Catalyst-Controlled Chemodivergent Annulation to Indolo/Pyrrolo-Fused Diazepine and Quinoxaline

Article abstract of DOI:10.1002/adsc.201900088

Catalyst-controlled chemodivergent annulation between o-indolo anilines and diazo compounds has explored for the synthesis of indolo-fused diazepine and quinoxaline. Under the Rh(III) catalyst, reaction proceeded through the free amine assisted C2?H activation followed by amidation leading to the diazepino[1,7-a]indole in a highly selective manner. While with Ru(II) catalyst, reaction involves formation Ru?carbene complex followed by ?NH₂ group insertion and cascade cyclization via metallo-ene type reaction, β-hydride elimination to furnish the indolo[1,2-a]quinoxaline as the predominating product. This strategy directs modular approach towards the construction of unique indolo-fused diazepine/quinoxaline as well as pyrrolo-fused diazepine/quinoxaline scaffolds in excellent yields. (Figure presented.).

Full text of DOI:10.1002/adsc.201900088

Title: Catalyst-Controlled Chemodivergent Annulation to Indolo/
Pyrrolo-Fused Diazepine and Quinoxaline
Authors: SANDIP DHOLE, Wei-Jung Chiu, and Chung-Ming Sun
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Catalyst-Controlled Chemodivergent Annulation to Indolo/
Pyrrolo-Fused Diazepine and Quinoxaline
Sandip Dhole,a,c Wei-Jung Chiu,a Chung-Ming Suna,b*
a
Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300-10, Taiwan, ROC
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, 100, Shih-Chuan 1st Road,
b
Kaohsiung 807-08, Taiwan, ROC
Department of Chemistry, Chandmal Tarachand Bora College, University of Pune, Maharashtra 412210, India.
c
Email: cmsun@nctu.edu.tw
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. Catalyst-controlled chemodivergent annulation quinoxaline as the predominating product. This strategy
between o-indolo anilines and diazo compounds has directs modular approach towards the construction of
explored for the synthesis of indolo-fused diazepine and unique indolo-fused diazepine/quinoxaline as well as
quinoxaline. Under the Rh(III) catalyst, reaction proceeded pyrrolo-fused diazepine/quinoxaline scaffolds in excellent
through the free amine assisted C2-H activation followed by yields.
amidation leading to the diazepino[1,7-a]indole in a highly
selective manner. While with Ru(II) catalyst, reaction
involves formation Ru-carbene complex followed by –NH2
group insertion and cascade cyclization via metallo-ene type
reaction, β-hydride elimination to furnish the indolo[1,2-a]
Keywords:
Annulation;
Quinoxaline.
Catalyst-controlled;
Indolo/Pyrrolo-Fused
Chemodivergent
Diazepine and
Figure 1. Biological important indole/pyrrole-fused
Introduction
diazepine and quinoxaline derivatives.
Indole and Pyrrole are the most abundant
heterocycles in natural products with valuable and
Accordingly, substantial attention focuses on the
construction of these fused heterocyclic architectures.
Nevertheless, there are few methods reported for the
synthesis of these uncommon heterocycles (Scheme
1). For example, Ohta reported one step synthesis of
indole-fused benzo-1,4-diazepines through Cu(I)
catalyzed domino three component cyclization of 2-
diverse
biological
properties.[1]
Especially,
indole/pyrrole tethered to other heterocycles such as
diazepine and quinoxaline are often considered as
important privileged scaffolds in drug discovery. For
examples, benzo][1,4]diazepino[1,7-a]indole (I) have
the anti-HCV activity,[2a] whereas diazepino-fused
pyrrole Laxivaptan (II) show anti-diuretic activity.[2b]
ethynylanilines
with
o-bromobenzylamines.[4a]
Likewise,
substituted
indolo/pyrrolo[1,2-
Mangette described the multistep synthesis of
a]quinoxalines at C-4 position (III, IV, and V)
exhibit antifungal[3a], anti-HIV[3b], and anti-secretory
[3c] activities (Figure 1).
indolo/pyrrolodiazepines
via
Cu
catalyzed
intramolecular
N-arylation.[4b]
Subsequently,
2
Srinivasulu described the SN -CuI catalyzed
annulation
benzo[6,7][1,4]diazepino[1,2-a]indole.[4c] A classical
method to synthesize indolo/pyrrolo-fused
for
the
synthesis
of
quinoxaline involves Pictet–Spengler reaction of
ortho-indolyl/pyrrolyl anilines with carbonyl
compounds.[5]
Yu
and
Patil
synthesized
by cascade
indolo/pyrrole[1,2-a]quinoxaline
hydroamination/hydroarylation
of
the
o-
indolo/pyrrolo anilines with terminal alkynes by
various metal catalysts.[6a-b] In 2011, Liu group
reported Au(I) catalyzed hydroamination and
hydroarylation of o-indolo/pyrrolo anilines with
internal alkyne to synthesize the indolo/pyrrolo[1,2-
a] quinoxalines.[6c] Xiao achieved indolo-fused
1
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
Results and Discussion
quinoxalines through Pd(II) catalyzed regioselective
C-H olefination, and cyclization of o-indolo aniline
with electron-withdrawing olefins.[6d] Although
aforementioned methods are encouraging, it is still
highly demand to employ the new straightforward
C−H activation strategy to access indolo/pyrrolo-
fused diazepine and quinoxaline scaffolds with
different substitution patterns.
We first used 2-(1H-indol-1-yl) aniline 1a as a
model substrate and diethyl diazomalonate 2a as a
coupling partner. In the presence of [Cp*RhCl2]2 (2.5
mol %)/AgSbF6 (20 mol %) catalyst and AcOH (2.5
equiv.) in EtOH at 60 °C for 1 h, both the C2 (3aa)
and C3 (4aa) alkylated intermediates were obtained
in 65 % and 25 % yield respectively (entry 1). When
the same reaction was heated for 3 h, the
intermediates 3aa was converted into diazepine
derivative 5aa in 70 % yield along with 20 % of C3-
alkylated product 4aa (entry 2). Interestingly, well-
resolved 1H and 13C NMR spectra of 5aa have shown
substantial peak doubling in acetone-d6 at room
temperature due the existence of rotamers. Variable
temperature NMR studies conducted to confirm the
interconverting rotamers (See SI, S28-S46). The
structure of 5aa is further established by X-ray
crystallographic analysis, which clearly indicates that
seven membered diazepine ring is slightly distorted
and fused at C2-postion of indole ring (Figure 2).
Scheme 1. Synthesis of indolo/pyrrole-fused diazepine/
quinoxaline derivatives
Over past decades, transition metal catalyzed
directed C-H functionalization of indole nucleus has
made significant progress and becomes powerful
strategy
for
assembling
indole-containing
heterocycle.[7] In particularly, heteroatom-assisted
selective C2-H functionalization/cascade annulation
of indoles is an alternating approach to construct
structurally diverse fused-indole heterocyclic
scaffolds.[8] Such an example, we have demonstrated
that the free amine assisted Pd(II) catalyzed
regioselective [5+2] annulation of unprotected
indoloanilines with internal alkynes.[9] In connection
with our research interest towards the synthesis of
Figure 2. X-ray structure of compound 5aa
structurally
diverse
important
heterocyclic
molecules,[10] herein we envisioned that metal
catalyzed reaction of o-indolo aniline with diazo as
coupling partner could deliver the indolo-fused
diazepine through free amine assisted C2-H
Next, replacing AcOH with PivOH did not observe
improvement in yield (entry 3). In the absence of co-
additives suppressed the formation of 4aa and the
yield of 5aa was significantly augmented to 92 %
(entry 4). A brief evaluation of other additives and
solvents indicated that AgSbF6 and EtOH are good
combination in this reaction (entries 5-11). There was
no change in yield when temperature raised to 100 oC,
but lower yield obtained at 30 oC (entries 12-13). The
importance of catalyst and additive also studied, as
reactions gave lower yield in the absence of additive,
whereas reaction did not proceed in the absence of
catalyst (entries 14-15). When [RhCp*Cl2]2 was
replaced by [CoCp*(CO)I2], PdCl2 or Pd(OAc)2, no
reaction occurred and starting material 1a was
recovered (entries 16-18). To our surprise, when
reaction was performed with [Ru(p-cymen)Cl2]2 (5
functionalization/cyclization.
During
our
optimization studies, a remarkable chemodivergent
annulation observed by switching the catalyst, which
enabled
facile
synthesis
of
hybrid
diazepine/quinoxaline-fused indole heterocycles
(Scheme 2).
O
mol%)/AgSbF6(20 mol%)in EtOH at 60 C for 12 h,
the new six membered indole-fused quinoxaline 7aa
(35 %) and N-alkylated product 6aa (55%) were
isolated instead of seven membered indole-fused
diazepine 5aa (entry 19). The structure of 7aa is
ascertained by X-ray single crystallography, which
demonstrates the newly formed six membered ring
adopts the boat conformation and overall structure is
planar (Figure 3).
Scheme 2. A transition metal controlled approach to the
different scaffolds
2
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
Table 1. Optimization for the synthesis of diazepino[1,7-a]indole (5aa)a
Yield (%)b
Temp
(°C)
Time
(h)
Entry
Catalyst
Additives
Acid
Solvent
3aa
4aa
5aa
1
2
3
4
5
6
7
8
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2-
-
AgSbF6
AgSbF6
AgSbF6
AgSbF6
CsOAc
NaOAc
AgNTf6
AgOTf
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
-
AcOH
AcOH
PivOH
-
-
-
-
-
-
-
-
-
-
-
-
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
DCE
60
60
60
60
60
60
60
60
100
60
100
100
30
60
60
60
60
60
60
1
3
3
3
3
3
3
3
6
3
3
3
12
12
3
10
10
10
12
65
0
0
0
0
0
0
0
0
15
0
0
0
0
0
0
0
0
25
20
25
0
0
0
20
35
0
0
0
0
70
72
92
0
0
65
45
72
80
0
82
50
35
0
0
0
0
0
9
10
11
12
13
14
15
16
17
18
19d
MeOH
ACN
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
0
20
15
0
0
0
AgSbF6
AgSbF6
Cu(OAc)2
Cu(OAc)2
AgSbF6
[Co Cp*(CO)I2]
AcOH
c
Pd(OAc)2
PdCl2
-
-
-
c
0
0
c
[Ru(p-cymen)Cl2]2
0
[a] Reaction conditions: 1a (0.48 mmol), 2a (0.96 mmol), catalyst (2.5 mol%), additive (20 mol%), solvent (4 mL).
[b]
Isolated yields. [c] catalyst (5 mol%).[d] Obtained 7aa in 35% and 6aa in 55% yield.
5ra). In the case of indole bearing methyl group at 3-
position and electron donating/withdrawing groups
on aniline ring (1g-1k) furnished the corresponding
products (5ga-5ka) in excellent yields, where
rotamers did not observe presumably due to the steric
hindrance of –Me group restricting the rotation of
ester group. Heterocyclic o-indolyl aniline (1o) is
also compatible and led to desired product 5oa in
74 % yield, whereas ortho-methyl substituted o-
indolyl aniline (1m) and free amine protected o-
indolyl aniline (1s) were not successful.
Furthermore, replacement of the indole core with the
pyrrole provided a new class of pyrrolo-fused
diazepine analogues (Table 2b). Various functional
group such as -H (5'a), -OMe (5'b), -CF3 (5'c), -
COOMe (5'd) on aniline ring are well-tolerated to
furnish pyrrolo[1,2-d][1,4]diazepine (5'aa-5'da) in
good yield. However, 2,4-dimethyl pyrrolyl aniline
(1'e) and 2-ethyl imidazolyl aniline (1'f) are not
suitable substrates for this cascade C-H/N-H
annulation. This may be because the steric hindrance
of 2,4-dimethyl pyrrolyl ring and strong metal-
chelating ability of the electron deficient imidazolyl
Figure 3. ORTEP diagram of compound 7aa
With an optimized condition in hand, we next
examined the substrate scope of various
indolyl/pyrrolyl anilines 1/1' with diazo compounds 2
(Table 2). The reactions of substrate having electron
donating/withdrawing groups on aniline (1a-1c, 1na-
pa) or indole ring (1d-1g, 1pa-ra) with diethyl
diazomalonate 2a proceeded smoothly to deliver the
desired products in excellent yield (5aa-5ga, 5na-
3
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
ring inhibit the formation of six-membered
rhodacycle intermediate. Afterward, we tested the
feasibility of different diazo malonates (Table 2c).
The dimethyl, dibenzyl diazomalonates (2b-c)
reacted efficiently with substrate o-indolo and pyrrolo
anilines (1a, 1'a) or 2-(3-methyl-1H-indolyl)aniline
1g to afford the corresponding products in excellent
yields (5ab-ac, 5gb-gc, and 5'ac), whereas diitertbuty
diazomalonates (2d) yielded the desired product in
good yields (5ad, 5gd, and 5'ad).
Table 2. A Rh(III) catalyzed synthesis of indolo/pyrrolo-fused diazepine (5)a,b
[a] Reaction conditions: 1 (0.48 mmol), 2 (0.96 mmol), [RhCp*Cl2]2 (2.5 mol%), AgSbF6 (20 mol%), EtOH (4 mL), 60 oC,
3h. [b] Isolated yields.
4
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
Next, we studied the reaction scope of various
Table 3. Optimization for the synthesis of Indolo[1,2-
a]quinoxalines (7aa)a
substituted o-indolyl aniline
1
with diethyl
diazomalonate 2a (Table 4a). Various electron
donating/withdrawing groups, halo substituent on
aniline moiety or indole moiety of o-indolyl aniline
are well-tolerated to construct the series of
indolo[1,2-a]quinoxalines (7aa-ga, 7la, 7na-ra) in
moderate to excellent yields. However, a methyl
group at ortho position of o-indolyl aniline 1m failed
to give the desired product, where N-alkylated
product 6ma obtained in 46 % yield. No product
formation was observed with NH-substituted o-
indolyl aniline (1s). The o-pyrrolyl aniline having
different substituents on aniline moiety were
efficiently engaged in reaction to led to the
corresponding pyrrolo[1,2-a]quinoxaline (Table 4b,
7'aa-da) in moderate to excellent yield. In addition,
pyrrole bearing methyl group on 2,4 position 1'e
smoothly furnished the expected product 7'ea in
80 % yield. No product formation observed with the
o-imidazolyl aniline (1'f) and starting material
remained unreacted. We also investigated scope and
reactivity of the various diazo compounds 2 with o-
indolyl/pyrrolyl aniline 1a and 1'a (Table 4c). The
reaction of dimethyl diazomalonate 2b or dibenzyl 2-
diazomalonate 2c with o-indolyl aniline 1a provided
the products 7ab and 7ac in 78 % and 64 % yield
respectively. Moreover, o-pyrrolyl aniline 1'a
smoothly reacted dibenzyl 2-diazomalonate 2c to
furnish the desired product 7’ac in excellent yield.
The di-tert-butyl diazomalonate 2d did not react with
o-indolyl/pyrrolyl aniline (1a/1'a) and the reaction
becomes sluggish.
Yield(%)b
Entry
Additive
Solvent
Time
7aa
6aa
1[c]
2[c]
3[c]
4[c]
5
6
7
8
9
10
11
12
13
14[d]
15[d],[e]
AcOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
TFE
CH3CN
DCE
TFE
TFE
TFE
12
12
12
12
12
12
12
12
12
12
12
12
12
6
13
10
61
0
73
70
0
trace
0
0
0
0
0
0
0
0
0
0
0
0
PivOH
NaOAc
Cu(OAc)2
NaOAc
KOAc
CsOAc
NaOPiv
CsOPiv
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
-
75
72
65
52
58
70
80
trace
45
87
85
0
6
24
16
[a]
Reaction conditions: 1a (0.48 mmol), 2a (.96 mmol),
catalyst (5 mol%), additive (20 mol%), oxidant (0.96
o
[b]
[c]
mmol), solvent (4 mL) at 60 C.
Isolated yields.
CuO used as an
[d]
AgSbF6 (20 mol%) used as a salt.
oxidant.[e] At 100 oC.
To shed light on mechanism of this catalyst
controlled chemodivergent annulation, a series of
control experiments were performed (Scheme 3). The
treatment of C2-alkylated intermediate 3aa under the
Rh catalyzed reaction condition resulted 5aa in 91 %
yield (Scheme 3a, right). Similarly, formation of 5aa
was observed in 70 % yield instead of indolo [1,2-
a]quinoxaline 7aa under the Ru catalyzed reaction
condition (Scheme 3a, left). These results suggest the
formation of 5aa takes place through the C2-H
activation followed by amide bond formation,
whereas formation of 6aa is not due to the Ru-
catalyzed C2−H bond activation. Next, we perform
the reaction of diazo malonate 2a with the [Ru(p-
cymene)Cl2]2 and NaOAc in TFE at room
temperature to deliver the Ru-carbene complex B
(Scheme 3b). Then, the reaction between Ru-carbene
complex B and o-indolo aniline in the presence
Next, we move our attention to find out the
reaction condition for serendipity discovered
indolo[1,2-a]quinoxaline 7aa by Ru(II) as a catalyst.
Initially, various additives such as PivOH, AcOH,
Cu(OAc)2, and NaOAc were evaluated (Table 3,
entries 2-5). Among them, NaOAc afforded the 7aa
in 61 % yield without formation of N-alkylated
product 6aa (entry 4). In the absence of AgSbF6, 7aa
increased to 75 % yield (Table 3, entry 5). Replacing
NaOAc with KOAc, CsOAc, NaOPiv, and CsOPiv
led to reduction in the yields (entries 6-9).
Subsequent solvent screening demonstrated 2,2,2,-
trifluoroethanol (TFE) to give 7aa in 80 % yield
(entry 11). Respectable improvement in the yield and
reaction time observed when CuO used as an oxidant,
afforded 7aa in 87 % yield in 6 h (entry 14). Rising
o
o
oxidant CuO in TFE at 60 C afforded the product
the temperature to 100 C did not affect the product
7aa in the 50 % yield along with N-alkylated product
6aa in 15 % yield (Scheme 3c). This result may
indicate the synthesis of indolo [1,2-a]quinoxaline is
initiated by the formation of Ru-carbene complex B.
Afterward, we carried out the competition
experiments of Ru and Rh catalyst using substrate 1a
and 2a. The Ru-catalyzed product 7aa obtained in
75 % yield, but no Rh-catalyzed product 5aa
observed (Scheme 3d) which may be due to the rapid
formation of Ru-carbene complex B to dominate
formation (entry 15). No product formation observed
when reaction conducted without a catalyst (entry 16).
Briefly screening showed that diethyl indolo[1,2-
a]quinoxaline-6,6(5H)-dicarboxylate
7aa
was
obtained in 87% yield when the o-indolo aniline 1aa
and diethyl diazo malonate 2aa in TFE were treated
with [Ru(p-cymene)Cl2]2 (5 mol%), additive NaOAc
(20 mol%), and oxidant CuO (2.0 equiv) at 60 °C for
6h (entry 14).
5
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
Table 4. A Ru(II) catalyzed synthesis of indolo/pyrrolo-fused quinoxaline (7)a,b
[a]Reaction conditions: 1a (0.48 mmol), 2a (0.96 mmol), [Ru(p-cymene)Cl2]2 (5 mol%), NaOAc (20 mol%), CuO (0.96
mmol), TFE (4 mL), 60 oC, 6 h. [b] Isolated yields.
reaction progress.
cleavage afforded six membered rhodacycle
intermediate II. Subsequently, coordination of
incoming diazo ester 2a to Rh(III) species II
followed by extrusion of nitrogen gave the metal-
carbene species IV. Later migratory insertion of the
Rh-C bond into the carbene moiety afford seven
membered rhodacycle intermediate V, which would
undergo the protonolysis to form C2 alkylated
intermediate VI. Finally, free amine group proceeded
On the basis of the experimental results and
precedent literature evidence,[11]
a
plausible
mechanism for the synthesis of diazepino [1,7-
a]indole is depicted in Scheme 4. First, active
dicationic Rh(III) species [RhCp*X2] was generated
from [RhCp*Cl2]2 and AgSbF6. Coordination of a
free amine group of o-indolyl aniline 1a to
[RhCp*X2] species I followed by selective C2-H
6
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
Scheme 3. A mechanistic study to probe the reaction pathway
nucleophilic attack towards the carbonyl group in
ester moiety VI where [RhCp*]2+ acted as a Lewis
acid to activate the carbonyl group to furnish
corresponding product 5aa with regeneration of
active catalyst I.
Scheme 5. A plausible pathway for the formation of indolo
Scheme 4: A plausible mechanism leading to the
formation of diazepino [1,7-a]indole 5aa
[1,2-a]quinoxaline 7
Although the formation of 7 remains unclear at this
stage, referring to the previous literatures[12] and our
experimental results, a plausible mechanism for the
formation of 7aa is proposed in Scheme 5. A [Ru(p-
cymene)Cl2]2 complex generates the active [Ru(p-
cymene)X2] species A which forms the Ru-carbene
intermediate B by elimination of –N2. Next, addition
of free amine group of o-indolo aniline to ruthenium
7
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10.1002/adsc.201900088
Advanced Synthesis & Catalysis
carbene intermediate B to give the N-ylide C[13]. After
1,3 Ru shift followed by metallo-ene reaction takes
place to afford the intermediate E. Finally, β-hydride
elimination furnishes the indolo-fused quinoxaline 7
along with Ru(0) intermediate which was further
reoxidized by CuO to regenerates the active catalyst
A to continue the catalytic cycle.[13b-c]
1H), 7.39-7.32 (m, 3H), 7.21 (t, J = 7.8 Hz, 1H), 7.16 (t, J
= 7.5 Hz, 1H), 6.69 (s, 1H), 5.10 (s, 1H), 3.74 (s, 2H), 0.80
(s, 3H).
A representative procedure for the synthesis of diethyl
indolo[1,2-a]quinoxaline-6,6(5H)-dicarboxylate (7aa)
A seal reaction tube was charged with o-indolo aniline 1a
(100 mg, 0.48 mmol), diethyl malonate 2a (178 mg, 0.96
mmol), [Ru(p-cymene)Cl2]2 (29.0 mg, 10 mol %), NaOAC
(8.0 mg, 20 mol %), CuO (75 mg, 0.96 mmol) in 2,2,2-
Trifluoroethanol (TFE) (5.0 mL). The mixture was stirred
at 60 °C for 6 h. After completion of reaction, reaction
mixture was diluted with EtOAc and filtered through the
celite. The solvent was removed under vacuum, and the
residue was purified by silica gel chromatography using
hexane/ethyl acetate (98:2 %) to afford product diethyl
indolo[1,2-a]quinoxaline-6,6(5H)-dicarboxylate 7aa as
white solid (140 mg, 85 % yield).
Conclusion
We have successfully explored catalyst-controlled
chemodivergent annulation strategy to access
diazepino [1,7-a]indole and indolo [1,2-a]quinoxaline
from reaction of readily available o-indolo anilines
with diazo esters as a coupling partner. Notably, the
product formation is exclusively dependent on choice
of transition metal catalysts. In the presence of
Rh(III) catalyst, indolo-fused diazepine was
selectively created via selective C2-H alkylation and
subsequently the amide bond formation was
proceeded. On other hand with Ru as a catalyst, the
indolo-fused quinoxaline afforded through insertion
of N-H bond to ruthenium carbene followed by
cyclization through metallo-ene type reaction. A
variety of o-indolo/pyrrolo anilines and diazo
compounds are amenable to the current catalyst-
controlled system to afford the indolo/pyrrolo-fused
diazepine and quinoxaline in excellent yields. Further
detailed mechanistic investigation for formation of
indolo [1,2-a]quinoxalines is underway in our
laboratory.
1
Mp 110-113 °C; H NMR (400 MHz, C3D6O) δ 8.10 (d, J
= 8.4 Hz, 1H), 7.97 (d, J =7.6 Hz, 1H), 7.68 (d, J =7.6 Hz,
1H),7.34 – 7.28 (m, 2H), 7.22 – 7.17 (t, J =7.44 Hz, 1H),
7.10 – 7.01 (q, J = 7.4 Hz, 2H), 6.83 (s, 1H), 6.32 (s, 1H),
4.27 (q, J = 7.1 Hz, 4H), 1.23 (t, J = 7.1 Hz, 6H); 13C NMR
(101 MHz, C3D6O) δ 167.1, 134.5, 134.0, 131.9, 129.3,
126.4, 124.3, 123.2, 121.4, 121.0, 120.3, 116.6, 116.4,
101.8, 101.7, 62.2, 13.4; MS (ESI) m/z: 365 (MH+);
HRMS (ESI, m/z) Calcd. C21H20N2NaO4 [M+Na]+:
387.1315; Found 387.1318 (M+Na)+.
Acknowledgements
The authors thank the Ministry of Science and Technology of
Taiwan for the financial assistance and the authorities of the
National Chiao Tung University for providing the laboratory
facilities.
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FULL PAPER
Catalyst-Controlled Chemodivergent Annulation to
Indolo/Pyrrolo-Fused Diazepine and Quinoxaline
Adv. Synth. Catal. Year, Volume, Page – Page
Sandip Dhole, Wei-Jung Chiu, Chung-Ming Sun*
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