Assembly of Polysubstituted Maleimides via Palladium-Catalyzed Cyclization Reaction of Alkynes with Isocyanides

Article abstract of DOI:10.1021/acs.joc.6b02227

An efficient and convenient palladium-catalyzed cyclization reaction of alkynes with isocyanides is described herein. This protocol allows the practical synthesis of many valuable polysubstituted maleimide derivatives after hydrolysis with a broad scope of substrates and mild reaction conditions. C-C, CO, and C-N bonds were constructed in this transformation with isocyanide serving as both C and N sources.

Full text of DOI:10.1021/acs.joc.6b02227

Subscriber access provided by Georgia Tech Library
Note
Assembly of Polysubstituted Maleimides via Palladium-
Catalyzed Cyclization Reaction of Alkynes with Isocyanides
Weigao Hu, Jia Zheng, Jianxiao Li, Bifu Liu, Wanqing Wu, Haiyang Liu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02227 • Publication Date (Web): 16 Nov 2016
Downloaded from http://pubs.acs.org on November 19, 2016
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 30
The Journal of Organic Chemistry
1
2
3
4
5
Assembly of Polysubstituted Maleimides via
6
7
Palladium-Catalyzed Cyclization Reaction of Alkynes
8
with Isocyanide
s
9
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
Weigao Hu, Jia Zheng, Jianxiao Li, Bifu Liu, Wanqing Wu, Haiyang Liu* and
Huanfeng Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640,
China
*E-mail: chhyliu@scut.edu.cn; jianghf@scut.edu.cn; Fax: (+86) 20-87112906
Abstract: An efficient and convenient palladium-catalyzed cyclization reaction of
alkynes with isocyanides is described herein. This protocol allows the practical
synthesis of many valuable polysubstituted maleimide derivatives after hydrolysis
with a broad scope of substrates and mild reaction conditions. C-C, C=O and C-N
bonds were constructed in this transformation with isocyanide serving as both C and
N sources.
The maleimide skeleton is commonly embedded in various natural products which
has been demonstrated an important class of extraordinary biological and
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 30
1
2
3
4
5
6
7
8
9
pharmaceutical properties.1 For example, compound SB 216763 has shown inhibition
to the R-isoform of GSK-3 in an ATP-competitive manner.1b Himanimide A and C are
used to inhibit the growth of bacteria and fungi. Granulatimide is commonly
identified as a checkpoint inhibitor exhibiting good anti-tumor activity1c (Figure 1). In
particular, the arylmaleimide derivatives are also important building blocks in
materials science.2
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
Figure 1. Selected examples containing maleimide motifs in medicine
Therefore, considerable efforts have been devoted towards their synthesis in the
past few decades. Generally, maleimides are prepared through an ammonolysis
reaction of maleic anhydrides with ammonia or an ammonium source (Scheme 1a)3.
However, this approach is unsuccessful for the synthesis of polysubstituted or
unsymmetrical maleimides. To overcome these difficulties, the strategy of
selective functionalization of 3,4-dihalomaleimide by Grignard addition4 and
cross-coupling reaction5 has been developed (Scheme 1b). Furthermore, in
2004, Chen and co-workers developed a convenient procedure for preparing
3,4-diaryl-substituted maleimides from diaryl-substituted fumaronitrile.6
2
ACS Paragon Plus Environment

Page 3 of 30
The Journal of Organic Chemistry
1
2
3
4
Scheme 1. Synthesis of Maleimide Derivatives
5
6
7
8
9
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
However, unavailable starting materials in these approaches significantly limited
their library synthesis and applications. As far as we know, there is few report on the
direct synthesis of polysubstituted maleimides from alkynes under transition metal
catalysis.7 In this regard, the development of rapid and straightforward strategy to
build small molecule libraries containing diverse maleimide moieties is highly
meaningful and desirable.
In addition, isocyanides have been recognized as valuable C1 building blocks in
organic synthesis because of their structural and reactive properties.8 Over the past
decade, transition metal-catalyzed reactions involving isocyanides have drawn wide
attention,9 especially for palladium catalysis.8f, 10 To the best of our knowledge,
isocyanides utilized as a source of amide has been achieved respectively by Cai,11
Zhu12 and our group.13 Inspired by our previous work on palladium-catalyzed
isocyanide insertion reactions13,14 and synthesis of important heterocyclic compounds
from alkynes.15 Herein, we would like to describe an efficient and practical
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 30
1
2
3
4
palladium-catalyzed intermolecular cyclization reaction of alkynes and isocyanides
5
6
7
for the synthesis of polysubstituted maleimides (Scheme 1c)
.
8
9
Our investigations were initiated with reaction of ethyl 3-phenylpropiolate (1a) and
tert-butyl isocyanide (2a) for reaction condition optimization (Table 1). Firstly,
various different palladium salts were examined in the presence of KBr (1.0 equiv) in
CH3CN at 80 oC for 12 h, and Pd(OAc)2 provided the best result, affording the desired
product in 78% yield (entries 1-3). As expected, no reaction occurred in the absence
of palladium catalyst (entry 4). Subsequently, a range of additives such as LiBr, LiCl,
and KI were evaluated (entries 5-7), and gave the similar results. Afterwards,
different solvents were screened, and toluene proved to be optimal (entries
8-10). However, a significant lower yield was observed when the reaction proceeded
without additives (entry 11). Reducing the loading of KBr led to slightly lower
yield of 81%, although increasing the amount of KBr did not give further
enhancement of the yield (entries 12-14). These results revealed that KBr
played a beneficial role in this process. Finally, with shortened or prolonged the
reaction time, the corresponding product was not increased (entries 15-16).
Table 1. Optimization of Reaction Conditionsa
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
Entry
1
[Pd]
Additive
KBr
Solvent
CH3CN
Yield (%)b
10
PdCl2
4
ACS Paragon Plus Environment

Page 5 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
2
3
Pd(OAc)2
Pd(PPh3)4
-
KBr
KBr
KBr
LiBr
LiCl
KI
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCE
78
trace
0
4
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
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
70
6
72
7
76
8
KBr
KBr
KBr
-
20
9
DMSO
Toluene
CH3CN
Toluene
Toluene
Toluene
Toluene
Toluene
30
10
11
12c
13d
14e
15f
16g
93 (86)
46
KBr
KBr
KBr
KBr
KBr
81
96
88
80
95
aReaction conditions: 1a (0.4 mmol), 2a (1.0 mmol), H2O (5 equiv, 2.0 mmol), [Pd] (5 mol %),
additive (1 equiv, 0.4 mmol) in 2 mL solvent at 80 °C for 12 h then cooled to room temperature,
followed by the addition of HCl (4 M, 0.5 mL) and heating at 80 °C for 1 h. b Yields were
analyzed by GC/MS using n-dodecane as an internal standard. Yields of isolated products were
given in parentheses. c0.2 mmol KBr. d 0.8 mmol KBr. e1.6 mmol KBr. f10 h. f14 h
With the optimized reaction conditions in hand, we next explored the scope and
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 30
1
2
3
4
5
6
7
8
9
limitation of the reaction between various alkynoates and isocyanides, and the results
are summarized in Scheme 2. Gratifyingly, good yields were obtained when tert-butyl
isocyanide 2a was reacted with methyl or benzyl alkynoates under the optimal
reaction conditions (3ba and 3ca). The structure of 3ba was unambiguously
determined by X-ray crystallographic analysis (see the Supporting Information for
details). Ethyl alkynoates bearing phenyl groups substituted at the para position with
electron-donating groups (Me, MeO) and electron-withdrawing ones (F, Cl, Br,
COOMe, CF3) all displayed high reactivity and the corresponding products 3da-3ma
were obtained in good to excellent yields. Substitution at the 3-, or 2-position of the
aromatic ring also worked well in this catalytic cycle (3ka, 3la and 3ma), which
revealed that there was no obvious steric hindrance effect for this reaction.
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
Gratifyingly,
ethyl
3-(benzo[d][1,3]dioxol-5-yl)propiolate
and
ethyl
3-(3,5-dichlorophenyl)propiolate were successfully converted into the maleimide
products 3na and 3oa in good yields. Notably, a vinyl group was tolerated under the
standard reaction conditions, thus providing 3pa in 80% yield. However, no desired
product was detected when alkyl alkynoate was used in this catalyst system. Moreover,
our system was widely applicable to alkynes activated by other electron-donating
groups and the corresponding products 3qa and 3ra in 54% and 77% yields,
respectively.
6
ACS Paragon Plus Environment

Page 7 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Scheme 2. Substrate Scope of Various Activated Alkynes and Isocyanidesa,b
8
9
1. Pd(OAc)2 (5 mol %)
O
KBr (1.0 equiv)
GF
R1
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
H2 (5.0 equiv)
R1
FG
C
N
2
R2
R2
N
+
toluene, 80 oC, 12 h
1
HCl, 80 oC, 1 h
O
2.
3
O
N
3da
3ea
3fa
3ga
3ha
3ia
, R=Me, 82%
, R=MeO, 86%
, R=F, 82%
, R=Cl, 84%
, R=Br, 53%
R2OOC
O
N
EtOOC
t-Bu
t-Bu
O
O
3aa, R2=Et, 86%
3ba, R2=Me, 84%
3ca, R2=Bn, 87%
, R=COOMe, 62%
, R=CF3, 87%
R
3ja
X-ray of 3ba
O
O
EtOOC
EtOOC
O
O
EtOOC
O
EtOOC
N
N
O
t-Bu
t-Bu
Cl
R
N
t-Bu
N
t-Bu
O
O
O
O
Cl
3oa,
73%
Cl
3ka
3la,
, R=Cl, 83%
R=Me, 80%
3na, 85%
3ma,70%
Ms
N
O
N
O
EtOOC
O
EtOOC
N
N
t-Bu
t-Bu
N
t-Bu
O
O
Ph
O
3qa, 54%
3pa, 80%
3ra, 77%
O
O
O
O
EtOOC
EtOOC
EtOOC
EtOOC
N
N
O
N
O
n-Bu
N
O
O
3acb, 56%
3adb, 49%
3aeb, 70%
3abb, 83%
aReaction conditions: 1 (0.4 mmol), 2 (1 mmol), Pd(OAc)2 (5mol %), KBr (0.4 mmol), H2O (2.0
mmol) and toluene (3 mL) were stirred 80 oC for 12 h then cooled to room temperature, followed
by the addition of HCl (4 M, 0.5 mL) and heating at 80 °C for 1 h. Yields of the isolated products
are given. b In DMSO
To further demonstrate the scope of the present reaction, various isocyanides were
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 30
1
2
3
4
5
6
7
8
9
employed in this transformation. Fortunately, almost all alkyl isocyanides were found
to be suitable for this transformation, affording the corresponding maleimides. For
instance, n-butyl isocyanide and cyclohexyl isocyanide were converted into the
desired products in 83% and 49% yields, respectively. Even sterically hindered
1,1,3,3-tetramethylbutyl isocyanide and admantyl isocyanide were also found to be
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
compatible
with
the
present
cycloaddition
protocol.
Unfortunately,
2,6-dimethylphenyl isocyanide and 4-methoxyphenyl isocyanide failed to afford the
desired products. It is proposed that the cyclopalladium intermediate is
non-productive during the reaction.
Subsequently, the scope of the reaction was further expanded to a variety of
unactivated alkynes despite the more harsh reaction conditions were required and the
results are summarized in Scheme 3. Symmetrical substituted diaryl acetylenes
bearing halogen or methyl groups at the para position delivered the desired products
5a-5c in 69−86% yields. Moreover, dithiophenylacetylene could also react smoothly
under the optimal conditions and afford the target molecule 5d in excellent 86% yield.
For unsymmetrical alkynes, the reactions also showed a remarkably wide scope. Only
trace amount of the cycloadducts was detected for 1-bromo-2-(phenylethynyl)benzene
(4i) and 46% yield was obtained when 1-(phenylethynyl)naphthalene (4j) was
employed as substrate, which revealed that the steric hindrance of substituents on the
phenyls did have a strong influence in this process. In addition, aryl alkyl alkynes
displayed good to high reactivity and gave the corresponding products 5l and 5m in
74% and 80% yields, respectively. Importantly, this catalytic system could be
8
ACS Paragon Plus Environment

Page 9 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
expanded to terminal alkynes even though a lower yield was obtained (5n). It is worth
noting that 1,4-diphenylbuta-1,3-diyne (1o) was also good substrate for this reaction
and converted to the desired products in 82% yield.
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
Scheme 3. Substrate Scope of Unactivated Alkynesa
aReaction conditions: 4 (0.4 mmol), 2a (1 mmol), Pd(OAc)2 (5 mol %), KBr (0.8 mmol), H2O (2.0
o
mmol) and toluene (3 mL) were stirred at 100 C for 24 h then cooled to room temperature,
followed by the addition of HCl (4 M, 0.5 mL) and heating at 80 °C for 1 h. Yields of the
isolated products are given.
Furthermore, the diyne 4p was transferred to the corresponding product 5p
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 30
1
2
3
4
5
6
containing two maleimide rings in 43% yield, and 5p’ bearing one maleimide ring
was also detected at the same time (Scheme 4).
7
8
9
Scheme 4. Substrate of 1,4-bis(Phenylethynyl)benzene
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
Ph
1. Pd(OAc)2 (5 mol %)
t-Bu
O
KBr (2.0 equiv)
N
Ph
Ph +
C
N
t-Bu
N
toluene, 100 oC, 24 h
2. HCl, 80 oC, 1 h
O
t-Bu
2a
4p
Ph
O
5p, 43%
1 equiv
5 equiv
O
Ph
N
t-Bu
O
5p'. 30%
Ph
The practicality of this method was demonstrated by the gram-scale reaction. Under
the standard reaction conditions, 1.42g of 1,2-diphenylethyne (4a, 8 mmol) was
readily converted into 5a in 69% yield (Scheme 5).
Scheme 5. Gram Scale Diphenylmaleimide Synthesis
In order to obtain more information on the reaction mechanism of the present
catalytic process, a control experiment was conducted as shown in Scheme 6. 5a-18O
was observed nearly as the sole product when 1,2-diphenylethyne 4a and tert-butyl
isocyanide 2a were treated in anhydrous toluene in the presence of H218O, which
indicated that the oxygen atom of the amide was grabbed from water.
Scheme 6. Control Experiment
10
ACS Paragon Plus Environment

Page 11 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
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
It is noteworthy that the newly formed N-tert-butyl maleimide products could be
further transformed to the unprotected maleimides according to the literature.16 For
example, when 1-(tert-butyl)-3,4-diphenyl-1H-pyrrole-2,5-dione 5a was heated to
reflux in trifluoroacetic acid for 24 h, the desired 3,4-diphenyl-1H-pyrrole-2,5-dione
6a was obtained in more than 80% yield (Scheme 7).
Scheme 7. Deprotection of N-tert-butylmaleimide 5a
CONCLUSION
In summary, we have developed an efficient and practical protocol for the synthesis
of various polysubstituted maleimide derivatives through the palladium-catalyzed
intermolecular cyclization reaction of alkynes with isocyanides. In this process,
isocyanides serve as both C and N sources and C-C, C=O and C-N bonds were
constructed in one pot. Furthermore, this reaction also demonstrated many advantages
such as good functional group compatibility, easily available starting materials, and
operational simplicity.
EXPERIMENTAL SECTION
General Methods. All reactions were carried out in 10 mL tubes under air
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 30
1
2
3
4
5
6
7
8
9
atmosphere. H and 13C NMR spectra were recorded using a 400 MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.26 and 77.0 ppm,
respectively, and chloroform is solvent with TMS as the internal standard. Reagents
and solvents were purchased commercially and used without further purification.
Mass spectra were recorded on a gas chromatograph-mass spectrometer. Melting
points were measured with a melting point apparatus. IR spectra were obtained either
as potassium bromide pellets or as liquid films between two potassium bromide
pellets with a spectrometer. The data of HRMS was carried out on a high-resolution
mass spectrometer (LCMS-IT-TOF). TLC was performed by using commercially
prepared 100–400 mesh silica gel plates. X-ray structural analyses were conducted on
an X-ray analysis instrument.
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
General Procedure for the Synthesis of Polymaleimides
A mixture of alkynes 1 or 4 (0.4 mmol), isocyanides 2 (1.0 mmol), H2O (2.0 mmol),
o
Pd(OAc)2 (5 mol %) and KBr (0.4 mmol) was stirred in toluene (2 mL) at 80 C (oil
bath temperature) for 12-24 h. After the resulting solution was cooled to room
o
temperature and HCl (4 M, 0.5 mml) was added and heated to 80 C for 1 h. The
reaction mixture was cooled to room temperature and quenched with water, extracted
by ethyl acetate (3 × 10 mL). The combined organic phases were dried over
anhydrous MgSO4, filtered and concentrated under reduced pressure. Purification
using flash chromatography on silica gel provided product 3 or 5 with petroleum
ether/ethyl acetate as the eluent.
12
ACS Paragon Plus Environment

Page 13 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Ethyl 1-(tert-butyl)-2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate (3aa).
Yellow solid (104 mg, 86%). Mp 74-75 oC. 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J
= 7.9, 1.4 Hz, 2H), 7.44 (m, 3H), 4.34 (q, J = 7.1 Hz, 2H), 1.64 (s, 9H), 1.28 (t, J =
7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.4, 168.2, 161.9, 141.1, 131.0, 123.0,
128.4, 128.3, 127.4, 62.2, 58.4, 28.8, 13.9. IR (KBr): 2992, 2358, 1833, 1633, 1497,
1378, 1243, 1055, 750 cm-1. ESI-HRMS calcd for C17H19NNaO4 [M + Na]+: 324.1206,
found: 324.1214.
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
Methyl 1-(tert-butyl)-2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate (3ba).
Yellow solid (96 mg, 84%). Mp 66-67 oC. 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J =
7.9, 1.5 Hz, 2H), 7.46 (m, 3H), 3.86 (s, 3H), 1.64 (s, 9H). 13C NMR (100 MHz,
CDCl3) δ 170.3, 168.2, 162.4, 141.8, 131.1, 130.0, 128.5, 127.8, 127.3, 58.5, 52.8,
28.8. IR (KBr): 2991, 2357, 1784, 1377, 1243, 1056 cm-1. ESI-HRMS calcd for
C16H17NNaO4 [M + Na]+: 310.1050, found: 310.1046.
Benzyl 1-(tert-butyl)-2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate (3ca).
o
1
Yellow solid (126 mg, 87%). Mp 91-92 C. H NMR (400 MHz, CDCl3) δ 7.52 (m,
2H), 7.43 (d, J = 7.5 Hz, 1H), 7.33 (m, 7H), 5.31 (s, 2H), 1.64 (s, 9H). 13C NMR (100
MHz, CDCl3) δ 170.3, 168.1, 161.7, 141.6, 134.5, 131.0, 130.0, 128.7, 128.6, 128.4,
127.2, 67.8, 58.5, 28.8. IR (KBr): 2990, 2357, 1763, 1705, 1243, 1056 cm-1.
ESI-HRMS calcd for C22H21NNaO4 [M + Na]+: 386.1363, found: 386.1369.
Ethyl 1-(tert-butyl)-2,5-dioxo-4-(p-tolyl)-2,5-dihydro-1H-pyrrole-3-carboxylate (3da).
Yellow solid (103 mg, 82%). Mp 65-66 oC. 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J =
8.1 Hz, 2H), 7.28 (d, J = 2.8 Hz, 2H), 4.37 (q, J = 7.1 Hz, 2H), 2.42 (s, 3H), 1.66 (s,
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 30
1
2
3
4
5
6
7
8
9
9H), 1.32 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.6, 168.4, 162.2,
141.8, 141.2, 130.1, 129.2, 127.3, 124.6, 62.1, 58.3, 28.9, 21.6, 14.0. IR (KBr): 2989,
2358, 1764, 1707, 1374, 1242, 1055 cm-1. ESI-HRMS calcd for C18H21NNaO4 [M +
Na]+: 338.1363, found: 338.1367.
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
Ethyl
1-(tert-butyl)-4-(4-methoxyphenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carboxylate
(3ea). Yellow solid (114 mg, 86%); Mp 48-49 oC. 1H NMR (400 MHz, CDCl3) δ 7.67
(d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H),
1.63 (s, 9H), 1.31 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.7, 168.6,
162.4, 162.1, 140.7, 132.1, 125.7, 119.9, 114.0, 62.1, 58.3, 55.4, 28.9, 14.0. IR (KBr):
2988, 2358, 1764, 1705, 1375, 1244, 1053 cm-1. ESI-HRMS calcd for C18H21NNaO5
[M + Na]+: 354.1312, found: 354.1314.
Ethyl
1-(tert-butyl)-4-(4-fluorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carboxylate
(3fa). Yellow solid (105 mg, 82%). Mp 62-63 oC. 1H NMR (400 MHz, CDCl3) δ 7.68
(dd, J = 8.6, 5.4 Hz, 2H), 7.13 (t, J = 8.6 Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 1.64 (s,
9H), 1.30 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.3, 168.1, 164.4 (d, J
= 252.3 Hz), 161.9, 140.2, 132.5, 132.4 (d, J = 8.7 Hz), 127.8, 123.5 (d, J = 3.2 Hz),
123.5, 115.8 (d, J = 21.8 Hz), 62.3, 58.5, 28.8, 14.0. IR (KBr): 2987, 2357, 1763,
1708, 1341, 1241, 1053 cm-1. ESI-HRMS calcd for C17H18FNNaO4 [M + Na]+:
342.1112, found: 342.1107.
Ethyl
14
ACS Paragon Plus Environment

Page 15 of 30
The Journal of Organic Chemistry
1
2
3
4
1-(tert-butyl)-4-(4-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carboxylate
5
6
o
1
(3ga). White solid (113 mg, 84%). Mp 68-69 C. H NMR (400 MHz, CDCl3) δ 7.60
(d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 1.63 (s, 9H),
1.30 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.1, 168.0, 161.7, 140.4,
137.8, 131.4, 128.8, 128.3, 125.8, 62.4, 58.6, 28.8, 14.0. IR (KBr): 2987, 2357, 1763,
1708, 1344, 1242, 1102, 1054 cm-1. ESI-HRMS calcd for C17H18ClNNaO4 [M + Na]+:
358.0817, found: 358.0824.
7
8
9
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
Ethyl
4-(4-bromophenyl)-1-(tert-butyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carboxylate
o
1
(3ha). Yellow solid (80 mg, 53%). Mp 75-76 C. H NMR (400 MHz, CDCl3) δ 7.58
(d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 1.63 (s, 9H),
1.30 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.1, 168.0, 161.7, 140.2,
131.8, 131.6, 128.4, 126.2, 126.1, 62.4, 58.6, 28.8, 14.0. IR (KBr): 2989, 2357, 1764,
1707, 1376, 1243, 1056 cm-1. ESI-HRMS calcd for C17H18BrNNaO4 [M + Na]+:
402.0311, found: 402.0310.
Ethyl1-(tert-butyl)-4-(4-(methoxycarbonyl)phenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-
3-carboxylate (3ia). Yellow oil (89 mg, 62%). 1H NMR (400 MHz, CDCl3) δ 8.09 (d,
J = 8.3 Hz, 2H), 7.70 (d, J = 8.3 Hz, 2H), 4.34 (q, J = 7.1 Hz, 2H), 3.94 (s, 3H), 1.64
(s, 9H), 1.29 (d, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.0, 167.8, 166.3,
161.5, 140.2, 132.1, 131.5, 130.0, 129.5, 129.4, 62.4, 58.7, 52.4, 28.8, 13.9. IR (KBr):
2989, 2357, 1763, 1715, 1373, 1242, 1055 cm-1. ESI-HRMS calcd for C19H21NNaO6
[M + Na]+: 382.1261, found: 382.1263.
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 30
1
2
3
4
5
6
Ethyl
1-(tert-butyl)-2,5-dioxo-4-(4-(trifluoromethyl)phenyl)-2,5-dihydro-1H-pyrrole-3-carb
7
8
9
o
1
oxylate (3ja). White solid (128 mg, 87%). Mp 103-104 C. H NMR (400 MHz,
CDCl3) δ 7.75 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 8.5 Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H),
1.64 (s, 9H), 1.29 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 169.9, 167.7,
161.4, 140.0, 132.6 (q, J = 32.6 Hz), 130.8, 130.4, 129.7, 125.3 (q, J = 3.7 Hz), 123.6
(q, J = 270.9 Hz), 62.5, 58.7, 28.8, 14.0. IR (KBr): 2987, 2357, 1710, 1337, 1168,
1113, 851 cm-1. ESI-HRMS calcd for C18H18F3NNaO4 [M + Na]+: 392.1080, found:
392.1079.
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
Ethyl
1-(tert-butyl)-4-(3-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carboxylate
o
1
(3ka). White solid (111 mg, 83%). mp 64-65 C. H NMR (400 MHz, CDCl3) δ 7.65
(s, 1H), 7.52 (d, J = 7.7 Hz, 1H), 7.45 (d, J = 8.1 Hz, 1H), 7.38 (t, J = 7.9 Hz, 1H),
4.36 (q, J = 7.1 Hz, 2H), 1.64 (s, 9H), 1.30 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ 170.0, 167.9, 161.5, 139.7, 134.5, 131.0, 129.9, 129.7, 129.1, 128.9, 128.1,
62.4, 58.6, 28.8, 14.0. IR (KBr): 2988, 2359, 1764, 1708, 1337, 1241, 1054 cm-1.
ESI-HRMS calcd for C17H18ClNNaO4 [M + Na]+: 358.0817, found: 358.0824.
Ethyl 1-(tert-butyl)-2,5-dioxo-4-(m-tolyl)-2,5-dihydro-1H-pyrrole-3-carboxylate (3la).
Yellow solid (101 mg, 80%). Mp 40-41 oC. 1H NMR (400 MHz, CDCl3) δ 7.47 – 7.39
(m, 2H), 7.35 – 7.27 (m, 2H), 4.34 (q, J = 7.1 Hz, 2H), 2.38 (s, 3H), 1.64 (s, 9H), 1.29
(t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.5, 168.3, 162.0, 141.3, 138.1,
131.9, 130.5, 128.3, 128.1, 127.3, 127.1, 62.1, 58.4, 28.8, 21.4, 14.0. IR (KBr): 2989,
16
ACS Paragon Plus Environment

Page 17 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
2359, 1765, 1706, 1375, 1339, 1243, 1055 cm-1. ESI-HRMS calcd for C18H21NNaO4
[M + Na]+: 338.1363, found: 338.1370.
7
8
9
Ethyl
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
1-(tert-butyl)-4-(2-chlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carboxylate
(3ma). Yellow liquid (94 mg, 70%). 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.7
Hz, 1H), 7.42 – 7.37 (m, 1H), 7.35 (d, J = 4.2 Hz, 2H), 4.23 (q, J = 7.1 Hz, 2H), 1.64
13
(s, 9H), 1.16 (t, J = 7.1 Hz, 3H). C NMR (100 MHz, CDCl3) δ 169.3, 167.6, 160.4,
143.2, 133.5, 131.3, 131.1, 130.0, 129.7, 127.1, 126.4, 61.9, 58.6, 28.8, 13.8. IR
(KBr): 2990, 2358, 1713, 1489, 1340, 1239, 1105, 1028 cm-1; ESI-HRMS calcd for
C17H18ClNNaO4 [M + Na]+: 358.0817, found: 358.0819.
Ethyl
4-(benzo[d][1,3]dioxol-5-yl)-1-(tert-butyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carbo
xylate (3na). Yellow liquid (117 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 7.20 (d, J =
6.6 Hz, 1H), 7.11 (d, J = 1.3 Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 5.96 (s, 2H), 4.29 (q, J
13
= 7.1 Hz, 2H), 1.56 (s, 9H), 1.25 (t, J = 7.1 Hz, 3H). C NMR (100 MHz, CDCl3) δ
170.5, 168.4, 162.3, 150.3, 147.9, 140.3, 126.5, 125.8, 121.2, 110.0, 108.5, 101.7,
62.2, 59.5, 28.9, 14.0. IR (KBr): 2989, 2359, 1764, 1704, 1337, 1244, 1050 cm-1.
ESI-HRMS calcd for C18H19NNaO6 [M + Na]+: 368.1105, found: 368.1106.
Ethyl
1-(tert-butyl)-4-(3,5-dichlorophenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carboxylate
1
(3oa). Brown liquid (128 mg, 87%). H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 1.8
Hz, 2H), 7.46 (t, J = 1.8 Hz, 1H), 4.37 (q, J = 7.1 Hz, 2H), 1.63 (s, 9H), 1.32 (t, J =
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 30
1
2
3
4
5
6
7
8
9
7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 169.5, 167.5, 161.0, 138.4, 135.2, 130.8,
129.9, 129.8, 128.3, 62.6, 58.8, 28.8, 14.0. IR (KBr): 2991, 2358, 1764, 1708, 1377,
1243, 1056 cm-1. ESI-HRMS calcd for C17H17Cl2NNaO4 [M + Na]+: 392.0427, found:
392.0440.
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
Ethyl
1-(tert-butyl)-2,5-dioxo-4-(4-vinylphenyl)-2,5-dihydro-1H-pyrrole-3-carboxylate
(3pa). Yellow solid (105 mg, 80%). Mp 67-68 oC. 1H NMR (400 MHz, CDCl3) δ 7.63
(d, J = 7.7 Hz, 2H), 7.46 (d, J = 7.7 Hz, 2H), 6.73 (dd, J = 17.5, 10.9 Hz, 1H), 5.85 (d,
J = 17.6 Hz, 1H), 5.37 (d, J = 10.8 Hz, 1H), 4.35 (q, J = 6.6 Hz, 2H), 1.64 (s, 9H),
1.30 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.4, 168.3, 162.1, 140.6,
140.3, 135.9, 130.4, 127.6, 126.7, 126.2, 116.3, 62.2, 58.4, 28.8, 14.0. IR (KBr): 2987,
2358, 1764, 1705, 1377, 1240, 1242, 1106, 1054 cm-1. ESI-HRMS calcd for
C19H21NNaO4 [M + Na]+: 350.1363, found: 350.1366.
N-(1-(tert-butyl)-2,5-dioxo-4-(p-tolyl)-2,5-dihydro-1H-pyrrol-3-yl)-N-methylmethanes
o
ulfonamide (3qa). Yellow solid (76 mg, 54%). mp 120-121 C. H NMR (400 MHz,
1
CDCl3) δ 7.69 (d, J = 7.5 Hz, 2H), 7.29 (d, J = 7.6 Hz, 2H), 3.36 (s, 3H), 3.02 (s, 3H),
13
2.41 (s, 3H), 1.65 (s, 9H). C NMR (100 MHz, CDCl3) δ 170.3, 168.8, 141.1, 135.5,
132.1, 129.7, 129.4, 124.2, 58.2, 40.0, 36.3, 29.0, 21.5. IR (KBr): 2985, 2928, 2358,
1764, 1706, 1348, 1243, 1054 cm-1. ESI-HRMS calcd for C17H22N2NaO4S [M + Na]+:
373.1192, found: 373.1190.
Ethyl
1-(1-(tert-butyl)-2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole-3-carbox
18
ACS Paragon Plus Environment

Page 19 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
ylate (3ra). Yellow solid (128 mg, 77%). Mp 185-186 oC. 1H NMR (400 MHz, CDCl3)
δ 8.20 (d, J = 7.8 Hz, 1H), 8.12 (s, 1H), 7.31 (s, 1H), 7.30 (s, 2H), 7.27 – 7.19 (m, 3H),
6.95 (t, J = 7.5 Hz, 1H), 6.59 (d, J = 8.2 Hz, 1H), 4.45 – 4.38 (m, 2H), 1.72 (s, 9H),
1.43 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.1, 167.7, 164.2, 134.4,
133.6, 130.8, 130.4, 129.6, 128.6, 127.2, 127.1, 127.0, 123.5, 123.2, 121.8, 112.8,
112.4, 60.1, 58.7, 29.0, 14.5. IR (KBr): 2985, 2357, 1764, 1707, 1548, 1456, 1355,
1245, 1200, 1053 cm-1. ESI-HRMS calcd for C25H25N2O4 [M + H]+: 417.1809, found:
417.1815.
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
Ethyl 1-butyl-2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate (3ab). Brown
oil (93 mg, 77%). 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 6.8 Hz, 2H), 7.50 – 7.43
(m, 3H), 4.35 (q, J = 7.1 Hz, 2H), 3.60 (t, J = 7.2 Hz, 2H), 1.65 – 1.59 (m, 2H), 1.39 –
1.33 (m, 2H), 1.29 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 169.4, 167.3, 161.7, 142.2, 131.4, 130.1, 128.5, 127.7, 127.3, 62.2, 38.4,
30.4, 19.9, 13.9, 13.5. IR (KBr): 2961, 1733, 1710, 1635, 1444, 1404, 1347, 1288,
1053 cm-1. ESI-HRMS calcd for C17H19NNaO4 [M + Na]+: 324.1206, found:
324.1204.
Ethyl
2,5-dioxo-4-phenyl-1-(2,4,4-trimethylpentan-2-yl)-2,5-dihydro-1H-pyrrole-3-carboxyl
ate (3ac). Yellow oil (80 mg, 56%). 1H NMR (400 MHz, CDCl3) δ 7.66 – 7.60 (m,
2H), 7.49 – 7.41 (m, 3H), 4.34 (q, J = 7.1 Hz, 2H), 1.95 (s, 2H), 1.72 (s, 6H), 1.29 (t,
J = 7.1 Hz, 4H), 0.97 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 170.9, 168.7, 161.9,
141.3, 131.1, 130.0, 128.4, 128.3, 127.4, 62.2, 61.9, 50.8, 31.6, 31.0, 29.8, 14.0. IR
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 30
1
2
3
4
5
6
(KBr): 2986, 2358, 1764, 1704, 1371, 1242, 1055 cm-1. ESI-HRMS calcd for
C21H27NNaO4 [M + Na]+: 380.1832, found: 380.1829.
7
8
9
Ethyl 1-cyclohexyl-2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate (3ad).
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
1
Yellow oil (73 mg, 56%). H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.2 Hz, 2H),
7.47 (dd, J = 10.7, 7.4 Hz, 3H), 4.35 (q, J = 7.1 Hz, 2H), 4.00 (ddd, J = 12.2, 8.0, 3.8
Hz, 1H), 2.10 (qd, J = 12.4, 3.0 Hz, 2H), 1.85 (d, J = 13.3 Hz, 2H), 1.72 (d, J = 14.1
Hz, 3H), 1.33 – 1.24 (m, 6H). 13C NMR (100 MHz, CDCl3) δ 169.3, 167.2, 161.8,
141.7, 131.3, 130.1, 128.5, 127.8, 127.4, 62.2, 51.6, 29.8, 25.9, 25.0, 13.9. IR (KBr):
2934,1769, 1734,1707, 1452, 1343, 1238, 1055 cm-1. ESI-HRMS calcd for
C19H21NNaO4 [M + Na]+: 350.1363, found: 350.1359.
Ethyl
1-((3s,5s,7s)-adamantan-1-yl)-2,5-dioxo-4-phenyl-2,5-dihydro-1H-pyrrole-3-carboxyl
ate (3ae). Yellow solid (106 mg, 70%); Mp 132-133 oC; 1H NMR (400 MHz, CDCl3)
δ 7.62 (dd, J = 8.0, 1.6 Hz, 2H), 7.44 (qd, J = 6.6, 3.3 Hz, 3H), 4.33 (q, J = 7.1 Hz,
2H), 2.44 (d, J = 2.7 Hz, 6H), 2.15 (s, 3H), 1.77-1.67 (m, 6H), 1.28 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 170.4, 168.3, 162.0, 140.8, 131.0, 130.0, 128.4, 128.1,
127.4, 62.2, 60.9, 40.0, 36.1, 29.7, 13.9. IR (KBr): 2918, 2860, 1710, 1455, 1234,
1055 cm-1. ESI-HRMS calcd for C23H25NNaO4 [M + Na]+: 402.1676, found:
402.1685.
1-(tert-Butyl)-3,4-Diphenyl-1H-pyrrole-2,5-dione (5a). Yellow solid (98 mg, 80%).
Mp 136-137 oC. 1H NMR (400 MHz, CDCl3) δ 7.43 (dd, J = 7.5, 1.8 Hz, 4H), 7.35 (t,
J = 6.3 Hz, 6H), 1.70 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.7, 136.0, 130.0,
20
ACS Paragon Plus Environment

Page 21 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
129.5, 128.8, 128.4, 57.8, 29.0. IR (KBr): 2987, 2358, 1762, 1701, 1348, 1243, 1054
cm-1. ESI-HRMS calcd for C20H19NNaO2 [M + Na]+: 328.1308, found: 328.1311.
3,4-bis(4-Bromophenyl)-1-(tert-butyl)-1H-pyrrole-2,5-dione (5b). Yellow solid (140
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
1
mg, 76%). mp 166-167 C. H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.4 Hz, 4H),
7.29 (d, J = 8.4 Hz, 4H), 1.67 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.1, 135.1,
131.9, 131.5, 127.4, 124.5, 58.1, 29.0. IR (KBr): 2924, 2357, 1764, 1700, 1646, 1348,
1243, 1065 cm-1. ESI-HRMS calcd for C20H17Br2NNaO2 [M + Na]+: 483.9518, found:
483.9522.
1-(tert-Butyl)-3,4-di-p-tolyl-1H-pyrrole-2,5-dione (5c). Yellow solid (92 mg, 69%).
mp 147-148 C. 1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.1 Hz, 4H), 7.14 (d, J =
o
13
8.0 Hz, 4H), 2.35 (s, 6H), 1.67 (s, 9H). C NMR (100 MHz, CDCl3) δ 172.1, 139.6,
135.4, 129.9, 129.1, 126.1, 57.7, 29.1, 21.4. IR (KBr): 2983, 2357, 1759, 1701, 1347,
1237, 1019 cm-1. ESI-HRMS calcd for C22H23NNaO2 [M + Na]+: 356.1621, found:
356.1627.
1-(tert-Butyl)-3,4-di(thiophen-2-yl)-1H-pyrrole-2,5-dione (5d)
Dark green solid (109 mg, 86%). Mp 77-78 oC. 1H NMR (400 MHz, CDCl3) δ 7.74 (d,
J = 0.9 Hz, 1H), 7.73 (d, J = 0.9 Hz, 1H), 7.57 (d, J = 0.9 Hz, 1H), 7.56 (d, J = 0.9 Hz,
1H), 7.11 (dd, J = 5.0, 3.8 Hz, 2H), 1.67 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.2,
130.8, 129.6, 127.5, 127.3, 58.1, 29.0. IR (KBr): 2986, 2358, 1763, 1698, 1351, 1243,
1058 cm-1. ESI-HRMS calcd for C16H15NNaO2S2 [M + Na]+: 340.0436, found:
340.0433.
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 30
1
2
3
4
1-(tert-Butyl)-3-phenyl-4-(4-(trifluoromethyl)phenyl)-1H-pyrrole-2,5-dione
(5e).
5
6
7
8
Yellow solid (125 mg, 84%). Mp 138-139 oC. 1H NMR (400 MHz, CDCl3) δ 7.59 (d,
J = 8.3 Hz, 2H), 7.54 (d, J = 8.3 Hz, 2H), 7.41 (s, 1H), 7.39 (s, 2H), 7.37 (d, J = 5.6
Hz, 2H), 1.69 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.3, 171.2, 137.6, 134.4,
132.5, 131.2 (q, J = 32.5 Hz), 130.4, 130.0, 129.9, 128.6, 128.2, 125.3 (q, J = 3.7 Hz),
123.8 (q, J = 270.7 Hz), 58.1, 29.0. IR (KBr): 2985, 2358, 1764, 1703, 1644, 1354,
1243, 1062 cm-1. ESI-HRMS calcd for C21H18F3NNaO2 [M + Na]+: 396.1182, found:
396.1179.
9
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
3-(4-Bromophenyl)-1-(tert-butyl)-4-phenyl-1H-pyrrole-2,5-dione (5f). Yellow solid
1
(119 mg, 78%). Mp 131-132oC. H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.4 Hz,
2H), 7.43 – 7.39 (m, 2H), 7.37 (d, J = 6.7 Hz, 2H), 7.35 (s, 1H), 7.31 (d, J = 8.4 Hz,
2H), 1.68 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.5, 171.4, 136.4, 134.8, 131.7,
131.6, 129.9, 129.8, 128.6, 128.5, 127.7, 124.2, 58.0, 29.0. IR (KBr): 2990, 2359,
1764, 1700, 1642, 1376, 1243, 1057 cm-1. ESI-HRMS calcd for C20H18BrNNaO2 [M
+ Na]+: 406.0413, found: 406.0408.
3-(3-Bromophenyl)-1-(tert-butyl)-4-phenyl-1H-pyrrole-2,5-dione (5g). Yellow solid
o
(113 mg, 74%). Mp 106-107 C. 1H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.49 (d,
J = 8.0 Hz, 1H), 7.44 – 7.40 (m, 2H), 7.38 (d, J = 7.5 Hz, 2H), 7.35 (s, 1H), 7.30 (d, J
= 7.8 Hz, 1H), 7.18 (t, J = 7.9 Hz, 1H), 1.68 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
171.4, 171.3, 137.00, 134.4, 132.8, 132.5, 130.8, 129.9, 129.9, 129.9, 128.5, 128.3,
122.4, 58.0, 29.0. IR (KBr): 2983, 2358, 1764, 1702, 1643, 1346, 1243, 1057 cm-1.
ESI-HRMS calcd for C20H18BrNNaO2 [M + Na]+: 406.0413, found: 406.0418.
22
ACS Paragon Plus Environment

Page 23 of 30
The Journal of Organic Chemistry
1
2
3
4
1-(tert-Butyl)-3-(4-methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)-1H-pyrrole-2,5-dion
5
6
o
1
e (5h). Yellow solid (132 mg, 82%). Mp 112-113 C. H NMR (400 MHz, CDCl3) δ
7.61 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 6.87 (d, J
= 8.8 Hz, 2H), 3.82 (s, 3H), 1.68 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.6, 171.5,
161.1, 137.1, 133.0, 132.5, 131.7, 131.0 (q, J = 32.4 Hz), 130.3, 125.3 (q, J = 3.7 Hz),
123.8 (q, J = 270.6 Hz), 120.4, 114.1, 57.9, 55.3, 29.0. IR (KBr): 2969,1765, 1702,
1462, 1350, 1257, 1067 cm-1. ESI-HRMS calcd for C22H20F3NNaO3 [M + Na]+:
426.1287, found: 426.1289.
7
8
9
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
1-(tert-Butyl)-3-(naphthalen-1-yl)-4-phenyl-1H-pyrrole-2,5-dione (5j). Yellow solid
o
1
(65 mg, 46%); Mp 115-116 C. H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.2 Hz,
1H), 7.77 (d, J = 8.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.44 – 7.39 (m, 1H), 7.34 (ddd,
J = 7.4, 5.0, 4.0 Hz, 2H), 7.31 – 7.24 (m, 3H), 7.14 – 7.10 (m, 1H), 7.05 (dd, J = 10.2,
4.6 Hz, 2H), 1.65 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.8, 171.8, 137.9, 136.5,
133.7, 130.6, 129.9, 129.8, 129.6, 128.8, 128.6, 128.3, 128.2, 127.1, 126.5, 126.1,
125.3, 125.2, 58.0, 29.1. IR (KBr): 2970,1764, 1702, 1460, 1345, 1260 cm-1.
ESI-HRMS calcd for C24H21NNaO2 [M + Na]+: 378.1464, found: 378.1466.
1-(tert-Butyl)-3-phenyl-4-(thiophen-2-yl)-1H-pyrrole-2,5-dione (5k). Dark green solid
(97 mg, 78%). Mp 53-54 oC. 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 3.8 Hz, 1H),
7.49 – 7.44 (m, 6H), 7.02 – 6.98 (m, 1H), 1.68 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
171.9, 171.4, 132.3, 131.4, 131.2, 130.2, 130.0, 129.6, 129.2, 128.7, 127.3, 57.9, 29.0.
IR (KBr): 2970, 2357, 1762, 1700, 1645, 1349, 1244, 1058 cm-1. ESI-HRMS calcd
for C18H17NNaO2S [M + Na]+: 334.0872, found: 334.0875.
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 30
1
2
3
4
1-(tert-Butyl)-3-methyl-4-phenyl-1H-pyrrole-2,5-dione (5l). Yellow solid (72 mg,
5
6
7
o
1
74%). Mp 110-111 C. H NMR (400 MHz, CDCl3) δ 7.53 (m, 2H), 7.44 (m, 3H),
8
9
13
2.12 (s, 3H), 1.63 (s, 9H). C NMR (100 MHz, CDCl3) δ 173.1, 172.1, 136.7, 136.4,
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
129.6, 129.3, 129.2, 128.4, 57.4, 29.0, 9.6. IR (KBr): 2991, 1766, 1707, 1462, 1376,
1243, 1056 cm-1. ESI-HRMS calcd for C15H17NNaO2 [M + Na]+: 266.1151, found:
266.1148.
1-(tert-Butyl)-3-butyl-4-phenyl-1H-pyrrole-2,5-dione (5m). Light yellow oil (91 mg,
1
80%). H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 6.6 Hz, 2H), 7.44 (s, 2H), 7.42 –
7.39 (m, 1H), 2.54 – 2.47 (m, 2H), 1.63 (s, 9H), 1.56 (dd, J = 9.8, 5.8 Hz, 2H), 1.36
(dd, J = 14.8, 7.4 Hz, 2H), 0.90 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ
172.9, 172.2, 140.7, 136.7, 129.4, 129.2, 128.4, 57.3, 30.8, 29.0,23.8, 22.9, 13.7. IR
(KBr): 2963,1766, 1701, 1461, 1351, 1243, 1055 cm-1. ESI-HRMS calcd for
C18H23NNaO2 [M + Na]+: 308.1621, found: 308.1618.
1-(tert-Butyl)-3-phenyl-1H-pyrrole-2,5-dione (5n). Light yellow oil (37 mg, 40%). 1H
NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 6.3, 2.7 Hz, 2H), 7.47 – 7.42 (m, 3H), 6.58 (s,
1H), 1.64 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 171.8, 171.7, 143.0, 130.7, 128.9,
128.8, 128.6, 124.7, 57.6, 29.0. IR (KBr): 2991, 2358, 1764, 1702, 1377, 1243, 1056
cm-1. ESI-HRMS calcd for C14H16NO2 [M + H]+: 230.1176, found: 230.1172.
1-(tert-Butyl)-3-phenyl-4-(phenylethynyl)-1H-pyrrole-2,5-dione (5o). Yellow solid
o
1
(108 mg, 82%). Mp 120-121 C. H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 6.1 Hz,
2H), 7.58 (d, J = 6.5 Hz, 2H), 7.50 (s, 1H), 7.48 (s, 2H), 7.41 (d, J = 6.6 Hz, 2H), 7.38
13
(d, J = 5.9 Hz, 1H), 1.68 (s, 9H). C NMR (100 MHz, CDCl3) δ 171.4, 168.6, 139.0,
24
ACS Paragon Plus Environment

Page 25 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
132.2, 130.7, 129.9, 129.6, 129.1, 128.5, 128.5, 121.8, 120.8, 106.3, 80.9, 58.2, 28.9.
IR (KBr): 2978, 2358, 1764, 1703, 1346, 1244, 1057 cm-1. ESI-HRMS calcd for
C22H19NNaO2 [M + Na]+: 352.1308, found: 352.1307.
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
4,4'-(1,4-Phenylene)bis(1-(tert-butyl)-3-phenyl-1H-pyrrole-2,5-dione) (5p). Yellow
solid (92 mg, 43%). Mp 242-243 oC. 1H NMR (400 MHz, CDCl3) δ 7.41 (s, 4H), 7.38
(dd, J = 7.6, 1.6 Hz, 4H), 7.33 (t, J = 7.1 Hz, 5H), 1.68 (s, 18H). 13C NMR (100 MHz,
CDCl3) δ 171.6, 171.5, 136.8, 135.0, 130.0, 129.9, 129.7, 128.5, 128.5, 58.0, 29.0. IR
(KBr): 2963, 1764, 1703, 1461, 1344, 1250, 1059 cm-1. ESI-HRMS calcd for
C34H32N2NaO4 [M + Na]+: 555.2254, found: 555.2256.
1-(tert-Butyl)-3-phenyl-4-(4-(phenylethynyl)phenyl)-1H-pyrrole-2,5-dione
(5p’).
Yellow solid (49 mg, 30%). Mp 143-144 oC. 1H NMR (400 MHz, CDCl3) δ 7.51 (dd,
J = 14.7, 6.1 Hz, 4H), 7.46 – 7.40 (m, 4H), 7.39 – 7.32 (m, 6H), 1.69 (s, 9H). 13C
NMR (100 MHz, CDCl3) δ 171.6, 136.3, 135.2, 131.7, 131.6, 130.0, 130.0, 129.7,
128.7, 128.6, 128.6, 128.5, 128.4, 124.6, 122.9, 91.3, 89.0, 58.0, 29.0. IR (KBr): 2971,
2926, 2358, 1763, 1700, 1345, 1242, 1016 cm-1. ESI-HRMS calcd for C28H23NNaO2
[M + Na]+: 428.1621, found: 428.1621.
[1]
3,4-Diphenyl-1H-pyrrole-2,5-dione (6a). Yellow solid (81 mg, 81%). Mp 213-214
oC. 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.47 (d, J = 7.6 Hz, 4H), 7.38 (p, J =
6.5 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 170.4, 137.1, 130.0, 129.9, 128.6, 128.3.
IR (KBr): 2925, 1715, 1451, 1389, 1266, 1062 cm-1. MS (EI) m/z 89, 152, 178, 205,
220, 230, 249.
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 30
1
2
3
4
ASSOCIATED CONTENT
5
6
7
Supporting Information
8
9
The Supporting Information is available free of charge on the ACS Publications
website at DOI:
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
Spectral data for all compounds (PDF)
Crystallographic data for 3ba (CIF)
Notes
The authors declare no competing financial interest
ACKNOWLEDGMENTS
The authors thank the National Key Research and Development Program of China
(2016YFA0602900), the National Natural Science Foundation of China
(21420102003 and 21490572), and the Fundamental Research Funds for the Central
Universities (2015ZY001) for financial support.
REFERENCES
1. (a) Coghlan, M.; Culbert, A.; Cross, D.; Corcoran, S.; Yates, J.; Pearce, N.; Rausch,
O.; Murphy, G.; Carter, P.; Cox, L.; Mills, D.; Brown, M.; Haigh, D.; Ward, R.;
Smith, D.; Murray, K.; Reith, A.; Holder, J. Chem. Biol. 2000, 7, 793. (b) Cheng,
C.-F.; Lai, Z.-C.; Lee, Y.-J. Tetrahedron 2008, 64, 4347. (c) Sortino, M.; Garibotto,
F.; Filho, V. C.; Gupta, M.; Enriz, R.; Zacchino, S. Bioorg. Med. Chem. 2011, 19,
2823. (d) Nirogi, R.; Dwarampudi, A.; Kambhampati, R.; Bhatta, V.; Kota, L.;
26
ACS Paragon Plus Environment

Page 27 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
Shinde, A.; Badange, R.; Jayarajan, P.; Bhyrapuneni, G.; Dubey, P. K. Bioorg. Med.
Chem. Lett. 2011, 21, 4577.
7
8
9
2. (a) Yeh, H.-C.; Wu, W.-C.; Chen, C.-T. Chem. Commun. 2003, 404. (b) Kaletas, B.
K.; Mandl, C.; Zwan, G. V. D.; Fanti, M.; Zerbetto, F.; Cola, L. D.; König, B.;
Williams, R. M. J. Phys. Chem. A. 2005, 109, 6440. (c) Yahyaoui, A. E.; Félix, G.;
Heynderickx, A.; Moustrou, C.; Samat, A.; Tetrahedron 2007, 63, 9482. (d)
Hugon, B.; Anizon, F.; Bailly, C.; Golsteyn, R. M.; Pierré, A.; Léonce, S.;
Hickman, J.; Pfeiffer, B.; Prudhomme, M. Bioorg. Med. Chem. 2007, 15, 5965. (e)
Nourmohammadian, F.; Wu, T.; Branda, N. R. Chem. Commun. 2011, 47, 10954.
(f) Ambrogi, M.; Ciogli, A.; Mancinelli, M.; Ranieri, S.; Mazzanti, A. J. Org.
Chem. 2013, 78, 3709.
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
3. (a) Shih, H.; Shih, R. J.; Carson, D. A. J. Heterocyclic Chem. 2011, 48, 1243. (b)
Sati, G. C.; Crich, D. Org. Lett., 2015, 17, 4122. (c) Thale, P. B.; Borase, P. N.;
Shankarling, G. S. Dalton Trans. 2015, 44, 13947. (d) Zhu, C.; Xu, G.; Ding, D.;
Qiu, L.; Sun, J. Org. Lett. 2015, 17, 4244.
4. Brenner. M, Rexhausen. H, Steffan. B, Steglich. W, Tetrahedron 1998, 44, 2887.
5. (a) Brenner, M.; Mayer, G.; Terpin, A.; Steglich, W. Chem. -Eur. J. 1997, 3, 70. (b)
Yahyaoui, A. E.; Félix, G.; Heynderickx, A.; Moustrou, C.; Samat, A. Tetrahedron
2007, 63, 9482. (c) Stewart, S. G.; Polomska, M. E.; Lim, R. W. Tetrahedron Lett.
2007, 48, 2241. (d) Bouissane, L.; Sestelo, J. P.; Sarandeses, L. A. Org. Lett. 2009,
11, 1285. (e) Awuah, E.; Capretta, A. J. Org. Chem. 2011, 76, 3122.
6. Yeh, H.-C.; Wu, W.-C.; Wen, Y.-S.; Dai, D.-C.; Wang, J.-K.; Chen, C.-T. J. Org.
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 30
1
2
3
4
Chem. 2004, 69, 6455.
5
6
7
8
9
7. (a) Kondo, T.; Nomura, M.; Ura, Y.; Wada, K.; Mitsudo, T.-A. J. Am. Chem. Soc.
2006, 128, 14816. (b) Inoue, S.; Fukumoto, Y.; Chatani, N. J. Org. Chem. 2007,
72, 6588.
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
8. For selected reviews, see: (a) Dömling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000,
39, 3168. (b) Nair, V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.;
Mathen, J. S.; Balagopal, L. Acc. Chem. Res. 2003, 36, 899. (c) Dömling, A.
Chem. Rev. 2006, 106, 17. (d) Gulevich, A. V.; Zhdanko, A. G.; Orru, R. V. A.;
Nenajdenko, V. G. Chem. Rev. 2010, 110, 5235. (e) Lygin, A. V.; Meijere, A. D.
Angew. Chem. Int. Ed. 2010, 49, 9094. (f) Vlaar, T.; Ruijter, E.; Maes, B. U. W.;
Orru, R. V. A. Angew. Chem. Int. Ed. 2013, 52, 7084. (g) Qiu, G.; Ding, Q.; Wu, J.
Chem. Soc. Rev. 2013, 42, 5257.
9. For selected references: (a) Kamijo, S.; Kanazawa, C.; Yamamoto, Y.; J. Am.
Chem. Soc., 2005, 127, 9260. (b) Zhu, C.; Xie, W.; Falck, J. R. Chem. -Eur. J.
2011, 17, 12591. (c) Zhu, T.-H.; Wang, S.-Y.; Tao, Y. Q.; Wei, T. Q.; Ji, S.-J. Org.
Lett. 2014, 16, 1260. (d) Wang, J.; Li, J; Zhu, Q. Org. Lett. 2015, 17, 5336. (e) Liu,
J.; Liu, Z.; Liao, P.; Zhang, L.; Tu, T.; Bi, X. Angew. Chem. Int. Ed. 2015, 54, 1. (f)
Liao, J.-Y.; Shao, P.-L.; Zhao, Y.; J. Am. Chem. Soc. 2015, 137, 628.
10. For recent selected examples, see: (a) Jiang, X.; Tang, T.; Wang, J.-M.; Chen, Z.;
Zhu, Y.-M.; Ji, S.-J. J. Org. Chem. 2014, 79, 5082. (b) Chen, Z.; Duan, H.-Q.;
Jiang, X.; Zhu, Y.-M.; Ji, S.-J.; Yang, S.-L. J. Org. Chem. 2015, 80, 8183. (c) Gu,
J.-W.; Zhang, X. Org. Lett. 2015, 17, 5384. (d) Dang, Y.; Deng, X.; Guo, J.; Song,
28
ACS Paragon Plus Environment

Page 29 of 30
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
C.; Hu, W.; Wang, Z.-X. J. Am. Chem. Soc. 2016, 138, 2712. (e) Kong, W.-J.; Liu,
Y.-J.; Xu, H.; Chen, Y.-Q.; Dai, H.-X.; Yu, J.-Q. J. Am. Chem. Soc. 2016, 138,
2146. (f) Chen, Z.-B.; Zhang, Y.; Yuan, Q.; Zhang, F.-L.; Zhu, Y.-M.; Shen, J.-K. J.
Org. Chem. 2016, 81, 1610.
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
11. Zhou, F.; Ding, K.; Cai, Q. Chem. -Eur. J. 2011, 17, 12268.
12. (a) Peng, J.; Liu, L.; Hu, Z.; Huang, J.; Zhu, Q. Chem. Commun. 2012, 48, 3772.
(b) Hu, Z.; Liang, D.; Zhao, J.; Huang, J.; Zhu, Q. Chem. Commun. 2012, 48,
7371.
13. (a) Jiang, H.; Liu, B.; Li, Y.; Wang, A.; Huang, H. Org. Lett. 2011, 13, 1028. (b) Li,
Y.; Zhao, J.; Chen, H.; Liu, B.; Jiang, H. Chem. Commun. 2012, 48, 3545. (c)
Jiang, H.; Yin, M.; Li, Y.; Liu, B.; Zhao, J.; Wu, W.; Chem. Commun. 2014, 50,
2037.
14. (a) Liu, B.; Li, Y.; Jiang, H; Yin, M.; Huang, H. Adv. Synth. Catal. 2012, 354,
2288. (b) Liu, B.; Li, Y.; Yin, M.; Wu, W.; Jiang, H. Chem. Commun. 2012, 48,
11446. (c) Liu, B.; Yin, M,; Gao, H.; Wu, W.; Jiang, H. J. Org. Chem. 2013, 78,
3009. (d) Liu, B.; Gao, H.; Yu, Y.; Wu, W.; Jiang, H. J. Org. Chem. 2013, 78,
10319. (e) Jiang, H.; Gao, H.; Liu, B.; Wu, W. RSC Adv. 2014, 4, 17222. (f) Jiang,
H.; Gao, H.; Liu, B.; Wu, W. Chem. Commun. 2014, 50, 15348.
15. (a) Wang, Q.; Liu, X.; Jiang, H. Angew. Chem. Int. Ed. 2012, 51, 5696. (b) Wu, W.;
Jiang, H. Acc. Chem. Res. 2014, 47, 2483. (c) Huang, L.; Wang, Q.; Wu, W.; Jiang,
H. J. Org. Chem. 2014, 79, 7734. (d) Yu, Y.; Huang, L.; Wu, W.; Jiang, H.; Org.
Lett. 2014, 16, 2146. (e) Li, J.; Yang, W.; Yang, S.; Huang, L.; Wu, W.; Sun, Y.;
29
ACS Paragon Plus Environment