Synthetic Routes to Isomeric Imidazoindoles by Regioselective Ring-Opening of Activated Aziridines Followed by Copper-Catalysed C–N Cyclization

Article abstract of DOI:10.1002/ejoc.201700267

Two new synthetic routes that deliver substituted imidazoindoles in high yields with excellent ee values have been developed. The reactions proceed through ring-opening of activated aziridines with 2,2-dibromovinylanilines or 2-bromoindoles, followed by a Cu-catalysed domino C–N,C–N-cyclization, or a C–N cyclization, respectively. The first route gives rise to one regioisomer, and the second route gives the other.

Full text of DOI:10.1002/ejoc.201700267

A Journal of
Accepted Article
Title: Synthetic Routes to Isomeric Imidazoindoles via Regioselective
Ring-Opening of Activated Aziridines Followed by Copper
Catalyzed C-N Cyclization
Authors: Masthanvali Sayyad, Imtiyaz Ahmad Wani, Deo Prakash
Tiwari, and Manas K. Ghorai
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700267
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700267
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European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
Synthetic Routes to Isomeric Imidazoindoles via Regioselective
Ring-Opening of Activated Aziridines Followed by Copper
Catalyzed C-N Cyclization
Masthanvali Sayyad, Imtiyaz Ahmad Wani, Deo Prakash Tiwari, and Manas K. Ghorai*[a]
Abstract: Two new synthetic routes to substituted imidazoindoles in
high yields and excellent ee have been developed via ring-opening
followed by Cu-catalyzed i) domino-C-N, C-N-cyclization and ii) C-N
cyclization of activated aziridines with 2,2-dibromovinylanilines and 2-
bromo indoles, respectively. The aforementioned first route gives rise
to one regioisomer whereas the second route leads to the formation
of other regiomer.
developed an efficient route for the synthesis of substituted
imidazoindolones from readily synthesized gem-
dibromovinylanilines.9a However, because of lack of availability of
general methodology for the synthesis of regioisomeric
imidazoindoles in enantiomerically pure forms, it is highly
desirable to develop new regio- and stereoselective strategies for
the synthesis of functionalized imidazoindoles. For a long period
of time, aziridines are being utilized as the building blocks for the
synthesis of numerous N-containing compounds of contemporary
synthetic and biological interest.10 In continuation of our efforts for
a
Introduction
the exploration and exploitation of
S
N
2-type ring opening
6
chemistry of activated aziridines and azetidines, we have
developed two related strategies for the synthesis of two different
regioisomers of the same imidazoindoles via ring-opening
followed by cyclization of activated aziridines employing 2-bromo
indoles and 2,2-dibromovinylanilines as the nucleophiles as
depicted in Scheme 1. To the best of our knowledge, this is the
first report of this kind.
The development of new synthetic protocols for selective
formation of carbon-carbon and carbon-heteroatom bonds
remains the main focus in organic synthesis for all time.1,2,3 In
recent years the coupling reactions have emerged as one of the
important tools for new C-C/C-X bond formation and are
frequently utilized as key steps for designing several domino
strategies.4,5 The prominent transition metal catalysts being used
in coupling based domino and multi-component reactions are
mostly Pd and Cu catalysts.4,5 Our keen interest in designing
coupling based domino synthetic routes to important heterocyclic
Scheme 1. Proposed Synthetic Routes to Regioisomeric Imidazoindoles
6
scaffolds inspired us to envision and develop two related Cu (I)
catalyzed domino and one pot strategies for the synthesis of
indole-based polycyclic molecular architectures.
Functionalized indoles and their derivatives play a key role in drug
discovery programs. Needless to mention that indole based
polycyclic systems having fused ring systems at C-2 and C-3
positions like pyrroloindoline, β-carboline, carbazole and higher
ring-size analogues are of contemporary synthetic interest.
However, N-1 and C-2 fused ring systems e.g. imidazoindoles are
less explored in spite of their significant biological activities and
chirality inducing properties.7 Cruz-Almanza et al. synthesized
imidazo[1,2-a]indole derivatives from 1-ω-azidoalkylindoles via
intramolecular 1,3-dipolar cycloaddition.8a Another synthetic route Results and Discussion
towards imidazo[1,2-a]indoles from heterocyclic ketene aminals
and 1,4-benzoquinones was described by Lin et al.8b gem-
Dibromovinylanilines9 are versatile intermediates introduced by
To test the feasibility of our approach we chose ring opening
product 3a as the model substrate which was synthesized from
the ring opening of 1a with 2a in the presence of LiClO (10 mol%)
4
as the Lewis acid (Scheme 2). Next, we studied a number of
reaction conditions (solvents, bases, ligands etc.) in the presence
of a Cu-catalyst to cyclize 3a to the corresponding imidazoindole
4a as shown in Table 1. When ethylene diamine (EDA) was used
[
a]
Masthanvali Sayyad, Imtiyaz Ahmad Wani, Deo Prakash Tiwari,
Manas K. Ghorai
Department of Chemistry
Indian Institute of Technology Kanpur
Kanpur 208016, Uttarpradesh (India)
E-mail: mkghorai@iitk.ac.in
2 3
as the ligand in the presence of K CO as the base in DMF, the
starting material was consumed in 12 h, however, a complex
reaction mixture was generated (entry 1, Table 1). Similar results
were obtained when EDA was replaced with L-proline (entry 2,
Table 1). When the reaction was performed in toluene, the tricyclic
compound 4a with two new C-N bonds was produced in 25% yield
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
Lautens et al. and later utilized by others for the synthesis of
indoles and 2-aminoindoles. In this context, Lautens et al. has
(
entry 3, Table 1). Use of EDA, glycine and 1, 10-phenanthroline
as the Cu (I)-binding ligands could not make any noticeable
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European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
Scheme 2. Substrate Scope of 3
improvement in the reaction (entry 4, 5 and 6, Table 1). To our
pleasure, when the reaction was performed using (±)-trans-1,2-
diaminocyclohexane as the ligand (entry 7, Table 1), 4a was
obtained with high yield (76%). Yield of the product 4a could not
be further improved using other bases like Cs
powder (entry 8-11, Table 1).
2 3
CO /NaH and Cu
Table 1. Optimization Studies of the Domino-C-N, C-N-Cyclization
entry
1
reaction conditions
yield (%)a
CuI (10 mol %), EDA (20 mol %), K
2 3
CO , DMF,
complex
mixture
120 °C, 12 h
2
3
4
5
6
7
CuI (10 mol %), L-proline (20 mol %), K
DMF, 120 °C, 12 h
2
CO
3
,
,
complex
mixture
Scheme 3. Synthesis of Racemic Imidazoindoles 4 via Domino C-N, C-N
Cyclization
CuI (10 mol %), L-proline (20 mol %), K
PhMe, 120 °C, 12 h
2
CO
3
25
35
22
35
76
CuI (10 mol %), EDA (20 mol %), K
20 °C, 12 h
2 3
CO , PhMe,
1
CuI (10 mol %), glycine (20 mol %), K
20 °C, 12 h
2 3
CO , PhMe,
1
CuI (10 mol %), 1, 10-phen (20 mol %), K
PhMe, 120 °C, 12 h
2 3
CO ,
CuI
(10
mol
%),
(±)-trans-1,2-
CO (2.0
diaminocyclohexane (20 mol %), K
equiv), PhMe, 120 °C, 12 h
2
3
8
9
CuI
(10
mol
%),
(±)-trans-1,2-
CO (2.0
67
diaminocyclohexane (20 mol %), Cs
equiv), PhMe, 120 °C, 12 h
2
3
CuI
(10
mol
%),
(±)-trans-1,2-
Complex
mixture
diaminocyclohexane (20 mol %), NaH (2.0 equiv),
PhMe, 120 °C, 12 h
Interestingly, tetracyclic indole derivatives 4f,g were obtained in
good yields from the corresponding racemic cyclopentyl and
cyclohexyl substituted substrates 3f,g (Scheme 4).
1
0
1
Cu powder (1.0 equiv.), PhMe, 120 °C, 12 h
Cu powder (1.0 equiv.), DMF, 120 °C, 12 h
NR
15
Scheme 4. Synthesis of Tetra-Cyclic Imidazoindoles 4
1
all the reactions were performed in pressure tubes. ayield of isolated
products.
To examine the substrate scope of our Cu-catalyzed domino
cyclization towards functionalized imidazoindoles, a number of
ring-opening products 3b-g were obtained from the reaction of the
corresponding aziridines 1a-b,j-m and dibromovinylanilines 2a-b
The synthetic potential of the strategy was further demonstrated
by the synthesis of non-racemic imidazoindoles. When the
enantiopure ring opening products (S)-3a and (R)-3b were
subjected to optimized domino-coupling conditions, the
corresponding cyclic products (S)-4a and (R)-4b, respectively,
were obtained with excellent enantiomeric excess (ee >99%,
Scheme 5).
(
Scheme 2). Next 3b-e were studied under the Cu(I) catalyzed
optimized conditions to furnish the corresponding cyclic products
b-e in good to excellent yields where the halo-substituents on
the aryl motif were well tolerated (Scheme 3).
4
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European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
Scheme 5. Synthesis of Non-racemic Imidazoindoles 4
Scheme 6. Two Step One-Pot Strategy for the Synthesis of Racemic
Regioisomeric Imidazolindoles 6
In order to generalize our approach further in terms of different
substitution patterns, next we attempted to synthesize C-2
regioisomer 6 of imidazoindoles 4. We anticipated that 2-
bromoindoles being bulky nucleophiles would undergo the ring-
opening of aziridines 5 from the less hindered site and generate
the corresponding ring-opening products D which could undergo
Cu-catalyzed C-N cyclization easily to produce the desired
regioisomeric imidazoindoles
6 under a two-step one-pot
conditions (Scheme 6). After screening several reaction
conditions (as shown in Table 2) when the aziridine 1a was
treated with 2-bromoindole 5a followed by Cu(I) catalyzed
cyclization of the corresponding in situ generated sulphonamide
intermediate (D), the C-2 substituted imidazoindoles 6a was
obtained in excellent yield 85% as shown in Table 2.
To our pleasure, when the enantiopure aziridines (S)-1a,e-i (both
2-aryl and 2-alkyl) were employed as the substrates, the
corresponding imidazoindoles (S)-6d,g-p were obtained in
Scheme 7. Two Step One-Pot Strategy for the Synthesis of Non-racemic
Regioisomeric Imidazolindoles 6
Table 2. Optimization of the Reaction Conditions for the Reaction of N-
tosylaziridine 1a with 2-bromoindole 5a
a
entry
base
NaH
solvent
DMF
time (h)
yield (%) of 6a
1
2
3
4
6
7
5
85
75
55
60
50
72
NaH
DMSO
DMF
8
t-BuOK
4
K
K
2
CO
3
3
DMF
15
20
6
2
CO
DMSO
NMP
NaH
Reaction conditions: 1a (1.0 equiv.), 5a (1.1 equiv), base (1.1 equiv.) under
atmosphere.
N
2
Further generalization of this approach is made by studying a
number of 2-bromoindioles (5a-c) with aziridines 1a-d as shown
in Scheme 6. The structure of 6d was confirmed by X-ray
crystallographic analysis.11
enantiopure forms (Scheme 7). Since in all these cases, the chiral
centers remained unperturbed during the ring opening step, the
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European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
imidazoindole derivatives (S)-6d,g-p were obtained in Conclusions
enantiomerically pure forms.
The plausible reaction mechanism for the formation of the
products is depicted in Scheme 8. In the case of domino strategy,
the first step is the formation of the indole B. Next, the liberated
active catalyst LCuX reacts with B via intermediate C to generate
In conclusion, we have developed Cu-catalyzed domino and one
pot processes for the syntheses of isomeric imidazoindoles from
activated aziridines in both racemic and enantiopure forms.
Further work for biological studies is in progress.
4. It is likely that the less acidic nitrogen (-NH) group of 3
coordinates with copper(I) catalyst to generate the complex A and
then oxidative addition followed by reductive elimination take
place with one of the bromide on gem-dibromide to give
intermediate B via a favourable six membered transition state.
From B, the same sequence of events (coordination, oxidative
addition followed by reductive elimination) leads to the formation
of the final product 4. Whereas, the coordination of copper(I) with
the more acidic (-NHTs) group would lead to the generation of a
less favourable nine membered TS. Probably because of this
reason, the copper(I) catalyst coordinates preferably with less
acidic nitrogen (-NH) group compared to NHTs group of 3c. The
one pot protocol proceeds with the formation of the ring-opening
product D in the first step and it undergoes cyclization in the next
step via intermediate E to produce the regiomer 6.
Experimental Section
General Procedures
Thin Layer Chromatography (TLC) was performed using silica gel 60 F254
pre-coated plates. UV lamp or I stain was used for visualization of spots.
2
Silica gel 100-200 and 230-400 mesh size was used for column
chromatography using ethyl acetate in petroleum ether as the eluent.
Unless noted, all reactions were carried out in oven-dried glassware under
an atmosphere of nitrogen/argon using anhydrous solvents. Where
appropriate, all reagents were purified prior to use following the guidelines
of Perrin and Armarego12 and Vogel.13 2-aryl-1-tosylaziridines and
cyclopentyl- and cyclohexyl-fused aziridines were prepared from styrene
derivatives following
a
reported procedure.14 Chiral 2-phenyl-1-
tosylaziridine and chiral 2-(2-chlorophenyl)-1-tosylaziridine and chiral
aliphatic aziridines were prepared from corresponding amino alcohol
following a reported procedure.15 Substrates 2a-b were synthesized from
Scheme 8. Plausible Mechanisms for the Synthesis of Imidazoindoles
2
-nitrobenzaldehyde derivatives following reported procedure.16a
Substrate 5a was synthesized from 2-(2,2-Dibromovinyl)aniline following
reported procedure.16b Substrates 5b was synthesized through
bromination of 3-methylindole with N-Bromosuccinimide following reported
procedure.17a Substrate 5c was synthesized from 3-bromoindole following
reported procedure.17b All commercial reagents were used as received
without prior purification unless mentioned. IR spectra were recorded in
potassium bromide (KBr) pellet, whereas liquid compounds were recorded
neat. Proton nuclear magnetic resonance (1H NMR) spectra were
recorded at 400 MHz and 500 MHz. Chemical shifts were recorded in parts
per million (ppm, δ) relative to tetramethylsilane (δ 0.00). 1H NMR splitting
patterns are designated as singlet (s), doublet (d), double doublet (dd),
triplet (t), quartet (q) or multiplet (m). Carbon nuclear magnetic resonance
(13C {1H} NMR) spectra were recorded at 100 MHz and 125 MHz. HRMS
were obtained using an (ESI) mass spectrometer (TOF). Melting point was
determined using a hot-stage apparatus and are reported as uncorrected.
Enantiomeric ratios (er) were determined by HPLC using chiralpak IA
chiralcel OD-H analytical column (detection at 254 nm). Optical rotations
were measured using a 6.0 mL cell with a 1.0 dm path length and are
reported as [α]25
(c in gm per 100 mL solvent) at 25 ºC.
D
Method A: General procedure for the ring opening of aziridines with
-(2,2-dibromovinyl)aniline 3. In a dry 10 mL two neck round bottom
flask under argon were added the 2-phenyl-1-tosylaziridine (54.7 mg,
.200 mmol), the 2-(2,2-dibromovinyl)aniline (55.4 mg, 0.200 mmol),
anhydrous LiClO (4.3 mg, 0.04 mmol ), and CH CN (0.2 mL). Reaction
mixture was stirred at 85 °C for 1 h. The reaction mixture was quenched
with H O. The aqueous layer was extracted with CH Cl (3 × 5.0 mL) and
dried over anhydrous Na SO . The crude product was purified by flash
2
0
4
3
2
2
2
2
4
column chromatography on silica gel (230−400 mesh) using 15% ethyl
acetate in petroleum ether to provide the pure product.
Method B: General procedure for Cu-catalyzed C–N cyclization of 3.
To an oven-dried sealed tube charged with ring opening product N-(2-(2-
(
2,2-dibromovinyl)phenylamino)-2-phenylethyl)-4-
methylbenzenesulfonamide 3a (69 mg, 0.125 mmol), CuI (2.4 mg, 10
mol %), (±)-trans 1,2-diaminocyclohexane (2.8 mg, 20 mol %), K CO
2
3
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European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
1
(34.5 mg 2.0 equiv), were dissolved in dry PhMe in 2.0 mL. The reaction
1092, 1025, 917, 814, 758, 678, 592, 576, 546; H NMR (500 MHz, CDCl
3
)
mixture was heated at 120 °C for the appropriate time, and the reaction
was monitored by TLC. It was cooled to room temperature, poured into
water, and extracted with ethyl acetate (3 × 10 mL). The combined organic
 = 2.22 (s, 3H), 3.03 (dd, J = 13.1, 6.9 Hz, 1H), 3.16 (dd, J = 13.7, 4.6 Hz,
1H), 4.25 (d, J = 7.4, 4.6 Hz, 1H), 4.53 (br s, 1H), 4.63 (t, J = 6.3 Hz, 1H),
6.11 (d, J = 8.0 Hz, 1H), 6.51 (t, J = 8.0 Hz, 1H), 6.82–6.86 (m, 1H), 7.07–
7.14 (m, 8H), 7.24 (s, 1H), 7.54 (d, J = 8.6 Hz, 2H); 13C{1H} NMR (100
extract was washed with H
Na SO . The solvent was removed under reduced pressure to give crude
product, which was purified by flash column chromatography on silica gel
230−400 mesh) using ethyl acetate in petroleum ether to afford the pure
2
O (3 × 10 mL) and brine (15 mL) and dried over
2
4
3
MHz, CDCl )  = 21.6, 49.1, 57.6, 93.8, 112.3, 117.6, 122.5, 126.6, 127.2,
128.1, 129.2, 129.3, 129.7, 129.9, 134.0, 136.9, 139.7, 143.6, 143.8;
+
(
HRMS (ESI-TOF): m/z calcd for C23
548.9849; [α]25
= –78.75 (c 0.16, CH
was determined by chiral HPLC analysis (Chiralcel IA column),
hexane/isopropanol = 95:5, flow rate = 1.0 mL min–1, t
(1) = 25.52 min
minor, R), t (2) = 36.78 min (major, S).
H23Br
2 2 2
N O S (M+H) 548.9847; found:
product as thick liquid.
D
2 2
Cl ) for a >99% ee sample, the ee
R
Method C: General procedure for a one-pot (Stepwise) protocol for
the synthesis of imidazoindoles 6. To a suspension of sodium hydride
(
R
(1.0 equiv) in Dry DMF (1.0 mL) was added 2-Bromo-1H-indole 5a (19.6
mg, 0.100 mmol), at room temperature under nitrogen atmosphere and
stirred for 5 minutes. Subsequently, solutions of 2-phenyl-1-tosylaziridine
(R)-N-(2-(2-Chlorophenyl)-2-(2-(2,2-
dibromovinyl)phenylamino)ethyl)-4-methylbenzenesulfonamide 3b.
The general method A described above was followed when (S)-1b (100
mg, 0.325 mmol) reacted with a 2-(2,2-dibromovinyl)aniline 2a (90.0 mg,
1
a (27.3 mg, 0.100 mmol) in dry DMF (1.0 mL) were added to the reaction
mixture. The reaction mixture was stirred at rt for the appropriate time. CuI
10 mol %), (±)-trans 1,2-diaminocyclohexane (20 mol %), K CO (1.0
equiv) were added subsequently to the reaction mixture was heated for at
20 °C for appropriate time. After complete consumption of ring opening
product (monitored by TLC), the reaction was quenched by addition of
saturated aqueous NH Cl (1.0 mL) solution. The organic phase was
separated, and the aqueous phase was extracted with ethylacetate
3×10.0 mL). The combined extracts were washed with brine and dried
(
2
3
0.325 mmol) in the presence of LiClO
(R)-3b (135.1 mg, 0.231 mmol) as a white solid in 71% yield: mp
155−157 °C; R = 0.51 (20 % ethyl acetate in petroleum ether); IR (KBr):
max = 3384, 3281, 2923, 2851, 1720, 1600, 1581, 1514, 1461, 1323, 1260,
4
(20 mol %) at 85 °C for 5 h to afford
1
f
ṽ
1
4
1185, 1158, 1092, 1035, 969, 871, 813, 748, 706, 661, 550; H NMR (500
MHz, CDCl )  = 2.40 (s, 3H), 3.18–25 (m, 1H), 3.41–3.46 (m, 1H), 4.78–
3
(
4.85 (br s, 2H), 4.96 (d, J = 5.2 Hz, 1H), 6.12 (d, J = 8.0 Hz, 1H), 6.70 (t, J
= 7.5 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 7.18–7.20 (m, 2H), 7.25–7.29 (m,
3H), 7.34–7.35 (m, 1H), 7.40–7.42 (m, 1H), 7.50 (s, 1H), 7.74 (d, J = 8.0
Hz, 2H); 13C{1H} NMR (125 MHz, CDCl
117.6, 122.4, 127.2, 127.7, 128.4, 129.2, 129.4, 129.7, 129.9, 130.0, 132.7,
over anhydrous sodium sulfate. After removal of the solvent under reduced
pressure, the crude reaction mixture was purified by flash column
chromatography on silica gel (230-400 mesh) using ethyl acetate in
petroleum ether as the eluent to afford the pure product 6a as white solid.
3
)  = 21.7, 46.7, 54.6, 93.8, 111.8,
1
34.1, 136.6, 136.9, 143.4, 143.9; HRMS (ESI-TOF): m/z calcd for
+
25
-(2,2-Dibromovinyl)aniline 2a.16a 1H NMR (500 MHz, CDCl
s, 2H), 6.70 (dd, J = 8.2, 0.9 Hz, 1H), 6.79 (t, J = 6.9 Hz, 1H), 7.16 (t, J =
C
23
H22Br
2
ClN
Cl ); for a ee 94% sample, the ee was determined by chiral HPLC
analysis (Chiralcel IA column), hexane/isopropanol = 95:5, flow rate = 1.0
mL min–1, t
(1) = 22.67 min (major, R) and t (2) = 39.55 min (minor, S).
O S (M+H) : 582.9457; found 582.9457; [α] = +86.19 (c
2 2 D
2
3
)  3.69 (br
0.21, CH
2
2
.0 Hz, 1H), 7.29 (d, J = 7.3 Hz, 1H), 7.33 (s, 1H); 13C { H} NMR (125 MHz,
1
8
R
R
CDCl
3
)  92.9, 115.9, 118.5, 121.9, 129.3, 129.8, 134.2, 143.7; HRMS
+
(ESI) calcd for C
8 8
H Br
2
N (M+H) 275.9023, found 275.9021.
N-(2-(2-(2,2-Dibromovinyl)phenylamino)-2-(4-fluorophenyl)ethyl)-4-
methylbenzenesulfonamide 3c. The general method A described above
was followed when 1j (58.2 mg, 0.200 mmol) reacted with a 2-(2,2-
-Chloro-2-(2,2-dibromovinyl)aniline 2b.16a 1H NMR (500 MHz, CDCl
3
)
4

7
9
3.70 (br s, 2H), 6.62 (d, J = 8.6 Hz, 1H), 7.09 (dd, J = 8.6, 2.4 Hz, 1H),
.25 (s, 1H), 7.26 (d, J = 2.6 Hz, 1H); 13C {1H} NMR (125 MHz, CDCl
dibromovinyl)aniline 2a (55.4 mg, 0.200 mmol) in the presence of LiClO
4
3
) 
(20 mol %) at 85 °C for 1 h to afford 3c (99.5 mg, 0.175 mmol) as a white
4.2, 117.0, 123.0, 123.1, 128.8, 129.6, 132.9, 142.3.
solid in 90% yield: mp 130−132 °C; R
f
= 0.52 (20 % ethyl acetate in
-Bromo-1H-indole 5a.16b 1H NMR (400 MHz, CDCl
)  6.53 (s, 1H), 7.10
petroleum ether); IR (KBr): ṽmax = 3390, 2926, 1600, 1508, 1459, 1321,
261, 1222, 1157, 1092, 870, 835, 813, 747, 661; 1H NMR (400 MHz,
CDCl )  = 2.40 (s, 3H), 3.15–3.22 (m, 1H), 3.32 (ddd, J = 11.3, 6.8, 4.0
2
(
3
1
t, J = 7.6 Hz, 1H), 7.16 (t, J = 7.1 Hz, 1H), 7.29 (dd, J = 8.0, 0.5 Hz, 1H),
.52 (d, J = 7.8 Hz, 1H), 8.07 (br s, 1H); 13C{1H} NMR (125 MHz, CDCl
3
7
3
)
Hz, 1H), 4.41–4.43 (m, 1H), 4.59 (br s, 1H), 4.74 (t, J = 6.3 Hz, 1H), 6.24
(d, J = 8.2 Hz, 1H), 6.70 (t, J = 7.3 Hz, 1H), 6.90–7.06 (m, 3H), 7.24–7.28

104.9, 108.7, 110.4, 119.7, 120.6, 122.4, 128.8, 136.5; HRMS (ESI)
+
calcd for C
8
H
5
BrN (M–H) 193.9605, found 193.9604.
(
m, 5H), 7.41 (s, 1H), 7.72 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl
3
)  = 21.7, 49.1, 57.1, 93.9, 112.2, 116.0, 116.2, 117.7, 122.5, 127.1,
2
3
7
1
-Bromo-3-methyl-1H-indole 5b.17a 1H NMR (400 MHz, CDCl
H), 7.08–7.18 (m, 2H), 7.25 (d, J = 9.85 Hz, 1H), 7.48 (d, J = 9.9 Hz, 1H),
3
)  2.25 (s,
1
2
5
28.2, 129.5, 130.0, 134.0, 135.4, 136.8, 143.5, 143.9, 162.4 (d, 1JC-F
46.0 Hz); HRMS (ESI-TOF): m/z calcd for C23
66.9753; found 566.9755.
=
S (M+H)+:
H22Br
FN O
2 2 2
.89 (br s, 1H); 13C{1H} NMR (125 MHz, CDCl
19.4, 122.1, 122.3, 123.8, 136.9.
3
)  9.8, 110.1, 112.8, 118.3,
N-(2-(4-Bromophenyl)-2-(2-(2,2-dibromovinyl)phenylamino)ethyl)-4-
methylbenzenesulfonamide 3d. The general method A described above
was followed when 1k (50.0 mg, 0.141 mmol) reacted with a 2-(2,2-
2
3
,3-Dibromo-1H-indole 5c.17b 1H NMR (400 MHz, CDCl
H), 7.49 (d, J = 7.3 Hz, 1H); 8.24 (br s, 1H): 13C{1H} NMR (125 MHz,
3
)  7.16–7.29 (m,
CDCl
3
)  94.6, 110.0, 110.8, 119.0, 121.3, 123.6, 127.6, 135.7; HRMS
dibromovinyl)aniline 2a (38.8 mg, 0.141 mmol) in the presence of LiClO
4
+
(ESI) calcd for C
8 4
H Br
2
N (M–H) 271.8710, found 271.8724.
(20 mol %) at 85 °C for 1 h to afford 3d (75.5 mg, 0.120 mmol) as a white
f
solid in 85% yield: mp 85−87 °C; R = 0.51 (20 % ethyl acetate in petroleum
ether); IR (KBr): ṽmax = 2932, 2858, 1597, 1558, 1457, 1396, 1375, 1364,
(
S)-N-(2-(2-(2,2-Dibromovinyl)phenylamino)-2-phenylethyl)-4-
methylbenzenesulfonamide 3a. The general method A described above
was followed when (R)-1a (54.7 mg, 0.200 mmol) reacted with a 2-(2,2-
1
7
3
4
=
=
304, 1275, 1224, 1185, 1171, 1147, 1090, 1050, 1013, 892, 868, 817,
1
63, 744, 706, 663, 614, 575, 550; H NMR (500 MHz, CDCl
3
)  = 2.40 (s,
dibromovinyl)aniline 2a (55.4 mg, 0.200 mmol) in the presence of LiClO
4
H), 3.15–3.19 (m, 1H), 3.30–3.35 (m, 1H), 4.39 (br s, 1H), 4.63 (br s, 1H),
.92 (br s, 1H), 6.22 (d, J = 8.2 Hz, 1H), 6.71 (t, J = 6.4 Hz, 1H), 7.02 (t, J
7.3 Hz, 1H), 7.16 (d, J = 6.4 Hz, 2H), 7.26 (d, J = 7.3 Hz, 3H), 7.42 (d, J
(20 mol %) at 85 °C for 1 h to afford (S)-3a (101.3 mg, 0.184 mmol) as a
f
white solid in 92% yield: mp 122−124 °C; R = 0.42 (20 % ethyl acetate
in petroleum ether); IR (KBr): ṽmax = 2959, 1596, 1439, 1327, 1184, 1162,
8.2 Hz, 3H), 7.71 (d, J = 7.3 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl
3
) 
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
=
1
21.6, 49.0, 57.3, 93.9, 112.2, 117.8, 121.9, 122.6, 127.1, 128.4, 129.4,
CDCl
3
)  = 2.38 (s, 3H), 3.98 (dd, J = 10.4, 6.1 Hz, 1H), 4.62 (dd, J = 10.4,
29.6, 130.0, 132.3, 134.0, 136.8, 138.9, 143.4, 144.0; HRMS (ESI-TOF):
7.8 Hz, 1H), 5.30 (dd, J = 8.6, 6.7 Hz, 1H), 6.30 (s, 1H), 6.56 (d, J = 7.9
Hz, 1H), 6.85–6.88 (m, 3H), 7.04 (t, J = 7.9 Hz, 1H), 7.19–7.29 (m, 5H),
+
m/z calcd for C23
H22Br
3 2
N
O
2
S (M+H) : 626.8952; found 626.8955.
7
.50 (d, J = 7.9 Hz, 1H), 7.77 (d, J = 8.5 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl
3
)  = 21.7, 58.2, 61.2, 83.4, 109.5, 120.4, 120.5, 126.3, 127.8, 128.8,
N-(2-((4-Chloro-2-(2,2-dibromovinyl)phenyl)amino)-2-phenylethyl)-4-
methylbenzenesulfonamide 3e. The general method A described above
was followed when 1a (80.6 mg, 0.295 mmol) reacted with a 4-chloro-2-
129.2, 129.9, 130.5, 132.6, 133.3, 137.8, 141.8, 145.0; HRMS (ESI-TOF):
+
25
D
m/z calcd for C23
35.62 (c 0.32, CH
analysis (Chiralcel IA column), hexane/isopropanol 95:5, flow rate = 1.0
mL min–1; t
(1) = 12.06 min (major, S), t (2) = 16.25 min (minor, R).
H
21
N
2
O
2
S (M+H) : 389.1324; found 389.1323; [α]
=
+
2 2
Cl ); for a >99% ee was determined by chiral HPLC
(
2,2-dibromovinyl)aniline 2b (91.9 mg, 0.295 mmol) in the presence of
LiClO (20 mol %) at 85 °C for 4 h to afford 3e (146.8 mg, 0.251 mmol) as
a white solid in 85% yield: mp 144−146 °C; R = 0.32 (20 % ethyl acetate
in petroleum ether); IR (KBr): ṽmax = 3383, 2924, 2853, 1597, 1507, 1452,
409, 1323, 1157, 1092, 911, 811, 701, 662, 552; 1H NMR (400 MHz,
CDCl )  = 2.39 (s, 3H), 3.19 (m, 1H), 3.35 (m, 1H), 4.38 (dd, J = 7.3, 4.1
Hz, 1H), 4.72 (br s, 1H), 4.80 (t, J = 6.9 Hz, 1H), 6.17 (d, J = 8.7 Hz, 1H),
4
R
R
f
1
(R)-3-(2-Chlorophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole
4b. The general method B described above was followed when (R)-3b
(48.0 mg, 0.082 mmol) was reacted with CuI (10 mol %), (±)-trans 1,2-
3
6
.94 (dd, J = 8.7, 5.9 Hz, 1H), 7.25 (m, 7H), 7.31 (m, 3H), 7.37 (s, 1H);
)  = 21.6, 49.1, 57.8, 95.0, 113.3, 122.1,
23.6, 126.5, 127.1, 128.2, 128.9, 129.2, 129.3, 130.0, 132.8, 136.8, 139.3,
diaminocyclohexane (20 mol %) and K
120 °C for 12 h to afford (R)-4b (22.0 mg, 0.052 mmol) as a thick liquid in
63% yield: R
= 0.26 (10 % ethyl acetate in petroleum ether); [α]25
+86.19 (c 0.21, CH Cl ); IR (KBr): ṽmax = 3055, 2926, 1617, 1596, 1567,
2 3
CO (22.6 mg, 0.164 mmol) at
1
3C{1H} NMR (100 MHz, CDCl
3
1
1
5
f
D
=
42.4, 144.0; HRMS (ESI-TOF): m/z calcd for C23
82.9457; found 582.9456.
H22Br
ClN O
2 2 2
S (M+H)+:
2
2
1477, 1455, 1422, 1364, 1306, 1276, 1218, 1185, 1107, 1090, 1052, 1037,
1
1
010, 905, 849, 807, 761, 744, 704, 683, 665, 586, 547, 538; H NMR (400
MHz, CDCl
3
)  = 2.38 (s, 3H), 4.08 (dd, J = 10.9, 4.1 Hz, 1H), 4.68 (d, J =
N-(2-(2-(2,2-Dibromovinyl)phenylamino)cyclopentyl)-4-
1
6
7
0.9, 8.6 Hz, 1H), 5.73 (dd, J = 8.2, 4.1 Hz, 1H), 6.11 (d, J = 7.3 Hz, 1H),
.33 (s, 1H), 6.69 (d, J = 8.2 Hz, 1H), 6.83 (t, J = 7.7 Hz, 1H), 6.94 (t, J =
.7 Hz, 1H), 7.07 (t, J = 7.3 Hz, 1H), 7.11–7.18 (m, 3H), 7.37 (d, J = 8.2
methylbenzenesulfonamide 3f. The general method A described above
was followed when 1l (70.0 mg, 0.295 mmol) reacted with a 2-(2,2-
dibromovinyl)aniline 1a (81.7 mg, 0.295 mmol) in the presence of LiClO
4
Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.70 (d, J = 8.6 Hz, 2H); 13C{1H} NMR
125 MHz, CDCl )  = 21.6, 54.9, 60.1, 83.8, 109.6, 120.6, 120.7, 120.8,
26.7, 127.5, 127.7, 129.4, 129.9, 130.3, 131.8, 132.7, 133.2, 135.7, 137.8,
41.8, 144.9; HRMS (ESI-TOF): m/z calcd for C23
S (M+H)+:
(20 mol %) at 85 °C for 4 h to afford 3f (129.1 mg, 0.251 mmol) as a white
(
1
1
3
f
solid in 85% yield: mp 144−146 °C; R = 0.32 (20 % ethyl acetate in
petroleum ether); IR (KBr): ṽmax = 3269, 2960, 2923, 2872, 1600, 1579,
2 2
H20ClN O
1
8
509, 1457, 1321, 1260, 1184, 1157, 1119, 1093, 1051, 1019, 899, 877,
54, 814, 747, 665, 568, 549; 1H NMR (500 MHz, CDCl
)  = 1.36–1.42
423.0934; found 423.0932.
3
(m, 1H), 1.44–1.50 (m, 1H), 1.71 (br s, 2H), 1.92 (br s, 1H), 2.16–2.39 (m,
1H), 2.40 (s, 3H), 3.37–3.42 (m, 1H), 3.50–3.53 (m, 1H), 3.78 (br s, 1H),
4.95 (br s, 1H), 6.56 (d, J = 8.0 Hz, 1H), 6.72 (t, J = 7.5 Hz, 1H), 7.17 (s,
1
H), 7.25–7.27 (m, 3H), 7.74–7.75 (d, J = 8.6 Hz, 2H); 13C {1H}NMR (100
3-(4-Fluorophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 4c.
The general method B described above was followed when 3c (85.0 mg,
0.150 mmol) was reacted with CuI (10 mol %), (±)-trans 1,2-
MHz, CDCl
22.1, 127.2, 127.4, 129.4, 129.9, 133.3, 137.3, 143.7, 144.4; HRMS (ESI-
3
)  = 20.6, 21.7, 30.6, 30.7, 59.9, 60.3, 93.0, 111.6, 117.3,
diaminocyclohexane (20 mol %) and K
120 °C for 12 h to afford 4c (38.6 mg, 0.095 mmol) as a thick liquid in 63%
yield: R 0.24 (10 % ethyl acetate in petroleum ether); IR (KBr): ṽmax = 3052,
924, 1605, 1567, 1510, 1477, 1456, 1418, 1363, 1306, 1123, 1186, 1170,
2 3
CO (41.5 mg, 0.300 mmol) at
1
+
TOF): m/z calcd for C20
H23Br
2 2 2
N O S (M+H) : 512.9847; found 512.9846.
f
2
1
1
089, 1066, 1011, 904, 835, 815, 792, 745, 665, 582, 546; H NMR (400
)  = 2.38 (s, 3H), 3.94 (dd, J = 10.9, 5.9 Hz, 1H), 4.60 (dd, J
10.4, 8.2 Hz, 1H), 5.30 (dd, J = 8.2, 5.9 Hz, 1H), 6.29 (s, 1H), 6.55 (d, J
N-(2-(2-(2,2-Dibromovinyl)phenylamino)cyclohexyl)-4-
methylbenzenesulfonamide 3g. The general method A described above
was followed when 1m (45 mg, 0.179 mmol) reacted with a 2-(2,2-
MHz, CDCl
3
=
=
1
2
1
1
8.2 Hz, 1H), 6.79–6.82 (m, 2H), 6.86–6.90 (m, 3H), 7.04 (t, J = 7.3 Hz,
H), 7.21 (d, J = 8.6 Hz, 2H), 7.50 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 8.2 Hz,
dibromovinyl)aniline 1a (49.6 mg, 0.179 mmol) in the presence of LiClO
4
(20 mol %) at 85 °C for 4 h to afford 3g (80.3 mg, 0.152 mmol) as a white
H); 13C{1H} NMR (100 MHz, CDCl
)  = 21.7, 57.3, 61.3, 83.3, 109.4,
3
f
solid in 85% yield: mp 175−177 °C; R = 0.37 (20 % ethyl acetate in
petroleum ether); IR (KBr): ṽmax = 3391, 3265, 2931, 2857, 1722, 1600,
16.1, 116.3, 120.6, 127.8, 127.9, 128.0, 130.0, 130.4, 132.5, 133.3, 133.7,
41.7, 145.1, 162.6 (d, 1JC-F = 248.9 Hz); HRMS (ESI-TOF): m/z calcd for
1
7
1
1
579, 1515, 1459, 1323, 1262, 1160, 1090, 1049, 967, 903, 877, 866, 813,
+
1
C
23
H
20FN
2
O
2
S (M+H) : 407.1230; found 407.1238.
46, 705, 665, 571, 549; H NMR (500 MHz, CDCl
3
)  = 1.06–1.14 (m, 1H),
.20–1.32 (m, 3H), 1.65 (d, J = 9.7 Hz, 2H), 1.96 (br s, 1H), 2.17 (d, J =
3.1 Hz, 1H), 2.42 (s, 3H), 2.94–3.00 (m, 1H), 3.11–3.12 (m, 1H), 3.67 (br
3-(4-Bromophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 4d.
The general method B described above was followed when 3d (150 mg,
0.239 mmol) was reacted with CuI (10 mol %), (±)-trans 1,2-
s, 1H), 4.85–4.97 (br s, 1H), 6.58 (d, J = 8.6 Hz, 1H), 6.72 (t, J = 8.0 Hz,
H), 7.18 (br s, 2H), 7.25–7.28 (m, 3H), 7.73 (d, J = 8.0 Hz, 2H); 13C{1H}
NMR (125 MHz, CDCl )  = 21.7, 24.2, 24.5, 32.2, 32.9, 56.6, 57.0, 93.5,
11.2, 117.3, 122.5, 127.1, 129.7, 129.9, 134.1, 137.5, 143.5, 144.1;
1
3
diaminocyclohexane (20 mol %) and K
120 °C for 12 h to afford 4d (80.4 mg, 0.172 mmol) as a thick liquid in 72%
yield: R = 0.28 (10 % ethyl acetate in petroleum ether); IR (KBr): ṽmax
3051, 2924, 1617, 1595, 1567, 1489, 1477, 1456, 1422, 1363, 1306, 1264,
2 3
CO (66.1 mg, 0.478 mmol) at
1
+
HRMS (ESI-TOF): m/z calcd for C21
H25Br
2 2
N
O
2
S (M+H) 527.0003; found
f
=
527.0007.
1
7
3
=
219, 1186, 1169, 1104, 1089, 1071, 1035, 1010, 903, 814, 803, 765, 744,
04, 666, 604, 582, 546, 530; 1H NMR (500 MHz, CDCl
3
)  = 2.39 (s, 3H),
(
S)-3-Phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 4a. The
general method B described above was followed when (S)-3a (69.0 mg,
.125 mmol) was reacted with CuI (10 mol %), (±)-trans 1,2-
diaminocyclohexane (20 mol %) and K CO (34.5 mg, 0.250 mmol) at
20 °C for 12 h to afford (S)-4a (36.5 mg, 0.094 mmol) as a thick liquid in
5% yield: R = 0.22 (10 % ethyl acetate in petroleum ether); IR (KBr): ṽmax
3054, 2958, 2924, 2853, 1731, 1616, 1597, 1567, 1494, 1477, 1455,
423, 1362, 1306, 1262, 1220, 1185, 1165, 1106, 1090, 1036, 1010, 903,
48, 806, 761, 743, 701, 666, 601, 586, 574, 547; 1H NMR (500 MHz,
.95 (dd, J = 10.9, 5.7 Hz, 1H), 4.62 (dd, J = 10.3, 8.0 Hz, 1H), 5.28 (dd, J
8.0, 5.2 Hz, 1H), 6.31 (s, 1H), 6.58 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 8.6
0
Hz, 2H), 6.89–6.92 (m, 1H), 7.03–7.06 (m, 1H), 7.19 (d, J = 8.0 Hz, 2H),
2
3
7
.29–7.31 (m, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.6 Hz, 2H);
)  = 21.7, 57.5, 61.0, 83.7, 109.4, 120.6,
20.7, 122.7, 127.7, 127.8, 129.9, 130.4, 132.3, 132.6, 133.3, 137.1, 138.3,
41.6, 145.2; HRMS (ESI-TOF): m/z calcd for C23
S (M+H)+:
1
7
=
1
8
1
3C{1H} NMR (125 MHz, CDCl
3
f
1
1
2 2
H20BrN O
467.0429; found 467.0429.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
7
-Chloro-3-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole
4e.
1H), 6.99–7.01 (m, 1H), 7.04–7.11 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.29–
7.36 (m, 5H), 7.52–7.55 (m, 1H), 7.67 (d, J = 8.5 Hz, 2H); 13C{1H} NMR
The general method B described above was followed when (R)-3e (130.0
mg, 0.270 mmol) was reacted with CuI (10 mol %), (±)-trans 1,2-
(100 MHz, CDCl )  = 21.7, 50.4, 68.5, 84.0, 108.9, 120.4, 120.6, 126.6,
3
diaminocyclohexane (20 mol %) and K
2
CO
3
(74.6 mg, 0.540 mmol) at
127.6, 128.7, 129.0, 129.9, 130.9, 133.1, 134.0, 139.5, 141.7, 144.8;
+
120 °C for 12 h to afford 4e (70 mg, 0.166 mmol) as a thick liquid in 61%
21 2 2
HRMS (ESI-TOF): m/z calcd for C23H N O S (M+H) : 389.1324; found
yield: R
f
= 0.25 (10 % ethyl acetate in petroleum ether); IR (KBr): ṽmax
=
389.1323.
2
8
3
924, 2853, 1740, 1596, 1566, 1456, 1364, 1313, 1168, 1215, 1089, 1063,
1
62, 813, 759, 700, 670, 586, 543; H NMR (400 MHz, CDCl
3
)  = 2.38 (s,
2
-(2-Chlorophenyl)-9-methyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-
a]indole 6b. The general method C described above was followed when
b (36.6 mg, 0.119 mmol) was reacted with indolide generated from 5b
5b (25.0 mg, 0.119 mmol), NaH (4.8 mg, 0.119 mmol)] at rt for 30 minutes
H), 3.97 (dd, J = 10.5, 6.4 Hz, 1H), 4.61 (dd, J = 10.5, 8.7 Hz, 1H), 5.29
(
3
(
dd, J = 8.7, 6.4 Hz, 1H), 6.23 (s, 1H), 6.44 (d, J = 8.2 Hz, 1H), 6.81 (m,
H), 7.19 (d, J = 7.3 Hz, 2H), 7.22 (m, 2H), 7.26 (d, J = 7.3 Hz, 1H), 7.45
d, J = 2.3 Hz, 1H), 7.75 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl )  = 21.7, 58.3, 61.1, 83.0, 110.3, 120.0, 120.6, 126.1, 126.2, 127.8,
28.8, 129.0, 129.3, 130.0, 132.6, 134.4, 137.4, 143.0, 145.1; HRMS (ESI-
1
[
followed by treatment with CuI (10 mol %) and (±)-trans 1,2-
diaminocyclohexane (20 mol %) at 120 °C for 3 h to afford 6b (39.8 mg,
3
1
0
.091 mmol) as a thick liquid in 76% yield: R
petroleum ether); IR (KBr): ṽmax = 3054, 2921, 1625, 1595, 1478, 1458,
408, 1365, 1294, 1236, 1171, 1128, 1089, 1038, 1006, 885, 813, 753,
739, 705, 678, 629, 604, 584, 557, 542; 1H NMR (400 MHz, CDCl
)  =
f
= 0.26 (10 % ethyl acetate in
+
2 2
TOF): m/z calcd for C23H20ClN O S (M+H) : 423.0934; found 423.0931.
1
4
-Tosyl-1,2,3,3a,4,10a-hexahydrocyclopenta[4,5]imidazo[1,2-
a]indole 4f. The general method B described above was followed when
f (58.0 mg, 0.113 mmol) was reacted with CuI (10 mol %), (±)-trans 1,2-
diaminocyclohexane (20 mol %) and K CO (31.2 mg, 0.226 mmol) at
20 °C for 12 h to afford 4f (27.5 mg, 0.078 mmol) as a white solid in 68%
yield: mp 137−138 °C; R = 0.40 (15 % ethyl acetate in petroleum ether);
IR (KBr): ṽmax = 3300, 2956, 2923, 2853, 1729, 1615, 1598, 1572, 1559,
3
2.36 (s, 3H), 2.60(s, 3H), 3.61 (dd, J = 8.9, 2.3 Hz, 1H), 3.85 (dd, J = 9.9,
7.8 Hz, 1H), 5.96 (dd, J = 7.6, 2.5 Hz, 1H), 6.86–6.88 (m, 1H), 7.04–7.11
(m, 2H), 7.17–7.23 (m, 4H), 7.35–7.37 (m, 1H), 7.44–7.48 (m, 1H), 7.53–
7.55 (m, 1H), 7.62 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl
= 8.9, 21.7, 48.2, 67.1, 97.5, 108.9, 119.3, 119.5, 121.5, 127.4, 127.6,
3
2
3
1
3
) 
f
129.4, 129.6, 130.1, 130.2, 130.6, 131.5, 133.3, 133.8, 136.7, 137.9,
144.9; HRMS (ESI-TOF): m/z calcd for C24
+
1477, 1458, 1377, 1362, 1328, 1306, 1258, 1212, 1185, 1170, 1125, 1092,
H22ClN
2
O
2
S (M+H) : 437.1091;
1
017, 1003, 967, 897, 880, 813, 766, 744, 720, 705, 665, 629, 613, 549;
found 437.1091.
1
H NMR (400 MHz, CDCl
.18 (m, 1H), 2.20–2.25 (m, 1H), 2.30–2.42 (m, 5H), 3.35 (td, J = 11.9, 6.4
Hz, 1H), 3.80 (td, J = 11.7, 6.2 Hz, 1H), 6.27 (s, 1H), 7.02–7.09 (m, 3H),
3
)  1.69–1.80 (m, 1H), 1.94–2.05 (m, 1H), 2.12–
2
2-(4-Chlorophenyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6c.
The general method C described above was followed when 1c (40.0 mg,
7
.26 (d, J = 8.7 Hz, 2H), 7.47–7.51 (m, 1H), 7.81 (d, J = 8.5 Hz, 2H);
)  = 21.7, 22.2, 22.8, 26.2, 65.0, 74.7, 86.2,
09.8, 120.6, 120.8, 128.2, 129.9, 131.7, 132.2, 132.5, 145.0, 149.5;
0
.130 mmol) was reacted with indolide generated from 5a [5a (25.5 mg,
1
3C{1H} NMR (100 MHz, CDCl
3
0.130 mmol), NaH (5.2 mg, 0.130 mmol)] at rt for 30 minutes followed by
1
treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20
mol %) at 120 °C for 3 h to afford 6c (41.9 mg, 0.099 mmol) as a thick
+
21 2 2
HRMS (ESI-TOF): m/z calcd for C20H N O S (M+H) : 353.1324; found
353.1323.
liquid in 76% yield: R
KBr): ṽmax = 3052, 2924, 1617, 1596, 1563, 1492, 1478, 1456, 1426, 1363,
1307, 1220, 1167, 1107, 1089, 1059, 1012, 906, 814, 772, 743, 704, 667,
599, 532; 1H NMR (400 MHz, CDCl
)  = 2.35 (s, 3H), 3.91 (dd, J = 9.6,
f
= 0.28 (10 % ethyl acetate in petroleum ether); IR
(
10-Tosyl-5a,6,8,9,9a,10-hexahydro-7H-benzo[4,5]imidazo[1,2-
a]indole 4g. The general method B described above was followed when
g (66.6 mg, 0.126 mmol) was reacted with CuI (10 mol %), (±)-trans 1,2-
diaminocyclohexane (20 mol %) and K CO (34.8 mg, 0.252 mmol) at
20 °C for 12 h to afford 4g (29.6 mg, 0.084 mmol) as a white solid in 67%
yield: mp 120−122 °C; R = 0.42 (15 % ethyl acetate in petroleum ether);
IR (KBr): ṽmax = 2932, 2858, 1614, 1597, 1571, 1558, 1493, 1478, 1457,
3
3
4.6 Hz, 1H), 4.25 (dd, J = 9.4, 8.2 Hz, 1H), 5.43 (dd, J = 8.4, 4.6 Hz, 1H),
6.31 (s, 1H), 6.99–7.01 (m, 1H), 7.04–7.11 (m, 2H), 7.18 (d, J = 8.0 Hz,
2H), 7.52–7.55 (m, 1H), 7.66 (d, J = 8.7 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl )  = 21.7, 50.3, 67.8, 84.1, 108.9, 120.5, 120.7, 120.8, 127.6, 128.0,
3
129.2, 129.9, 130.9, 133.1, 133.8, 134.7, 137.9, 141.5, 145.0; HRMS (ESI-
2
3
1
f
+
1
1
7
=
2
=
1
2
7
1
3
396, 1375, 1363, 1320, 1304, 1275, 1239, 1223, 1185, 1170, 1168, 1132,
107, 1090, 1068, 1050, 1027, 1013, 950, 902, 892, 868, 846, 817, 801,
86, 763, 744, 706, 663, 625, 614, 575, 550; H NMR (400 MHz, CDCl
1.32–1.52 (m, 2H), 1.68 (dq, J = 11.8, 3.6 Hz, 1H), 1.82–1.99 (m, 3H),
.37 (s, 3H), 2.69–2.72 (m, 2H), 3.07 (dt, J = 11.8, 3.2 Hz, 1H), 3.58 (dt, J
11.3, 3.2 Hz, 1H), 6.29 (s, 1H), 6.99–7.07 (m, 2H), 7.16 (d, J = 8.2 Hz,
H), 7.25 (d, J = 6.8 Hz, 2H), 7.49 (d, J = 7.3 Hz, 1H), 7.77 (d, J = 8.6 Hz,
H); 13C{1H} NMR (100 MHz, CDCl
1.5, 84.8, 109.8, 120.4, 120.5, 120.6, 127.8, 129.9, 131.9, 132.2, 133.1,
43.3, 144.9; HRMS (ESI-TOF): m/z calcd for C21H N O
S (M+H)+:
23 2 2
TOF): m/z calcd for C23
H20ClN
2
O
2
S (M+H) : 423.0934; found 423.0937.
1
3
) 
(
S)-9-Bromo-2-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6d.
The general method C described above was followed when (S)-1a (27.9
mg, 0.102 mmol) was reacted with indolide generated from 5c [5c (28.1
mg, 0.102 mmol), NaH (4.1 mg, 0.102 mmol)] at rt for 30 minutes followed
by treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane
3
)  = 21.7, 23.6, 24.3, 29.5, 29.6, 62.3,
(
20 mol %) at 120 °C for 3.5 h to afford (S)-6d (36.9 mg, 0.079 mmol) as
a white solid in 77% yield: mp 140–142 °C; R = 0.15 (10 % ethyl acetate
in petroleum ether); IR (KBr): ṽmax = 3059, 2923, 1615, 1595, 1567, 1494,
f
67.1480; found 367.1481.
1480, 1456, 1403, 1366, 1337, 1305, 1222, 1186, 1171, 1131, 1028, 1005,
1
943, 874, 741, 705, 673, 654, 612, 576, 549; H NMR (400 MHz, CDCl
3
) 
2
-Phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6a. The general
= 2.35 (s, 3H), 3.86 (dd, J = 9.6, 2.3, Hz, 1H), 3.98 (dd, J = 9.6, 7.6 Hz,
1H), 5.80 (dd, J = 7.6, 2.4 Hz, 1H), 6.96 (dd, J = 7.1, 2.5 Hz, 1H), 7.12–
7.20 (m, 4H), 7.23–7.25 (m, 2H), 7.26–7.30 (m, 3H), 7.55 (dd, J = 6.0, 1.8
method C described above was followed when 1a (35.0 mg, 0.128 mmol)
was reacted with indolide generated from 5a [5a (25.0 mg, 0.128 mmol),
NaH (5.1 mg, 0.128 mmol)] at rt for 30 minutes followed by treatment with
CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20 mol %) at 120 °C
for 3.5 h to afford 6a (42.3 mg, 0.109 mmol) as a white solid in 85% yield:
Hz, 1H), 7.67 (d, J = 8.5 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl
)  = 21.7,
3
49.1, 69.9, 76.2, 109.2, 120.0, 120.9, 122.6, 126.0, 127.8, 128.7, 129.2,
130.0, 130.3, 132.1, 134.4, 137.1, 139.6, 145.0; HRMS (ESI-TOF): calcd
+
25
mp 131−133 °C; R
f
= 0.21 (10 % ethyl acetate in petroleum ether); IR
for C23
0.21, CH
H20BrN O S (M+H) : 467.0429; found 467.0426; [α] = –12.38 (c
2
2
D
(KBr): ṽmax = 3053, 2923, 1617, 1596, 1562, 1477, 1457, 1425, 1362, 1307,
2
Cl
2
); for a >99% ee was determined by chiral HPLC analysis
(Chiralcel OD-H column), hexane/isopropanol 95:5, flow rate = 1.0 mL min
1; t
(1) = 21.63 min (major, S), t (2) = 33.15 min (minor, R).
–
1
5
1
209, 1089, 1167, 1107, 1008, 905, 813, 761, 743, 702, 666, 602, 574,
43; H NMR (400 MHz, CDCl
H), 4.25 (dd, J = 9.4, 8.5 Hz, 1H), 5.47 (dd, J = 8.5, 4.6 Hz, 1H), 6.32 (s,
1
3
)  = 2.35 (s, 3H), 3.95 (d, J = 9.6, 5.6 Hz,
R
R
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
1
9
-Methyl-2-(p-tolyl)-1-(m-tolylsulfonyl)-2,3-dihydro-1H-imidazo[1,2-
a]indole 6e. The general method C described above was followed when
d (29.0 mg, 0.101 mmol) was reacted with indolide generated from 5b
5b (21.2 mg, 0.101 mmol), NaH (4.1 mg, 0.101 mmol)] at rt for 30 minutes
875, 813, 740, 706, 686, 660, 629, 582, 559; H NMR (400 MHz, CDCl
3
) 
= 0.90 (t, J = 6.9 H, 6H), 1.90–1.98 (m, 1H), 2.32 (s, 3H), 2.47 (s, 3H),
3.26 (dd, J = 9.6, 7.3 Hz, 1H), 3.50 (dd, J = 9.9, 1.8 Hz, 1H), 4.39 (ddd, J
= 7.6, 6.2, 1.8 Hz, 1H), 6.91–6.95 (m, 1H), 7.06–7.13 (m, 4H), 7.46–7.52
)  = 8.8, 17.8, 17.9, 21.7, 33.1,
42.4, 72.7, 97.4, 108.7, 111.7, 119.2, 120.6, 121.1, 122.5, 127.4, 129.9,
1
[
followed by treatment with CuI (10 mol %) and (±)-trans 1,2-
diaminocyclohexane (20 mol %) at 120 °C for 4 h to afford 6e (33.7 mg,
(m, 3H); 13C{1H} NMR (100 MHz, CDCl
3
0
.081 mmol) as a thick liquid in 80% yield: R
f
= 0.28 (10 % ethyl acetate in
130.3, 133.0, 134.3, 136.9, 144.5; HRMS (ESI-TOF): m/z calcd for
+
petroleum ether); IR (KBr): ṽmax = 2922, 1626, 1595, 1514, 1479, 1458,
21 25 2 2
C H N O S (M+H) : 369.1637; found 369.1639.
1
6
3
6
1
2
1
406, 1293, 1236, 1185, 1168, 1089, 1042, 1007, 885, 813, 740, 682, 658,
1
27, 586, 566, 545; H NMR (400 MHz, CDCl
3
)  = 2.28 (s, 3H), 2.35 (s,
(
S)-2-Isobutyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6i. The
H), 2.51 (s, 3H), 3.69–3.77 (m, 2H), 5.59 (dd, J = 6.6, 2.5 Hz, 1H), 6.91–
.93 (m, 1H), 7.06–7.11 (m, 6H), 7.16 (d, J = 8.0 Hz, 2H), 7.53–7.55 (m,
general method C described above was followed when (S)-1f (25.0 mg,
0
0
treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20
mol %) at 120 °C for 6 h to afford (S)-6i (28.4 mg, 0.077 mmol) as a white
solid in 78% yield: mp 120−122 °C; R
petroleum ether); [α]25
.099 mmol) was reacted with indolide generated from 5a [5a (19.4 mg,
.099 mmol), NaH (4.0 mg, 0.099 mmol)] at rt for 30 minutes followed by
H), 7.58 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl
)  = 8.9, 21.2,
3
1.7, 48.0, 69.5, 97.6, 108.6, 119.3, 119.5, 121.3, 126.0, 127.5, 129.7,
30.0, 130.7, 133.5, 134.3, 136.5, 137.3, 138.2, 144.6; HRMS (ESI-TOF):
+
m/z calcd for C25
H
25
N
2
O
2
S (M+H) : 417.1637; found 417.1635.
f
= 0.27 (10 % ethyl acetate in
Cl ); IR (KBr): ṽmax = 3052,
D
= –9.26 (c 0.16, CH
2
2
9
-Methyl-2-phenyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole
6f.
2956, 2926, 1618, 1597, 1562, 1478, 1457, 1425, 1360, 1315, 1293, 1185,
1168, 1089, 1037, 1009, 921, 879, 813, 763, 743, 705, 665, 601, 549; H
1
The general method C described above was followed when 1a (32.0 mg,
0.117 mmol) was reacted with indolide generated from 5b [5b (24.6 mg,
3
NMR (400 MHz, CDCl )  = 0.98 (d, J = 6.6 Hz, 3H), 1.03 (d, J = 6.6 Hz,
0
.117 mmol), NaH (4.7 mg, 0.117 mmol)] at rt for 30 minutes followed by
3H), 1.64 (ddd, J = 14.0, 8.2, 6.1 Hz, 1H), 1.78–1.88 (m, 1H), 2.01 (ddd, J
= 14.0, 7.8, 6.4 Hz, 1H), 2.33 (s, 3H), 3.62 (dd, J = 9.4, 3.7 Hz, 1H), 3.75
(dd, J = 9.4, 7.8 Hz, 1H), 4.46–4.53 (m, 1H), 6.28 (s, 1H), 6.97–7.00 (m,
1H), 7.02–7.08 (m, 2H), 7.16 (d, J = 8.2 Hz, 2H), 7.49–7.53 (m, 1H), 7.65
treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20
mol %) at 120 °C for 3.5 h to afford 6f (38.2 mg, 0.095 mmol) as a thick
liquid in 81% yield: R
f
= 0.25 (10 % ethyl acetate in petroleum ether); IR
(KBr): ṽmax = 3053, 2922, 1625, 1596, 1479, 1458, 1408, 1360, 1293, 1237,
(d, J = 8.2 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl
3
)  = 21.7, 22.3, 23.1,
1
6
3
7
209, 1184, 1169, 1122, 1088, 1028, 1007, 882, 813, 740, 705, 681, 658,
24.8, 45.0, 47.1, 64.8, 85.4, 108.8, 120.1, 120.6, 120.7, 127.5, 129.9,
29, 600, 585, 540; 1H NMR (400 MHz, CDCl
130.8, 132.7, 133.9, 141.0, 144.7; HRMS (ESI-TOF): m/z calcd for
3
)  =2.35 (s, 3H), 2.52 (s,
+
H), 3.71–3.79 (m, 2H), 3.9 (dd, J = 6.6, 2.8 Hz, 1H), 6.916.94 (m, 1H),
.07–7.12 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.19–7.23 (m, 2H), 7.25–7.31
m, 3H), 7.53–7.57 (m, 1H), 7.59 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (100
C
21
H
25
N
2
O
2
S (M+H) : 369.1637; found 369.1637.
(
(
S)-2-Benzyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole
6j.
The
MHz, CDCl
3
)  = 8.9, 21.7, 48.1, 69.6, 97.7, 108.9, 119.4, 119.5, 121.4,
general method C described above was followed when (S)-1g (29.0 mg,
1
1
4
26.1, 127.5, 128.4, 129.0, 130.0, 130.7, 133.5, 134.3, 136.5, 140.3,
0
.101 mmol) was reacted with indolide generated from 5a [5a (19.8 mg,
+
23 2 2
44.7; HRMS (ESI-TOF): calcd for C24H N O S (M+H) : 403.1480; found
0.101 mmol), NaH (4.1 mg, 0.101 mmol)] at rt for 30 minutes followed by
03.1483.
treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20
mol %) at 120 °C for 5 h to afford (S)-6j (29.8 mg, 0.074 mmol) as a white
(
S)-2-Isopropyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6g. The
solid in 73% yield: mp 140−142 °C; R
petroleum ether); [α]25
= –150.38 (c 0.26, CH
2922, 1617, 1597, 1561, 1478, 1456, 1429, 1362, 1306, 1167, 1109, 1088,
1005, 813, 742, 704, 664, 600, 572, 547; 1H NMR (400 MHz, CDCl
)  =
f
= 0.23 (10 % ethyl acetate in
general method C described above was followed when (S)-1e (37.0 mg,
0
0
D
2
Cl ); IR (KBr): ṽmax = 3027,
2
.156 mmol) was reacted with indolide generated from 5a [5a (30.6 mg,
.156 mmol), NaH (6.3 mg, 0.156 mmol)] at rt for 30 minutes followed by
3
treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20
mol %) at 120 °C for 3.5 h to afford (S)-6g (51.0 mg, 0.144 mmol) as a
2.33 (s, 3H), 3.04 (dd, J = 13.5, 10.3 Hz, 1H), 3.58–3.66 (m, 2H), 3.75 (dd,
J = 9.9, 4.4 Hz, 1H), 4.66 (ddd, J = 11.9, 8.0, 4.1 Hz, 1H), 6.27 (s, 1H),
6.94–6.96 (m, 1H), 7.03–7.08 (m, 2H), 7.19 (d, J = 8.2 Hz, 2H), 7.27 (d, J
= 6.4 Hz, 3H), 7.32–7.35 (m, 2H), 7.50 (dd, J = 6.2, 1.8 Hz, 1H), 7.74 (d, J
white solid in 92% yield: mp 115–117 °C; [α]25
= –231.12 (c 0.68, CH
D
2 2
Cl );
R
f
= 0.21 (10 % ethyl acetate in petroleum ether); IR (KBr): ṽmax = 3050,
2
1
5
=
963, 1616, 1597, 1559, 1477, 1457, 1429, 1390, 1358, 1307, 1222, 1185,
167, 1108, 1089, 1039, 10008, 916, 810, 759, 741, 705, 665, 601, 541,
= 8.2 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl
3
)  = 21.7, 41.8, 45.7, 66.9,
84.5, 108.8, 120.2, 120.5, 120.6, 127.3, 127.5, 129.0, 129.6, 130.0, 130.9,
73; 1H NMR (400 MHz, CDCl
)  = 0.95 (d, J = 6.9 Hz, 3H), 0.98 (d, J
6.9 Hz, 3H), 2.29–2.35 (m, 4H), 3.61 (dd, J = 9.6, 8.0 Hz, 1H), 3.77 (dd,
132.8, 133.8, 136.2, 141.2, 144.9; HRMS (ESI-TOF): m/z calcd for
3
+
C
24
H
23
N
2
O
2
S (M+H) : 403.1480; found 403.1481.
J = 9.6, 3.2 Hz, 1H), 4.39 (ddd, J = 8.2, 4.8, 3.4 Hz, 1H), 6.27 (s, 1H), 6.99–
7
1
1
1
.01 (m, 1H), 7.03–7.07 (m, 2H), 7.15 (d, J = 8.5 Hz, 2H), 7.49–7.52 (m,
(
6
S)-2-Isobutyl-9-methyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole
k. The general method C described above was followed when (S)-1f
H), 7.66 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl
3
)  = 16.3,
8.2, 21.7, 32.6, 42.5, 70.9, 84.9, 108.7, 120.1, 120.5, 120.7, 127.5, 129.9,
(25.0 mg, 0.099 mmol) was reacted with indolide generated from 5b [5b
30.6, 132.7, 134.0, 141.5, 144.7; HRMS (ESI-TOF): m/z calcd for
(20.8 mg, 0.099 mmol), NaH (4.0 mg, 0.099 mmol)] at rt for 30 minutes
+
C
20
H
23
N
2
O
2
S (M+H) : 355.1480; found 355.1481.
followed by treatment with CuI (10 mol %) and (±)-trans 1,2-
diaminocyclohexane (20 mol %) at 120 °C for 5 h to afford (S)-6k (31.0 mg,
(
6
S)-2-Isopropyl-9-methyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole
h. The general method C described above was followed when (S)-1e
0.081 mmol) as a white solid in 82% yield: mp 162−164 °C;
R
f
= 0.29
Cl );
(10 % ethyl acetate in petroleum ether); [α]25
= –13.71 (c 0.35, CH
D
2
2
(
37.3 mg, 0.156 mmol) was reacted with indolide generated from 5b [5b
IR (KBr): ṽmax = 2955, 2924, 1626, 1596, 1480, 1459, 1407, 1358, 1295,
1229, 1169, 1089, 983, 813, 739, 704, 681, 659, 626, 582, 561; 1H NMR
(32.8 mg, 0.156 mmol), NaH (6.3 mg, 0.156 mmol)] at rt for 30 minutes
followed by treatment with CuI (10 mol %) and (±)-trans 1,2-
diaminocyclohexane (20 mol %) at 120 °C for 3.5 h to afford (S)-6h (51.6
3
(400 MHz, CDCl )  = 0.93 (d, J = 6.6 Hz, 3H), 1.02 (d, J = 6.6 Hz, 3H),
1.27–1.36 (m, 1H), 1.64–1.71 (m, 1H), 1.89–1.96 (m, 1H), 2.32 (s, 3H),
2.46 (s, 3H), 3.27–3.34 (m, 2H), 4.64 (ddd, J = 10.8, 6.2, 2.1 Hz, 1H), 6.91
(td, J = 7.3, 4.4 Hz, 1H), 7.06–7.12 (m, 4H), 7.48 (d, J = 8.5 Hz, 2H), 7.51–
mg, 0.140 mmol) as a white solid in 90% yield: mp 110–112 °C; [α]25
= –
= 0.23 (10 % ethyl acetate in petroleum ether);
IR (KBr): ṽmax = 3051, 2964, 2926, 2885, 1626, 1596, 1480, 1459, 1411,
383, 1359, 1293, 1239, 1202, 1185, 1170, 1122, 1089, 1027, 1007, 980,
D
2 2 f
259.67 (c 0.72, CH Cl ); R
7.53 (m, 1H); 13C{1H} NMR (100 MHz, CDCl
24.5, 44.9, 45.8, 66.2, 98.4, 108.7, 119.3, 121.2, 127.4, 129.9, 130.6,
3
)  = 8.8, 21.7, 22.3, 22.9,
1
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700267
FULL PAPER
1
33.0, 134.4, 135.6, 144.5; HRMS (ESI-TOF): m/z calcd for C22
H
27
N
2
O
2
S
mg, 0.080 mmol) as a thick liquid in 78% yield: R
acetate in petroleum ether); [α]25
= –283.23 (c 0.66, CH
max = 3051, 2962, 2924, 1627, 1596, 1480, 1457, 1399, 1383, 1358, 1293,
f
= 0.38 (10 % ethyl
+
(
M+H) : 383.1793; found 383.1799.
D
2
Cl ); IR (KBr):
2
ṽ
1
6
239, 1204, 1185, 1122, 1089, 1062, 1015, 959, 879, 813, 739, 715, 706,
(
S)-2-Benzyl-9-methyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6l.
1
60, 629, 588, 562, 539; H NMR (500 MHz, CDCl
3
)  = 0.86 (s, 9H), 2.32
The general method C described above was followed when (S)-1g (29.0
mg, 0.101 mmol) was reacted with indolide generated from 5b [5b (21.2
mg, 0.101 mmol), NaH (4.1 mg, 0.101 mmol)] at rt for 30 minutes followed
by treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane
(
4
(
s, 3H), 2.47 (s, 3H), 3.13 (dd, J = 10.4, 7.3 Hz, 1H), 3.58–3.60 (m, 1H),
.27 (dd, J = 7.3, 1.2 Hz, 1H), 6.91–6.93 (m, 1H), 7.06–7.10 (m, 4H), 7.46
d, J = 8.6 Hz, 2H), 7.50–7.52 (m, 1H); 13C{1H} NMR (125 MHz, CDCl
) 
3
=
1
C
8.7, 21.7, 25.6, 35.3, 40.9, 76.1, 97.8, 108.7, 119.2, 119.3, 121.1, 127.5,
(
20 mol %) at 120 °C for 4 h to afford (S)-6l (31.7 mg, 0.076 mmol) as a
29.8, 130.1, 132.8, 134.2, 137.4, 144.5; HRMS (ESI-TOF): m/z calcd for
f
thick liquid in 75% yield: R = 0.22 (10 % ethyl acetate in petroleum ether);
+
α]25
22
H
27
N
2
O
2
S (M+H) : 383.1793; found 383.1790.
[
D
= –140.6 (c 0.5, CH
2
Cl
2
); IR (KBr): ṽmax = 2923, 1624, 1596,1458,
1
1
406, 1364, 1235, 1169, 1089, 813, 744, 699, 659, 631, 580, 552; H NMR
(
500 MHz, CDCl
3
)  = 2.31 (s, 3H), 2.49 (s, 3H), 2.79 (dd, J = 13.8, 10.3
(S)-2-(tert-Butyl)-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6p. The
general method C described above was followed when (S)-1i (26.1 mg,
0.103 mmol) was reacted with indolide generated from 5a [5a (20.2 mg,
0.103 mmol), NaH (4.1 mg, 0.103 mmol)] at rt for 30 minutes followed by
treatment with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20
mol %) at 120 °C for 5 h to afford (S)-6i (30.7 mg, 0.083 mmol) as a thick
Hz, 1H), 3.23 (dd, J = 9.8, 7.6 Hz, 1H), 3.33 (dd, J = 13.2, 4.6 Hz, 1H),
3
7
.49 (dd, J = 9.8, 1.7 Hz, 1H), 4.78–4.82 (m, 1H), 6.89–6.91 (m, 1H), 7.08–
.12 (m, 4H), 7.18–7.31 (m, 5H), 7.52 (d, J = 8.0 Hz, 3H); 13C{1H} NMR
3
(100 MHz, CDCl )  = 8.8, 21.7, 41.7, 44.0, 68.5, 97.7, 108.7, 119.3, 119.4,
1
1
21.2, 127.2, 127.4, 128.8, 129.6, 130.0, 130.7, 133.2, 134.2, 136.0, 136.3,
44.6; HRMS (ESI-TOF): m/z calcd for C25
+
= 0.28 (10 % ethyl acetate in petroleum ether); [α]25
Cl ); IR (KBr): ṽmax = 3048, 2962, 1616, 1596, 1559,
H N O
25 2 2
S (M+H) : 417.1637;
liquid in 81% yield: R
f
D
found 417.1635.
= –202.81 (c 0.57, CH
2
2
1
9
=
1
495, 1477, 1458, 1429, 1353, 1314, 1265, 1185, 1164, 1089, 1062, 1024,
1
87, 904, 811, 780, 758, 742, 658, 601, 545; H NMR (400 MHz, CDCl
3
) 
(
S)-2,9-Dimethyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6m. The
general method C described above was followed when (S)-1h (21.0 mg,
.1 mmol) was reacted with indolide generated from 5b [5b (21.0 mg, 0.1
0.944 (s, 9H), 2.30 (s, 3H), 3.30 (dd, J = 9.8, 7.3 Hz, 1H), 3.79 (dd, J =
0.4, 1.4 Hz, 1H), 4.28 (dd, J = 7.7, 1.8 Hz, 1H), 6.31 (s, 1H), 6.96–6.99
0
(
m, 1H), 7.04–7.07 (m, 2H), 7.09 (d, J = 7.7 Hz, 2H), 7.51–7.56 (m, 3H);
mmol), NaH (4.0 mg, 0.1 mmol)] at rt for 30 minutes followed by treatment
with CuI (10 mol %) and (±)-trans 1,2-diaminocyclohexane (20 mol %) at
1
3C {1H} NMR (100 MHz, CDCl
3
)  = 21.6, 25.8, 35.5, 42.1, 75.0, 87.0,
1
08.8, 119.6, 120.8, 121.0, 127.5, 129.8, 130.2, 132.4, 134.4, 141.4,
1
7
1
1
6
3
9
2
20 °C for 3.5 h to afford (S)-6m (26.6 mg, 0.078 mmol) as a thick liquid in
+
= 0.15 (10 % ethyl acetate in petroleum ether); [α]25
21 25 2 2
144.6; HRMS (ESI-TOF): m/z calcd for C H N O S (M+H) : 369.1637;
found 369.1630.
8% yield: R
f
D
= –
2 2
00.0 (c 0.44, CH Cl ); IR (KBr): ṽmax = 2924, 1623, 1596, 1460, 1407,
362, 1234, 1185, 1169, 1131, 1089, 1054, 1025, 943, 869, 812, 739, 705,
1
88, 658, 630, 586, 560; H NMR (500 MHz, CDCl
3
)  =1.47 (d, J = 6.9 Hz,
H), 2.33 (s, 3H), 2.48 (s, 3H), 3.33 (dd, J = 9.2, 1.7 Hz, 1H), 3.45 (dd, J =
.2, 6.9 Hz, 1H), 4.71–4.74 (m, 1H), 6.93–6.94 (m, 1H), 7.09 (dd, J = 5.7,
.9 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.50–7.53 (m, 3H); 13C{1H} NMR
Acknowledgements ((optional))
M.K.G. thanks IIT-Kanpur and CSIR, India, for financial support
for conducting this research. M.S. thanks CSIR, India and I.A.W.
thanks UGC, India, for research fellowships.
(
1
3
100 MHz, CDCl )  = 8.8, 21.7, 22.5, 47.0, 63.5, 97.5, 108.7, 119.2, 119.4,
21.2, 127.4, 129.9, 130.6, 133.3, 134.1, 135.9, 144.5; HRMS (ESI-TOF):
+
m/z calcd for C19
H
21
N
2
O
2
S (M+H) : 341.1324; found 341.1327.
(
S)-2-Methyl-1-tosyl-2,3-dihydro-1H-imidazo[1,2-a]indole 6n. The
Keywords: Aziridines • Stereoselective-synthesis •
Regioisomeric • Imidazoindoles • Copper(I)-catalyzed
general method C described above was followed when (S)-1h (27.0 mg,
0
.128 mmol) was reacted with indolide generated from 5a [5a (25.1 mg,
0
.128 mmol), NaH (5.1 mg, 0.128 mmol) ] at rt for 30 minutes followed by
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thick liquid in 82% yield: R
(
f
= 0.15 (10 % ethyl acetate in petroleum ether);
4
IR (KBr): ṽmax = 2925, 2854, 1744, 1618, 1598, 1562, 1478, 1456, 1429,
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360, 1290, 1261, 1221, 1168, 1090, 1008, 903, 813, 765, 743, 705, 657,
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CDCl
3
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3508; (d) A. Dömling, W. Wang, K. Wang, Chem. Rev. 2012, 112, 3083.
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1
6
7
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f
o
u
n
d
3
2
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.
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1
6
3
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[
α
]
D
= –52.54 (c 0.24,
CH
2
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S)-1i (26.0 mg, 0.103 mmol) was reacted with indolide generated from 5b
5b (21.6 mg, 0.103 mmol), NaH (4.1 mg, 0.103 mmol)] at rt for 30 minutes
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(
[
(
followed by treatment with CuI (10 mol %) and (±)-trans 1,2-
diaminocyclohexane (20 mol %) at 120 °C for 4.5 h to afford (S)-6o (30.6
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European Journal of Organic Chemistry
10.1002/ejoc.201700267
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European Journal of Organic Chemistry
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FULL PAPER
Key Topic: Synthesis Design
FULL PAPER
Masthanvali Sayyad, Imtiyaz Ahmad
Wani, Deo Prakash Tiwari, and Manas
K. Ghorai*[a]
Page No. – Page No.
Synthetic
Routes
to
Isomeric
Imidazoindoles via Regioselective
Ring-Opening of Activated Aziridines
Followed by Copper Catalyzed C-N
Cyclization
The ring-opening followed by Cu-catalyzed cyclization of activated aziridines with i) 2,2-
dibromovinylanilines and ii) 2-bromo indoles gives rise to different regioisomers of
imidazoindoles. The first route generates one regioisomer whereas the second route affords
the other regiomer.
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