Oxidative Recyclization of 1H-Indoles for Synthesis of 2-Indolylbenzoxazinones via Cleavage of the C2-C3 Bond with AIBN under Air

Article abstract of DOI:10.1021/acs.joc.6b02893

A novel and concise method for the oxidation of unprotected indole derivatives to synthesize 2-indolylbenzoxazinones in the presence of AIBN under open air has been successfully demonstrated. This metal-free reaction is both atom- and step-efficient and is applicable to a broad scope of substrates. This new methodology provides a facile pathway for oxidative C2-C3 bond cleavage and recyclization of 1H-indoles.

Full text of DOI:10.1021/acs.joc.6b02893

Subscriber access provided by University of Newcastle, Australia
Article
Oxidative Re-Cyclization of 1H-Indoles for Synthesis of 2-
Indolylbenzoxazinones via Cleavage C2-C3 bond with AIBN Under Air
Xing-Xing Liu, Xinliang Luo, Zhao-Yang Wu, Xin-Feng
Cui, Xiaoqiang Zhou, Yong-Qin He, and Guosheng Huang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02893 • Publication Date (Web): 25 Jan 2017
Downloaded from http://pubs.acs.org on January 26, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 12
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Oxidative Re-Cyclization of 1H-Indoles for Synthesis of
2
-Indolylbenzoxazinones via Cleavage C2-C3 bond with
AIBN Under Air
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
†
†
‡
†
XingꢀXing Liu, XinꢀLiang Luo, ZhaoꢀYang Wu, XinꢀFeng Cui, XiaoꢀQiang
†
†
*,†
Zhou, YongꢀQin He and GuoꢀSheng Huang
†
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal
Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou
University, Lanzhou 730000, China.
‡
The Environmental Protection Agency of Rudong Coastal Economic Development Zone,
Nantong 226400, China
O
O
R
Air, no metal-catalysis
R
R
o
N
H
Toluene, 60 C
N
NH
metal-free
atom and step efficient
oxidative dearomatization
mild reaction conditions
ABSTRACT
A novel and concise method for the oxidation of unprotected indole derivatives to synthesize
2ꢀindolylbenzoxazinones in the presence of AIBN under open air has been firstly successfully
demonstrated. This metalꢀfree reaction is both atom and step efficient and is applicable to a broad
scope of substrates. This new methodology provides a facile pathway for the oxidative C2ꢀC3
bond cleavage and reꢀcyclization of 1Hꢀindoles.
INTRODUCTION
Figure 1. Structures of some bioactive 4Hꢀ3,1ꢀbenzoxazinꢀ4ꢀones.
4
Hꢀ3, 1ꢀBenzoxazinꢀ4ꢀones as a class has been known for more than a century. Compounds
possessing this skeleton system are found in a number of physiologically and pharmaceutically
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 12
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
bioactive natural products with diverse bioactivities, such as HSVꢀ1 protease inhibition,
1
chymotrypsin inactivation, antifungal and others. A few representative compounds are outlined in
2
Figure 1. Besides, benzoxazinones are useful synthetic intermediates for some pharmaceutically
3
4
active compounds, and they also serve as useful building blocks in organic synthesis. Therefore,
benzoxazinones represent a class of annulated nitrogen heterocycles that have attracted much
interest from both organic and pharmaceutical chemists. In the past decade, great efforts have been
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
5
ꢀ7
devoted to these moieties and a number of synthetic methods have been reported. Among the
5
different methodologies developed for their preparation, the most popular synthetic pathways
involve the use of anthranilic acid or its derivatives, Nꢀacylanthranilic acids, or isatonic
6
anhydride.
Other synthetic methods such as oxidation of 2ꢀsubstituted indoles and
2
ꢀphenylindoleninꢀ3ꢀones, [4 + 2] cycloaddition of 1,2,3ꢀbenzotriazin4ꢀones with benzaldehydes,
electrochemical cyclization of oꢀtrichloroacetylanilides, and solidꢀphase synthesis were described.
7
Although alternative methodologies are known, some of them still suffer from hazardous
materials or harsh reaction conditions. Hence, it is still desirable to extend known protocols for
benzoxazinone synthesis.
As we all know, indoles are structural motifs prevalent in bioactive synthetic and natural
8
products. They are employed widely in medicinal chemistry, pharmacological research, and
9
material applications. Consequently, the development of efficient methodologies for the
preparation and functionalization of various indole derivatives has been a subject of intense
research efforts. Notably, to our knowledge, there is yet no report for direct functionalization of
1Hꢀindoles to afford 2ꢀindolylbenzoxazinones. Herein, we present a facile route for the
construction of the benzoxazinone skeleton through the oxidative cleavage of 1Hꢀindoles C2ꢀC3
bond along with reꢀcyclization in the presence of AIBN and air.
RESULTS AND DISCUSSION
Initially, we proposed that indole could react with the toluene through the oxidative crossꢀcoupling
reaction. We chose 1Hꢀindole 1a as the model to optimize the conditions. By treating the substrate
o
1
a with AIBN (2.0 equiv) at 60 C for 6 h in toluene under air, surprisingly, an unexpected product
2
ꢀ(1Hꢀindolꢀ3ꢀyl)ꢀ4Hꢀbenzo[d][1,3]oxazinꢀ4ꢀone 2a was obtained in 30% yield, and the structure
of 2a was confirmed unambiguously through an Xꢀraycrystal analysis (SI, CCDC 1496619).
2ꢀ(1Hꢀindolꢀ3ꢀyl)ꢀ4Hꢀbenzo[d][1,3]oxazinꢀ4ꢀone was natural product as known as cephalandole A,
showed significant cytotoxicity against human breast carcinoma (MCFꢀ7), lung carcinoma
10
(
NCIꢀH460), and central nervous system carcinoma (SFꢀ268) cell lines. Moreover,
2
ꢀ(1Hꢀindolꢀ3ꢀyl)ꢀ4Hꢀbenzo[d][1,3]oxazinꢀ4ꢀone was also the intermediate for some other natural
11
alkaloids (Figure 2). This discover attracted our interest. Encouraged by this result, a variety of
oxidants such as O , Oxone , DTBP, PhI(OAc) and H O were screened, but all failed to give the
2
2
2
2
desired product in better results than air (entries 1−6; Table 1). Subsequently, a series of additives,
including Et N, HOAc, PivOH, CF COOH, TsOH were examined. PivOH was clearly the most
3
3
effective, giving 2a in 76% yield (entries 7ꢀ11; Table 1). However, no matter we increased or
decreased the amount of PivOH, no better yield was abtained (entries 12−13; Table 1).
Optimization of different solvents revealed that DMF, DMSO, PhCl, and DMC were inferior to
toluene in the reaction (entries 14ꢀ17; Table 1). It should be noted that lower yields of product
2
ꢀ(1Hꢀindolꢀ3ꢀyl)ꢀ4Hꢀbenzo[d][1,3]oxazinꢀ4ꢀone 2a was obtained when we changed the amount
ACS Paragon Plus Environment

Page 3 of 12
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
o
of AIBN (entry 18; Table 1). The reaction temperature and time were also varied; 60 C and 6 h
gave the best result (entries 19–21; Table 1). Moreover, when we used TBHP, I , Na S O and
2
2
2
8
2 2
H O to replace AIBN, however, we all failed to detect the desired product (entry 22; Table 1).
Finally, the best result was obtained by using AIBN (2.0 equiv) in the presence of PivOH (1.0
equiv) in toulene at 60 °C under air for 6 h ( entry 9; Table 1).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
Figure 2. The applications of 2a: (i) NH OAc, DMF, 70 °C, 2 h; (ii) Xylenes, pꢀTsOH (cat.),
reflux, (DeanꢀStarktrap), 24 h; (iii) formamide (neat), 200 °C, 10 min, MW; (iiii) MeOH, reflux, 4
h, 99%.
a
Table 1. Optimization Studies .
o
b
Entry
Oxidant
Additive
(equiv)
Solvent
Temp. ( C)
Yield (%)
(
equiv)
Air
1
2
3
4
5
6
7
8
9
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
Tol.
60
60
60
60
60
60
60
60
60
60
60
60
60
30
15
O
2
Oxone
DTBP
PIDA
16
20
24
H O2
2
8
Air
Air
Air
Air
Air
Air
Air
Et
3
N
35
HOAc (1.0)
PivOH (1.0)
TFA (1.0)
58
76
1
0
1
N.D.
N.D.
45
1
TsOH (1.0)
PivOH (0.5)
PivOH (2.0)
12
13
68
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 12
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
14
Air
Air
Air
Air
Air
Air
Air
Air
Air
PivOH (1.0)
PivOH (1.0)
PivOH (1.0)
PivOH (1.0)
PivOH (1.0)
PivOH (1.0)
PivOH (1.0)
PivOH (1.0)
PivOH (1.0)
DMF
DMSO
PhCl
DMC
Tol.
60
60
60
60
60
60
40
80
60
trace
N.D.
66
15
16
17
45
c
d
f
18
45 ,46
e
1
9
0
Tol.
46 ,64
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
g
2
Tol.
30
21
Tol.
55
h
22
Tol.
N.D.
a
o
b
Indole 1a (0.5 mmol), AIBN (1.0 mmol, 2.0 equiv), oxidant, additive and solvent (2 mL) at 60 C for 6 h.
c
d
e
f
g
Yield of isolated product. AIBN (0.5 mmol, 1.0 equiv). AIBN (1.5 mmol, 3.0 equiv). 4 h. 8 h. the reaction
h
prolonged to 8h. THBP (2.0 equiv), I
2
(2.0 equiv), Na
2
S
2
O
8
(2.0 equiv), H
2
O
2
(2.0 equiv) instead of AIBN. AIBN
=
azobis(isobutyronitrile), DTBP = tertꢀButyl peroxide, PIDA = Iodobenzene diacetate, TFA = trifluoroacetic
acid, Tol. = toluene, TBHP = tertꢀButyl hydroperoxide, HOAc = acetic acid, PivOH = Trimethylacetic acid, TsOH
= 4ꢀmethylbenzenesulfonic acid, DMF = Dimethyl Formamide, DMSO = dimethylsulfoxide, DMC = Dimethyl
phosphate, N.D. = no detection.
With the optimized reaction conditions established, the scope and generality of the reaction were
investigated (Table 2). Delightly, a relatively broad range of indole derivatives with a substituent
at C4, C5, C6, or C7 position of the indole ring were mostly successfully transformed to desired
products in moderate yields. For example, indoles with a methyl at the 4ꢀ, 5ꢀ, 6ꢀ or 7ꢀpositions
were examined, affording the desired products in 54%, 62%, 43% and 68%, respectively (Table 2,
entries 2b, 2f, 2l, 2o). Unfortunately, we did not detect the product when a methoxy at C4 of
1
Hꢀindole (Table 2, entry 2c), but the indoles with methoxy at C5, C6 and C7 positions could
afford the products 2g, 2m and 2p in 50 %, 44% and 28% (Table 2, entries 2g, 2m, 2p). In
addition, some halogen substituents (F, Cl, or Br) were tested under the optimal conditions, except
the bromo group (Table 2, entry 2k), the others could be smoothly transformed into the desired
products (Table 2, entries 2e, 2i-2j, 2n, 2q). However, 7ꢀazaindole (1r) failed to produce the
desired product under the optimal conditions (2r).
ACS Paragon Plus Environment

Page 5 of 12
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
a
Table 2. Oxidation of 1Hꢀindoles for the synthesis of 2ꢀindolylbenzoxazinones with AIBN
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
N
O
N
OMe O
N
O
O
O
NH
O
NH
NH
2a, 76%
2b, 54%
2
c, N.D.
F
O
O
O
N
O
O
O
O
F
O
O
N
N
NH
NH
NH
2d, 40%
2e, 38%
2f, 62%
O
O
O
O
O
O
F
OMe
MeO
F
O
N
O
O
N
O
N
NH
NH
NH
NH
2g, 50%
2h, trace
2i, 46%
O
O
O
Cl
Br
Br
Cl
O
N
O
N
O
N
NH
NH
2
j, 48%
2l, 43%
2
k, N.D.
O
O
O
O
N
O
N
O
F
OMe
F
MeO
N
NH
NH
NH
2
n, 54%
2
m, 44%
2o, 68%
O
O
N
O
O
N
O
O
N
N
N
F
OMe
F
OMe
NH
NH
NH
2q, 32%
2
r, N.D.
2
p, 28%
a
o
Reaction conditions: 1a (0.5 mmol), AIBN (1.0 mmol, 2.0equiv) in toluene (2 mL) at 60 C
under air for 6 h. Isolated yield. N.D. = not detection.
b
In order to explore the reaction mechanism, some control experiments were conducted (Scheme 1).
According to the results of the transformations, we proposed that the 3Hꢀindolꢀ3ꢀones may in fact
be the crucial intermediates in the reaction. Unfortunately, under the optimized conditions, none of
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 12
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
the intermediates formed in isolable quantities. Therefore, we performed a control experiment in
the absence of PivOH, the high resolution mass spectrum of crude mixtures (see the supporting
information) withdrawn at
2
h
indicated the formation of 3Hꢀindolꢀ3ꢀone 3,
1
'H,3Hꢀ[2,3'ꢀbiindol]ꢀ3ꢀone 4 (Scheme 1, Eq.1). As shown in Equation 2 and 3, we conducted
the reaction in the absence of AIBN and air, respectively (Scheme 1, Eq. 2 and 3). The recations
both failed to afford the product 2a. The results indicated that AIBN and air were important
factors in the conversion of 1a to 2a. Moreover, we added 2.0 equivalent radicalꢀtrapping reagents
TEMPO (2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy) and BHT (2,6ꢀdiꢀtertꢀbutylꢀpꢀcresol) into the
reaction system, respectively, resulting in no formation of desired products (Scheme 1, Eq.4). The
results implied that the radical mechanism might be responsible for the reaction. Then, we used
the substrates 2ꢀmethyꢀ1Hꢀlindole 1s and 3ꢀmethyꢀ1Hꢀlindole 1t to perform the reactions (Scheme
1, Eq. 5 and 6). Under the standard conditions, 2ꢀmethyꢀ1Hꢀlindole could generate
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
2
3
ꢀmethylꢀ4Hꢀbenzo[d][1,3]oxazinꢀ4ꢀone
2s
in
30%
and
ꢀmethylꢀ2ꢀ(2ꢀmethylꢀ1Hꢀindolꢀ3ꢀyl)indolinꢀ3ꢀone 4s in 48%; however, the transformation of
ꢀmethyꢀ1Hꢀlindole was not very positive, we just detected only a trace amount of
3ꢀmethylindolinꢀ2ꢀone 3t. Consequently, the results of equations 5 and 6 could also provide an
evidence for the intermediate of 4.
Scheme 1. Different Control Experiments
O
O
Air, AIBN
Eq. 1
2a
N
H
NH
Toulene, 2h
N
N
1a
3
4
N , AIBN, PivOH
2
2
a, N.D.
a, N.D.
Eq. 2
Eq. 3
N
H
Toulene
1a
Air, PivOH
Toulene
2
N
H
1a
Tempo/ BHT
2
a, N.D.
Eq. 4
Eq. 5
N
H
Air, AIBN, PivOH, Toulene
1
a
O
O
N
O
Standard conditions
Standard conditions
NH
N
N
H
H
1
s
2s, 30%
4
s, 48%
O
Eq.6
N
H
NH
N
H
N
H
1t
O
3
t, trace
4
t, N.D.
12ꢀ26
Based on the above results and literature reports,
the proposed mechanism is outlined in
Scheme 2. Firstly, an initial hydrogen abstraction from the nitrogen atom of the indole ring by
AIBN leads to the formation of an indolyl radical 7. Then, in the prensence of dioxygen, the
ACS Paragon Plus Environment

Page 7 of 12
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
formation of a C3ꢀlocated indole hydroperoxide 8 followed by its fractionation to the intermediate
3Hꢀindolꢀ3ꢀone 3. Subsequently, the 1Hꢀindole 1a undergoes nucleophilic attack to 3 mediated by
acid to produce another crucial intermediate 4. Shortly afterwards, Baeyer−Villiger oxidation of 4
by 5 or 9 occurs leading to generating the product 2a through C2ꢀC3 bond cleavage.
Scheme 2. Plausible mechanism
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CONCLUSIONS
In summary, we have developed a new, simple and practical method for the oxidative
reꢀcyclization of 1Hꢀindoles through the cleavage of C2ꢀC3 bond to synthesize
2
ꢀindolylbenzoxazinones in the presence of AIBN under open air. This strategy features tolerance
of a relatively wide range of functional groups, easily available starting materials, simple
operation and mild reaction conditions. To the best of our knowledge, this is the first example of
constructing benzoxazinones from easily available unprotected indole derivatives through oneꢀpot
method.
EXPERIMENTAL SECTION
General information All of the reactions were carried out in ovenꢀdried flask. Products were
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 12
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
purified by flash chromatography on 200–300 mesh silica gels. Analytical TLC was performed
with Merck silica gel 60 F254 plates, and the products were visualized by UV detection. Unless
1
otherwise noted, chemical shifts (δ) are reported in ppm using TMS as internal standard; H NMR
1
3
(
3
400 MHz) and C NMR (100 MHz) spectras were recorded in CDCl (δ = 77.00 ppm) and
dꢀDMSO (δ = 39.50 ppm). The high resolution mass spectra (HRMS) were recorded on an
FTꢀICR mass spectrometer using electrospray ionization (ESI). Melting points were determined on
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
13
a microscopic apparatus. Copies of H NMR and C NMR spectra are provided. Commercially
available reagents were used without further purification.
Typical Experimental Procedure for the Synthesis of 2-Indolylbenzoxazinones (2) An
ovenꢀdried tube with a magnetic stir bar was charged with the 1Hꢀindole compound 1 (0.5 mmol,
1
.0 equiv.), AIBN (1.0 mmol, 2.0 equiv.), PivOH (0.5 mmol, 1.0 equiv.) and toluene (2 mL). Then
o
the reaction mixture was stirred at 60 C under air until complete consumption of starting material
as monitored by TLC. After the reaction was finished, the mixture was concentrated in vacuum,
and the residues were purified by silica gel column chromatography (hexane/ethyl acetate = 4:1)
to afford the desired product 2.
27
1
2-methyl-4H-benzo[d][1,3]oxazin-4-one (2s) , yield 30%, 24.2 mg; brown solid; H NMR (400
MHz, CDCl ) δ: 8.12 (dd, J = 7.9 Hz, J = 1.1 Hz, 1H), 7.77ꢀ7.73 (m, 1H), 7.50ꢀ7.43 (m, 2H),
3
1
2
13
2
.42 (s, 3H); C NMR (100 MHz, CDCl
3
) δ: 160.0, 159.5, 146.3, 136.4, 128.3, 128.0, 126.2,
1
16.5, 21.2.
2
0
1
2-methyl-2-(2-methyl-1H-indol-3-yl)indolin-3-one (4s) , yield 48%, 33.1 mg; yellow solid; H
NMR (400 MHz, dꢀDMSO) δ: 10.90 (s, 1H), 7.74 (s, 1H), 7.52ꢀ7.45 (m, 2H), 7.23 (t, J = 8.0 Hz,
2
H), 6.94 (dt, J = 7.1 Hz, J = 0.9 Hz, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.81ꢀ 6.77 (m, 1H), 6.74ꢀ6.70
1 2
1
3
(
m, 1H), 2.40 (s, 3H), 1.74 (s, 3H); C NMR (100 MHz, dꢀDMSO) δ: 203.9, 159.9, 137.5, 134.7,
133.0, 127.2, 124.4, 120.0, 119.4, 118.4, 117.7, 117.0, 111.8, 110.5, 108.5, 66.3, 24.4, 14.0.
2
2
1
-(1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2a), yield 76%, 49.8 mg; yellow solid; m.p.:
1
24ꢀ226 °C; H NMR (400 MHz, dꢀDMSO) δ: 12.12 (s, 1H), 8.43 (dd, J
1
= 6.0 Hz, J
2
= 3.2 Hz,
H), 8.29 (d, J = 2.8 Hz, 1H), 8.10 (dd, J = 7.6 Hz, J = 1.2 Hz, 1H), 7.90ꢀ7.86 (m, 1H), 7.66 (d, J
1
2
13
= 8.0 Hz, 1H), 7.54ꢀ7.47 (m, 2H), 7.29ꢀ7.25 (m, 2H) ; C NMR (100 MHz, dꢀDMSO) δ: 159.2,
1
1
5
55.6, 147.6, 137.0, 136.7, 131.6, 128.0, 126.8, 126.2, 124.9, 122.9, 121.4, 121.3, 116.2, 112.5,
+
+
10 2 2
06.4; HRMS: [M+H] m/z calcd for C16H N O H : 263.0815, found: 263.0819.
-methyl-2-(4-methyl-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2b), yield 54%, 39.1 mg;
1
yellow solid; m.p.: 222ꢀ224 °C; H NMR (400 MHz, dꢀDMSO) δ:12.05 (s, 1H), 8.18 (d, J = 3.1
Hz, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.28(d, J =
1
3
7
.5Hz, 1H), 7.12 (t, J = 8.0 Hz, 1H), 6.96 (d, J = 7.2 Hz, 1H), 2.89 (s, 3H), 2.71 (s, 3H) ;
C
NMR (100 MHz, dꢀDMSO) δ: 158.9, 155.5, 148.8, 141.7, 137.6, 135.7, 132.4, 131.3, 129.3, 124.1,
+
123.54, 123.49, 122.9, 114.4, 110.3, 108.3, 23.1, 22.2; HRMS: [M+H] m/z calcd for
+
C H N O H : 291.1128, found: 291.1132.
1
8
14
2
2
Methyl
benzo[d][1,3]oxazine-5-carboxylate
2-(4-(methoxycarbonyl)-1H-indol-3-yl)-4-oxo-4H-
1
(2d), yield 40%, 37.8 mg; yellow oil; H NMR (400
MHz, CDCl3) δ: 10.12 (s, 1H), 7.94 (d, J = 3.0 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.61 (d, J = 8.2
Hz, 1H), 7.53ꢀ7.50 (m, 2H), 7.39 (d, J = 7.4Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 4.00 (s, 3H), 3.79 (s,
1
3
3
H) ; C NMR (100 MHz, CDCl ) δ: 170.3, 169.0, 158.1, 155.9, 148.2, 137.4, 136.0, 134.9,
3
+
132.4, 128.0, 126.1, 125.5, 123.0, 122.9, 121.2, 115.4, 112.9, 108.2, 53.2, 52.3; HRMS: [M+H]
+
m/z calcd for C20
H
14
N O
2 6
H : 379.0925, found: 379.0931.
ACS Paragon Plus Environment

Page 9 of 12
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
5-fluoro-2-(4-fluoro-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2e), yield 38 %, 28.31 mg;
1
yellow solid; m.p.: 258ꢀ260 °C; H NMR (400 MHz, dꢀDMSO) δ:12.46 (s, 1H), 8.36 (s, 1H),
13
7
.89ꢀ7.84 (m, 1H), 7.37 (t, J = 8.5 Hz, 2H), 7.32ꢀ7.22 (m, 2H), 7.01ꢀ6.97 (m, 1H); C NMR (100
MHz, dꢀDMSO) δ: 161.0 (d, J = 262.6 Hz), 155.7, 155.4 (d, J = 249.6 Hz), 154.9 (d, J = 4.8 Hz),
149.4, 139.9 (d, J = 10.0 Hz), 137.5 (d, J = 10.8 Hz) , 133.3, 123.8 (d, J = 7.6 Hz), 122.2 (d, J =
3
.6 Hz) , 113.6 (d, J = 20.3 Hz), 112.6 (d, J = 19.2 Hz), 109.0 (d, J = 3.7Hz), 107.4 (d, J = 20.6Hz),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
+
105.9 (d, J = 3.1Hz), 105.5 (d, J = 7.1Hz). HRMS: [M+H] m/z calcd for C H F N O H :
16 8 2 2 2
299.0627, found: 299.0622.
6-methyl-2-(5-methyl-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2f), yield 62%, 44.7 mg;
1
yellow solid; m.p.: 252ꢀ254 °C; H NMR (400 MHz, dꢀDMSO) δ: 11.97 (s, 1H), 8.19 (d, J = 2.8
Hz, 2H), 7.89 (d, J = 0.8 Hz, 1H), 7.70 (dd, J 8.2 Hz, J = 2.0 Hz, 1H), 7.57 (d, J = 8.4 Hz,
1H), 7.40 (d, J = 8.4 Hz, 1H), 7.08 (dd, J =8.2 Hz, J = 1.6 Hz, 1H), 2.47 (s, 3H), 2.43 (s, 3H) ;
1
=
2
1
2
13
C NMR (100 MHz, dꢀDMSO) δ: 159.3, 155.1, 145.5, 137.8, 136.6, 135.3, 131.2, 130.2, 127.4,
+
1
26.0, 125.1, 124.3, 120.9, 115.8, 112.1, 106.0, 21.4, 20.6; HRMS: [M+H] m/z calcd for
+
C
H
18 14
N
O
2 2
H : 291.1128, found: 291.1133.
6-methoxy-2-(5-methoxy-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2g), yield 50%, 40.2
1
mg; yellow solid; m.p.: 243ꢀ246 °C; H NMR (400 MHz, dꢀDMSO) δ: 11.92 (d, J =1.6 Hz, 1H),
8
7
.16 (d, J = 3.2 Hz, 1H), 7.92 (d, J = 2.8 Hz, 1H), 7.64 (d, J = 8.8 Hz, 1H), 7.50ꢀ7.47 (m, 2H),
1
3
1 2
.41 (d, J = 8.8 Hz, 1H), 6.90 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H); C
NMR (100 MHz, dꢀDMSO) δ: 159.3, 157.7, 155.0, 153.9, 141.7, 131.8, 130.9, 127.9, 125.6, 125.4,
+
1
16.7, 113.137, 112.5, 108.7, 106.1, 103.4, 55.8, 55.3; HRMS: [M+H] m/z calcd for
+
C H N O H : 323.1026, found: 323.1029.
1
8
14
2
4
6-fluoro-2-(5-fluoro-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2i), yield 46%, 34.3 mg;
1
yellow solid; m.p.: 265ꢀ268 °C; H NMR (400 MHz, dꢀDMSO) δ: :12.21 (s, 1H), 8.30 (d, J = 8.7
Hz,1H), 8.05 (dd, J = 10.0 Hz, 2.6 Hz, 1H ), 7.78 (dt, J
1
= 8.4 Hz, J
2
= 1.7 Hz, 1H ), 7.74 (dd, J
1
=
6
.5 Hz, J = 1.7 Hz, 2H ), 7.51 (dd, J = 8.9 Hz, J = 4.6 Hz, 1H), 7.11(td, J
2
1
1
2
1
=
9.2 Hz, J = 2.6
2
3
Hz, 1H); C NMR (100 MHz, dꢀDMSO) δ: 159.8 (d, J = 246.6 Hz), 158.5 (d, J=3.2 Hz), 158.3 (d,
J=235.1 Hz), 154.7, 144.3, 133.6, 132.9, 128.9 (d, J=8.4Hz), 125.4 (d, J=11.2 Hz), 124.6 (d,
J=23.9 Hz), 117.4 (d, J=8.8 Hz), 113.8 (d, J=10.0 Hz), 113.0 (d, J=24.10 Hz), 111.1 (d, J=26.2 Hz),
+
+
106.3 (d, J=4.4 Hz), 106.1 (d, J=25.0 Hz); HRMS: [M+H] m/z calcd for C16
H
8
F
2
N
2
O
2
H :
299.0627, found: 299.0632.
6-chloro-2-(5-chloro-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2j), yield 48%, 39.6 mg;
1
yellow solid; m.p.: 248ꢀ251 °C; H NMR (400 MHz, dꢀDMSO) δ: 12.33 (s, 1H), 8.36ꢀ8.35 (m,
2
H), 8.03 (d, J = 2.4 Hz, 1H), 7.91ꢀ7.88 (m, 1H), 7.71 (d, J = 8.6 Hz, 1H), 7.54 (d, J = 8.6 Hz, 1H),
13
7
.30ꢀ7.27 (m, 1H); C NMR (100 MHz, dꢀDMSO) δ: 158.1, 155.4, 146.2, 136.5, 135.5, 133.2,
+
130.7, 128.3, 126.8, 126.3, 125.9, 123.0, 120.3, 117.7, 114.2, 106.0; HRMS: [M+H] m/z calcd
+
for C H Cl N O H : 331.0036, found: 331.0043.
1
6
8
2
2
2
7-methyl-2-(6-methyl-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2l), yield 43%, 37.2 mg;
1
yellow solid; m.p.: 246ꢀ248 °C; H NMR (400 MHz, dꢀDMSO) δ: 11.97 (s, 1H), 8.27 (d, J = 8.0
1 2
Hz, 1H), 8.18 (d, J = 3.2 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.47 (s, 1H), 7.30 (dd, J = 7.2 Hz, J
13
=
1 2
1.2 Hz, 2H), 7.09 (dd, J = 8.2 Hz, J = 1.2 Hz, 1H), 2.46 (s, 3H), 2.44 (s, 3H); C NMR (100
MHz, dꢀDMSO) δ: 159.2, 155.8, 147.7, 147.7, 137.4, 132.2, 130.9, 128.1, 127.8, 126.1, 123.12,
+
+
122.8, 121.0, 113.5, 112.2, 106.4, 21.5, 21.3; HRMS: [M+H] m/z calcd for C18
14 2 2
H N O H :
291.1128, found: 291.1133.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 12
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
7-methoxy-2-(6-methoxy-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2m), yield 44%, 35.4
1
mg; yellow solid; m.p.: 250ꢀ251 °C; H NMR (400 MHz, dꢀDMSO) δ: 11.91 (s, 1H), 8.29 (d, J =
8
.7 Hz, 1H), 8.14 (d, J = 2.5 Hz, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.13 (d, J = 2.4 Hz, 1H), 7.05ꢀ7.00
13
(
m, 2H), 6.91ꢀ6.89 (m, 1H), 3.94 (s, 3H), 3.81 (s, 3H); C NMR (100 MHz, dꢀDMSO) δ: 165.9,
158.8, 156.5, 156.4, 150.1, 137.8, 130.5, 129.7, 122.0, 118.8, 115.8, 111.6, 108.8, 108.1, 106.5,
+
+
9
14 2 4
5.2, 39.1,38.9; HRMS: [M+H] m/z calcd for C18H N O H : 323.1026, found: 323.1029.
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
-fluoro-2-(6-fluoro-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2n), yield 54%, 40.2 mg;
1
yellow solid; m.p.: 278ꢀ280 °C; H NMR (400 MHz, dꢀDMSO) δ: 12.17 (s, 1H), 8.34(dd, J
1
= 8.8
= 6.2 Hz, 1H), 7.42ꢀ7.39
2
= 2.4Hz, 1H); C NMR (100 MHz, dꢀDMSO)
Hz, J
2
= 5.6 Hz, 1H), 8.26 (d, J=2.8 Hz, 1H), 8.11 (dd, J
1 2
= 8.7 Hz, J
13
(
m, 1H), 7.32ꢀ7.26 (m, 2H), 7.10 (dt, J
1
= 9.2 Hz, J
δ: 167.0 (d, J = 254.7 Hz), 160.6, 158.2, 156.5, 150.0 (d, J=13.9 Hz), 137.0 (d, J=12.64 Hz), 132.7
(d, J=2.4 Hz), 131.1 (d, J=11.3 Hz), 122.4 (d, J=9.9 Hz), 121.5, 115.0 (d, J=23.6 Hz), 113.2 (d,
J=1.8 Hz), 111.8 (d, J=22.7 Hz), 110.0 (d, J=24.1 Hz), 106.3, 98.7 (d, J=26.0 Hz); HRMS:
+
+
[
8 2 2 2
M+H] m/z calcd for C16H F N O H : 299.0627, found: 299.0630.
8
-methyl-2-(7-methyl-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2o), yield 68%, 49.3 mg;
1
yellow solid; m.p.: 266ꢀ268 °C; H NMR (400 MHz, dꢀDMSO) δ: 12.14 (s, 1H), 8.26ꢀ8.24 (m,
2
7
1
H), 7.94ꢀ7.92 (m, 1H), 7.75 (d, J=6.9 Hz, 1H), 7.37 (t, J=7.6 Hz, 1H), 7.18 (t, J=7.5 Hz, 1H),
13
.06 (d, J=7.1 Hz, 1H), 2.62 (s, 3H), 2.52 (s, 3H); C NMR (100 MHz, dꢀDMSO) δ: 159.6, 154.6,
45.9, 137.0, 136.5, 134.3, 130.9, 126.2, 125.5, 124.8, 123.4, 121.8, 121.7, 118.8, 115.9, 107.1,
+
+
14 2 2
16.9, 16.7; HRMS: [M+H] m/z calcd for C18H N O H : 291.1128, found: 291.1132.
8
-methoxy-2-(7-methoxy-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2p), yield 28%, 22.5
1
mg; yellow solid; m.p.: 225ꢀ228 °C; H NMR (400 MHz, dꢀDMSO) δ: 12.26 (s, 1H), 8.06ꢀ8.03 (m,
2
1 2
H), 7.66 (dd, J = 7.6 Hz, J = 1.2 Hz, 1H), 7.50ꢀ7.48 (m, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.19 (t, J
13
= 8.0 Hz, 1H), 6.84 (d, J = 7.6 Hz, 1H), 3.99 (s, 3H), 3.96 (s, 3H); C NMR (100 MHz, dꢀDMSO)
δ: 159.3, 154.4, 153.6, 146.4, 137.6, 130.1, 127.1, 126.9, 126.5, 122.2, 118.9, 117.9, 116.9, 114.0,
+
+
1
07.4, 103.5, 56.4, 55.3; HRMS: [M+H] m/z calcd for C18
H
14
N
2
O
4
H : 323.1026, found:
323.1030.
8-fluoro-2-(7-fluoro-1H-indol-3-yl)-4H-benzo[d][1,3]oxazin-4-one (2q), yield 32%, 23.8 mg;
1
yellow solid; m.p.: 276ꢀ278 °C; H NMR (400 MHz, dꢀDMSO) δ: 12.74 (s, 1H), 8.33 (d, J = 2.0
Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 7.7 Hz, 1H), 7.80ꢀ7.75 (m, 1H), 7.50ꢀ7.45 (m, 1H),
13
7
.28ꢀ7.23 (m, 1H), 7.14ꢀ7.09 (m, 1H); C NMR (100 MHz, dꢀDMSO) δ: 158.1, 158.0, 155.8,
155.4 (d, J = 251.8 Hz), 149.2 (d, J = 243.3 Hz) , 136.4 (d, J = 12.0 Hz), 132.5, 128.5 (d, J = 5.0
Hz), 127.2 (d, J = 7.6 Hz), 124.9 (d, J = 13.9 Hz), 123.7 (d, J = 3.8 Hz) , 122.3 (d, J = 13.8 Hz),
+
1
22.2, 118.3, 117.3 (d, J = 3.4 Hz), 108.0 (d, J = 15.6 Hz), 107.5; HRMS: [M+H] m/z calcd for
+
C
16
H
8
F
2 2
N O
2
H : 299.0627, found: 299.0624.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
1
13
Experimental procedures, characterization data, H/ C NMR spectra of all products (PDF)
The high resolution mass spectrum of crude mixtures (PDF)
Xꢀray crystallographic data of compound 2a (CIF)
ACS Paragon Plus Environment

Page 11 of 12
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
AUTHOR INFORMATION
Corresponding Author
*
Eꢀmail: hgs@lzu.edu.cn
Notes
The authors declare no competing financial interest.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
REFERENCES
[
1] (a) Pramanik S.; Reddy R. R.; Ghorai P. Org. Lett. 2015, 17, 1393. (b) Jarvest R. L.; Parratt
M. J.; Debouck C. M.; Gorniak J. G.; Jennings L. J.; Serafinowska H. T. and Strickler J. E. Bioorg.
Med. Chem. Lett., 1996, 6, 2463. (c) Hedstrom L.; Moorman A. R.; Dobbs J. and Abeles R. H.
Biochemistry, 1984, 23, 1753. (d) Stein R. L.; Strimpler A. M.; Viscarello B. R.; Wildonger R. A.;
Mauger R. C. and Trainor D. A. Biochemistry, 1987, 26, 4126. (e) Krantz A.; Spencer R. W.; Tam
T. F.; Liak T. J.; Copp L. J.; Thomas E. M.and Rafferty S. P. J. Med. Chem., 1990, 33, 464.(f)
Eissa A. M. F.; ElꢀSayed R. J. Heterocycl. Chem., 2006, 43, 1161; (g) Neumann U.; Schechter M.
N.; Gütschow M. Bioorg. Med. Chem., 2001, 9, 947.
[
2] ( a) Krantz A.; Spencer R. W.; Tam T. F.; Liak T. J.; Copp L. J.; Thomas E. M.; Rafferty S. P.
J. Med. Chem., 1990, 33, 464. (b) Yamada Y.; Kato T.; Ogino H.; Ashina S.; Kato K. Horm. Metab.
Res., 2008, 40, 539. (c) Kopelman P.; Bryson A.; Hickling R.; Rissanen A.; Rossner S.; Toubro S.;
Valensi P. Int. J. Obes., 2006, 31, 494. (d) Halford J. C. Curr. Opin. Investig. Drugs, 2006, 7,
312. (e) Padwal R. Curr. Opin. Investig. Drugs, 2008, 9, 414.
[
3] (a) Coppola G. M. J. Heterocycl. Chem., 1999, 36, 563. (b) Powers J. C.; Asgian J. L.; Ekici
O. D.and James K. E. Chem. Rev., 2002, 102, 4639; (c) Kopelman P.; Bryson A.; Hickling R.;
Rissanen A.; Rossner S.; Toubro S. and Valensi P. Int. J. Obes., 2006, 31, 494; (d) Padwal R.
Curr. Opin. Investig. Drugs, 2008, 9, 414.
[
4] (a) Allendörfer N.; EsꢀSayed M.; Nieger M. and Bräse S. Tetrahedron Lett., 2012, 53, 388;
(b) Mosley C. A.; Acker T. M.; Hansen K. B.; Mullasseril P.; Andersen K. T.; Le P.; Vellano K. M.;
BräunerꢀOsborne H.; Liotta D. C. and Traynelis S. F. J. Med. Chem., 2010, 53, 5476; (c) Larksarp
C. and Alper H. Org. Lett., 1999, 1, 1619; (d) Houlden C. E.; Hutchby M.; Bailey C. D.; Ford J.
G.; Tyler S. N. G.; Gagné M. R.; LloydꢀJones G. C. and BookerꢀMilburn K. I. Angew. Che. Int.
Ed., 2009, 48, 1830.
[
5] For reviews of the synthesis of benzoxazinones, see: (a) Coppola G. M. J. Heterocycl. Chem.,
999, 36, 563. (b) Coppola G. M. J. Heterocycl. Chem. 2000, 37, 1369.
6] (a) Beck J. R.; Yahner J. A. J. Org. Chem. 1973, 38, 2450. (b) Xue S.; McKenna J.; Shieh W.
1
[
C. and Repic O. J. Org. Chem., 2004, 69, 6474; (c) Papadopoulos E. P. and Torres C. D.
Heterocycles, 1982, 19, 1039; (d) Clayden J.; Vallverdú L.;. Helliwell M. Org. Biomol. Chem.,
2006, 4, 2106; (e) Vostrov E. S.; Novikov A. A.; Maslivets A. N. and Aliev Z. G. Russ. J. Org.
Chem., 2007, 43, 224; (f) Nayak M. K.; Kim B. H.; Kwon J. E.; Park S.; Seo J.; Chung J. W. and
Park S. Y. Chem. Eur. J., 2010, 16, 7437; (g) Manivannan E. and Chaturvedi S. C. Bioorg.
Med .Chem., 2011, 19, 4520.
[
7] (a) Bristow T. H. C.; Foster H. E. and Hooper M.; Chem. Commun. 1974, 17, 677; (b)
Crabtree H. E.; Smalley R. K. and Suschitzky H. J. Chem. Soc. C., 1968, 2730; (c) Smalley R.
K. and Suschitzky H. Tetrahedron Lett., 1966, 29, 3465; (d) Archer J. G.; Barker A. J. and Smalley
R. K. J. Chem. Soc., Perkin Trans., 1973, 4, 1169; (e) Molina P.; Conesa C. Velasco M. D.;
Tetrahedron Lett., 1993, 34, 175; (f) Gordeev M. F. Biotechnol. Bioeng., 1998, 61, 13; (g)
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 12
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
Salvadori J.; Balducci E.; Zaza S.; Petricci E. and Taddei M. J. Org. Chem., 2010, 75, 1841; (h)
Giri R.; Lam J. K. and Yu J. Q. J. Am. Chem. Soc., 2010, 132, 686.
[
8] (a) Sundberg R. J. in: The Chemistry of Indoles, (Eds.: Katritzky A. R., MethꢀCohn O., Rees
C. W.), Academic Press, New York, 1996; (b) Ryan K. S. and Drennan C. L. Chem. Biol., 2009, 16,
351; (c) Humphrey G. R. and Kuethe J.T. Chem. Rev., 2006, 106, 2875; (d) Cacchi S. and Fabrizi
G. Chem. Rev., 2005, 105, 2873; (e) Shiri M. Chem. Rev., 2012, 112, 3508; (f) Shiri M., Zolfigol
M. A., Kruger H. G. and Tanbakouchian Z. Chem. Rev., 2010, 110, 2250; (g) Brancale A. and
Silvestri R. Med. Res. Rev., 2007, 27, 209.
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
[
9] (a) Sundberg R. J. Comprehensive Heterocyclic Chemistry II; Katritzky A. R., Rees C. W.,
Scriven E. F. V., Eds.; Pergamon Press: Oxford, U.K., 1996; Vol. 2, p 119. (b) Katritzky A. R.,
Pozharskii A. F. Handbook of Heterocyclic Chemistry; Pergamon Press: Oxford, U.K., 2000. (c)
Lebsack A. D.; Link J. T.; Overman L. E. and Stearn B. A. J. Am. Chem. Soc., 2002, 124, 9008; (d)
Somei M. and Yamada F. Nat. Prod. Rep., 2005, 22, 73; (e) Humphrey G. R. and Kuethe J. T.
Chem. Rev., 2006, 106, 2875; (f) Movassaghi M. and Schmidt M. A. Angew. Chem., Int. Ed., 2007,
46, 3725.
[
10] Wu, P.ꢀL.; Hsu, Y.ꢀL. and Jao, C.ꢀW. J. Nat. Prod., 2006, 69, 1467.
11] Mason J. J.; Bergman J. and Janosik T. J. Nat. Prod., 2008, 71, 1447.
12] Ganachaud C.; Garfagnoli V.; Tron T. and Iacazio G. Tetrahedron Lett., 2008, 49, 2476.
[13] Capdevielle P. and Maumy M.; Tetrahedron Lett. 1993, 34, 2953.
14] Lian X. L.; Lei H.; Quan X. J.; Ren Z. H.; Wang Y. Y. and Guan Z. H. Chem. Commun.,
013, 49, 8196
15] Guchhait S. K.; Chaudhary V.; Rana V. A.; Priyadarshani G.; Kandekar S. and Kashyap
M. Org. Lett., 2016, 18, 1534.
[
[
[
2
[
[
[
[
16] Ling K. Q. Synth. Commun., 1996, 26, 149.
17] Yamashita M. and Iida A. Tetrahedron Lett., 2014, 55, 2991.
18] Feng Y. D.; Li Y. D.; Cheng G. L.; Wang L. H. and Cui X. L. J. Org. Chem., 2015, 80, 7099.
[19] Liu Q. L., Chen P. H. and Liu G. S. ACS Catal., 2013, 3, 178.
[
[
[
20] Lin F.; Chen Y.; Wang B. S.; Qin W. B. and Liu L. X. RSC Adv., 2015, 3, 37018.
21] Astolfi P.; Panagiotaki M.; Rizzoli C. and Greci L. Org. Biomol. Chem., 2006, 4, 3282.
22] Baloghꢀhergovich É. and Speier G., Journal of Molecular catalysis, 1989, 57, 9.
[23] Sheng R., Zhu J.W. and Hu Y.Z., Molecules, 2012, 17, 1177.
[
[
[
24] Saito I.; Imuta M.; Matsugo S.; Yamamoto H. and Matsuura T., Synthesis, 1976, 255.
25] Carniaux J. F.; KanꢀFan C.; Royer J. and Huason H.P., Tetrahedron Lett. 1997, 38, 2997.
26] Saito I.; Imuta M. and Matsuura T., Chemistry Lett., 1972, 1173.
[27] Penhoat M.; Bohn P.; Dupas G.; Papamicaël C.; Marsais F. and Levacher V., Tetrahedron:
Asymmetry, 2006, 17, 281.
ACS Paragon Plus Environment