Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and Mechanistic Insights

Article abstract of DOI:10.1002/jhet.2457

Bi(NO₃)₃·5H₂O-Catalyzed redox amination scope and mechanistic insights of benzylic ketones with indoline are discussed. The experimental results demonstrate that the formation of N-alkyl-substituted indole/indoline derivatives over typically competitive redox and reductive amination processes is depending upon the reaction condition for the benzylic ketones.

Full text of DOI:10.1002/jhet.2457

1
540
Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
Mechanistic Insights
Omer Aydin, Haydar Kilic, Sinan Bayindir, Esra Erdogan, and Nurullah Saracoglu *
Vol 52
a
a
a,b
a
a
a
Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, 25240, Turkey
b
Department of Chemistry, Faculty of Arts and Sciences, Bingöl University, Bingöl, 12000, Turkey
*
E-mail: nsarac@atauni.edu.tr
Additional Supporting Information may be found in the online version of this article.
Received February 27, 2015
DOI 10.1002/jhet.2457
Published online 13 August 2015 in Wiley Online Library (wileyonlinelibrary.com).
3 3 2
Bi(NO ) ·5H O-Catalyzed redox amination scope and mechanistic insights of benzylic ketones with
indoline are discussed. The experimental results demonstrate that the formation of N-alkyl-substituted
indole/indoline derivatives over typically competitive redox and reductive amination processes is depending
upon the reaction condition for the benzylic ketones.
J. Heterocyclic Chem., 52, 1540 (2015).
INTRODUCTION
reductive amination of indoline with enolizable aliphatic
ketones (Scheme 2) [18]. Here, we report on our detailed
results on the bismuth nitrate-catalyzed redox amination of
a wide range of benzylic ketones with indoline.
The indoles possess an important role in organic chemis-
try because of their significance in biological and naturally
occurring molecules [1–3]. Therefore, the synthesis of
functionalized indoles has become a preferred platform
to develop innovative strategies [4, 5]. Recently, it has been
shown that the redox amination (or isomerization) reaction is
one of the most efficient routes used to obtain N1-substituted
indoles and pyrroles [6–12]. Independently, Pan and Siedel
screened the redox amination between aryl aldehydes and
indolines to provide N-alkylindoles (Scheme 1) [13–17]. Al-
though the redox-type amination reactions for indoline pro-
vide a one-pot reaction with a high synthetic efficiency and
atom-economy and step-economy, the applications of the
method have been limited to non-enolizable aldehydes. Fur-
thermore, both groups observed reductive amination to yield
N-alkylindolines with intermolecular hydride transfer from
indoline instead of redox amination when salicylaldehydes
were used as the substrate (Scheme 1).
RESULTS AND DISCUSSIONS
Under a similar protocol in connection with our initial
study, we next examined the redox amination scope of
indoline with aryl ketones as summarized in Table 1.
Bismuth nitrate-catalyzed reactions of benzophenone
(5b) with indoline (1) in a sealed tube at 120°C in
acetonitrile and at 140°C without solvent a mixture of
1-benzhydrylindoline (10b), 1-benzhydryl-1H-indole
(6b) and indole (4) as the redox amination product and
reductive alkylation products (Entries 1 and 2 in Table 1).
When 5:1 ratio of indoline to benzophenone (5b) was
used at 120°C under solvent-free conditions the product
distribution changed dramatically, and the reductive alkyl-
ation products 10b and 4 that were accompanied by a
trace amount of 6b were observed in 66 and 27% yield,
Recently, we communicated our results to access N1- and
excessive substituted indoles via a competitive redox and
©
2015 HeteroCorporation

September 2015
Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
Mechanistic Insights
1541
Scheme 1. Reaction of aryl aldehydes and salicylaldehydes with indoline.
Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
respectively. Oxidation of 1-benzhydrylindoline (10f) with
[
MnO in methylene chloride resulted in the formation of
2
6
f in 96% yield.
Reactions of acetophenone (5c) and 1-(naphthalene-2-
yl)ethan-1-one (5d) with indoline were also examined at
the same conditions, and both ketone showed similar re-
sults (Entries 4–9 in Table 1). But, the reaction setting
5
:1 ratio of indoline to 5c at 120°C under solvent-free con-
ditions gave redox amination product as a minor product
8%), whereas the redox amination products for benzophe-
(
none and acetophenone were obtained in amounts. Com-
pared with aliphatic ketones, the electronic nature of the
ketones 5a-c and the amounts of used indoline appeared
to have an impact on reaction outcome, and reductive
amination products were predominantly obtained for the
first time. Based on these results, a formation mechanism
of 6b (or 6c-d) and 10b (or 10c-d) was proposed in
Scheme 3. It is interesting to compare the kinetic and ther-
modynamic control of the reaction pathways through the
carbocation intermediates (Scheme 3). We suggest that
iminium ions would be formed from condensation of
indoline and ketone, and that these intermediates subse-
quently could be regenerated in the carbocation intermedi-
ates [19, 20]. The driving force for this process is the
stabilization of these carbocation intermediates. While the
secondary carbocation structure then restores the redox
amination by expelling a hydrogen atom from the interme-
diate, the more stable tertiary structure due to the delocal-
ization or resonance of the double bonds of the ring reacts
to give the reductive alkylation product with indoline as
reductant.
Scheme 2. Reaction of cyclohexanone (5a) with indoline.
Table 1
3 3 2
Reaction of indoline with benzylic ketones 5a-c (1 equiv) catalyzed by Bi(NO ) ·5H O (0.1 mM).
Product (yield%)
Entry
Ketone
= R = Ph
Indoline (equiv)
Temperature (°C)
Solvent
10
6
4
1
2
3
4
5
6
7
8
9
5b R
1
2
1
1
5
1
1
5
1
1
5
120
140
120
120
140
120
120
140
120
MeCN
–
–
MeCN
–
–
MeCN
–
–
38
18
66
40
15
58
52
12
59
13
56
Trace
14
56
Trace
14
16
6
27
16
8
31
24
9
5c R
1
= Ph, R
2
= Me
5d R
1
= Np, R
2
= Me
47
8
27
No reaction took place in the presence of PhCOOH or TFA as catalyst under the same reaction conditions.
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O. Aydin, H. Kilic, S. Bayindir, E. Erdogan, and N. Saracoglu
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Scheme 3. Proposed mechanism for the formation 6a and 10a.
In another set of experiments, we evaluated 1-indanone
5e) and 2-indanone (5f), which are not benzylic ketones,
in the reaction conditions produced a dramatic effect on the
outcome of the reaction, resulting in the formation of prod-
ucts comprising condensation, redox amination, and reduc-
tive alkylation products as outlined in Table 2. These
results show that full-conjugation or cross-conjugation the
nitrogen atom on the enamine backbone can play an impor-
tant role in controlling of the condensation products 15 and
16. It also should be noticed that no condensation product
16 was obtained from the reaction of 2-indanone (5f) with
excess indoline at 140°C. Therefore, we attempted to deter-
mine whether the condensation product 16 could be isomer-
ized into redox amination product 6f. Upon treatment of the
condensation product 16 with bismuth nitrate catalyst in a
sealed tube at 140°C, the expected intramolecular isomeriza-
tion did not take place to give the corresponding 6f
(Scheme 5). When the product 16 was heated under the same
conditions and in the presence of 8.4mM of indoline (1), a
(
as electrophiles in this process (Schemes 4 and 5). Treat-
ment of a mixture of indoline and 1-indanone in acetoni-
trile at 120°C with bismuth nitrate catalyst afforded redox
amination together with reductive amination products in
proportions of 59:23:10, respectively (Scheme 4).
However, increasing the indoline content in the mixture
and carrying out the reaction at 140°C exhibited similar
trends. We believe that indoline reacts with 1-indanone in a
way similar to its reaction with acetophenone and benzophe-
none. This reaction must be operating to permit both reduc-
tive amination and redox alkylation. Performing the
reaction of indoline with 2-indanone under the reaction con-
ditions at 120°C in acetonitrile led to a full conversion and
formation of a new single condensation product 16 in 91%
yield (Scheme 5 and Entry 1 in Table 2). However, a change
Scheme 4. Reactions of indoline (1, 1 equiv) with 1-indanone (5e) (1 equiv).
Scheme 5. Isomerization attempts of 16. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
Mechanistic Insights
1543
Table 2
Reaction of indoline with 2-indanone (5f) catalyzed by Bi(NO
3
)
3
·5H
2
O (0.1 mM) in a sealed tube.
Product (yield%)
Entry
Indoline: 2-indanone ratio
Solvent
CH CN
Temp. (°C)
Time (h)
16
10f
6f
4
1
2
3
4
1:1
1:1
5:1
5:1
3
120
140
120
140
1
91
61
61
–
–
8
10
23
–
10
8
–
4
18
14
–
–
–
5
10
3
35
mixture of reductive amination products 10f and 4 and redox
amination product 6f was obtained (Scheme 5).
The proposed reaction pathways for the formation of 10f,
However, in order to test the effect of cyclopropyl
group, the cyclopropyl phenyl ketone (5g) was subjected
to redox amination reaction under the same reaction condi-
tions, from which a mixture of the products, separable by
chromatography, was obtained (Scheme 7). The use of an
excess of indoline (1) resulted in a similar product mixture
except for 4-(1H-indol-1-yl)-1-phenylbutan-1-one (21).
We assume that 20 is a primary product and the others
(19, 21, and 4) are secondary products, and they are formed
during the reductive amination reaction of 20 under the
given reaction conditions. Path A was postulated to explain
these results, which begins with coordination of the cata-
lyst with the carbonyl oxygen promoting the ring opening
(Scheme 8). The subsequent nucleophilic attack of indoline
to the cyclopropane ring affords the homo-Michael adduct
6
f, and 4 were described in Scheme 6. This possible mech-
anism with Bi(III)/H O-catalyzed recondensation of the
2
condensation product 16 to enamine ion 17. The initially
formed enamine ion 17 is converted to reductive amination
products 10f and 4, followed by an intermolecular hydride
transfer from indoline (1) and deprotonation steps. Then,
the iminium ion 17 may undergo isomerization to the
iminium ion 18. The subsequent deprotonation forms the
redox amination product 6f. Oxidations of N-alkyl
indolines 10e and 10f to indoles 6e and 6f were also realized
by MnO in 95% and 97% yields, respectively.
2
2
0. This product could then undergo the reductive
Scheme 6. Proposed mechanism for isomerization of 15 to 10f. [Color figure
can be viewed in the online issue, which is available at wileyonlinelibrary.
com.]
amination onto the carbonyl catalyzed by the Lewis acid
to give bisindoline product 19. During the reductive
amination process, indoline (1) and indoline derivative 20
serve as hydride ion sources to form indole (4) and indole
derivative 21. We proposed the possibility of an alternative
second path wherein the indoline might react with the car-
bonyl group to generate reductive or redox amination prod-
ucts transiently (Scheme 8, path B). In this situation, it is
necessary to observe the formation of the most favorable
cyclopropane ring-opening product(s) (25 and 26) as well
as 19. As a consequence, path A appears to be more favor-
able than path B.
Scheme 7. Reaction of indoline (1 equiv) with the cyclopropyl phenyl ketone (5g; 1 equiv).
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O. Aydin, H. Kilic, S. Bayindir, E. Erdogan, and N. Saracoglu
Vol 52
Scheme 8. Proposed mechanism for reaction of indoline with the cyclopropyl phenyl ketone (5g). [Color figure can be viewed in the online issue, which
is available at wileyonlinelibrary.com.]
In another series of experiments, we tried to use 2-ace-
tyl-5-membered heterocyclic (thiophene, pyrrole, and fu-
ran) ketones as an electrophile for various alkylation
products. The use of 2-acetylthiophene (5h) in acetonitrile
at 120°C resulted in the formation of corresponding prod-
ucts 10h, 6h, and 4 (Scheme 9). The reaction performed
in 5 mM of indoline as solvent-free gave the reductive
amination products 6h and 4. The oxidation of indoline
When N-Boc-2-acetylpyrrole (27) reacted with indoline
as depicted in Scheme 10 (or 5 mM of indoline, without
solvent), in all cases, a quantitative migration of the t-
Boc protecting group at the pyrrole nitrogen to nitrogen
of indoline was found (Scheme 10). We assume that the
migration occurs via an intermolecular mechanism.
Another unexpected reaction was observed when 2-
acetylfuran (5j) was treated with indoline at 120°C as
depicted in Scheme 11. The envisioned redox amination
of indoline (1) with 5j under Lewis acidic conditions led
to the formation of three unexpected products (29–31) to-
gether with indole (4). The repeated reaction under the same
conditions in excess indoline afforded all of the products
(29, 30, 4) except for indole-phenol compound 31. Both
1,1′-(propane-1,2-diyl)diindoline (29) and 3-(indolin-1-yl)
1
0h to indole 6h was also performed by manganese diox-
ide in 95% yield.
In contrast, the reaction of 2-acetylpyrrole (5i) failed to
produce the desired compounds under the aforementioned
conditions for 2-acetylthiophene (5h) (Scheme 10). All of
these reactions only lead to the recovery of the starting ma-
terial. We assume that the resonance contribution like 5i′
could decrease the susceptibility of ketone carbonyl carbon
toward the nucleophilic attack. Therefore, we protected the
nitrogen of 2-acetylpyrrole using di-tert-butyl dicarbonate
in the presence of one equivalent of sodium hydride in tet-
rahydrofuran (THF).
phenol (30) were then subjected to MnO -oxidation to give
2
the corresponding indoles. But, we determined that
bisindoline 29 was unstable toward the oxidation reaction.
We also protected the phenolic oxygen with acetic anhy-
dride in order to detect the free phenolic hydroxyl group
of 30 (Scheme 12). Oxidation of the acetylated product 32
Scheme 9. Reaction of indoline (1; 1 equiv) with 2-acetylthiophene (5h;
with MnO was carried out in methylene chloride to give
2
1
equiv).
the N-phenyl-indole 33 (Scheme 12).
The structural analyses of the products obtained clearly
show that the products do not possess a furan skeleton.
Scheme 11. Reaction of indoline (1; 1 equiv) with 2-acetylfuran (5j; 1 equiv).
Scheme 10. Reaction of indoline (1; 1 or 5 equiv) with N-Boc-2-acetylpyrrole
5i; 1 equiv). [Color figure can be viewed in the online issue, which is available
at wileyonlinelibrary.com.]
(
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Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
Mechanistic Insights
1545
2
Scheme 12. Acetylation of phenol 30 and oxidation of 32 with MnO .
serve as a hydride source to give indole (4) and 3-(1H-
indol-1-yl)phenol (31) during the reductive alkylation
process. On the basis of the results obtained, a plausible
mechanism for the phenolic-type products is proposed as
depicted in Scheme 14. First, the mechanism likely in-
volves the formation of 1,6-addition product 35 (an amino
acetal) by attack of indoline to the coordination of the
catalyst-furan, followed by intermolecular ring opening,
providing zwitterionic intermediates 36–38. The intermo-
lecular condensation of the enolat and iminium components
built the construction of six-membered ring 39 as a precur-
sor of the phenol ring. A sequential tautomerization–
dehydration process of 40 leads to 30.
Indeed, the retrosynthetic analysis illustrated in Scheme 13
guide us that bisindoline 29 can be produced through a se-
quential reductive alkylation reaction between indoline
and methylglyoxal (34). We reasoned that 2-acetylfuran
(
5j) would be unstable to yield methylglyoxal under our re-
action conditions. In order to test this foresight, 2-
acetylfuran was subjected to the same reaction conditions
without indoline, but no transformation to methylglyoxal
took place, and in each case, the starting material was re-
covered unchanged. Consequently, an alternative pathway
was followed; one possible route is depicted in Scheme 14:
the indoline (1) and 3-(indolin-1-yl)phenol (30), which
Once the formation of unexpected products was deter-
mined for 2-acetylfuran (5j), the chemistry was extended
to 2-acetylbenzofuran (5k). When the 2-acetylbenzofuran
(
4
5k) was submitted to the same conditions, bisarylmethane
3 as a new product was formed in addition to the reduc-
tive amination products 10k, 4, and redox isomerization
product 6k (Scheme 15). Much to our surprise, the forma-
tion of 5,5′-bisarylmethane-type product 43 was firstly iso-
lated in 12% yields. When the reaction was carried out
with excess indoline at 120°C under solvent-free condi-
tions, the products obtained were reductive amination
products 10k, 4, and bisarylmethanes 43 and 44. Although
the bisarylmethanes 43 and 44 could not be separated by
silica gel chromatography, both in case of the mixture of
Scheme 13. Retrosynthetic analysis for 29. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
Scheme 14. Proposed formation mechanism for 29 and 30. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Scheme 15. Reaction of indoline (1; 1 equiv) with 2-acetylbenzofuran (6o; 1 equiv).
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Scheme 16. Synthesis of 43 from 41 and a mixture of 41 and 42. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Scheme 17. Formation of 43 and 44. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
the bisarylmethanes (43, 44) and the pure 43 were oxidized
EXPERIMENTAL
with MnO2 to the corresponding bis(indolyl)methane
4
5, respectively (Scheme 16). We propose that the
General.
All reagents and solvents were purchased
bisarylmethane 43 is formed by subsequent Friedel–Crafts
C-alkylation between 2-acetylbenzofuran (5k) and 2 equiv-
alent of indoline, which can react on C-5 carbon to yield
the Friedel–Crafts product (Scheme 17). We postulate that
indoline acts as an ambident nucleophile, and the outcome
of the reaction strongly depends on the structure of the ke-
tone moiety. Furthermore, the bisarylmethane 43 takes part
in the reductive amination process to form 44 by releasing
a hydride followed by a proton loss.
from commercial suppliers and used without further
purification. Column chromatography and thin-layer
chromatography (TLC) were performed using Silica gel
60 (70-230 Fluka) and Silica gel 60 HF254 (Fluka),
respectively. Melting points were determined on a Buchi
539 capillary melting apparatus and uncorrected. Infrared
spectra were recorded on a Mattson 1000 FT-IR
1
13
spectrophotometer. H NMR and
C NMR spectra
were recorded on 400 (100) MHz Varian and Bruker
spectrometers and are reported in d units with SiMe as
4
the internal standard. Elemental analyses were carried out
CONCLUSION
on a Leco CHNS-932 instrument.
General procedure 1 (GP1): the reaction of indoline (1; 1
equiv) with ketone (5b-k; 1 equiv) at 120°C. To a solution
In conclusion, this study elucidated for the first time a
new type of the alkylation products with redox and/or re-
ductive aminations that can occur upon treatment of
indoline with a wide variety of benzylic ketones in the
presence of a bismuth nitrate catalyst. The present experi-
mental study has provided important mechanistic insights
into the role of the electronic nature of the ketones on the
course of the reaction. The key step for these reactions is
the formation of an iminium ion from a ketone group and
indoline. For the redox amination reaction, the iminium
ion transforms to N-alkyl indoles by isomerization during
the reaction sequence. Moreover, the inherent reducing
power of indoline allows for an intermolecular hydride
transfer to this iminium ion and opens up a new path for
N-alkyl indolines via a (this) reductive amination protocol.
Further studies aimed at examining the redox amination
scope of diketones with indoline are currently in progress
in our lab.
of indoline (1; 1.0 equiv) in MeCN (5 mL) was added
ketone (5b-k, 1.0 equiv) and Bi(NO ) ·5H O (0.1 mM).
3
3
2
Reaction mixture was stirred magnetically in a sealed tube
at 120°C. The reaction was monitored by TLC. After the
completion of the reaction, the mixture was diluted with
ethylacetate (30 mL) and washed with water (2 × 50mL),
and organic phase was dried over Na SO . The crude
2
4
product was purified by silica gel column chromatograph,
and isolated compounds were given according to elution
sequence (EtOAc/Hexane or hexane) in general.
General procedure 2 (GP2): the reaction of indoline (1; 1
equiv) with ketone (5b-k; 1 equiv) at 140°C. A mixture of
indoline (1; 1.0 mM), ketone (5b-k, 1.0 equiv) and
Bi(NO ) ·5H O (0.1 equiv) was stirred magnetically in a
3
3
2
sealed tube at 140°C. The reaction was monitored by
TLC. After the completion of the reaction, the mixture
was diluted with ethylacetate (30 mL) and washed with
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Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
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1547
water (2× 50mL), and organic phase was dried over
4.94, found: C, 89.05; H, 6.04; N, 4.93. Indole (4). 202 mg,
Na SO . The crude product was purified by silica gel
column chromatograph, and isolated compounds were
given according to elution sequence (EtOAc/Hexane or
16%, eluent: EtOAc/hexane (40%), Rf=0.26 (254nm).
2
4
Reaction of indoline (1) with benzophenone (5b) at 140°C.
.
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of indoline
3 3
2
hexane) in general.
General procedure 3 (GP3): the reaction of indoline (1; 5
equiv) with ketone (5b-k; 1 equiv) at 120°C in solvent-free
(1; 500mg, 4.2 mM) with benzophenone (5b; 765mg,
4.2 mM) was performed at 140°C for 1 h in solvent-free
condition according to GP2. N-Benzhydryl indoline
condition. A mixture of indoline (1, 5.0 equiv), ketone
(10b). 230mg, 18%. N-Benzhydryl-1H-indole (6b).
.
3
(
5b-k, 1.0 equiv) and Bi(NO ) 5H O (0.1 mM) was
3
2
705 mg, 56%. Indole (4). 70mg, 6%.
stirred magnetically in a sealed tube at 120°C under
solvent-free condition. The reaction was monitored by
TLC. After the completion of the reaction, the mixture
was diluted with ethylacetate (30 mL) and washed with
water (2× 50mL), and organic phase was dried over
Na SO . The crude product was purified by silica gel
Reaction of indoline (1) with benzophenone (5b) at 120°C.
.
Bi(NO ) 5H O (0.1 mmol)-Catalyzed reaction of indoline
3
3
2
(1; 1 g, 8.4 mM) with benzophenone (5a; 305mg, 1.7 mM)
was performed at 120°C for 1 h in solvent-free condition
according to GP3. N-Benzhydryl indoline (10b). 465mg,
66%. Indole (4). 189mg, 27%. Indoline (1). 405mg
2
4
column chromatograph, and isolated compounds were
given according to elution sequence (EtOAc/Hexane or
hexane) in general.
(
3.5 mM) was recovered. N-Benzhydryl-1H-indole (6b).
N-Benzhydryl-1H-indole (6b) was obtained as colorless
viscous liquid (429mg, 96%) from the oxidation of N-
benzhydryl indoline (10b; 450 mg, 1.6 mM) with MnO2
General procedure for MnO
2
oxidation: from N-alkyl
indoline (10b-k) to N-alkyl indole (6b-k). To a solution of
(
1.37 g, 16.0 mM) in CH Cl at room temperature for 12h
2 2
N-alkyl indolines (10b-k; 1.0 equiv) in CH Cl (10 mL)
2
2
according to general procedure.
was added the active MnO (10.0 equiv). The mixture
2
Reaction of indoline (1) with acetophenone (5c). Bi(NO ) ·5H O
3
3
2
was stirred at room temperature for 12 h. The reaction
was monitored by TLC. After filtration, the mixture was
evaporated under reduced pressure, and the compound
(
4
0.1 mM)-Catalyzed reaction of indoline (1; 500 mg,
.2 mM) with acetophenone (5c; 504 mg, 4.2 mM) was
performed at 120°C for 3 h in MeCN according to GP1.
N-(1-Phenylethyl)indoline (10c) [21–25]. 405 mg, 40%,
dark viscous liquid, eluent: EtOAc/hexane (30%),
Rf = 0.72 (254 nm). H NMR (400 MHz, CDCl ): δ 7.42
(
7a-o) was purified by silica gel column chromatography,
and isolated compounds were given according to elution
sequence (EtOAc/Hexane or hexane) in general.
1
3
Reaction of indoline (1) with benzophenone (5b). Bi(NO ) ·5H O
3
3
2
(d, J=7.4Hz, =CH, 1H), 7.36–7.33 (m, =CH, 2H), 7.28–
(0.1mmol) catalyzed the reaction of indoline (1; 500mg, 4.2
7
.25 (m, =CH, 2H), 7.06 (d, J=7.4Hz, =CH, 1H), 7.00
mM) with benzophenone (5b; 765mg, 4.2 mM) was
performed at 120°C for 4h in MeCN according to GP1. N-
Benzhydryl indoline (10b) [21, 22]. 480mg, 38%,
(
(
(
(
(
t, J=7.4Hz, =CH, 1H), 6.61 (t, J= 7.4 Hz, =CH, 1H), 6.36
d, J=7.4Hz, =CH, 1H), 4.73 (q, J= 7.0 Hz, CH, 1H), 3.40
dd, A part of AB system, J=16.7, 8.5Hz, CH , 1H), 3.33
dd, A part of AB system, J=16.7, 8.5Hz, CH , 1H), 2.96
2
colorless viscous liquid, eluent: EtOAc/hexane (30%),
2
1
Rf=0.81 (254nm). H NMR (400MHz, CDCl ): δ
13
3
t, J=8.5Hz, CH , 2H), 1.54 (d, J=7.0Hz, CH , 3H).
C
2
3
7
6
1
.36–7.24 (m, =CH, 10H), 7.07 (d, J=6.2Hz, =CH, 1H),
.92 (t, J=7.7Hz, =CH, 1H), 6.63 (t, J=7.0Hz, =CH,
H), 6.19 (d, J=7.7Hz, =CH, 1H), 5.55 (s, CH, 1H), 3.19
NMR (100MHz, CDCl ): δ 151.7, 143.2, 130.4, 128.7,
3
1
1
1
1
8
27.5, 127.4, 127.2, 124.7, 117.3, 107.5, 54.8, 48.2, 28.5,
À1
6.8. IR (KBr, cm ): 3029, 2978, 2928, 2109, 1509, 1463,
13
(t, J=8.3Hz, CH , 2H), 2.94 (t, J=8.3Hz, CH , 2H).
C
2
2
457, 1401, 1355, 1310, 1300, 1228, 1190, 1163, 1122,
NMR (100MHz, CDCl ): δ 152.1, 141.5, 130.6 (2C),
3
084, 979, 908, 858, 811. Anal. Calcd. for C H N: C,
16 17
1
28.7, 127.4, 127.3, 124.5, 117.7, 108.3, 66.8, 51.7, 28.5.
6.05; H, 7.67; N, 6.27, found: C, 86.11; H, 7.64; N, 6.30.
À1
IR (KBr, cm ): 2978, 2928, 2109, 1463, 1457, 1401,
N-(1-Phenylethyl)-1H-indole (6c) [26, 27]. 145mg, 14%,
yellow viscous liquid, eluent: EtOAc/hexane (20%),
Rf =0.53 (254nm). H NMR (400MHz, CDCl ): δ 7.65 (d,
J=8.1Hz, =CH, 1H), 7.31–7.22 (m, =CH, 5H), 7.15–7.06
1
8
355, 1310, 1228, 1190, 1163, 1122, 1084, 979, 908, 858,
11. Anal. Calcd. for C H N: C, 88.38; H, 6.71; N, 4.91,
1
2
1 19
3
found: C, 88.35; H, 6.67; N, 4.93. N-Benzhydryl-1H-
indole (6b) [23, 24]. 158mg, 13%, colorless viscous
(
(
(
m, =CH, 4H), 6.58 (d, J= 3.3Hz, =CH, 1H), 5.70–5.66
1
liquid, eluent: EtOAc/hexane (30%), Rf =0.55 (254nm). H
13
m, CH, 1H), 1.93 (d, J=7.3Hz, CH , 3H). C NMR
100MHz, CDCl ): δ 142.9, 136.3, 129,0, 128.9, 127.7,
3
NMR (400MHz, CDCl ): δ 7.65–7.63 (m, =CH, 1H),
3
3
7
.35–7.26 (m, =CH, 7H), 7.25–7.08 (m, =CH, 6H), 6.83 (d,
1
26.1, 125.1, 121.7, 121.1, 119.8, 110.3, 101.7, 55.0, 22.0.
13
À1
J=3.0Hz, =CH, 2H), 6.50 (d, J=1.3Hz, =CH, 1H).
C
IR (KBr, cm ): 2978, 2928, 2109, 1509, 1463, 1457,
1401, 1355, 1310, 1300, 1228, 1190, 1163, 1122, 1084,
979, 858, 811. Anal. Calcd. for C H N: C, 86.84; H, 6.83;
N, 6.33, found: C, 86.86; H, 6.82; N, 6.38. Indole (4).
160mg, 16%, eluent: EtOAc/hexane (40%), Rf =0.26
(254nm).
NMR (100MHz, CDCl ): δ 139.9, 136.6, 128.9, 128.7,
3
1
28.4, 127.9, 126.9, 121.6, 120.9, 119.8, 110.2, 101.4, 63.7.
16 15
À1
IR (KBr, cm ): 3029, 2978, 2928, 2109, 1509, 1463,
1457, 1355, 1310, 1300, 1228, 1190, 1163, 1122, 979, 908,
8
58, 811. Anal. Calcd. for C H N: C, 89.01; H, 6.05; N,
2
1 17
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1
548
O. Aydin, H. Kilic, S. Bayindir, E. Erdogan, and N. Saracoglu
Vol 52
Reaction of indoline (1) with acetophenone (5c) at 140°C.
H, 6.31; N, 5.16 found: C, 88.44; H, 6.38; N, 5.12. Indole
(4). 143 mg, 24%, eluent: EtOAc/hexane (40%), Rf=0.26
(254nm).
.
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of indoline
3
3
2
(
4
1; 500mg, 4.2 mM) with acetophenone (5b; 504mg,
.2mM) was performed at 140°C for 1h in solvent-free
condition according to GP2. N-(1-Phenylethyl)indoline
10c). 151mg, 15%. N-(1-Phenylethyl)-1H-indole (6c).
Reaction of indoline (1) with 1-(naphthalen-2-yl)ethan-1-one
.
(
5d) at 140°C. Bi(NO ) 5H O (0.1mM)-Catalyzed reaction
3 3
2
of indoline (1; 500mg, 4.2mM) with 1-(naphthalen-2-yl)
ethan-1-one (5d; 714mg, 4.2mM) was performed at 140°C
for 2 h in solvent-free condition according to GP2. N-(1-
(Naphthalen-2-yl)ethyl)indoline (10d). 149 mg, 12%. N-(1-
(Naphthalen-2-yl)ethyl)-1H-indole (6d). 567 mg, 47%.
Indole (4). 95mg, 9%.
(
5
60mg, 56%. Indole (4). 81mg, 8%.
Reaction of indoline (1) with acetophenone (5c) at 120°C.
.
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of indoline
3
3
2
(
1; 1 g, 8.4mM) with acetophenone (5c; 202 mg, 1.7 mM)
was performed at 120°C for 1 h in solvent-free condition
according to GP3. N-(1-Phenylethyl)indoline (10c).
52mg, 58%. Indole (4). 187mg, 31%. Indoline (1).
10mg (4.4 mM) was recovered. N-(1-Phenylethyl)-1H-
indole (6c). N-(1-phenylethyl)-1H-indole (6c) was
obtained as yellow viscous liquid (304mg, 88%) from
the oxidation of N-(1-phenylethyl)indoline (10c; 350mg,
Reaction of indoline (1) with 1-(naphthalen-2-yl)ethan-1-one
.
(
5d) at 120°C. Bi(NO ) 5H O (0.1mM)-Catalyzed reaction
3
3
2
3
5
of indoline (1; 1.5g, 12.6 mM) with 1-(naphthalen-2-yl)ethan-
1
3
-one (5d; 429mg, 2.5 mM) was performed at 120°C for
h in solvent-free condition according to GP3. N-(1-
(
(
(
naphthalen-2-yl)ethyl)indoline (10d). 605mg, 59%. N-(1-
Naphthalen-2-yl)ethyl)-1H-indole (6d). 83mg, 8%. Indole
4). 276 mg, 27%. Indoline (1). 852mg (7.3mM) was
1
.6mM) with MnO (1.37 g, 16mM) in CH Cl at room
2 2 2
temperature for 12h according to general procedure.
recovered. N-(1-(Naphthalen-2-yl)ethyl)-1H-indole (6d).
N-(1-(Naphthalen-2-yl)ethyl)-1H-indole (6d) was obtained
as pale yellow solid (270mg, 97%, m.p. = 75–76°C
(hexane)) from the oxidation of N-(1-(naphthalen-2-yl)ethyl)
indoline (10d; 280mg, 1.0mM) with MnO2 (890 g,
10.0mM) in CH Cl at room temperature for 12h according
Reaction of indoline (1) with 1-(naphthalen-2-yl)ethan-1-one
.
(
5d).
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of
3
3
2
indoline (1; 500mg, 4.2mM) with 1-(naphthalen-2-yl)
ethan-1-one (5d; 714 mg, 4.2 mM) was performed at
1
(
20°C for 8h in MeCN according to GP1. N-(1-
Naphthalen-2-yl)ethyl)indoline (10d). 630mg, 52%, gray
solid, m.p. = 102–103°C (hexane), eluent: EtOAc/hexane
2
2
to general procedure.
Reaction of indoline (1) with 1-indanone (5e). Bi(NO ) ·5H O
3 3 2
1
(
10%), Rf=0.85 (254nm). H NMR (400MHz, CDCl ): δ
3
7
1
6
1
1
1
1
3
1
1
.82–7.78 (m, =CH, 4H), 7.55 (dd, J=8.5, 1.7Hz, =CH,
H), 7.48–7.42 (m, =CH, 2H), 7.05 (d, J=7.4, =CH, 1H),
.97 (t, J=7.4Hz, =CH, 1H), 6.60 (t, J=7.4Hz, =CH,
H), 6.38 (d, J= 7.4 Hz, =CH, 1H), 4.83 (q, J=6.9Hz, CH,
H), 3.38 (dd, A part of AB system, J=16.8, 8.3Hz, CH2,
H), 3.30 (dd, B part of AB system, J=16.8, 8.3Hz, CH2,
H), 2.94 (t, J=8.3Hz, CH , 2H) 1.59 (d, J=6.9Hz, CH ,
(0.1mM)-Catalyzed reaction of indoline (1; 500mg,
4.2mM) with 1-indanone (5e; 555mg, 4.2mM) was
performed at 120°C for 2h in MeCN according to GP1. 1-
(2,3-Dihydro-1H-inden-1-yl)indoline (10e). 415mg, 59%,
white solid, m.p. = 98–99°C (CH
EtOAc/hexane (20%), Rf=0.69 (254nm). H NMR
(400MHz, CDCl ): δ 7.36–7.25 (m, =CH, 3H), 7.24–7.19
Cl /hexane), eluent:
2
2
1
2
3
3
13
H). C NMR (100MHz, CDCl ): δ 151.5, 140.0, 133.4,
(m, =CH, 1H), 7.18–7.03 (m, =CH, 2H), 6.64 (t,
J=7.5Hz, =CH, 1H), 6.53 (d, J=7.5Hz, =CH, 1H), 5.30
3
32.7, 130.3, 128.2, 128.0, 127.7, 127.3, 126.1, 126.1,
25.7, 125.2, 124.5, 117.2, 107.4, 54.8, 48.2, 28.3, 16.3.
(t, J=8.0Hz, CH, 1H), 3.24 (dd, J=17.5, 8.0Hz, CH
1H), 3.14 (dd, J=16.5, 8.0Hz, CH
CH , 4H), 2.39–2.31 (m, CH , 1H), 2.12–2.02 (m, CH
1H). C NMR (100MHz, CDCl
2
,
À1
IR (KBr, cm ): 3375, 3043, 2934, 2847, 1613, 1574,
2
, 1H), 3.04–2.86 (m,
1
1
493, 1474, 1453, 1371, 1321, 1298, 1249, 1177, 1159,
107, 1053, 1023, 938, 883, 811. Anal. Calcd. for
2
2
,
2
13
): δ 151.6, 143.7, 142.1,
3
C H N: C, C, 87.87; H, 7.01; N, 5.12, found: C, 87.82;
H, 7.11; N, 5.10. N-(1-(Naphthalen-2-yl)ethyl)-1H-indole
130.4, 127.6, 127.3, 126.3, 125.0, 124.9, 124.5, 117.3,
107.3, 61.1, 47.7, 30.6, 28.2, 27.0. IR (KBr, cm ): 2948,
20 19
À1
(6d). 172mg, 14%, pale yellow solid, m.p. = 75–76°C
2851, 1605, 1483, 1458, 1255, 1022, 938, 883, 811. Anal.
(
hexane), eluent: EtOAc/hexane (10%), Rf=0.73 (254nm).
Calcd. for C17H17N: C, 86.77; H, 7.28; N, 5.95, found: C,
1
H NMR (400MHz, CDCl ): δ 7.92–7.84 (m, =CH, 4H),
86.81; H, 7.31; N, 5.93. 1-(2,3-Dihydro-1H-inden-1-yl)-
1H-indole (6e). 246mg, 23%, pale yellow solid, m.p. =
63–64°C (CH Cl /hexane), eluent: EtOAc/hexane (20%),
3
7
.75 (s, =CH, 1H), 7.61–7.57 (m, =CH, 2H), 7.44 (dd,
J=9.9, 4.2Hz, =CH, 2H), 7.35 (dd, J= 8.5, 1.6 Hz, =CH,
H), 7.28 (dd, J=5.5, 3.5Hz, =CH, 2H), 5.92 (q, J=7.0Hz,
2
2
1
2
Rf=0.38 (254nm). H NMR (400MHz, CDCl ): δ 7.64
3
13
CH, 1H), 2.09 (d, J=7.0Hz, CH , 3H). C NMR
(d, J=7.7Hz, =CH, 1H), 7.37–7.29 (m, =CH, 3H), 7.21–
7.17 (m, =CH, 2H), 7.14–7.09 (m, =CH, 2H), 6.91 (d,
J=3.2Hz, =CH, 1H), 6.48 (d, J=3.2Hz, =CH, 1H), 6.01
3
(100 MHz, CDCl ): δ 140.5, 136.6, 133.7, 133.1, 129.3,
3
1
29.0, 128.4, 128.1, 126.7, 126.4, 125.4, 124.8, 124.8,
1
21.9, 121.4, 120.1, 110.5, 102.0, 55.3, 22.0. IR (KBr,
(t, J=7.4Hz, CH, 1H), 3.18–3.11 (m, CH , 1H), 3.06–2.98
2
À1
cm ): 3375, 3043, 2934, 2847, 1613, 1574, 1493, 1474,
(m, CH , 1H), 2.75–2.67 (m, CH , 1H), 2.30–2.11
2
2
13
1453, 1371, 1321, 1298, 1249, 1177, 1159, 1107, 1053,
(m, CH , 1H). C NMR (100MHz, CDCl ): δ 143.8,
2
3
1
023, 938, 883, 811. Anal. Calcd. for C H N: C, 88.52;
141.8, 136.3, 129.2, 128.7, 127.2, 126.1, 125.3, 125.2,
2
0 17
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2015
Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
Mechanistic Insights
1549
1
3
1
21.5, 121.3, 119.7, 110.0, 101.7, 61.3, 33.9, 30.7. IR (KBr,
6.2Hz, CH
(100MHz, CDCl
2
, 2H), 2.90 (t, J=8.1Hz, CH
, 2H). C NMR
2
À1
cm ): 3027, 2948, 2851, 1605, 1483, 1458, 1255, 1022,
3
): δ 151.4, 141.6, 130.6, 127.3, 126.6,
9
6
38, 883, 811. Anal. Calcd. for C H N: C, 87.52; H,
.48; N, 6.00, found: C, 87.47; H, 6.51; N, 5.97. Indole
126.5, 124.4, 117.6, 107.5, 56.7, 48.3, 35.3, 28.4. IR (KBr,
cm ): 3303, 3029, 1657, 1523, 1450, 1337, 1250, 1207,
1
7 15
À1
(
4). 110mg, 10%, eluent: EtOAc/hexane (40%), Rf=0.31
1126, 1018, 1199, 938, 883, 811. Anal. Calcd. for
(254nm).
C H
17
17N: C, 86.77; H, 7.28; N, 5.95, found: C, 86.71; H,
7.23; N, 5.98. 1-(2,3-Dihydro-1H-inden-2-yl)-1H-indole
(6f). 106mg, 10%, white solid, m.p. = 107–108°C (CH Cl
hexane), eluent: EtOAc/hexane (20%), Rf =0.41 (254nm).
Reaction of indoline (1) with 1-indanone (5e) at 140°C.
.
Bi(NO ) 5H O (0.1mM) catalyzed the reaction of indoline
2
/
2
3
3
2
(1; 500mg, 4.2mM) with 1-indanone (5e; 555mg, 4.2mM)
1
was performed at 140°C for 1h in solvent-free condition
H NMR (400MHz, CDCl ): δ 7.63 (d, J=7.7Hz, =CH,
3
according to GP2. 1-(2,3-Dihydro-1H-inden-1-yl)indoline
1H), 7.41 (d, J=8.4Hz, =CH, 1H), 7.31–7.20 (m, =CH,
5H), 7.12 (t, J=7.7Hz, =CH, 1H), 7.07 (d, J=3.3Hz,
(10e): 206mg, 20%. 1-(2,3-Dihydro-1H-inden-1-yl)-1H-
=
CH, 1H), 6.45 (d, J=3.3Hz, =CH, 1H), 5.38–5.32
(m, CH, 1H), 3.55 (dd, J= 16.5, 7.7 Hz, CH , 2H), 3.33
, 2H). C NMR (100MHz,
): δ 140.7, 135.8, 128.8, 127.1, 124.8, 124.7, 121.4,
indole (6e). 565mg, 54%. Indole (4). 80mg, 8%.
Reaction of indoline (1) with 1-indanone (5e) at 120°C.
2
.
13
Bi(NO ) 5H O (0.1mM)-Catalyzed reaction of indoline
(dd, J= 16.5, 5.6Hz, CH
CDCl
121.1, 119.5, 109.6, 101.5, 56.0, 39.8. IR (KBr, cm ):
3018, 2919, 2848, 2605, 1480, 1450, 1445, 1249, 1199,
2
3
3
2
(1; 1g, 8.4mM) with 1-indanone (5e; 221mg, 1.7mM) was
3
À1
performed at 120°C for 1h in solvent-free condition
according to GP3. 1-(2,3-Dihydro-1H-inden-1-yl)indoline
(
(
10e). 385mg, 62%. Indole (4). 184mg, 29%. Indoline
1). 430mg (3.7mM) was recovered. 1-(2,3-Dihydro-1H-
938, 883, 811. Anal. Calcd. for C17H15N: C, 87.52; H, 6.48;
N, 6.00, found: C, 87.57; H, 6.45; N, 5.97. Indole (4).
4
0mg, 4%, eluent: EtOAc/hexane (40%), Rf =0.31 (254nm).
inden-1-yl)-1H-indole (6e). 1-(2,3-Dihydro-1H-inden-1-
yl)-1H-indole (6e) was obtained as pale yellow solid
Reaction of indoline (1) with 1-(1H-inden-2-yl)indoline
.
(
15).
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of
3
3
2
(
329mg, 95%) from the reaction of 1-(2,3-dihydro-1H-
inden-1-yl)indoline (10e; 350mg, 1.5mM) with MnO2
1.29g, 15.0mM) in CH Cl at room temperature for 12h
indoline (1; 1.0 g, 8.4 mM) with 1-(1H-inden-2-yl)indoline
16; 391mg, 1.7 mM) was performed at 140°C for 5 h in
solvent-free condition according to GP2. 1-(2,3-Dihydro-
H-inden-2-yl)indoline (10f). 280mg, 53%. 1-(2,3-
(
(
2
2
according to general procedure.
1
Reaction of indoline (1) with 2-indanone (5f) at 120°C.
.
Dihydro-1H-inden-2-yl)-1H-indole (6f): 143mg, 27%.
Bi(NO ) 5H O (0.1mM)-Catalyzed reaction of indoline
3
3
2
Indole (4). 40mg, 4%.
(1; 500mg, 4.2mM) with 2-indanone (5f; 555mg, 4.2mM)
Reaction of indoline (1) with 2-indanone (5f). Bi(NO ) ·5H O
3
3
2
was performed at 120°C for 1h in MeCN according to
GP1. 1-(1H-Inden-2-yl)indoline (15). 961mg, 91%, pale
brown solid, m.p. = 117–118°C (CH Cl /hexane), eluent:
(
8
0.1 mM)-Catalyzed reaction of indoline (1; 1.0 g,
.4 mM) with 2-indanone (5f; 221 mg, 1.7 mM) was
2
2
1
performed at 140°C for 3 h in solvent-free condition
according to GP2. 1-(2,3-Dihydro-1H-inden-2-yl)indoline
EtOAc/hexane (20%), Rf=0.67 (254nm). H NMR
(
400MHz, CDCl ): δ 7.36 (d, J=7.0Hz, =CH, 1H), 7.26–
3
(10f). 143mg, 23%. 1-(2,3-Dihydro-1H-inden-2-yl)-1H-
7
.13 (m, =CH, 5H), 7.02–6.99 (m, =CH, 1H), 6.86–6.82
indole (6f). 216 mg, 35%. Indole (4). 87mg, 14%.
Indoline (1). 610mg (5.2mM) was recovered. 1-(2,3-
Dihydro-1H-inden-2-yl)-1H-indole (6f). 1-(2,3-Dihydro-
(
2
m, =CH, 1H), 5.83 (s, =CH, 1H), 3.97 (t, J=8.9Hz, CH ,
2
13
H), 3.82 (s, CH , 2H), 3.22 (t, J=8.9Hz, CH , 2H).
C
2
2
NMR (100MHz, CDCl ): δ 149.2, 146.0, 145.8, 137.2,
3
1H-inden-2-yl)-1H-indole (6f) was obtained as white solid
1
1
3
9
6
31.4, 127.8, 127.1, 125.3, 123.2, 121.3, 119.6, 118.1,
09.8, 102.6, 51.1, 39.1, 27.9. IR (KBr, cm ): 3303,
029, 1657, 1523, 1450, 1337, 1250, 1207, 1126, 1018,
À1
(192mg, 97%) from the oxidation of 1-(2,3-dihydro-1H-
inden-2-yl)indoline (10f; 200mg, 0.9mM) with MnO2
(
740mg, 9.0mM) in CH Cl at room temperature for 12h
2 2
38, 883, 811. Anal. Calcd. for C H N: C, 87.52; H,
1
7 15
according to general procedure.
.48; N, 6.00, found: C, 87.55; H, 6.41; N, 6.04.
Reaction of indoline (1) with 1-cyclopropylethan-1-one
Reaction of indoline (1) with 2-indanone (5f) at 140°C.
.
(5g).
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of
.
3 3
2
Bi(NO ) 5H O (0.1mM)-Catalyzed reaction of indoline
3
3
2
indoline (1; 500mg, 4.2 mM) with 1-cyclopropylethan-1-
one (5g; 613mg, 4.2 mM) was performed at 120°C for
(1; 500mg, 4.2mM) with 2-indanone (5f; 555 mg, 4.2 mM)
was performed at 140°C for 5 h in solvent-free condition
according to GP2. 1-(1H-Inden-2-yl)indoline (16). 642mg,
8
1
h in MeCN according to GP1. 1,1′-(1-Phenylbutane-
,4-diyl)diindoline (19). 492mg, 44%, yellow viscous
6
8
1%. 1-(2,3-Dihydro-1H-inden-2-yl)indoline (10f). 85mg,
%, pale yellow solid, m.p. = 175–176°C (CH Cl /hexane),
liquid, eluent: EtOAc/hexane (10%), Rf = 0.74 (254nm).
2
2
1
1
H NMR (400MHz, CDCl ): δ 7.47–7.40 (m, =CH, 4H),
eluent: EtOAc/hexane (20%), Rf= 0.67 (254 nm). H NMR
3
7
.35 (t, J= 6.9 Hz, =CH, 1H), 7.19–7.12 (m, =CH, 4H),
6.76 (t, J =7.6 Hz, =CH, 1H), 6.69 (t, J = 7.6 Hz, =CH,
1H), 6.62 (d, J = 7.6 Hz, =CH, 1H), 6.56 (d, J = 7.6Hz, =
CH, 1H), 4.77 (t, J = 7.6 Hz, CH, 1H), 3.62–3.55
(
400MHz, CDCl ): δ 7.24–7.22 (m, =CH, 2H), 7.19–7.16
3
(m, =CH, 2H), 7.09–7.05 (m, =CH, 2H), 6.66 (t, J=7.7Hz,
=CH, 1H), 6.55 (d, J=7.7Hz, =CH, 1H), 4.55–4.50
(
m, CH, 1H), 3.25–7.17 (m, CH , 4H), 3.07 (dd, J= 16.1,
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1
550
O. Aydin, H. Kilic, S. Bayindir, E. Erdogan, and N. Saracoglu
Vol 52
(
m, CH , 1H), 3.40–3.34 (m, CH , 3H), 3.21 (t, J=7.1Hz,
(10%), Rf = 0.62 (254nm)) from the oxidation of 1,1′-(1-
phenylbutane-1,4-diyl) diindoline (19; 100mg, 0.3mM)
2
2
CH , 2H), 3.10–3.00 (m, CH , 4H), 2.26–2.19 (m, CH ,
2
2
2
2
13
H), 1.90–1.72 (m, CH , 2H). C NMR (100MHz,
with MnO
(260mg, 3.0 mM) in CH Cl at room
2 2 2
2
CDCl ): δ 153.1, 151.9, 140.8, 130.4, 129.9, 128.7, 128.2,
temperature for 12h according to general procedure. 1,1′-
3
1
(
(
(
1-Phenylbutane-1,4-diyl) bis-1H-indole (22). H NMR
1
1
27.7, 127.6 (2C), 124.9, 124.8, 117.8, 116.9, 107.3,
400 MHz, CDCl ): δ 7.63–7.59 (m, =CH, 2H), 7.20–7.12
06.8, 59.1, 53.5, 49.6, 47.3, 29.3, 28.9, 28.5, 25.2. IR
3
À1
m, =CH, 6H), 7.10–7.04 (m, =CH, 4H), 7.02 (dd, J = 7.5,
(
KBr, cm ): 3046, 3025, 2946, 2843, 1606, 1488, 1472,
1
.6 Hz, =CH, 2H), 6.94 (d, J= 3.1 Hz, =CH, 1H), 6.52 (d,
J = 3.1 Hz, =CH, 1H), 6.46 (d, J =3.1 Hz, =CH, 1H), 5.29
dd, J= 9.4, 6.8 Hz, CH, 1H), 4.02 (t, J = 6.8 Hz, CH2,
H), 2.32–2.12 (m, CH , 2H), 1.84–1.73 (m, CH , 2H).
1
459, 1388, 1329, 1304, 1259, 1156, 1023, 915, 864, 815.
Anal. Calcd. for C H N : C, 84.74; H, 7.66; N, 7.60,
2
6 28 2
(
found: C, 84.74; H, 7.58; N, 7.49. 4-(Indolin-1-yl)-1-
phenylbutan-1-one (20). 220mg, 20%, dark brown
2
2
2
13
C NMR (100 MHz, CDCl ): δ 141.3 (2C), 136.6, 136.2,
3
viscous liquid, eluent: EtOAc/hexane (10%), Rf=0.68
1
129.0 (2C), 128.9, 128.0, 126.6, 125.0, 122.0, 121.9,
(
254nm). H NMR (400MHz, CDCl ): δ 7.95 (d,
3
1
5
2
1
8
21.4, 121.3, 120.0, 119.7, 110.1, 109.6, 102.5, 101.7,
9.4, 46.1, 32.8, 27.6. IR (KBr, cm ): 3048, 3021, 2957,
834, 1606, 1474, 1452, 1437, 1392, 1329, 1308, 1262,
J=7.5Hz, =CH, 2H), 7.54 (t, J=7.5Hz, =CH, 1H), 7.44
t, J=7.5Hz, =CH, 2H), 7.04 (t, J=7.7Hz, =CH, 2H),
À1
(
6
1
2
2
.63 (t, J=7.7Hz, =CH, 1H), 6.47 (d, J=7.7Hz, =CH,
H), 3.33 (t, J= 8.3Hz, CH , 2H), 3.15 (t, J= 7.0Hz, CH ,
171, 1019, 932, 871, 811. Anal. Calcd. for C H N : C,
26 24 2
2
2
5.68; H, 6.64; N, 7.69, found: C, 85.56; H, 6.72; N, 7.80.
H), 3.09 (t, J= 7.0Hz, CH , 2H), 2.94 (t, J= 8.3Hz, CH ,
2
2
Reaction of indoline (1) with 2-acetylthiophene (5h).
1
3
H), 2.10–2.03 (m, CH , 2H). C NMR (100MHz,
.
2
Bi(NO ) 5H O (0.1mM)-Catalyzed reaction of indoline
3
3
2
CDCl ): δ 200.1, 152.9, 137.2, 133.2, 130.2, 128.8, 128.3,
3
(
4
1; 500mg, 4.2mM) with 2-acetylthiophene (5h; 529mg,
.2mM) was performed at 120°C for 6h in MeCN
according to GP1. N-(1-(Thiophen-2-yl) ethyl) indoline
10h). 596mg, 58%, dark brown viscous liquid, eluent:
1
27.5, 124.6, 117.8, 107.2, 53.4, 49.0, 36.0, 28.8, 22.4. IR
À1
(
KBr, cm ): 3054, 2949, 2816, 1684, 1606, 1489, 1459,
1
8
5
449, 1366, 1317, 1270, 1247, 1209, 1015, 1001, 868,
14. Anal. Calcd. for C H NO: C, 81.47; H, 7.22; N,
.28, found: C, 81.42; H, 7.24; N, 5.30. 4-(1H-Indol-1-
(
1
1
8
19
EtOAc/hexane (10%), Rf=0.81 (254nm). H NMR
(
400MHz, CDCl ): δ 7.17 (t, J= 3.4 Hz, =CH, 1H), 7.02–
3
yl)-1-phenylbutan-1-one (21). 115mg, 10%, brown solid,
7
.06 (m, =CH, 2H), 6.92–6.95 (m, =CH, 2H), 6.63 (t,
m.p. = 74–78°C (hexane), eluent: EtOAc/hexane (10%),
J=7.6Hz, =CH, 1H), 6.51 (d, J=7.6Hz, =CH, 1H), 5.02
(q, J=6.9Hz, CH, 1H), 3.38 (dd, A part of AB system,
1
Rf= 0.31 (254nm). H NMR (400MHz, CDCl ): δ 7.95
3
(bd, J= 7.3Hz, =CH, 2H), 7.81 (d, J =7.7Hz, =CH, 1H),
J=16.9, 8.5Hz, CH , 1H), 3.27 (dd, B part of AB system,
2
7
7
.62–7.61 (m, =CH, 1H), 7.52–7.48 (m, =CH, 3H), 7.38–
.34 (m, =CH, 1H), 7.30–7.26 (m, =CH, 1H), 7.18 (bd,
J=16.9, 8.5Hz, CH , 1H), 2.92 (t, J=8.5Hz, CH , 2H),
2
2
13
1.60 (d, J=6.9Hz, CH , 3H). C NMR (100MHz,
3
J= 2.9Hz, =CH, 1H), 6.66–6.65 (m, =CH, 1H), 4.27
CDCl ): δ 150.7, 146.4, 130.3, 127.2, 126.4, 124.6, 124.3,
3
(
(
t, J =6.9Hz, CH , 2H), 2.92 (t, J=6.9Hz, CH , 2H), 2.34
124.2, 117.6, 107.7, 50.5, 47.0, 28.1, 17.0. IR (KBr,
cm ): 3070, 3042, 2974, 2845, 1606, 1486, 1459, 1385,
2
2
1
3
À1
p, J= 6.9, CH , 2H) C NMR (100MHz, CDCl ): δ
2
3
1
1
99.5, 136.9 (2C), 136.2, 133.4, 128.9, 128.2, 128.1,
1328, 1302, 1256, 1235, 1184, 1024, 850, 831. Anal.
21.8, 121.2, 119.6, 109.7, 101.5, 45.6, 35.2, 24.7. IR
Calcd. for C H NS: C, 73.32; H, 6.59; N, 6.11; S,
14 15
À1
(KBr, cm ): 3053, 2947, 2824, 1678, 1606, 1499, 1459,
13.98, found: C, 73.32; H, 6.65; N, 6.20; S, 13.94. N-(1-
(Thiophen-2-yl) ethyl)-1H-indole (6h). 125 mg, 12%,
1
447, 1356, 1311, 1280, 1239, 1209, 1017, 976, 867, 811.
Anal. Calcd. for C H NO: C, 82.10; H, 6.51; N, 5.32,
found: C, 82.22; H, 6.44; N, 5.30. Indole (4). 188mg,
dark yellow viscous liquid, eluent: EtOAc/hexane (10%),
1
8 17
1
Rf=0.77 (254nm). H NMR (400MHz, CDCl
): δ 7.64
3
1
7%, eluent: EtOAc/hexane (20%), Rf= 0.26 (254nm).
(t, J=7.7Hz, =CH, 1H), 7.37 (d, J=7.7Hz, =CH, 1H),
7.21–7.17 (m, =CH, 2H), 7.11 (t, J=7.7Hz, =CH, 1H),
6.92 (dd, J=5.1, 3.7Hz, =CH, 1H), 6.87 (d, J=3.7Hz,
Reaction of indoline (1) with 1-cyclopropylethan-1-one
.
(
5g).
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of
3
3
2
indoline (1; 1.5 g, 12.6mM) with 1-cyclopropylethan-1-
one (5g; 613mg, 4.2mM) was performed at 120°C for
=
CH, 1H), 6.54 (d, J=3.3Hz, =CH, 1H), 5.92 (q,
13
J=7.0Hz, CH, 1H), 1.97 (d, J=7.0Hz, CH , 3H).
C
3
8
h in solvent-free condition. 1,1′-(1-Phenylbutane-1,4-
NMR (100MHz, CDCl ): δ 146.1 (2C), 128.7, 126.7,
3
diyl) diindoline (19). 390mg, 41%. 4-(Indolin-1-yl)-1-
phenylbutan-1-one (20). 214mg, 22%. Indole (4).
124.8, 124.7, 124.4, 121.5, 121.1, 119.6, 109.6, 102.0,
50.7, 22.2. IR (KBr, cm ): 3082, 3028, 2972, 2839,
À1
2
85mg, 30%. Indoline (1). 858mg (7.3 mM) was
1605, 1479, 1452, 1384, 1332, 1309, 1256, 1232, 1184,
1
023, 882, 824. Anal. Calcd. for C H NS: C, 73.97; H,
14 13
recovered.
1
,1′-(1-Phenylbutane-1,4-diyl) bis-1H-indole (22).
1,1′-
1-Phenylbutane-1,4-diyl) bis-1H-indole (22) was obtained
as yellow viscous liquid (94 mg, 94%, eluent: EtOAc/hexane
5.76; N, 6.16; S, 14.11, found: C, 73.88; H, 5.72; N, 6.24;
S, 14.13. Indole (4). 212mg, 21%, eluent: EtOAc/hexane
(20%), Rf=0.26 (254nm).
(
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2015
Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
Mechanistic Insights
1551
1
Reaction of indoline (1) with 2-acetylthiophene (5h).
eluent: EtOAc/hexane (15%), Rf = 0.73 (254 nm).
H
.
Bi(NO ) 5H O (0.1mM) catalyzed the reaction of indoline
NMR (400MHz, CDCl ): δ 7.13–7.02 (m, =CH, 4H),
3
3
2
3
(1; 1.5g, 12.6mM) with 2-acetylthiophene (5h; 318mg,
6.67–6.59 (m, =CH, 2H), 6.49–6.44 (m, =CH, 2H), 4.00–
2
.5 mM) was performed at 120°C for 2 h in solvent-
3.91 (m, CH, 1H), 3.52–3.32 (m, CH
part of AB system, J = 13.5, 6.7 Hz, CH
part of AB system, J= 13.4, 6.0 Hz, CH , 1H), 2.99–2.94
2
, 4H), 3.24 (dd, A
free condition according to GP3. N-(1-(Thiophen-2-
yl) ethyl) indoline (10h). 542 mg, 59%. Indole (4):
, 1H), 3.13 (dd, B
2
2
13
(
(
(
4
2
1
m, CH , 4H), 1.21 (d, J =6.7 Hz, CH , 3H). C NMR
2
85 mg, 31%. Indoline (1). 872 mg (7.5 mM) was
recovered. N-(1-(Thiophen-2-yl) ethyl)-1H-indole
6h). N-(1-(Thiophen-2-yl) ethyl)-1H-indole (6h) was
2
3
100 MHz, CDCl ): δ 152.9, 151.4, 130.1, 129.8, 127.5
3
2C), 124.7 (2C), 117.5, 117.0, 106.6, 106.4, 54.1, 53.2,
(
À1
9.6, 46.3, 28.9, 28.5, 14.1. IR (KBr, cm ): 3439, 3315,
930, 1734, 1690, 1620, 1548, 1469, 1401, 1345, 1315,
266, 1217, 1161, 1119, 917, 898, 849. Anal. Calcd. for
obtained as dark yellow viscous liquid (235 mg, 95%)
from the oxidation of N-(1-(thiophen-2-yl) ethyl)
indoline (10h; 250 mg, 1.1 mM) with MnO (948 mg,
1
2
C H N : C, 81.97; H, 7.97; N, 10.06, found: 81.88; H,
19 22 2
1.0 mM) in CH Cl at room temperature for 12 h
2 2
7
.92; N, 10.11. 3-(Indolin-1-yl) phenol (30). 475mg,
according to general procedure.
4
9%, brown viscous liquid, eluent: EtOAc/hexane (15%),
N-Boc-2-acetylpyrrole (27) [28].
To a solution of 2-
1
Rf = 0.65 (254nm). H NMR (400MHz, CDCl ): δ 7.25–
3
acetylpyrrole (5i; 500mg, 4.6mM) and di-tert-butyl
dicarbonate (1.1g, 5.0mM) in freshly distilled THF
7
(
1
.21 (m, =CH, 3H), 7.11–7.05 (m, =CH, 2H), 6.99–6.94
m, =CH, 1H), 6.87–6.83 (m, =CH, 1H), 6.36 (bs, OH,
H), 6.34 (d, J = 7.7 Hz, =CH, 1H), 3.74 (t, J =8.1 Hz,
(50mL) was added slowly NaH (0.314g, 2.8mM) in
freshly distilled THF (50mL). The mixture was stirred at
room temperature for 1h. Then the reaction mixture was
solved with EtOAc (3×30mL) and the organic phase was
washed with NH Cl (5%, 3×30mL) and dried over
Na SO . The crude product (958mg) was purified on silica
13
CH , 2H), 3.19 (t, J= 8.1 Hz, CH , 2H). C NMR
2
2
(
100 MHz, CDCl ): δ 153.5, 151.3, 132.8, 130.9, 128.1,
3
1
2
27.7, 125.0, 124.9, 121.3, 120.1, 115.3, 109.9, 56.0,
9.4. IR (KBr, cm ): 3421, 3046, 2955, 2929, 2849,
À1
4
2
4
1603, 1496, 1459, 1366, 1288, 1262, 1227, 1186, 1174,
151, 1113, 1055, 1036, 1026, 927, 872, 820. Anal.
Calcd. for C H NO: C, 79.59; H, 6.20; N, 6.63, found:
gel column (25g) with EtOAc/hexane (13%) to yield N-
Boc-2-acetylpyrrole (27; 912mg, 95%, colorless viscous
1
14 13
liquid, Rf=0.52 (254nm)). N-Boc-2-acetylpyrrole (27).
C, 79.58; H, 6.31; N, 6.50. 3-(1H-Indol-1-yl) phenol
(31). 152mg, 16%, black viscous liquid, eluent:
1
H NMR (400MHz, CDCl ): δ 7.24–7.23 (m, =CH, 1H),
3
1
6
.78 (dd, J=3.6, 1.6Hz, =CH, 1H), 6.08 (t, J=3.6Hz,
EtOAc/hexane (15%), Rf = 0.56 (254nm). H NMR
13
=
CH, 1H), 2.36 (s, CH , 3H), 1.50 (s, CH , 9H). C NMR
(400 MHz, CDCl ): δ 7.71 (dd, J = 7.0, 1.5 Hz, =CH, 1H),
3
3
3
(
100MHz, CDCl ): δ 188.3, 148.9, 134.1, 127.8, 121.1,
7.37 (t, J= 7.7 Hz, =CH, 1H), 7.30–7.01 (m, =CH, 6H),
3
À1
1
2
1
09.9, 84.7, 27.8, 27.4. IR (KBr, cm ): 3150, 2982, 2936,
906, 1749, 1618,1544, 1477, 1442, 1390, 1372, 1339,
300, 1251, 1166, 1126, 1066, 1016, 894, 846.
7.05 (t, J= 7.7 Hz, =CH, 1H), 6.75 (d, J = 3.3 Hz, =CH,
1
3
1H), 5.00 (bs, OH, 1H). C NMR (100MHz, CDCl
51.7, 136.8, 130.0, 129.1, 128.8, 128.5, 126.0, 123.1,
): δ
3
1
À1
Reaction of indoline (1) with N-Boc-2-acetylpyrrole (27).
121.5, 121.4, 121.0, 117.1, 110.7, 104.6. IR (KBr, cm ):
.
3
1
1
480, 3051, 2925, 2854, 1705, 1593, 1515, 1499, 1455,
332, 1309, 1291, 1230, 1214, 1188, 1137, 1116, 1098,
061, 1033, 1012, 957, 937, 883, 854, 824. Anal. Calcd.
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of indoline
(
8
MeCN according to GP1. tert-Butyl indoline-1-
carboxylate (28) [27–30]. 615mg, 45%, yellow viscous
3
3
2
1; 500mg, 4.2 mM) with N-Boc-2-acetylpyrrole (27;
78mg, 4.2mM) was performed at 120°C for 6 h in
for C H NO: C, 80.36; H, 5.30; N, 6.69, found: C,
14 11
8
0.43; H, 5.42; N, 6.57. Indole (4). 188mg, 20%, eluent:
EtOAc/hexane (20%), Rf =0.26 (254nm).
liquid, eluent: EtOAc/hexane (10%), Rf =0.71 (254nm).
1
3-(1H-Indol-1-yl) phenol (31). 3-(1H-Indol-1-yl) phenol
H NMR (400 MHz, CDCl ): δ 7.85 (bs, =CH, 0.7H),
3
(31) was obtained as pale brown viscous liquid (279mg,
7
6
2
.45 (bs, =CH, 0.3H), 7.16–7.11 (m, =CH, 2H), 6.95–
9
4%) from the oxidation of 3-(indolin-1-yl) phenol (30;
.88 (m, J = 7.4, 1.0 Hz, =CH, 2H), 3.97–3.94 (m, =CH,
13
brown viscous liquid, 300 mg, 1.4 mM) with MnO
2
H), 3.08 (t, J =8.7Hz, 2H), 1.58 (s, CH , 9H).
C
3
(
1.23 g, 14.0 mM) in CH Cl at room temperature for 12h
2 2
NMR (100 MHz, CDCl ): δ 127.6, 124.9, 122.3, 114.9,
3
À1
according to general procedure.
4
1
9
7
7.8, 28.7, 27.6. IR (KBr, cm ): 3042, 2938, 2850,
769, 1606, 1498, 1462, 1368, 1298, 1288, 1069, 1013,
79, 924, 887, 817. Anal. Calcd. for C H NO : C,
3
-(Indolin-1-yl) phenyl acetate (32).
To a solution of
3
-(indolin-1-yl) phenol (30; 300mg, 1.42mM) in pyridine
1
3
17
2
(
5 mL) was added 0.4 mL (4.3 mM) of Ac O. The mixture
2
1.21; H, 7.81; N, 6.39, found: C, 71.33; H, 7.72; N, 6.34.
was stirred at room temperature for 12h. The reaction
was monitored by TLC. Then the mixture was solved
with EtOAc (3 × 30mL) and the organic phase was
washed with H O (3× 30mL) and dried over Na SO .
2 2 4
The solvent was removed under reduced pressure.
Reaction of indoline (1) with 1-(furan-2-yl) ethan-1-one
.
(
5j).
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of
3
3
2
indoline (1; 500 mg, 4.2mM) with 1-(furan-2-yl) ethan-1-
one (5j; 462mg, 4.2mM) was performed at 120°C for 8h
in MeCN according to GP1. 1,1′-(Propane-1,2-diyl)
diindole (29). 45 mg, 5%, dark yellow viscous liquid,
3-(Indolin-1-yl) phenyl acetate (32; 338mg, black viscous
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1
552
O. Aydin, H. Kilic, S. Bayindir, E. Erdogan, and N. Saracoglu
Vol 52
liquid, 94%, eluent: EtOAc/hexane (20%), Rf= 0.52 (254nm))
811. Anal. Calcd. for C H NO: C, 82.10; H, 6.51; N,
1
8 17
was purified on a silica gel column chromatograph with
EtOAc/hexane. 3-(Indolin-1-yl) phenyl acetate (32). H
5.32, found: C, 82.03; H, 6.58; N, 5.29. 1-(1-(Benzofuran-
2-yl) methyl)-1H-indole (6k). 186mg, 16%, dark yellow
1
NMR (400 MHz, CDCl ): δ 7.41 (dd, J =8.2, 0.9 Hz,
viscous liquid, eluent: EtOAc/hexane (15%), Rf=0.73
3
1
=
CH, 1H), 7.30–7.26 (m, =CH, 1H), 7.24–7.18 (m, =CH,
H), 7.07 (t, J= 7.6Hz, =CH, 1H), 6.77 (t, J= 7.6 Hz,
CH, 1H), 6.52 (d, J = 7.6Hz, =CH, 1H), 3.91 (t,
J =8.5 Hz, CH , 2H), 3.16 (t, J =8.5 Hz, CH , 2H), 2.06
(254nm). H NMR (400MHz, CDCl ): δ 7.81 (d,
3
3
=
J=7.7Hz, =CH, 1H), 7.61 (dd, J=7.9, 1.0Hz, =CH, 1H),
7.55 (d, J=8.1Hz, =CH, 2H) 7.40–7.27 (m, =CH, 5H),
6.72 (d, J=2.9Hz, =CH, 1H), 6.58 (s, =CH, 1H), 5.92
2
2
1
3
13
(
s, CH , 3H). C NMR (100 MHz, CDCl ): δ 169.2,
(q, J=7.1Hz, CH, 1H), 2.08 (d, J =7.1Hz, CH
, 3H).
3
C
3
3
NMR (100MHz, CDCl ): δ 157.5, 155.3, 136.2, 129.1,
1
1
48.7, 145.8, 137.3, 130.5, 127.2, 127.1, 125.3, 124.8,
3
1
1
3
1
8
28.3, 125.3, 124.7, 123.2, 122.1, 121.5, 121.4, 120.1,
11.7, 109.9, 103.8, 102.6, 49.8, 19.5. IR (KBr, cm ):
374, 2978, 2934, 2847, 1613, 1574, 1493, 1474, 1453,
371, 1321, 1249, 1177, 1159, 1107, 1053, 1023, 938,
24.4, 123.8, 118.8, 109.4, 54.0, 29.1, 21.0. IR (KBr,
À1
À1
cm ): 3028, 2933, 2850, 1769, 1597, 1498, 1462, 1368,
1
9
331, 1316, 1298, 1263, 1108, 1093, 1043, 1010, 938,
03, 817. Anal. Calcd. for C H NO : C, 75.87; H, 5.97;
1
6
15
2
83, 811. Anal. Calcd. for C H NO: C, 82.73; H, 5.79;
N, 5.53, found: C, 75.79; H, 5.86; N, 5.52.
-(1H-Indol-1-yl) phenyl acetate (33). 3-(1H-Indol-1-yl)
18 15
3
N, 5.36, found: C, 82.63; H, 5.72; N, 5.34. 5,5′-(1-
(Benzofuran-2-yl) ethane-1,1-diyl) diindoline (43).
phenyl acetate (32) was obtained as pale brown viscous
liquid (286 mg, 96%, eluent: EtOAc/hexane (15%),
Rf = 0.44 (254 nm)) from the oxidation of 3-(indolin-1-yl)
phenyl acetate (32; 300mg, 1.2mM) with MnO2 (1 g,
143mg, 12%, brown viscous liquid, eluent: EtOAc/hexane
1
(15%), Rf=0.73 (254nm). H NMR (400MHz, CDCl
): δ
3
7.44–7.38 (m, =CH, 2H), 7.20–7.12 (m, =CH, 2H), 6.94
(s, =CH, 2H), 6.83 (dd, J=8.2, 1.8Hz, =CH, 2H), 6.51
(d, J=8.2Hz, =CH, 2H), 6.22 (s, =CH, 1H), 3.60 (bs, NH,
2H), 3.47 (t, J=8.3Hz, CH , 4H), 2.92 (t, J=8.3Hz, CH ,
1
2.0mM) in CH Cl at room temperature for 12h
2 2
according to general procedure. 3-(1H-Indol-1-yl) phenyl
1
acetate (33). H NMR (400MHz, CDCl ): δ 7.64 (d,
3
2
2
13
J=7.7Hz, =CH, 1H), 7.46 (dd, J=7.7, 1.7Hz, =CH, 1H),
4H), 2.09 (s, CH , 3H). C NMR (100MHz, CDCl ): δ
3
3
7
.42–7.38 (m, =CH, 1H), 7.36–7.32 (m, =CH, 1H), 7.23
165.6, 155.2, 150.2, 137.9, 129.5, 128.9, 127.3, 124.7,
123.6, 122.7, 120.8, 111.5, 109.0, 104.8, 49.2, 47.8, 30.2,
28.5. IR (KBr, cm ): 3380, 2930, 2857, 1615, 1547,
(dd, J=7.7, 1.2Hz, =CH, 1H), 7.22–7.11 (m, =CH, 4H),
13
À1
6
.64 (d, J=3.2Hz, =CH, 1H), 1.82 (s, CH , 3H).
C
3
NMR (100MHz, CDCl ): δ 168.9, 146.2, 136.7, 132.3,
1495, 1455, 1345, 1252, 1111, 1051, 934, 884, 808. Anal.
3
1
1
2
1
9
7
28.9, 128.8, 128.7, 128.5, 127.2, 124.2, 122.6, 121.1,
20.6, 111.0, 103.8, 20.6. IR (KBr, cm ): 3106, 3066,
Calcd. for C H N O: C, 82.07; H, 6.36; N, 7.36, found:
C, 82.08; H, 6.43; N, 7.28. Indole (4). 231mg (21%),
26 24 2
À1
926, 2853, 1768, 1605, 1518, 1500, 1476, 1459, 1369,
333, 1308, 1268, 1238, 1188, 1137, 1101, 1064, 1038,
47, 906, 866, 820. Anal. Calcd. for C H NO : C,
eluent: EtOAc/hexane (20%), Rf=0.26 (254nm).
Reaction of indoline (1) with 1-(benzofuran-2-yl) ethan-1-one
.
(5k). Bi(NO
)
5H O (0.1mM) catalyzed the reaction of
2
1
6
13
2
3
3
6.48; H, 5.21; N, 5.57, found: C, 76.52; H, 5.26; N, 5.45.
indoline (1; 1.5 g, 12.6 mM) with 1-(benzofuran-2-yl)ethan-
1-one (5k; 403mg, 2.5mM) was performed at 120°C for
Reaction of indoline (1) with 1-(benzofuran-2-yl) ethan-1-one
.
(
5k).
Bi(NO ) 5H O (0.1 mM)-Catalyzed reaction of
3
3
2
2
0h in solvent-free condition according to GP3. 1-(1-
indoline (1; 500mg, 4.2mM) with 1-(benzofuran-2-yl)
ethan-1-one (5k; 672mg, 4.2mM) was performed at 120°C
for 20h in MeCN according to GP1. 1-(1-(Benzofuran-2-
yl) ethyl) indoline (10k). 497mg, 42%, yellow solid, m.p.
(Benzofuran-2-yl) ethyl) indoline (10k). 553 mg; 55%.
Indole (4). 282mg, 28%. 868mg (7.4mM) of indoline (1)
was recovered. A mixture of 5,5′-(1-(benzofuran-2-yl)
ethane-1,1-diyl)diindoline (43) and 5-(1-(benzofuran-2-yl)-
=
112–113°C (hexane), eluent: EtOAc/hexane (15%),
1
4
-(indolin-5-yl)ethyl)-1H-indole (44): 95mg, 10%, ratio of
3:44 according to H NMR is 2:3, brown viscous liquid,
1
Rf = 0.76 (254 nm). H NMR (400MHz, CDCl ): δ 7.55
1
3
(dd, J =7.8, 1.0 Hz, =CH, 1H), 7.50 (d, J = 8.1 Hz, =CH,
eluent: 20% EtOAc/hexane.
1H), 7.31–7.22 (m, =CH, 2H), 7.12 (t, J = 7.0 Hz, =CH,
2H), 6. 71 (t, J =7.0 Hz, =CH, 1H), 6.64–6.60 (m, =CH,
2H), 5.02 (q, J = 7.0Hz, CH, 1H), 3.57 (dd, A part of AB
1
-(1-(Benzofuran-2-yl) methyl)-1H-indole (6k).
1-(1-
(Benzofuran-2-yl) methyl)-1H-indole (6k) was obtained
as dark yellow viscous liquid (238mg, 96%) from the
oxidation of 1-(1-(benzofuran-2-yl) ethyl) indoline (10k;
system, J = 16.9, 8.5Hz, CH , 1H), 3.38 (dd, B part of AB
system, J =16.9, 8.5Hz, CH , 1H), 3.01 (t, J= 8.5 Hz,
CH , 2H), 1.68 (d, J= 7.0Hz, CH , 3H). C NMR
2
2
2
50 mg, 1.0 mM) with MnO2 (825mg, 10.0 mM) in
1
3
2
3
CH Cl at room temperature for 12h according to general
2
2
(100 MHz, CDCl ): δ 158.3, 155.0, 150.9, 130.4, 128.5,
3
procedure.
1
1
2
1
27.5, 124.8, 124.1, 122.9, 121.0, 117.9, 111.5, 107.7,
5,5′-(1-(Benzofuran-2-yl)ethane-1,1-diyl)bis(1H-indole)
À1
03.9, 49.4, 47.8, 28.4, 15.0. IR (KBr, cm ): 3374,
(45).
5,5′-(1-(Benzofuran-2-yl)ethane-1,1-diyl)bis(1H-
978, 2934, 2847, 1613, 1574, 1493, 1474, 1453, 1371,
321, 1249, 1177, 1159, 1107, 1053, 1023, 938, 883,
indole) (45) was obtained as yellow viscous liquid
(112mg, 94%, eluent: EtOAc/hexane (15%), Rf=0.10
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2015
Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and
Mechanistic Insights
1553
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1
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CH, 2H), 6.29 (s, CH, 1H), 2.35 (s, CH , 3H). C NMR
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m, =CH, 4H), 7.28–7.12 (m, =CH, 8H), 6.48–6.46 (m, =
13
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(100MHz, CDCl ): δ 165.7, 155.2, 139.1, 134.6, 128.9,
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2
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27.7, 124.6, 123.5, 123.4, 122.6, 120.8, 120.1, 111.6,
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À1
10.7, 105.1, 103.2, 50.1, 28.9. IR (KBr, cm ): 3415,
925, 2846, 1625, 1546, 1469, 1454, 1415, 1343, 1319,
[
251, 1094, 935, 885, 805. Anal. Calcd. for C H N O:
26
20
2
C, 82.95; H, 5.35; N, 7.44, found: C, 82.86; H, 5.41; N, 7.53.
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5
,1-diyl)diindoline (43) and 5-(1-(benzofuran-2-yl)-1-(indolin-
-yl)ethyl)-1H-indole (44). 5,5′-(1-(Benzofuran-2-yl)ethane-
6
[
1
,1-diyl)bis(1H-indole) (45) was obtained as yellow viscous
liquid (83 mg, 93%) from the oxidation of a mixture of
,5′-(1-(benzofuran-2-yl)ethane-1,1-diyl)diindoline (43): 5-(1-
benzofuran-2-yl)-1-(indolin-5-yl)ethyl)-1H-indole (44)
96mg, 2: 3 ratio) with MnO (250mg, 2.9mM) in CH Cl
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2
Acknowledgments. Authors are indebted to The Scientific and
Technical Research Council of Turkey (TUBITAK, grant no.
TBAG-112T600), Department of Chemistry at Ataturk
University for their financial support for this study.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet