Ruthenium Pincer Complex Catalyzed Selective Synthesis of C-3 Alkylated Indoles and Bisindolylmethanes Directly from Indoles and Alcohols

Article abstract of DOI:10.1002/adsc.202000326

Herein, we presented Ru-SNS complex that serves as a useful catalyst for C-3 alkylation of 1H-indoles with various aliphatic primary and secondary alcohols including cyclic alcohols as well as benzylic alcohols. The selective synthesis of bisindolylmethane derivatives is also achieved from the same set of indole and alcohol just by altering the reaction parameters. Furthermore, the sustainable synthesis of C-3 alkylated indoles directly from 2-(2-nitrophenyl)ethan-1-ol and alcohols catalysed by a Ru-complex via “borrowing hydrogen” strategy is reported. This protocol provides an atom-economical sustainable route to access structurally important compounds like arundine, vibrindole A and tryptamine based derivatives. (Figure presented.).

Full text of DOI:10.1002/adsc.202000326

Title: Ruthenium Pincer Complex Catalyzed Selective Synthesis of C-3
Alkylated Indoles and Bisindolylmethanes Directly from Indoles
and Alcohols
Authors: Nandita Biswas, Rahul Sharma, and Dipankar Srimani
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000326
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10.1002/adsc.202000326
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Ruthenium Pincer Complex Catalyzed Selective Synthesis of C-
3 Alkylated Indoles and Bisindolylmethanes Directly from
Indoles and Alcohols
Nandita Biswasa, Rahul Sharmaa and Dipankar Srimania,*
a
Department of Chemistry, Indian Institute of Technology Guwahati, Assam, India, 781039 Fax: (+91)-361-258-2349;
phone: (+91)-361-258-3312; e-mail: dsrimani@iitg.ac.in
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. Herein, we presented Ru-SNS complex that serves nitrophenyl)ethan-1-ol and alcohols catalysed by a Ru-
as a useful catalyst for C-3 alkylation of 1H-indoles with complex via “borrowing hydrogen” strategy is reported.
various aliphatic primary and secondary alcohols including This protocol provides an atom-economical sustainable
cyclic alcohols as well as benzylic alcohols. The selective route to access structurally important compounds like
synthesis of bisindolylmethane derivatives is also achieved arundine, vibrindole A and tryptamine based derivatives.
from the same set of indole and alcohol just by altering the Keywords: Ruthenium, homogeneous catalysis, tridentate
reaction parameters. Furthermore, the sustainable synthesis ligands, alkylation, borrowing hydrogen, indole.
of C-3 alkylated indoles directly from 2-(2-
a
unsaturated imine (vinylogous imine)
Introduction
derivative
iii)hydrogenationofunsaturated
imine derivative to C-3 alkylated indole (Scheme 1).
Indoles and their derivatives are considered to be
among the most important heterocyclic scaffolds
owing to their prevalence in many bioactive
compounds,[1] natural products,[2] pharmaceuticals,[3]
agro-chemicals[4] and functional materials.[5] Thus,
the synthesis and functionalization of indole moiety
have attracted significant attention. However,
classical approach[6] for the synthesis of indole
[7]
moiety or its selective functionalization
involves
the use of toxic reagents, harsh reaction condition
and/or pre-functionalization of substrates, which
generates substantial amount of waste materials.
Hence the development of green, atom-efficient and
sustainable strategies for the synthesis of indole as
well as C-3 functionalization of this scaffold is an
area of intense research. In this perspective,
acceptorless dehydrogenative (AD) synthesis of
indole is considered as highly atom-economical and
environmentally benign approach. Likewise C-3
alkylation[8] of 1H-indole using alcohols as alkylating
agents via Borrowing Hydrogen Catalysis (BH)[9] is
substantially more advantageous than conventional
Friedel-Crafts type reaction,[7a] as the former does not
necessitate the use Lewis and Brønsted acids[7b] or
organocatalysts.[7d] The only byproduct formed in the
process is water, which makes the overall system
environmentally benign. The strategy comprises of
three steps i) dehydrogenation of alcohol to form
carbonyl compound ii) condensation reaction to form
Scheme 1. Alkylation of 1H-indole via the borrowing
hydrogen strategy.
In 2002, Yamaguchi and coworkers[10] reported an
elegant method to synthesize indole via oxidative
annulation of 2-aminophenethyl alcohol catalysed by
iridium complex. In 2007, in a seminal work Grigg
and coworkers[11] demonstrated [Cp*IrCl2]2 catalysed
synthesis of indole as well as C-3 alkylation of 1H-
indole moiety. C-3 functionalization of indoles with
wide range of aliphatic amines as alkylating agents
was first illustrated by Beller and coworkers.[12] The
use of alcohols as alkylating agent is highly
advantageous as alcohols can be renewably obtained
1
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10.1002/adsc.202000326
Advanced Synthesis & Catalysis
from lignocellose biomass[13] and water is the only
byproduct formed. The use of a diverse range of
aliphatic alcohols as alkylating partners is
challenging and hence has been largely unexplored.
whereas CsOH.H2O and Na2CO3 gave poor yield
(Table 1, Entries 14 and 15).[19] Thus, the observed
selectivity is highly dependent on the nature and
stoichiometry of the applied base and amount of the
alkylating agent. We also tried solvent such as
toluene (Table 1, entry 9) where the yield of the
desired C-3 alkylated indole was found to be very
poor.[20] Under the optimized reaction conditions,
complex 2 or 3 gave inferior yield of the desired
product 6e (Table 1, Entries 16 and 17). Without the
presence of any base, catalyst 1 failed to activate the
alcohol. Similarly, in absence of catalyst 1, 0.5 mmol
KOH did not yield any desired 3-octyl-1H-indole
(Table 1, Entries 19, 20). Thus the above results
clearly underpin the importance of both catalyst and
the base for the progress of the reaction.
[8d,8h-8k,14,15]
Shimizu and coworkers reported first
heterogeneous Pt-catalysed C-3 alkylation of indoles
with a diverse range of aliphatic alcohols.[14]
However their protocol failed to achieve alkylation of
indole with secondary alcohols. Very recently,
synthesis of C-3 alkylated indoles was achieved
directly from indoline and aliphatic primary alcohols
in the presence of iridium catalyst.[15] Therefore, there
is an increasing demand to develop new sustainable
catalytic protocols to achieve C-3 functionalized
indoles using both aliphatic primary and secondary
alcohols as alkylating agents.
Engrossed by the striking benefit of AD[16] and
BH[9] reaction and motivated by our continuous
interests in heterocyclic synthesis,[17] herein, we
Table 1. Optimization of the reaction condition for the C3-
alkylation of indole.[a]
described
SNS-acridine
derived
Ru-pincer
complex[17a] catalysed C-3 alkylation of indoles to get
3-substituted indoles. The one pot synthesis of C-3
alkylated indoles was also achieved directly from 2-
(2-nitrophenyl)ethan-1-ol and primary alcohols via
sequential multistep reaction. Furthermore, the
selective synthesis of bis(indolyl)methane derivatives
was also demonstrated.
Figure 1. Ruthenium pincer complexes.
Results and Discussion
At the outset, the catalytic applicability of complex
1-3 toward the C-3 alkylation of indoles with various
primary alcohols was examined. To find out the
optimum reaction conditions, various reaction
parameters were screened employing indole and 1-
octanol as model substrates. When, a mixture of
indole (1 mmol), 1-octanol (1 mmol) and KOH (1
°
[18]
mmol) was heated at 135 C
under neat condition
for 18 h in Ace pressure tube in the presence of 1
mol % catalyst 1, 10% 3-octyl-1H-indole (6e) was
obtained along with 65% 3,3'-(octane-1,1-
diyl)bis(1H-indole) (7d) (Table 1, Entry 1). In an
attempt to improve the yield of the 3-octyl-1H-indole
(6e), the ratio of indole: 1-octanol was increased to
1:5 which resulted in 40% isolation of 6e (Table 1,
Entry 4). Gratifyingly, the yield of 6e was further
improved from 40% to 86% simply by lowering the
amount of KOH to 0.5 mmol (Table 1, Entry 5).
However, further lowering of the amount of base
resulted in decrease of yield of the desired 3-octyl-
1H-indole (Table 1, Entry 7). Bases like Cs2CO3,
tBuOK and NaOH gave moderate yield (Table 1,
Entries 11-13) under the similar reaction condition
[a]
Reaction conditions: Indole (1 mmol), 1-octanol (5
mmol), Cat 1 (0.01 mmol, 1 mol %), 30 mL Ace pressure
tube, 135 °C, 18 h.
catalyst 1 loading.
[b]
[c]
In toluene (1 mL)
0.5 mol %
After achieving the optimized reaction condition,
we sought to explore the generality and the
limitations of the developed protocol. To manifest the
practical applicability of the system, various alcohols
and representative substituted indoles were
investigated. The reactions of indoles with a variety
of primary aliphatic alcohols afforded C-3 alkylated
2
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10.1002/adsc.202000326
Advanced Synthesis & Catalysis
product from good to excellent yields (6a-6f 60-95%). were able to synthesize 6ae directly from indole and
Thermodynamic data suggested that activating
methanol to its corresponding formaldehyde required
large enthalpy (approx. 31.0 Kcal)[16a] which in many
cases can limit the scope of the reaction. In contrast,
to our delight, reaction of indole with methanol
resulted in excellent conversion to the desired product
6a with yield of 95%. Similarly, ethanol and butanol
also gave rise to good yield of the desired products
6b and 6c (78% and 60% respectively). Excellent
yields of the desired C-3 alkylated indoles were
obtained by employing longer chain alcohols as
alkylating agents. (Table 2, Entries 6d-6f). Intrigued
by this result, we moved our attention to probe the
reactivity of secondary aliphatic alcohols like 2-
butanol, 2-octanol, 2-decanol toward the alkylation of
indole. We were pleased to observe that the reaction
afforded excellent yield of the desired products
(Table 2, Entries 6g-6i); however, it requires higher
loading of catalyst 1 (2 mol %) as well as longer
N,N-Dimethylethanolamine in one step (63% yield).
Table 2. Substrate scope for C-3 alkylation of indole with
alcohols.[a]
reaction time (36 h). This is
a
significant
improvement compared to the work of Shimizu and
coworkers who achieved a low yield of 4% using 2-
octanol.[14] Interestingly, cyclic alcohols too could be
easily applied as alkylating agents in the present
protocol (Table 2, Entries 6j & 6k ). For aromatic
alcohols the yields were moderate to good 6l-6l3
55%-62%,
indolyl)phenylmethane[21] derivatives as minor
products. Heteroaromatic alcohol like 2-
with
useful
bis(3-
thiophenemethanol worked well in our present
catalytic system with 72% of 6m being isolated. Next,
we investigated the reaction of substituted indoles
with primary as well as secondary aliphatic alcohols.
2-methyl-indole reacted smoothly with primary
alcohols to give the corresponding products in high
yield 6o-6r (66-80%). However in case of secondary
aliphatic alcohols, no product formation was
observed. This might be due to the steric effect from
the methyl group towards the incoming alkylating
agents.[12] Indoles having both activating and
deactivating groups were compatible with both
primary and secondary aliphatic alcohols for C-3
alkylation and afforded good to excellent isolated
yields of 6s-6z (52-89%). 5-Bromoindole gave
moderate yield of the corresponding product 6w-6x
with some dehalogenated by-product. Our catalyst
failed to activate 2,2,2-trifluoroethanol as desired 6aa
was not formed. Also N-methylindole did not
undergo C-3 alkylation (Table 2, Entry 6ac), which
suggested that the anion generated on the nitrogen
atom in the presence of base plays an important role
in this reaction.
[a]
Reaction condition: Indole (1 mmol), 1-octanol (5
mmol), Cat 1 (0.01 mmol, 1 mol %), KOH (0.5 mmol), 30
mL Ace pressure tube, 135 °C, 18-36 h. [b] 1 mL alcohol. [c]
[d]
2 mol % catalyst 1, 36 h. Catalyst 1 (2 mol %), Cs2CO3
(1.1 mmol), 24 h.
During the course of our optimization reaction
condition for the synthesis of C-3 alkylated indoles,
we found that the 3,3'-(octane-1,1-diyl)bis(1H-indole)
was obtained as major product when the reaction was
performed either in toluene solvent or with the lower
amount of alcohol (Table 1, Entries 1 & 9). Thus, we
were interested toward the synthesis of
bisindolylmethane derivatives as they are found in
many natural product and bioactive compounds.[25]
They are also used as antibacterial, anti-inflammatory,
anticancer and anti-fungal agent.[26] Although the
concept of the synthesis of bisindolylmethane
derivatives directly from indole with activated benzyl
To examine the practical applicability of the
present protocol, we extended our study to synthesize
tryptamine based alkaloid derivatives, which are
known
for
their
biological
importance.[22]
Conventionally, multistep reactions[23] are involved in
the synthesis of 2-(5-methoxy-1H-indol-3-yl)-N,N-
dimethylethan-1-amine 6ae which is an intermediate
of biologically active Bufotinine.[24] Gratifyingly, we
3
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10.1002/adsc.202000326
Advanced Synthesis & Catalysis
alcohols has been largely explored,[27,8d] the
were reacted with wide range of aliphatic alcohols to
obtain moderate to good yield of the corresponding
product (7c, 7e-7l). Benzyl alcohols reacted well with
indoles and structurally important [31] 7n and 7o were
isolated in excellent yield (81% and 89%
respectively).
construction
of
structurally
important
bisindolylalkanes using aliphatic alcohols as
alkylating agent is very scanty.[28] Therefore,
synthesis of diverse range of bisindolylalkanes using
indole and aliphatic alcohols is highly desirable.
Thus, when a mixture of indole (1 mmol), 1-
octanol (0.5 mmol), KOH (0.25 mmol) and catalyst 1
(1 mol %) was refluxed in toluene (1 mL) in an argon
atmosphere for 18 h, 75% 3,3'-(octane-1,1-
diyl)bis(1H-indole) 7d was isolated. Further increase
of the chain length of alcohol resulted in slight
Presently, the major natural source of indole is coal
tar,[32] from where it has been isolated. In the context
of the rapid depletion of fossil fuels and growing
environmental awareness, the synthesis of indole via
atom economical, environmentally benign approach
has attracted significant attention in the recent years.
increase of the yield to 81% (Table 3, Entry 7e). Next, In this context, the dehydrogenative N-
we were interested to synthesize arundine (7a)[29]
which is known as preventive for breast cancers. To
our delight, we were able to isolate arundine (7a) in
68% yield by reacting indole with MeOH.
heterocyclization of 2-aminophenethyl alcohol in
presence of various transition metal catalysts has
been reported.[33] Recently, the strategy of reducing
nitro group to the amine group via hydrogen auto-
transfer and subsequent condensation with the formed
carbonyl compounds showed their efficacy toward
the synthesis of heterocyclic compounds.[34, 10,11] Thus,
we envisioned the synthesis and functionalization of
indole in one pot via sequential de(hydrogenation)
reactions. Therefore, the scope of our catalyst to
Table 3. Substrate Scope for the synthesis of
bisindolylmethane. [a]
synthesize
indole
directly
from
2-(2-
nitrophenyl)ethan-1-ol (8a)[10] was first studied.
Scheme 2. Indole synthesis from 2-(2-nitrophenyl)ethan-1-
ol.
In order to utilize the liberated hydrogen molecule
from dehydrogenation of alcohols, we used 2-(2-
nitrophenyl)ethan-1-ol as a starting reagent to form
indole. When, 2-(2-nitrophenyl)ethan-1-ol (0.5
mmol), KOH (5 mol %), catalyst 1 (2 mol %) were
°
refluxed at 135 C for 24 h in 15 mL Ace pressure
tube, 17% indole was isolated. Inspired by our initial
effort, we were interested to study the scope and
limitaion of our protocol toward the one-pot synthesis
of C-3 alkylated indoles directly from 2-(2-
nitrophenyl)ethan-1-ol and aliphatic alcohols. On
initial trial, a mixture of 2-(2-nitrophenyl)ethan-1-ol
(0.5 mmol) and 1-hexanol (1.5 mmol) was heated in
an Ace pressure tube in the presence of catalyst 1 (2
mol %) and KOH (0.5 mmol) for 48 h. The desired 3-
hexyl-1H-indole 6d was obtained in 20% yield (Table
4, Entry 1). Interestingly, with increasing the amount
of alcohol (2.5 mmol), the yield of 6d was enhanced
to 40% (Table 4, Entry 2). The yield of 6d was
further improved to 70% just by increasing the
amount of the base (Table 4, Entry 3). Here the
excess base is required possibly to assist the multiple
oxidation and reduction steps. [11] Next, we focussed
on the effect of different bases toward the progress of
[a]
Reaction conditions: Indole (1 mmol), alcohol (0.5
mmol), catalyst 1 (0.005 mmol, 1 mol %), KOH (0.25
°
mmol), toluene (1 mL), 135 C, 18 h. [b] 0.5 mL MeOH,
Indole (2 mmol), KOH (1.5 mmol) Toluene (1 mL), 100
mL Ace pressure tube 0.5 mL EtOH, Indole (2 mmol),
Toluene (1 mL), 100 mL Ace pressure tube.
BuOH, Indole (2 mmol), Toluene (1 mL), 100 mL Ace
pressure tube.
[c]
[d]
0.5 mL
t
Our protocol also provides a route to synthesize
vibrindole A (7b)[30] in excellent yield (85%).
Vibrindole A is used to treat fibromyalgia and bowel
syndrome. Afterwards differently substituted indoles
the reaction. It was observed that bases like BuOK,
K3PO4, Cs2CO3 and K2CO3 proved incompetent for
the improvements of the yields (Table 4, Entries 5, 7,
8 & 9).
4
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10.1002/adsc.202000326
Advanced Synthesis & Catalysis
Table 4. Optimization of the reaction condition for the
synthesis of C-3 alkylated indoles from 2-(2-
nitrophenyl)ethan-1-ol and alcohols. [a]
The
reactions
between
substituted
2-(2-
nitrophenyl)ethan-1-ol and other primary alcohols has
also been studied. The representative substrates
reacted well with methanol, 1-hexanol and 1-octanol,
1-decanol (Table-5, Entries 6bb-6hh) under same
condition. Secondary alcohol like 2-octanol furnish
desired product with 35% yield (6h).
Scheme 3. C-3 alkylated indoles from 2-(2-
Aminophenyl)ethan-1-ol.
To prove that the reaction proceeds through the
formation of 2-(2-Aminophenyl)ethan-1-ol (9a), we
reacted octanol with it under the standard reaction
conditions. To our delight, the desired C-3 alkylated
indole was isolated in good yield which indicated the
involvement of 2-(2-Aminophenyl)ethan-1-ol as an
intermediate in the reaction.
[a]
Reaction conditions: 2-(2-nitrophenyl)ethan-1-ol (0.5
mmol), 1-hexanol (2.5 mmol), Cat 1 (0.01 mmol, 2 mol %)
15 mL Ace pressure tube, 135 °C, 48 h.
Next, we turned our attention to investigate the
scope and limitation of the present protocol with
respect to various aliphatic alcohols. Various primary
aliphatic alcohols responded well with 2-(2-
nitrophenyl)ethan-1-ol providing moderate to good
yield (40%-75%) (Table 5, Entries 6a-6n).
Table 5. Substrate scope for the synthesis of C-3 alkylated
indoles from 2-(2-nitrophenyl)ethan-1-ol and alcohols.[a]
Scheme 4. Competitive Reactions.
It was of interest to us to explore the reactivity and
selectivity difference between indole and 2-
substituted indole and primary and secondary alcohol
(Scheme 4). Thus, when an equimolar mixture of
indole and 2-methylindole (1 mmol) was reacted with
1-hexanol (5 mmol) in presence of 1 mol% cat 1 and
0.5 mmol base, 6d and 6p were formed in a ratio of
72:28 after 18 h. Under the similar reaction condition
when the equimolar mixture of indole and 2-methyl
indole was reacted with secondary alcohol such as 2-
hexanol, 6h was obtained in 84% yield whereas no
6ab was isolated. Thus, in the competitive C-3
alkylation, 2-methylindole reacts slower. Next, we
[a]
Reaction conditions: 2-(2-nitrophenyl)ethan-1-ol (0.5
mmol), 1-hexanol (2.5 mmol), catalyst 1 (0.01 mmol, 2
mol %), KOH (1 mmol), 15 mL Ace pressure tube, 135 °C,
48 h. [b] 1 mL alcohol. [c] 72 h.
5
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10.1002/adsc.202000326
Advanced Synthesis & Catalysis
Conclusion
thought to examine the scope of our protocol to
synthesize unsymmetrical bis(indolyl)methanes [35] by
reacting 1:1 mixture of indole and 1-methylindole
with benzyl alcohol. However, exclusively
symmetrical bis(indolyl)methanes 7l was isolated in
85% yield.
In summary, we have developed an acridine-derived
air-stable ruthenium pincer complex catalysed C-3
alkylation of indoles with alcohols. A highly atom
economical and environmentally benign “borrowing
hydrogen” strategy was applied to activate a wide
range of primary and secondary aliphatic alcohols for
the synthesis of several C-3 alkylated indoles.
Interestingly, we are also able to construct selectively
bis(indolyl)methane scaffold from the same set of
alcohols and indoles just by tuning the reaction
conditions. The present protocol is successfully
applied to synthesize different structurally important
compounds such as arundine, vibrindole A and
tryptamine based alkaloid derivatives. Furthermore,
we demonstrated the first ruthenium catalysed one-
pot synthesis of C-3 alkylated indole directly from 2-
(2-nitrophenyl)ethan-1-ol and primary alcohol via
sequential multistep reaction.
To shed light on the proposed mechanistic pathway,
we performed some control experiments (Scheme 5).
During the synthesis of C-3 alkylated indole, the
corresponding aldehyde is detected which indicates
the dehydrogenation of the alcohol under the reaction
conditions. Then, we wanted to investigate the
hydrogenation step of unsaturated imine
(vinylogous imine). Thus, indole was reacted with a
mixture of benzaldehyde and 4-methoxybenzyl
alcohol under the optimized reaction condition. 3,3'-
(Phenylmethylene)bis(1H-indole) 7l was obtained
exclusively (85%) and no 3-benzylated indole was
observed. This suggested that the rate of formation of
3,3'-(phenylmethylene)bis(1H-indole) from indole
and aldehyde is much faster than the dehydrogenation.
Hence, vinylogous imine converted completely to the Experimental Section
bisindolylmethane before the generation of
a
General procedure for C-3 alkylation of indoles:
sufficient amount of H2. Then, we reacted indole with
octanal/benzaldehyde under H2 pressure. We
observed the formation of C-3 alkylated indole
together with bisindolylmethane. Interestingly, the
hydrogenation of aldehyde to the corresponding
alcohol was also observed. These results suggested
that the developed catalyst is capable of
dehydrogenating alcohol and also can hydrogenate
aldehyde under H2 pressure. In the C-3 alkylation
reaction, the formed aldehyde is immediately
captured by the indole to form vinylogous imine,
which is only available for hydrogenation to give the
desired C-3 alkylated indole. These results strongly
allowed us to hypothesize that the slow generation of
aldehyde and its coordination to the complex might
be the key factor to get the good yield of the desired
product in the C-3 alkylation reaction of indole.
Indole (1 mmol), alcohol (5 mmol), complex 1 (7.6 mg,
0.01 mmol), and KOH (28 mg, 0.5 mmol) were placed in a
30 mL Ace pressure tube under argon atmosphere. The
tube was sealed with screw cap and then it was immersed
°
in an oil bath at 135 C and stirred at this temperature for
18 h. After that, the reaction mixture was cooled to room
temperature, diluted with dichloromethane, and filtered
over a plug of celite. The solvent was evaporated under
reduced pressure and the residue obtained was purified by
column chromatography (Hexane:Ethylacetate 50:1) on
silica gel to afford the desired product.
General procedure for synthesis of bisindolylmethane
from indoles and alcohols:
Indole (1 mmol), alcohol (0.5 mmol), complex 1 (3.8 mg,
0.005 mmol), and KOH (14 mg, 0.25 mmol) were placed
in a 2-neckd round bottom flask fitted with a coil
condenser in argon atmosphere and added 1 mL toluene.
°
Then, the reaction was refluxed for 18 h at 135 C. After
that, the reaction mixture was filtered through celite and
the purification of the crude product was done by column
chromatography using 10% ethylacetate in hexane.
General procedure for one-pot synthesis of substituted
indoles from 2-(2-nitrophenyl)ethan-1-ol and alcohols:
2-(2-nitrophenyl)ethan-1-ol (0.5 mmol), alcohol (2.5
mmol), complex 1 (7.6 mg, 0.01), and KOH (28 mg, 0.5
mmol) were placed in a 15 mL Ace pressure tube under
argon atmosphere. The tube was sealed with screw cap and
°
then it was immersed in an oil bath at 135 C and stirred at
this temperature for 48 h. After that, the reaction mixture
was cooled to room temperature, diluted with
dichloromethane and filtered over a plug of celite. The
solvent was evaporated under reduced pressure and the
residue obtained was purified by flash chromatography
(Hexane:Ethylacetate 50:1).
Acknowledgements
Scheme 5. Control experiments
We would like to thank SERB, DST (ECR/2016/000108) and
DST-INSPIRE (IFA-14-CH-143) for the financial support. We
6
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10.1002/adsc.202000326
Advanced Synthesis & Catalysis
are also thankful to the CIF and the Department of Chemistry,
IIT-Guwahati, for the instrumental facilities, infrastructural
support and startup grant. N. B. and R. S. thank the institute for
their fellowship
Angew. Chem. Int. Ed. 2018, 130, 6274-6278; e) S.
Elangovan, J. Neumann, J. B. Sortais, K. Junge, C.
Darcel, M. Beller, Nat. Commun. 2016, 7, 1-8; f) F.
Huang, Z. Liu, Z. Yu, Angew. Chem. Int. Ed. 2016, 55,
862-875; g) B. G. Berendt, K. Polidano, L. C. Morrill,
Org. Biomol. Chem. 2019, 17, 1595-1607; h) L. Alig,
M. Fritz, S. Schneider, Chem. Rev. 2019, 119, 2681-
2751; i) T. Irrgang, R. Kempe, Chem. Rev. 2019, 119,
2524-2549; j) A. Quintard, J. Rodriguez,
ChemSusChem 2016, 9, 28-30; k) A. J. A. Watson, J.
M. J. Williams, Science 2010, 329, 635-636; l) B. Paul,
M. Maji, K. Chakrabarti, S. Kundu, Org. Biomol. Chem.
2020, 18, 2193-2214.
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Advanced Synthesis & Catalysis
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8
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FULL PAPER
Ruthenium Pincer Catalyzed Selective Synthesis of
C-3 Alkylated Indoles and Bisindolylmethanes
Directly from Indoles and Alcohols
Adv. Synth. Catal. Year, Volume, Page – Page
Nandita Biswasa, Rahul Sharmaa and Dipankar
Srimania,*
9
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