Cross dehydrogenative coupling of: N -aryltetrahydroisoquinolines (sp3 C-H) with indoles (sp2 C-H) using a heterogeneous mesoporous manganese oxide catalyst

Article abstract of DOI:10.1039/c7gc01919j

We disclose a novel, heterogeneous catalytic approach for selective coupling of C1 of N-aryltetrahydroisoquinolines with C3 of indoles in the presence of mesoporous manganese oxides. Our work involves a detailed mechanistic investigation of the reaction on the catalyst surface, backed by DFT computational studies, to understand the superior catalytic activity of manganese oxides.

Full text of DOI:10.1039/c7gc01919j

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Cross Dehydrogenative Coupling of N-Aryltetrahydroisoquinolines
3
2
(
sp C-H) with Indoles (sp C-H) Using Heterogeneous Mesoporous
Manganese Oxide Catalyst
Received 26rd June 2017
a
b
a
c
a
a
a
a
B. Dutta, V. Sharma, N. Sassu, Y. Dang, C. Weerakkody, J. Macharia, R. Miao, A. R. Howell,
a, c, *
and S. L. Suib.
www.rsc.org/
3
2
We disclose a novel, heterogeneous catalytic approach for isoquinoline. Some metal free CDCs have also been reported using
t
28,33
bases (KO Bu), Grignard reagents, and hypervalent iodines.
selective coupling of C1 of N-aryltetrahydroisoquinolines with C3
of indoles in the presence of mesoporous manganese oxides. Our
work involves a detailed mechanistic investigation of the reaction
on the catalyst surface, backed by the DFT computational studies,
to understanding the superior catalytic activity of manganese
oxides.
Despite being inter-
Previous works
Metal ligand/ salt catalyst
TBHP, heat
N
R
+
V O (10 mol%)
2
5
N
, 24 h, 100 oC, ref 26
N
O
2
R
H
NH
Introduction
Meso-MnOx-550
This work
Air balloon, 5 h, 100 oC,
C-H bond activation reactions are currently under focus due to their
applications for the formation of C-C bonds in the synthesis of
complex natural products and pharmaceuticals. Conventionally, C-
1
Scheme 1. Catalytic routes for oxidative dehydrogenative coupling of indoles with
tetrahydroisoquinoline.
2
C bond formation required functional group handles. In recent
years, interest has grown in oxidative cross-coupling reactions, also
known as cross-dehydrogenative coupling (CDC). The properties
which make the cross- dehydrogenative coupling (CDC) reactions
-
esting, these procedures lack operational simplicity and
environmental friendliness. Moreover, none of the procedures
claimed to be completely heterogeneous except the system using
Fe(terpy)/TBHP, which however is industrially infeasible due to the
aggregation of active sites. These existing systems mostly suffer
from the a) use of toxic catalysts or oxidants, b) poor selectivity due
to formation of by-products, c) use of bases or air sensitive Grignard
reagents, d) operational complexity, and e) poor reusability of the
3
–5
popular are their i) ‘atom economy’ ii) prior activation or leaving
2
group free chemistry, and iii) cost-effective procedures. Moreover,
6
,7
2
many CDCs have only water as the by-product. Direct CDC of sp -
3
sp is recently gaining interest due to their prevalence in natural
8
products.
2
Among numerous substrates that can be exploited for C-C (sp - catalysts. Therefore, the development of an i) efficient, ii) base /
sp ) coupling reactions using CDC, amines are most popular.
3
9
additive free, iii) non-toxic, iv) reusable and v) cost effective
Amines, in particular N-aryltetrahydroisoquinolines and indoles, catalytic system is required to meet the measures of green
3
4
have been used the most by different research groups due to their chemistry. To the best of our knowledge, no catalyst having all
1
0,11
abundance and their prevalence in natural products.
studies by Murahashi and Li,
Pioneering these properties together has been reported to date.
led to the development of
In recent years, transition metal-based catalytic processes have
interesting procedures which include the discovery of different gained significant attention for the synthesis of small organic
1
2
8,13
14
14
14–18
35
catalysts, oxidants, and nucleophiles.
In multiple studies, molecules. We have previously reported highly efficient methods
and TBHP
or DTBP as oxidants. Studies have been reported to use different manganese oxides,
8,9,19–25
8,26,20,21,27
toxic Cu or Fe salts were used as catalysts
to synthesize amines and azo compounds using mesoporous
28
36,37
synthesized by an inverse micelle assembled
29
27
38
catalytic systems, such as PtCl
2
/molecular sieves, NaAuCl
4
/TBHP,
soft templated method. Versatile structural forms with high
30
31
,
Ru porphyrin/ TBHP,
V
2
O
5
/O
2
SBA-15 supported Fe(terpy)/ thermal stability and redox cycling of manganese (Mn) have been
and phosphoric acid on dearomatic arylation of found to influence the catalytic and oxidizing properties of these
materials, respectively. Intrigued by these findings, we explored
20
39 36
TBHP,
their scope in CDC of N-aryltetrahydroisoquinolines with indoles.
Herein, we demonstrate a facile, additive, and toxic catalyst free,
highly selective CDC between the C1 of N-
a
Department of Chemistry, University of Connecticut, Storrs, CT 06279 (USA).
b
Material Science and Technology Division, Oak Ridge National Laboratory, Oak
Ridge, TN 37831 (USA)
aryltetrahydroisoquinolines and C3 of indoles using reusable meso-
MnOx as catalyst. This is the first catalytic process to satisfy all
measures of green chemistry and can compete with the
c
Institute of Materials Science, University of Connecticut, U-3060, 55 North Eagleville
Rd., Storrs, Connecticut 06269 (USA).
34
selectivity, efficiency and cost of existing systems.
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Most procedures reported to date used i) oxidizing agents, such from air or O to N (Table S3, entry 1, 4, 5). This demonstrates the
2
2
as TBHP, DTBP, and ii) toxic Cu(II)-Cu(I) chemistry, to form an importance of oxygen for the reaction. The selectivity dropped from
intermediate (iminium ion) which couples with indoles. Therefore, > 99 % to 76 % in the presence of peroxides (H O and TBHP),
2
2
the use of manganese oxide (MnOx), known for oxidative probably due to the formation of amine-peroxide by-product (Table
3
7,40
dehydrogenative catalysis,
could be a better option to replace S3, entry 2, 3). A similar oxidation of amines was observed under a
existing environmentally hazardous protocols. A comparative study high pressure oxygen atmosphere, which severely impacted the
of different phases of manganese oxide (Table 1), performed on a selectivity of the coupling reaction (Table S3, entry 6, 7). Solvent
model reaction between N-phenyltetrahydroisoquinoline (1a) (N- selection (Table S4, entry 1-5) and concentration (Table S5, entry 1-
Ph-THIQ) and indole, revealed meso-MnOx-550 as the best catalyst 6) were optimized, where 0.25 mL of toluene (Table S5, entry 2)
with 42% conversion (Table 1, entry 7). Thus, subsequent studies emerged as the best solvent system for the reaction. Finally, the
were continued with meso-MnOx-550 which has a spherical optimized ratio (1 to 1.2 equivalent) of 1a and Indole (2a) (Table S6,
morphology, and crystalline Mn
2 3
O phase (as revealed by the XRD, entry 4) was assessed prior to conducting experiments with
SEM and HR-TEM data, Table S2, Figure S2) with BET surface area of different catalyst loading. A continual increase in conversion with
2
7
1 m /g (Table S2, Figure S3, a) and mesoporous size distribution catalyst loading (Figure S4), indicates the independence of this
4
1
(
pore diameter 6.6 nm) (Table S2, Figure S3, b).
protocol from mass transfer and adsorption. Therefore, after
screening the reaction parameters, the optimum conditions for CDC
of 0.25 mmol of N-phenyltetrahydroisoquinoline were determined
to be 25 mg of meso-MnOx-550 catalyst in 0.25 mL of toluene at
Commercially available Mn O (c- Mn O ) (surface area 11 m2/g)
2
3
2 3
(Table 1, entry 9) and amorphous manganese oxide (AMO) (Table 1,
entry 10) yielded only 23 % and 32 %, respectively, probably due to
the lack of lattice oxygen, required active sites, and high surface
area. Mn rich Mn(III) acetate, which lacked only labile lattice
oxygens and high surface area (Table 1, entry 11), produced only 13
1
00 °C and an indole to N-phenyltetrahydroisoquinoline (1a) ratio
3
+
of 1.2 equivalents with the reaction conducted under an air balloon.
Further investigations were continued under the optimized reaction
conditions.
%
conversion, while no reaction occurred in the absence of catalyst
(Table 1, entry 12). These results suggest a probable combination of
properties—high surface area, lattice oxygen and active sites— Table 2. Cross coupling of N-Phenyltetrahydroisoquinolines (1a) with differently
a
substituted indole derivatives in presence of meso-MnOx catalyst.
required for the reaction.
Table 1. Aerobic oxidative cross-coupling of N-phenyltetrahydroisoquinoline with
a
indole in presence of different catalysts.
c
Entry Indole
Conversion (%) Selectivity (%) TOF
b
b
-
1
(
h )
d
j
1
2
3
4
5
6
.
.
.
.
.
.
indole (2a)
6-Cl (2b)
98
80
71
78
>99 (3aa) (89)
>99 (3ab) (72)
>99 (3ac)
0.30
0.07
0.09
0.10
0.06
0.05
b
b
c
Entry Catalyst
Conversion (%)
Selectivity (%)
TOF
e
j
-
1
(
h )
f
2-Me (2c)
5-Me (2d)
d
1
.
.
MnOx-150
MnOx-250
MnOx-350
MnOx-450
MnOx-450
MnOx-450
MnOx-550
MnOx-650
17
26
35
39
30
37
42
42
32
23
> 99
> 99
> 99
> 99
76
0.09
0.14
0.18
0.20
0.16
0.19
0.22
0.22
0.17
0.12
f
j
>99 (3ad) (72)
>99 (3ae)
d
2
f, i
g, i
5-OMe (2e) 89
d
d
3
.
.
5-COOMe
2f)
35
>99 (3af)
4
(
d, e
d, f
d
g, i
h
5.
6.
7.
8.
9.
1
1
7.
8.
N-Me (2g)
53
98
>99 (3ag)
0.07
0.51
j
> 99
> 99
> 99
> 99
> 99
7-NO (2h)
2
>99 (3ah) (91)
a
Reaction conditions: amine derivative (0.25 mmol), indole derivative (1.2 eqv.),
b
d
100 °C, 0.25 mL toluene, 25 mg catalyst.
determined by GC-MS. TOF= TON/ hours, TON = no of moles of amine derivative
converted to the product per mole of catalyst. 5 h. 18 h, 12 h, 24 h, 3 h, 50 mg
Conversions and selectivities were
c
d
e
f
g
h
i
C-Mn
AMO
2 3
O
j
catalyst. numbers in parenthesis represents the isolated yields the products
.
0.
1.
g
Mn(III)
acetate
To explore the generalizability of our protocol, we evaluated its
scope in the presence of different N-arylltetrahydroisoquinolines
and indoles. Under optimized reaction conditions, N-
phenyltetrahydroisoquinoline (1a) and indole derivatives with
electron-rich (Table 2, entry 3-5, 7) and electron-deficient (Table 2,
1
0
3
> 99
0
0.07
N/A
1
2.
no
a
Reaction conditions: N-phenyltetrahydroisoquinoline (0.25 mmol), indole (1.2 eqv.)
°
b
toluene (0.5 mL), 25 mg of catalyst, 100 C, 3 h. Conversions and selectivities were
c
determined by GC-MS. TOF= TON/ hours, TON = no of moles of limiting reagent entry 2, 6, 8) groups responded well and produced corresponding C-
d
e
f
converted to product per mole of catalyst. Mesoporous catalyst, TBHP (1.5 eqv.),
C coupled products with moderate (53- 71 %) to high (78-98 %)
conversion and excellent selectivity (>99 %). The result with 6-
chloroindole (2b) (Table 2, entry 2) is noteworthy. It is common for
g
3 2
toluene (1 mL), Mn(OAc) ·2H O (85 mg, 0.16 mmol).
While investigating the effect of oxidants, their impact on both such systems to undergo dehalogenation in the presence of
4
2
conversion and selectivity was discovered. A sharp drop in heterogeneous catalysts. . In the case of an ester-substituted
conversion was noted as the reaction atmosphere was switched indole (5-COOMe-indole), a maximum of 35 % yield (Table 2, entry
2
| J. Name., 2012, 00, 1-3
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7) was obtained, probably due to steric hindrance. N-Methylindole significantly (Table 3, entry 16), while the electron-rich aryl rings
(2g) yielded only 53 %; again, it is likely that steric hindrance played accelerated the rate (Table 3, entry 1, 9).
a role.
The excellent activity of the catalyst for coupling 1a with
differently substituted indoles spurred us to investigate the effect
of different N-substituted tetrahydroisoquinolines with indole
derivatives. Superb reactivity was seen for electron rich N-aryl
groups (N-(4-Me-Ph)-tetrahydroisoquinoline (1b) (Table 3, entry 1-
Although the experiments described above demonstrate the
presence of an iminium ion intermediate, they do not rule out
radical intermediates. More experiments were conducted to
explore this possibility.
methylphenol) was used to potentially couple with radical species
that might be present. reaction containing 1,2,3,4-
A radical trap (2,6-di-tert-butyl-4-
A
7) and N-(4-OMe-Ph)-tetrahydroisoquinoline (1c) (Table 3, entry 8-
tetrahydroisoquinoline, indole and the radical trap yielded an
adduct of the trap and the amine (based on the mass spectra,
Figure S12, c) instead of a C-C coupled product (Figure S12, b). This
is consistent with the presence of a radical intermediate B (Scheme
13)), while sluggish rates of reaction were observed with an
electron
withdrawing
N-aryl
group
(N-(4-NO -Ph)-
2
tetrahydroisoquinoline (1d) (Table 3, entry 14-17)). Depending on
the amine and indole precursors used, reaction conditions were
modified in several instances to optimize conversion (70 % to as
high as 98 %) and selectivity (> 99 %). Taken together, the results
demonstrate the broad utility of our protocol.
2
). However, N-phenyltetrahydroisoquinoline failed to form the
coupled product with the trap, probably due to steric hindrance of
bulky groups (Figure S12, a).
To determine if the observed catalysis was resulting from leached
active sites, the solid catalyst was separated from the reaction
mixture by filtration after 3 h (at about 42 % conversion). The
filtrate was then stirred under the optimized reaction conditions for
Table 3. Cross coupling of differently substituted N-aryltetrahydroisoquinolines with
different in presence of meso-MnOx catalyst.
a
5
more hours. Aliquots collected after each hour were analyzed by
GC-MS to track the progress of the reaction. No further increase in
GC-MS yield after the first 3 hours (Figure S5), indicated the
absence of leached active species in the solvent. For a more
convincing result, the filtrate was analyzed by inductively coupled
plasma mass spectrometry (ICP-MS), where the manganese (Mn)
was found in very low amount (165 ppm). To evaluate the
reusability of the catalyst, separated (>90 % by filtration) catalyst
was washed with toluene and ethanol to remove adsorbed organic
compounds prior to reactivating at 250 °C for 1 hour. A similar
1
2
d
Entry
R
R
Conversion Selectivity
TOF
c
c
(
%)
(%)
e
1
2
3
.
.
.
1b indole (2a)
6-Cl (2b)
83
87
87
85
>99 (3ba)
>99 (3bb)
>99 (3bc)
>99 (3bd)
>99 (3be)
>99 (3bg)
0.08
f
0
0
0
0
0
.06
.11
.11
.05
.05
e
e
f
2-Me (2c)
approach was followed to recycle the catalyst after every cycle. 4.
Retrieved catalysts were successfully reused for three more cycles
with a drop of activity of only 14 % (Figure S6).
5-Me (2d)
5
6
7
.
.
.
5-OMe (2e) 75
f
N-Me (2g)
7-NO (2h)
77
96
Kinetic studies (Figure S7) revealed a first order rate equation
e
(
0
Figure S9) with respect to the amine (1a), having a rate constant of
2
>99
(3bh)
m
-1
(
88)
>99 (3ca)
>99 (3cc)
.24 h . Similar time-dependent studies were conducted at
0.12
°
°
°
h
h
different temperatures (25 C, 50 C and 75 C) to determine the 8.
1c
indole (2a)
2-Me (2c)
83
94
0
.22
a
apparent activation energy (E ) as 21.12 KJ/mol, from an Arrhenius
plot (Figure S10).
9
.
m
(
84)
0
0
0
0
.24
.09
.10
.11
To explore in more depth the reaction kinetics, a time-
dependent reaction was performed between N-
phenyltetrahydroisoquinoline (1a) and indole (2a) (Figure S7). 11.
Interestingly, an intermediate with a mass one-unit lower than 1a
was tracked in the kinetic profile along with the expected coupled
product (3aa) and unreacted substrates. That intermediate
disappeared by the end of the reaction (Figure S7). To determine 14.
the nature of the intermediate, another time-dependent study was
executed in the presence of 1,2,3,4-tetrahydroisoquinoline and
indole (2a) under similar reaction conditions. Formation of the
e
1
0.
5-Me (2d)
71
>99 (3cd)
>99 (3ce)
>99 (3cg)
>99 (3ch)
> 99 (3da)
> 99 (3dc)
> 99 (3dd)
> 99 (3dg)
e
5-OMe (2e) 88
e
1
1
2.
3.
N-Me (2g)
7-NO (2h)
87
72
28
78
55
86
i
2
0.12
j, k
j, k
j, k
f
1d indole (2a)
2-Me (2c)
0
0
.01
.02
1
1
5.
6.
5-Me (2d)
0.01
.03
corresponding C-C coupled product with a lower rate of reaction 17.
Figure S8) is consistent with the presence of charged
N-Me (2g)
0
(
a
a
Reaction conditions: amine derivative (0.25 mmol), indole derivative (1.2 eqv.),
00 °C, 0.25 mL toluene, 25 mg catalyst. 1b = 4-Me-Ph; 1c = 4-OMe-Ph; 1d = 4-NO
Conversions and selectivities were determined by GC-MS. TOF = TON/ hours, TON =
intermediate (see Scheme 2, D), which was further supported by
the reaction kinetics of its neutral counterpart (Figure S14). The
charge on nitrogen can be stabilized by the N-substituted aryl ring
b
1
2
-Ph.
c
d
e
f
no of moles of amine derivative converted to product per mole of catalyst. 12 h. 24 h,
g
h
i
j
k
m
1
8 h, 6 h, 30 h, 36 h, 50 mg catalyst. numbers in parenthesis represents the
(depending on the electronic nature of the aryl ring), which would
isolated yields the products.
enhance the coupling rate. A significant decrease of turnover
frequency (TOF) upon changing electron rich (4-Me-Ph (1b) and 4-
Combining the evidence, we propose a mechanism, shown in
Scheme 2, for this meso-MnOx CDC. We assume the formation of
radical intermediate B is driven by the reduction potential of
manganese and that the active species removes an electron from
2
OMe-Ph (1c)) groups with an electron deficient 4-NO -Ph (1d) group
suggested the presence of a positive charge on the intermediate.
The electron-deficient aryl ring also lowered the rate of reaction
3
7
the lone pair on the nitrogen. Reduction of surface active
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manganese is known to simultaneously release labile lattice oxygen 10). This indicated a role for aerobic oxygens in catalyzing these
4
3
molecules due to structural changes. Based on prior studies we reactions. The lower conversions that were observed for reactions
4
5
believe these lattice oxygens deprotonate B to form intermediate C. under nitrogen, were presumably due to existing lattice oxygens.
Loss of an electron transforms C to D which is a stable intermediate The increased efficiency under aerobic conditions supports the
which was tracked in minute amounts by GC-MS analysis (Figure theory of a collected contribution from aerobic and lattice
4
5
S7). This intermediate (D) was reacted with indole to form the oxygens. The increase of conversion under nitrogen with
intermediate F, which after the subsequent loss of a proton calcination temperatures was probably due to the increasing
produced the expected product G. The released lattice oxygen accessibility of the labile lattice oxygens (Table S8, entry 2, 5, 8, 11).
combines with the protons and electrons over the course of the Experiments to compare the reusability of all materials (Table S8,
reaction to produce water as a by-product.
entries 3 (vs 1), 6 (vs 4), 9 (vs 7), 12 (vs 10)) showed that reusability
increased with calcination temperature. This may be due to the
improved oxygen mobility. The ease of replenishing oxygen
vacancies increased with calcination temperature. The decreasing
distance between reduction peaks (Figure S15) reflects the
The increase in conversion (Table 1) with the increment of
calcination temperature (from 250 to 650 °C) prompted us to
investigate the chemistry behind the efficiency of manganese
oxides during the reaction. Significantly, the amount of Mn , as
revealed by X-ray photoelectron spectroscopic (XPS) analysis,
increased with calcination temperatures (Table S1). This led us to
3
+
3
+
2+
2+
3+
increasingly facile transformation of Mn to Mn and Mn to Mn ,
preserving its catalytic properties. This comparison of results of
each material under air and nitrogen and of first reuse shows
3
+
presume
a
correlation between the amount of Mn
and
3
+
2+
3
+
2+
agreement with the feasibility of Mn to Mn transformation and
the availability of lattice oxygens with increased calcination
temperatures.
conversion. The facile transformation of Mn to Mn probably
drove the reaction forward with increasing efficiency. To support
2
this, H -TPR (temperature programmed reduction) studies were
performed on the meso-MnOx materials; these exposed a two-step
Density functional theory calculations were performed with a
followed by frozen core projector augmented wave method as implemented in
Vienna Ab-Initio Simulation Package (VASP) code, to further
3
+
2+
2 3 3 4
reduction process of Mn to Mn (Mn O to Mn O
4
4
3 4
Mn O to MnO) (Figure S15).
validate our proposed reaction mechanism. Exchange and
Interestingly, the two reduction peaks were observed to shift
closer to each other with rising calcination temperatures and
eventually merged at 650 °C. This indicates a high probability of an
correlation interactions were treated using a generalized gradient
approximation with the Perdew-Burke-Ernzerhof (PBE) function. To
expand the crystal wave functions, a plane wave basis cutoff of 400
eV was used. In addition, to estimate the Mn oxidation states, DFT
calculations were carried out on mesoporous manganese oxides
(meso-MnOx).
3
+
2+
Mn to Mn transformation, which probably facilitated the first
Scheme 2, A to B) and third C to D (Scheme 2) steps of the
reaction. As mentioned above, the lattice oxygens released during
(
3
+
2+
the Mn to Mn transformation are believed to deprotonate the
intermediates (B and F) and catalyze the reaction. Thus, increased
3
+
2+
transformation of Mn to Mn may enhance the release of lattice
oxygens and, hence, the reaction rate, as deprotonations are
considered to be more energy demanding than electron
5
Path A-D
Path E-G
C
G
D
3
7
abstractions. The growth of the lattice oxygen content (Table S1)
with increasing calcination temperatures led us to design a
comparative study to probe the enhanced accessibility of the lattice
oxygens.
F
E
A
0
B
Figure 1. Energy profile of the reaction in the gas phase, as
determined by DFT calculations.
N
Ph
N
O
2
(air)
C
Ph
3+
Energy profiles for the C-C coupling reaction are shown in Figure
1. The energy corresponding to A was the reference energy. Under
optimized conditions, the scope of the coupling reaction for the
most feasible mechanism was investigated. The relative energies
(Kcal.mol ) are based on the summations of the representative
total energies (Etotal) of all species.
A
H
2
Mn
NH
Mn2+
G
N
H
Mn3+
Mn2+
Ph
N
-1
B
C
Ph
N
H
2
2
O (lattice)
F
+
-
RDS
H+
4
H
+
2
e
-
Mn3+
2
H
2
O
The reaction energy profiles shown in Figure 1 suggest that the
RDS
H+
3
+
-
steps A to B and C to D, where Mn abstracts electrons to form
E
N
N
C
Mn2+
Ph
2+
HN
D
Ph Mn2+
Mn3+
C
H
Mn , are energetically more favorable. The steps B to C and F to G,
which involve proton abstraction by lattice oxygens, are
energetically unfavorable. The possibility of intermediate C’ could
be neglected due to its higher relaxed energy (135.62 kcal/mol)
than the intermediate C (76.69 kcal/mol). As per our DFT
calculations, step F to G is energetically more favorable, probably
due to the energy of aromatization, than B to C. This makes B to C
the rate-determining step, which was supported by a primary
N
C
Ph
C'
H
Scheme 2: The proposed reaction mechanism.
A set of experiments was performed under nitrogen and air for
each material to identify the role of different available oxygens. The
reactions performed under a nitrogen atmosphere (Table S8, entry
H D
kinetic isotope effect (K /K = 2.49, Figure S10). DFT computation
based Bader charge analysis supports that, for intermediate B, the
2
, 5, 8, 11), showed a dramatic drop in product formation compared
to reaction run under aerobic conditions (Table S8, entry 1, 4, 7,
4
| J. Name., 2012, 00, 1-3
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Pleas Ge rdeo e nn o Ct ah de j mu si ts mt r ya rgins
View Article Online
DOI: 10.1039/C7GC01919J
Journal Name
COMMUNICATION
3
+
2+
active Mn species was reduced to Mn with a calculated charge 18
of 2.12 e- on Mn.
C. Huo, C. Wang, M. Wu, X. Jia, X. Wang, Y. Yuan and H. Xie,
Org. Biomol. Chem., 2014, 12, 3123–3128.
In conclusion, a unique noble metal free, non-toxic, reusable, 19
and cost-effective catalytic protocol has been developed to couple 20
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various N-aryltetrahydroisoquinolines (sp C-H) and Indoles (sp C-
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manganese oxides. The use of air and manganese oxides as the
oxidants make our protocol interesting and appealing as compared
to the other reported systems. The mechanistic investigation led by
experimental evidence and DFT computations validated the
proposed mechanism. Studies showed the efficiency of manganese
oxides and their role in the mechanism. Research to apply our
protocol to other types of C-C coupling reactions is underway.
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2
2
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S.L.S. is grateful for support from the US Department of Energy,
Office of Basic Energy Sciences, Division of Chemical, Biological and
Geological Sciences under Grant DE-FG02-86ER13622.A000.
VS and FAR are supported by the U.S. Department of Energy, Office
of Science, Basic Energy Sciences, Materials Sciences and
Engineering Division. VS acknowledges the XSEDE computational
resource allocation number TG-DMR160051.
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