Reactivity of indole-3-alkoxides in the absence of acids: Rapid synthesis of homo-bisindolylmethanes

Article abstract of DOI:10.1016/j.tet.2016.10.067

An unprecedented behaviour of in situ generated indole-3-alkoxides (MgX or Li) has been reported. Tuning the electronic properties of the alkoxides offered the direct and selective construction of bisindolylmethanes and indole-3-carbinols. This process shows very broad scope and represents the reagent (external) free, greener synthesis of structurally divergent bisindolylmethanes.

Full text of DOI:10.1016/j.tet.2016.10.067

Accepted Manuscript
Reactivity of indole-3-alkoxides in the absence of acids: Rapid synthesis of
homo-bisindolylmethanes
Bhavani Shankar Chinta, Beeraiah Baire
PII:
S0040-4020(16)31126-7
10.1016/j.tet.2016.10.067
TET 28208
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 12 September 2016
Revised Date: 24 October 2016
Accepted Date: 25 October 2016
Please cite this article as: Chinta BS, Baire B, Reactivity of indole-3-alkoxides in the absence of acids:
Rapid synthesis of homo-bisindolylmethanes, Tetrahedron (2016), doi: 10.1016/j.tet.2016.10.067.
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Reactivity of indole-3-alkoxides in the
absence of acids: Rapid synthesis of homo-
bisindolylmethanes
Leave this area blank for abstract info.
Bhavani Shankar Chinta, and Beeraiah Baire*
Department of Chemistry, Indian Institute of Technology Madras, Chennai-36, Tamilnadu, India.

1
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Tetrahedron
journal homepage: www.elsevier.com
Reactivity of indole-3-alkoxides in the absence of acids: Rapid synthesis of homo-
bisindolylmethanes
Bhavani Shankar Chinta and Beeraiah Baire*
Department of Chemistry, Indian Institute of Technology Madras, Chennai-600036, Tamilnadu, India.
ARTICLE INFO
ABSTRACT
Article history:
Received
An unprecedented behavior of in situ generated indole-3-alkoxides (MgX or Li) has been
reported. Tuning the electronic properties of the alkoxides offered the direct and selective
Received in revised form
Accepted
Available online
construction of bisindolylmethanes and indole-3-carbinols. This process shows very broad scope
and represents the reagent (external) free, greener synthesis of structurally divergent
bisindolylmethanes.
2009 Elsevier Ltd. All rights reserved.
Keywords:
Bisindolylmethanes
Alkoxides
Cascade reactions
Reagent free strategy
Indole carbinols
1. Introduction
Tandem or cascade reactions are highly atom and step
economic as multiple events occur in one step and hence provide
quick access to complex frameworks.1 These factors created
increasing interest among the synthetic community to design and
develop novel cascade strategies.2 Indole is an important
heterocyclic system present in many bioactive natural products,
drugs and biological systems.3 It has been well utilized in many
interesting cascade methodologies to synthesize structurally
divergent systems, like bisindolylmethanes4 (Scheme 1A).
Bisindolylmethanes (BIMs) are an important class of
compounds which exhibits a broad range of biological properties
such as antifungal, anti-inflammatory, antibacterial and
antimicrobial activity.5 There are numerous methods exists for
the synthesis of bisindolylmethanes,6 nevertheless, development
of new, general and eco-friendly protocols still remains as
challenge to synthetic organic chemists. The most common
methods for the synthesis of BIMs involves i) consecutive
nucleophilic addition of two molecules of indole (nucleophile) to
an aldehyde (electrophile) and ii) homodimerization of indole-3-
carbinols in presence of a Lewis acid or Brønsted acid (Scheme
1A).7 Herein we report our findings for the rapid synthesis of
homo-BIMs8 by exploring the divergent reactivity of in situ
generated indole-3-alkoxides in the absence of any external
additives (Scheme 1B).
Scheme 1. A) General Method for BIMs, B) Our approach for the selective
synthesis of BIMs and indole-3-carbinols via indole-3-alkoxides (MgX/Li)
2. Results and Discussion
Our aim was to systematically study the behaviour of indole-
3-alkoxides in the absence of any added acid reagents. Initial
investigation started with the reaction of an aldehyde 1a with
PhMgBr in THF (0.06 M) at 0 °C. When the reaction was
stopped after complete consumption of aldehyde 1a i.e., 1 h as
expected gave a homo-bisindolylmethane derivative 3aa (entry 1,
Table 1) but only in poor yield (25%). Later allowing the reaction
mixture at 0 °C for 4 h slightly improved the yield (32%). But to
our delight, BIM 3aa was isolated in 87% yield after 12 h (entry
3) at 0 °C along with benzaldehyde. Interestingly, there was no
detection of indole-3-carbinol 2aa. Encouraged by this result, we

2
Tetrahedron
then investigated for optimized reaction conditions. At RT (30
The single crystal X-ray diffraction analysis unambiguously
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°C, entry 4, Table 1) the isolated yield (84%) of BIM 3aa was
comparable to 0 °C whereas at –78 °C (entry 5) reaction was very
slow (20 h) and less efficient (74%). Different concentrations
(0.04 & 0.02 M) of reaction mixture at 0 °C, did not improve the
yield of 3aa (entries 6, 7).
confirmed the structure of homo-BIM 3af (see Supporting
Information, SI).10
Table 1. Formation of homo-BIMs via magnesium alkoxides; and reaction
optimization
With the optimized reaction conditions (0 °C or RT, and 0.06
M) in hand, we then investigated a scope study for various
Grignard reagents (Csp, Csp2 and Csp3 MgX) as well as for
electron donating N-protecting groups (Scheme 2A). Various
aliphatic, aromatic, heteroaromatic and alkynyl Grignard
reagents9 smoothly underwent the cascade process to afford
corresponding BIMs 3ab-3ah in good yields. The aldehydes 1b
and 1c with different electron donating (ED) N-protecting groups
Bn, and n-hexyl respectively, upon reaction with various
Grignard reagents gave the BIMs 3ba, 3bb, 3b’a, 3b’b, 3ca &
3cb in good yields.
Scheme 3. Scope sudy for lithium indole-3-propargyloxides to generate BIMs
Having developed a cascade process for the direct conversion
of indole-3-carbaldehydes to homo-BIMs, via Magnesium
alkoxides, we next turned our attention to alkyl lithium (Csp,
Csp2 and Csp3 Li) reagents. Various Csp2 and Csp3 lithium
reagents (Scheme 2B) smoothly afforded the expected homo-
BIMs 3aa, 3ab, and 3ag. Interestingly, the aldehyde 1a when
treated with LiAlH4 in THF at 0 °C for 12 h gave the
corresponding bisindolylmethane 3ai, in 57% yield.
Subsequently, we have carried out a scope study for various
alkynyl lithium reagents (Csp) as well as for aldehyde substrates
1a-g (Scheme 3) at 0 °C and 0.04 M concentration. All the
aldehydes 1a-g and alkynyl lithiums have smoothly underwent
the cascade reaction and gave structurally divergent homo-BIMs
4 in varying amounts (56 to 91% yields).
In continuation, we have extended this reaction to electron
withdrawing (EW) protecting groups like, N-(p-toluenesulfonyl)
(Scheme 4). The observed results are quite contrary to the case of
electron donating protecting groups (Scheme 2, 3). When N-Ts-
indole-3-carbaldehyde 5a was treated with various Grignard
reagents (ethynyl, vinyl, methyl, phenyl, 2-thienyl) and lithium
reagents (alkynyl and n-butyl) afforded only the corresponding
alcohols 6aa-6ah in excellent yields. Even after prolonged
reaction times (24 h at 0 °C–RT) no BIMs were detected.
Interestingly, N-methyl (and benzyl)-7-azaindole-3-carbaldehyde
5b or 5c, upon treatment with various RMgBr and RLi reagents
gave only the corresponding secondary alcohols 6ba, 6bb & 6ca-
6cc. This may be due to the fact that, though 5b and 5c have ED
protecting groups, the nitrogen at 7th position behaves as a strong
EWG on pyrrole unit, via –M effect and controls the product
formation. Hence we propose that it is not the ED N-protecting
groups but the electron rich nature of indole-3-aldehydes there by
indole-3-alkoxides is necessary to promote this cascade process
to generate the BIMs.
Scheme 2. Scope study for A) Grignard reagents, N-protecting groups and B)
alkyl lithium (Csp2 and Csp3 Li) reagents

3
THF for 12 h. To our surprise, BIM 3aa was formed in both the
cases in about ~ 65% yield (Scheme 6).
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Scheme 6. Control experiment
Scheme 4. Differential behaviour of e-poor indole-3-alkoxides to give indole-
carbinols and scope study
After finding the differential reactivity of electron deficient
and electron-rich indole-3-alkoxides, we next focused to see
evaluate the possibility for the heterodimerization process to
generate hetero-BIMs (Scheme 5). Two combinations of indole-
3-carbaldehydes which differ in their electronic properties have
been employed for this purpose. In first experiment, we
employed electron deficient aldehyde 5a and electron rich
aldehyde 1a, and 2-thienylmagnesium bromide as the Grignard
reagent. But, to our disappointment, there was no hetero-BIM
product observed, instead we could only isolate the homo-BIM
3ag along with the alcohol 6ae. We next employed two
aldehydes with electron donating groups on N-atom of the indole,
i.e., aldehyde 1a and 1b'. In this case, we could identify the
possible three BIMs, i.e. two homo-BIMs 3ag, 3b'b and the
hetero-BIM 7 in almost (1:1:1) ratios. Hence at this stage we
propose that obtaining hetero-BIMs selectively and exclusively
employing this strategy is highly feasible.
Scheme 7. Proposed mechanism
Based on the above observation we proposed a possible
mechanism (Scheme 7). Reaction of the aldehyde with RM will
initially forms the alkoxide 8. When R1 = EDG, one of the
alkoxide 8 can act as a nucleophiles through C3-carbon and the
other as an electrophile via 9 to form the Zwitter ionic
intermediate 10.11 This 10 in presence of Li+ or Mg+2 may
undergo a disproportionation to generate the homo-BIM 11 and
aldehyde 12. On the other hand, when R1 = EWG, nitrogen atom
there by indole ring of alkoxide 8 becomes electron deficient and
hence no formation of 9 (and 10), so stops at alcohol stage.
3. Conclusions
In conclusion we have developed an unprecedented, acid free
cascade methodology for the rapid and selective synthesis of
homobisindolylmethanes, and indole-3-carbinols by tuning the
reactivity of indole-3-alkoxides (MgX or Li). This process had
shown excellent substrate scope for indole-3-carbaldehydes as
well as RMgX and RLi reagents.
4. Experimental section
4.1. General methods
Scheme 5. Attempts to generate hetero-BIMs employing current strategy
To show the preparatoy value of the developed strategy we
performed the reaction of 1a with PhMgBr on 1.9 mmol (300
mg) scale (Figure 2). We pleased to see not much loss in the
yield (76%, where as 87% for 0.32 mmol scale, entry 3, Table 1)
of the 3aa.
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
1
spectrometers. 13C and H chemical shifts in NMR spectra were
1
referenced relative to signals of CDCl3 (δ 7.263 ppm for H and
77.16 ppm for 13C). HRMS were recorded by electron spray
ionization (ESI) method on a Q-TOF Micro. 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.
Figure 2. Scale up reaction
Finally to get insights into the mechanistic details of the
cascade process, and to support that the alkoxides are solely
involved in the formation of BIMs, we have prepared the alcohol
2aa, and treated with MeLi and MeMgBr separately at 0 °C in

4
Tetrahedron
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General Procedure: For the synthesis of BIMs from indole-
Followed general procedure. The aldehyde12 1a (50 mg 0.32
3-carbaxaldehydes and Grignard reagents (or) alkyllithium
reagents.
mmol), THF (3 mL), n-propyl magnesium bromide (2 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from CH3CH2CH2-Br
and Mg). Yield of BIM 3ad (35 mg, 0.11 mmol, 70%, yellow
oil); Rf = 0.5 (9:1, hexane:EtOAc); IR (neat): 3052, 2956, 2928,
2871, 1734, 1614, 1543, 1373, 1327, 1264, 1155, 1131, 1100,
1048, 1013, 896, 738, 699, 565, 451 and 421 cm-1; 1H NMR (400
MHz, CDCl3): δ = 7.60 (2 H, d, J = 7.9 Hz), 7.23 (2 H, t, J = 8.2
Hz), 7.16 (2 H, t, J = 7.0 Hz), 7.02 (2 H, td, J = 1.0 & 8.0 Hz),
6.82 (2 H, s), 4.47 (1 H, t, J = 7.4 Hz), 3.68 (6 H, s), 2.15 (2 H,
To the ice-cold solution of aldehyde in THF was added, the
solution of alkylmagnesium halide or alkyllithium in THF (1.3
eq., at 0 °C). The reaction was stirred at 0 °C for 1 h, diluted with
saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous
layer was extracted with ethyl acetate (2 x 10 mL). The combined
organic layers were washed with brine (10 mL), and dried over
Na2SO4. Evaporation of the solvent and purification of the crude
mixture by column chromatography (9:1, hexane: EtOAc) gave
the corresponding bisindolylmethane derivatives (BIM) up to 92
% yields along with the by-product aldehyde.
q, J = 7.4 Hz), 1.37-1.46 (2 H, m), 0.94 (3 H, t, J = 7.2 Hz); 13
NMR (100 MHz, CDCl3): δ = 137.4, 127.7, 126.3, 121.3, 119.8,
119.4, 118.5, 109.2, 38.8, 33.6, 32.7, 21.6 and 14.3. HRESI-MS:
[C22H25N2]+ = [M+H]+ requires 317.2018; found 317.2016.
C
4.1.1. 3,3'-(Phenylmethylene)bis(1-methyl-1H-indole) (3aa)
4.1.5. 3,3'-(p-Tolylmethylene)bis(1-methyl-1H-indole) (3ae)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (3 mL), phenyl magnesium bromide (2 mL in THF,
1.3 eq., 0.41 mmol, freshly prepared from PhBr and Mg). Yield
of BIM 3aa (48 mg, 0.137 mmol, 87%, light pink solid); Rf = 0.6
(4:1; hexane:EtOAc); IR (neat): 3055, 3019, 2924, 2852, 1734,
1717, 1700, 1684, 1652, 1615, 1559, 1541, 1522, 1507, 1471,
1421, 1371, 1327, 1231, 1154, 1119, 1049, 1013, 920, 795, 740,
701, 669, 510, 475 and 419 cm-1; 1H NMR (400 MHz, CDCl3): δ
= 7.37 (2 H, td, J = 0.8 & 7.9 Hz), 7.34 (2 H, d, J = 7.0 Hz), 7.24-
7.29 (4 H, m), 7.16-7.21 (3 H, m), 6.98 (2 H, ddd, J = 1.0, 7.0 &
8.0 Hz), 6.52 (2 H, d, J = 0.8 Hz), 5.87 (1 H, s), 3.67 (6 H, s);
13C NMR (100 MHz, CDCl3): δ = 144.6, 137.5, 128.8, 128.4,
128.3, 127.6, 126.1, 121.5, 120.2, 118.8, 118.4, 109.2, 40.2 and
32.7; HRESI-MS: [C25H23N2]+ = [M+H]+ requires 351.1861;
found 351.1861; M.P.: 180-183 °C.
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (3 mL), p-tolylmagnesium bromide (2 mL in THF,
1.3 eq., 0.41 mmol, freshly prepared from 4-bromotoluene and
Mg). Yield of BIM 3ae (44 mg, 0.12 mmol, 77%, light pink
solid); Rf = 0.6 (4:1, hexane:EtOAc); IR (neat): 3050, 3019,
2923, 2853, 1734, 1717, 1700, 1684, 1652, 1616, 1558, 1541,
1508, 1471, 1420, 1370, 1327, 1228, 1153, 1118, 1013, 795, 739,
669, 519, 474, 443 and 418 cm-1; 1H NMR (400 MHz, CDCl3): δ
= 7.37 (2 H, d, J = 7.9 Hz), 7.27 (2 H, d, J = 8.2 Hz), 7.16-7.23
(4 H, m), 7.06 (2 H, d, J = 7.9 Hz), 6.97 (2 H, ddd, J = 1.0,7.1 &
7.8 Hz), 6.52 (2 H, s), 5.83 (1 H, s), 3.66 (6 H, s), 2.31 (3 H, s);
13C NMR (100 MHz, CDCl3): δ = 141.6, 137.5, 135.4, 129.0,
128.6, 128.3, 127.6, 121.5, 120.2, 118.7, 118.6, 109.1, 39.8, 32.7
and 21.2; HRESI-MS: [C26H25N2]+ = [M+H]+ requires 365.2018;
found 365.2016; M.P: 178-180 °C
4.1.2. 3,3'-(Ethane-1,1-diyl)bis(1-methyl-1H-indole) (3ab)
4.1.6.3,3'-[(4-Methoxyphenyl)methylene]bis(1-methyl-1H-indole)
Followed general procedure. The aldehyde12 1a (30 mg 0.19
mmol), THF (3 mL), methyl magnesium chloride (0.1 mL of 3 M
in THF, 0.25 mmol). Yield of BIM 3ab (18 mg, 0.06 mmol,
67%, yellow oil); Rf = 0.5 (9:1, hexane:EtOAc); IR (neat): 3053,
3019, 2926, 2854, 1597, 1448, 1423, 1372, 1327, 1265, 1216,
1174, 1124, 1089, 1054, 1018, 962, 811, 766, 704, 671, 589, 572,
538, 460, 437, 427 and 410 cm-1; 1H NMR (400 MHz, CDCl3): δ
= 7.57 (2 H, d, J = 7.9 Hz), 7.26 (2 H, d, J = 8.2 Hz), 7.18 (2 H, t,
J = 7.3 Hz), 7.02 (2 H, t, J = 7.3 Hz), 6.70 (2 H, s), 4.66 (1 H, q,
J = 7.1 Hz), 3.67 (6 H, s), 1.78 (3 H, d, J = 7.1 Hz); 13C NMR
(100 MHz, CDCl3): δ = 137.4, 127.4, 126.1, 121.4, 120.4, 119.9,
(3af)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (3 mL), p-OMePhMgBr (2 mL in THF, 1.3 eq., 0.41
mmol, freshly prepared from p-OMePhBr and Mg). Yield of
BIM 3af (48 mg, 0.126 mmol, 81%, red solid). 3af was
recrystallized from toluene at RT to get a single crystal and
studied its X-ray diffraction analysis; Rf
= 0.6 (4:1,
hexane:EtOAc); IR (neat): 3051, 3020, 2923, 2850, 2738, 1684,
1599, 1578, 1509, 1462, 1426, 1369, 1315, 1261, 1216, 1159,
1108, 1025, 833, 740, 641, 603, 554, 514, 485, 463, 422 and 403
cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.37 (2 H, d, J = 7.9 Hz),
7.22-7.27 (4 H, m), 7.18 (2 H, td, J = 1.0 & 7.2 Hz), 6.97 (2 H,
ddd, J = 1.0, 7.0 & 7.9 Hz), 6.80 (2 H, d, J = 8.7 Hz), 6.50 (2 H,
d, J = 0.7 Hz), 5.84 (1 H, s), 3.77 (3 H, s), 3.65 (6 H, s); 13C
NMR (100 MHz, CDCl3): δ = 157.9, 137.5, 136.8, 132.1, 129.6,
128.3, 127.5, 121.5, 120.2, 118.7, 113.6, 109.1, 55.3, 39.3 and
32.7; HRESI-MS: [C26H25N2O]+ = [M+H]+ requires 381.1967;
found 381.1965; M.P: 187-190 °C.
118.5, 109.2, 32.7, 28.1 and 22.3; HRESI-MS: [C20H21N2]+
[M+H]+ requires 289.1705; found 289.1703.
=
4.1.3. 3,3'-(Propane-1,1-diyl)bis(1-methyl-1H-indole) (3ac)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (3 mL), ethyl magnesium bromide (2 mL in THF,
1.3 eq., 0.41 mmol, freshly prepared from EtBr and Mg). Yield
of BIM 3ac (34 mg, 0.11 mmol, 72%, yellow oil); Rf = 0.5 (9:1,
hexane:EtOAc); IR (neat): 3050, 2956, 2927, 2871, 1717, 1653,
1613, 1544, 1470, 1422, 1372, 1326, 1304, 1250, 1231, 1205,
1155, 1130, 1087, 1050, 1012, 922, 900, 797, 738, 692, 659, 555,
4.1.7.
(3ag)
3,3'-(Thiophen-2-ylmethylene)bis(1-methyl-1H-indole)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (3 mL), 2-thiophenylmagnesium bromide (2 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from 2-
bromothiophene and Mg). Yield of BIM 3ag (48 mg, 0.135
1
456 and 431 cm-1; H NMR (400 MHz, CDCl3): δ = 7.60 (2 H,
dd, J = 2.0 & 7.8 Hz), 7.24 (2 H, dd, J = 2.2 & 8.1 Hz), 7.17 (2
H, ddd, J = 2.0, 7.0 & 8.0 Hz), 7.02 (2 H, dt, J = 2.1 & 7.1 Hz),
6.82 (2 H, d, J = 2.6 Hz), 4.35 (1 H, td, J = 2.2 & 7.2 Hz), 3.67
mmol, 86%, dark brown viscous oil); Rf
= 0.6 (4:1,
(6 H, s ), 2.17-2.25 (2 H, m), 1.00 (3 H, td, J = 3.0 & 7.3 Hz); 13
C
hexane:EtOAc); IR (neat): 3052, 2923, 2852, 1734, 1717, 1652,
1613, 1542, 1522, 1507, 1471, 1421, 1371, 1328, 1265, 1154,
1118, 1045, 1012, 895, 852, 739, 701, 539 and 420 cm-1;1H NMR
(400 MHz, CDCl3): δ = 7.45 (2 H, d, J = 7.8 Hz), 7.28 (2 H, d, J
= 8.0 Hz), 7.17-7.23 (2 H, m), 7.11 (1 H, d, J = 4.5 Hz), 7.01 (2
H, t, J = 7.2 Hz), 6.88 (2 H, d, J = 5.2 Hz), 6.68 (2 H, s), 6.12 (1
H, s), 3.66 (6 H, s); 13C NMR (100 MHz, CDCl3): δ = 149.3,
NMR (100 MHz, CDCl3): δ = 137.4, 127.7, 126.3, 121.3, 119.9,
119.1, 118.5, 109.1, 35.8, 32.7, 29.3 and 13.2; HRESI-MS:
[C21H23N2]+ = [M+H]+ requires 303.1861; found 303.1860.
4.1.4. 3,3'-(Butane-1,1-diyl)bis(1-methyl-1H-indole) (3ad)

5
137.4, 127.9, 127.2, 126.4, 125.0, 123.5, 121.6, 119.9, 118.9,
118.3, 109.2, 35.3 and 32.7; HRESI-MS: [C23H21N2S]+ = [M+H]+
requires 357.1425; found 357.1423.
7.23 (2 H, d, J = 8.4 Hz), 7.15 (2 H, ddd, J = 1.0, 7.0 & 8.1 Hz),
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6.91-6.95 (4 H, m), 6.51 (2 H, s), 5.79 (1 H, s), 3.98 (4 H, t, J =
7.1 Hz), 3.77 (3 H, s), 1.73 (4 H, t, J = 6.7 Hz), 1.22 ( 13 H, m),
0.84 (5 H, t, J = 6.6 Hz); 13C NMR (100 MHz, CDCl3): δ =
157.9, 136.9, 136.8, 133.6, 129.7, 127.8, 127.7, 127.4, 120.3,
118.5, 113.6, 109.3, 55.3, 46.3, 39.5, 31.5, 30.3, 26.7, 22.6 and
14.1; HRESI-MS: [C36H45N2O]+ = [M+H]+ requires 521.3532;
found 521.3531.
4.1.8. 3,3'-(Prop-2-yne-1,1-diyl)bis(1-methyl-1H-indole) (3ah)
Followed general procedure-A. The aldehyde12 1a (50 mg
0.32 mmol), THF (4 mL), ethynylmagnesium bromide (1 mL of
0.5 M in THF, 0.42 mmol). Yield of BIM 3ag (32 mg, 0.11
mmol, 68%, brown oil); Rf = 0.5 (9:1, hexane:EtOAc); IR (neat):
3432, 3289, 3051, 2928, 2881, 2822, 1611, 1549, 1524, 1470,
1422, 1370, 1330, 1261, 1232, 1197, 1155, 1124, 1061, 1013,
789, 741, 695, 636, 422 and 401 cm-1 ;1H NMR (400 MHz,
CDCl3): δ = 7.68 (2 H, d, J = 7.9 Hz), 7.27 (2 H, d, J = 8.2 Hz),
7.18-7.22 (2 H, m), 7.06 (2 H, ddd, J = 1.0, 7.0 & 7.9 Hz), 6.96
(2 H, s), 5.51 (1 H, d, J = 2.6 Hz), 3.96 (6 H, s), 2.35 (1 H, d, J =
2.6 Hz); 13C NMR (100 MHz, CDCl3): δ = 137.5, 127.3, 126.7,
121.7, 119.8, 119.0, 114.2, 109.4, 85.4, 69.6, 32.8 and 26.0;
HRESI-MS: [C21H19N2]+ = [M+H]+ requires 299.1548; found
299.1545.
4.1.12.
(3cb)
3,3'-(Thiophen-2-ylmethylene)bis(1-hexyl-1H-indole)
Followed general procedure. The aldehyde14 1c (50 mg 0.22
mmol), THF (2 mL), 2-thiophenylmagnesium bromide (2 mL in
THF, 1.3 eq., 0.29 mmol, freshly prepared from 2-
bromothiophene and Mg). Yield of BIM 3cb (50 mg, 0.1 mmol,
92%, brown viscous oil); Rf = 0.6 (9:1, hexane:EtOAc); IR
(neat): 3050, 2957, 2930, 2857, 1735, 1656, 1612, 1546, 1467,
1394, 1363, 1334, 1265, 1221, 1177, 1155, 1121, 1087, 1038,
1014, 894, 853, 735, 702, 618, 567, 533, 495, 473 and 446 cm-1;
1H NMR (400 MHz, CDCl3): δ = 7.43 (2 H, d, J = 7.9 Hz), 7.29
(2 H, d, J = 8.3 Hz), 7.11-7.20 (3 H, m), 6.98 (2 H, ddd, J = 1.0,
7.1 & 7.9 Hz), 6.87-6.90 (2 H, m), 6.73 (2 H, s), 6.13 (1 H, s),
3.99 (4 H, t, J = 7.1 Hz), 1.74 (4 H, t, J = 6.7 Hz), 1.24 (12 H, m),
0.84 (6 H, t, J = 6.7 Hz); 13C NMR (100 MHz, CDCl3): δ =
149.4, 136.6, 127.4, 127.0, 126.4, 125.1, 123.5, 121.3, 120.0,
118.7, 118.1, 109.4, 46.3, 35.4, 31.5, 30.2, 26.7, 22.6 and 14.1;
HRESI-MS: [C33H41N2S]+ = [M+H]+ requires 497.2990; found
497.2988.
4.1.9. 3,3'-[(4-Methoxyphenyl)methylene]bis(1-benzyl-1H-indole)
(3ba)
Followed general procedure. The aldehyde13 1b (50 mg 0.212
mmol), THF (2 mL), p-OMePhMgBr (2 mL in THF, 1.3 eq., 0.28
mmol, freshly prepared from p-OMePhBr and Mg). Yield of
BIM 3ba (49 mg, 0.09 mmol, 87%, brown viscous oil); Rf = 0.6
(4:1, hexane:EtOAc); IR (neat): 3058, 2954, 2924, 2853, 1656,
1598, 1545, 1509, 1462, 1352, 1032, 828, 733, 640, 571, 557,
1
533, 454, 429 and 403 cm-1; H NMR (400 MHz, CDCl3): δ =
4.1.13. 1-Benzyl-3-[1-(1-benzyl-5-methoxyindolin-3-yl) ethyl]-5-
7.40 (2 H, dd, J = 0.8 & 7.8 Hz), 7.17-7.26 (11 H, m), 7.11 (2 H,
td, J = 1.0 & 7.0 Hz), 7.02 (3 H, d, J = 6.4 Hz), 6.97 (2 H, ddd, J
= 1.0, 7.0 & 7.9 Hz), 6.81 (2 H, d, J = 8.7 Hz), 6.64 (2 H, d, J =
0.8 Hz), 5.86 (1 H, s), 5.19 (4 H, s), 3.75 (3 H, s); 13C NMR (100
MHz, CDCl3): δ = 158.0, 138.0, 137.2, 136.4, 129.7, 128.7,
127.97, 127.94, 127.5, 126.6, 121.7, 120.3, 119.3, 119.0, 113.7,
109.8, 55.3, 50.0 and 39.5; HRESI-MS: [C38H33N2O]+ = [M+H]+
requires 533.2593; found 533.2590.
methoxy-1H-indole (3bc)
Followed general procedure. The aldehyde15 1b (45 mg 0.17
mmol), THF (3 mL), and MeMgCl (0.1 mL in THF, 1.3 eq., 0.22
mmol). Yield of BIM 3bc (35 mg, 0.07 mmol, 83%, pale yellow
viscous oil); Rf = 0.5 (9:1, hexane:EtOAc); IR (neat):3059, 3031,
2956, 2929, 2871, 1617, 1578, 1485, 1450, 1392, 1355, 1326,
1275, 1219, 1174, 1107, 1070, 1035, 892, 872, 837, 794, 737,
701, 647, 603, 566, 527 and 509 cm-1; H NMR (400 MHz,
1
4.1.10.
3,3'-(Thiophen-2-ylmethylene)bis(1-benzyl-1H-indole)
CDCl3): δ = 7.21-7.25 (6 H, m), 7.09 (2 H, d, J = 8.8 Hz), 7.05 (4
H, d, J = 8.0 Hz), 7.00 (2 H, d, J = 2.4 Hz), 6.88 (2 H, s), 6.77 (2
H, dd, J = 2.4 & 8.8 Hz), 5.19 (4 H, s), 4.59 (1 H, q, J = 7.1 Hz),
3.69 (6 H, s), 1.79 (3 H, d, J = 7.1 Hz); 13C NMR (100 MHz,
CDCl3): δ = 153.6, 138.1, 132.5, 128.8, 128.0, 127.5, 126.6,
126.3, 120.2, 111.6, 110.5, 102.1, 56.0, 50.2, 28.4 and 21.8;
HRESI-MS: [C34H33N2O2]+ = [M+H]+ requires 501.2542; found
501.2540.
(3bb)
Followed general procedure. The aldehyde13 1b (50 mg 0.212
mmol), THF (2 mL), 2-thiophenylmagnesium bromide (2 mL in
THF, 1.3 eq., 0.28 mmol, freshly prepared from 2-
bromothiophene and Mg). Yield of BIM 3bb (40 mg, 0.08 mmol,
74%, brown viscous oil); Rf = 0.6 (4:1, hexane:EtOAc); IR
(neat): 3057, 3029, 2923, 2854, 1672, 1610, 1547, 1522, 1493,
1464, 1419, 1390, 1354, 1332, 1265, 1200, 1173, 1106, 1076,
1028, 1028, 1014, 852, 810, 739, 698, 623, 561, 532, 473 and
4.1.14. 1-Benzyl-3-[(1-benzyl-5-methoxyindolin-3-yl)(thiophen-2-
yl)methyl]-5-methoxy-1H-indole (3bd)
1
460 cm-1; H NMR (400 MHz, CDCl3): δ = 7.47 (2 H, d, J = 8.0
Hz), 7.20-7.27 (8 H, m), 7.10-7.14 (3 H, m), 6.99-7.04 (6 H, m),
Followed general procedure. The aldehyde15 1b (45 mg 0.17
mmol), THF (1.5 mL), and 2-thiophenylmagnesium bromide (1.5
mL in THF, 1.3 eq., 0.22 mmol, freshly prepared from 2-
bromothiophene and Mg). BIM 3bd (38 mg, 0.07 mmol, yield =
79%) a brown viscous oil; Rf = 0.6 (4:1, hexane:EtOAc); IR
(neat): 3062, 3031, 2993, 2924, 2852, 1618, 1578, 1547, 1485,
1450, 1392, 1354, 1312, 1269, 1220, 1173, 1125, 1102, 1076,
1038, 909, 836, 793, 736, 700, 637, 595, 567. 523 and 495 cm-1;
1H NMR (400 MHz, CDCl3): δ = 7.20-7.26 (6 H, m), 7.15 (1 H,
dd, J = 1.5 & 5.0 Hz), 7.07 (2 H, d, J = 8.9 Hz), 7.02 (4 H, d, J =
8.0 Hz), 6.92 (1 H, s), 6.91 (1 H, d, J = 3.2 Hz), 6.89 (2 H, d, J =
2.4 Hz), 6.83 (2 H, s), 6.77 (2 H, dd, J = 2.4 & 8.9 Hz), 6.08 (1
H, s), 5.19 (4 H, s), 3.67 (6 H, s); 13C NMR (100 MHz, CDCl3): δ
= 153.8, 148.9, 138.0, 132.3, 128.8, 128.1, 127.9, 127.5, 126.5,
125.2, 123.7, 120.1, 118.2, 111.9, 110.6, 102.1, 55.9, 50.3, 35.6;
HRESI-MS: [C34H33N2O2S]+ = [M+H]+ requires 569.2263; found
569.2260.
6.90-6.92 (2 H, m), 6.85 (2 H, s), 6.21 (1 H, s), 5.22 (4 H, s); 13
C
NMR (100 MHz, CDCl3): δ = 148.9, 137.9, 137.0, 136.3, 135.2,
128.7, 127.58, 127.52, 126.58, 126.53, 125.2, 123.7, 121.8,
120.1, 119.2, 118.9, 50.0 and 35.5; HRESI-MS: [C35H29N2S]+ =
[M+H]+ requires 509.2051; found 509.2050.
4.1.11. 3,3'-((4-Methoxyphenyl)methylene)bis(1-hexyl-1H-indole)
(3ca)
Followed general procedure. The aldehyde14 1c (50 mg 0.22
mmol), THF (2 mL), p-OMePhMgBr (2 mL in THF, 1.3 eq., 0.29
mmol, freshly prepared from 4-bromoanisole and Mg). Yield of
BIM 3ca (35 mg, 0.07 mmol, 62%, brown viscous oil); Rf = 0.6
(9:1, hexane:EtOAc); IR (neat): 3050, 2954, 2926, 2855, 1721,
1721, 1655, 1464, 1363, 1178, 1121, 1039, 823, 808, 738, 592,
535, 513, 486, 471, 434 and 414 cm-1;1H NMR (400 MHz,
CDCl3): δ = 7.35 (2 H, d, J = 7.8 Hz), 7.29 (2 H, d, J = 8.2 Hz),

6
Tetrahedron
4.1.15. 3,3'-(Thiophen-2-ylmethylene)bis(1-methyl-1H-indole)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
ACCEPTED MANUSCRIPT
(3ag)
mmol), THF (4 mL), and trimethylsilylethynyllithium [4 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from TMS-acetylene
and BuLi (1.6 M in hexane)]. BIM 4ab (22 mg, 0.16 mmol,
Followed general procedure. The aldehyde12 1a (50 mg 0.32
n
mmol), THF (3 mL), 2-thiophenyllithium [2 mL in THF, 1.3 eq.,
yield = 38%) as a dark pink oil, and the by-product aldehyde
4ab'17; Rf = 0.6 (4:1, hexane:EtOAc); IR (neat): 3052, 2956,
2928, 2853, 2823, 2169, 1716, 1613, 1546, 1522, 1470, 1423,
1371, 1329, 1249, 1220, 1196, 1155, 1129, 1064, 1036, 1036,
n
0.41 mmol, freshly prepared from 2-bromothiophene and BuLi
(1.6 M in hexane)]. Yield of BIM 3ag (44 mg, 0.124 mmol, 79%,
dark brown viscous oil).
1
1021, 1012, 977, 843, 739, 700, 667, 627, 569 and 425 cm-1; H
4.1.16. 3,3'-(Phenylmethylene)bis(1-methyl-1H-indole) (3aa)
NMR (400 MHz, CDCl3): δ = 7.82 (2 H, d, J = 7.9 Hz), 7.36 (2
H, d, J = 8.1 Hz), 7.31 (2 H, t, J = 7.4 Hz), 7.17 (2 H, t, J = 7.0
Hz), 7.01 (2 H, s), 5.65 (1 H, s), 3.76 (6 H, s), 0.29 (9 H, s); 13C
NMR (100 MHz, CDCl3): δ = 137.5, 127.2, 126.8, 121.6, 120.0,
118.8, 114.6, 109.3, 107.6, 85.5, 32.7, 27.3 and 0.33; HR ESI-
MS: [C24H26N2Si]+ = [M+H]+ requires 371.1899; found 371.1898
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), phenyl lithium (4 mL in THF, 1.3 eq., 0.41
mmol, freshly prepared from PhBr and Mg). Yield of BIM 3aa
(46 mg, 0.131 mmol, 84%, light pink solid).
4.1.17. 3,3'-(Ethane-1,1-diyl)bis(1-methyl-1H-indole) (3ab)
Followed general procedure. The aldehyde12 1a (40 mg 0.26
mmol), THF (6 mL), MeLi (0.2 mL of 1.6 M in Et2O, 0.34
mmol,). Yield of BIM 3ab (26 mg, 0.09 mmol, 71%, light yellow
oil).
4.1.21. 3,3'-(Undec-2-yn-1,1-diyl)bis(1-methyl-1H-indole) (4ac)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and dec-1-ynyllithium [4 mL in THF, 1.3
n
eq., 0.41 mmol, freshly prepared from 1-decyne and BuLi (1.6
M in hexane)]. BIM 4ac (46 mg, 0.11 mmol, 71%) as a dark
brown oil and the by-product aldehyde;16 Rf = 0.6 (4:1,
hexane:EtOAc); IR (neat):3053, 2924, 2851, 2745, 2681, 1878,
1738, 1738, 1669, 1612, 1559, 1544, 1468, 1437, 1415, 1376,
1327, 1263, 1236, 1194, 1156, 1130, 1061, 1023, 1008, 1130,
1061, 1023, 1008, 909, 818, 783, 734, 703, 647, 567 and 426 cm-
4.1.18. Bis(1-methyl-1H-indol-3-yl)methane (3ai)
To the ice-cold solution of N-Me-indole-3-aldehyde 1a (40 mg,
0.253 mmol) in THF (5 mL) was added, lithium aluminum
hydride (LAH) (40 mg, 1.01 mmol). The reaction was stirred at 0
°C for 12 h. Quenched with ethyl acetate (2 mL) and filtered
over a celite bed using ethyl acetate. Evaporation of the solvent
and purification of the crude mixture by column chromatography
(9:1, hexane: EtOAc) gave the corresponding BIM 3ai (20 mg,
0.072 mmol 57%) as a pale brown oil; Rf = 0.5 (9:1;
hexane:EtOAc); IR (neat): 3059, 2975, 2926, 1726, 1646, 1607,
1468, 1416, 1372, 1330, 1262, 1120, 1044, 740, 703, 671, 599,
553 and 425 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.61 (2 H, d,
J = 7.1 Hz), 7.28 (2 H, d, J = 7.5 Hz), 7.20 (2 H, d, J = 6.9 Hz),
7.08 (2 H, s), 6.77 (2 H, s), 4.21 (2 H, s), 3.68 (6 H, s); 13C NMR
(100 MHz, CDCl3): δ = 137.2, 128.0, 127.0, 121.5, 119.4, 118.6,
114.4, 109.2, 32.7 and 21.0; HRESI-MS: [C19H19N2]+ = [M+H]+
requires 275.1548; found 275.1545.
1
1; H NMR (400 MHz, CDCl3): δ = 7.66 (2 H, d, J = 7.9 Hz),
7.25 (2 H, d, J = 8.2 Hz), 7.18 (2 H, td, J = 1.0 & 7.0 Hz), 7.04
(2 H, ddd, J = 1.0, 7.0 & 7.9 Hz), 6.91 (2 H, s), 5.48 (1 H, s),
3.67 (6 H, s), 2.22 (2 H, td, J = 2.2 & 7.1 Hz), 1.50-1.56 (3 H,
m), 1.37-1.40 (2 H, m), 1.15-1.27 (7 H, m), 0.85-0.89 (3 H, m) ;
13C NMR (100 MHz, CDCl3): δ =137.6, 127.1, 126.9, 121.5,
120.0, 118.8, 115.7, 109.2, 81.7, 81.3, 32.7, 31.9, 29.39, 29.31,
29.2, 29.1, 26.2, 22.8, 19.1 and 14.2; HR ESI-MS: [C29H34N2]+ =
[M+H]+ requires 411.2756; found 411.2753.
4.1.22. 3,3'-(Hept-2-yn-1,1-diyl)bis(1-methyl-1H-indole) (4ad)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and hexynyllithium [4 mL in THF, 1.3 eq.,
0.41 mmol, freshly prepared from 1-hexyne and BuLi (1.6 M in
4.1.19.
indole) (4aa)
3,3'-(3-Phenylprop-2-yne-1,1-diyl)bis(1-methyl-1H-
n
hexane)]. BIM 4ad (43 mg, 0.12 mmol, 77%) as a brown oil; Rf
= 0.6 (4:1, hexane: EtOAc); IR (neat): 3050, 3025, 2956, 2930,
2871, 1656, 1614, 1546, 1468, 1424, 1372, 1327, 1266, 1228,
1195, 1155, 1130, 1060, 1012, 923, 784, 688, 555, 500, 472, 455,
444 and 424 cm-1; 1H NMR (400 MHz, CDCl3): δ =7.68 (2 H, d,
J = 7.9 Hz), 7.25 (2 H, d, J = 8.1 Hz), 7.19 (2 H, t, J = 7.1 Hz),
7.05 (2 H, t, J = 7.0 Hz), 6.91 (2 H, s), 5.48 (1 H, s), 3.68 (6 H,
s), 2.23 (2 H, q, J = 7.3 Hz), 1.52 (2 H, t, J = 7.6 Hz), 1.37-1.46
(2 H, m), 0.89 (3 H, t, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3):
δ = 137.5, 127.1, 126.9, 121.5, 120.0, 118.7, 115.6, 109.2, 81.6,
81.2, 32.7, 31.3, 26.2, 22.1, 18.8 and 13.7; HR ESI-MS:
[C25H26N2]+ = [M+H]+ requires 355.2130; found 355.2129.
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and phenylethynyllithium [4 mL in THF,
1.3 eq., 0.41 mmol, freshly prepared from phenylacetylene and
nBuLi (1.6 M in hexane)]. BIM 4aa (44 mg, 0.12 mmol, yield =
75%) as a brown viscous oil, and the by-product aldehyde 4aa';16
Rf = 0.6 (4:1, hexane:EtOAc); IR (neat): 3052, 2925, 2851, 2818,
1614, 1597, 1546, 1470, 1423, 1371, 1329, 1263, 1226, 1195,
1155, 1119, 1063, 1012, 918, 791, 740, 692, 528 and 430 cm-1;
1H NMR (400 MHz, CDCl3): δ = 7.25 (2 H, d, J = 7.9 Hz), 7.41
(2 H, dd, J = 2.0 & 6.0 Hz), 7.16-7.25 (7 H, m), 7.03-7.07 (2 H,
m), 6.95 (2 H, s), 5.85 (1 H, s), 3.65 (6 H, s); 13C NMR (100
MHz, CDCl3): δ =137.6, 131.8, 128.2, 127.7, 127.3, 126.9,
124.1, 121.7, 120.0, 119.0, 114.9, 109.3, 91.2, 81.7, 32.7 and
26.9; HRESI-MS: [C27H22N2]+ = [M+H]+ requires 375.1817;
found 375.1815.
4.1.23. 3,3'-(4-Methylpent-4-en-2-yn-1,1-diyl)bis(1-methyl-1H-
indole) (4ae)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and 3-methylbut-3-en-1-ynyllithium [4 mL
in THF, 1.3 eq., 0.41 mmol, freshly prepared from 2-methylbut-
3-Phenylpropiolaldehyde (4aa’)
1H NMR (400 MHz, CDCl3): δ = 9.39 (1 H, d, J = 0.6 Hz),
7.57 (2 H, d, J = 7.8 Hz), 7.46 (1 H, t, J = 7.1 Hz), 7.37 (2 H, t, J
= 7.9 Hz); 13C NMR (100 MHz, CDCl3): δ = 176.8, 133.3, 131.7,
131.3, 128.8, 95.2 and 88.5.
n
1-en-3-yne and BuLi (1.6 M in hexane)]. BIM 4ae (36 mg,
0.106 mmol, 67%) as a brown solid and the by-product
aldehyde;19 Rf = 0.6 (4:1, hexane: EtOAc); IR (neat): 3051, 2924,
2853, 1734, 1717, 1653, 1653, 1613, 1544, 1522, 1470, 1423,
1371, 1329, 1293, 1264, 1226, 1195, 1155, 1129, 1061, 1012,
4.1.20. 3,3'-[3-(Trimethylsilyl)prop-2-yne-1,1-diyl]bis(1-methyl-
1H-indole) (4ab)
1
895, 739, 703, 571, 548 and 423 cm-1; H NMR (400 MHz,
CDCl3): δ = 7.69 (2 H, dt, J = 0.8 & 7.9 Hz), 7.27 (2 H, d, J =
8.2 Hz), 7.20 (2 H, ddd, J = 1.0, 7.0 & 8.2 Hz), 7.06 (2 H, ddd, J

7
= 1.0, 7.0 & 8.0 Hz), 6.93 (2 H, s), 5.62 ( 1 H, s), 5.25 (1 H, m),
15.5; HRESI-MS: [C29H26N2]+ = [M+H]+ requires 403.2130;
found 403.2130.
ACCEPTED MANUSCRIPT
5.14-5.15 (1 H, m), 3.69 (6 H, s), 1.89 (3 H, t, J = 1.1 Hz); 13C
NMR (100 MHz, CDCl3): δ = 137.5, 127.4, 127.2, 126.8, 121.6,
120.8, 120.0, 118.9, 114.9, 109.3, 90.1, 83.0, 32.8, 26.7 and 23.9;
HRESI-MS: [C24H22N2]+ = [M+H]+ requires 339.1817; found
339.1817; M.P: 82-84 °C.
3-(4-Ethylphenyl)propionaldehyde (4ah’)
1H NMR (400 MHz, CDCl3): δ = 9.41 (1 H, s), 7.52 (2 H, d, J
= 8.2 Hz), 7.23 (2 H, d, J = 8.4 Hz), 2.68 (2 H, q, J = 7.6 Hz),
1.24 (3 H, t, J = 7.6 Hz); 13C NMR (100 MHz, CDCl3): δ =
176.8, 133.6, 131.7, 128.5, 127.8, 96.0, 88.6, 29.1 and 15.1.
4.1.24. 3,3'-(3-Cyclopropylprop-2-yne-1,1-diyl)bis(1-methyl-1H-
indole) (4af)
4.1.27.
methyl-1H-indole) (4ai)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and (4-fluorophenyl)ethynyllithium [4 mL
in THF, 1.3 eq., 0.41 mmol, freshly prepared from (4-
3,3'-[3-(4-Fluorophenyl)prop-2-yne-1,1-diyl]bis(1-
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and cyclopropylethynyllithium [4 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from
ethynylcyclopropane and nBuLi (1.6 M in hexane)]. BIM 4af (47
mg, 0.14 mmol, 88%) as a brown oil and the by-product
aldehyde;20 Rf = 0.6 (4:1, hexane: EtOAc); IR (neat): 3050, 3009,
2926, 2853, 1734, 1653, 1614, 1545, 1470, 1423, 1371, 1328,
1266, 1228, 1194, 1155, 1129, 1059, 1012, 924, 890, 812, 788,
n
fluorophenylacetylene and BuLi (1.6 M in hexane)]. BIM 4ai
(54 mg, 0.14 mmol, 87%) as a violet solid and the by-product
aldehyde 4ai’;10 Rf = 0.6 (4:1, hexane: EtOAc); IR (neat): 3052,
2924, 2852, 1718, 1599, 1544, 1506, 1471, 1423, 1371, 1329,
1228, 1155, 1119, 1091, 1062, 1012, 836, 806, 788, 740, 530,
460 and 425 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.74 (2 H, d,
J = 8.0 Hz), 7.38 (2 H, dd, J = 5.4 & 8.8 Hz), 7.27 (2 H, d, J =
8.2 Hz), 7.20 (2 H, td, J = 0.9 & 7.0 Hz), 7.07 (2 H, ddd, J = 1.0,
7.0 & 8.0 Hz), 6.95 (2 H, s), 6.93 (2 H, t, J = 8.8 Hz), 5.71 (1 H,
s), 3.66 (6 H, s); 13C NMR (100 MHz, CDCl3): δ = 163.4, 160.9,
137.5, 133.6, 133.5, 127.2, 126.8, 121.7, 119.9, 119.0, 115.5,
115.3, 114.6, 109.4, 90.8, 80.6, 32.7 and 26.8; HRESI-MS:
[C27H21N2F]+ = [M+H]+ requires 393.1722; found 393.1720;
M.P: 130-132 °C.
1
890, 571, 548, 506, 454 and 427 cm-1; H NMR (400 MHz,
CDCl3): δ = 7.66 (2 H, d, J = 8.0 Hz), 7.23 (2 H, d, J = 8.2 Hz),
7.17 (2 H, t, J = 7.7 Hz), 7.04 (2 H, ddd, J = 0.9, 6.9 & 7.8 Hz),
6.88 (2 H, s), 5.44 (1 H, s), 3.63 (6 H, s),1.25-1.27 (2 H, m),
0.65-0.69 (3 H, m); 13C NMR (100 MHz, CDCl3): δ = 137.4,
127.1, 126.8, 121.5, 119.9, 118.7, 115.4, 109.2, 84.5, 76.5, 32.7,
26.1, 8.23 and -0.05; HRESI-MS: [C24H22N2]+ = [M+H]+ requires
339.1817; found 339.1815.
4.1.25.
3,3'-[3-(p-Tolyl)prop-2-yn-1,1-diyl]bis(1-methyl-1H-
indole) (4ag)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and p-tolylethynyllithium [4 mL in THF,
1.3 eq., 0.41 mmol, freshly prepared from 4-
4.1.28.
methyl-1H-indole) (4aj)
3,3'-{3-[4-(tert-Butyl)phenyl]prop-2-yn-1,1-diyl}bis(1-
n
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and (4-tert-butylphenyl)ethynyllithium [4
mL in THF, 1.3 eq., 0.41 mmol, freshly prepared from 4-tert-
butylphenylacetylene and nBuLi (1.6 M in hexane)]. BIM 4aj (51
mg, 0.12 mmol, 75%) as a brown oil and the by-product aldehyde
4aj’;21 Rf = 0.5 (4:1, hexane: EtOAc); IR (neat): 3050, 2961,
2865, 1655, 1611, 1545, 1503, 1468, 1423, 1370, 1328, 1266,
1220, 1196, 1117, 1061, 1013, 835, 739, 668, 563, 452 and 426
cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.75 ( 2 H, d, J = 7.9 Hz),
7.37 (2 H, d, J = 8.5 Hz), 7.26 (4 H, dd, J = 3.3 & 5.3 Hz), 7.20
(2 H, td, J = 1.0 & 7.0 Hz), 7.05 (2 H, ddd, J = 1.1, 6.9 & 8.0
Hz), 6.96 (2 H, s), 5.71 (1 H, s), 3.65 (6 H, s), 1.27 (9 H, s); 13C
NMR (100 MHz, CDCl3): δ =150.9, 137.5, 131.5, 127.3, 126.9,
125.2, 121.6, 121.1, 120.0, 118.9, 115.0, 109.3, 90.5, 81.7, 34.7,
32.7, 31.3 and 26.9; HRESI-MS: [C31H31N2]+ = [M+K]+ requires
431.2487 ; found 431.2483.
methyphenylacetylene and BuLi (1.6 M in hexane)]. BIM 4ag
(47 mg, 0.12 mmol, 77%) as a brown oil and the by-product
aldehyde 4ag’;19 Rf = 0.6 (4:1, hexane: EtOAc); IR (neat): 3050,
3019, 2923, 2853, 1734, 1717, 1700, 1684, 1652, 1616, 1558,
1541, 1508, 1471, 1420, 1370, 1327, 1228, 1153, 1118, 1013,
1
795, 739, 669, 519, 474, 443, 418 and 405 cm-1; H NMR (400
MHz, CDCl3): δ = 7.75 (2 H, d, J = 7.9 Hz), 7.33 (2 H, d, J = 8.1
Hz), 7.29 (2 H, d, J = 8.2 Hz), 7.21 (2 H, td, J = 1.1 & 7.0 Hz),
7.03-7.07 (4 H, m), 6.99 (2 H, d, J = 0.5 Hz), 5.87 (1 H, s), 3.69
(6 H, s), 2.29 (3 H, s); 13C NMR (100 MHz, CDCl3): δ = 137.7,
137.6, 131.7, 128.9, 127.3, 126.9, 121.6, 121.09, 121.06, 118.9,
115.0, 109.3, 90.4, 81.8, 32.8, 26.9 and 21.5; HRESI-MS:
[C28H24N2]+ = [M+H]+ requires 389.1973; found 389.1972.
3-(p-Tolyl)propionaldehyde (4ag’)
1H NMR (400 MHz, CDCl3): δ = 9.40 (1 H, s), 7.49 (2 H, d, J
= 8.2 Hz), 7.19 (2 H, d, J = 8.4 Hz), 2.38 (3 H, s).
3-[4-(tert-Butyl)phenyl]propiolaldehyde (4aj’)
4.1.26. 3,3'-[3-(4-Ethylphenyl)prop-2-yne-1,1-diyl]bis(1-methyl-
1H-indole) (4ah)
1H NMR (400 MHz, CDCl3): δ = 9.38 (1 H, s), 7.52 (2 H, d, J
= 8.7 Hz), 7.39 (2 H, d, J = 8.7 Hz), 1.30 (9 H, s); 13C NMR (100
MHz, CDCl3): δ = 176.8, 133.3, 131.4, 125.9, 125.2, 96.0, 88.5
and 31.1.
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and (4-ethylphenyl)ethynyllithium [4 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from 4-
ethyphenylacetylene and nBuLi (1.6 M in hexane)]. BIM 4ah (52
mg, 0.13 mmol, 82%) as a brown oil and the by-product aldehyde
4ah’;21 Rf = 0.6 (4:1, hexane: EtOAc); IR (neat): 3050, 3019,
2962, 2929, 2874, 1655, 1610, 1546, 1509, 1469, 1421, 1370,
1329, 1255, 1226, 1195, 1155, 1121, 1059, 1013, 962, 924, 834,
785, 739, 687, 553,461 and 413 cm-1; 1H NMR (400 MHz,
CDCl3): δ = 7.74 (2 H, d, J = 8.0 Hz), 7.35 (2 H, d, J = 8.1 Hz),
7.25 (2 H, d, J = 8.2 Hz), 7.19 (2 H, t, J = 7.0 Hz), 7.06 (4 H, t, J
= 8.0 Hz), 6.97 (2 H, s), 5.71 (1 H, s), 3.66 (6 H, s), 2.58 (2 H, q,
J = 7.6 Hz), 1.18 (3 H, t, J = 7.6 Hz); 13C NMR (100 MHz,
CDCl3): δ =144.0, 137.6, 131.8, 127.7, 127.3, 126.9, 121.6,
121.3, 120.0, 118.9, 115.0, 109.3, 90.4, 81.8, 32.7, 28.8, 26.9 and
4.1.29.
3,3'-[3-(3-Fluorophenyl)prop-2-yne-1,1-diyl]bis(1-
methyl-1H-indole) (4ak)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and (3-fluorophenyl)ethynyllithium [4 mL
in THF, 1.3 eq., 0.41 mmol, freshly prepared from 3-
n
fluorophenylacetylene and BuLi (1.6 M in hexane)]. BIM 4ak
(35 mg, 0.09 mmol, 56%) as a brown oil and the by-product
aldehyde;21 Rf = 0.5 (4:1, hexane: EtOAc); IR (neat): 3051, 2930,
2885, 2851, 1759, 1658, 1608, 1578, 1548, 1473, 1427, 1370,
1330, 1287, 1262, 1230, 1152, 1125, 1057, 1011, 985, 874, 848,
1
786, 769, 740, 679, 569, 520 and 420 cm-1; H NMR (400 MHz,

8
Tetrahedron
ACCEPTED MANUSCRIPT
CDCl3): δ = 7.73 (2 H, d, J = 8.0 Hz), 7.28 (2 H, d, J = 8.2 Hz),
1046, 969, 894, 739, 704, 608, 581, 528, 492, 459, 438 and 423
7.20 (4 H, m), 7.08 (3 H, ddd, J = 1.0, 6.9 & 8.0 Hz), 6.96 (2 H,
s), 6.90-6.95 (1 H, m), 5.72 (1 H, s), 3.69 (6 H, s); 13C NMR (100
MHz, CDCl3): δ =163.7, 161.2, 137.9, 129.79, 129.71, 127.74,
127.70, 127.3, 126.8, 126.0, 125.9, 121.8, 119.9, 119.1, 118.7,
118.5, 115.1, 114.9, 114.5, 109.4, 92.3, 80.66, 80.63, 32.8 and
26.9; HRESI-MS: [C27H21FKN2]+ = [M+K]+ requires 431.1326 ;
found 431.1333.
cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.73 (2 H, d, J = 7.9 Hz),
7.42 (2 H, dd, J = 2.3 & 7.4 Hz), 7.02-7.26 (12 H, m), 7.11 (4 H,
td, J = 1.1 & 8.2 Hz), 7.06 (4 H, ddd, J = 1.8, 5.6 & 8.2 Hz), 7.02
(1 H, dd, J = 1.0 & 7.0 Hz), 5.74 (1 H, s), 5.26 (4 H, s); 13C NMR
(100 MHz, CDCl3): δ = 137.8, 137.2, 131.8, 128.8, 128.2, 127.7,
127.6, 127.2, 126.9, 126.8, 124.0, 121.9, 120.2, 119.2, 115.3,
109.9, 90.9, 82.0, 50.1 and 27.3; HRESI-MS: [C39H31N2]+
[M+H]+ requires 527.2487; found 527.2485.
=
4.1.30.
3,3'-[3-(Cyclohex-1-en-1-yl)prop-2-yn-1,1-diyl]bis(1-
methyl-1H-indole) (4al)
4.1.34. 3,3'-(3-(Trimethylsilyl)prop-2-yn-1,1-diyl)bis(1-benzyl-
1H-indole) (4bb)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and 1-ethynylcyclohexenyllithium [4 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from 1-
Followed general procedure. The aldehyde13 1b (50 mg 0.213
mmol), THF (2.5 mL), and 4,4’-trimethylsilylethynyllithium [3
mL in THF, 1.3 eq., 0.28 mmol, freshly prepared from 4,4’-
n
cyclohexenylacetylene and BuLi (1.6 M in hexane)]. BIM 4al
n
(46 mg, 0.12 mmol, 77%) as a brown oil, and the by-product
aldehyde;22 Rf = 0.6 (4:1, hexane: EtOAc); IR (neat): 3051, 3025,
2927, 2855, 1702, 1654, 1614, 1542, 1521, 1469, 1423, 1371,
biphenylacetylene and BuLi (1.6 M in hexane)]. BIM 4bb (48
mg, 0.092 mmol, 87%) as brown oil and the by-product
aldehyde;17 Rf = 0.5 (4:1, hexane:EtOAc); IR (neat): 3059, 3030,
2957, 2926, 2856, 1706, 1656, 1610, 1546, 1522, 1494, 1465,
1389, 1354, 1333, 1248, 1172, 1125, 1100, 1077, 1050, 1014,
1
1329, 1220, 1155, 1128, 1081, 1012, 919, 739 and 420 cm-1; H
NMR (400 MHz, CDCl3): δ = 7.69 (2 H, d, J = 7.9 Hz), 7.25 (2
H, t, J = 8.2 Hz), 7.19 (2 H, t, J = 7.7 Hz), 7.03-7.07 (2 H, m),
6.93 (2 H, s), 6.04-6.06 (1 H, m), 5.60 (1 H, m), 2.04-2.14 (4 H,
m), 1.53-1.61 (4 H, m); 13C NMR (100 MHz, CDCl3): δ =137.6,
133.5, 127.2, 126.9, 121.6, 121.2, 120.0, 118.8, 115.3, 109.2,
88.1, 83.5, 32.7, 29.6, 26.7, 25.7, 22.5 and 21.7; HRESI-MS:
[C27H26N2Na]+ = [M+Na]+ requires 401.1994; found 401.1986.
981, 843, 739, 672,607, 552, 499 and 467 cm-1; H NMR (400
1
MHz, CDCl3): δ = 7.51 (2 H, d, J = 7.9 Hz), 7.03-7.09 (8 H, m),
6.96 (2 H, td, J =1.0 & 7.0 Hz), 6.88-6.91 (7 H, m), 6.86 (1 H, d,
J = 7.0 Hz), 5.39 (1 H, s), 5.06 (4 H, s), –0.02 (9 H, s); 13C NMR
(100 MHz, CDCl3): δ = 137.7, 137.2, 128.8, 127.6, 127.1, 126.9,
126.8, 121.8, 120.2, 119.1, 115.0, 109.8, 107.4, 85.9, 50.0, 27.69
and 0.30; HRESI-MS: [C36H35N2Si]+
523.2570; found 523.2568.
=
[M+H]+ requires
3-(Cyclohex-1-en-1-yl)propionaldehyde (4al’)
1H NMR (400 MHz, CDCl3): δ = 9.29 (1 H, s), 6.52-6.53 (1
H, m), 2.17-2.18 (4 H, m), 1.59-1.67 (4 H, m).
4.1.35. 3,3'-(3-Phenylprop-2-yn-1,1-diyl)bis(1-hexyl-1H-indole)
(4ea)
4.1.31.
methyl-1H-indole) (4am)
Followed general procedure. The aldehyde12 1a (50 mg 0.32
mmol), THF (4 mL), and 4,4’-biphenylethynyllithium [4 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from 4,4’-
3,3'-{3-[(1,1'-Biphenyl)-4-yl]prop-2-yn-1,1-diyl}bis(1-
Followed general procedure. The aldehyde14 1e (50 mg 0.22
mmol), THF (2.5 mL), and 4,4’-phenylethynyllithium [3 mL in
THF, 1.3 eq., 0.29 mmol, freshly prepared from 4,4’-
phenylacetylene and nBuLi (1.6 M in hexane)]. BIM 4ea (50 mg,
0.11 mmol, 91%) as brown oil and the by-product aldehyde;16 Rf
= 0.6 (4:1, hexane:EtOAc); IR (neat): 3052, 2954, 2928, 2856,
1658, 1597, 1547, 1524, 1466, 1395, 1363, 1176, 1122, 1015,
976, 916, 691, 646, 618, 559, 527, 514, 485, 467, 454, 431and
410 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.72 (2 H, tt, J = 0.8
& 7.9 Hz), 7.42-7.45 (2 H, m), 7.30 (2 H, tt, J = 0.7 & 8.3
Hz),7.22-7.27 (3 H, m), 7.17 ( 2 H, ddd, J = 1.1, 7.1 & 8.6 Hz),
7.02-7.06 (4 H, m), 5.73 (1 H, s), 4.02 (4 H, t, J = 6.8 Hz), 1.77
(4 H, t, J = 6.1 Hz), 1.27 (12 H, m), 0.84 (6 H, s); 13C NMR (100
MHz, CDCl3): δ = 136.8, 131.8, 128.2, 127.6, 127.0, 126.4,
124.2, 121.4, 120.1, 118.8, 114.6, 109.5, 91.3, 81.7, 46.4, 31.5,
30.3, 27.1, 26.8, 22.6 and 14.1;
n
biphenylacetylene and BuLi (1.6 M in hexane)]. BIM 4am (49
mg, 0.11 mmol, 69%) as brown oil and the by-product aldehyde
4am';23 Rf = 0.5 (4:1, hexane:EtOAc); IR (neat): 3053, 3028,
2925, 2853, 1734, 1654, 1613, 1545, 1519, 1483, 1471, 1423,
1371, 1329, 1263, 1195, 1155, 1119, 1061, 1011, 917, 841, 764,
740, 697, 558, 506, 472 and 423 cm-1; H NMR (400 MHz,
1
CDCl3): δ = 7.77 (2 H, d, J = 7.9 Hz), 7.57 (2 H, m), 7.50 (4 H,
s), 7.42 (2 H, t, J = 7.2 Hz), 7.29-7.34 (3 H, m), 7.20-7.24 (2 H,
m), 7.07-7.11 (2 H, m), 7.01 (2 H, s), 5.75 (1 H, s), 3.73 (6 H, s);
13C NMR (100 MHz, CDCl3): δ =140.6, 140.4, 137.6, 132.2,
128.9, 127.5, 127.3, 127.1, 126.94, 126.90, 123.1, 121.7, 120.0,
119.0, 114.8, 109.4, 91.9, 81.6, 32.8 and 27.0; HRESI-MS:
[C33H26N2Na]+ = [M+Na]+ requires 473.1994 ; found 473.2000.
4.1.36. 3,3'-(3-(Trimethylsilyl)prop-2-yn-1,1-diyl)bis(1-hexyl-1H-
indole) (4eb)
3-[(1,1'-biphenyl)-4-yl]propionaldehyde (4am’)
Followed general procedure. The aldehyde14 1e (50 mg 0.22
mmol), THF (2.5 mL), and trimethylsilylethynyllithium [3 mL in
THF, 1.3 eq., 0.29 mmol, freshly prepared from TMS-acetylene
and nBuLi (1.6 M in hexane)]. BIM 4eb (49 mg, 0.1 mmol, 90%)
as brown oil and the by-product aldehyde;17 Rf = 0.6 (4:1,
hexane:EtOAc); IR (neat): 3048, 2927, 2856, 1704, 1655, 1612,
1546, 1465, 1397, 1364, 1248, 1177, 1122, 1042, 1015, 980, 844,
1H NMR (400 MHz, CDCl3): δ = 9.42 (1 H, s), 7.63 (3 H, dd,
J = 2.0 & 8.6 Hz), 7.58 (1 H, dd, J = 1.5 & 6.0 Hz), 7.49 (1 H, d,
J = 1.8 Hz), 7.44 (3 H, dd, J = 1.5 & 6.2 Hz), 7.40 (1 H, dt, J =
1.3 & 7.3 Hz).
4.1.33. 3,3'-(3-Phenylprop-2-yn-1,1-diyl)bis(1-benzyl-1H-indole)
(4ba)
1
738, 625, 557, 512, 498,450 and 408 cm-1; H NMR (400 MHz,
Followed general procedure. The aldehyde13 1b (50 mg 0.213
mmol), THF (2.5 mL), and 4,4’-phenylethynyllithium [3 mL in
THF, 1.3 eq., 0.28 mmol, freshly prepared from 4,4’-
phenylacetylene and nBuLi (1.6 M in hexane)]. BIM 4ba (47 mg,
0.09 mmol, 84%) as brown oil and the by-product aldehyde;16 Rf
= 0.5 (4:1, hexane:EtOAc); IR (neat): 3054, 2959, 2926, 2855,
1734, 1656, 1600, 1523, 1491, 1465, 1375, 1265, 1176, 1079,
CDCl3): δ = 7.49 (2 H, d, J = 8.0 Hz), 7.10 (2 H, d, J = 8.0 Hz),
6.98 (2 H, td, J = 1.0 & 6.8 Hz), 6.84 (2 H, td, J = 0.9 & 8.0 Hz),
6.78 (2 H, s), 5.34 (1 H, s), 3.83 (4 H, t, J = 7.1 Hz), 1.59 (4 H, t,
J = 7.0 Hz), 1.08-1.09 (12 H, m), 0.67 (6 H, t, J = 6.6 Hz), –0.01
(9 H, s); 13C NMR (100 MHz, CDCl3): δ = 136.8, 126.9, 126.4,
121.3, 120.2, 118.6, 114.3, 109.4, 107.8, 85.5, 46.4, 31.5, 30.3,
27.5, 26.7, 22.6, 14.1 and 0.33.

9
1
4.1.37. 3,3'-(3-(Trimethylsilyl)prop-2-yn-1,1-diyl)bis(5-bromo-1-
methyl-1H-indole) (4ga)
638,569 and 547 cm-1; H NMR (400 MHz, CDCl3): δ = 7.03-
ACCEPTED MANUSCRIPT
7.07 (6 H, m), 6.95 (2 H, d, J = 2.4 Hz), 6.92 (1 H, s), 6.88-6.90
(5 H, m), 6.83 (2 H, s), 6.60 (2 H, dd, J = 2.4 & 8.9 Hz), 5.12 (4
H, s), 3.53 (6 H, s), -0.02 (9 H, s); 13C NMR (100 MHz, CDCl3):
δ = 153.8, 137.8, 132.5, 128.8, 127.6, 127.5, 127.4, 126.8, 114.3,
112.2, 110.6, 107.2, 101.9, 85.8, 55.8, 50.3, 27.7 and 0.38;
HRESI-MS: [C38H29N2O2Si]+ = [M+H]+ requires 583.2781;
found 583.2780; M.P: 142-144°C.
Followed general procedure. The aldehyde24 1g (50 mg 0.22
mmol), THF (2.5 mL), and trimethylsilylethynyllithium [34 mL
in THF, 1.3 eq., 0.29 mmol, freshly prepared from TMS-
n
acetylene and BuLi (1.6 M in hexane)]. BIM 4ga (49 mg, 0.09
mmol, 84%) as brown oil and the by-product aldehyde;17 Rf = 0.6
(4:1, hexane:EtOAc); IR (neat): 3052, 3018, 2958, 2925, 2854,
1734, 1671, 1609, 1561, 1543, 1474, 1422, 1374, 1264, 1216,
1144, 1123, 1074, 1046, 980, 895, 846, 792, 756, 703, 669, 629,
591, 531, 458, 429 and 412 cm-1; 1H NMR (400 MHz, CDCl3): δ
= 7.63 (2 H, d, J = 1.8 Hz), 7.05 (2 H, dd, J = 1.9 & 8.7 Hz), 6.89
(2 H, d, J = 8.7 Hz), 6.64 (2 H, s), 5.15 (1 H, s), 3.45 (6 H, s), -
0.0185 (9 H, s); 13C NMR (100 MHz, CDCl3): δ = 136.3, 131.8,
128.2, 124.6, 122.5, 113.8, 112.4, 110.9, 106.5, 86.7, 33.03,
27.3and 0.2.
4.1.41. 1-(1-Tosyl-1H-indol-3-yl)prop-2-yn-1-ol (6aa)
Followed general procedure. The aldehyde27 5a (50 mg 0.17
mmol), THF (3 mL), and ethynylmagnesium bromide [0.5 mL
(0.5 M in THF), 0.22 mmol]. Alcohol 6aa (51 mg, 0.16 mmol,
93%) as a light yellow oil; Rf = 0.4 (4:1, hexane:EtOAc); IR
(neat): 3447, 3292, 2919, 2850, 1596, 1542, 1492, 1448, 1400,
1369, 1275, 1212, 1173, 1120, 1098, 1082, 1019, 982, 917, 812,
748, 703, 683, 660, 588, 572, 536, 488, 442, 433 and 412 cm-1;
1H NMR (400 MHz, CDCl3): δ = 7.92-7.94 (1 H, d, J = 8.4 Hz),
7.72-7.74 (2 H, d, J = 8.3 Hz), 7.68-7.70 (2 H, t, J = 3.2 Hz),
7.27-7.31 (1 H, ddd, J = 0.9, 7.3 & 8.2 Hz), 7.18-7.22 (1 H, t, J =
7.7 Hz), 7.13-7.15 (2 H, d, J = 8.1 Hz), 5.61 (1 H, s), 2.64 (1 H,
br s), 2.63 (1 H, d, J = 2.2 Hz), 2.26 (3 H, s); 13C NMR (100
MHz, CDCl3): δ = 145.2, 135.6, 135.1, 130.0, 128.3, 126.9,
125.1, 124.3, 123.4, 122.0, 120.5, 113.7, 82.4, 74.4, 57.8 and
21.5.
4.1.38. 3,3'-(3-Phenylprop-2-yn-1,1-diyl)bis(5-methoxy-1-methyl-
1H-indole) (4fa)
Followed general procedure. The aldehyde25 1f (50 mg 0.264
mmol), THF (3 mL), and phenylethynyllithium [3.5 mL in THF,
1.3 eq., 0.41 mmol, freshly prepared from phenylacetylene and
nBuLi (1.6 M in hexane)]. BIM 4fa (45 mg, 0.103 mmol, 78%) as
violet colour solid and the by-product aldehyde;16 Rf = 0.6 (4:1,
hexane:EtOAc); IR (neat): 3053, 2994, 2936, 2830, 1620, 1576,
1543, 1489, 1454, 1423, 1376, 1348, 1302, 1264, 1217, 1173,
1135, 1057, 1034, 910, 889, 834, 795, 757. 734, 692, 670, 635,
4.1.42. 1-(1-Tosyl-1H-indol-3-yl)prop-2-en-1-ol (6ab)
Followed general procedure-A. The aldehyde27 5a (40 mg
0.134 mmol), THF (3 mL), and vinylmagnesium bromide [0.4
mL (0.5 M in THF), 0.18 mmol]. Alcohol 6ab (41 mg, 0.13
mmol, 93%) as light yellow oil; Rf = 0.4 (4:1, hexane:EtOAc); IR
(neat): 3590, 3441, 3055, 3021, 2983, 2927, 2867, 1599, 1443,
1370, 1267, 1215, 1176, 1125, 1093, 1023, 981, 932, 803, 743,
1
611, 527, 494 and 444 cm-1; H NMR (400 MHz, CDCl3): δ =
7.43 (2 H, dd, J = 2.1 & 7.6 Hz), 7.23 (5 H, m), 7.17 (2 H, d, J =
8.8 Hz), 6.92 (2 H, s), 6.87 (2 H, dd, J = 2.4 & 8.8 Hz), 5.64 (1
H, s), 3.77 (6 H, s), 3.66 (6 H, s); 13C NMR (100 MHz, CDCl3): δ
= 153.8, 133.0, 131.8, 128.2, 127.9, 127.7, 127.2, 124.1, 114.2,
112.0, 110.1, 101.9, 91.1, 81.8, 56.0, 32.9 and 26.9; M.P: 158-
160 °C.
670, 580, 540 and 434 cm-1; H NMR (400 MHz, CDCl3): δ =
1
7.94-7.96 (1 H, d, J = 8.3 Hz), 7.73-7.75 (2 H, d, J = 8.3 Hz),
7.60-7.61 (1 H, d, J = 7.8 Hz), 7.51 (1 H, s), 7.27-7.31 (1 H, t, J =
7.3 Hz), 7.16-7.22 (3 H, m), 6.08-6.16 (1 H, m), 5.38-5.42 (2 H,
t, J = 6.8 Hz), 5.23-5.26 (1 H, d, J = 10.3 Hz), 2.29 (3 H, s), 2.25
(1 H, br s); 13C NMR (100 MHz, CDCl3): δ = 145.09, 138.6,
135.6, 135.2, 129.9, 128.9, 126.9, 124.9, 124.1, 123.3, 123.2,
120.6, 116.3, 113.7, 68.9 and 21.6.
4.1.39. 3,3'-(3-Phenylprop-2-yn-1,1-diyl)bis(1-benzyl-5-bromo-
1H-indole) (4da)
Followed general procedure. The aldehyde26 1d (50 mg 0.16
mmol), THF (2 mL), and 4,4’-phenylethynyllithium [2 mL in
THF, 1.3 eq., 0.21 mmol, freshly prepared from 4,4’-
n
biphenylacetylene and BuLi (1.6 M in hexane)]. BIM 4da (38
mg, 0.06 mmol, 71%) as brown oil and the by-product
aldehyde;16 Rf = 0.5 (4:1, hexane:EtOAc); IR (neat): 3054, 3031,
2925, 2856, 1733, 1604, 1561, 1545, 1490, 1469, 1453, 1390,
1373, 1354, 1298, 1265, 1216, 1170, 1077, 1054, 1028, 894, 851,
4.1.43. 1-(1-Tosyl-1H-indol-3-yl)ethan-1-ol (6ac)
Followed general procedure-A. The aldehyde27 5a (30 mg 0.1
mmol), THF (3 mL), and vinylmagnesium bromide [0.1 mL (3 M
in THF), 0.13 mmol]. Alcohol 6ac (29 mg, 0.09 mmol, 91%) as
light yellow oil; Rf = 0.4 (4:1, hexane:EtOAc); IR (neat): 3430,
3051, 2924, 2857, 1598, 1459, 1369, 1269, 1173, 1124, 1048,
962, 673, 578, 541 and 441 cm-1; 1H NMR (400 MHz, CDCl3): δ
=7.94-7.96 (1 H, d, J = 8.3 Hz), 7.72-7.74 (1 H, d, J = 8.3
Hz),7.61-7.63 (1 H, d, J = 7.8 Hz), 7.48 (1 H, s), 7.27-7.31 (1 H,
t, J = 7.4 Hz), 7.06-7.23 (3 H, m), 5.06-5.11 (1 H, q, J = 6.3 Hz),
1
815, 793, 700, 668, 630, 594, 564, 529, 457 and 420 cm-1; H
NMR (400 MHz, CDCl3): δ = 7.80 (2 H, d, J = 1.7 Hz), 7.44 (2
H, dd, J = 2.3 & 6.0 Hz), 7.24-7.33 (9 H, s), 7.21 (1 H, d, J = 1.9
Hz), 7.19 (3 H, m), 7.07 (6 H, dd, J = 2.6 & 8.8 Hz), 5.62 (1 H,
s), 5.26 (4 H, s); 13C NMR (100 MHz, CDCl3): δ = 137.1, 136.0,
131.8, 129.1, 128.6, 128.3, 128.07, 128.03, 127.8, 126.6, 124.9,
123.6, 122.6, 114.4, 112.8, 111.6, 89.7, 82.7, 50.4 and 27.2;
HRESI-MS: [C39H29N2Br2]+ = [M+H]+ requires 685.0677; found
685.0675.
2.30 (3 H, s), 1.96 (1 H, br s), 1.57-1.59 (3 H, d, J = 6.5 Hz); 13
NMR (100 MHz, CDCl3): δ =145.0, 135.6, 135.3, 130.0, 129.0,
127.1, 126.9, 124.9, 123.2, 122.2, 120.5, 113.8, 63.9, 23.5 and
21.6.
C
4.1.40. 3,3'-(3-(Trimethylsilyl)prop-2-yn-1,1-diyl)bis(1-benzyl-5-
methoxy-1H-indole) (4ca)
4.1.44. Phenyl (1-tosyl-1H-indol-3-yl) methanol (6ad)
Followed general procedure. The aldehyde15 1c (50 mg 0.19
mmol), THF (2.5 mL), and trimethylsilylethynyllithium [3 mL in
THF, 1.3 eq., 0.41 mmol, freshly prepared from TMS-acetylene
Followed general procedure-A. The aldehyde27 5a (40 mg
0.134 mmol), THF (3 mL), and phenylmagnesium bromide [2
mL in THF, 0.18 mmol, freshly prepared from PhBr and Mg].
Alcohol 6ad (47 mg, 0.124 mmol, 94%) as a colorless solid; Rf =
0.4 (4:1, hexane:EtOAc); IR (neat): 3413, 3059, 3032, 2924,
2924, 2856, 1646, 1598, 1449, 1368, 1271, 1172, 1124, 1090,
n
and BuLi (1.6 M in hexane)]. BIM 4ca (45 mg, 0.08 mmol,
82%) as brown oil and the by-product aldehyde;17 Rf = 0.5 (4:1,
hexane:EtOAc); IR (neat): 3061, 3030, 2955, 2937, 2861, 2832,
1655, 1619, 1579, 1545, 1486, 1452, 1396, 1354, 1309, 1267,
1248, 1216, 1174, 1101, 1044, 987, 843, 795, 760, 735, 701,
1021, 971, 806, 752, 692, 672, 575, 539 and 432 cm-1; H NMR
1
(400 MHz, CDCl3): δ = 7.91-7.93 (1 H, d, J = 8.3 Hz), 7.68-7.70

10
Tetrahedron
ACCEPTED MANUSCRIPT
(2 H, d, J = 8.3 Hz), 7.42 (1 H, s), 7.33-7.35 (3 H, d, J = 7.6
H, d, J = 8.3 Hz), 7.75-7.78 (2 H, m), 7.72- 7.73 (2 H, d, J = 4.7
Hz), 7.21-7.31 (4 H, m), 7.13-7.15 (2 H, d, J = 8.1 Hz), 7.07-7.10
(1 H, t, J = 7.6 Hz), 5.93 (1 H, s), 2.51 (1 H, br s), 2.27 (3 H, s);
13C NMR (100 MHz, CDCl3): δ = 145.0, 142.1, 135.7, 135.2,
130.0, 129.9, 129.0, 128.7, 128.2, 126.9, 126.8, 125.6, 124.9,
124.0, 123.3, 120.6, 70.4 and 21.6; M.P: 122-125°C.
Hz), 7.42-7.44 (2 H, dd, J = 2.3 & 7.8 Hz), 7.26-7.32 (4 H, m),
7.20-7.24 (1 H, t, J = 7.9 Hz), 7.14-7.16 (2 H, d, J = 8.2 Hz), 5.84
(1 H, s), 2.54 (1 H, br s), 2.26 (3 H, s); 13C NMR (100 MHz,
CDCl3): δ = 145.2, 135.7, 135.3, 131.9, 130.0, 128.8, 128.5,
128.4, 127.0, 125.1, 124.2, 123.4, 122.5, 122.2, 120.6, 113.7,
87.7, 86.1, 58.5 and 21.6.
4.1.45. Thiophen-2-yl(1-tosyl-1H-indol-3-yl)methanol (6ae)
4.1.49.
1-(1-Methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-
Followed general procedure. The aldehyde27 5a (40 mg 0.134
mmol), THF (3 mL), and 2-thiophenylmagnesium bromide [2 mL
in THF, 0.18 mmol, freshly prepared from 2-bromothiophene and
Mg]. Alcohol 6ae (47 mg, 0.122 mmol, 91%) as a brown oil; Rf
= 0.4 (4:1, hexane:EtOAc); IR (neat): 3429, 3053, 3021, 2985,
2927, 1597, 1428, 1375, 1265, 1218, 1177, 1042, 894, 754, 576
(trimethylsilyl)prop-2-yn-1-ol (6ba)
Followed general procedure. The aldehyde27 5b (50 mg 0.312
mmol), THF (4 mL), and trimethylsilylethynyllithium [4 mL in
THF, 0.41 mmol, freshly prepared from phenylacetylene and
nBuLi (1.6 M in hexanes)]. Alcohol 6ba (60 mg, 0.232 mmol,
75%) as brown oil; Rf = 0.4 (4:1, hexane:EtOAc); IR (neat):
3408, 3053, 2961, 1665, 1599, 1543, 1490, 1460, 1409, 1350,
1298, 1265, 1197, 1141, 1069, 1003, 974, 854, 797, 739, 702,
629, 586, 509, 478,458 and 421 cm-1; 1H NMR (400 MHz,
CDCl3): δ = 8.08-8.09 (1 H, dd, J = 1.6 & 3.1 Hz), 7.89-7.92 (1
H, dd, J = 1.1 & 7.8 Hz), 6.97 (1 H, s), 6.81-6.84 (1 H, m), 5.48
(1 H, s), 3.56 (3 H, s), 3.35 (1 H, br s), -0.02 (9 H, s); 13C NMR
(100 MHz, CDCl3): δ = 148.1, 143.3, 128.2, 127.4, 118.5, 115.6,
113.5, 105.4, 89.2, 58.4, 31.3 and -0.03.
1
and 539 cm-1; H NMR (400 MHz, CDCl3): δ = 7.93-7.96 (1 H,
d, J = 8.4 Hz), 7.72-7.74 (2 H, d, J = 8.4 Hz), 7.59 (1 H, d, J =
0.8 Hz), 7.41-7.43 (1 H, d, J =7.9 Hz), 7.21-7.27 (2 H, m), 7.15-
7.17 (2 H, d, J = 8.2 Hz), 7.10-7.14 (1 H, ddd, J = 0.8, 7.2 & 8.0
Hz), 6.89-6.93 (2 H, m), 2.7 (1 H, br s), 2.28 (3 H, s); 13C NMR
(100 MHz, CDCl3): δ = 146.3, 145.1, 135.6, 135.1, 133.5, 129.9,
128.7, 126.9, 126.8, 125.7, 125.3, 125.1, 125.0, 123.9, 123.3,
120.6, 66.2 and 21.6.
4.1.46. 1-(1-Tosyl-1H-indol-3-yl)pentan-1-ol (6af)
4.1.50.
phenylprop-2-yn-1-ol (6bb)
Followed general procedure. The aldehyde27 5b (50 mg 0.312
mmol), THF (4 mL), and phenylethynyllithium [4 mL in THF,
1-(1-Methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-
Followed general procedure. The aldehyde27 5a (40 mg 0.134
mmol), THF (3 mL), and nBuLi [0.1 mL (1.6 M in hexanes), 0.18
mmol]. Alcohol 6af (35 mg, 0.1 mmol, 74%) as light yellow oil;
Rf = 0.5 (4:1, hexane:EtOAc); IR (neat): 3439, 3132, 3055, 2983,
2959, 2932, 2862, 1731, 1677, 1598, 1546, 1490, 1446, 1424,
1372, 1266, 1210, 1174, 1124, 1095, 1041, 1017, 972, 895,
n
0.41 mmol, freshly prepared from phenylacetylene and BuLi
(1.6 M in hexanes)]. Alcohol 6bb (65 mg, 0.25 mmol, 80%) as
brown oil; Rf = 0.4 (4:1, hexane:EtOAc); IR (neat): 3304, 3055,
2939, 2857, 1720, 1706, 1658, 1599, 1573, 1542, 1489, 1460,
1408, 1351, 1299, 1266, 1196, 1142, 1124, 1069, 1027, 996, 940,
912, 798, 756 and 737, 653, 605, 586, 534, 478 and 434 cm-1; 1H
NMR (400 MHz, CDCl3): δ = 8.29-8.30 (1 H, dd, J = 1.5 & 4.8
Hz), 8.15-8.17 (1 H, dd, J = 1.6 & 7.8 Hz), 7.42-7.45 (2 H, m),
7.28-7.30 (3 H, dd, J = 1.9 & 5.2 Hz), 7.24 (1 H, s),7.01-7.04 (1
H, dd, J = 4.8 & 7.9 Hz), 5.93 (1 H, s), 3.96 (1 H, br s), 3.76 (3
H, s); 13C NMR (100 MHz, CDCl3): δ =148.1, 143.2, 131.7,
128.5, 128.4, 128.2, 127.4, 122.6, 118.6, 115.7, 113.8, 89.1, 85.1,
58.5 and 31.2.
1
812,741, 685, 617, 554, 513 and 430 cm-1; H NMR (400 MHz,
CDCl3): δ =7.94-7.96 (1 H, d, J = 8.3 Hz), 7.71-7.73 (2 H, d, J =
8.3 Hz), 7.60-7.62 (1 H, d, J = 7.8 Hz), 7.47 (1 H, s), 7.24-7.28 (1
H, t, J = 7.1 Hz),7.15-7.23 (3 H, m), 4.86-4.90 (1 H, t, J = 6.5
Hz), 2.29 (3 H, s), 2.12(1 H, br s) 1.83-1.89 (2 H, q, J = 6.0 Hz),
1.23-1.36 (4 H, m), 0.83-0.87 (3 H, t, J = 6.8 Hz); 13C NMR (100
MHz, CDCl3): δ = 145.0, 135.7, 135.3, 130.4, 129.9, 127.3,
126.9, 124.9, 123.2, 122.8, 120.5, 113.9, 68.1, 36.9, 28.0, 22.6,
21.6 and 14.1.
4.1.47. 1-(1-Tosyl-1H-indol-3-yl)-3-(trimethylsilyl)prop-2-yn-1-
ol (6ag)
4.1.51.
1-(1-Benzyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-
Followed general procedure. The aldehyde27 5a (50 mg 0.17
mmol), THF (2 mL), and trimethylsilylethynyllithium [2 mL in
THF, 0.22 mmol, freshly prepared from TMS-acetylene and
nBuLi (1.6 M in hexanes)]. Alcohol 6ag (52 mg, 0.13 mmol,
78%) as yellow oil; Rf = 0.4 (4:1, hexane:EtOAc); IR (neat):
3408, 3053, 2961, 1665, 1599, 1543, 1490, 1350, 1298, 1265,
1197, 1141, 1069, 1003, 974, 854, 797, 739, 702, 629, 586, 509,
(trimethylsilyl)prop-2-yn-1-ol (6ca)
Followed general procedure. The aldehyde27 5c (50 mg 0.21
mmol), THF (2.5 mL), and trimethylsilylethynyllithium [3 mL in
THF, 0.27 mmol, freshly prepared from TMS-acetylene and
nBuLi (1.6 M in hexanes)]. Alcohol 6ca (66 mg, 0.2 mmol, 93%)
as brown oil; Rf = 0.4 (4:1, hexane:EtOAc); IR (neat): 3365,
3059, 3031, 2958, 2928, 1657, 1598, 1574, 1542, 1490, 1452,
1399, 1357, 1301, 1250, 1202, 1172, 1131, 1027, 948, 844, 798,
757, 717, 684, 607 and 553 cm-1; 1H NMR (400 MHz, CDCl3): δ
= 8.13-8.15 (1 H, dd, J = 1.5 & 4.7 Hz), 7.95-7.97 (1 H, dd, J =
1.5 & 7.9 Hz),7.03-7.08 (3 H, m), 6.99-7.01 (3 H, m), 6.86-6.89
(1 H, dd, J = 4.8 & 7.9 Hz), 5.48 (1H, s), 5.18 (2 H, s), 3.20 (1 H,
br s), -0.01 (9 H, s); 13C NMR (100 MHz, CDCl3): δ =148.0,
143.4, 137.3, 128.8, 128.4, 127.8, 127.8, 126.3, 118.6, 116.0,
114.1, 105.3, 90.1, 58.6, 47.9 and -0.07.
1
491, 478, 458 and 421 cm-1; H NMR (400 MHz, CDCl3): δ =
7.98-8.0 (1 H, d, J = 8.3 Hz), 7.76-7.80 (3 H, t, J = 8.9 Hz), 7.70-
7.71 (1 H, d, J = 1.0 Hz), 7.33-7.37 (1 H, ddd, J = 1.2, 7.2 & 8.2
Hz), 7.22-7.29 (3 H, m), 5.66 (1 H, s), 2.44 (1 H, br s ), 2.34 (3
H, s), 0.25 (9 H, s); 13C NMR (100 MHz, CDCl3): δ = 145.2,
135.6, 135.3, 130.0, 128.4, 127.0, 125.1, 124.3, 123.3, 122.3,
120.6, 113.7, 103.9, 91.2, 58.4, 21.6 and -0.11;
4.1.48. 3-Phenyl-1-(1-tosyl-1H-indol-3-yl)prop-2-yn-1-ol (6ah)
Followed general procedure. The aldehyde27 5a (50 mg 0.17
4.1.52.
phenylprop-2-yn-1-ol (6cb)
Followed general procedure. The aldehyde27 5c (50 mg 0.21
mmol), THF (3 mL), and phenylethynyllithium [2.5 mL in THF,
0.27 mmol, freshly prepared from phenylacetylene and BuLi
(1.6 M in hexanes)]. Alcohol 6cb (66 mg, 0.2 mmol, 92%) as
brown oil; Rf = 0.4 (4:1, hexane:EtOAc); IR (neat):3379, 3057,
1-(1-Benzyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-
mmol), THF (2 mL), and phenylethynyllithium [2 mL in THF,
n
0.22 mmol, freshly prepared from phenylacetylene and BuLi
(1.6 M in hexanes)]. Alcohol 6ah (57 mg, 0.141 mmol, 85%) as
brown oil; Rf = 0.4 (4:1, hexane:EtOAc); IR (neat): 3392, 2921,
2852, 1596, 1490, 1446, 1373, 1272, 1211, 1172, 1119, 1097,
1018, 983, 811, 757, 684, 658, 593, 572, 536, 526, 498, 487, 462,
441 and 430 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.94-7.96 (1
n

11
2, 312-318; (d) Qian, S.; Zhao, G. Chem. Commun., 2012, 48, 3530–
3033, 2959, 2926, 2897, 1657, 1598, 1543, 1491, 1452, 1400,
1358, 1302, 1265, 1251, 1172, 1130, 1027, 951, 845, 797, 757,
739, 700, 643, 630 and 589 cm-1; 1H NMR (400 MHz, CDCl3): δ
= 8.29-8.30 (1 H, dd, J = 1.5 & 4.7 Hz), 8.15-8.18 (1 H, dd, J =
1.6 & 7.9 Hz), 7.37-7.39 (2 H, dd, J = 2.6 & 7.8 Hz),7.19-7.27 (7
H, m), 7.13-7.15 (2 H, m),7.0-7.04 (1 H, dd, J = 4.8 & 7.9 Hz),
5.87 (1 H, s), 5.36 (2 H, s), 3.53 (1 H, br s); 13C NMR (100 MHz,
CDCl3): δ = 148.1, 143.5, 137.4, 131.8, 128.7, 128.6, 128.48,
128.40, 127.7, 127.6, 126.2, 122.5, 118.6, 116.1, 114.4, 88.9,
85.3, 58.7 and 47.9.
ACCEPTED MANUSCRIPT
3532; (e) Zhao, H.; Meng, X.; Huang, Y. Chem. Commun., 2013, 49,
10513-10515; (f) Ilangovan, A.; Sakthivel, P. RSC Adv., 2014, 4,
55150–55161.
(a) Ruiz-Sanchis, P.; Savina, S. A.; Albericio, F.; Álvarez, M. Chem. –
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Chem. 2010, 26, 1–480; (c) Vicente, R. Org. Biomol. Chem. 2011, 9,
6469–6480. And references cited therein.
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Stuttgart, 2000; chapter 10.13; (b) Humphrey, G. R.; Kuethe, J. T.
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Tommasi, S.; Umani-Ronchi, A. Synlett 2005, 1199–1222; (d)
Marqués-López, E.; Diez-Martinez, A.; Merino, P.; Herrera, R. P. Curr.
Org. Chem. 2009, 13, 1585–1609; (e) Bandini, M.; Eichholzer, A.
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Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010, 110,
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4.1.53.
(1-Benzyl-1H-pyrrolo[2,3-b]pyridin-3-yl)
(phenyl)
methanol (6cc)
Followed general procedure. The aldehyde27 5c (50 mg 0.21
mmol), THF (2 mL), and phenylmagnesium bromide [2 mL in
THF, 0.27 mmol, freshly prepared from PhBr and Mg]. Alcohol
6cc (43 mg, 0.14 mmol, 65%) as brown oil; Rf = 0.4 (4:1,
hexane:EtOAc); IR (neat): 3408, 3060, 3031, 2926, 2856, 1656,
1597, 1542, 1491, 1491, 1450, 1432, 1401, 1358, 1303, 1172,
1035, 1001, 801, 770, 738, 700, 646, 578 and 417 cm-1; 1H NMR
(400 MHz, CDCl3): δ = 8.19-8.21 (1 H, dd, J = 1.5 & 4.7 Hz),
7.72-7.74 (2 H, dd, J = 1.6 & 7.9 Hz),7.38-7.39 (2 H, d, J = 7.1
Hz), 7.26-7.30 (2 H, td, J = 1.5 & 8.6 Hz), 7.19-7.23 (4 H, m),
7.10-7.13 (2 H, dd, J = 2.1 & 7.9 Hz), 6.94 (1 H, s), 6.90-6.93 (1
H, dd, J = 4.8 & 7.9 Hz), 5.99 (1 H, s), 5.34 ( 2 H, s), 2.99 (1 H,
br s); 13C NMR (100 MHz, CDCl3): δ = 148.1, 143.4, 143.38,
143.34, 143.31, 137.7, 128.7, 128.4, 127.6, 127.5, 126.5, 126.0,
118.8, 117.5, 115.8, 70.5 and 47.8.
4.1.54.
1-Hexyl-3-((1-methyl-1H-indol-3-yl)(thiophen-2-
yl)methyl)-1H-indole (7)
Followed general procedure. The aldehyde 1a (50 mg, 0.314
mmol) and N-hexylindole-3-carboxaldehyde 1b’ (79 mg, 0.314
mmol), THF (5 mL), and 2-thienylmagnesium bromide (3 mL,
0.82 mmol; freshly prepared from 2-bromothiophene and Mg).
BIM 3cb (23 mg, 0.06 mmol, 19%) as a brown viscous oil; BIM
3ag (20 mg, 0.06 mmol, 18%) as a brown viscous oil; hetero
BIM 7 (30 mg, 0.07 mmol, 22%), Rf = 0.6 (9:1, hexane:EtOAc);
IR (neat): 3050, 2957, 2922, 2857, 1735, 1656, 1612, 1546,
1465, 1394, 1363, 1327, 1265, 1221, 1177, 1155, 1121, 1087,
1038, 1012, 894, 853, and 690 cm-1; 1H NMR (400 MHz, CDCl3):
δ = 7.37 (2 H, dd, J = 2.6 & 7.8 Hz), 7.22 (2 H, t, J = 8.3 Hz),
7.05-7.16 (3 H, m), 6.93 (2 H, t, J = 5.7 Hz), 6.80-6.84 (2 H, m),
6.67 (1 H, s), 6.62 (1 H, s), 6.07 (1 H, s), 3.93 (2 H, t, J = 7.1
Hz), 3.61 (3 H, s), 1.68 (2 H, t, J = 6.2 Hz), 1.18-1.21 (6 H, m),
0.77 (3 H, t, J = 6.4 Hz); 13C NMR (100 MHz, CDCl3): δ =
149.4, 137.4, 136.6, 127.9, 127.4, 127.3, 127.0, 126.4, 125.1,
123.5, 121.8, 121.6, 121.4, 120.0, 118.8, 118.7, 118.4, 118.1,
109.5, 109.2, 46.4, 35.3, 32.8, 31.5, 30.2, 26.7, 22.6, 14.1.
8. During the review process of this manuscript, there was a publication
appeared on similar work. Bahuguna, A.; Sharma, R.; Sagara, P. S.;
Ravikumar, P. C. Synlett, 2016, (e-first) DOI: 10.1055/s-0036-
1588885.
9. In case of arylmagnesium halides, we have always isolated byproducts
aldehydes but with low molecular weight Grignard reagents e.g,
MeMgCl or EtMgBr it was not. This may be due to the fact that, the
aldehydes formed (Me-CHO or Et-CHO) might be too volatile to isolate
from column chromatography.
Acknowledgments
We thank CSIR-India for financial support. BSC thanks IIT
Madras for fellowship.
References and notes
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ACCEPTED MANUSCRIPT
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Supplementary Material
Supplementary data (1H, 13C NMR spectra for all new
synthesized compounds and X-ray diffraction data for compound
3af ) (PDF) associated with this article can be found in the online
version, at http:// dx.doi.org/xxxxxxxxxx.
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