 539.2088.
Ethyl 1'-benzyl-5'-chloro-7-methyl-2'-oxo-1,2,3,4,4a,5,7,11c-octahydrospiro[benzo[c]
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carbazole-6,3'-indoline]-5-carboxylate (3f): white solid, 66%, 0.182 g, m.p. 255-257℃; H
NMR (400 MHz, CDCl3) δ: 7.80 (d, J = 8.0 Hz, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.36-7.31 (m, 4H),
7.27-7.25 (m, 1H), 7.18-7.14 (m, 1H), 7.10-7.04 (m, 2H), 6.91 (d, J = 8.0 Hz, 1H), 5.04 (d, J =
14.8 Hz, 1H), 4.86 (d, J = 15.2 Hz, 1H), 3.79-3.70 (m, 3H), 3.53 (s, 1H), 3.04-2.96 (m, 1H), 2.77
(s, 3H), 2.63-2.57 (m, 1H), 2.09 (d, J = 10.0 Hz, 1H), 1.93-1.87 (m, 1H), 1.75-1.70 (m, 2H),
1.64-1.61 (m, 1H), 1.46-1.35 (m, 2H), 0.83 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
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