Visible light-catalyzed cascade radical cyclization of n-propargylindoles with acyl chlorides for the synthesis of 2-acyl-9 h-pyrrolo[1,2- a]indoles

Article abstract of DOI:10.1021/acs.joc.9b03090

A novel and convenient visible light-catalyzed tandem radical cyclization of N-propargylindoles with acyl chlorides for accessing 2-acyl-9H-pyrrolo[1,2-a]indoles is established. This transformation involves sequential addition of the acyl radical to the c

Full text of DOI:10.1021/acs.joc.9b03090

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Article
Visible-Light-Catalyzed Cascade Radical Cyclization of N-propargylindoles
with Acyl Chlorides for the Synthesis of 2-Acyl-9H-pyrrolo[1,2-a]indoles
Yu Liu, Zan Chen, Qiao-Lin Wang, Pu Chen, Jun Xie, Biquan Xiong, Pan-Liang Zhang, and Ke-Wen Tang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 13 Jan 2020
Downloaded from pubs.acs.org on January 13, 2020
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The Journal of Organic Chemistry
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Visible-Light-Catalyzed Cascade Radical Cyclization
of N-propargylindoles with Acyl Chlorides for the
Synthesis of 2-Acyl-9H-pyrrolo[1,2-a]indoles
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Yu Liu,* Zan Chen, Qiao-Lin Wang, Pu Chen, Jun Xie,* Bi-Quan Xiong, Pan-Liang Zhang, and Ke-
Wen Tang*
Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology,
Yueyang 414006, China
Email: lyxtmj_613@163.com (Yu Liu), xiejun12018014@163.com (Jun Xie) and tangkewen@sina.com
(Ke-Wen Tang)
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
Abstract
R1
R1
R3
O
[Ir(ppy)3] (1 mol %)
Et3N (3 equiv)
R4
+ R4 Cl
R2
N
N
CH CN (2 mL), Ar, 100 oC
R2
3
R3
5 W blue LED light, 20 h
O
R1 = H, Mer
Visible-light-catalyzed
Carbon-centered radical strategy
R2 = OMe, Me, F, Cl, Br
R3 = Ar, naphthyl, thienyl R4 = Ar, thienyl
Broad substrate scope
36 examples up to 86% yield
A novel and convenient visible-light-catalyzed tandem radical cyclization of N-propargylindoles with
acyl chlorides for accessing 2-acyl-9H-pyrrolo[1,2-a]indoles is established. This transformation
undergoes sequential addition of acyl radical to the carbon–carbon triple bond, intramolecular cylization
with 2-position of indole and isomerisation of carbon–carbon double bond. The experiment results
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indicate that show that this reaction contains a radical pathway and radical chain process is not the
majoy pathway for the formation of product.
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Introduction
Indole derivatives, especially polycyclic indoles, are important heterocycle structures, due to their
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particular pharmacological and biological activities. For instance, the pyrrolo[1,2-a]indole skeletons
2
are distinctive motifs existed in numerous pharmaceutical chemicals and natural products. Pyrrolo[1,2-
a]indoles, which possess the characteristics of anti-tumor, anti-diabetes and anti-cancer, have become a
3
class of indispensable pharmacophores. Additionally, they also show unique optical and electrical
4
prooerties. Herein, the development of simple and efficient methods for the preparation of pyrrolo[1,2-
5
a]indoles has attracted considerable attention. Recently, several groups have reported that N-
propargylindoles could capture free radicals (including P, S and sulfonyl-containing radicals), which
underwent cascade cyclization to access 2-substituted pyrrolo[1,2-a]indole compounds (Scheme 1a).6-7
6a
6b
Zhao’s group and Zhu’s group developed the tandem cyclization of N-propargylindoles with P(O)-H
derivatives for the generation of 2-phosphoryl-pyrrolo[1,2-a]indoles. In 2017, Cheng and co-workers6c
developed the cascade cyclization of N-propargylindoles with arylsulfonyl hydrazides for the
preparation
of
2-arylthiolyl-3H-pyrrolo[1,2-a]indoles.
Several
chemists
presented
sulfonylation/cyclization of N-propargylindoles with different kinds of sulfonyl radical sources (such as
sulfonyl hydrazides,7a–c sulfinic acids,7d aryldiazonium tetrafluoroborates and DABCO·(SO2)27e or
7
f
sulfonyl chlorides ) to furnish 2-sulfonyl-pyrrolo[1,2-a]indoles. However, these methods only disclosed
the tandem annulations of N-propargylindoles with hetero–centered radicals. The methods for cascade
radical cyclization of N-propargylindoles with carbon–centered radicals are lacking.
8
9
10
Acyl radicals, which can generate from aldehydes, α-ketoacids, aromatic carboxylic acids, acyl
11
12
chlorides, and other acyl radical sources, are valuable reaction intermediates. However, beside high
temperature and transition-metals, the generation of acyl radicals usually needs strong oxidants. These
strict conditions limited the application of acyl radicals in pharmaceutical and organic synthesis.
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The Journal of Organic Chemistry
In recent years, visible-light-catalysis, which possessed the advantages of high efficiency, safety,
1
2
availability and mild reaction conditions, was considered as an efficient and fascinating tool in organic
synthesis.13-15 Therefore, we report the visible-light-mediated cascade radical cyclization of N-
propargylindoles with acyl chlorides to prepare 2-acyl-9H-pyrrolo[1,2-a]indoles, which sequentially
undergoes addition of acyl radical to the carbon–carbon triple bond, intramolecular cyclization with the
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-position of indole and isomerisation of carbon–carbon double bond (Scheme 1b).
(a) Previous work
1
R
R1
R3
+
R
R2
N
R2
N
R3
R = P, S or sulfonyl-containing radicals
R
(b) This work
R1
R1
R3
O
[Ir(ppy) ] (1 mol %)
3
Et N (3 equiv)
CH CN (2 mL), Ar, 100 C R2
W blue LED light, 20 h
R4
3
R4
R2
+
Cl
N
N
o
3
R3
5
O
Scheme 1. The Cascade Radical Cyclization of N-propargylindoles
Results and discussion
We started our investigation by using 1-(3-phenylprop-2-yn-1-yl)-1H-indole (1a, 0.2 mmol) and 4-
methylbenzoyl chloride (2a, 61.6 mg, 0.4 mmol) as the model substrates to identify the best reaction
conditions (Table 1). To our surprise, the desired acylation product (1-phenyl-9H-pyrrolo[1,2-a]indol-2-
yl)(p-tolyl)methanone (3aa) could be obtained in 80% yield by employing [Ir(ppy) ] (1.3 mg,
3
o
0
.002mmol) as photocatalyst, Et N (60.6 mg, 0.6 mmol) as base and MeCN (2 mL) as solvent at 100 C
3
(oil bath) in Ar atmosphere under blue LED light for 20 h (entry 1). Inspired by this result, two other
photocatalysts, Ru(bpy) Cl and Eosin Y, were examined. However, they were failed to increase the
3
2
reaction yields (entries 2–3). The photocatalyst was indispensable for this transformation as the
cyclization product could not be obtained in the absence of photocatalyst (entry 4). Next, a series of
different visible-light sources, including 36 W compact fluorescent light, 12 W blue LED light and 3 W
blue LED light, were successively studied. None of them afforded higher yields (entries 5–7). The
experimental results indicated that the visible-light irradiation was also indispensable for the tandem
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cyclization (entry 8). Other bases, such as Cs CO , Na CO , DABCO and 2,6-lutidine, were screened.
2
3
2
3
1
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3
4
5
6
7
8
9
1
1
1
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6
All of them were inferior to Et N according to the reaction yields (entries 9–12). However, DABCO and
3
2,6-lutidine provided the target pyrrolo[1,2-a]indole 3aa in 78% and 74% yields, respectively (entries
1
1–12). Several solvents, including DCE,
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9
0
Table 1. Screening Optimal Conditionsa
O
Cl
[
Ir(ppy) ] (1 mol %)
Ph
3
Et N (3 equiv)
3
N
+
N
o
CH CN (2 mL), Ar, 100 C
Ph
3
5 W blue LED light, 20 h
O
1a
2a
3aa
Entry
1
Variation from the standard conditions
none
Yield (%)b
80
44
31
0
2
[Ru(bpy) Cl ] instead of [Ir(ppy) ]
3
2
3
3
Eosin Y instead of [Ir(ppy)3]
without [Ir(ppy)3]
none
4c
5d
6e
7f
62
72
57
0
none
none
8c
without additional light
Cs CO instead of Et N
9
38
55
78
74
38
29
40
31
0
2
3
3
1
1
1
1
0
1
2
3
Na CO instead of Et N
2 3 3
DABCO instead of Et N
3
2,6-lutidine instead of Et N
3
DCE instead of CH CN
3
14
THF instead of CH CN
3
1
1
5
6
Toluene instead of CH CN
3
DMF instead of CH CN
3
1
7c
DMSO instead of CH CN
3
1
8
at 110 °C
at 90 °C
75
66
13
78
63
19
2
0c
at room temperature
for 30 h
21
2
2g
none
a
Reaction conditions: 1a (0.2 mmol, 0.1 M), 2a (0.6 mmol, 3 equiv),
[Ir(ppy) ] (1.3 mg, 0.002 mmol), Et N (60.6 mg,0.6 mmol), CH CN (2 mL)
3
3
3
at 100 °C (oil bath) under Ar atmosphere and irradiation by 5 W blue LED
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The Journal of Organic Chemistry
light for 20 h. Isolated yield. c Most of the starting materials 1a was
recovered. 36 W compact fluorescent light instead of 5 W blue LED light.
b
1
2
3
4
5
6
7
d
e
f
12 W blue LED light instead of 5 W blue LED light. 3 W blue LED light
g
instead of 5 W blue LED light. 1a (1.0 g, 4.33 mmol) and solvent (10 mL)
for 60 h.
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
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5
5
6
THF, toluene, DMF and DMSO, were tested. None of them gave higher yield than that of
0
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9
0
CH CN(entries 13–17). The isolated yield of pyrrolo[1,2-a]indole 3aa also decreased when the
3
o
o
reactions were conducted at 110 C or at 90 C (entries 18–19). Conducting the reaction at room
temperature only afforded the product 3aa in 13% yield and most of the starting materials 1a was
recovered (entry 20). Moreover, the prolonged time could not deliver product 3aa in higher yield (entry
2
1). It is noticeable that the scale-up experiment could also assemble the acylated pyrrolo[1,2-a]indole
aa in 63% yield (entry 21).
3
As the standard conditions for the tandem cyclization reaction were established, we set out to study
the scope of N-propargyl-substituted indoles in the presence of 4-methylbenzoyl chloride (2a) (Table 2).
Firstly, a series of N-propargylindoles 1a–n, which had different substituted phenyl groups at terminal
position of the triple bonds, were investigated. The results suggested that both electricity and hindrance
of the substituents had influence on the yields of products (products 3aa–na). As for the para-
substituted substrates, the substrates bearing electron-withdrawing substituents delivered lower yields
than that of substrates bearing electron-donating substituents (products 3ba–ia). Moreover, the ortho-
substituted substrates showed lower reactivity than that of para-substituted ones (products 3ba, 3ja and
3
la). In particular, compounds bearing 1-naphthyl or 2-thienyl groups at terminal position of the triple
bond could also install the corresponding acylation products 3oa and 3pa in 68% and 64% yields,
1
1
respectively. Both substrate 1q (R = Me) and substrate 1r (R = H) were not suitable for this tandem
cyclization (products 3qa and 3ra). Next, a variety of indole derivatives 1s–z was used to react with
acyl chloride 2a. The indoles with methyl group on the indole skeleton, such as 3-methyl, 4-methyl, 6-
methyl and 7-methyl, reacted smoothly and delivered the corresponding polycyclic indoles in 76%-82%
yields (products 3sa, 3ta, 3xa and 3za). An isomerisation process must be contained in this reaction
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according to the structure of product 3sa. Halogen substituted substrates 1u, 1w and 1y were tolerated in
this transformation, which offer a possibility for further modification of the products (products 3ua, 3wa
and 3ya).
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2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
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4
4
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5
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5
5
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5
5
6
Table 2. Screening Scope of N-propargylindoles (1) a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
R2
R2
N
[
Ir(ppy) ] (1 mol %)
3
Et N (3 equiv)
3
R1
O
+
Ar
2a
Cl
o
Ar
N
CH CN (2 mL), 100 C
3
W blue LED light, 20 h
R3
R1
5
R3
O
1
6
Ar = 4-MeC H4
3
R = 4-CN, 3ha, 69%
R = 4-OMe, 3ba, 86%
R = 4-Me, 3ca, 81%
R
R = 4-CF , 3ia, 66%
3
R = 3-OMe, 3ja, 82%
R = 3-Me, 3ka, 76%
R = 2-OMe, 3la, 77%
R = 2-Me, 3ma, 70%
R = 4-Ph, 3da, 78%
t
Ar R = 4- Bu,
3ea, 80%
N
Ar
N
R = 4-F,
3fa, 75%
O
R = 4-Cl, 3ga, 76%
R = 3,5-diMe, 3na, 68%
O
3oa, 68%
S
Me
H
Ph
Ar
Ar
Ar
Ar
Ar
N
N
N
N
O
O
O
O
3qa, 0%b
3ra, 0%b
3
pa, 64%
3sa, 77%
R
Ph
Ph
Ph
Ph
R
Ar
Ar
Ar
N
N
N
N
O
R
O
O
O
R = Me, 3ta, 80%
R = Cl, 3ua, 72%
R = OMe, 3va, 78%
R = Br, 3wa, 66%
R = Me, 3xa, 82%
R = F, 3ya, 73%
3za, 76%
a
Reaction conditions: 1 (0.2 mmol, 0.1 M), 2a (0.6 mmol, 3 equiv), [Ir(ppy)3]
1.3 mg, 0.002 mmol), Et N (60.6 mg, 0.6 mmol), CH CN (2 mL) at 100 °C (oil
(
3
3
bath) under Ar atmosphere and irradiation by 5 W blue LED light for 20 h;
b
isolated yields are reported. Most of the starting materials 1 was decomposed.
Subsequently, a variety of acyl chlorides 2 were used to react with N-propargylindole 1a under the
best conditions (Table 3). To our delight, a series of benzoyl chlorides (2b−p) bearing substituents on
the benzene rings underwent the radical cyclization smoothly and installed the corresponding polycyclic
indoles 3 in moderate to good yields (products 3ab−ap). Both electron-withdrawing and electron-
donating group substituted benzoyl chlorides were all good candidates in the transformation.
Furthermore, the results indicated that the electronic effects and steric effects had influence on the
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The Journal of Organic Chemistry
reaction, and the cyclization order of benzoyl chlorides is electron-donating > electron-withdrawing
products 3ab−ah) and para > meta > ortho (products 3aa, 3aj and 3an). However, 4-nitrobenzoyl
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
chloride 2f could not convert into the desired product 3af as the formation of 4-nitrobenzoyl radical
under this conditions was difficult due to its instability. Dichloro-substituted benzoyl chloride 2p could
undergo this cascade cycylization smoothly (product 3ap). 1-naphthoyl chloride 2q and thenoyl chloride
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
r were suitable for this cascade cylcization and led to the corresponding products 3aq and 3ar in 60%
and 55% yields, respectively. Finally, cinnamoyl chloride, 2-phenylacetyl chloride and pentanoyl
chloride were tested and all of them failed to assemble the acylation products.
Table 3. Screening Scope of Acyl Chlorides (2) a
[
Ir(ppy) ] (1 mol %)
Et N (3 equiv)
3
Ph
3
O
R4
+
N
R4 Cl CH CN (2 mL), Ar, 100 C
o
N
3
Ph
Ph
5
W blue LED light, 20 h
O
1a
2
3
R
Ph
R = OMe, 3ai, 81%
R = Me, 3aj, 75%
R = F, 3ak, 70%
R = Cl, 3al, 68%
N
R
N
O
O
R = Me, 3aa, 80%
R = OMe, 3ab, 84%
R = F, 3ac, 76%
R = Cl, 3ad, 77%
R = Br, 3ae, 70%
R = NO , 3af, 0%
R = CF , 3ag, 62%
Ph
R = OMe, 3am, 77%
R = Me, 3an, 70%
R = F, 3ao, 65%
N
b
R
2
O
3
R = H, 3ah, 80%
Cl
Ph
S
Ph
Ph
N
N
Cl
N
O
O
O
3ar, 55%
3
ap, 58%
3
aq, 60%
a
Reaction conditions: 1 (0.2 mmol, 0.1 M), 2a (0.6 mmol, 3 equiv), [Ir(ppy)3]
1.3 mg, 0.002 mmol), Et N (60.6 mg, 0.6 mmol), CH CN (2 mL) at 100 °C (oil
(
3
3
bath) under Ar atmosphere and irradiation by 5 W blue LED light for 20 h;
b
isolated yields are reported. Most of the starting materials 1 was decomposed.
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Several control experiments were carried out as shown in Scheme 2 to understand the mechanism of
this cascade radical cyclization. Initially, subjecting of radical scavengers, including TEMPO, BHT,
hydroquinone and 1,1-diphenylethylene, to the optimized conditions afforded the product 3aa in very
low yields (Scheme 2a−b). The trapping product 4 (1-(4-methoxyphenyl)-3,3-diphenylprop-2-en-1-one)
could be isolated in 63% yields when 1,1-diphenylethylene was employed into the reaction (Scheme 2b).
These results showed that this transformation definitely contained an acyl radical forming process. Then,
another acyl group source 5 (benzoyl bromide) was employed into the reaction and generated the
product 3aa in 33% yield (Scheme 2c). We have tested the ternary system 1-methyl-1H-indole 6,
phenylacetylene 7 and acylchloride 2a under the conditions. The GC-MS analysis result showed that no
target product was detected (Scheme 2d).
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 2. Control Experiments.
quencher
3aa
0%
4%
[
Ir(ppy) ] (1 mol %)
3
Et N (3 equiv)
3
8
TEMPO
BHT
hydroquinone 7%
1a + 2a
3aa
o
(a)
CH CN (2 mL), Ar, 100 C
5
3
10%
W blue LED light, 20 h
[
Ir(ppy) ] (1 mol %)
Et N (3 equiv)
3
Ph
3
Ph
Ph
1a + 2b +
3aa
+
10%
o
Ph
OMe (b)
CH CN (2 mL), Ar, 100 C
5 W blue LED light, 20 h
3
O
3
equiv
4
, 63%
Ph
[
Ir(ppy) ] (1 mol %)
3
Et N (3 equiv)
3
O
Ph
1a +
N
(c)
(d)
Ph
Br
o
CH CN (2 mL), Ar, 100 C
3
O
5, 3 equiv
5 W blue LED light, 20 h
3
aa, 33%
standard conditions
3aa
0%
+
Ph
+
2a
N
7
6
The light on/off experiment verified the necessity of continuous irradiation of visible light and
suggested that chain propagation is not the predominant mechanistic pathway (Figure 1).
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 1. Profile of 3aa with Light on or off over Time. GC yield using biphenyl as an internal
standard.
Based on recent reports and our experimental results,7,12-14 a possible mechanistic pathway was
III
III
proposed as outline in Scheme 3. First, Ir (ppy) is converted into the strong reductant *Ir (ppy) under
3
3
III
the irradiation of visible-light. Then, acyl chloride 2a is reduced by *Ir (ppy) via single-electron
3
IV
transfer (SET) process and releases of chloride ion to give the acyl radical A and producing Ir (ppy) .
3
Next, the intermediate A attacks the carbon−carbon triple bond of N-propargylindole 1a to produce the
stable benzyl radical B. The intermediate B goes through intramolecular cyclization with 2-position of
IV
indole to deliver intermediate C, which is oxidized by Ir (ppy) to provide cation D, accompany with
3
III
regenerating Ir (ppy) . The intermediate E, which comes from deprotonation of the intermediate D,
3
goes through isomerization to furnish the target product 3aa.
Scheme 3. Possible Mechanisms.
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Ph
Ar = 4-MeC H
6
4
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Ph
N
O
cyclization
Ar
N
Ar
B
O
C
O
Cl-
IrIV
-
Ar
SET
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
A
O
Ar
Cl
SET
2a
IrIII
N
Ph
1a
IrIII
hv
Ph
Ph
- H+
Ar
Ar
product isomerization
aa
N
N
3
O
O
E
D
Conclusions
In conclusion, we have reported the visible-light-catalyzed tandem radical cyclization of N-
propargylindoles with acyl chlorides for accessing 2-acyl-9H-pyrrolo[1,2-a]indoles. This cyclization
reaction proceeds sequentially addition of acyl radical to the carbon–carbon triple bond, intramolecular
cyclization with 2-position of indole and isomerisation of carbon–carbon double bond. This reaction is a
simple and green strategy for accessing 2-acyl-9H-pyrrolo[1,2-a]indole skeletons. The results of the
control experiments show that this reaction contains a radical pathway and radical chain process is not
the majoy pathway for the formation of product. Further researches on the mechanism and development
of tandem radical cyclization are currently underway in our laboratory.
Experimental Section
General Considerations:
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13
The H and C NMR spectra were recorded in CDCl solvent on a NMR spectrometer using TMS as
3
1
2
internal standard. LRMS was performed on a GC-MS instrument and HRMS was measured on an
electrospray ionization (ESI) apparatus using time-of-flight (TOF) mass spectrometry. Melting points
are uncorrected.
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Preparation of N-propargylindoles 1:
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N-propargylindoles 15-7 were synthesized according to the literatures.
6
a
6b
N-propargylindoles 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1i, 1k, 1m, 1o, 1p, 1q, 1s, 1v, 1x, 1y, 1z; 1t; 1h,
1
w;6c 1n;7d and 1r5d were reported in previous literatures, N-propargylindoles 1j, 1l and 1u were
reported for the first time and its physical data and spectroscopic were presented as follow:
1-(3-(3-Methoxyphenyl)prop-2-yn-1-yl)-1H-indole (1j): Yield: 555.9 mg, 71%; brown solid; mp 45.0-
o
1
4
6.5 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.64 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 8.4 Hz, 1H),
3
7
.27-7.25 (m, 2H), 7.23-7.14 (m, 2H), 7.02-7.00 (m, 1H), 6.93-6.92 (m, 1H), 6.87-6.84 (m, 1H), 6.54-
1
3
1
6.53 (m, 1H), 5.06 (s, 2H), 3.74 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 159.2, 135.8, 129.3, 128.3,
3
1
27.3, 124.2, 123.2, 121.8, 121.0, 119.7, 116.5, 115.1, 109.4, 101.8, 85.0, 82.9, 55.2, 36.5; HRMS (ESI-
+
TOF) m/z: C H NO (M + H) calcd for 262.1226, found 262.1230.
1
8
16
1
1-(3-(2-Methoxyphenyl)prop-2-yn-1-yl)-1H-indole (1l): Yield: 532.4 mg, 68%; yellow oil; H NMR
(
400 MHz, CDCl ) : 7.64 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.37-7.34 (m, 2H), 7.27-7.22
3
(m, 2H), 7.14 (t, J = 6.8 Hz, 1H), 6.88-6.83 (m, 2H), 6.53-6.52 (m, 1H), 5.12 (s, 2H), 3.85 (s, 3H);
1
3
1
C{ H}NMR (100 MHz, CDCl ) δ: 160.1, 135.8, 133.7, 130.0, 128.8, 127.4, 121.6, 120.9, 120.4, 119.6,
3
+
1
2
11.4, 110.5, 109.5, 101.6, 86.9, 81.8, 55.7, 36.9; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for
1
8
16
62.1226, found 262.1230.
4-Chloro-1-(3-phenylprop-2-yn-1-yl)-1H-indole (1u): Yield: 604.2 mg, 76%; yellow solid; mp 80.6-
o
1
8
1.2 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.42-7.39 (m, 2H), 7.38-7.35 (m, 1H), 7.32-7.28
3
1
3
1
(
m, 4H), 7.23-7.14 (m, 2H), 6.65-6.64 (m, 1H), 5.07 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 136.5,
3
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31.7, 128.7, 128.3, 127.9, 127.6, 126.2, 122.4, 122.0, 119.6, 108.1, 100.5, 85.5, 82.5, 37.0; HRMS
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
(ESI-TOF) m/z: C H ClN (M + H) calcd for 266.0731, found 266.0736.
1
7
13
Typical Experimental Procedure for the Visible-Light-Catalyzed Cascade Radical Cyclization
of N-propargylindoles with Acyl Chlorides for the Synthesis of 2-Acyl-9H-pyrrolo[1,2-a]indoles
To a Schlenk tube were added N-propargylindoles 1 (0.2 mmol, 0.1 M), acyl chlorides 2 (0.6 mmol, 3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
equiv), [Ir(ppy) ] (1.3 mg, 0.002 mmol), Et N (60.6 mg, 0.6 mmol) and CH CN (2 mL). Then the tube
3
3
3
o
was stirred at 100 C (oil bath) in Ar atmosphere under 5 W blue LED light for the indicated time until
complete consumption of starting material as monitored by TLC analysis. After the reaction was
finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with EtOAc
(3 × 10 mL). The combined organic extracts were dried over Na SO and concentrated in vacuum. The
2
4
residue was purified by silica gel flash column chromatography (hexane/ethyl acetate = 15 : 1) to afford
the desired products 3. An amplified experiment conducted in the presence of N-propargylindole 1a
(1155 mg, 5 mmol), 4-methylbenzoyl chloride 2a (3 equiv, 15 mmol), [Ir(ppy) ] (32.8 mg, 0.05 mmol),
3
o
Et N (1515 mg, 15 mmol) and CH CN (50 mL) at 100 C under argon atmosphere for 120 h could
3
3
deliver the target product 3aa in 51% yield (890.0 mg).
(1-Phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3aa): Yield: 55.8 mg, 80%; yellow oil;
1
H NMR (400 MHz, CDCl ) : 7.80 (d, J = 8.0 Hz, 2H), 7.53 (s, 1H), 7.46 (t, J = 6.8 Hz, 3H), 7.37-7.30
3
1
3
1
(m, 4H), 7.22-7.19 (m, 4H), 4.05 (s, 2H), 2.41 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 142.3,
3
1
1
3
39.8, 137.1, 134.7, 134.5, 134.4, 129.8, 128.7, 128.6, 128.6, 128.1, 127.8, 126.2, 126.1, 124.8, 119.7,
+
17.7, 110.6, 29.4, 21.6; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 350.1539, found
2
5
20
50.1544.
(1-(4-Methoxyphenyl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3ba): Yield: 65.2 mg, 86%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.0 Hz, 2H), 7.48 (s, 1H), 7.44 (d, J = 7.6 Hz,
3
1
H), 7.38 (t, J = 8.8 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 7.21 (d, J = 7.6 Hz, 2H), 7.19-7.16 (m, 1H), 6.87
1
3
1
(d, J = 8.8 Hz, 2H), 4.00 (s, 2H), 3.80 (s, 3H), 2.41 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2,
3
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57.9, 142.2, 139.7, 137.2, 134.5, 134.1, 129.7, 129.7, 128.7, 127.7, 126.8, 126.1, 125.9, 124.7, 119.3,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
1
17.7, 113.5, 110.5, 55.2, 29.3, 21.5; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 380.1645,
2
6
22
2
found 380.1650.
p-Tolyl(1-(p-tolyl)-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ca): Yield: 58.8 mg, 81%; yellow solid;
o
1
mp 156.0-156.5 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.81 (d, J = 8.4 Hz, 2H), 7.50 (s, 1H),
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7.46 (d, J = 7.2 Hz, 1H), 7.36-7.32 (m, 4H), 7.23-7.18 (m, 3H), 7.14 (d, J = 8.0 Hz, 2H), 4.03 (s, 2H),
13
1
2
1
.41 (s, 3H), 2.35 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.1, 142.3, 139.8, 137.2, 135.7, 134.5,
3
34.4, 131.4, 129.7, 128.8, 128.7, 128.4, 127.8, 126.2, 126.1, 124.7, 119.6, 117.6, 110.5, 29.3, 21.6,
+
21.2; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 364.1696, found 364.1703.
2
6
22
(1-([1,1'-Biphenyl]-4-yl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3da): Yield: 66.3 mg,
o
1
7
8%; yellow solid; mp 159.8-160.7 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.83 (d, J = 8.0 Hz,
3
2H), 7.61 (d, J = 7.2 Hz, 2H), 7.58-7.52 (m, 5H), 7.49-7.42 (m, 3H), 7.37-7.31 (m, 3H), 7.24-7.20 (m,
13
1
3
1
1
4
H), 4.09 (s, 2H), 2.42 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 142.4, 141.1, 139.7, 138.8,
3
37.2, 134.8, 134.5, 133.4, 129.8, 128.9, 128.8, 128.8, 128.7, 127.8, 127.0, 126.8, 126.2, 126.1, 124.8,
+
19.3, 117.9, 110.6, 29.5, 21.6; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 426.1852, found
31 24
26.1860.
(1-(4-(tert-Butyl)phenyl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3ea): Yield: 64.8 mg, 80%;
o
1
yellow solid; mp 156.4-157.3 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.78 (d, J = 8.4 Hz, 2H),
3
7
1
1
.52 (s, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.40-7.32 (m, 6H), 7.22-7.18 (m, 3H), 4.05 (s, 2H), 2.40 (s, 3H),
1
3
1
.32 (s, 9H); C{ H}NMR (100 MHz, CDCl ) δ: 191.3, 148.8, 142.2, 139.8, 137.3, 134.6, 134.5, 131.3,
3
29.8, 128.6, 128.2, 127.8, 126.2, 126.1, 125.0, 124.7, 119.6, 117.7, 110.5, 34.4, 31.3, 29.4, 21.5;
+
HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 406.2165, found 406.2174.
2
9
28
(1-(4-Fluorophenyl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3fa): Yield: 55.1 mg, 75%;
o
1
white solid; mp 154.7-155.2 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.0 Hz, 2H),
3
7
.52 (s, 1H), 7.47 (d, J = 7.2 Hz, 1H), 7.44-7.40 (m, 2H), 7.39-7.34 (m, 2H), 7.24-7.20 (m, 3H), 7.05-
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1
6
.99 (m, 2H), 4.01 (s, 2H), 2.42 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 161.4 (d, J = 243.6
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Hz, 1C), 142.4, 139.7, 137.1, 134.6, 134.4, 130.2 (d, J = 7.9 Hz, 1C), 129.7, 128.8, 127.9, 126.2, 125.9,
1
9
124.9, 118.7, 117.8, 115.1, 114.8, 110.6, 29.2, 21.6; F NMR (282 MHz, CDCl ) : -116.5 (s, 1F);
3
19
+
HRMS (ESI-TOF) m/z: C H FNO (M + H) calcd for 368.1445, found 368.1450.
2
5
19
(1-(4-Chlorophenyl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3ga): Yield: 58.3 mg, 76%;
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
yellow solid; mp 105.3-105.8 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.0 Hz, 2H),
3
7
2
.52 (s, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.40-7.34 (m, 4H), 7.31-7.27 (m, 2H), 7.24-7.20 (m, 3H), 4.02 (s,
1
3
1
H), 2.43 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.1, 142.5, 139.6, 137.1, 134.9, 134.3, 132.9,
3
131.8, 129.8, 129.7, 128.8, 128.2, 127.9, 126.2, 125.9, 124.9, 118.6, 118.0, 110.6, 29.3, 21.6; HRMS
35
+
(
ESI-TOF) m/z: C H ClNO (M + H) calcd for 384.1150, found 384.1158.
25 19
4
-(2-(4-Methylbenzoyl)-9H-pyrrolo[1,2-a]indol-1-yl)benzonitrile (3ha): Yield: 51.6 mg, 69%; yellow
o
1
solid; mp 90.0-90.6 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.80 (d, J = 8.0 Hz, 2H), 7.62-7.60
3
(m, 2H), 7.56-7.54 (m, 3H), 7.50 (d, J = 7.6 Hz, 1H), 7.42-7.36 (m, 2H), 7.26-7.23 (m, 3H), 4.06 (s, 2H),
1
3
1
2
.44 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 190.9, 142.9, 139.5, 139.4, 136.8, 135.9, 134.0, 131.9,
3
129.7, 129.0, 128.9, 128.1, 126.2, 126.0, 125.2, 119.3, 118.5, 118.1, 110.8, 109.3, 29.6, 21.6; HRMS
+
(
ESI-TOF) m/z: C H N O (M + H) calcd for 375.1492, found 375.1499.
2
6
19
2
p-Tolyl(1-(4-(Trifluoromethyl)phenyl)-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ia): Yield: 55.0 mg,
o
1
66%; yellow solid; mp 152.8-153.2 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.80 (d, J = 8.4 Hz,
3
2
2
H), 7.59-7.53 (m, 5H), 7.49 (d, J = 7.6 Hz, 1H), 7.41-7.36 (m, 2H), 7.25-7.22 (m, 3H), 4.05 (s, 2H),
1
3
1
.42 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 190.9, 142.6, 139.5, 136.9, 138.2 (2C), 135.5, 134.2,
3
129.7, 128.4, 128.0, 127.9 (q, J = 32.1 Hz, 1C), 126.2, 126.0, 125.1, 125.0 (q, J = 3.8 Hz, 1C), 124.3 (q,
19
J = 270.1 Hz, 1C), 118.4, 118.2, 110.7, 29.4, 21.5; F NMR (282 MHz, CDCl ) : -62.3 (s, 3F);HRMS
3
1
9
+
(
ESI-TOF) m/z: C H F NO (M + H) calcd for 418.1413, found 418.1420.
26 19 3
(1-(3-Methoxyphenyl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3ja): Yield: 62.2 mg, 82%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.0 Hz, 2H), 7.53 (s, 1H), 7.46 (d, J = 7.2 Hz,
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H), 7.38-7.33 (m, 2H), 7.23-7.19 (m, 4H), 7.04 (d, J = 7.6 Hz, 1H), 6.99 (s, 1H), 6.77-6.75 (m, 1H),
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
1
4
.05 (s, 2H), 3.77 (s, 3H), 2.40 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 159.3, 142.4, 139.7,
3
137.1, 135.8, 134.8, 134.5, 129.8, 129.0, 128.7, 127.8, 126.3, 126.2, 124.8, 121.1, 119.4, 117.6, 114.2,
+
1
3
11.8, 110.6, 55.2, 29.5, 21.6; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 380.1645, found
2
6
22
2
80.1650.
p-Tolyl(1-(m-tolyl)-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ka): Yield: 55.2 mg, 76%; yellow oil;
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.4 Hz, 2H), 7.52 (s, 1H), 7.46 (d, J = 7.2 Hz, 1H), 7.38-
3
7
.33 (m, 2H), 7.26-7.18 (m, 6H), 7.03 (d, J = 7.2 Hz, 1H), 4.05 (s, 2H), 2.41 (s, 3H), 2.32 (s, 3H);
1
3
1
C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 142.3, 139.8, 137.5, 137.2, 134.6, 134.5, 134.2, 129.7, 129.3,
3
1
28.7, 128.0, 127.8, 126.9, 126.2, 126.1, 125.7, 124.7, 119.7, 117.6, 110.6, 29.4, 21.6, 21.5; HRMS
+
(ESI-TOF) m/z: C H NO (M + H) calcd for 364.1696, found 364.1703.
2
6
22
(1-(2-Methoxyphenyl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3la): Yield: 58.4 mg, 77%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.75 (d, J = 8.0 Hz, 2H), 7.56(s, 1H), 7.44 (d, J = 7.6 Hz,
3
1
H), 7.38-7.34 (m, 3H), 7.22-7.17 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.95 (t, J = 7.6 Hz, 1H), 6.78 (d, J
1
3
1
=
8.0 Hz, 1H), 3.95 (s, 2H), 3.62 (s, 3H), 2.37 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 156.1,
3
1
1
3
42.0, 140.1, 136.7, 135.0, 134.7, 130.1, 129.6, 128.4, 127.9, 127.7, 127.6, 126.1, 124.4, 123.6, 120.4,
+
16.0, 115.1, 110.5, 110.4, 55.0, 29.3, 21.5; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for
2
6
22
2
80.1645, found 380.1650.
p-Tolyl(1-(o-tolyl)-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ma): Yield: 50.8 mg, 70%; yellow oil;
1
H NMR (400 MHz, CDCl ) : 7.74 (d, J = 8.4 Hz, 2H), 7.57 (s, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.37 (d,
3
J = 4.0 Hz, 2H), 7.29-7.27 (m, 1H), 7.24-7.17 (m, 6H), 3.84 (t, J = 7.2 Hz, 2H), 2.40 (s, 3H), 2.21 (s,
1
3
1
3H); C{ H}NMR (100 MHz, CDCl ) δ: 190.9, 142.0, 140.0, 137.1, 136.7, 134.8, 134.6, 134.4, 129.8,
3
1
29.8, 129.5, 128.7, 127.8, 127.4, 126.9, 126.2, 125.4, 124.7, 119.2, 116.9, 110.6, 28.8, 21.5, 20.1;
+
HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 364.1696, found 364.1703.
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1-(3,5-Dimethylphenyl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3na): Yield: 51.5 mg, 68%;
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.78 (d, J = 8.0 Hz, 2H), 7.51 (s, 1H), 7.47 (t, J = 7.2 Hz,
3
1H), 7.36-7.33 (m, 2H), 7.21 (d, J = 7.6 Hz, 3H), 7.05 (s, 2H), 6.85 (s, 1H), 4.05 (s, 2H), 2.41 (s, 3H),
13
1
2
1
.29 (s, 6H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 142.2, 139.8, 137.4, 137.3, 134.6, 134.5, 134.1,
3
29.7, 128.7, 127.9, 127.8, 126.4, 126.3, 126.1, 124.7, 119.8, 117.6, 110.5, 29.4, 21.6, 21.3; HRMS
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
(ESI-TOF) m/z: C H NO (M + H) calcd for 378.1852, found 378.1856.
2
7
24
(1-(Naphthalen-1-yl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3oa): Yield: 54.3 mg, 68%;
o
1
yellow solid; mp 153.8-154.2 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.88 (d, J = 8.4 Hz, 1H),
3
7.83 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.69 (t, J = 8.4 Hz, 3H), 7.48-7.36 (m, 7H), 7.20 (t, J
13
1
=
7.2 Hz, 1H), 7.07 (d, J = 8.0 Hz, 2H), 3.86-3.73 (m, 2H), 2.33 (s, 3H); C{ H}NMR (100 MHz,
CDCl ) δ: 190.9, 141.9, 140.0, 137.1, 135.6, 134.7, 133.7, 132.6, 132.0, 129.3, 128.4, 128.3, 128.0,
3
127.8, 127.5, 127.2, 126.2, 125.8, 125.7, 125.4, 125.3, 124.8, 117.7, 116.9, 110.7, 29.0, 21.5; HRMS
+
(
ESI-TOF) m/z: C H NO (M + H) calcd for 400.1700, found 400.1708.
2
9
22
(1-(Thiophen-2-yl)-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3pa): Yield: 45.4 mg, 64%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.82 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 7.2 Hz, 1H), 7.46 (t, J =
3
3
3
.2 Hz, 2H), 7.37-7.32 (m, 2H), 7.27 (s, 1H), 7.25-7.23 (m, 3H), 7.05-7.03 (m, 1H), 4.11 (s, 2H), 2.44 (s,
1
3
1
H); C{ H}NMR (100 MHz, CDCl ) δ: 191.1, 142.5, 139.6, 137.4, 136.2, 134.9, 134.5, 129.8, 128.8,
3
127.9, 127.2, 126.2, 125.9, 125.8, 124.9, 123.5, 118.1, 113.1, 110.7, 30.4, 21.6; HRMS (ESI-TOF) m/z:
+
C H NOS (M + H) calcd for 356.1104, found 356.1110.
2
3
18
(9-Methyl-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3sa): Yield: 55.9 mg, 77%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.78 (d, J = 8.0 Hz, 2H), 7.47-7.44 (m, 3H), 7.41 (d, J = 7.2
3
Hz, 1H), 7.36-7.30 (m, 4H), 7.24-7.19 (m, 4H), 4.41-4.36 (m, 1H), 2.40 (s, 3H), 1.37 (d, J = 3H);
1
3
1
C{ H}NMR (100 MHz, CDCl ) δ: 191.1, 142.2, 140.7, 139.6, 138.9, 137.2, 134.1, 129.7, 129.1, 128.7,
3
1
27.9, 127.8, 126.4, 126.2, 125.0, 124.9, 120.1, 117.1, 110.5, 36.1, 21.5, 17.2; HRMS (ESI-TOF) m/z:
+
C H NO (M + H) calcd for 364.1696, found 364.1703.
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8-Methyl-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3ta): Yield: 58.1 mg, 80%;
1
2
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.80 (d, J = 8.0 Hz, 2H), 7.50 (s, 1H), 7.48-7.45 (m, 2H),
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
7.33 (t, J = 7.6 Hz, 2H), 7.27 (d, J = 7.6Hz, 1H), 7.24-7.16 (m, 4H), 7.02 (d, J = 7.6 Hz, 1H), 3.93 (s,
13
1
2
H), 2.40 (s, 3H), 2.37 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 142.3, 139.4, 137.2, 135.8,
3
1
34.7, 134.5, 133.3, 129.7, 128.7, 128.6, 128.6, 128.1, 127.8, 126.1, 125.9, 119.6, 117.8, 108.0, 28.4,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
21.6, 18.5; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 364.1696, found 364.1703.
2
6
22
(8-Chloro-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3ua): Yield: 55.2 mg, 72%;
o
1
yellow solid; mp 59.9-60.8 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.0 Hz, 2H),
3
7.51 (s, 1H), 7.45-7.43 (m, 2H), 7.33 (t, J = 8.0 Hz, 3H), 7.26-7.19 (m, 5H), 4.06 (s, 2H), 2.41 (s, 3H);
13
1
C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 142.6, 140.9, 136.9, 134.0, 133.8, 133.0, 131.8, 129.8, 129.3,
3
1
28.8, 128.5, 128.2, 126.6, 126.3, 124.9, 120.0, 117.6, 108.9, 29.2, 21.6; HRMS (ESI-TOF) m/z:
3
5
+
C H ClNO (M + H) calcd for 384.1150, found 384.1158.
2
5
19
(7-Methoxy-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3va): Yield: 59.1 mg, 78%;
o
1
yellow solid; mp 170.7-171.2 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.0 Hz, 2H),
3
7.45 (t, J = 7.2 Hz, 3H), 7.32 (t, J = 7.6 Hz, 2H), 7.26 (d, J = 3.2 Hz, 1H), 7.23-7.19 (m, 3H), 7.03 (d, J
13
1
=
2.0 Hz, 1H), 6.89-6.86 (m, 1H), 4.01 (s, 2H), 3.84 (s, 3H), 2.41 (s, 3H); C{ H}NMR (100 MHz,
CDCl ) δ: 191.1, 157.5, 142.2, 137.3, 136.1, 134.6, 134.5, 133.6, 129.7, 128.7, 128.6, 128.1, 126.1,
3
+
125.5, 119.8, 117.6, 112.6, 112.6, 110.9, 55.8, 29.6, 21.5; HRMS (ESI-TOF) m/z: C H NO (M + H)
2
6
22
2
calcd for 380.1645, found 380.1650.
7-Bromo-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3wa): Yield: 56.5 mg, 66%;
(
o
1
yellow solid; mp 147.2-147.8 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.78 (d, J = 8.0 Hz, 2H),
3
7
4
1
.57 (s, 1H), 7.48-7.46 (m, 2H), 7.41 (t, J = 7.2 Hz, 2H), 7.31 (t, J = 8.0 Hz, 2H), 7.22-7.18 (m, 4H),
1
3
1
.01 (s, 2H), 2.40 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.1, 142.5, 138.9, 136.9, 136.6, 134.2,
3
34.0, 130.8, 129.7, 129.3, 128.7, 128.5, 128.1, 126.6, 126.3, 120.0, 117.6, 117.5, 111.8, 29.3, 21.6;
7
9
+
HRMS (ESI-TOF) m/z: C H BrNO (M + H) calcd for 428.0645, found 428.0653.
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6-Methyl-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3xa): Yield: 59.5 mg, 82%;
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
1
yellow solid; mp 136.9-137.4 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.80 (d, J = 8.0 Hz, 2H),
3
7.50 (s, 1H), 7.46-7.44 (m, 2H), 7.32 (t, J = 7.6 Hz, 3H), 7.22-7.18 (m, 3H), 7.17 (s, 1H), 7.01 (d, J =
13
1
7
1
.6 Hz, 1H), 4.00 (s, 2H), 2.43 (s, 3H), 2.41 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.2, 142.3,
3
39.9, 138.0, 137.2, 135.2, 134.4, 131.5, 129.7, 128.7, 128.6, 128.6, 128.1, 126.1, 125.9, 125.7, 125.5,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
119.6, 117.7, 111.3, 29.1, 21.6; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 364.1696, found
2
6
22
3
64.1703.
6-Fluoro-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3ya): Yield: 53.6 mg, 73%;
(
o
1
yellow solid; mp 90.2-90.8 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.79 (d, J = 7.6 Hz, 2H),
3
7
.47 (s, 1H), 7.43 (d, J = 7.2 Hz, 2H), 7.40-7.37 (m, 1H), 7.34-7.30 (m, 2H), 7.23-7.20 (m, 3H), 7.07-
1
3
1
7
.05 (m, 1H), 6.93-6.88 (m, 1H), 4.00 (s, 2H), 2.41 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.1,
3
162.6 (d, J = 244.1 Hz, 1C), 142.6, 140.8 (d, J = 11.5 Hz, 1C), 136.9, 135.5, 134.1, 129.8 (d, J = 5.2 Hz,
1
C), 128.8, 128.5, 128.1, 126.9, 126.8, 126.6, 126.3, 119.9, 117.5, 111.3 (d, J = 12.5 Hz, 1C), 99.2 (d, J
1
9
=
17.1 Hz, 1C), 28.9, 21.6; F NMR (282 MHz, CDCl ) : -113.0 (s, 1F); HRMS (ESI-TOF) m/z:
3
1
9
+
C H FNO (M + H) calcd for 368.1445, found 368.1450.
2
5
19
(5-Methyl-1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(p-tolyl)methanone (3za): Yield: 55.2 mg, 76%;
o
1
yellow solid; mp 141.3-141.7 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.79 (d, J = 8.4 Hz, 2H),
3
7.68 (s, 1H), 7.42 (t, J = 7.2 Hz, 2H), 7.32-7.28 (m, 3H), 7.21-7.18 (m, 3H), 7.15-7.09 (m, 2H), 4.04 (s,
13
1
2
1
H), 2.58 (s, 3H), 2.39 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 191.4, 142.3, 138.7, 137.0, 135.1,
3
34.6, 134.4, 130.0, 129.8, 128.7, 128.6, 128.1, 126.2, 126.0, 124.6, 123.7, 122.5, 120.3, 119.1, 29.3,
+
21.6, 18.5; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 364.1696, found 364.1703.
2
6
22
(4-Methoxyphenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ab): Yield: 61.3 mg, 84%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.90 (d, J = 8.8 Hz, 2H), 7.53 (s, 1H), 7.47 (d, J = 7.6 Hz,
3
1H), 7.43 (t, J = 6.8 Hz, 2H), 7.36 (t, J = 2.8 Hz, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.23-7.18 (m, 2H), 6.89
13
1
(
d, J = 8.8 Hz, 2H), 4.05 (s, 2H), 3.85 (s, 3H); C{ H}NMR (100 MHz, CDCl ) δ: 190.4, 162.7, 139.8,
3
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34.5, 134.5, 134.4, 132.4, 131.9, 128.5, 128.1, 127.8, 126.3, 126.2, 126.1, 124.7, 119.5, 117.0, 113.2,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
10.5, 55.4, 29.4; HRMS (ESI-TOF) m/z: C H NO (M + H) calcd for 366.1489, found 366.1495.
2
5
20
2
(4-Fluorophenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ac): Yield: 53.7 mg, 76%;
o
1
yellow solid; mp 84.4-84.7 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.91-7.86 (m, 2H), 7.56 (s,
3
1
H), 7.47 (d, J = 7.6 Hz, 1H), 7.41-7.37 (m, 4H), 7.31 (t, J = 8.0 Hz, 2H), 7.25-7.19 (m, 2H), 7.08-7.02
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1
(m, 2H), 4.05 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 190.1, 165.0 (d, J = 251.0 Hz, 1C), 139.7,
3
1
35.9 (d, J = 2.9 Hz, 1C), 134.8, 134.5, 134.2, 132.0 (d, J = 8.9 Hz, 1C), 128.6, 128.1, 127.9, 126.2 (d, J
1
9
=
4.0 Hz, 1C), 125.9, 124.9, 119.7, 117.5, 115.1, 114.9, 110.7, 29.4; F NMR (282 MHz, CDCl ) : -
3
1
9
+
107.5 (s, 1F); HRMS (ESI-TOF) m/z: C H FNO (M + H) calcd for 354.1289, found 354.1294.
2
4
17
(4-Chlorophenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ad): Yield: 56.8 mg, 77%;
o
1
yellow solid; mp 145.9-146.1 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.80 (d, J = 8.4 Hz, 2H),
3
1
3
1
7.55 (s, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.42-7.30 (m, 8H), 7.25-7.20 (m, 2H), 4.05 (s, 2H); C{ H}NMR
(100 MHz, CDCl ) δ: 190.2, 139.6, 138.1, 137.9, 134.9, 134.5, 134.1, 130.9, 128.6, 128.3, 128.1, 127.9,
3
1
26.3, 126.2, 125.8, 125.0, 119.7, 117.7, 110.7, 29.3; HRMS (ESI-TOF) m/z: C H 35ClNO (M + H)+
24 17
calcd for 370.0993, found 370.0998.
(4-Bromophenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ae): Yield: 57.8 mg, 70%;
o
1
brown solid; mp 132.9-136.3 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.73 (d, J = 8.4 Hz, 2H),
3
7.55-7.52 (m, 3H), 7.48 (d, J = 7.6 Hz, 1H), 7.43-7.36 (m, 4H), 7.32 (t, J = 8.0 Hz, 2H), 7.25-7.20 (m,
13
1
2
1
H), 4.05 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 190.3, 139.6, 138.6, 134.9, 134.5, 134.1, 131.3,
3
31,1, 128.6, 128.1, 127.9, 126.5, 126.3, 126.2, 125.7, 125.0, 119.7, 117.8, 110.7, 29.3; HRMS (ESI-
7
9
+
TOF) m/z: C H BrNO (M + H) calcd for 414.0488, found 414.0497.
2
4
17
(1-Phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(4-(trifluoromethyl)phenyl)methanone (3ag): Yield: 50.0 mg,
o
1
6
2%; yellow solid; mp 150.9-151.2 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.92 (d, J = 8.0 Hz,
3
2H), 7.65 (d, J = 8.0 Hz, 2H), 7.56 (s, 1H), 7.48 (d, J = 7.2 Hz, 1H), 7.43-7.38 (m, 4H), 7.34-7.30 (m,
13
1
2
H), 7.25-7.20 (m, 2H), 4.05 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 190.2, 143.0, 139.5, 135.1,
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34.5, 134.0, 132.9 (q, J = 32.3 Hz, 1C), 129.6, 128.7, 128.1, 127.9, 126.4, 126.2, 125.6, 125.2, 125.0 (q,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
9
J = 3.8 Hz, 1C), 123.8 (q, J = 270.9 Hz, 1C), 119.8, 118.3, 110.8, 29.3; F NMR (282 MHz, CDCl ) :
3
1
9
+
-62.9 (s, 3F); HRMS (ESI-TOF) m/z: C H F NO (M + H) calcd for 404.1257, found 404.1265.
2
5
17
3
Phenyl(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ah): Yield: 53.6 mg, 80%; yellow solid;
o
1
mp 95.1-95.6 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.87 (t, J = 6.8 Hz, 2H), 7.55 (s, 1H),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
7
.53-7.46 (m, 3H), 7.42 (t, J = 7.6 Hz, 3H), 7.37 (t, J = 6.4 Hz, 2H), 7.32 (t, J = 8.0 Hz, 2H), 7.24-7.20
1
3
1
(m, 2H), 4.06 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 191.5, 139.9, 139.7, 134.8, 134.5, 134.3,
3
1
31.7, 129.6, 128.6, 128.6, 128.1, 128.0, 127.8, 126.2, 126.0, 124.9, 119.8, 118.0, 110.7, 29.4; HRMS
+
(ESI-TOF) m/z: C H NO (M + H) calcd for 336.1383, found 336.1390.
2
4
18
(3-methoxyphenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ai): Yield: 58.4 mg, 81%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.57 (s, 1H), 7.48-7.44 (m, 4H), 7.41-7.40 (m, 1H), 7.36-
3
1
3
1
7.29 (m, 5H), 7.23-7.19 (m, 2H), 7.07-7.04 (m, 1H), 4.04 (m, 2H), 3.81 (m, 3H); C{ H}NMR (100
MHz, CDCl ) δ: 191.1, 159.3, 141.1, 139.7, 134.8, 134.5, 134.3, 129.0, 128.6, 128.1, 127.8, 126.2,
3
1
26.2, 125.9, 124.9, 122.3, 119.7, 118.3, 118.0, 113.8, 110.7, 55.4, 29.4; HRMS (ESI-TOF) m/z:
+
C H NO (M + H) calcd for 366.1489, found 366.1495.
2
5
20
2
(1-Phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(m-tolyl)methanone (3aj): Yield: 52.4 mg, 75%; yellow solid;
o
1
mp 106.2-106.5 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.67 (t, J = 5.2 Hz, 2H), 7.55 (s, 1H),
3
7.47-7.43 (m, 3H), 7.36 (t, J = 3.6 Hz, 2H), 7.33-7.28 (m, 4H), 7.23-7.18 (m, 2H), 4.05 (s, 2H), 2.36 (s,
13
1
3
1
H); C{ H}NMR (100 MHz, CDCl ) δ: 191.7, 139.8, 139.7, 137.8, 134.7, 134.5, 134.4, 132.5, 130.2,
3
28.6, 128.0, 128.0, 127.9, 127.8, 126.8, 126.2, 126.1, 124.8, 119.7, 117.9, 110.6, 29.4, 21.3; HRMS
+
(ESI-TOF) m/z: C H NO (M + H) calcd for 350.1539, found 350.1544.
2
5
20
(3-fluorophenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ak): Yield: 49.4 mg, 70%; yell
1
ow oil; H NMR (400 MHz, CDCl ) : 7.64 (d, J = 7.6 Hz, 1H), 7.57-7.53 (m, 2H), 7.48-7.30 (m, 8H),
3
1
3
1
7.25-7.16 (m, 3H), 4.04 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 189.9, 162.3 (d, J = 245.6 Hz, 1C),
3
1
41.9 (d, J = 6.1 Hz, 1C), 139.6, 135.0, 134.5, 134.1, 129.6 (d, J = 7.7 Hz, 1C), 128.6, 128.1, 127.9,
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26.3, 126.2, 125.6, 125.3 (d, J = 3.0 Hz, 1C), 125.0, 119.8, 118.6 (d, J = 21.3 Hz, 1C), 118.0, 116.3 (d,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
9
J = 22.1 Hz, 1C), 110.8, 29.3; F NMR (282 MHz, CDCl ) : -112.8 (s, 1F); HRMS (ESI-TOF) m/z:
3
1
9
+
C H FNO (M + H) calcd for 354.1289, found 354.1294.
2
4
17
(3-chlorophenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3al): Yield: 50.3 mg, 68%;
o
1
yellow solid; mp 133.9-134.3 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.81 (t, J = 2.0 Hz, 1H),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
7
2
1
.73-7.70 (m, 1H), 7.57 (s, 1H), 7.48-7.43 (m, 2H), 7.42-7.40 (m, 4H), 7.39-7.30 (m, 3H), 7.25-7.21 (m,
1
3
H), 4.04 (s, 2H); C{1H}NMR (100 MHz, CDCl ) δ: 189.9, 141.4, 139.6, 135.0, 134.5, 134.1, 131.6,
3
29.5, 129.3, 128.6, 128.6, 128.1, 127.9, 127.6, 126.3, 126.2, 125.6, 125.0, 119.8, 117.9, 110.8, 29.3;
3
5
+
HRMS (ESI-TOF) m/z: C H ClNO (M + H) calcd for 370.0993, found 370.0998.
2
4
17
(2-methoxyphenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3am): Yield: 56.2 mg, 77%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 7.50-7.47 (m, 3H), 7.44-7.40 (m, 2H), 7.35-7.28 (m, 5H),
3
7.22-7.19 (m, 2H), 6.95 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 3.99 (s, 2H), 3.74 (s, 3H);
13
1
C{ H}NMR (100 MHz, CDCl ) δ: 190.8, 157.1, 139.7, 134.9, 134.5, 134.2, 131.1, 131.0, 129.3, 129.0,
3
1
27.8, 127.7, 127.6, 126.2, 126.1, 124.8, 119.9, 119.5, 118.8, 111.2, 110.7, 55.6, 29.2; HRMS (ESI-
+
TOF) m/z: C H NO (M + H) calcd for 366.1489, found 366.1495.
2
5
20
2
(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(o-tolyl)methanone (3an): Yield: 48.9 mg, 70%; yellow solid;
o
1
mp 129.3-129.6 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.54 (t, J = 7.2 Hz, 2H), 7.49 (d, J =
3
7.6 Hz, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.38-7.28 (m, 6H), 7.27-7.18 (m, 4H), 4.02 (s, 2H), 2.42 (s, 3H);
13
1
C{ H}NMR (100 MHz, CDCl ) δ: 193.3, 140.7, 139.6, 136.6, 135.3, 134.5, 134.2, 130.7, 129.6, 128.8,
3
1
28.5, 128.0, 127.8, 127.2, 126.4, 126.2, 125.0, 124.9, 119.6, 119.4, 110.7, 29.3, 19.9; HRMS (ESI-
+
TOF) m/z: C H NO (M + H) calcd for 350.1539, found 350.1544.
2
5
20
(2-Fluorophenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ao): Yield: 45.9 mg, 65%;
o
1
yellow solid; mp 125.9-126.2 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.57-7.53 (m, 2H), 7.48-
3
7.43 (m, 3H), 7.40-7.38 (m, 1H), 7.36-7.29 (m, 4H), 7.23-7.19 (m, 2H), 7.17-7.13 (m, 1H), 7.02 (t, J =
13
1
8
.4 Hz, 1H), 4.00 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 187.6, 159.8 (d, J = 249.7 Hz, 1C), 139.5,
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35.1, 134.5, 134.0, 132.0 (d, J = 7.2 Hz, 1C), 130.4 (d, J = 3.0 Hz, 1C), 129.4, 129.2, 128.9, 127.8 (d, J
5.9 Hz, 1C), 127.0, 126.3 (d, J = 18.3 Hz, 1C), 125.1, 123.8 (d, J = 3.6 Hz, 1C), 119.6, 118.7, 116.1,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
=
115.8, 110.8, 29.2; F NMR (282 MHz, CDCl ) : -113.0 (s, 1F); HRMS (ESI-TOF) m/z: C H1719FNO
1
9
3
24
+
(M + H) calcd for 354.1289, found 354.1294.
(3,5-Dichlorophenyl)(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ap): Yield: 46.7 mg, 58%;
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
yellow oil; H NMR (400 MHz, CDCl ) : 8.43-8.41 (m, 1H), 7.80 (s, 1H), 7.70 (d, J = 2.0 Hz, 2H),
3
1
3
1
7
.56-7.53 (m, 2H), 7.44-7.39 (m, 4H), 7.36-7.32 (m, 3H), 5.17 (s, 2H); C{ H}NMR (100 MHz, CDCl )
3
δ: 187.4, 143.3, 136.7, 136.3, 135.1, 131.7, 130.9, 129.1, 128.4, 127.2, 127.0, 124.3, 123.4, 122.8, 121.5,
3
5
+
115.4, 110.0, 87.2, 80.9, 37.6; HRMS (ESI-TOF) m/z: C H Cl NO (M + H) calcd for 404.0604,
2
4
16
2
found 404.0612.
naphthalen-1-yl(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)methanone (3ap): Yield: 46.2 mg, 60%;
1
yellow oil; H NMR (400 MHz, CDCl ) : 8.32-8.29 (m, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.88-7.86 (m,
3
1
H), 7.77-7.75 (m, 1H), 7.56 (t, J = 7.2 Hz, 2H), 7.50-7.47 (m, 2H), 7.45 (t, J = 7.2 Hz, 2H), 7.39 (s,
1
3
1
1
H), 7.34-7.29 (m, 3H), 7.23-7.17 (m, 3H), 4.03 (s, 2H); C{ H}NMR (100 MHz, CDCl ) δ: 192.5,
3
139.5, 138.5, 135.2, 134.5, 134.1, 133.6, 131.0, 130.6, 128.8, 128.1, 127.9, 127.8, 127.8, 127.2, 126.9,
26.4, 126.2, 126.2, 126.0, 125.0, 124.2, 119.9, 119.5, 110.8, 29.3; HRMS (ESI-TOF) m/z: C H NO
1
2
8
20
+
(M + H) calcd for 386.1539, found 386.1547.
(1-phenyl-9H-pyrrolo[1,2-a]indol-2-yl)(thiophen-2-yl)methanone (3ar): Yield: 37.5 mg, 55%; yellow
1
oil; H NMR (400 MHz, CDCl ) : 7.71 (s, 1H), 7.70 (t, J = 2.4 Hz, 1H), 7.61-7.60 (m, 1H), 7.48-7.46
3
1
3
1
(m, 3H), 7.39-7.32 (m, 4H), 7.24-7.20 (m, 2H), 7.09-7.07 (m, 1H), 4.04 (s, 2H); C{ H}NMR (100
MHz, CDCl ) δ: 182.8, 145.6, 139.7, 134.8, 134.4, 134.2, 133.1, 132.6, 128.5, 128.2, 127.8, 127.5,
3
+
1
26.2, 126.0, 124.8, 119.3, 116.5, 110.6, 29.4; HRMS (ESI-TOF) m/z: C H NOS (M + H) calcd for
2
2
16
3
42.0947, found 342.0955.
-(4-Methoxyphenyl)-3,3-diphenylprop-2-en-1-one (4): Yield: 39.6 mg, 63%; yellow solid; mp 95.1-
1
o
1
9
5.6 C (uncorrected); H NMR (400 MHz, CDCl ) : 7.91 (d, J = 8.8 Hz, 2H), 7.39-7.36 (m, 5H), 7.27-
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3
7
.25 (m, 3H), 7.19-7.17 (m, 2H), 7.08 (s, 1H), 6.86 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H); C{1H}NMR
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
100 MHz, CDCl ) δ: 191.4, 163.2, 153.5, 141.5, 139.1, 131.1, 129.7, 128.5, 128.4, 128.2, 128.0, 113.5,
3
+
55.4; HRMS (ESI-TOF) m/z: C H O (M + H) calcd for 315.1380, found 315.1386.
2
2
19
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Supporting Information Available: The copies of spectra. This material is available free of charge
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via the Internet at http://pubs.acs.org.
Acknowledgments. We thank the Scientific Research Fund of Hunan Provincial Education
Department (No. 16A087 and 18B350), Hunan Provincial Innovation Foundation For Postgraduate
(CX20190921), Natural Science Foundation of Hunan Province (No. 2018JJ3208) and National Natural
Science Foundation of China (No. 21602056 and 51874132) for financial support.
References and notes
(
1) (a) Toyota, M.; Ihara, M. Recent Progress in the Chemistry of Non-monoterpenoid Indole
Alkaloids. Nat. Prod. Rep. 1998, 15, 327−340. (b) Monakhova, N.; Ryabova, S.; Makarov, V.
Synthesis and Some Biological Properties of Pyrrolo[1,2‐a]indoles. J. Heterocycl. Chem. 2016, 53,
685−709. (c) Lorton, C.; Voituriez, A. Synthesis and Applications of 9H-Pyrrolo[1,2-a]indole and
9
H-Pyrrolo[1,2-a]indol-9-one Derivatives. Eur. J. Org. Chem. 2019, 5133−5150.
(
2) (a) Galm, U.; Hager, M.-H.; Lanen, S.-G.-V.; Ju, J.-H.; Thorson, J.-S.; Shen, B. Antitumor
Antibiotics: Bleomycin, Enediynes, and Mitomycin. Chem. Rev. 2005, 105, 739−758. (b)
Kakadiya, R.; Dong, H.-J.; Lee, P.-C.; Kapuriya, N.; Zhang, X.-G.; Chou, T.-C.; Lee, T.-C.;
Kapuriya, K.; Shah, A.; Su, T.-L. Potent Antitumor Bifunctional DNA Alkylating Agents,
Synthesis and Biological Activities of 3a-aza-cyclopenta[a]indenes. Bioorg. Med. Chem. 2009,
1
7, 5614−5626. (c) Bass, P.-D.; Gubler, D.-A.; Judd, T.-C.; Williams, R.-M. Mitomycinoid
Alkaloids: Mechanism of Action, Biosynthesis, Total Syntheses, and Synthetic Approaches. Chem.
Rev. 2013, 113, 6816−6863. (d) Huang, X.; Zhu, S.-G.; Shen, R.-W. Palladium-Catalyzed
ACS Paragon Plus Environment
2
3

The Journal of Organic Chemistry
Page 24 of 31
Sequential Reactions via Allene Intermediates for the Rapid Synthesis of Fused Polycyclic Pyrrole
Derivatives. Adv. Synth. Catal. 2009, 351, 3118−3122. (e) Tomasz, M.; Palom, Y. The Mitomycin
Bioreductive Antitumor Agents: Cross-Linking and Alkylation of DNA as the Molecular Basis of
Their Activity. Pharmacol. Ther. 1997, 76, 73−87.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
3) (a) Wolkenberg, S.-E.; Boger, D. L. Mechanisms of in Situ Activation for DNA-Targeting
Antitumor Agents. Chem. Rev. 2002, 102, 2477−2496. (b) Tanaka, M.; Ubukata, M.; Yasue, K.;
Matsumoto, K.; Kajimoto, Y.; Ogo, T.; Inaba, T. One-Step Synthesis of Heteroaromatic-Fused
Pyrrolidines via Cyclopropane Ring-Opening Reaction: Application to the PKCβ Inhibitor JTT-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
010. Org. Lett. 2007, 9, 3331−3334. (c) Ren, H.-J.; Knochel, P. Chemoselective Benzylic C-H
Activations for the Preparation of Condensed N-Heterocycles. Angew.Chem. Int. Ed. 2006, 45,
3
462−3465. (d) Dethe, D.-H.; Erande, R.-D.; Ranjan, A. Biomimetic Total Syntheses of
Flinderoles B and C. J. Am. Chem. Soc. 2011, 133, 2864−2867. (e) Hao, L.; Pan, Y.-M.; Wang, T.;
Lin, M.; Chen, L.; Zhan, Z.-P. Chemoselective Cascade Synthesis of N-Fused Heterocycles via
Silver(I) Triflate-Catalyzed Friedel–Crafts/N−C Bond Formation Sequence. Adv. Synth. Catal.
2
010, 352, 3215−3222. (f) Bradner, W.-T. Mitomycin C: A Clinical Update. Cancer Treat. Rev.
001, 27, 35−50. (g) Liu, J.-F.; Jiang, Z.-Y.; Wang, R.-R.; Zheng, Y.-T.; Chen, J.-J.; Zhang, X.-M.;
2
Ma, Y.-B. Isatisine A, a Novel Alkaloid with an Unprecedented Skeleton from Leaves of Isatis
indigotica. Org. Lett. 2007, 9, 4127−4129.
(4) Yoshihara, T.; Druzhinin, S.-I.; Zachariasse, K.-A. Fast Intramolecular Charge Transfer with a
Planar Rigidized Electron Donor/Acceptor Molecule. J. Am. Chem. Soc. 2004, 126, 8535−8539.
(
5) (a) Huang, H.-G.; Yu, M.-L.; Su, X.-L.; Guo, P.; Zhao, J.; Li, Y. Sustainable Radical Cascades to
Synthesize Difluoroalkylated Pyrrolo[1,2‑a]indoles. J. Org. Chem. 2018, 83, 2425−2437. (b)
Casado-Sánchez, A.; Domingo-Legarda, P.; Cabrera, S.; Alemán, J. Visible Light Photocatalytic
Asymmetric Synthesis of Pyrrolo[1,2a]indoles via Intermolecular [3+2] Cycloaddition. Chem.
Commun. 2019, 55, 11303−11306. (c) Tucker, J.-W.; Narayanam, J. M. R.; Krabbe, S.-W.;
Stephenson, C. R. J. Electron Transfer Photoredox Catalysis: Intramolecular Radical Addition to
ACS Paragon Plus Environment
2
4

Page 25 of 31
The Journal of Organic Chemistry
Indoles and Pyrroles. Org. Lett. 2010, 12, 368−371. (d) Li, T.; Yang, P. Au(I)-Catalyzed Access to
1
2
3
4
5
6
7
1
H‑Pyrrolo[1,2‑a]indol-2(3‑H)‑ones via Oxidation of Terminal Alkynes. J. Org. Chem. 2018, 83,
14751−14757.
6) (a) Chen, S.; Zhang, P.-B.; Shu, W.-Y.; Gao, Y.-Z.; Tang, G.; Zhao, Y.-F. Cascade
Phosphinoylation/Cyclization/Isomerization Process for the Synthesis of
‑Phosphinoyl‑9H‑pyrrolo[1,2‑a]indoles. Org. Lett. 2016, 18, 5712−5715. (b) Zhang, H.-L.; Li,
(
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
W.-P.; Zhu, C.-J. Copper-Catalyzed Cascade Phosphorylation Initiated Radical Cyclization:
Access to 2-Phosphorylated Pyrrolo[1,2-a]indole. J. Org. Chem. 2017, 82, 2199−2204. (c) Zhu, J.-
W.; Sun, S.; Xia, M.-F.; Gu, N.; Cheng, J. Copper-Catalyzed Radical 1,2-Cyclization of Indoles
with Arylsulfonyl Hydrazides: Access to 2-Thiolated 3H-pyrrolo[1, 2-a]indoles. Org. Chem.
Front. 2017, 4, 2153−2155. (d) Gharpure, S.-J.; Shelke, Y.-G. Cascade Radical Cyclization of
N‑Propargylindoles: Substituents Dictate Stereoselective Formation of N‑Fused Indolines versus
Indoles. Org. Lett. 2017, 19, 5022−5025.
(
7) (a) Zhu, X.-Y.; Li, M.; Han, Y.-P.; Chen, S.; Li, X.-S.; Liang, Y.-M. Copper-catalyzed Oxidative
Cyclization of Alkynes with Sulfonylhydrazides Leading to 2-Sulfonated 9H-Pyrrolo[1,2-a]indol-
9
-ones. J. Org. Chem. 2017, 82, 8761−8768. (b) Zhu, X.-Y.; Han, Y.-P.; Li, M.; Li, X.-S.; Liang,
Y.-M. Copper-Catalyzed Radical Sulfonylation of N-Propargylindoles with Concomitant 1,2-Aryl
Migration. Adv. Synth. Catal. 2018, 360, 3460−3465. (c) Zhang, P.-B.; Gao, Y.-Z.; Chen, S.; Tang,
G.; Zhao, Y.-F. Direct Synthesis of 2-Sulfonated 9H-Pyrrolo[1,2-a]indoles via NaI-Catalyzed
Cascade Radical Addition/Cyclization/Isomerization. Org. Chem. Front. 2017, 4, 1350−1353. (d)
Xie, X.-Y.; Li, P.-H.; Wang, L. Synthesis of 2-Sulfonated-9H-Pyrrolo[1,2-a]indoles via a Ag-
Promoted Cascade Sulfonation and Cyclization. Eur. J. Org. Chem. 2019, 221−227. (e) Chen, H.-
J.; Liu, M.-L.; Qiu, G.-Y.-S.; Wu, J. A Three-Component Reaction of Aryldiazonium
Tetrafluoroborates, Sulfur Dioxide, and 1-(Prop-2-yn-1yl)indoles under Catalyst-Free Conditions.
Adv. Synth. Catal. 2019, 361, 146−150. (f) Zhang, P.-B.; Shi, S.-S.; Gao, X.; Han, S.; Lin, J.-M.;
Zhao, Y.-F. Photoredox-catalyzed Cascade Annulation of N-propargylindoles with Sulfonyl
ACS Paragon Plus Environment
2
5

The Journal of Organic Chemistry
Page 26 of 31
chlorides: access to 2-Sulfonated 9H-pyrrolo[1,2-a]indoles. Org. Biomol. Chem. 2019, 17,
873−2876.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
(8) (a) Zhou, M.-B.; Song, R.-J.; Ouyang, X.-H.; Liu, Y.; Wei, W.-T.; Deng, G.-B.; Li, J.-H. Metal-
2
free Oxidative Tandem Coupling of Activated Alkenes with Carbonyl C(sp )-H bonds and Aryl
2
C(sp )-H Bonds using TBHP. Chem. Sci. 2013, 4, 2690−2694. (b) Liu, Y.; Wang, Q.-L.; Zhou, C.-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
S.; Xiong, B.-Q.; Zhang, P.-L.; Yang, C.-A.; Tang, K.-W. Oxidative C−C Bond Functionalization
of Methylenecyclopropanes with Aldehydes for the Formation of 2-Acyl-3,4-dihydronaphthalenes.
J. Org. Chem. 2018, 83, 4657−4664. (c) Pan, C.-D.; Ni, Q.-T.; Fu, Y.; Yu, J.-T. Radical 1,2-
Alkylarylation/Acylarylation of Allylic Alcohols with Aldehydes via Neophyl Rearrangement. J.
Org. Chem. 2017, 82, 7683−7688. (d) Li, Y.; Li, J.-X.; Ouyang, X.-H.; Wang, Q.-A.; Li, J.-H.
Manganese-Catalyzed Intermolecular Oxidative Annulation of Alkynes with γ-Vinyl Aldehydes:
An Entry to Bridged Carbocyclic Systems. Org. Lett. 2017, 19, 6172−6175. (e) Lv, L.-Y.; Li, Z.-P.
Iron-Catalyzed Radical [2 + 2 + 2] Annulation of Benzene-Linked 1,7-Enynes with Aldehydes:
Fused Pyran Compounds. Org. Lett. 2016, 18, 2264−2267. (f) Lv, L.-Y.; Xi, H.; Bai, X.-B.; Li, Z.-
P. Iron-Catalyzed Convergent Radical Cyclization of Aldehydes with Two Alkenes to 3,4-
Dihydropyrans. Org. Lett. 2015, 17, 4324−4327. (g) Liu, W.-P.; Li, Y.-M.; Liu, K.-S.; Li, Z.-P.
Iron-Catalyzed Carbonylation-Peroxidation of Alkenes with Aldehydes and Hydroperoxides. J.
Am. Chem. Soc. 2011, 133, 10756−10759. (h) Mukherjee, S.; Garza-Sanchez, R.-A.; Tlahuext-Aca,
A.; Glorius, F. Alkynylation of C (O)–H Bonds Enabled by Photoredox-Mediated Hydrogen-
sp2
Atom Transfer. Angew. Chem. Int. Ed. 2017, 56, 14723−14726 (i) Zhang, X.; MacMillan, D. W. C.
Direct Aldehyde C-H Arylation and Alkylation via the Combination of Nickel, Hydrogen Atom
Transfer, and Photoredox Catalysis. J. Am. Chem. Soc. 2017, 139, 11353−11356.
(9) (a) Fang, P.; Li, M.-Z.; Ge, H.-B. Room Temperature Palladium-Catalyzed Decarboxylative ortho-
Acylation of Acetanilides with α-Oxocarboxylic Acids. J. Am. Chem. Soc. 2010, 132,
1
1898−11899. (b) Zhou, C.; Li, P.-H.; Zhu, X.-J.; Wang, L. Merging Photoredox with Palladium
Catalysis: Decarboxylative ortho-Acylation of Acetanilides with α-Oxocarboxylic Acids under
ACS Paragon Plus Environment
2
6

Page 27 of 31
The Journal of Organic Chemistry
Mild Reaction Conditions. Org. Lett. 2015, 17, 6198−6201. (c) Li, D.-K.; Wang, M.; Liu, J.; Zhao,
Q.; Wang, L. Cu(II)-Catalyzed Decarboxylative Acylation of Acyl C–H of Formamides with α-
Oxocarboxylic Acids Leading to α-Ketoamides. Chem. Commun. 2013, 49, 3640−3642. (d) Chu,
L.-L.; Lipshultz, J.-M.; Macmillan, D.-W.-C. Merging Photoredox and Nickel Catalysis: The
Direct Synthesis of Ketones by the Decarboxylative Arylation of α-Oxo Acids. Angew .Chem. Int.
Ed. 2015, 54, 7929−7933. (e) Liu, J.; Liu, Q.; Yi, H.; Qin, C.; Bai, R.; Qi, X.; Lan, Y.; Lei, A.
Visible-Light-Mediated Decarboxylation/Oxidative Amidation of α-Keto Acids with Amines
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
under Mild Reaction Conditions Using O . Angew. Chem. Int. Ed. 2014, 53, 502−506. (f) Huang,
2
H.; Zhang, G.; Chen, Y. Dual Hypervalent Iodine(III) Reagents and Photoredox Catalysis Enable
Decarboxylative Ynonylation under Mild Conditions. Angew. Chem. Int. Ed. 2015, 54, 7872−7876.
(g) Tan, H.; Li, H.; Ji, W.; Wang, L. Sunlight-Driven Decarboxylative Alkynylation of α-Keto
Acids with Bromoacetylenes by Hypervalent Iodine Reagent Catalysis: A Facile Approach to
Ynones. Angew. Chem., Int. Ed. 2015, 54, 8374−8377. (h) Ji, W.-Q.; Tan, H.; Wang, M.; Li, P.-G.;
Wang, L. Photocatalyst-free Hypervalent Iodine Reagent Catalyzed Decarboxylative Acylarylation
of Acrylamides with α-Oxocarboxylic Acids driven by Visible-Light Irradiation. Chem. Commun.
2
016, 52, 1462−1465.
(
10) (a) Bergonzini, G.; Cassani, C.; Wallentin, C.-J. Acyl Radicals from Aromatic Carboxylic Acids
by Means of Visible-Light Photoredox Catalysis. Angew. Chem. Int. Ed. 2015, 54, 14066−14069.
(
b) Zhang, M.; Ruzi, R.; Xi, J.; Li, N.; Wu, Z.; Li, W.; Yu, S.; Zhu, C. Photoredox-Catalyzed
Hydroacylation of Olefins Employing Carboxylic Acids and Hydrosilanes. Org. Lett. 2017, 19,
430−3433. (c) Zhang, M.; Xie, J.; Zhu, C. A General Deoxygenation Approach for Synthesis of
3
Ketones from Aromatic Carboxylic Acids and Alkenes. Nat. Commun. 2018, 9, 3517. (d) Stache,
E.-E.; Ertel, A. B.; Rovis, T.; Doyle, A. L. G. Generation of Phosphoranyl Radicals via Photoredox
Catalysis Enables Voltage-Independent Activation of Strong C−O Bonds. ACS Catal. 2018, 8,
1
1134−11139. (e) Bergonzini, G.; Cassani, C.; Lorimer-Olsson, H.; Hörberg, J.; Wallentin, C.-J.
Visible-Light-Mediated Photocatalytic Difunctionalization of Olefins by Radical Acylarylation
ACS Paragon Plus Environment
2
7

The Journal of Organic Chemistry
Page 28 of 31
and Tandem Acylation/Semipinacol Rearrangement. Chem. – Eur. J. 2016, 22, 3292−3295. (f)
Pettersson,F.; Bergonzini, G.; Cassani, C.; Wallentin, C.-J. Redox-Neutral Dual Functionalization
of Electron-Deficient Alkenes. Chem. – Eur. J. 2017, 23, 7444−7447.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
11) (a) Xu, S.-M.; Chen, J.-Q.; Liu, D.; Bao, Y.; Liang, Y.-M.; Xu, P.-F. Aroyl Chlorides as Novel
Acyl Radical Precursors via Visible-Light Photoredox Catalysis. Org. Chem. Front. 2017, 4,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
331−1335. (b) Liu, Y.; Wang, Q.-L.; Zhou, C.-S.; Xiong. B.-Q.; Zhang, P.-L.; Yang, C.-A.; Tang,
K.-W. Visible-Light-Mediated Ipso-Carboacylation of Alkynes: Synthesis of 3-
Acylspiro[4,5]trienones from N-(p-Methoxyaryl)propiolamides and Acyl Chlorides. J. Org. Chem.
2
018, 83, 2210−2218. (c) Li, C.-G.; Xu, G.-Q.; Xu, P.-F. Synthesis of Fused Pyran Derivatives via
Visible-Light-Induced Cascade Cyclization of 1,7-Enynes with Acyl Chlorides. Org. Lett. 2017,
9, 512−515. (d) Wei, Y.-L.; Chen, J.-Q.; Sun, B.; Xu, P.-F. Synthesis of Indolo[2,1-a]isoquinoline
1
Derivatives via Visible-Light-Induced Radical Cascade Cyclization Reactions. Chem. Commun.
2019, 55, 5922−5925. (e) Liu, Y.; Wang, Q.-L.; Zhou, C.-S.; Xiong, B.-Q.; Zhang, P.-L.; Kang, S.-
J.; Yang, C.-A.; Tang, K.-W. Visible-Light-Mediated Cascade Difunctionalization/Cyclization of
Alkynoates with Acyl Chlorides for Synthesis of 3-Acylcoumarins. Tetrahedron Lett. 2018, 59,
2
038−2041. (f) Bogonda, G.; Patil, D.-V.; Kim, H.-Y.; Oh, K. Visible-Light-Promoted Thiyl
Radical Generation from Sodium Sulfinates: A Radical-Radical Coupling to Thioesters. Org. Lett.
019, 21, 3774−3779.
2
(
12) (a) Aruri, H.; Singh, U.; Kumar, S.; Kushwaha, M.; Gupta, A.-P.; Vsihwakarma, R.-A.; Singh, P.-
P. I /Aqueous TBHP-Catalyzed Coupling of Amides with Methylarenes/Aldehydes/Alcohols:
2
Metal-Free Synthesis of Imides. Org. Lett. 2016, 18, 3638−3641. (b) Fan, X.-W.; Lei, T.; Chen, B.;
Tung, C.-H.; Wu, L.-Z. Photocatalytic C–C Bond Activation of Oxime Ester for Acyl Radical
Generation and Application. Org. Lett. 2019, 21, 4153−4158. (c) Lei, L.; Guo, S.; Wang, Q.; Zhu,
J. Acyl Radicals from Benzothiazolines: Synthons for Alkylation, Alkenylation, and Alkynylation
Reactions. Org. Lett. 2019, 21, 5462−5466. (d) Petersen, W.-F.; Taylor, R.-J.-K.; Donald, J.-R.
Photoredox-Catalyzed Procedure for Carbamoyl Radical Generation: 3,4-Dihydroquinolin-2-one
ACS Paragon Plus Environment
2
8

Page 29 of 31
The Journal of Organic Chemistry
and Quinolin-2-one Synthesis. Org. Biomol. Chem. 2017, 15, 5831−5845. (e) Bennasar, M.-L.;
Roca, T.; Griera, R.; Bosch, J. Generation and Intermolecular Reactions of 2-Indolylacyl Radicals.
1
2
3
4
5
6
7
8
9
Org. Lett. 2001, 3, 1697−1700. (f) Vanjari, R.; Guntreddi, T.; Singh, K.-N. MnO Promoted
2
Sequential C−O and C−N Bond Formation via C−H Activation of Methylarenes: A New Approach
to Amides. Org. Lett. 2013, 15, 4908−4911. (g) Ouyang, X.-H.; Song, R.-J.; Li, J.-H. Iron-
Catalyzed Oxidative 1,2-Carboacylation of Activated Alkenes with Alcohols: A Tandem Route to
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
-(2-Oxoethyl)indolin-2-ones. Eur. J. Org. Chem. 2014, 3395−3401. (h) Zhang, M.-Z.; Ji, P.-Y.;
Liu, Y.-F.; Guo, C.-C. Transition-Metal-Free Synthesis of Carbonyl-Containing Oxindoles from
N-Arylacrylamides and α-Diketones via TBHP- or Oxone-Mediated Oxidative Cleavage of C(sp2)
2
−C(sp ) Bonds. J. Org. Chem. 2015, 80, 10777−10786. (i) Capaldo, L.; Riccardi, R.; Ravelli, D.;
Fagnoni, M. Acyl Radicals from Acylsilanes: Photoredox-Catalyzed Synthesis of Unsymmetrical
Ketones. ACS Catal. 2018, 8, 304−309.
(13) (a) Xuan, J.; Xiao, W.-J. Visible-Light Photoredox Catalysis. Angew. Chem. Int. Ed. 2012, 51,
6
828−6838. (b) Ouyang, X.-H.; Cheng, J.; Li, J.-H. 1,2-Diarylation of Alkenes with Aryldiazonium
Salts and Arenes Enabled by Visible Light Photoredox Catalysis. Chem. Commun. 2018, 54,
745−8748. (c) Hari, D.-P.; König, B. The Photocatalyzed Meerwein Arylation: Classic Reaction
8
of Aryl Diazonium Salts in a New Light. Angew. Chem. Int. Ed. 2013, 52, 4734−4743. (d) Hari,
D.-P.; Schroll, P.; König, B. Metal-Free, Visible-Light-Mediated Direct C−H Arylation of
Heteroarenes with Aryl Diazonium Salts. J. Am. Chem. Soc. 2012, 134, 2958−2961. (e) Ding, W.;
Lu, L.-Q.; Zhou, Q.-Q.; Wei, Y.; Chen, J.-R.; Xiao, W.-J. Bifunctional Photocatalysts for
Enantioselective Aerobic Oxidation of β-Ketoesters. J. Am. Chem. Soc. 2017, 139, 63−66; (f)
Zhang, M.-L.; Li, N. Tao, X.-Y.; Ruzi, R.; Yu, S.-Y.; Zhu, C.-J. Selective Reduction of Carboxylic
Acids to Aldehydes with Hydrosilane via Photoredox Catalysis. Chem. Commun. 2017, 53,
1
0228−10231. (g) Jiang, H.; Cheng, Y.-Z.; Wang, R.-Z.; Zhang, Y.; Yu, S.-Y. Synthesis of
Isoquinolines via Visible Light-Promoted Insertion of Vinyl Isocyanides with Diaryliodonium
Salts. Chem. Commun. 2014, 50, 6164−6167.
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