Transition-Metal-Free, Br?nsted Acid-Mediated Cascade Sequence in the Reaction of Propargyl Alcohols with Sulfonamido-indoles/-indolines: Highly Substituted δ- And α-Carbolines

Article abstract of DOI:10.1021/acs.joc.8b02293

Br?nsted acid-mediated, transition-metal-free reaction of propargyl alcohols with sulfonamido-indoles/-indolines under mild conditions affords highly substituted δ- or α-carbolines in good to excellent yields. This protocol involves cascade reaction seque

Full text of DOI:10.1021/acs.joc.8b02293

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Article
Transition Metal-free, Brønsted Acid Mediated Cascade Sequence
in the Reaction of Propargyl Alcohols with Sulfonamido-
indoles/-indolines: Highly Substituted #- and #-Carbolines
Karuppu Selvaraj, and K C Kumara Swamy
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02293 • Publication Date (Web): 19 Nov 2018
Downloaded from http://pubs.acs.org on November 20, 2018
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Transition Metal-free, Brønsted Acid Mediated Cascade Sequence in the Reaction of
Propargyl Alcohols with Sulfonamido-indoles/-indolines: Highly Substituted δ- and α-
Carbolines
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Karuppu Selvaraj and K. C. Kumara Swamy*
School of Chemistry, University of Hyderabad, Hyderabad -500046, Telangana, India
ABSTRACT: Brønsted acid mediated, transition metal free, reaction of propargyl alcohols
with sulfonamido-indoles/-indolines under mild conditions affords highly substituted δ- or α-
carbolines in good to excellent yields. This protocol involves cascade reaction sequences of
Friedel-Crafts alkylation/ [1,5]-hydrogen shift/ electrocyclization/ elimination/ [1,2]-aryl
migration followed by aromatization. An unexpected regioselective tosyl group migration
from indole 2- to 6-position and arene elimination leading to α-carbolines has also been
discovered.
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INTRODUCTION
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Carboline motif is found in a multitude of natural alkaloids and pharmaceutically active
compounds.1,2 Although β- and γ-carbolines are relatively well studied, there has also been a
significant interest in the α- and δ-carbolines. Benzo-fused α- and δ-carbolines are active as
antiviral, antitumor, antimalarial, antiproliferative, antifungal, antibacterial, central nervous
system stimulating and antiplasmodial agents.3 In particular, δ-carbolines are potential cancer
therapeutics (e.g., SYUIQ-5)4 and α-carboline mescengricin5 is a potential neural protective
agent (cf. Figure 1). A Pd-catalyzed Ullmann cross-coupling/reductive cyclization route by
Banwell and coworkers and a rhodium catalyzed syntheses via aryl azides by Driver and
coworkers for such isomeric carbolines are known.6 Otherwise, only a limited number of
methods are available for the synthesis of α- and δ-carbolines.7 Some recently reported
methods for the latter class of compounds include (i) DDQ mediated regioselective switching
approach of indolylchalcone oxime esters,8 (ii) Ni-catalyzed [2+2+2] cycloaddition of
ynamide-nitriles or alkyne cyanamides with alkynes,9 (iii) Suzuki-Miyaura reactions of 1-
chloro-2-bromopyridine or 2,3-dibromopyridine with 2-bromophenylboronic acid,10 (iv)
reaction using indolylchalcone oxime esters,11 (v) Pd-catalyzed sequential reaction of 2-
iodoanilines with N-tosyl-enynamines,12 (vi) decarboxylative nitrile insertion of indole-2-
carboxylic acids13 and (vii) thermal rearrangement of indolylchalcone oxime esters.14
Important methods for syntheses of α-carbolines include annulation reaction of azaindoles,
intramolecular Diels-Alder reaction, Graebe-Ullmann reaction of triazoles, and palladium
catalyzed arylamination followed by intramolecular coupling reactions.15 Indoloquinazolines
also contain nitrogen atoms at 1,3-positions but form another interesting class of fused
hetereocycles.16 Many of these methods involve multi-steps, harsh reaction conditions, and
use of expensive metal catalysts. In continuation of our studies on the chemistry of
propargylic alcohols,17 we herein describe a transition metal-free cascade approach for the
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syntheses of highly substituted δ- and α-carbolines via Brønsted acid mediated [1,2]-aryl
migration of propargyl alcohols with sulfonamido-indoles/-indolines. In addition, a unique
tosyl group migration with concomitant arene elimination is also highlighted.
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Figure 1. Examples of biologically active δ- and α-carbolines
RESULTS AND DISCUSSION
To begin with, from the reaction between 3-sulfonamidoindole 1a and propargylic alcohol 2a
using an equiv amount of p-toluenesulfonic acid (PTSA) at 0 °C for 18 h in dichloromethane
(DCM), surprisingly, we isolated the δ-carboline 3aa [cf. condition (i) in Scheme 1, and
Figure S1 (X-ray) SI] in 52% yield via [1,2]-aryl migration. Subsequently, we evaluated the
influence of R group on sulfonyl moiety of sulfonamidoindoles 1ai-iv and found that tosyl
group still was the best choice [under condition (ii)] for reactions shown in Scheme 1.
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Scheme 1. Formation of α-Carboline 3aa from Brønsted Acid Mediated [1,2]-Aryl
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Migration/Cyclization of Propargyl Alcohol 2a with Sulfonamidoindoles 1
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Based on the first reaction (Table 1, entries 1-2), we screened the reaction conditions by
changing the catalyst,18 solvent, temperature, time etc. The reaction time could be
significantly shortened by performing the reaction using 1.5 equiv (instead of 1 equiv) of
o
PTSA at rt (25 C) to obtain the highest yield of 3aa (Table 1, entry 3). The reaction
conducted in dichloromethane (DCM) at 40 °C led to lower yield (entry 4). The effectiveness
of a few other acid catalysts such as FeCl3, AlCl3, I2 and, BF3.OEt2 was also checked, and it
was found that product 3aa was obtained in lower yields (entries 5-8). The best solvent was
dichloromethane (DCM, entry 3) which provided a higher yield than other solvents such as
dichloroethane (DCE), acetonitrile (CH3CN), tetrahydrofuran (THF), toluene (PhMe),
dimethyl sulfoxide (DMSO), or 1,4-dioxane (entries 9-14). Transition metal compounds like
Sc(OTf)3, Yb(OTf)3, In(OTf)3 and InCl3 were not useful for this transformation (entries 15-
18). No reaction occurred in the absence of the catalyst (entry 19). Increasing the catalyst
amount and reaction timing did not improve yield of the reaction (entries 20-21). Brønsted
acids such as TfOH, MsOH and AcOH were also checked for their efficiency. While TfOH
and MsOH gave slightly lower yields of the product 3aa (entries 22-23) compared to PTSA
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(entry 3), no reaction is occurred when AcOH was used (entry 24). Thus PTSA in DCM at rt
(entry 3) was the best for this transformation.
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Table 1. Screening of reaction conditionsa
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catalyst (equiv.)
temp (°C)
solvent
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCE
time (h) yield (%)b 3aa
entry
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9
PTSA (1.0)
PTSA (1.0)
PTSA (1.5)
PTSA (1.5)
FeCl3 (1.5)
AlCl3 (1.5)
I2 (1.5)
0
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trace
trace
nrc
nr
rt
rt
40
rt
rt
rt
rt
rt
rt
rt
rt
rt
BF3.OEt2 (1.5)
PTSA (1.5)
10 PTSA (1.5)
CH3CN
THF
PTSA (1.5)
PTSA (1.5)
PTSA (1.5)
PTSA (1.5)
Sc(OTf)3 (1.5)
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toluene
DMSO
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15
1,4-dioxane rt
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
16 Yb(OTf)3 (1.5)
17 In(OTf)3 (1.5)
18 InCl3 (1.5)
19 no catalyst
20 PTSA (2.0)
21 PTSA (2.5)
22 TfOH
nr
nr
nr
88
89
80
76
nr
23 MsOH
24 AcOH
aReaction conditions: 1a (0.100 g, 0.33 mmol), 2a (0.113 g, 0.40 mmol), solvent (5 mL).
bYield after isolation is based on 1a. cnr = no reaction.
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Next, we synthesized highly substituted δ-carbolines 3aa-3fb via [1,2]-aryl migration by
varying 3-sulfonamidoindoles 1a-fa and propargylic alcohols 2a-s. The substituent on the N-
position (R5) of the 3-sulfonamidoindoles 1 could be methyl, ethyl, allyl, or benzyl, providing
the δ-carbolines 3aa-3da in 79-83% yield. The 3-toluenesulfonamidoindole with -OMe or -
Br substituent at the 5-position (R4) also led to the products 3eb and 3fb in excellent yields. A
variety of -substituted propargyl alcohols 2 readily afforded the products 3ac-3be (Table 2).
Electron-donating substituent (OMe, Me; 3ac-3bb) at the para-position (R1 = R2) provided
higher yields than those with electron-withdrawing substituent (F, Cl; 3bd-3be), suggesting
the intermediacy of a carbocation in this reaction. When propargylic alcohols 2f-2k with two
different -aryl groups (electron-rich and electron-poor) were employed, the electron-rich
aryl group migrated preferentially to yield the products 3bf-3bk (X-ray for 3bj in Figure S2,
SI).19 Electron-donating substituent (R3) at para-position of the phenyl ring gave higher yield
(e.g., 3bl) than an electron-withdrawing group at meta- or para-position (3bm-3bn, 3ao).
This reaction also worked well when R2 was methyl or thiophene (2p-2q) giving the products
3bp-3bq in moderate yields. The reaction failed when R3 = n-butyl or cyclopropyl. With 9-
fluorenyl-substituted propargyl alcohol 2r; the benzo-annulated quinoline 3br (X-ray, Figure
S3, SI) was obtained as a single product in 71% yield. Interestingly, the propargylic alcohol
2s with different aryl groups (R1 = Ph; R2 = biphenyl) gave both [1,2]-phenyl migrated δ-
carboline 3bs and [1,2]-biphenyl migrated δ-carboline 3bs’ in 25% and 64% yields,
respectively (Table 2).
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Table 2. Scope of the reaction of 3-sulfonamidoindole 1 with propargylic alcohols 2a,b
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aReaction conditions: 3-sulfonamidoindoles 1 (1.0 equiv), propargylic alcohols 2 (1.2 equiv),
solvent (DCM, 5 mL), 12 h, 25 oC. bYield after isolation.
Next, we turned our attention to α-carbolines. Towards this, 2-sulfonamidoindolines 4a-b and
propargylic alcohols 2b-c were tested as substrates (Scheme 2) under the above optimized
conditions, but cyclized products were not observed. The conjugated sulfonamidoindolines
5ab (X-ray, Figure S4, SI) and 5bc were formed as the only isolable compounds. We believe
that under these conditions, the highly activated propargyl alcohols 2b-2c undergo Friedel-
Crafts reaction with sulfonamidoindolines followed by [1,5]-hydride shift (Scheme 2a).
Compound 5ab upon heating in toluene (reflux, 18 h) underwent 6π-electrocyclization to
afford the rather unexpected 6-sulfonyl substituted α-carboline 6ab via regioselective
migration of sulfonyl group and α-carboline 7ab in 24% and 72% yields, respectively
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(Scheme 2b). The cross-over experiment between equiv amounts of compound 5ab and
PhSO2Na did not lead to the incorporation of PhSO2 moiety at the 6-position. Also, by the
use of an equiv amount of PTSA in toluene under reflux conditions, compound 5ab afforded
higher yield of α-carboline 7ab and lower yield of tosyl migrated product 6ab. The reaction
took place equally well under nitrogen atmosphere also indicating that it is most likely not an
oxidative elimination reaction. Based on these observations we opine that the tosyl group has
migrated from indole substrate only, although a detailed pathway could not be ascertained.
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Scheme 2. Reaction of 2-Sulfonamidoindolines 4 with Propargylic Alcohols 2
Although the yield of 6ab is moderate, this tosyl migration is interesting because it takes
place without the intervention of a base or a metal catalyst or a Lewis acid.20 Thus we have
been successful in isolating 6-sulfonyl substituted α-carbolines 6 also readily (X-ray for 6ap
in Figure S5, SI). The unsymmetrical propargyl alcohol 2j gave the tosyl migrated products
6aj+6aj’ and the α-carboline 7aj (Table 3). To the best of our knowledge, this is the first
report to directly introduce sulfonyl group on C-6 position of indole without the use of a
catalyst. Further, to check the elimination of alkyl group (R1 or R2) on tosyl migration
product 6, we treated the propargyl alcohol 2t (R1 = CH3 and R2 = Me2CHCH2) with 2-
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sulfonamidoindoline 4a under optimized conditions, but the reaction did not occur; both
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starting materials were recovered.
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Table 3. Scope of tosyl migration in the reaction of 2-sulfonamidoindolines 4 and
propargylic alcohols 2a
aReaction conditions: 2-sulfonamidoindolines 4 (1.0 equiv), propargylic alcohol 2 (1.2
b
equiv), (i) solvent DCM (5 mL), 12 h, (ii) solvent toluene (5 mL), 12 h. Yields of the
isolated products.
In the next step, we found that the -carboline 7aa is the only product if the reaction of 4a
with 2a is conducted in the presence of equiv amount of PTSA in refluxing toluene for 12 h.
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By this minor modification, we were able to obtain an easier route to the -carbolines 7aa-
7be (X-ray for 7bc in Figure S6, SI) exclusively in one pot as shown in Scheme 3. Use of 2-
sulfonamido-indoline 4e (R4 = R5 = H) and the propargyl alcohol (4-MeOC6H4)2 (HO)C CPh
(2b) under the conditions employed here afforded the , -unsaturated ketone (4-
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1
MeOC6H4)2C=CHC(O)Ph (major product, ca 85%; H NMR, HRMS) and the butadiene
substituted
isomeric
N-((E)-3-(3,3-bis(4-methoxyphenyl)-1-phenylallylidene)indolin-2-
ylidene)-4-methylbenzenesulfonamide 5 (minor product, ca 15%; 1H NMR, HRMS).
Scheme 3. One Pot Synthesis of -Carbolines 7aa-7bea,b
aReaction conditions: 2-sulfonamidoindoles 4 (1.0 equiv), propargylic alcohols 2 (1.2 equiv),
solvent (Toluene, 5 mL), 12 h, 110 oC. bYield after isolation.
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In order to explore the reaction pathway, we treated benzenesulfonamide 8 with 2a in the
presence of PTSA and found that 8-tosyl-1,2-dihydroquinoline 9 is the sole product, via tosyl
migration instead of aryl migration (Scheme 4a). An isomeric compound 9’ without tosyl
migration was reported earlier.21 Thus our result shows that indole moiety is necessary for the
[1,2]-aryl migration. We then reasoned that the reaction could go through an allenic
intermediate and indeed were able to isolate the allene 10 from the reaction of 3-
sulfonamidoindoles 1b with propargyl alcohol 2a by slightly altering the reaction conditions
as shown in Scheme 4b.
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Scheme 4. Additional Reactions to Explore the Reaction Pathway
A possible pathway for the formation of 6-sulfonyl substituted α-carbolines 6 and
-
carbolines 7 is shown in Scheme 5. Some of the steps observed here are similar to that
recently observed in transition metal catalyzed carbazole synthesis.19 First, propargylic
alcohol 2 is converted to the allenic carbocation A in the presence of PTSA via Meyer-
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Schuster rearrangement,22 which would then undergo Friedel-Crafts-type reaction with 4 to
form the allene intermediate B, as supported by the isolation of compound 10 (cf. Scheme
4b). Then intermediate B would be transformed to imine C via [1,5]-hydride shift. This step
supported by the isolation of the compound 5 (cf. Scheme 2). Then species C undergoes
cascade reaction of 6π-electrocylization (D) and elimination of p-toluenesulfonyl anion to
give E. Intermediate E may follow two pathways. In path a, it undergoes [1,2]-aryl shift to
afford F and subsequent aromatization to deliver the δ-carboline 7. In path b, intermediate E
undergoes migration of p-toluenesulfonyl anion to the indole C-6 position to give G followed
by elimination of aromatic group23 to lead to 6-sulfonyl substituted -carboline 6 via H. It is
possible that the [1,2]-aryl migration (path a) from E is faster than tosyl migration (path b) in
the presence of pTSA. This may be the reason for selective formation of 7 (cf. Scheme 3).
Since the reaction was conducted in toluene, we had difficulty in identifying traces of
liberated arene arising from tosyl migration/arene expulsion. The δ-carbolines 3 are formed in
a manner similar to 7.
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Scheme 5. Possible Pathway for the Formation of 6-Sulfonyl Substituted -Carbolines 6
and -Carbolines 7 (or 3)
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CONCLUSIONS
In summary, we have demonstrated a transition metal-free method for the synthesis of highly
substituted δ- and α-carbolines via Brønsted acid mediated reaction of propargyl alcohols
with sulfonamido-indoles/-indolines. The reaction involves a cascade sequence of Friedel-
Crafts/ [1,5]-hydride shift/ electrocyclization/ elimination/ [1,2]-aryl migration and
aromatization leading to δ- and α- carbolines in good to excellent yields. A novel route for
the synthesis of 6-sulfonyl substituted α-carbolines via unexpected tosyl group migration/
arene elimination has been developed.
EXPERIMENTAL SECTION
General Methods. All reactions were carried out in air, unless otherwise specified. All
Chemicals were procured from Aldrich or local manufacturers and used as purchased without
further purification, unless noted. Sulfonamido-indoles/-indolines and propargyl alcohols
were prepared using known literature methods.24-25 Melting points were determined using a
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SUPERFIT hot stage apparatus and were uncorrected. H and 13C NMR spectra were
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recorded using 5 mm tubes on a Bruker 400 and 500 MHz NMR spectrometer [field
strengths: 400/ 100 or 500/ 125 MHz respectively] in CDCl3 solution (unless specified
otherwise) with shifts referenced to TMS (1H, 13C: = 0). All J values are in Hz. Infrared
spectra were recorded using ATR technique on a Bruker Alpha FT-IR spectrophotometer.
Mass spectra were recorded using HRMS (ESI-TOF analyzer) equipment. Crystallographic
data were collected at 293 K on an X-ray diffractometer system using Mo-Kα radiation (λ =
0.71073 Å) or Cu-Kα (λ = 1.54184 Å) radiation. Structures were solved and refined using
standard methods.26 Thin-layer chromatography was performed on silica/alumina plates and
components were visualized by observation under iodine/UV light at 254 nm. Column
chromatography was performed on silica gel (100-200 mesh)/neutral alumina, for column
elution process hexane-EtOAc mixture was used as the eluent unless otherwise stated.
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(i) General procedure for the synthesis of sulfonamido-indoles/-indolines 1a-f and 4a-e.24
An oven dried 25 mL round-bottomed flask was charged with 1-methyl indole (0.5 g, 3.8
mmol) and p-toluenesulfonyl azide (1.05 g, 5.3 mmol) in 5 mL of dry 1,4-dioxane under
nitrogen atmosphere. The mixture was stirred with heating (oil bath temperature at 75-80 °C)
for 18-24 h, and cooled. Addition of ethanol (25 mL) resulted in most of 2-
sulfonamidoindoline 4 to crystallize/precipitate from the solution. The solvent was removed
from the mother liquor and the residue purified by column chromatography on silica gel
using hexane/ethyl acetate (70:30) to obtain the 3-sulfonamidoindole 1 (lower Rf than
compound 4). Compounds 1b-f and 4b-e were prepared from the appropriate N-substituted
indole and p-toluenesulfonyl azide by using the same procedure using same molar quantities.
Among these, 1a, 4d, and 4e are known; 24 compounds 1b, 1c, 1d, 1e, 1f, 4a, 4b, and 4c are
new.
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N-(1-Ethyl-1H-indol-3-yl)-4-methylbenzenesulfonamide (1b). White solid, yield 0.350 g
(32%); mp 146-148 ºC; 1H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 2H), 7.29 (d, J =
9.0 Hz, 1H), 7.19-7.13 (m, 4H), 7.08 (s, 1H), 6.98 (dd→t, J = 7.5 Hz, 1H), 6.32 (s, 1H), 4.12
(qrt, J = 7.5 Hz, 2H), 2.38 (s, 3H), 1.43 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 143.4, 136.8, 134.3, 129.4, 127.4, 124.6, 124.4, 122.0, 119.7, 117.8, 110.8, 109.4, 41.0,
21.5, 15.4; IR (neat): νmax 3261, 3062, 2976, 1471, 1447, 1337, 1302, 1235, 1160, 1135,
1093, 813, 742, 663 cm-1; HRMS (ESI): Calcd. for C17H18N2O2SNa (M+ + Na): m/z
337.0987. Found: 337.0988.
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N-(1-Allyl-1H-indol-3-yl)-4-methylbenzenesulfonamide (1c). White solid, yield 0.315 g
(30%); mp 123-125 ºC; 1H NMR (500 MHz, CDCl3) δ 7.66-7.64 (m, 2H), 7.26 (d, J = 8.0 Hz,
1H), 7.18-7.15 (m, 4H), 7.06 (s, 1H), 6.99 (td, J = 7.0, 1.0 Hz, 1H), 6.33 (s, 1H), 5.99-5.91
(m, 1H), 5.21 (dd, J = 10.5, 1.0 Hz, 1H), 5.02 (dd, J = 17.0, 1.0 Hz, 1H), 4.67 (~dt, J = 5.0,
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1.0 Hz, 2H), 2.38 (s, 3H); C{1H} NMR (125 MHz, CDCl3) δ 143.4, 136.6, 134.7, 132.9,
129.4, 127.4, 125.0, 124.6, 122.3, 119.9, 117.8, 117.5, 111.2, 109.8, 48.8, 21.5; IR (neat):
νmax 3264, 3049, 2923, 1597, 1464, 1370, 1335, 1303, 1285, 1149, 1087, 946, 895, 809, 733,
663 cm-1; HRMS (ESI): Calcd. for C18H18N2O2SNa (M+ + Na): m/z 349.0987. Found:
349.0986.
N-(1-Benzyl-1H-indol-3-yl)-4-methylbenzenesulfonamide (1d). White solid, yield 0.323 g
(35%); mp 142-144 ºC; 1H NMR (500 MHz, CDCl3) δ 7.66-7.65 (m, 2H), 7.33-7.23 (m, 5H),
7.17-7.13 (m, 3H), 7.06-7.01 (m, 4H), 6.44 (s, 1H), 5.25 (s, 2H), 2.38 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 143.5, 136.5, 136.4, 134.9, 129.4, 128.8, 127.8, 127.5, 126.7, 125.2,
124.7, 122.5, 120.1, 117.9, 111.5, 109.9, 50.1, 21.5; IR (neat): νmax 3248, 3056, 1593, 1493,
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1462, 1347, 1297, 1253, 1207, 1153, 1089, 1032, 887, 814, 753, 704 cm-1; HRMS (ESI):
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Calcd. for C22H21N2O2S (M+ + H): m/z 377.1324. Found: 377.1322.
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N-(1-Ethyl-5-methoxy-1H-indol-3-yl)-4-methylbenzenesulfonamide (1e). White solid, yield
0.291 g (29%); mp 165-167 ºC; 1H NMR (500 MHz, CDCl3) δ 7.68-7.66 (m, 2H), 7.21-7.16
(m, 3H), 7.01 (s, 1H), 6.81 (dd, J = 9.0, 2.5 Hz, 1H), 6.46 (d, J = 2.5 Hz, 1H), 6.23 (s, 1H),
4.08 (qrt, J = 7.5 Hz, 2H), 3.66 (s, 3H), 2.40 (s, 3H), 1.42 (t, J = 7.5 Hz, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 154.3, 143.3, 137.0, 129.6, 129.4, 127.6, 125.4, 125.2, 112.9, 110.4,
110.3, 98.9, 55.5, 41.2, 21.5, 15.4; IR (neat): νmax 3256, 2941, 1597, 1483, 1448, 1323, 1299,
1211, 1155, 1091, 1010, 916, 814, 798, 658 cm-1; HRMS (ESI): Calcd. for C18H21N2O3S (M+
+ H): m/z 345.1273. Found: 345.1275.
N-(5-Bromo-1-ethyl-1H-indol-3-yl)-4-methylbenzenesulfonamide (1f). White solid, yield
0.248 g (28%); mp 213-215 ºC; 1H NMR (500 MHz, CDCl3) δ 7.63-7.61 (m, 2H), 7.23-7.21
(m, 3H), 7.15 (t, J = 8.5 Hz, 1H), 7.12 (s, 1H), 6.90 (d, J = 1.5 Hz, 1H), 6.10 (s, 1H), 4.12
(qrt, J = 7.5 Hz, 2H), 2.44 (s, 3H), 1.44 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 143.9, 136.6, 133.0, 129.5, 127.5, 126.6, 126.4, 124.9, 120.3, 113.3, 111.0, 110.1, 41.3,
21.5, 15.2; IR (neat): νmax 3257, 3129, 2923, 1562, 1456, 1404, 1326, 1275, 1161, 1091,
1049, 884, 862, 810, 791, 694 cm-1; HRMS (ESI): Calcd. for C17H18BrN2O2S (M+ + H): m/z
393.0272. Found: 393.0272.
(Z)-N-(1-Ethylindolin-2-ylidene)-4-methylbenzenesulfonamide (4a). Pale yellow solid, yield
0.520 g (48%); mp 164-166 ºC; 1H NMR (400 MHz, CDCl3) δ 7.91-7.88 (m, 2H), 7.35-7.29
(m, 4H), 7.12 (td, J = 8.0, 0.4 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 4.20 (s, 2H), 3.94 (qrt, J =
7.2 Hz, 2H), 2.42 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.2,
143.0, 142.7, 139.5, 129.5, 128.1, 126.63, 126.57, 124.6, 123.6, 109.3, 37.0, 36.2, 21.5, 12.1;
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IR (neat): νmax 3063, 2978, 2935, 1557, 1455, 1364, 1351, 1276, 1179, 1083, 993, 851, 815,
746, 677 cm-1; HRMS (ESI): Calcd. for C17H19N2O2S (M+ + H): m/z 315.1167. Found:
315.1168.
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(Z)-N-(5-Bromo-1-ethylindolin-2-ylidene)-4-methylbenzenesulfonamide (4b). White solid,
yield 0.520 g (59%); mp 221-223 ºC; 1H NMR (500 MHz, CDCl3) δ 7.89-7.88 (m, 2H), 7.47-
7.44 (m, 2H), 7.31 (d, J = 7.2 Hz, 2H), 6.84 (d, J = 8.5 Hz, 1H), 4.22 (s, 2H), 3.91 (qrt, J =
7.5 Hz, 2H), 2.43 (s, 3H), 1.26 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 168.5,
142.9, 142.2, 139.2, 131.0, 129.4, 128.6, 127.8, 126.4, 116.3, 110.5, 37.1, 36.0, 21.5, 11.9; IR
(neat): νmax 3066, 2973, 2925, 1560, 1476, 1365, 1348, 1272, 1142, 1082, 1054, 987, 810,
764, 691 cm-1; HRMS (ESI): Calcd. for C17H18BrN2O2S (M+ + H): m/z 393.0272. Found:
393.0275.
(Z)-N-(1-Ethyl-5-methoxyindolin-2-ylidene)-4-methylbenzenesulfonamide (4c). Pale yellow
solid, yield 0.623 g (63%); mp 176-178 ºC; 1H NMR (500 MHz, CDCl3) δ 7.90-7.88 (m, 2H),
7.31-7.28 (m, 2H), 6.96-6.94 (m, 1H), 6.88-6.83 (m, 2H), 4.17 (s, 2H), 3.92 (qrt, J = 7.5 Hz,
2H), 3.81 (s, 3H), 2.42 (s, 3H), 1.27 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
168.6, 156.7, 142.6, 139.7, 136.4, 129.3, 127.9, 126.6, 112.6, 111.5, 109.7, 55.8, 37.0, 36.4,
21.5, 12.0; IR (neat): νmax 2975, 1555, 1489, 1458, 1438, 1270, 1143, 1077, 986, 913, 808,
766, 701 cm-1; HRMS (ESI): Calcd. for C18H21N2O3S (M+ + H): m/z 345.1273. Found:
345.1275.
(ii) General procedure for synthesis of propargyl alcohols 2a-t. A literature procedure was
followed.25a To a THF solution (10 mL) of phenylacetylene (1.12 g, 10.9 mmol) was added n-
BuLi (8.5 mmol, 1.6 M in hexane) drop-wise over a period of 5 min at -78 °C under nitrogen
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atmosphere. The solution was allowed to warm to 0 °C over 1 h and held at 0 °C for an
additional 30 min. The solution was then recooled to -78 °C and benzophenone (1.00 g, 5.4
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mmol) was added in one portion. The solution was allowed to warm to 25 C over 1 h and
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held at this temperature for an additional 3 h. Saturated aqueous NH4Cl solution was added to
quench the reaction and the mixture was extracted with ethyl acetate (3 x 25 mL). The
organic layer was washed with water (2 x 25 mL) and brine solution (25 mL). This was then
dried over anh. Na2SO4, filtered, and concentrated. The crude material thus obtained was
purified by column chromatography on silica gel using hexane/ethyl acetate (95:5) to obtain
the pure propargylic alcohol 2a. Compounds 2b-t were prepared from appropriate acetylene
and ketone by using the same procedure. Among these, 2a,25a 2b, 2d, 2e, 2l, 2n, 2o, 2q,25b
2p,25c 2c, 2m,25d 2h, 2k, 2s,25e 2r,25f and 2t25g are known compounds and 2f, 2g, 2i, and 2j are
new.
1-(2-Chloro-5-nitrophenyl)-1,3-diphenylprop-2-yn-1-ol (2f). White solid, yield 1.28 g (92%);
mp 109-111 °C; 1H NMR (500 MHz, CDCl3) δ 9.08 (d, J = 3.0 Hz, 1H), 8.18 (dd, J = 8.5, 3.0
Hz, 1H), 7.62-7.60 (m, 2H), 7.55-7.52 (m, 3H), 7.42-7.35 (m, 7H), 3.16 (s, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 146.5, 143.2, 141.9, 139.7, 132.2, 131.8, 129.1, 128.7, 128.6,
128.5, 126.9, 124.0, 122.9, 121.9, 88.1, 88.0, 73.3; IR (neat): νmax 3350, 3085, 1606, 1517,
1490, 1342, 1297, 1245, 1166, 1048, 944, 772, 742, 755, 699 cm-1; HRMS (ESI): Calcd. for
C21H14ClNO3Na (M+ + Na): m/z 386.0560. Found: 386.0561.
1-(4-Methoxyphenyl)-1-phenyl-3-(p-tolyl)prop-2-yn-1-ol (2g). Colourless liquid, yield 1.30 g
(84%); 1H NMR (500 MHz, CDCl3) δ 7.69 (d, J = 7.0 Hz, 2H), 7.62-7.59 (m, 2H), 7.43 (d, J
= 8.0 Hz, 2H), 7.39-7.36 (m, 2H), 7.31-7.29 (m, 1H), 7.16 (d, J = 7.5 Hz, 2H), 6.91-6.88 (m,
2H), 3.82 (s, 3H), 2.85 (s, 1H), 2.38 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.1,
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145.5, 138.8, 137.6, 131.7, 129.1, 128.3, 127.6, 127.5, 126.1, 119.5, 113.6, 91.4, 87.2, 74.6,
55.3, 21.5; IR (neat): νmax 3547, 3493, 3031, 1605, 1506, 1449, 1242, 1168, 1046, 988, 815,
724 cm-1; HRMS (ESI): Calcd. for C23H20O2Na (M+ + Na): m/z 351.1361. Found: 351.1360.
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1-(4-Chlorophenyl)-1-phenyl-3-(p-tolyl)prop-2-yn-1-ol (2i). White solid, yield 1.38 g (90%);
mp 71-73 °C; 1H NMR (500 MHz, CDCl3) δ 7.69-7.66 (m, 2H), 7.64-7.61 (m, 2H), 7.43-7.36
(m, 4H), 7.34-7.29 (m, 3H), 7.17 (d, J = 7.5 Hz, 2H), 2.89 (s, 1H), 2.39 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 144.8, 143.8, 139.1, 133.6, 131.8, 129.2, 128.50, 128.47, 128.0,
127.6, 126.1, 119.1, 90.6, 87.8, 74.5, 21.6; IR (neat): νmax 3341, 3056, 3025, 2360, 2221,
1509, 1484, 1447, 1174, 1090, 1041, 1013, 990, 895, 817, 747, 701 cm-1; HRMS (ESI):
Calcd. for C22H17ClONa (M+ + Na): m/z 355.0866. Found: 355.0866.
3-(4-(Tert-butyl)phenyl)-1-(3,4-dichlorophenyl)-1-phenylprop-2-yn-1-ol (2j). Colourless
liquid, yield 1.53 g (94%); 1H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 2.0 Hz, 1H), 7.69-7.66
(m, 2H), 7.50-7.46 (m, 3H), 7.42-7.37 (m, 5H), 7.33 (tt, J = 7.5, 1.0 Hz, 1H), 2.92 (s, 1H),
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1.43 (s, 9H); C{1H} NMR (125 MHz, CDCl3) δ 152.5, 145.5, 144.3, 132.4, 131.8, 131.7,
130.3, 128.6, 128.22, 128.18, 126.0, 125.7, 125.5, 118.9, 90.1, 88.2, 74.1, 34.9, 31.2; IR
(neat): νmax 3341, 3056, 3025, 2360, 2221, 1509, 1484, 1447, 1403, 1174, 1090, 1013, 990,
816, 701 cm-1; HRMS (ESI): Calcd. for C25H22Cl2ONa (M+ + Na): m/z 431.0945. Found:
431.0946.
(iii) General procedure for the synthesis of δ-carbolines 3aa-3fb, 5ab, and 5bc. An oven
dried 25 mL round-bottomed flask was charged with 3-sulfonamidoindole 1a (0.100 g, 0.33
mmol), propargyl alcohol 2a (0.113 g, 0.40 mmol) and PTSA (1.5 equiv) in dichloromethane
o
(10 mL). The mixture was stirred at room temperature (25 C) in open air for 12 hours and
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monitored by TLC for the disappearance of starting materials. After the appropriate period,
the reaction mixture was treated with dichloromethane (10 mL) and water (15 mL). The
organic phase was separated and the aqueous layer washed with dichloromethane (10 mL).
The combined organic part was dried over anhydrous Na2SO4 and the solvent removed under
reduced pressure to afford the crude product. Purification by column chromatography (ethyl
acetate: hexane 1:9) afforded the desired product 3aa as a white solid. Compounds 3ac-3fb,
5ab and 5bc were prepared from appropriate 3-sulfonamidoindole and propargyl alcohol by
using the same procedure.
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5-Methyl-2,3,4-triphenyl-5H-pyrido[3,2-b]indole (3aa). White solid, yield 0.112 g (82%); mp
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163-165 ºC; H NMR (400 MHz, CDCl3) δ 8.56-8.54 (m, 1H), 7.61-7.57 (m, 1H), 7.43-7.34
(m, 4H), 7.30-7.18 (m, 8H), 7.03-6.99 (m, 3H), 6.96-6.93 (m, 2H), 3.27 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 150.6, 143.3, 141.8, 141.3, 138.6, 136.4, 132.9, 132.4, 131.7,
131.3, 130.8, 130.4, 127.7, 127.58, 127.55, 127.5, 127.2, 126.7, 126.1, 122.1, 121.2, 119.9,
109.0, 31.7; IR (neat): νmax 3056, 2926, 2853, 1618, 1542, 1491, 1442, 1385, 1213, 1154,
912, 748, 701 cm-1; HRMS (ESI): Calcd. for C30H23N2 (M+ + H): m/z 411.1861. Found:
411.1853.
2,3-Bis(4-methoxyphenyl)-5-methyl-4-phenyl-5H-pyrido[3,2-b]indole (3ac). White solid,
yield 0.141 g (90%); mp 209-211 ºC; 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J = 7.5 Hz, 1H),
7.59-7.56 (m, 1H), 7.39-7.32 (m, 4H), 7.30-7.29 (m, 3H), 7.24-7.21 (m, 2H), 6.85-6.82 (m,
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2H), 6.78-6.75 (m, 2H), 6.59-6.56 (m, 2H), 3.79 (s, 3H), 3.71 (s, 3H), 3.23 (s, 3H); C{1H}
NMR (125 MHz, CDCl3) δ 158.4, 157.7, 150.5, 143.2, 141.1, 136.6, 134.7, 132.7, 132.6,
132.3, 131.6, 131.2, 131.1, 130.8, 127.61, 127.56, 127.4, 122.2, 121.1, 119.8, 113.1, 112.8,
108.9, 55.2, 55.0, 31.6; IR (neat): νmax 3055, 2932, 2838, 1611, 1513, 1448, 1384, 1331,
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1289, 1246, 1177, 1032, 835, 745, 704 cm-1; HRMS (ESI): Calcd. for C32H27N2O2 (M+ + H):
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m/z 471.2072. Found: 471.2078.
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2-(4-Chlorophenyl)-5-methyl-3,4-diphenyl-5H-pyrido[3,2-b]indole (3ao). White solid, yield
0.121 g (81%); mp 208-210 ºC; 1H NMR (500 MHz, CDCl3) δ 8.53 (d, J = 7.5 Hz, 1H), 7.61-
7.58 (m, 1H), 7.41-7.35 (m, 4H), 7.30-7.28 (m, 3H), 7.24-7.22 (m, 2H), 7.20-7.18 (m, 2H),
7.05-7.04 (m, 3H), 6.94-6.93 (m, 2H), 3.26 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
149.1, 143.4, 141.4, 140.3, 138.3, 136.1, 132.81, 132.78, 132.5, 131.7, 131.6, 131.3, 130.7,
127.9, 127.7, 127.6, 127.4, 127.3, 122.0, 121.1, 120.0, 109.0, 31.7; IR (neat): νmax 3058,
2926, 2854, 1619, 1490, 1442, 1386, 1331, 1214, 1155, 1091, 838, 747, 704 cm-1; HRMS
(ESI): Calcd. for C30H22ClN2 (M+ + H): m/z 445.1471. Found: 445.1476.
5-Ethyl-2,3,4-triphenyl-5H-pyrido[3,2-b]indole (3ba). White solid, yield 0.110 g (81%); mp
204-206 ºC; 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 7.2 Hz, 1H), 7.61-7.57 (m, 1H), 7.45-
7.42 (m, 3H), 7.38-7.34 (m, 1H), 7.30-7.26 (m, 5H), 7.24-7.18 (m, 3H), 7.02-6.99 (m, 3H),
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6.97-6.95 (m, 2H), 3.78 (qrt, J = 7.0 Hz, 2H), 1.02 (t, J = 7.0 Hz, 3H); C{1H} NMR (100
MHz, CDCl3) δ 150.6, 142.3, 141.9, 141.6, 138.7, 136.6, 133.0, 132.3, 131.8, 130.4, 130.31,
130.26, 127.74, 127.70, 127.66, 127.5, 127.1, 126.7, 126.0, 122.6, 121.4, 119.9, 109.3, 38.6,
14.3; IR (neat): νmax 3056, 2974, 2925, 2856, 1616, 1542, 1466, 1385, 1338, 1205, 917, 752,
702 cm-1; HRMS (ESI): Calcd. for C31H25N2 (M+ + H): m/z 425.2017. Found: 425.2012.
5-Ethyl-2,3-bis(4-methylphenyl)-4-phenyl-5H-pyrido[3,2-b]indole (3bb). White solid, yield
0.125 g (87%); mp 207-209 ºC; 1H NMR (500 MHz, CDCl3) δ 8.54 (d, J = 7.5 Hz, 1H), 7.58-
7.55 (m, 1H), 7.41 (d, J = 8.5 Hz, 1H), 7.36-7.32 (m, 3H), 7.30-7.24 (m, 5H), 7.03 (d, J = 8.0
Hz, 2H), 6.84-6.80 (m, 4H), 3.74 (qrt, J = 7.0 Hz, 2H), 2.31 (s, 3H), 2.20 (s, 3H), 0.99 (t, J =
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7.0 Hz, 3H); C{1H} NMR (125 MHz, CDCl3) δ 150.7, 142.2, 141.5, 139.2, 136.8, 136.1,
135.8, 135.3, 132.9, 132.4, 131.5, 130.29, 130.26, 128.3, 127.9, 127.7, 127.6, 127.5, 122.7,
121.3, 119.8, 109.2, 38.5, 21.3, 21.2, 14.2; IR (neat): νmax 3027, 2972, 2924, 2858, 1618,
1515, 1465, 1385, 1340, 1203, 824, 744, 706 cm-1; HRMS (ESI): Calcd. for C33H29N2 (M+ +
H): m/z 453.2330. Found: 453.2332.
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2,3-Bis(4-fluorophenyl)-5-methyl-4-phenyl-5H-pyrido[3,2-b]indole (3bd). White solid, yield
0.181 g (84%); mp 232-234 ºC; 1H NMR (500 MHz, CDCl3) δ 8.53 (d, J = 8.0 Hz, 1H), 7.61-
7.58 (m, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.39-7.35 (m, 3H), 7.33-7.30 (m, 3H), 7.26-7.23 (m,
2H), 6.94-6.87 (m, 4H), 6.75-6.71 (m, 2H), 3.77 (qrt, J = 7.0 Hz, 2H), 1.01 (t, J = 7.0 Hz,
3H); C{1H} NMR (125 MHz, CDCl3) δ 161.9 (d, J = 244.7 Hz), 161.2 (d, J = 244.4 Hz),
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149.5, 142.3, 141.8, 137.8 (d, J = 3.5 Hz), 136.3, 134.6 (d, J = 3.5 Hz), 133.1 (d, J = 7.9 Hz),
132.5, 132.0 (d, J = 7.9 Hz), 131.8, 130.3, 130.1, 127.94, 127.87, 127.8, 122.4, 121.3, 120.1,
114.5 (d, J = 24.3 Hz), 114.4 (d, J = 24.3 Hz), 109.3, 38.6, 14.2; IR (neat): νmax 3058, 2978,
2928, 1607, 1510, 1466, 1387, 1338, 1215, 1155, 838, 745 cm-1; HRMS (ESI): Calcd. for
C31H23F2N2 (M+ + H): m/z 461.1829. Found: 461.1831.
2,3-Bis(4-chlorophenyl)-5-ethyl-4-phenyl-5H-pyrido[3,2-b]indole (3be). White solid, yield
0.133g (86%); mp 236-238 ºC; 1H NMR (500 MHz, CDCl3) δ 8.53 (d, J = 8.0 Hz, 1H), 7.61-
7.58 (m, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.38-7.30 (m, 6H), 7.25-7.20 (m, 4H), 7.02-7.00 (m,
2H), 6.88-6.85 (m, 2H), 3.77 (qrt, J = 7.0 Hz, 2H), 1.01 (t, J = 7.0 Hz, 3H); C{1H} NMR
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(100 MHz, CDCl3) δ 148.9, 142.4, 142.0, 140.1, 137.1, 136.0, 133.0, 132.9, 132.33, 132.32,
131.7, 131.5, 130.3, 130.1, 128.1, 128.0, 127.95, 127.90, 127.6, 122.3, 121.3, 120.2, 109.4,
38.6, 14.2; IR (neat): νmax 3058, 2976, 2928, 1618, 1491, 1387, 1341, 1205, 1090, 1015, 833,
744 cm-1; HRMS (ESI): Calcd. for C31H23Cl2N2 (M+ + H): m/z 493.1238. Found: 493.1252.
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2-(2-Chloro-5-nitrophenyl)-5-ethyl-3,4-diphenyl-5H-pyrido[3,2-b]indole (3bf). White solid,
yield 0.136 g (81%); mp 197-199 ºC; 1H NMR (500 MHz, CDCl3) δ 8.51 (d, J = 8.0 Hz, 1H),
8.22 (d, J = 3.0 Hz, 1H), 8.50 (dd, J = 9.0, 3.0 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.45 (t, J =
9.0 Hz, 2H), 7.37 (d, J = 7.5 Hz, 1H), 7.29 (s, 5H), 6.96 (s, 5H), 3.82 (qrt, J = 7.0 Hz, 2H),
1.05 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 146.4, 145.7, 142.4, 142.2,
141.6, 140.9, 137.1, 135.8, 133.8, 132.2, 130.8, 130.14, 130.08, 128.2, 127.9, 127.8, 127.3,
127.1, 126.6, 123.3, 122.0, 121.3, 120.3, 109.4, 38.7, 14.2; IR (neat): νmax 3059, 2976, 2926,
2857, 1526, 1385, 1343, 1208, 1108, 905, 830, 744, 704 cm-1; HRMS (ESI): Calcd. for
C31H23ClN3O2 (M+ + H): m/z 504.1479. Found: 504.1481.
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5-Ethyl-3-(4-methoxyphenyl)-4-(4-methylphenyl)-2-phenyl-5H-pyrido[3,2-b]indole
(3bg).
White solid, yield 0.123 g (82%); mp 181-183 ºC; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J =
7.6 Hz, 1H), 7.59-7.55 (m, 1H), 7.45-7.41 (m, 3H), 7.35 (t, J = 7.2 Hz, 1H), 7.25-7.17 (m,
3H), 7.15-7.09 (m, 4H), 6.86-6.83 (m, 2H), 6.58-6.54 (m, 2H), 3.78 (qrt, J = 6.8 Hz, 2H),
3.70 (s, 3H), 2.37 (s, 3H), 1.01 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
157.7, 150.9, 142.24, 142.15, 141.4, 137.2, 133.6, 132.82, 132.76, 131.1, 130.6, 130.4, 130.1,
128.5, 127.6, 127.5, 126.6, 122.6, 121.3, 119.8, 112.6, 109.3, 55.0, 38.5, 21.4, 14.3; IR
(neat): νmax 3049, 2970, 2927, 1614, 1513, 1463, 1384, 1337, 1245, 1204, 1030, 745, 701 cm-
1; HRMS (ESI): Calcd. for C33H29N2O (M+ + H): m/z 469.2280. Found: 469.2286.
5-Ethyl-3,4-bis(4-methylphenyl)-2-phenyl-5H-pyrido[3,2-b]indole (3bh). White solid, yield
0.119 g (83%); mp 196-198 ºC; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 7.6 Hz, 1H), 7.59-
7.54 (m, 1H), 7.43-7.40 (m, 3H), 7.36-7.32 (m, 1H), 7.23-7.17 (m, 3H), 7.16-7.08 (m, 4H),
6.81 (s, 4H), 3.76 (qrt, J = 6.8 Hz, 2H), 2.37 (s, 3H), 2.20 (s, 3H), 1.00 (t, J = 7.2 Hz, 3H);
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13C{1H} NMR (100 MHz, CDCl3) δ 150.7, 142.2, 142.1, 141.4, 137.1, 135.7, 135.3, 133.5,
133.1, 132.6, 131.5, 130.6, 130.4, 130.0, 128.4, 127.8, 127.5, 127.4, 126.5, 122.6, 121.3,
119.2, 109.3, 38.5, 21.4, 21.2, 14.2; IR (neat): νmax 3048, 2975, 2924, 1618, 1511, 1464,
1384, 1339, 1204, 1023, 823, 744, 701 cm-1; HRMS (ESI): Calcd. for C33H29N2 (M+ + H):
m/z 453.2331. Found: 453.2332.
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2-(4-Chlorophenyl)-5-ethyl-4-(4-methylphenyl)-3-phenyl-5H-pyrido[3,2-b]indole
(3bi).
White solid, yield 0.119 g (79%); mp 254-256 ºC; 1H NMR (500 MHz, CDCl3) δ 8.50 (d, J =
7.5 Hz, 1H), 7.60-7.56 (m, 1H), 7.42 (d, J = 8.5 Hz, 1H), 7.37-7.34 (m, 3H), 7.18-7.16 (m,
2H), 7.13-7.07 (m, 4H), 7.05-7.02 (m, 3H), 6.94-6.92 (m, 2H), 3.78 (qrt, J = 7.0 Hz, 2H),
2.35 (s, 3H), 1.01 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 149.1, 142.3,
141.7, 140.4, 138.6, 137.3, 133.2, 133.1, 132.7, 132.6, 131.70, 131.67, 130.6, 130.0, 128.4,
127.8, 127.7, 127.3, 126.1, 122.4, 121.2, 120.0, 109.3, 38.5, 21.3, 14.2; IR (neat): νmax 3053,
2975, 2926, 1617, 1494, 1386, 1340, 1205, 1090, 1016, 829, 745, 703 cm-1; HRMS (ESI):
Calcd. for C32H26ClN2 (M+ + H): m/z 473.1784. Found: 473.1789.
4-(4-Tert-butylphenyl)-2-(2,3-dichlorophenyl)-5-ethyl-3-phenyl-5H-pyrido[3,2-b]indole
(3bj). White solid, yield 0.150 g (86%); mp 241-243 ºC; 1H NMR (500 MHz, CDCl3) δ 8.54
(d, J = 8.0 Hz, 1H), 7.69-7.68 (m, 1H), 7.61-7.58 (m, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.37 (t, J
= 7.5 Hz, 1H), 7.31-7.28 (m, 2H), 7.21 (d, J = 8.5 Hz, 1H), 7.17-7.15 (m, 3H), 7.07-7.04 (m,
3H), 6.95-6.93 (m, 2H), 3.79 (qrt, J = 7.0 Hz, 2H), 1.33 (s, 9H), 1.01 (t, J = 7.0 Hz, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 150.9, 147.6, 142.4, 142.0, 141.7, 138.2, 133.1, 132.9,
132.7, 132.4, 131.7, 131.6, 130.80, 130.76, 129.8, 129.7, 129.2, 127.9, 127.4, 126.4, 124.5,
122.4, 121.3, 120.1, 109.3, 38.6, 34.6, 31.3, 14.2; IR (neat): νmax 3057, 2963, 2869, 1618,
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1469, 1386, 1344, 1205, 1136, 1028, 888, 748, 704 cm-1; HRMS (ESI): Calcd. for
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C35H31Cl2N2 (M+ + H): m/z 549.1864. Found: 549.1868.
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2-(4-Bromophenyl)-5-ethyl-4-(4-methylphenyl)-3-phenyl-5H-pyrido[3,2-b]indole
(3bk).
White solid, yield 0.129 g (78%); mp 250-252 ºC; 1H NMR (500 MHz, CDCl3) δ 8.53 (d, J =
6.4 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.37-7.28 (m, 5H), 7.14-7.08
(m, 4H), 7.05-7.04 (m, 3H), 6.95-6.93 (m, 2H), 3.79 (qrt, J = 7.0 Hz, 2H), 2.36 (s, 3H), 1.02
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(t, J = 7.0 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 149.1, 142.3, 141.7, 140.9, 138.6,
137.3, 133.2, 133.0, 132.6, 132.1, 131.7, 130.6, 130.0, 128.4, 127.8, 127.3, 126.2, 122.5,
121.3, 121.1, 120.0, 109.3, 38.6, 21.4, 14.2; IR (neat): νmax 3053, 2973, 2925, 1617, 1475,
1386, 1340, 1205, 1076, 1013, 828, 746, 702 cm-1; HRMS (ESI): Calcd. for C32H26BrN2 (M+
+ H): m/z 517.1279. Found: 517.1280.
5-Ethyl-4-(4-methoxyphenyl)-2,3-diphenyl-5H-pyrido[3,2-b]indole (3bl). White solid, yield
0.128 g (88%); mp 209-211 ºC; 1H NMR (500 MHz, CDCl3) δ 8.55 (d, J = 7.5 Hz, 1H), 7.59-
7.56 (m, 1H), 7.45-7.41 (m, 3H), 7.37-7.34 (m, 1H), 7.32-7.19 (m, 8H), 6.86-6.83 (m, 2H),
6.57-6.54 (m, 2H), 3.76 (qrt, J = 7.0 Hz, 2H), 3.69 (s, 3H), 1.01 (t, J = 7.0 Hz, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 157.7, 150.8, 142.2, 142.1, 141.5, 136.7, 132.7, 132.62, 132.58,
131.0, 130.4, 130.2, 127.7, 127.63, 127.59, 127.56, 126.5, 122.6, 121.3, 119.9, 112.6, 109.2,
55.0, 38.5, 14.2; IR (neat): νmax 3054, 2968, 2926, 1613, 1513, 1461, 1384, 1335, 1245, 1202,
1030, 744, 701 cm-1; HRMS (ESI): Calcd. for C32H27N2O (M+ + H): m/z 455.2123. Found:
455.2124.
5-Ethyl-4-(3-fluorophenyl)-2,3-diphenyl-5H-pyrido[3,2-b]indole (3bm). White solid, yield
0.107 g (76%); mp 176-178 ºC; 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J = 7.5 Hz, 1H), 7.61-
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7.58 (m, 1H), 7.45-7.42 (m, 3H), 7.39-7.36 (m, 1H), 7.28-7.19 (m, 4H), 7.08-6.94 (m, 8H),
3.81 (qrt, J = 7.5 Hz, 2H), 1.06 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 162.0
(d, J = 245.8 Hz), 150.6, 142.3, 141.8, 141.6, 138.8 (d, J = 7.7 Hz), 138.4, 132.8, 131.6 (d, J
= 7.1 Hz), 130.8, 130.7, 130.4, 130.0, 129.4 (d, J = 8.3 Hz), 127.9, 127.5, 127.3, 127.2,
126.8, 126.27, 126.26, 122.5, 121.4, 120.1, 117.4 (d, J = 21.3 Hz), 114.7 (d, J = 21.8 Hz),
109.3, 38.6, 14.2; IR (neat): νmax 3057, 2975, 2927, 1614, 1583, 1483, 1386, 1339, 1206,
1146, 782, 744, 702 cm-1; HRMS (ESI): Calcd. for C31H24FN2 (M+ + H): m/z 443.1924.
Found: 443.1923.
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4-(4-Bromophenyl)-5-ethyl-2,3-diphenyl-5H-pyrido[3,2-b]indole (3bn). White solid, yield
0.125 g (78%); mp 225-227 ºC; 1H NMR (500 MHz, CDCl3) δ 8.55 (d, J = 8.0 Hz, 1H), 7.61-
7.58 (m, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.39-7.25 (m, 10H), 7.06-7.03 (m, 3H), 6.96-6.94 (m,
2H), 3.78 (qrt, J = 7.0 Hz, 2H), 1.02 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
149.1, 142.3, 141.8, 140.8, 138.4, 136.3, 132.9, 132.4, 132.1, 130.6, 130.4, 130.2, 127.9,
127.7, 127.3, 126.3, 122.4, 121.3, 121.1, 120.1, 109.3, 38.6, 14.2; IR (neat): νmax 3056, 2976,
2929, 1617, 1542, 1385, 1337, 1203, 1074, 1010, 832, 740, 702 cm-1; HRMS (ESI): Calcd.
for C31H24BrN2 (M+ + H): m/z 503.1123. Found: 503.1124.
5-Ethyl-3-(4-methoxyphenyl)-4-phenyl-2-(thiophen-2-yl)-5H-pyrido[3,2-b]indole
(3bp).
White solid, yield 0.110 g (75%); mp 252-254 ºC; 1H NMR (500 MHz, CDCl3) δ 8.53 (d, J =
7.5 Hz, 1H), 7.58-7.55 (m, 1H), 7.39-7.34 (m, 2H), 7.28-7.27 (m, 3H), 7.23-7.20 (m, 3H),
7.00 (d, J = 8.5 Hz, 2H), 6.82-6.81 (m, 1H), 6.73 (d, J = 8.5 Hz, 2H), 6.45-6.44 (m, 1H), 3.78
(s, 3H), 3.68 (qrt, J = 7.0 Hz, 2H), 0.98 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3)
δ 158.6, 146.5, 143.8, 142.3, 141.4, 136.4, 132.9, 131.3, 130.8, 130.2, 130.1, 127.8, 127.7,
127.5, 127.1, 126.6, 126.2, 122.5, 121.4, 119.9, 113.4, 109.2, 55.1, 38.5, 14.1; IR (neat): νmax
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3056, 2969, 2928, 1612, 1513, 1457, 1387, 1324, 1240, 1195, 1030, 836, 744, 703 cm-1;
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HRMS (ESI): Calcd. for C30H25N2OS (M+ + H): m/z 461.1688. Found: 461.1689.
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5-Ethyl-2-methyl-3,4-diphenyl-5H-pyrido[3,2-b]indole (3bq). White solid, yield 0.085 g
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(73%); mp 215-217 ºC; H NMR (500 MHz, CDCl3) δ 8.50 (dd, J = 7.5 Hz, 0.5 Hz, 1H),
7.57-7.53 (m, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.35-7.32 (m, 1H), 7.26-7.19 (m, 7H), 7.17-7.14
(m, 1H), 7.08-7.06 (m, 2H), 3.72 (qrt, J = 7.0 Hz, 2H), 2.53 (s, 3H), 0.97 (t, J = 7.0 Hz, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 148.4, 141.8, 140.9, 139.2, 136.5, 133.7, 132.0, 130.3,
129.9, 129.7, 127.7, 127.6, 127.5, 127.3, 126.4, 122.2, 120.8, 119.7, 109.2, 38.4, 24.3, 14.1;
IR (neat): νmax 3056, 2975, 2925, 1616, 1548, 1457, 1386, 1338, 1212, 1128, 744, 702 cm-1;
HRMS (ESI): Calcd. for C26H23N2 (M+ + H): m/z 363.1861. Found: 363.1867.
14-Ethyl-15-phenyl-14H-dibenzo[f,h]indolo[3,2-b]Quinoline (3br). White solid, yield 0.096
g (71%); mp 227-229 ºC; 1H NMR (400 MHz, CDCl3) δ 9.73 (dd, J = 8.4, 1.2 Hz, 1H), 8.69
(d, J = 7.6 Hz, 1H), 8.65 (d, J = 8.0 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 7.79 (td, J = 7.2, 1.2
Hz, 1H), 7.74-7.60 (m, 8H), 7.51-7.47 (m, 1H), 7.44-7.40 (m, 2H), 7.08-7.04 (m, 1H), 3.65
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(qrt, J = 7.2 Hz, 2H), 0.97 (t, J = 6.8 Hz, 3H); C{1H} NMR (125 MHz, CDCl3) δ 144.2,
142.8, 141.8, 139.5, 132.3, 131.9, 131.2, 130.5, 130.4, 130.2, 129.5, 129.12, 129.06, 128.7,
128.6, 127.8, 127.4, 126.3, 125.9, 125.2, 123.3, 122.5, 122.2, 121.6, 121.2, 120.0, 109.5,
39.0, 14.2; IR (neat): νmax 3053, 2976, 2928, 1615, 1486, 1385, 1338, 1203, 1149, 915, 743,
700 cm-1; HRMS (ESI): Calcd. for C31H23N2 (M+ + H): m/z 423.1861. Found: 423.1870.
3-([1,1'-Biphenyl]-4-yl)-5-ethyl-2,4-diphenyl-5H-pyrido[3,2-b]indole (3bs). White solid,
yield 0.040 g (25%); mp 228-230 ºC; 1H NMR (500 MHz, CDCl3) δ 8.57 (d, J = 7.5 Hz, 1H),
7.61-7.57 (m, 3H), 7.52-7.51 (m, 2H), 7.47-7.41 (m, 5H), 7.38-7.27 (m, 8H), 7.04-7.01 (m,
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3H), 7.00-6.98 (m, 2H), 3.78 (qrt, J = 7.0 Hz, 2H), 1.02 (t, J = 7.0 Hz, 3H); C{1H} NMR
(125 MHz, CDCl3) δ 150.1, 142.3, 141.7, 141.1, 140.9, 139.3, 138.7, 136.5, 133.0, 132.4,
131.8, 130.8, 130.31, 130.27, 128.7, 127.73, 127.67, 127.63, 127.2, 127.1, 127.0, 126.3, 126.1,
122.6, 121.3, 119.9, 109.2, 38.6, 14.2; IR (neat): νmax 3055, 2971, 2924, 1616, 1485, 1387,
1339, 1205, 846, 751, 703 cm-1; HRMS (ESI): Calcd. for C37H29N2 (M+ + H): m/z 501.2331.
Found: 501.2338.
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2-([1,1'-Biphenyl]-4-yl)-5-ethyl-3,4-diphenyl-5H-pyrido[3,2-b]indole (3bs’). White solid,
yield 0.101 g (64%); mp 222-224 ºC; 1H NMR (500 MHz, CDCl3) δ 8.57 (d, J = 8.0 Hz, 1H),
7.61-7.58 (m, 1H), 7.54-7.52 (m, 2H), 7.49-7.46 (m, 2H), 7.44-7.35 (m, 4H), 7.33-7.27 (m,
8H), 7.24-7.17 (m, 3H), 7.02-7.00 (m, 2H), 3.79 (qrt, J = 7.0 Hz, 2H), 1.02 (t, J = 7.0 Hz,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 150.6, 142.3, 141.9, 141.8, 140.6, 138.3, 137.9,
136.6, 132.6, 132.4, 132.2, 130.5, 130.4, 130.3, 128.7, 127.8, 127.7, 127.6, 127.1, 126.79,
126.75, 125.6, 122.6, 121.4, 120.0, 109.3, 38.6, 14.2; IR (neat): νmax 3053, 2976, 2928, 1615,
1486, 1385, 1338, 1203, 1149, 915, 743, 700 cm-1; HRMS (ESI): Calcd. for C37H29N2 (M+ +
H): m/z 501.2331. Found: 501.2341.
2,3,4-Triphenyl-5-(prop-2-en-1-yl)-5H-pyrido[3,2-b]indole (3ca). White solid, yield 0.111 g
(83%); mp 205-207 ºC; 1H NMR (400 MHz, CDCl3) δ 8.57-8.54 (m, 1H), 7.58-7.54 (m, 1H),
7.44-7.41 (m, 2H), 7.38-7.34 (m, 2H), 7.28-7.18 (m, 8H), 7.01-6.98 (m, 3H), 6.94-6.92 (m,
2H), 5.61-5.52 (m, 1H), 5.00 (dd, J = 10.4, 1.0 Hz, 1H), 4.65 (dd, J = 17.2, 1.0 Hz, 1H), 4.33-
4.31 (m, 2H); C{1H} NMR (100 MHz, CDCl3) δ 150.8, 142.8, 141.8, 141.5, 138.6, 136.1,
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133.1, 132.9, 132.5, 131.7, 130.6, 130.45, 130.39, 127.8, 127.7, 127.6, 127.5, 127.1, 126.8,
126.0, 122.4, 121.2, 120.2, 116.0, 109.8. 46.1; IR (neat): νmax 3056, 2923, 2858, 1616, 1490,
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