Unusual Formation of Cyclopenta[ b]indoles from 3-Indolylmethanols and Alkynes

Article abstract of DOI:10.1021/acs.joc.8b03027

Acid-promoted synthesis of cyclopenta[b]indole frameworks from 3-indolylmethanols and alkynes has been reported. The overall transformation represents a formal [3 + 2] annulation via rearrangement. This protocol showed good generality for the carbinol substrates as well as alkynes and allowed the generation of structurally diverse cyclopenta[b]indoles. Terminal alkynes, dialkyl-substituted internal alkynes, and alkynes with electron-deficient substituents were found to be not suitable for this transformation. Similarly, N-Ts and N-Boc groups were compatible with reaction conditions, whereas N-Ac and N-Tf failed to undergo this reaction. Isolation of vinyl chloride intermediate suggested the involvement of a vinylic carbocation intermediate. A mechanism has been proposed involving a ring-opening-ring-closing cascade followed by a 1,3-indole migration process via a spirocyclobutene intermediate.

Full text of DOI:10.1021/acs.joc.8b03027

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Article
Unusual formation of Cyclopenta[b]indoles
from 3-Indolylmethanols and Alkynes
Soniya Gandhi, and Beeraiah Baire
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03027 • Publication Date (Web): 11 Mar 2019
Downloaded from http://pubs.acs.org on March 11, 2019
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Unusual formation of Cyclopenta[b]indoles from 3-Indolylmethanols and Alkynes
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Soniya Gandhi and Beeraiah Baire*
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Department of Chemistry, Indian Institute of Technology Madras, Chennai-600036, Tamilnadu, India.
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ABSTRACT: An acid promoted, synthesis of cyclopenta[b]indole frameworks from 3-indolylmethanols and alkynes has been
reported. The overall transformation represents a formal [3+2] annulation via rearrangement. This protocol showed good generality
for the carbinol substrates as well as alkynes and allowed the generation of structurally diverse cyclopenta[b]indoles. Terminal
alkynes, dialkyl substituted internal alkynes and alkynes with electron deficient substituents were found to be not suitable for this
transformation. Similarly, N-Ts and N-Boc groups were compatible with reaction conditions, whereas N-Ac, and N-Tf failed to
undergo this reaction. Isolation of vinyl chloride intermediate suggested the involvement of a vinylic carbocation intermediate. A
mechanism has been proposed involving a ring opening-ring closing cascade followed by a 1,3-indole migration process, via a
spirocyclobutene intermediate.
formal
Ar1
[2+2]
HO
N
Ar2
Ar2
R
R
cyloaddition
R
1,3-indole
migration-
cyclization
Ar1
Ar2
Ar1
N
R1
FeCl3, 1,2-DCE
55 °C
R1
N
R1
formal [3+2] annulation
via rearrangement
INTRODUCTION
Indole is an important heterocyclic system present in many bioactive natural products and drugs.1 Among several of its
derivatives, cyclopenta[b]indoles constitute an important class by exhibiting diverse biological and pharmaceutical properties.2 They
are also part of various bioactive natural products (Figure 1).3 Accordingly, many synthetic approaches have been developed for the
synthesis of these privileged structural units.4 Among various methods available, a formal [3+2] annulation between 3-
indolylmethanols and olefins is an atom economic strategy,5 for the generation of 1,2,3-trisubstituted cyclopenta[b]indole units.
However, owing to their importance in various fields, development of an economic, efficient and diversity oriented approaches are
still in high demand and attract the attention of synthetic organic chemists. 3-Indolylmethanols are important building blocks for the
synthesis of indole based structurally divergent scaffolds such as cyclopenta[b]indoles, bisindolylmethanes, and carboline
derivatives etc.6
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H
MeO2C
N
F
Me
H
NC
H
N
Cl
CO2H
Cl
H
N
MeO2S
7
8
9
HN
N
H
H
Cl
N
H
Cl
spiroindimicin B
N
H
yeuhchukene
fischerindole L
MK-0524
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Figure 1. Representative examples of (1,2,3-trisubstituted)cyclopenta[b]indole natural products and bioactive molecules
To the best of our knowledge, there was no strategy reported, for the synthesis of 1,2,3-trisubstituted cyclopenta[b]indoles via a
formal [3+2] annulation between indole-carbinols (2- or 3-) and alkynes. Here in we report the discovery and development of such
an unprecedented strategy for the synthesis of cyclopenta[b]indoles from 3-indolylmethanols and alkynes under acidic conditions.
According to our initial design (Scheme 1), the indole-3-carbinol 1 can undergo a dehydrative formal [3+2] cycloaddition with a
disubstituted alkyne 2 through C2 and C–carbons to give the cyclopenta[b]indole 3.
Scheme 1. Initial design for the cyclopenta[b]indoles from 3-indolylmethanols and alkynes
R
R2
R1
HO
R1
Lewis or
R1
R
Bronsted acid
R2
+
R
-H2O
N
R3
N
R3
N
R3
R2
formal
2
[3+2] annulation
rearranged
compound
1
3
cyclopenta[b]indole
4
RESULTS AND DISCUSSION
Our investigation began with the reaction between indole-3-carbinol 1a and diphenylacetylene 2a (Table 1). Treatment of a 1,2-
dichloroethane (1,2-DCE) solution of 1a (1 equiv) and 2a (2 equiv) with TfOH (2 equiv) gave the cyclopenta[b]indole 4aa in 35%
yield as the sole product (entry 1, Table 1) after 15 min at 0 °C. There was no detection of any traces of isomeric compounds.
Subsequently, we focused to improve the yield of the product 4aa, by performing an optimization study. Accordingly, various
Brønsted acids were screened against different solvents, temperatures and equivalents. Performing the reaction in presence of
pTSA (2 equiv., entry 2) resulted poor yield (10%) of the product 4aa. On the other hand MsOH (entry 3) gave an improved yield for
4aa (45%). Next, we screened various Lewis acids such as BF3.Et2O, BiCl3, AlCl3 and FeCl3 (entries 4-7). Among the four Lewis
acids (2 equiv) screened, FeCl3 (entry 7) found to be highly suitable for the condensation between 1a and 2a. This resulted in 72%
yield of the cyclopenta[b]indole 4aa within 2.5 h at 0 °C. Increase in temperature from 0 °C to rt to 55 °C (entries 8 and 9) resulted in
the formation of 4aa in 70% and 73% respective yields with reduced reaction times (1 h and 15 min). Further increase to 80 °C
(entry 10) gave reduced yield (65%) of 4aa. Having found the best acid (FeCl3), and temperature (0 °C or 55 °C) we turned our
attention to study this transformation under catalytic conditions. Performing the reaction with 1.3 and 0.5 equivalents (entries 11 and
12) of FeCl3 in 1,2-DCE at 55 °C gave 4aa in 72% yield within 15 min.7 Further decrease to 0.2 equivalents (entry 13) resulted in
reduced yield (60%) of 4aa. When other solvents like toluene, dichloromethane and 1,2-dichlorobenzene (entries 14-16) were
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employed in place of 1,2-DCE, there was no improvement observed in the yield of product 4aa. There was no reaction took place in
ethyl acetate and acetonitrile solvents. It is noteworthy here that, only chlorinated solvents were found to be suitable for this
transformation. When we performed the reaction with 1 equiv. of alkyne 2a (entry 17), 4aa was isolated in 33% yield as the minor
product along with 53% of another cyclopenta[b]indole derivative 5a. The formation of 5a is already precedent in the literature via
the homodimerization of the corresponding 3-vinylindole 6.
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Table 1. Reaction optimization study
Me
Me
acid
Ph
Ph
Ph
Ph
solvent
OH
temperature
Me
N
Ts
N
N
Ts
Ph
Ph
2a
Ts
1aa
(2 equiv.)
4aa
solvent
3aa
, not observed
entry
1
acid
equiv
2
T (°C)
time (h)
0.25
1.5
yield (%)b
35
TfOH
pTSA
MsOH
BF3.Et2O
BiCl3
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
toluene
0
0
2
2
10
3
2
0
0.5
43
4
2
0
0.25
13
59
5
2
0
40
6
AlCl3
2
0
24
12
7
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
aq. HCl
FeCl3
FeCl3
FeCl3
2
0
2.5
72
8
2
RT
55
80
55
55
55
55
55
55
55
55
55
55
55
1
70
9
2
0.25
10 min
0.25
0.25
3
73
10
11
12
13
14
15
16
17c
18
19f
20g
21h
2
65
1.3
0.5
0.2
0.5
0.5
0.5
0.5
1.5
0.5
0.5
0.5
72
72
60
2
10
CH2Cl2
5 min
10 min
20 min
6
50
1,2-DCB
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
60
33d
e
24
NR
5i
24
0.25
65
FeCl3
Me
Me2N
NMe2
N
N
Ts
Ts
proton sponge
possible complex
6
(8%)
5a
(53%)
N
Ts
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a
b
c
all the reactions were carried out with 0.1 mmol of 1a; yields are after chromatographic purification; 1 equiv. of alkyne 2a
4
5
6
was used; d along with 4aa (33%) another cyclopenta[b]indole 5a was isolated (53%); e 8% of the dehydrated product, 3-vinylindole
f
g
h
6 was isolated along with a complex mixture; 1 equiv. of proton sponge was used; 0.5 equiv. of proton sponge was used; 0.1
7
8
equiv. of proton sponge was used; i 10% conversion.
9
Practically, FeCl3 (0.5 equiv.) can undergo hydrolysis under reaction conditions, to produce the HCl (1.5 equiv.), and this can
also possibly promote the observed formal [3+2] annulation reaction. To test this hypothesis, we also performed the reaction with aq.
HCl [1.5 equiv., 35% (v/v)]. But the reaction did not result in the formation of cyclopenta[b]indole 4aa instead gave the 3-vinylindole
6 (8%) along unidentifiable complex mixture (entry 18). This observation clearly rules out the involvement of HCl. Furthermore, we
have also performed the reaction in the presence of a proton sponge, i.e., 1,8-bis(dimethylamino)naphthalene. In presence of 1
equiv. of sponge (entry 19), there was no reaction observed, whereas 0.5 equiv. (entry 20), resulted in 10% of conversion and 5% of
4aa after 24 h at 55 °C. Surprisingly, in the presence of 0.1 equiv. of sponge (entry 21), reaction was completed in 15 min, to yield
65% yield of 4aa. From these observations, we propose that, there may not be any HCl formation during the reaction. The failure of
the reaction with more than 0.5 equiv. of sponge might be due to the formation of a Lewis acid-base complex between sponge and
FeCl3. Therefore, the optimized condition for the formal [3+2] annulation between 3-indolylmethanols and alkynes to generate the
cyclopenta[b]indoles found to be FeCl3 (0.5 equiv), 1,2-DCE, 55 °C and acetylene derivative (2 equiv).8
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Since at this stage we were not indisputable between two possible isomeric structures i.e., cyclopenta[b]indoles 4aa and 3aa,
we performed the reaction with a 2-indolylmethanol 7a (eq. 1). This substrate 7a can only undergo a formal [3+2] cycloaddition to
give the corresponding product 4aa, which is the rearranged product from indole-3-carbinol 1a. Surprisingly, the product isolated
(27%) from this reaction was exactly matching with that obtained from the indole-3-carbinol 1a. This result suggests that, the
reaction between 1a and diphenylacetylene 2a might involve a rearrangement during the proposed formal [3+2] annulation (see
Scheme 6 for proposed mechanism).
Ph
Ph
2a
(2 equiv)
Me
OH
(via direct
FeCl3 (0.5 equiv)
1,2-DCE, 55 °C
10 min, 27%
(eq. 1)
Me
[3+2] annulation)
N
N
Ts
Ts
4aa
7a
After finding the optimized conditions and confirming the product as cyclopenta[b]indole 4aa, next we performed a scope study
to evaluate the substrate generality. Initially, the 3-indolylmethanols 1b-f possessing variable alkyl groups at carbinol centre
(Scheme 2) were subjected to optimized reaction condition [FeCl3 (0.5 equiv), 1,2-DCE, 55 °C, and 2a (2 equiv.)]. The reaction
found to be feasible and clean with various alkyl groups such as n-butyl, n-hexyl, n-octyl and n-decyl 1b-f to afford the
corresponding cyclopenta[b]indoles 4ba-fa in moderate yields (50-71%) with short reaction times (10-15 min). 4-Bromo-, 5-bromo-,
6-bromo- and 5-phenyl- substituted 3-indolylmethanols 1g-j also underwent the formal [3+2] annulation to generate the
corresponding cyclopenta[b]indole derivatives 4ga-ja in good yields (63-70%). Further, presence of the cyclopenta[b]indole
framework was unambiguously confirmed by a single crystal X-ray diffraction analysis for the compound 4ba (Scheme 2).9
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Scheme 2. a) Scope study for 3-indolylmethanols; b) The ORTEP diagram of 4ba (CCDC 1820473)
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Me
Me
Me
( )5
Me
( )7
( )3
N
Ts
N
Ts
N
Ts
N
Ts
4ba
4ca
4ea
, 15 min, 61%
, 10 min, 71%
, 10 min, 50%
4da
, 10 min, 60%
Br
Br
Me
( )9
Me
N
Me
N
Me
N
Ts
Br
N
Ts
Ts
Ts
4ia
, 40 min, 63%
4fa
, 12 min, 58%
4ga
, 20 min, 70%
4ha
, 15 min, 65%
Me
N
Ts
4ba
4ja
, 20 min, 70%
Reaction conditions: 1b-j (1 equiv), 2a (2 equiv), FeCl3 (0.5 equiv.), 1,2-DCE, 55 °C
Next, unsymmetrical acetylene derivatives were employed to generate a structural library of cyclopenta[b]indoles (Scheme 3).
The unsymmetrical diarylacetylenes (with electron rich aryl and phenyl group on both ends) 2b-c upon reaction with 1a under
standard reaction conditions, always gave single regioisomeric cyclopenta[b]indoles 4ab-ac in good yields. In none of the cases,
other regioisomeric cyclopenta[b]indoles were observed. The alkynes with m-CF3 and p-Ph substituents 2d and 2e, gave
corresponding products 4ad (74%, 10 min) and 4ae (75%, 12 min) as single regio-isomeric products. On the other hand, p-F alkyne
2f gave a (1:0.68) mixture of 4af:4af’ in 50% yield. To get the evidence for the proposed regio-chemical outcome, we have
performed a H1-H1 2D NOESY (Nuclear Overhauser Spectroscopy) experiment of compound 4ad (Scheme 3). the observed
correlations between two ortho-protons on CF3-Ar ring vs. allyl proton as well as allylic methyl group supported the proposed
regiochemistry for all the compounds derived from unsymmetrical diarylalkynes (see Supporting Information for spectroscopic data).
Additionally, a single crystal X-ray diffraction analysis for the compound 4ab (Scheme 3) has also confirmed the regiochemistry in
the cyclopenta[b]indole.10
The arylalkylacetylenes 2g-k also resulted in the exclusive formation of single isomers 4ag-4ak in excellent yields (70-72%).
This regiochemistry was further confirmed by H1-H1 2D NOESY (Nuclear Overhauser Spectroscopy) experiment of compound 4ak.
Here we observed correlation between olefin methyl protons vs. allyl protons and also between olefin methyl protons vs. allyl methyl
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protons. This assignment further confirms the proposed regiochemistry for all the compounds present in Scheme 3 (see Supporting
Information for spectrum).
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8
Scheme 3. Scope study for unsymmetrical diarylacetylenes, ORTEP diagram for compound 4ab and NOE correlations for
compounds 4ad and 4ak to confirm the regio-chemical outcome of the products
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R2
R1
Me
2b-k
OH
R1
R2
R1
R2
(2 equiv)
(and/or)
(4/4')
Me
Me
N
Ts
N
Ts
N
FeCl3 (0.5 equiv)
1,2-DCE, 55 °C
(if R1 is electron-rich than R2
Ts
(none
(exclusive
or Major)
)
1a
or Minor)
Me
Me
Me
Me
Me
N
Ts
Me
N
Ts
4ac,
4ab
7 min, 75%
4ab
, 15 min, 50%
CF3
Ph
H
CF3
N
H
H
Me
Me
Ts
N
N
Ts
Me
, 10 min, 74%
Ts
NOE correlations
4ad
observed for
4ad
4ae
9 min, 75% (1:0.33)
Me
F
F
Me
( )3
Me
( )3
Me
Me
Me
Me
N
N
Ts
N
N
Ts
Ts
Ts
, 10 min, 72%
4af'
4ag
4ah
7 min, 65% (1:0.68)
Me
, 10 min, 72%
4af
Me
( )7
Me
( )7
Me
Me
Me
H
N
Me
Me
N
Ts
Me
N
N
Ts
Ts
, 7 min, 72%
NOE correlations
Ts
, 10 min, 70%
4ak
observed for
4ai
4ak
, 10 min, 71%
4aj
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We also studied various unsymmetrical diarylalkynes 2l-m, which carries p-NO2 and p-COMe group on one of the arene, and
an electron deficient symmetrical disubstituted alkyne 2n (dimethyl acetylenedicarboxylate) under standard reaction conditions with
1a (Scheme 4). In all cases, only the corresponding homodimerized cyclopenta[b]indole 5a was isolated in good yields (50-65%)
after 10-30 min. instead of the expected products 4al-an. 3-Indolylmethanols possessing various N-protecting groups 1k-m were
also screened against the alkyne 2a. In case of N-Boc 1k, the expected product 4ka was isolated in 30% yield, whereas in case of
N-Tf substrate 1l, a complex mixture was generated. The N-Ac 5m gave the corresponding homodimerized product 5m in 65% yield
after 5 h. When we employed a terminal alkyne, such as phenylacetylene against compound 1a, a complex mixture consisting of
multiple compounds has been isolated.
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Scheme 4. Employing various electron deficient alkynes, terminal alkyne and N-protecting groups on 3-indolylmethanols
Me
R1/2
R1
(2 equiv.)
R2
Me
R2/1
OH
FeCl3 (0.5 equiv.)
1,2-DCE, 55 °C
10-30 min
N
N
Ts
Ts
Me
N
4al-am
N
not observed
5a
(50-65%)
Ts
Ts
1a
Ph
Ph
COCH3
NO2
MeO2C
CO2Me
2l
2m
2n
Ph
(2 equiv.)
FeCl3
Ph
Me
1k
4ka
; R = BOC; 30 min;
, 30%
Me
OH
1l
1m
; R = Tf; 24 h; complex mixture
N
Ac
5m
; R = Ac; 5 h,
Ph
, 65%
(0.5 equiv.)
1,2-DCE
55 °C
N
R
N
Ph
5m
Ac
N
4ka
Boc
Me
Ph
(2 equiv.)
H
Me
OH
FeCl3 (0.5 equiv.)
1,2-DCE, 55 °C
30 min
Complex Mixture
N
Ts
1a
We next screened various dialkylacetylenes such as dimethylacetylene, dibutylacetylene and 5-tetradecyne. When we used
dimethylacetylene as alkyne partner with 1a under standard reaction conditions (Scheme 5), a (1:1) E/Z mixture of new compound,
i.e., vinyl chloride 9 was obtained instead of the corresponding cyclopenta[b]indole. Formation of 9 can be explained via trapping of
the initially formed vinyl carbocation 8 by the chloride ion (from FeCl3). In addition to spectroscopic data, the structure of 9 was
unambiguously confirmed by a single crystal X-ray diffraction analysis.11 Other dialkylacetylenes failed to undergo a clean reaction
and gave an unidentifiable mixture of products. We also employed 2-methyl-indole-3-carbinol 1a' under standard reaction conditions.
This substrate 1a' after 5 min at 50 °C, gave a (1:0.25) E:Z mixture of vinyl chlorides 10 in 65% yield. No other product was
identified in this reaction.
Based on the observations made from eq. 1, and scheme 5, we proposed a possible mechanistic pathway (Scheme 6). In
presence of acid, the reaction between indole-3-carbinol 1 and an alkyne 2 undergo a regioselective nucleophilic substitution to give
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the vinylic carbocation 11 (possibly via an SN1 type nucleophilic substitution).12 This 11 can be trapped in an intramolecular fashion
by the C3-carbon of the indole to give a spiro-cyclobutene intermediate 12 in a net dehydrative [2+2] cycloaddition process from 1
and 2. Next, the spiro-cyclobutene 12 can undergo a ring opening-rearrangement13 to give the 1,4-pentadienyl cation 13/13’, via a
1,3-indole migration. Further, cyclization (Nazarov like) of 13/13’ followed by aromatization of resultant tricyclic carbocation 14/14’
gives the cyclopenta[b]indole product 4. On the other hand, the spiro-cyclobutene 12 can also involve a 1,2-alkyl migration14 to
directly produce 14/14’.
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Scheme 5. a) Use of dialkylacetylenes and 2-methylindole-3-carbinol; b) The ORTEP diagram of 9 (CCDC 1857221)
Me
Me
Me
Me
(2 equiv.)
Me
OH
Me
Me
Me
Cl
[FeCl3(OH)]
55%
FeCl3 (0.5 equiv.)
1,2-DCE, 55 °C
5 min
N
Me
N
Ts
Ts
8
1a
9
(1:1; E/Z)
Bu
R
(2 equiv.)
FeCl3 (0.5 equiv.)
1,2-DCE, 55 °C
(R = n-Bu, n-octyl)
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Complex mixture
Cl
2a
(2 equiv.)
HO
Me
Ph
Me
Me
FeCl3 (50 mol%)
1,2-DCE, 50 °C
5 min, 65%
Ph
Me
N
Ts
N
Ts
10
1a'
(E:Z = 1:0.25)
Scheme 6. Possible mechanistic pathway
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R1
HO
N
R2
R
rearranged
cyclopenta[b]indoles
Lewis or
4
R
Bronsted Acid
R1
N
R1
R2
R1
1
7
8
9
R1
R2
aromatization
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FeCl3
R1
R1
R2
R2
R2
R
R
R
H
N
R1
H
N
R1
R1
14
14'
N
R1
11
1,2-alkyl shift
cyclization
R2
R1
R2
R1
R2
R
R1
ring opening
R
R
1,3-indole migration
N
R1
spirocyclobutene
N
R1
12
N
R1
13
13'
Scheme 7. Testing the primary- and tertiary- 3-indolylmethanols under standard conditions
2a
(2 equiv)
OH
FeCl3 (0.5 equiv)
1,2-DCE, 55 oC
N
Ts
TsN
NTs
15
10 h, 31%
17
2a
Me
Me
Me
Me
(2 equiv)
Me
OH
[3+2]
cycloaddition
FeCl3
(0.5 equiv)
1,2-DCE, rt
2 min, 98%
N
N
Me
N
Ts
Ts
Ts
NTs
16
18
Finally, we also employed primary and tertiary 3-indolylmethanols 15 and 16 under standard reaction conditions (Scheme 7)
with diphenylacetylene 2a. Surprisingly, in both cases, there was no detection of any traces of expected cyclopenta[b]indole
products. In case of primary alcohol 15 the reaction was not very clean and gave a bisindolylmethane derivative 17 in 31% yield.15
Whereas the tertiary alcohol 16 underwent a homodimerization to generate the cyclopenta[b]indole product 18 in near quantitative
yield (98%) via a dehydrative cyclization process as reported in the literature.16
CONCLUSIONS
In conclusion, we discovered and developed an unprecedented formal [3+2] annulation strategy via a skeletal rearrangement,
for the synthesis of cyclopenta[b]indole frameworks employing 3-indolylmethanols and alkynes. The process exhibited a good
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structural diversity for the alkynes, indoles and alcohols. Terminal alkynes, dialkyl substituted internal alkynes and alkynes with
electron deficient substituent's were found to be not suitable for this transformation. Similarly, N-Ts and N-Boc groups were
compatible with reaction conditions, whereas N-Ac, and N-Tf failed to undergo this reaction. Isolation of vinyl chloride suggested that
the mechanism might involve the formation of an initial vinylic carbocation. A mechanism has been proposed involving a ring
opening-ring closing cascade followed by a 1,3-indole migration process, via a spirocyclobutene intermediate
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EXPERIMENTAL SECTION
General Methods. Reactions were monitored by thin-layer chromatography (TLC) carried out on Merck-silica plates using UV-light
and anisaldehyde or potassium permanganate stains for visualization. Column chromatography was performed on silica gel
(60−120 mesh) using hexanes and ethyl acetate as eluents unless otherwise specified. Evaporation of solvents was conducted
under reduced pressure at temperatures less than 45 °C using rotary evaporator. NMR data were recorded on 400 and 500 MHz
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spectrometers. 13C and H chemical shifts in NMR spectra were referenced relative to signals of CDCl3 (δ 7.263 ppm for H and
77.16 ppm for 13C). HRMS were recorded by electron spry ionization (ESI) method on a Q-TOF Micro with lock spray source.
Chemical shifts δ and coupling constants J are given in ppm (parts per million) and Hz (hertz), respectively. All reactions were
carried out using reaction tubes. Known compounds data have been compared with the reported data and references were given
appropriately. Characterization data for new compounds is given below and soft copy of each 1H, 13C NMR spectra for all new
compounds were given in accompanying supporting information file.
General procedure: Synthesis of dihydrocyclopenta[b]indole derivative
To a solution of the indole-3-carbinols (1 equiv.) and alkyne (2 equiv.) in dry 1,2-dichloro-ethane (1,2-DCE) (0.12 mmol/3 mL, 0.04
M) under nitrogen atmosphere was added FeCl3 (0.5 equiv.). The reaction tube was stirred at 55 °C in oil bath for 5-30 min. After
completion of the reaction (by TLC analysis), saturated NaHCO3 and CH2Cl2 were added to reaction mixture and extracted with
CH2Cl2. The combined organic layer was washed with the brine, dried (MgSO4) and solvent was evaporated under reduced
pressure. The crude material was purified by flash column chromatography using hexane-ethyl acetate mixture as eluent to yield the
corresponding cyclopenta[b]indole derivatives.
3-Methyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4aa)
The indole-3-carbinol 1a15e (40 mg, 0.13 mmol), alkyne 2a (46 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred
for 15 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4aa (44 mg,
0.09 mmol, 72%) as a pale yellow solid. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.07 (1 H, d, J = 8.4 Hz), 7.73
(2 H, d, J = 7.7 Hz), 7.45-7.42 (2 H, m), 7.38-7.28 (4 H, m), 7.25-7.26 (8 H, m), 7.12 (1 H, t, J = 7.6 Hz), 4.33 (1 H, q, J = 7.2 Hz),
2.31 (3 H, s) and 1.51 (3 H, d, J = 7.2 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 149.5, 145.3, 145.0, 140.4, 135.9, 135.6,
135.3, 133.9, 130.2, 129.9, 129.4, 129.3, 128.6, 128.3, 127.6, 126.8, 126.7, 125.3, 123.8, 123.7, 120.0, 115.1, 44.3, 21.7 and 17.6
ppm. IR (neat): 2926, 1598, 1448, 1371, 1174, 1090 and 700 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C31H26NO2S, 476.1679;
Found 476.1685. Melting point (°C): 139-141°C.
3-Ethyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ba)
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The indole-3-carbinol 1b (40 mg, 0.12 mmol), alkyne 2a (42 mg, 0.24 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 7b (42 mg, 0.086
mmol, 71%) as a pale yellow solid. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.10 (1 H, d, J = 8.4 Hz), 7.72 (2 H,
d, J = 7.7 Hz), 7.43-7.29 (2 H, m), 7.37-7.29 (4 H, m), 7.26-7.22 (2 H, m), 7.19-7.14 (6 H, m), 7.12 (1 H, t, J = 7.6 Hz), 4.49 (1 H, t, J
= 4.5 Hz), 2.66-2.56 (1 H, m), 2.29 (3 H, s), 1.91-1.78 (1 H, m) and 0.36 (3 H, t, J = 7.2 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3): 
= 147.0, 145.0, 143.1, 140.7, 135.9, 135.7, 135.7, 135.2, 131.9, 129.9, 129.4, 129.4, 128.6, 128.3, 127.5, 126.8, 126.7, 125.3,
123.7, 123.7, 119.9, 115.2, 49.6, 23.0, 21.7 and 7.1 ppm. IR (neat): 2929, 1597, 1448, 1369, 1174, 1090, 917 and 701 cm-1. HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for C32H27NO2SNa, 512.1655; found 512.1649. Melting point (°C): 163-165 °C.
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3-Butyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ca)
The indole-3-carbinol 1c15e (40 mg, 0.11 mmol), alkyne 2a (39 mg, 0.22 mmol), FeCl3 (9 mg, 0.05 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography, gave cyclopenta[b]indole derivative 4ca (28 mg, 0.055 mmol, 50%) as a
pale yellow oil. Rf = 0.35 (19:1 hexane:EtOAc) 1H NMR (400 MHz, CDCl3):  = 8.11 (1 H, d, J = 8.0 Hz), 7.43 (2 H, d, J = 8.3 Hz),
7.42-7.30 (5 H, m), 7.26-7.10 (10 H, m), 4.47 (1 H, q, J = 4.0 Hz), 2.52-2.47 (1 H, m), 2.32 (3 H, s), 1.79-1.73 (1 H, m), 1.03-0.95 (2
H, m), 0.88-0.64 (2 H, m) and 0.59 (3 H, d, J = 7.3 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 147.5, 145.1, 143.5, 140.7, 135.9,
135.8, 135.4, 135.3, 131.5, 129.9, 129.4, 129.3, 128.6, 128.3, 127.5, 126.8, 126.7, 125.2, 123.7, 123.6, 119.9, 115.2, 49.2, 29.4,
24.8, 22.6, 21.7 and 13.9 ppm. IR (neat): 2925, 2858, 1594, 1452, 1370, 1177, 1085 and 697 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+
Calcd for C34H31NO2SNa, 540.1968; found 540.1963
3-Hexyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4da)
The indole-3-carbinol 1d (40 mg, 0.10 mmol), alkyne 2a (37 mg, 0.21 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4cd (32 mg, 0.06
mmol, 60%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.12 (1 H, d, J = 8.3 Hz), 7.73 (2 H, d,
J = 8.3 Hz), 7.43-7.40 (2 H, m), 7.37-7.24 (4 H, m), 7.27-7.21 (4 H, m), 7.19-7.10 (4 H, m), 7.05 (1 H, t, J = 7.1 Hz), 4.46 (1 H, q, J =
4.9 Hz), 2.52-2.46 (1 H, m), 2.30 (3 H, s), 1.80-1.72 (1 H, m), 1.20-1.17 (2 H, m), 1.07-0.92 (6 H, m) and 0.71 (3 H, d, J = 7.3 Hz)
ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 147.5, 145.0, 143.6, 140.7, 135.9, 135.8, 135.5, 135.3, 131.5, 130.6, 129.9, 129.4, 128.5,
128.3, 127.5, 126.7, 126.6, 125.2, 123.7, 123.7, 119.9, 115.2, 49.2, 31.6, 29.6, 29.2, 22.6, 22.5, 21.7 and 14.0 (2C) ppm. IR (neat):
2926, 1598, 1448, 1371, 1174, 1090 and 700 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C36H36NO2S, 546.2461; found
546.2440.
3-Octyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ea)
The indole-3-carbinol 1e (40 mg, 0.097 mmol), alkyne 2a (35 mg, 0.2 mmol), FeCl3 (8 mg, 0.048 mmol), 1,2-DCE (3 mL) stirred for
15 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ea (34 mg,
0.059 mmol, 60%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.12 (1 H, d, J = 8.3 Hz), 7.73
(2 H, d, J = 8.3 Hz), 7.35-7.32 (2 H, m), 7.30-7.23 (3 H, m), 7.19-7.07 (9 H, m), 7.05 (1 H, t, J = 7.1 Hz), 4.46 (1 H, q, J = 4.9 Hz),
2.52-2.46 (1 H, m), 2.30 (3 H, s), 1.78-1.72 (1 H, m), 1.21-1.117 (3 H, m), 1.16-0.93 (9 H, m) and 0.71 (3 H, d, J = 7.3 Hz) ppm. Rf =
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0.35 (19:1, Hex/EtOAc) 13C{1H} NMR (100 MHz, CDCl3):  = 147.5, 144.9, 143.6, 140.7, 135.9, 135.8, 135.5, 135.3, 131.5, 129.9,
129.4, 128.5, 128.3, 127.5, 126.7, 126.6, 125.2, 123.7, 123.6, 119.9, 115.2, 49.2, 32.0, 29.7, 29.5, 29.3, 29.2, 22.7, 22.6, 21.7 and
14.3 ppm. IR (neat): 2949, 2837, 1653, 1464, 1370, 1117, 1024 and 694 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ calcd for C38H40NO2S,
574.2774 found 574.2767.
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3-Decyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4fa)
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The indole-3-carbinol 1f (40 mg, 0.09 mmol), alkyne 2a (32 mg, 0.18 mmol), FeCl3 (7 mg, 0.045 mmol), 1,2-DCE (3 mL) stirred for
12 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indolederivative 4fa (31 mg, 0.052
mmol, 58%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.12 (1 H, d, J = 8.3 Hz), 7.73 (2 H, d,
J = 8.3 Hz), 7.43-7.40 (2 H, m), 7.37-7.29 (4 H, m), 7.27-7.22 (3 H, m), 7.19-7.11 (6 H, m), 4.46 (1 H, q, J = 4.9 Hz), 2.52-2.46 (1 H,
m), 2.30 (3 H, s), 1.79-1.72 (1 H, m), 1.21-1.17 (6 H, m), 1.13-0.84 (10 H, m) and 0.79 (3 H, t, J = 4.9 Hz) ppm. 13C{1H} NMR (100
MHz, CDCl3):  = 147.5, 144.9, 143.6, 140.7, 135.9, 135.8, 135.5, 135.3, 131.5, 129.9, 129.4, 128.5, 128.3, 127.7, 127.5, 126.7,
126.6, 125.2, 123.7, 123.6, 119.9, 115.2, 49.2, 31.8, 29.7, 29.6, 29.5, 29.3, 29.2, 22.7, 22.6, 21.6 and 14.2 ppm. IR (neat): 2925,
2852, 1598, 1447, 1370, 1154, 1089, 1030 and 697 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C40H43NO2SNa, 624.2907; found
624.2907.
8-Bromo-3-methyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ga)
The indole-3-carbinol 1g (40 mg, 0.10 mmol), alkyne 2a (35 mg, 0.20 mmol), FeCl3 (8 mg, 0.05 mmol), 1,2-DCE (3 mL) stirred for 20
min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ga (39 mg, 0.07
mmol, 70%) as a pale yellow solid. Rf = 0.30 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.04 (1 H, d, J = 8.3 Hz), 7.74 (2 H,
d, J = 8.3 Hz), 7.57-7.52 (1 H, m), 7.42-7.40 (1 H, m), 7.34-7.32 (1 H, m), 7.29-7.17 (7 H, m), 7.14-7.12 (3 H, m), 7.03 (1 H, t, J = 7.2
Hz), 4.32 (1 H, q, J = 7.1 Hz), 2.34 (3 H, s) and 1.54 (3 H, d, J = 7.1 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 151.1, 146.2,
145.5, 141.0, 138.2, 135.4, 134.7, 134.6, 132.0, 130.2, 130.1, 129.4, 129.0, 128.9, 128.1, 127.5, 126.8, 126.7, 126.6, 124.4, 113.8,
113.1, 43.2, 21.8 and 18.4 ppm. IR (neat): 2925, 2853, 1596, 1447, 1376, 1174, 1089 and 700 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+
Calcd for C31H24BrNNaO2S, 576.0603; found 576.0597. Melting point (°C): 135-137°C
7-Bromo-3-methyl-1,2-diphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ha)
The indole-3-carbinol25 1h (40 mg, 0.10 mmol), alkyne 2a (35 mg, 0.20 mmol), FeCl3 (8 mg, 0.05 mmol), 1,2-DCE (3 mL) stirred for
15 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ha (36 mg,
0.065 mmol, 65%) as a light yellow solid. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.93 (1 H, d, J = 8.8 Hz), 7.70
(2 H, d, J = 8.0 Hz), 7.40-7.32 (6 H, m), 7.26-7.17 (8 H, m), 4.08 (1 H, q, J = 7.1 Hz), 2.32 (3 H, s) and 1.50 (3 H, d, J = 7.0 Hz) ppm.
13C{1H} NMR (100 MHz, CDCl3):  = 150.7, 145.6, 145.4, 139.1, 135.5, 135.3, 135.0, 133.4, 130.1, 129.3, 129.2, 128.8, 128.4,
127.8, 126.9, 126.8, 126.7, 126.6, 122.7, 117.3, 116.4, 44.3, 21.7 and 17.5 ppm. IR (neat): 2926, 2853, 1592, 1443, 1370, 1177,
1086 and 703 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C31H24BrNNaO2S, 576.0603; found 576.0615. Melting point (°C):
145-147°C.
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The indole-3-carbinol 4i (40 mg, 0.10 mmol), alkyne 2a (35 mg, 0.20 mmol), FeCl3 (8 mg, 0.05 mmol), 1,2-DCE (3 mL) stirred for 40
min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ia (35 mg, 0.063
mmol, 62%) as yellow solid. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.26 (1 H, s), 7.72 (2 H, d, J = 7.7 Hz),
7.41-7.32 (5 H, m), 7.27-7.21 (6 H, m), 7.18-7.14 (3 H, m), 4.29 (1 H, q, J = 7.4 Hz), 2.34 (3 H, s) and 1.49 (3 H, d, J = 7.0 Hz) ppm.
13C{1H} NMR (100 MHz, CDCl3):  = 149.8, 145.6, 145.4, 140.9, 135.6, 135.3, 135.0, 133.4, 130.1, 129.8, 129.3, 128.7, 128.4,
127.7, 126.9, 126.9, 126.8, 124.0, 120.9, 118.2, 117.2, 44.3, 21.7 and 17.4 ppm. IR (neat): 2922, 2852, 1596, 1432, 1376, 1174,
1021 and 771 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C31H24BrNNaO2S, 576.0603; found 576.0614. Melting point (°C):
145-147°C.
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3-Methyl-1,2,7-triphenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ja)
The indole-3-carbinol 1j (40 mg, 0.10 mmol), alkyne 2a (35 mg, 0.20 mmol), FeCl3 (8 mg, 0.05 mmol), 1,2-DCE (3 mL) stirred for 20
min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ja (39 mg, 0.07
mmol, 70%) as a white solid. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.12 (1 H, d, J = 8.7 Hz), 7.76 (2 H, d, J =
8.7 Hz), 7.52 (1 H, s), 7.49-7.45 (5 H, m), 7.40-7.19 (13 H, m), 4.34 (1 H, q, J = 7.3 Hz), 2.31 (3 H, s) and 1.53 (3 H, d, J = 7.3 Hz)
ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 150.1, 145.4, 145.1, 141.4, 139.8, 137.0, 135.9, 135.5, 135.2, 133.9, 130.3, 130.0, 129.4,
129.3, 128.9, 128.6, 128.4, 127.7, 127.3, 127.1, 126.8, 126.8, 125.8, 123.3, 118.4, 115.3, 44.3, 21.7 and 17.6 ppm. IR (neat): 2922,
2847, 1596, 1452, 1369, 1175, 1091 and 706 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C37H30NO2S, 552.1992; found 552.1968.
Melting point (°C): 130-132°C.
tert-butyl 3-methyl-1,2-diphenylcyclopenta[b]indole-4(3H)-carboxylate (4ka)
The indole-3-carbinol 1k21 (40 mg, 0.15 mmol), alkyne 2a (53 mg, 0.3 mmol), FeCl3 (10 mg, 0.075 mmol), 1,2-DCE (3 mL) stirred for
30 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ka (19 mg, 0.05
mmol, 30%) as a pale yellow solid. Rf = 0.6 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.24 (1 H, d, J = 8.3 Hz), 7.48 (2 H,
d, J = 7.0 Hz), 7.40-7.31 (4 H, m), 7.25-7.21 (3 H, m), 7.18-7.12 (4 H, m), 4.27 (1 H, q, J = 7.2 Hz), 1.75 (9 H, s) and 1.39 (3 H, d, J
= 7.2 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 149.9, 149.6, 143.9, 140.0, 136.4, 136.0, 134.4, 129.5, 129.4, 128.6, 128.3,
127.8, 127.4, 126.4, 124.6, 123.4, 122.9, 119.5, 116.2, 84.0, 44.4, 28.4 and 15.9 ppm. IR (neat): 3018, 2982, 2932, 1729, 1453,
1372, 1309, 1216, 1158, 1102, 1065, 855, 755 and 668 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C29H28NO2, 422.2115; found
422.2108. Melting point (°C): 152-154°C.
1-(4-tert-butylphenyl)-3-methyl-2-phenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ab)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2b17 (57 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
15 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ab (41 mg,
0.08mmol, 60%) as a pale yellow solid. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.06 (1 H, d, J = 8.0 Hz), 7.70
(2 H, d, J = 8.3 Hz), 7.39-7.34 (5 H, m), 7.25-7.11 (9 H, m), 4.30 (1 H, q, J = 6.5 Hz), 2.30 (3 H, s), 1.49 (3 H, d, J = 6.5 Hz) and 1.35
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(9 H, s) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 150.6, 149.5, 145.0, 140.5, 135.8, 135.3, 133.8, 132.7, 130.4, 129.9, 129.4,
129.1, 128.6, 128.3, 126.7, 126.6, 125.5, 125.4, 123.8, 123.7, 120.2, 115.2, 44.3, 34.3, 31.5, 21.7 and 17.5 ppm. IR (neat): 2926,
2853, 1600, 1447, 1373, 1095 and 756 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C35H33NO2SNa, 554.2124; found 554.2122.
Melting Point (°C) = 135-137°C
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The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2c17 (48 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
7 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ac (46 mg, 0.097
mmol, 75%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.07 (1 H, d, J = 8.0 Hz), 7.72 (2 H, d,
J = 8.3 Hz), 7.37-7.27 (3 H, m), 7.24-7.10 (11 H, m), 4.31 (1 H, q, J = 7.0 Hz), 2.38 (3 H, s), 2.30 (3 H, s) and 1.51 (3 H, d, J = 7.0
Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 149.4, 145.0, 144.9, 140.4, 137.2, 135.7, 135.3, 133.9, 132.8, 130.4, 129.9, 129.3,
129.2, 128.6, 128.3, 126.7, 126.6, 125.4, 123.7, 123.6, 120.0, 115.1, 44.2, 21.7, 21.5 and 17.5 ppm. IR (neat): 2926, 2853, 1547,
1441, 1371, 1217, 1172, 910, 813 and 734 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C32H28NO2S, 490.1835; found 490.1828.
3-Methyl-2-phenyl-4-tosyl-1-(3-(trifluoromethyl)phenyl)-3,4-dihydrocyclopenta[b]indole(4ad)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2d18 (60 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ad (52 mg, 0.09
mmol, 74%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (500 MHz, CDCl3):  = 8.07 (1 H, d, J = 8.3 Hz), 7.74 (2 H, d,
J = 8.3 Hz), 7.43-7.35 (7 H, m), 7.35-7.32 (2 H, m), 7.30 (1 H, d, J = 8.0 Hz), 7.25 (1 H, t, J = 6.8 Hz), 7.20 (2 H, d, J = 7.8 Hz), 7.13
(1 H, t, J = 7.7 Hz), 4.36 (1 H, q, J = 7.2 Hz), 2.32 (3 H, s) and 1.52 (3 H, d, J = 7.2 Hz) ppm. 13C{1H} NMR (125 MHz, CDCl3):  =
149.8, 145.2, 143.3, 140.4, 136.3, 135.7, 135.3, 135.2, 132.4, 130.8 (q, J = 32.0 Hz), 130.0, 129.2, 128.9, 128.8, 128.1, 126.8,
125.8 (q, J = 4.1 Hz), 125.1, 1243.2 (q, J = 270 Hz), 124.1, 123.8, 123.2 (q, J = 4.1 Hz), 119.9, 115.2, 44.1, 21.7 and 17.5 ppm. 19
F
NMR (282 MHz, CDCl3):  = -62.8 (s, 3 F; CF3) ppm. IR (neat): 2960, 2868, 1598, 1512, 1412, 1370, 1174, 981, 670 and 574 cm-1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C32H24F3NO2SNa, 566.1372; found 566.1373.
2-([1,1'-Biphenyl]-4-yl)-3-methyl-1-phenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ae)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2e17 (63 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
7 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ae (53 mg, 0.097
mmol, 75%) as a light yellow foam. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.09 (1 H, d, J = 8.7 Hz), 7.75 (2 H,
d, J = 8.3 Hz), 7.66 (2 H, d, J = 7.30 Hz), 7.62 (2 H, d, J = 8.1 Hz), 7.52 (2 H, d, J = 8.3 Hz), 7.45 (2 H, t, J = 7.8 Hz), 7.42-7.35 (2 H,
m), 7.32-7.24 (6 H, m), 7.22 (2 H, d, J = 8.1 Hz), 7.13 (1 H, t, J = 7.3 Hz), 4.35 (1 H, q, J = 7.4 Hz), 2.32 (3 H, s) and 1.52 (3 H, d, J
= 7.4 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 149.6, 145.5, 145.1, 140.7, 140.1, 135.6, 135.2, 134.9, 133.5, 130.1, 130.0,
129.9, 129.4, 129.0, 128.4, 127.5, 127.2, 127.1, 126.8, 125.3, 123.8, 123.7, 120.1, 115.2, 44.4, 21.7 and 17.6 ppm. IR (neat): 2925,
2853, 1599, 1447, 1373, 1174, 1088, 746, 661 and 576 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C37H30NO2S, 552.1992; found
552.1982. Melting Point (°C) = 189-191°C.
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The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2f17 (50 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
7 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative (mixture of regio-
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H, t, J = 9.2 Hz), 4.31 (1 H, q, J = 7.4 Hz), 2.31 (4 H, s) and 1.51 (3 H, d, J = 7.1 Hz) ppm. 13C{1H} NMR (125 MHz, CDCl3):  =
162.3 (d, J = 248.0 Hz), 149.5, 145.6, 145.1, 144.1, 140.4, 135.3, 135.1, 132.8, 131.8 (d, J = 3.5 Hz), 131.1 (d, J = 7.8 Hz), 129.9,
129.3, 128.4, 127.7, 126.8, 125.1, 123.9, 123.7, 119.7, 115.7 (d, J = 21 Hz), 115.2, 44.3, 21.7 and 17.4 ppm. 19F NMR (470 MHz,
CDCl3):  = -114.3 (s, 1 F; F) ppm. Minor diastereomer: 8.07 (1 H, d, J = 8.3 Hz), 7.71 (2 H, d, J = 8.4 Hz), 7.43-7.10 (12 H, m),
6.94 (2 H, t, J = 9.2 Hz), 4.27 (1 H, q, J = 7.4 Hz), 2.31 (4 H, s) and 1.49 (3 H, d, J = 7.1 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3): 
= 161.7 (d, J = 248.0 Hz), 149.3, 145.6, 145.1, 144.1, 135.7, 135.3, 135.2, 133.9, 131.6 (d, J = 3.5 Hz), 130.9 (d, J = 7.8 Hz), 129.9,
129.4, 128.7, 127.7, 126.8, 125.2, 123.8, 123.7, 119.7, 115.4 (d, J = 21 Hz), 115.1, 44.3, 21.7 and 17.5 ppm. 19F NMR (470 MHz,
CDCl3):  = -115.3 (s, 1 F; F) ppm. IR (neat): 2959, 2870, 1598, 1511, 1447, 1370, 1247, 1174, 1105, 802, 747 and 669 cm-1. HRMS
(ESI-TOF) m/z: M+Na]+ Calcd for C31H24FNaNO2S, 516.1404; found 516.1385.
2-Butyl-3-methyl-1-phenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ag)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2g19 (40 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ag (42 mg, 0.09
mmol, 72%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (500 MHz, CDCl3):  = 8.04 (1 H, d, J = 8.0 Hz), 7.66 (2 H, d,
J = 8.3 Hz), 7.45-7.42 (4 H, m), 7.35-7.34 (1 H, m), 7.26-7.24 (1 H, m), 7.19-7.14 (3 H, m), 7.09 (1 H, t, J = 7.7 Hz), 3.81 (1 H, q, J =
7.4 Hz), 2.65-2.57 (1 H, m), 2.38-2.32 (1 H, m), 2.30 (3 H, s), 1.58 (3 H, d, J = 7.4 Hz), 1.53-1.47 (1 H, m), 1.35-1.28 (3 H, m) and
0.90 (3 H, t, J = 7.4 Hz) ppm. 13C{1H} NMR (125 MHz, CDCl3):  = 148.5, 147.7, 144.8, 140.5, 135.8, 135.2, 132.6, 130.2, 129.8,
129.1, 128.4, 127.2, 126.7, 125.4, 123.6, 123.5, 119.8, 115.2, 43.3, 32.8, 26.6, 22.9, 21.7, 16.9 and 14.1 ppm. IR (neat): 2957,
2863, 1585, 1447, 1354, 1152 and 784 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C29H30NO2S, 456.1992; found 456.1994.
2-Butyl-3-methyl-1-p-tolyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ah)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2h19 (46 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ah (47 mg,
0.097 mmol, 72%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.03 (1 H, d, J = 8.3 Hz), 7.67
(2 H, d, J = 8.3 Hz), 7.34 (2 H, d, J = 8.2 Hz), 7.29-7.23 (3 H, m), 7.21-7.14 (3 H, m), 7.09 (1 H, t, J = 7.3 Hz), 3.81 (1 H, q, J = 7.4
Hz), 2.65-2.57 (1 H, m), 2.41 (3 H, s), 2.38-2.31 (1 H, m), 2.30 (3 H, s), 1.57 (3 H, d, J = 7.4 Hz), 1.47-1.42 (1 H, m), 1.39-1.26 (3 H,
m) and 0.90 (3 H, t, J = 7.3 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 148.4, 147.7, 144.8, 140.5, 136.8, 135.2, 132.8, 132.4,
130.4, 129.8, 129.1, 128.9, 126.7, 125.5, 123.5, 123.4, 119.9, 115.2, 43.2, 32.9, 26.6, 22.9, 21.7, 21.9, 16.8 and 14.1 ppm. IR
(neat): 2957, 2868, 2360, 1541, 1452, 1370, 1152, 815 and 781 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C30H32NO2S,
470.2148; found 470.2150.
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The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2i20 (50 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
7 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ai (49 mg, 0.09
mmol, 72%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.04 (1 H, d, J = 8.3 Hz), 7.67 (2 H, d,
J = 8.3 Hz), 7.39-7.31 (3 H, m), 7.30-6.99 (7 H, m), 3.80 (1 H, q, J = 7.0 Hz), 2.64-2.57 (1 H, m), 2.41-2.33 (1 H, m), 2.30 (3 H, s),
1.58 (3 H, d, J = 7.3 Hz), 1.50-1.06 (12 H, m) and 0.9-0.8 (3 H, m) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 148.4, 147.8, 144.8,
140.6, 135.8, 135.2, 132.6, 130.3, 129.8, 129.1, 128.4, 127.2, 126.7, 125.4, 123.6, 123.5, 119.8, 115.3, 43.3, 32.0, 30.6, 29.8, 29.5,
29.4, 26.8, 22.8, 21.6, 16.8 and 14.2 ppm. IR (neat): 2928, 2856, 2361, 1541, 1457, 1373, 1179 and 787 cm-1. HRMS (ESI-TOF)
m/z: [M+H]+ Calcd for C33H38NO2S, 512.2618; found 512.2611.
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3-Methyl-2-octyl-1-p-tolyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4aj)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2j20 (57 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4aj (47 mg, 0.09
mmol, 70%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.04 (1 H, d, J = 8.3 Hz), 7.66 (2 H, d,
J = 8.3 Hz), 7.34 (2 H, d, J =8.2 Hz), 7.29-7.23 (3 H, m), 7.21-7.17 (1 H, m), 7.15-7.07 (3 H, m), 3.81 (1 H, q, J = 7.3 Hz), 2.71-2.57
(1 H, m), 2.40 (3 H, s), 2.38-2.30 (1 H, m), 2.30 (3 H, s), 1.58 (3 H, d, J = 7.3 Hz), 1.33-1.28 (12 H, m) and 0.88 (3 H, t, J = 7.1 Hz)
ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 148.4, 147.3, 144.8, 140.5, 136.8, 135.1, 132.7, 132.4, 130.4, 129.8, 129.0, 128.9, 126.7,
125.5, 123.5, 123.4, 119.8, 115.2, 43.3, 31.9, 30.5, 29.7, 29.5, 29.4, 26.7, 22.7, 21.6, 21.4, 16.8 and 14.2 ppm. IR (neat): 2928,
2856, 2361, 1541, 1457, 1373, 1179 and 787 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C34H40NO2S, 526.2774; found
526.2774.
2,3-Dimethyl-1-phenyl-4-tosyl-3,4-dihydrocyclopenta[b]indole (4ak)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2k (29 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for
10 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave cyclopenta[b]indole derivative 4ak (38 mg, 0.09
mmol, 71%) as a pale yellow oil. Rf = 0.35 (19:1, Hex/EtOAc). 1H NMR (500 MHz, CDCl3):  = 8.06 (1 H, d, J = 8.0 Hz), 7.66 (2 H, d,
J = 8.3 Hz), 7.45-7.42 (4 H, m), 7.35-7.30 (2 H, m), 7.24-7.19 (1 H, m), 7.15-7.09 (3 H, m), 3.66 (1 H, q, J = 7.6 Hz), 2.29 (3 H, s),
2.10 (3 H, s), 1.60 (3 H, d, J = 7.6 Hz) ppm. 13C{1H} NMR (125 MHz, CDCl3):  = 148.5, 144.8, 142.8, 140.6, 135.6, 135.1, 132.6,
130.3, 129.8, 129.1, 128.4, 127.2, 126.7, 125.5, 123.6, 123.5, 119.9, 115.3, 46.1, 21.6, 16.9 and 13.2 ppm. IR (neat): 2958, 2867,
1581, 1443, 1353, 1151 and 790 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C26H23NaNO2S, 436.1342; found 436.1341.
1-Methyl-4-tosyl-3-(1-tosyl-1H-indol-3-yl)-1,2,3,4-tetrahydrocyclopenta[b]indole (5a)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), alkyne 2a (25 mg, 0.13 mmol), FeCl3 (10 mg, 0.063 mmol) in 1,2-DCE (4 mL) were
stirred for 2 min at 55 °C to rt. Purification by flash column chromatography (9:1 hexane:EtOAc) gave the homodimer product as
diastereomeric mixture (1:0.27) 5a (45 mg, 0.148 mmol, 53%) as a pale yellow oil. Rf = 0.35 (9:1, Hex/EtOAc). Major isomer 1H
NMR (400 MHz, CDCl3):  = 8.05 (1 H, d, J = 7.8 Hz), 7.89 (1 H, d, J = 7.8 Hz), 7.71 (2 H, d, J = 7.9 Hz), 7.60-7.52 (1 H, m), 7.28-
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7.01 (10 H, m), 6.75 (2 H, d, J = 7.8 Hz), 4.89 (1 H, dd, J = 8.2 & 3.8 Hz), 3.74-3.71 (1 H, m), 2.78-2.48 (2 H, m), 2.22 (3 H, s), 2.20
(3 H, s) and 1.39 (3 H, d, J = 6.9 Hz) ppm. Minor isomer 1H NMR (400 MHz, CDCl3):  = 8.10 (1 H, d, J = 7.8 Hz), 7.98 (1 H, d, J =
7.8 Hz), 7.71 (2 H, d, J = 7.9 Hz), 7.60-7.52 (1 H, m), 7.28-7.01 (10 H, m), 6.83 (2 H, d, J = 7.8 Hz), 4.82 (1 H, dd, J = 8.2 & 3.8 Hz),
3.35-3.23 (1 H, m), 2.78-2.48 (2 H, m), 2.31 (3 H, s), 2.23 (3 H, s) and 1.29 (3 H, d, J = 6.9 Hz) ppm. 13C{1H} NMR (100 MHz,
CDCl3): (Major isomer)  = 144.8, 144.4, 142.8, 140.8, 135.6, 135.5, 135.2, 131.7, 129.9, 129.4, 127.0, 126.7, 126.3, 126.2, 124.9,
124.4, 124.0, 123.7, 123.4, 123.2, 123.1, 119.8, 119.4, 114.9, 113.7, 47.0, 37.4, 32.3, 21.6, 21.5 and 20.5 ppm. IR (neat): 2923,
1639, 1599, 1531, 1509, 1457, 1417, 1380, 1257, 1175, 1030, 978, 884, 815, 667, 594 and 522 cm-1. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for C34H30N2NaO4S2, 617.1539; found 617.1527.
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1-(3-(4-Acetyl-1-methyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)-1H-indol-1-yl)ethan-1-one (5m)
The indole-3-carbinol22b 1m (40 mg, 0.2 mmol), alkyne 2a (71 mg, 0.4 mmol), FeCl3 (16 mg, 0.098 mmol) in 1,2-DCE (5 mL) were
stirred for 5 h at 55 °C to rt. Purification by flash column chromatography (9:1 hexane:EtOAc) gave the homodimer product as
diastereomeric mixture (1:0.48) 5m (24 mg, 0.064 mmol, 65%) as a pale yellow semisolid. Rf = 0.35 (9:1, Hex/EtOAc). Major
diastereomer 1H NMR (400 MHz, CDCl3):  = 8.46 (2 H, m), 7.52-7.25 (6 H, m), 6.86 (1 H, s), 4.79 (1 H, d, J = 8.03 Hz), 3.45-3.46
(1 H, m), 2.70-2.55 (2 H, m), 2.47 (3 H, s), 2.38 (3 H, s) and 1.32 (3 H, d, J = 6.8 Hz) ppm. Minor diastereomer 1H NMR (400 MHz,
CDCl3):  = 8.46 (2 H, m), 7.52-7.25 (6 H, m), 6.72 (1 H, s), 4.82 (1 H, d, J = 8.03 Hz), 3.45-3.46 (1 H, m), 2.70-2.55 (2 H, m), 2.44
(3 H, s), 2.43 (3 H, s) and 1.46 (3 H, d, J = 6.8 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3): Major isomer)  = 169.2, 168.6, 141.4,
141.3, 133.7, 132.8, 125.9, 125.0, 124.8, 123.9, 123.8, 121.4, 118.9, 118.8, 117.8, 117.1, 47.1, 45.8, 38.7, 31.8, 25.2, 24.2 and 20.1
ppm. IR (neat): 2926, 2855, 1699, 1451, 1387, 1331, 1217, 1129, 932, 771 and 669 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C24H22N2NaO2, 393.1573; found 393.1559.
3-(4-Chloro-3-methylpent-3-en-2-yl)-1-tosyl-1H-indole (9)
The indole-3-carbinol 1a (40 mg, 0.13 mmol), 2-Butyne (15 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred for 5
min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave vinyl- chloride derivative 9 (27 mg, 0.07 mmol,
55%) as a colorless solid diastereoisomer (E:Z isomer = 1:1). Rf = 0.35 (19:1, Hex/EtOAc). 1st Diastereomer : 1H NMR (400 MHz,
CDCl3):  = 7.95-7.93 (1 H, m), 7.71 (2 H, d, J = 7.7 Hz), 7.36-7.37 (1 H, m), 7.32-7.24 (2 H, m), 7.21-7.15 (3 H, m), 4.55 (1 H, q, J =
6.6 Hz), 2.31 (6 H, s), (3 H, s), 1.44 (3 H, s) and 1.40 (3 H, d, J = 6.6 Hz) ppm. 2nd Diastereomer : 1H NMR (400 MHz, CDCl3):  =
7.95-7.93 (1 H, m), 7.71 (2 H, d, J = 7.7 Hz), 7.46 (1 H, d, J = 7.6 Hz), 7.36-7.37 (1 H, m), 7.32-7.24 (1 H, m), 7.21-7.15 (3 H, m),
4.09 (1 H, q, J = 6.6 Hz), 2.31 (3 H, s), 2.10 (3 H, s), 1.40 (3 H, d, J = 6.6 Hz) and 1.33 (3 H, s) ppm. 13C{1H} NMR (100 MHz,
CDCl3) Mixture of diastereomer:  = 144.9, 144.8, 135.6, 135.57, 135.3, 135.3, 133.4, 132.36, 130.9, 130.6, 129.9, 126.8, 126.4,
125.1, 124.9, 124.87, 123.6, 123.4, 123.37, 123.2, 122.9, 120.3, 119.8, 113.9, 113.7, 34.6, 34.0, 22.9, 22.3, 21.6, 17.4, 16.4, 15.2
and 13.7 ppm. IR (neat): 2967, 2927, 1599, 1484, 1454, 1365, 1237, 1217, 1187, 1155, 1091, 812, 761 and 668 cm-1. HRMS (ESI-
TOF) m/z: [M+H]+ Calcd for C21H23ClNO2S, 388.1125; found 388.1133.
3-(4-Chloro-3,4-diphenylbut-3-en-2-yl)-2-methyl-1-tosyl-1H-indole (10)
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The indole-3-carbinol25 1a’ (40 mg, 0.13 mmol), Alkyne 2a (47 mg, 0.25 mmol), FeCl3 (10 mg, 0.06 mmol), 1,2-DCE (3 mL) stirred
for 5 min at 55 °C. Purification by column chromatography (19:1 hexane:EtOAc) gave vinyl-chloride derivative 10 (42 mg, 0.08
mmol, 65%) as a pale yellow oil diastereoisomer (E:Z = 1:0.25) Rf = 0.4 (19:1, Hex/EtOAc). 1st Diastereomer : 1H NMR (400 MHz,
CDCl3): 8.26 (1 H, d, J = 8.4 Hz), 7.67 (2 H, d, J = 4.1 Hz), 7.61-7.55 (1 H, m), 7.51 (1 H, d, J = 6.5 Hz), 7.35-7.31 (1 H, m), 7.25-
7.10 (10 H, m), 6.95-6.87 (1 H, m), 6.81-6.75 (1 H, m), 4.17-4.10 (1 H, m), 2.55 (3 H, s), 2.40 (3 H, s) and 1.39 (3 H, d, J = 6.6 Hz)
ppm. 2nd Diastereomer : 1H NMR (400 MHz, CDCl3): 8.20 (1 H, d, J = 8.4 Hz), 7.67 (2 H, d, J = 4.1 Hz), 7.61-7.55 (1 H, m), 7.51 (1
H, d, J = 6.5 Hz), 7.35-7.31 (1 H, m), 7.25-7.12 (10 H, m), 6.95-6.87 (1 H, m), 6.81-6.75 (1 H, m), 4.17-4.10 (1 H, m), 2.16 (3 H, s),
2.04 (3 H, s), 1.34 (3 H, d, J = 6.6 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3): Mixture of diastereomers  = 150.7, 148.3, 144.7,
144.2, 137.1, 136.3, 135.4, 134.9, 129.8, 129.4, 128.2, 127.0, 126.7, 126.4, 126.3, 125.3, 124.2, 123.4, 122.9, 120.3, 119.8, 114.7,
45.8, 21.6, 17.5 and 14.6 ppm. IR (neat): 2951, 2861, 1580, 1353, 1023 and 791 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C32H28ClNO2SNa, 548.1421; found 548.1436.
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Bis(1-tosyl-1H-indol-3-yl)methane (17)
The indole-3-carbinol22a 15 (50 mg, 0.17 mmol), alkyne 2a (60 mg, 0.33 mmol), FeCl3 (13 mg, 0.08 mmol) in 1,2-DCE (5 mL) were
stirred for 10 h at rt. Purification by flash column chromatography (19:1 hexane:EtOAc) gave the bisindole 17 (28 mg, 0.05 mmol,
30%) as a pale yellow colour semisolid. Rf = 0.30 (19:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.99 (2 H, d, J = 8.2 Hz), 7.64
(4 H, d, J = 8.2 Hz), 7.33-7.29 (4 H, m), 7.21-7.14 (8 H, m), 4.02 (2 H, s) and 2.33 (6 H, s) ppm. 13C{1H} NMR (100 MHz, CDCl3):  =
145.0, 135.7, 135.2, 130.7, 130.0, 126.8, 125.0, 124.2, 123.3, 120.7, 119.7, 114.2, 21.7 and 21.3 ppm. IR (neat): 2924, 2853, 1448,
1367, 1174, 1120, 974, 748, 610 and 575 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C31H26N2NaO4S2, 577.1226; found
577.1224.
1,1,3-Trimethyl-4-tosyl-3-(1-tosyl-1H-indol-3-yl)-1,2,3,4-tetrahydrocyclopenta[b]indole (18)
The indole-3-carbinol21 16 (50 mg, 0.15 mmol), alkyne 2a (54 mg, 0.30 mmol), FeCl3 (12 mg, 0.075 mmol) in 1,2-DCE (5 mL) were
stirred for 2 min at 55 °C to rt. Purification by flash column chromatography (9:1 hexane:EtOAc) gave the dimer 18 (45 mg, 0.148
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mmol, 98%) as a white solid. Rf = 0.35 (9:1, Hex/EtOAc). H NMR (400 MHz, CDCl3):  = 8.07-8.05 (1 H, m), 7.90 (1 H, d, J = 8.0
Hz), 7.86 (2 H, d, J = 8.0 Hz), 7.61 (1 H, s), 7.58-7.56 (1 H, m), 7.28-7.26 (2 H, m), 7.16-7.08 (3 H, m), 6.78 (1 H, t, J = 8.0 Hz), 6.64
(1 H, t, J = 7.3 Hz), 6.49 (2 H, d, J = 8.2 Hz), 6.29 (2 H, d, J = 8.2 Hz), 2.87 (1 H, d, J = 13.2 Hz), 2.33 (1 H, d, J = 13.2 Hz), 2.13 (3
H, s), 2.08 (3 H, s), 2.07 (3 H, s), 1.52 (3 H, s) and 1.49 (3 H, s) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 144.9, 144.8, 143.6,
141.1, 135.6,135.4, 135.2, 133.9 131.7, 130.0, 129.8, 128.8, 128.5, 127.3, 125.8, 125.2, 124.0, 123.7, 123.6, 123.1, 122.8, 120.9,
119.1, 115.1, 113.8, 62.4, 45.1, 37.8, 30.3, 28.9, 27.8, 21.5 and 21.4 ppm. IR (neat): 2969, 2929, 2855, 1593, 1444, 1364, 1358,
1264, 1089, 800 and 701 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C36H34N2NaO4S2, 645.1852; found 645.1859. Melting
point (°C): 170-172 °C.
General Procedure of Sonogashira cross-coupling reaction:
To a solution of aryl halide (1 equiv.) and propargylic alkyne (1.0 equiv.) in anhydrous THF and triethyl amine (Et3N) at 0 °C, CuI (15
mol%), and Pd(PPh3)2Cl2 (1 mol%) under nitrogen atmosphere were added, stirred the reaction mixture for 30 min at 0 °C. The
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reaction mixture was allowed to warm to room temperature (RT) and continued the stirring for 1-8 h at RT. Reaction progress was
monitored by the thin layer chromatography (TLC) analysis. After complete consumption of the starting material, reaction was
quenched with saturated NH4Cl and extracted with ethyl acetate (EtOAc). The combined organic layer was washed with brine, dried
(MgSO4) and solvent was removed under reduced pressure. The crude material was typically purified by flash column
chromatography using hexane/ethyl acetate mixture as eluent to yield the corresponding coupled product.
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Preparation of indole-3-carbinol derivatives:
a) General Procedure for the Synthesis of indole-3-carbaldehyde derivatives
Phosphorous oxychloride (2.5 equiv.) was added dropwise to dimethylformamide (DMF), (5 mL per 1 mL of POCl3) at 0 °C. The
mixture was stirred for 5 minutes then desired indole (1 equiv.) was added as a dimethylformamide solution (5 mL per 0.5 g of
indole). The mixture was then allowed to warm to room temperature and stirred for 2 hours. Add saturated aqueous sodium
bicarbonate and ethyl acetate until the mixture became clear and organic layer was separated, dried (MgSO4), filtered and solvent
was evaporated under reduced pressure. The crude material was purified by flash column chromatography using hexane-ethyl
acetate mixture as eluent to yield the corresponding indole-3-carbaldehyde.
b) General Procedure for the Protection of indole-3-carbaldehyde
1H-indole-3-carbaldehyde (2 mmol, 1 equiv) was suspended in dichloromethane (3 mL) and cooled at 0 °C Et3N (1.3 equiv) was
added and resulting solution was stirred for 10 min. 4-toluenesulphonyl chloride was added and the reaction mixture stirred at rt for
2-5 h. After completion of the reaction, the reaction mixture was quenched with water and DCM, organic layer was separated, dried
(MgSO4), filtered and solvent was evaporated under reduced pressure. The crude material was purified by flash column
chromatography using hexane-ethylacetate mixture as eluent to yield the corresponding 3-indole carbaldehyde.
5-Phenyl-1-tosyl-1H-indole-3-carbaldehyde (S1)
The 5-phenyl-indole-3-carbaldehyde23 (200 mg, 1.0 mmol), Tosyl chloride (380 mg, 1.3 mmol) in anhydrous DCM (7 mL) were
stirred for 2 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave tosylated indole derivative S1
(345 mg, 0.9 mmol, 90%) as yellow colour oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 10.11 (1 H, s), 8.47 (1 H,
s), 8.24 (1 H, s), 8.00 (1 H, d, J = 8.51 Hz), 7.88 (2 H, d, J = 8.10 Hz), 7.61 (2 H, d, J = 8.8 Hz), 7.43 (1 H, t, J = 7.5 Hz), 7.35 (2 H,
d, J = 6.9 Hz), 7.31 (3 H, d, J = 8.1 Hz ) and 2.38 (3 H, s) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 185.4, 146.4, 140.8, 138.8,
136.8, 134.7, 134.5, 130.5, 128.9, 127.6, 127.5, 127.4, 127.0, 126.0, 122.7, 121.1, 113.6 and 21.8 ppm. IR (neat): 2923, 2361,
1637, 1600, 1535, 1376, 1256, 1174, 974, 772 and 575 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H18NO3S, 376.1002; found
376.0995.
c) General procedure for RMgX reactions
Magnesium turnings (3.0 equiv.) were taken in a dry two-neck round-bottom flask equipped with a stir bar and condenser. The
reaction apparatus was flame-dried under vacuum and cooled under nitrogen atmosphere. Single crystal of I2 (ca. 2 mg) was added
followed by anhydrous THF. The organo-halide (3.0 equiv.) was added drop wise. The reaction was stirred at ambient temperature
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for an additional 30 min. A solution of alkyl magnesium bromide was added drop wise to the solution of the carbonyl compound (1.0
equiv.) in anhydrous THF at 0 °C under nitrogen atmosphere. The reaction mixture was allowed to warm to room temperature.
Reaction progress was monitored by the thin layer chromatography (TLC) analysis. After completion of the reaction the reaction
mixture was quenched with saturated aqueous NH4Cl solution and extracted with EtOAc.). The combined organic layer was washed
with brine and dried (MgSO4). Evaporation of the solvent and purification of the crude mixture by column chromatography (3:1,
hexane: EtOAc) gave the corresponding indole-3-carbinol derivatives.
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1-(1-Tosyl-1H-indol-3-yl)propan-1-ol (1b)
The indole-3-carbaldehyde15e (200 mg, 0.7 mmol), Mg (17 mg, 2 mmol) and ethyliodide (310 mg, 2.0 mmol, 0.2 mL) in anhydrous
Ether:THF (1:1) (10 mL) were stirred for 2.0 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave
indole-3-carbinol 1b (209 mg, 0.64 mmol, 91%) as a light red colour oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  =
7.97 (1 H, d, J = 8.3 Hz), 7.74 (2 H, d, J = 8.3 Hz), 7.62 (1 H, d, J = 7.8 Hz), 7.49 (1 H, s), 7.32-7.28 (1 H, m), 7.24-7.17 (3 H, m),
4.93 (1 H, t, J = 6.5 Hz), 2.31 (3 H, s), 2.03 (1 H, br, s), 1.92-1.83 (2 H, m) and 0.92 (3 H, t, J = 6.5 Hz) ppm. 13C{1H} NMR (100
MHz, CDCl3):  = 145.0, 135.7, 135.3, 129.9, 129.1, 126.9, 125.8, 124.9, 123.2, 122.0, 120.6, 113.9, 69.5, 30.0, 21.6 and 10.1 ppm.
IR (neat): 3425, 2926, 2361, 1590, 1300, 1105, 784, 732 and 680 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C18H19NNaO3S,
352.0978; found 352.0980.
1-(1-Tosyl-1H-indol-3-yl)heptan-1-ol (1d)
The indole-3-carbaldehyde (200 mg, 0.7 mmol), Mg (17 mg, 2 mmol) and 1-Bromohexane (332 mg, 2.0 mmol, 0.28 mL) in
anhydrous THF (15 mL) were stirred for 2.5 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave
indole-3-carbinol 1d (242 mg, 0.63 mmol, 90%) as a colour less oil. Rf = 0.30 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.97
(1 H, d, J = 8.3 Hz), 7.75 (2 H, d, J = 8.3 Hz), 7.64 (1 H, d, J = 8.3 Hz), 7.49 (1 H, s), 7.33-7.28 (1 H, m), 7.24-7.19 (3 H, m), 4.90 (1
H, t, J = 6.5 Hz), 2.32 (3 H, s), 1.92-1.83 (3 H, m), 1.35-1.25 (8 H, m) and 0.87 (3 H, t, J = 6.5 Hz) ppm. 13C{1H} NMR (100 MHz,
CDCl3):  = 145.0, 135.7, 135.3, 129.9, 129.1, 126.9, 126.3, 124.9, 123.2, 122.0, 120.6, 113.9, 68.2, 37.2, 31.9, 29.3, 25.9, 22.7,
21.7 and 14.2 ppm. IR (neat): 3412 (OH), 2953, 2364, 1581, 1300, 1105, 1044, 786, 733 and 680 cm-1. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for C22H27NNaO3S, 408.1604; found 408.1607
1-(1-Tosyl-1H-indol-3-yl)nonan-1-ol (1e)
The indole-3-carbaldehyde (200 mg, 0.7 mmol), Mg (17 mg, 2 mmol) and 1-Bromooctane (466 mg, 2.0 mmol, 0.43 mL) in
anhydrous THF (15 mL) were stirred for 2.5 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave
indole-3-carbinol 1e (245 mg, 0.59 mmol, 85%) as a white solid. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.97 (1
H, d, J = 8.3 Hz), 7.74 (2 H, d, J = 8.3 Hz), 7.62 (1 H, d, J = 8.3 Hz), 7.49 (1 H, s), 7.32-7.28 (1 H, m), 7.23-7.17 (3 H, m), 4.83 (1 H,
t, J = 6.5 Hz), 2.32 (3 H, s), 1.92-1.80 (3 H, m), 1.33-1.117 (12 H, m) and 0.87 (3 H, t, J = 6.5 Hz) ppm. 13C{1H} NMR (100 MHz,
CDCl3):  = 145.0, 135.7, 135.4, 130.0, 129.1, 126.9, 126.3, 124.9, 123.3, 122.8, 120.6, 113.9, 68.2, 37.2, 31.9, 29.8, 29.6, 29.4,
25.9, 22.8, 21.7 and 14.3 ppm. IR (neat): 3401 (OH), 2962, 2360, 1580, 1452, 1365, 1299, 1120, 1038, 787, 733 and 678 cm-1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C24H31NNaO3S, 436.1917; found 436.1923. Melting point (°C): 55-57 °C
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The indole-3-carbaldehyde (200 mg, 0.7 mmol), Mg (17 mg, 2 mmol) and 1-Bromodecane (386 mg, 2.0 mmol, 0.33 mL) in
anhydrous THF (15 mL) were stirred for 2.5 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave
indole-3-carbinol 1f (246 mg, 0.56 mmol, 88%) as a colour less oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.97
(1 H, d, J = 8.3 Hz), 7.74 (2 H, d, J = 8.3 Hz), 7.62 (1 H, d, J = 8.3 Hz), 7.49 (1 H, s), 7.32-7.28 (1 H, m), 7.23-7.17 (3 H, m), 4.83 (1
H, t, J = 6.5 Hz), 2.32 (3 H, s), 1.92-1.80 (2 H, m), 1.79 (1 H, br s), 1.33-1.117 (16 H, m) and 0.88 (3 H, t, J = 6.5 Hz) ppm. 13C{1H}
NMR (100 MHz, CDCl3):  = 144.9, 135.7, 135.4, 130.0, 129.1, 126.9, 126.3, 124.9, 123.2, 122.8, 120.6, 113.9, 68.2, 37.2, 32.1,
29.8, 29.7, 29.6, 29.5, 29.3, 25.9, 22.7, 21.7 and 14.2 ppm. IR (neat): 3392 (OH), 2926, 2364, 1579, 1396, 1105, 1043, 785, 731
and 680 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C26H35NNaO3S, 464.2230; found 464.2227. Melting point (°C): 63-65°C
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1-(4-Bromo-1-tosyl-1H-indol-3-yl)ethanol (1g)
The 4-bromo-indole-3-carbaldehyde24 (200 mg, 0.53 mmol), MeMgBr (0.2 mL, 0.69 mmol, 3 M in ether) in anhydrous THF (10 mL)
were stirred for 2.0 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave indole-3-carbinol 1g (188
mg, 0.47 mmol, 90%) as a pale yellow colour oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.97 (1 H, d, J = 8.3
Hz), 7.74 (2 H, d, J = 8.3 Hz), 7.70 (1 H, s), 7.40 (1 H, d, J = 8.1 Hz), 7.24 (2 H, d, J = 8.1 Hz), 7.14 (1 H, t, J = 8.2 Hz), 5.64 (1 H, q,
J = 6.5 Hz), 2.35 (3 H, s), 2.26 (1 H, br, s) and 1.64 (3 H, d, J = 6.5 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 145.5, 136.7,
135.0, 130.2, 128.0, 127.9, 127.7, 127.0, 125.7, 124.2, 113.8, 113.0, 62.3, 23.5 and 21.7 ppm. IR (neat): 3425, 2926, 2361, 1590,
1300, 1105, 784, 732 and 680 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H16BrNNaO3S, 415.9926; found 415.9926
1-(5-Bromo-1-tosyl-1H-indol-3-yl)ethanol (1h)25
The 5-bromo-indole-3-carbaldehyde25 (200 mg, 0.53 mmol), MeMgBr (0.2 mL, 0.69 mmol, 3 M in ether) in anhydrous THF (10 mL)
were stirred for 2.0 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave indole-3-carbinol 1h (170
mg, 0.45 mmol, 85%) as a pale yellow colour oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.82 (1 H, d, J = 8.6
Hz), 7.79 (1 H, d, J = 8.3 Hz), 7.72 (2 H, d, J = 8.3 Hz), 7.48 (1 H, s), 7.39 (1 H, dd, J = 8.8 and 1.3 Hz), 7.22 (2 H, d, J = 8.1 Hz),
5.06 (1 H, q, J = 6.5 Hz), 2.34 (3 H, s), 2.26 (1 H, br, s) and 1.59 (3 H, d, J = 6.5 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  =
145.5, 135.1, 134.3, 130.8, 130.1, 127.8, 126.9, 126.5, 123.5, 123.4, 116.8, 115.2, 63.8, 23.6 and 21.7 ppm. IR (neat): 3425, 2926,
2361, 1590, 1300, 1105, 784, 732 and 680 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H16BrNNaO3S, 415.9926; found
415.9915
1-(6-Bromo-1-tosyl-1H-indol-3-yl)ethanol (1i)
The 6-bromo-indole-3-carbaldehyde26 (200 mg, 0.53 mmol), MeMgBr (0.2 mL, 0.69 mmol, 3 M in ether) in anhydrous THF (10 mL)
were stirred for 2.0 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave indole-3-carbinol 1i (188
mg, 0.47 mmol, 91%) as a pale yellow colour oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.15 (1 H, s), 7.76 (2
H, d, J = 8.3 Hz), 7.51 (1 H, d, J = 8.1 Hz), 7.46 (1 H, s), 7.33 (1 H, d, J = 8.2 Hz), 7.25 (2 H, d, J = 8.0 Hz), 5.64 (1 H, q, J = 6.1 Hz),
2.35 (3 H, s) and 1.59 (3 H, d, J = 6.1 Hz) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 145.5, 136.3, 135.1, 130.2, 127.9, 127.0,
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126.9, 126.6, 122.6, 121.8, 118.7, 116.8, 63.9, 23.6 and 21.7 ppm. IR (neat): 3423, 2927, 2360, 1589, 1302, 1107, 790, 741 and
681 cm-1. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H16BrNNaO3S, 415.9926; found 415.9924.
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1-(5-Phenyl-1-tosyl-1H-indol-3-yl)ethanol (1j)
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The 5-phenyl-indole-3-carbaldehyde S1 (200 mg, 0.51 mmol), MeMgBr (0.2 mL, 0.69 mmol, 3 M in ether) in anhydrous THF (10 mL)
were stirred for 2.0 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave indole-3-carbinol 1j (170
mg, 0.43 mmol, 85%) as a pale yellow colour oil. Rf = 0.3 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.03 (1 H, d, J = 8.3
Hz), 7.84 (1 H, s) 7.80 (2 H, d, J = 8.3 Hz), 7.59-7.56 (2 H, m), 7.54-7.53 (1 H, m), 7.43 (2 H, t, J = 7.38 Hz), 7.35-7.29 (2 H, m),
7.24 (2 H, d, J = 8.6 Hz), 5.64 (1 H, q, J = 6.5 Hz), 2.35 (3 H, s), 2.26 (1 H, br, s) and 1.64 (3 H, d, J = 6.5 Hz) ppm. 13C{1H} NMR
(100 MHz, CDCl3):  = 145.3, 143.5, 141.4, 139.2, 136.9, 135.0, 130.2, 128.9, 127.5, 127.3, 127.2, 127.0, 124.7, 122.8, 119.0,
114.0, 64.0, 23.7 and 21.7 ppm. IR (neat): 3396, 2922, 2852, 1652, 1596, 1495, 1373, 1261, 1216, 1188, 1019, 869, 805, 772 and
667 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C23H22NO3S, 392.1315; found 392.1318
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1-(3-(1-Hydroxyethyl)-1H-indol-1-yl)ethan-1-one (1m)22b
The indole-3-carbaldehyde22a (200 mg, 1.0 mmol), MeMgBr (0.4 mL, 1.37 mmol, 3 M in ether) in anhydrous THF (10 mL) were
stirred for 2.0 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave indole-3-carbinol 1m (150 mg,
0.74 mmol, 70%) as colourless oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 8.38 (1 H, d, J = 7.5 Hz), 7.63 (1 H,
d, J =7.6 Hz), 7.35-7.22 (3 H, m), 5.13 (1 H, q, J = 6.3 Hz), 2.66 (1 H, s br), 2.44 (3 H, s) and 1.62 (3 H, d, J = 6.3 Hz) ppm. 13C{1H}
NMR (100 MHz, CDCl3):  = 168.9, 136.3, 128.7, 127.3, 125.4, 123.7, 121.2, 119.8, 116.8, 63.8, 23.9 and 23.8 ppm. IR (neat):
3396, 2922, 2361, 1652, 1596, 1373, 1174 and 772 cm-1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C12H14NO2, 204.1019; found
204.1018.
1-(1-((trifluoromethyl)sulfonyl)-1H-indol-3-yl)ethan-1-ol (1l)
The indole-3-carbaldehyde22a (150 mg, 0.53 mmol), MeMgBr (0.2 mL, 0.69 mmol, 3 M in ether) in anhydrous THF (10 mL) were
stirred for 2.0 h at 0 °C to rt. Purification by flash column chromatography (4:1 hexane:EtOAc) gave indole-3-carbinol 1l (125 mg,
0.43 mmol, 80%) as a pale red colour oil. Rf = 0.35 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.90 (1 H, d, J = 8.0 Hz), 7.74
(1 H, d, J =7.2 Hz), 7.43-7.35 (2 H, m), 7.32 (1 H, s), 5.21-5.14 (1 H, m), 2.10 (1 H, s br) and 1.64 (3 H, d, J = 6.5 Hz) ppm. 13C{1H}
NMR (100 MHz, CDCl3):  = 136.2, 129.8, 129.2, 126.1, 124.9, 122.0, 121.0, 114.1, 63.8 and 23.8 ppm. IR (neat): 3376, 2978,
1471, 1286, 1205, 1112, 1025, 745 and 612 cm-1. HRMS (ESI-TOF) m/z: [M-CF3]+ Calcd for C10H10NO3S, 224.0381; found 224.0371
1-Tosyl-3-vinyl-1H-indole (6)27
The indole-3-carbinol 5a (40 mg, 0.13 mmol), alkyne (41 mg, 0.25 mmol), aq. HCl, 1,2-DCE (3 mL) stirred for 24 h at 55 °C.
Purification by column chromatography (19:1 hexane:EtOAc) gave corresponding vinyl derivative 6 (3.5 mg, 0.09 mmol, 8%) as a
pale yellow oil. Rf = 0.6 (4:1, Hex/EtOAc). 1H NMR (400 MHz, CDCl3):  = 7.99 (1 H, d, J = 8.2 Hz), 7.75 (2 H, t, J = 8.3 Hz), 7.60 (1
H), 7.34-7.25 (2 H, m), 7.21 (2 H, d, J = 7.7 Hz), 6.76 (1 H, dd, J = 17.0 & 11.0 Hz), 5.79 (1 H, d, J = 17.0 Hz), 5.34 (1 H, d, J = 11.0
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Hz) and 2.32 (3 H, s) ppm. 13C{1H} NMR (100 MHz, CDCl3):  = 145.2, 135.6, 135.3, 130.0, 130.0, 129.1, 127.7, 127.0, 125.0,
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124.2, 123.6, 121.2, 120.5, 115.5, 113.9 and 21.7 ppm.
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Reaction of indole-3-carbinol (1a) and Phenylacetylene with FeCl3 :
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The indole-3-carbinol 1a (40 mg, 0.13 mmol) and phenylactylene (0.25 mmol), stirred for 15 min at 55 °C. Purification by column
chromatography (19:1 hexane:EtOAc) gave mixture (30 mg) as a pale yellow oil. Rf = 0.6 (4:1, Hex/EtOAc). NMR and HRMS show
the probability of all isomers HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C25H22NO2S, 400.1366; found 400.1370. HRMS (ESI-TOF)
m/z: [M+H]+ Calcd for C25H23ClNO2S, 436.1133; found 436.1130 (see in SI).
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ASSOCIATED CONTENT
Supporting Information
Soft copies of both 1H and 13C{1H} NMR spectra of all new compounds synthesized during this study, few starting materials
preparations and their data, along with single crystal X-diffraction analysis data for compounds 4ab, 4ba, and 9 can be found in this
file. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Email: beeru@iitm.ac.in.
Notes
The authors declare no competing financial interest
ACKNOWLEDGEMENTS
We thank the Indian Institute of Technology Madras, Chennai for the infrastructural facility. We thank SERB-INDIA for financial
support through EMR/2016/000041 grant. SG thanks IIT Madras for HTRA fellowship. We thank Mr. Ramkumar for single crystal X-
ray analysis.
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