Palladium-catalyzed oxidative O-H/N-H carbonylation of hydrazides: Access to substituted 1,3,4-oxadiazole-2(3 H)-ones

Article abstract of DOI:10.1021/acs.joc.5b00664

A novel palladium-catalyzed oxidative annulation reaction for the C-O, C-N bond formations is developed. The intramolecular cyclocarbonylation provides an efficient and direct approach for the construction of valuable 1,3,4-oxadiazole-2(3H)-ones and their

Full text of DOI:10.1021/acs.joc.5b00664

Subscriber access provided by UB + Fachbibliothek Chemie | (FU-Bibliothekssystem)
Article
Palladium-Catalyzed Oxidative O-H/N-H Carbonylation of
Hydrazides: Access to Substituted 1,3,4-Oxadiazole-2(3H)-ones
Fanghua Ji, Xianwei Li, Wei Guo, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 14 May 2015
Downloaded from http://pubs.acs.org on May 15, 2015
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 21
The Journal of Organic Chemistry
1
2
3
4
5
6
Palladium-Catalyzed Oxidative O-H/N-H Carbonylation of
Hydrazides: Access to Substituted
7
8
9
1,3,4-Oxadiazole-2(3H)-ones
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
Fanghua Ji, Xianwei Li, Wei Guo, Wanqing Wu, and Huanfeng Jiang*
School of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China
Fax: (+86) 20ꢀ8711ꢀ2906; Eꢀmail: jianghf@scut.edu.cn
Abstract: A novel palladiumꢀcatalyzed oxidative annulation reaction for the CꢀO,
CꢀN bond formations is developed. The intramolecular cyclocarbonylation provides
an efficient and direct approach for the construction of valuable
1,3,4ꢀoxadiazoleꢀ2(3H)ꢀones and their derivatives. The reaction also facilitated the
convenient synthesis of BMSꢀ191011, an opener of the cloned largeꢀconductance
Ca2+ꢀactivated potassium channel, providing an attractive method for medicinal
chemistry.
INTRODUCTION
1,3,4ꢀOxadiazole core is a popular bioisostere for improving the pharmacological
profile of biologically active amides, esters, and ureas.1 Compounds bearing
1,3,4ꢀoxadiazole skeleton have been found to exhibit a wide spectrum of biological
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 21
1
2
3
4
5
6
7
8
9
activities such as antiꢀHCV and antiꢀtumour agents (1),2 GABAA receptor agonists
(2),3 BMSꢀ191011: opener of largeꢀconductance Ca2+ꢀactivated potassium (MaxiꢀK)
channels (3)4 and fungicides (4)5 (Figure 1). This heterocycle is a privileged scaffold
in medicinal chemistry. The representative methods for the synthesis of substituted
1,3,4ꢀoxadiazoleꢀ2(3H)ꢀones have been reported in the literature.6 Although these
procedures are useful for the construction of 1,3,4ꢀoxadiazole cores, most of them still
suffer from some limitations such as the use of toxic and hazardous reagents,6c
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
harmful organic solvents, and laborious reaction procedures with unsatisfactory yields
6d
(Scheme 1a).6b,
Therefore, the development of simple, efficient, and
atomꢀeconomical method to access structurally diverse 1,3,4ꢀoxadiazoles remains
highly desirable.
Figure 1. Structures of Pharmacologically Important Substituted
1,3,4-Oxadiazole-2(3H)-ones
Oxidative carbonylation reactions have continued to be an important strategy
for the construction of carbocyclic and heterocyclic compounds.7 Enormous efforts
have gone into the synthesis of heterocyclic framework through the oxidative
ACS Paragon Plus Environment

Page 3 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
carbonylation. Carbon monoxide (CO) as carbonꢀatom source holds the synthetic
advantages of inexpensive and readily available nature.8 Heterocyclic compounds,
which are highly important in different research fields such as pharmaceutical
chemistry and electroactive materials.9 Considering the importance of both topics,
herein, we report our recent effort on palladiumꢀcatalyzed oxidative carbonylation
of hydrazines, whereby a sequential CO insertion into the NꢀH and OꢀH bonds
occurs to form substituted 1,3,4ꢀoxadiazoleꢀ2(3H)ꢀones (Scheme 1b).
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 1. Selected Synthetic Methods for 1,3,4-Oxadiazole Cores
Previous work
This work
O
O
O
[Pd]
COCl2 or CDI
O
(b)
R
N NH2
(a)
NH
R
N NH2
CO
H
H
N
R
toxic, hazardous;
low yields
mild conditions
good to excellent yields
RESULTS AND DISCUSSION
To explore this approach, initial studies were focused on using benzohydrazide
(1a) as a model substrate (Table 1). Treatment of 1a using 5 mol % of Pd(OAc)2 as
catalyst in DMSO under CO/O2 atmosphere and TFA as an additive at 60 oC afforded
the desired product 5ꢀphenylꢀ1,3,4ꢀoxadiazolꢀ2(3H)ꢀone (2a) in only 36% yield
(Table 1, entry 1). Intriguingly, the use of Pd(TFA)2 as a catalyst gave a further
improvement in the yield of 2a, while other catalysts were ineffective for this
transformation (entries 2, 3, 5). Furthermore, the additive was found to be vital to the
catalytic system, and the yield was decreased to 23% without the use of TFA (entry 6).
Other additives such as LiBr or PivOH just gave low yield (entries 7 and 8). By
switching different oxidants, CuO resulted in a decent boost in the yield of 2a (entry
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 21
1
2
3
4
5
6
7
8
9
14); other oxidants such as BQ, Cu(OAc)2, Ag2CO3 and K2S2O8 turned out to be
unfavorable in the system (entries 9ꢀ13). When CH3CN was used as the reaction
solvent, the yield was slightly increased (entry 18), while toluene, THF and DMF all
gave disappointing results (entries 15ꢀ17). In addition, no reaction could be observed
in the absence of the Pd catalyst (entry 19).
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
Table 1. Optimization of the Reaction Conditionsa
Entry
[M]
[O]
Additive
Solvent
Yield b(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Pd(OAc)2
PdCl2
PdI2
Pd(TFA)2
PdBr2
O2
O2
O2
O2
O2
O2
O2
O2
BQ
TFA
TFA
TFA
TFA
TFA
_
LiBr
PivOH
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
toluene
THF
36
trace
trace
41
trace
23
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
_
5
11
trace
27
trace
trace
trace
75
n.d.
trace
59
MnO2
Cu(OAc)2
Ag2CO3
K2S2O8
CuO
CuO
CuO
CuO
CuO
CuO
DMF
CH3CN
CH3CN
81
n.d.
a
Reaction conditions: unless otherwise noted, all reactions were performed with 1 (0.2
o
mmol), catalyst (5 mol %), oxidant (1.5 equiv), additive (0.6 mmol) at 60 C for 12 h, CO (1
balloon). b Isolated yield.
Having identified our optimized reaction conditions, we next investigated the
ACS Paragon Plus Environment

Page 5 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
scope of the reaction, as illustrated in Table 2. The intramolecular
cyclocarbonylation reaction displayed a good functionalꢀgroup tolerance.
Benzohydrazides bearing various substituents all gave the desired products in
moderate to good yields regardless of their electronic properties (2aꢀ2g). It is
worth noting that the substrates with sensitive functional groups such as fluoro,
chloro and bromo groups all gave the corresponding products in high to excellent
yields, which could be subjected to further functionalization (2hꢀ2j). Treatment of
substrates bearing different substitution positions also afforded the desired
products in good yields (2kꢀ2m). Di/trisubstitutedꢀhydrazides all gave the targeted
products in moderate yields (2oꢀ2q). To our delight, substrates with naphthalene or
heterocyclic ring were also tolerated in the system, which expanded the scope of
this kind of reactions significantly (2r-2t). However, aliphatic hydrazide did not
work in this reaction system.
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
Table 2. Pd-Catalyzed Synthesis of Substitued 1,3,4-Oxadiazole-2(3H)-onesa
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 21
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
a The reactions were carried out at 60 °C, using 1 (0.2 mmol), CuO (0.3 mmol), TFA (0.6 mmol),
CO (1 balloon), Pd(TFA)2 (5 mol %) in CH3CN (2 mL) at 60 oC for 12 h. Yields refer to isolated
yield.
To further demonstrate the efficiency and generality of this reaction system, we
then explored the transformation of Nꢀaryl substituted derivatives (Table 3). However,
when N'ꢀphenylbenzohydrazide (3a) was subjected to the standard reaction conditions,
the corresponding product 3,5ꢀdiphenylꢀ1,3,4ꢀoxadiazolꢀ2(3H)ꢀone (4a) was obtained
in only 15 % yield. After careful modification of the reaction conditions, we found
that only the employment of Ag2CO3 as the oxidant at 60 oC for 6 h could provide the
ACS Paragon Plus Environment

Page 7 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
desired product 4a in 62% yield, while other oxidants were inactive (See the
Supporting Information for details). Under the optimized conditions, the
carbonylation reaction proceeded smoothly to give the corresponding Nꢀsubstituted
1,3,4ꢀoxadiazoles in good yields (4aꢀ4h). Various substituents at the aryl, such as
methyl, methoxyl, trimethyl were tolerated well, affording the corresponding products
in good to excellent yields (4aꢀ4e). It is noteworthy that halide substituents (4fꢀ4h)
could survive in the reaction system, which allowed further functionalization such as
metalꢀcatalyzed crossꢀcoupling reactions.
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
Table 3. The Synthesis of N-Substituted 1,3,4-Oxadiazoles.a
a The reactions were carried out at 60 °C, using 1 (0.2 mmol), Ag2CO3 (0.3 mmol), TFA (0.6
o
mmol), CO (1 balloon), Pd(TFA)2 (5 mol %) in CH3CN (2 mL) at 60 C for 12 h. Yields refer to
isolated yield.
The ready access to the Nꢀsubstituted 1,3,4ꢀoxadiazoleꢀ2(3H)ꢀones through this
chemistry offers a novel strategy for many biologically active compounds.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 21
1
2
3
4
5
6
7
8
9
Noteworthy, it is found that the wellꢀknown maxiꢀK opener could be synthesized from
the newly formed 2f. After methylation, Mitsunobu reaction and deprotection,
compound 2f was successfully converted to the corresponding BMSꢀ191011 in 78%
yield (Scheme 2). Therefore, this reaction system could be potentially used in drug
discovery for the preparation of BMSꢀ191011.4,10
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 2. Preparation for BMS-191011
A plausible reaction mechanism is proposed for the construction of
11
substitutedꢀ1,3,4ꢀoxadiazoleꢀ2(3H)ꢀones as shown in Scheme 3. The intermediate A
is first formed by NꢀH activation of 1. Subsequently, the coordination of carbonyl
group with Pd complex affords a fiveꢀmembered palladacycle B, which further reacts
with CO to form intermediate C. Finally, reductive elimination of C gives the desired
carbonylation product 2 and Pd(0) is then reoxidized by CuO or Ag2CO3 to regenerate
the Pd(II) species.
Scheme 3. Proposed Mechanism
ACS Paragon Plus Environment

Page 9 of 21
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
CONCLUSION
In conclusion, we have developed the first palladiumꢀcatalyzed OꢀH/NꢀH
carbonylation for the synthesis of various 1,3,4ꢀoxadiazoles. The reaction starts
from commercially available hydrazides and proceeds under mild reaction
conditions. This novel palladiumꢀcatalyzed carbonylation reaction features a broad
substrates scope and excellent functionalꢀgroup tolerance. Notably, this protocol
provides a useful tool for the convenient synthesis of BMSꢀ191011.
EXPERIMENTAL SECTION
General Information. Melting points were measured with a melting point instrument
and were uncorrected. 1H and 13C NMR spectra were recorded using a 400MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.24 and 77.0 ppm,
respectively, and chloroform is solvent with TMS as the internal standard. IR spectra
were obtained either as potassium bromide pellets or as liquid films between two
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 21
1
2
3
4
5
6
7
8
9
potassium bromide pellets with a spectrometer. GC–MS was obtained using electron
ionization. HRMS was obtained with a LCMSꢀITꢀTOF mass spectrometer. TLC was
performed by using commercially prepared 100–400 mesh silica gel plates and
visualization was effected at 254 nm.
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
Typical Experimental Procedure for Synthesis of 2a-2t. The mixture of 1 (0.2
mmol), CuO (0.3 mmol), Pd(TFA)2 (5 mol %) and TFA (0.6 mmol) was stirred in
o
CH3CN (2.0 mL) at 60 C, in a 20 mL tube with a balloon CO for 12 h. When the
reaction was complete (detected by TLC), the mixture was cooled to room
temperature. The residue was purified by column chromatography on silica gel to
afford the corresponding products 2 with petroleum ether/ethyl acetate as the eluent.
Typical Experimental Procedure for Synthesis of 4a-4h. The mixture of 1 (0.2
mmol), Ag2CO3 (0.3 mmol), Pd(TFA)2 (5 mol %) and TFA (0.6 mmol) was stirred in
o
CH3CN (2.0 mL) at 60 C, in a 20 mL tube with a balloon CO for 12 h. When the
reaction was complete (detected by TLC), the mixture was cooled to room
temperature. The residue was purified by column chromatography on silica gel to
afford the corresponding products 4 with petroleum ether/ethyl acetate as the eluent.
5-Phenyl-1,3,4-oxadiazol-2(3H)-one (2a): White solid (26 mg, 81%); mp:
1
137.2ꢀ138.6; IR (KBr):3216, 1739, 1569, 1413, 687; H NMR (400 MHz, CDCl3) δ
9.64 (s, 1H), 7.86 (d, J = 7.6 Hz, 2H), 7.61 – 7.38 (m, 3H); 13C NMR (101 MHz,
CDCl3) δ 155.4, 155.0, 131.8, 129.0, 125.8, 123.8; HRMS (ESI) m/z: calcd for
C8H6N2NaO2 [M+Na]+, 185.0321; found, 185.0322
ACS Paragon Plus Environment

Page 11 of 21
The Journal of Organic Chemistry
1
2
3
4
5-(p-Tolyl)-1,3,4-oxadiazol-2(3H)-one (2b): White solid (29 mg, 83%); mp:
5
6
7
1
167.2ꢀ168.7; IR (KBr): 3207, 1791, 1613, 1568, 1412, 731; H NMR (400 MHz,
8
9
DMSO) δ 7.68 (d, J = 7.6 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 2.37 (s, 3H); 13C NMR
(101 MHz, DMSO) δ 154.5, 153.9, 141.5, 129.7, 125.2, 121.2, 21.0; HRMS (ESI)
m/z: calcd for C9H8N2NaO2 [M+Na]+, 199.0478; found, 199.0481.
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-(4-Methoxyphenyl)-1,3,4-oxadiazol-2(3H)-one (2c): White solid (31 mg, 80%);
mp: 192.1ꢀ193.6; IR (KBr): 3359, 1769, 1568, 1415, 1021, 757; 1H NMR (400 MHz,
DMSO) δ 12.41 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 3.84 (s,
3H); 13C NMR (101 MHz, DMSO) δ 161.6, 154.5, 153.8, 127.0, 116.3, 114.7, 55.4;
HRMS (ESI) m/z: calcd for C9H8N2NaO3 [M+Na]+, 215.0427; found, 215.0429.
5-(4-(tert-Butyl)phenyl)-1,3,4-oxadiazol-2(3H)-one (2d): White solid (31 mg, 71%);
mp: 134.2ꢀ135.8; IR (KBr): 3270, 2964, 1783, 1619, 1346, 923; 1H NMR (400 MHz,
DMSO) δ 7.72 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 1.30 (s, 9H); 13C NMR
(101 MHz, DMSO) δ 154.5, 154.3, 153.9, 126.0, 125.1, 121.2, 34.7, 30.8; HRMS
(ESI) m/z: calcd for C12H15N2O2 [M+H]+, 219.1128; found, 219.1128.
5-([1,1'-Biphenyl]-4-yl)-1,3,4-oxadiazol-2(3H)-one (2e): White solid (35 mg, 74%);
mp: 254.2ꢀ255.8; IR (KBr): 2922, 1572, 1410, 957, 768; 1H NMR (400 MHz, DMSO)
δ 8.08 – 7.82 (m, 4H), 7.75 (t, J = 7.4 Hz, 2H), 7.51 (t, J = 7.0 Hz, 2H), 7.43 (t, J =
7.0 Hz, 1H); 13C NMR (101 MHz, DMSO) δ 154.5, 153.6, 142.8, 138.8, 129.1, 128.2,
127.4, 126.8, 125.8, 122.9;HRMS (ESI) m/z: calcd for C14H11N2O2 [M+H]+,
239.0815; found, 239.0813.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 21
1
2
3
4
5
6
7
8
9
5-(4-(Trifluoromethyl)phenyl)-1,3,4-oxadiazol-2(3H)-one (2f): White solid (34 mg,
73%); mp: 213.7ꢀ215.0; IR (KBr): 3420, 1571, 1415, 1322, 1128, 709; 1H NMR (400
MHz, DMSO) δ 12.81 (s, 1H), 8.00 (d, J = 8.0 Hz, 2H), 7.91 (d, J = 8.0 Hz, 2H); 13C
NMR (101 MHz, DMSO) δ 154.74, 153.14, 131.97, 131.65, 131.33, 131.01, 128.22,
128.02, 127.63, 127.45, 126.69, 126.66, 126.62, 126.58, 126.52, 125.57, 122.86;
HRMS (ESI) m/z: calcd for C9H5F3N2NaO2 [M+Na]+, 253.0195; found, 253.0201.
5-(4-Nitrophenyl)-1,3,4-oxadiazol-2(3H)-one (2g)12: White solid (34 mg, 83%); mp:
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
250.1ꢀ251.6; IR (KBr): 3441, 2923, 2384, 1647, 1516, 1338, 1268, 753; H NMR
(400 MHz, DMSO) δ 12.91 (s, 1H), 8.35 (d, J = 8.4 Hz, 2H), 8.02 (d, J = 8.4 Hz, 2H);
13C NMR (101 MHz, DMSO) δ 154.2, 152.3, 148.7, 129.5, 126.5, 124.4; MS (EI) m/z
104.10, 133.13, 163.10, 177.09, 207.09.
5-(4-Fluorophenyl)-1,3,4-oxadiazol-2(3H)-one (2h): White solid (30 mg, 82%); mp:
1
169.9ꢀ171.7; IR (KBr): 3072, 1774, 1616, 1510, 1235, 1026, 841, 730, 698, 513; H
NMR (400 MHz, DMSO) δ 7.85 (dd, J = 7.2, 6.0 Hz, 2H), 7.39 (t, J = 8.6 Hz, 2H);
13C NMR (101 MHz, DMSO) δ 164.9, 162.5, 154.4, 153.1, 127.9, 127.8, 120.6, 120.6,
116.5, 116.3; HRMS (ESI) m/z: calcd for C8H5FN2NaO2 [M+Na]+, 203.0227; found,
203.0225
5-(4-Chlorophenyl)-1,3,4-oxadiazol-2(3H)-one (2i): White solid (29 mg, 75%); mp:
1
226.4ꢀ227.6; IR (KBr): 3449, 1840, 1652, 1563, 1411, 725; H NMR (400 MHz,
DMSO) δ 12.63 (s, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H); 13C NMR
(101 MHz, DMSO) δ 154.3, 153.0, 136.1, 129.4, 127.0, 122.8; HRMS (ESI) m/z:
calcd for C8H5ClN2NaO2 [M+Na]+, 218.9932; found, 218.9933.
ACS Paragon Plus Environment

Page 13 of 21
The Journal of Organic Chemistry
1
2
3
4
5-(4-Bromophenyl)-1,3,4-oxadiazol-2(3H)-one (2j): White solid (37 mg, 77%); mp:
5
6
7
1
238.3ꢀ239.9; IR (KBr): 3449, 1568, 1412, 1018, 752; H NMR (400 MHz, DMSO) δ
8
9
12.68 (s, 1H), 7.74 (q, J = 8.4 Hz, 4H); 13C NMR (101 MHz, DMSO) δ 154.3, 153.1,
132.3, 127.2, 124.9, 123.2; HRMS (ESI) m/z: calcd for C8H5BrN2NaO2 [M+Na]+,
262.9427; found, 262.9429.
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-(m-Tolyl)-1,3,4-oxadiazol-2(3H)-one (2k): White solid (30 mg, 85%); mp:
1
112.3ꢀ113.7; IR (KBr): 3219, 1762, 1583, 1326, 966, 708; H NMR (400 MHz,
CDCl3) δ 10.13 (s, 1H), 7.65 (d, J = 9.6 Hz, 2H), 7.36ꢀ7.30 (m, 2H), 2.41 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 155.5, 155.4, 138.9, 132.6, 128.9, 126.3, 123.7, 123.0,
21.3; HRMS (ESI) m/z: calcd for C9H8N2NaO2 [M+Na]+, 199.0478; found, 199.0479.
5-(o-Tolyl)-1,3,4-oxadiazol-2(3H)-one (2l): White solid (31 mg, 87%); mp:
87.7ꢀ89.6; IR (KBr): 3115, 1775, 1733, 974, 727; 1H NMR (400 MHz, DMSO) δ 7.71
(d, J = 7.6 Hz, 1H), 7.45 (t, J = 7.2 Hz, 1H), 7.42 – 7.26 (m, 2H), 2.53 (s, 3H); 13C
NMR (101 MHz, DMSO) δ 154.3, 154.1, 136.8, 131.6, 130.9, 127.7, 126.3, 122.8,
21.3; HRMS (ESI) m/z: calcd for C9H8N2NaO2 [M+Na]+, 199.0478; found, 199.0479
5-(2-Chlorophenyl)-1,3,4-oxadiazol-2(3H)-one (2m): White solid (25 mg, 65%); mp:
1
156.9ꢀ158.6; IR (KBr): 3746, 2926, 2381, 1645, 1270, 752; H NMR (400 MHz,
DMSO) δ 7.83 (d, J = 7.6 Hz, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H),
13
7.52 (t, J = 7.4 Hz, 1H); C NMR (101 MHz, DMSO) δ 154.3, 151.9, 132.7, 131.1,
131.1, 130.3, 127.7, 122.8; HRMS (ESI) m/z: calcd for C8H5ClN2NaO2 [M+Na]+,
218.9932; found, 218.9932.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 21
1
2
3
4
5
6
7
8
9
5-(4-(Dimethylamino)phenyl)-1,3,4-oxadiazol-2(3H)-one (2n): White solid (29mg,
70%); mp: 231.4ꢀ233.3; IR (KBr): 2922, 1773, 1670, 1608, 1413, 1189, 1025, 826,
772; 1H NMR (400 MHz, DMSO) δ 12.09 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 6.70 (d, J
= 8.4 Hz, 2H), 2.99 (s, 6H); 13C NMR (101 MHz, DMSO) δ 167.5, 153.4, 153.0,
130.9, 116.9, 110.7, 29.2; HRMS (ESI) m/z: calcd for C10H12N3O2 [M+H]+, 206.0924;
found, 206.0926.
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-(3,5-Dichlorophenyl)-1,3,4-oxadiazol-2(3H)-one (2o)13: White solid (33 mg, 71%);
1
mp: 99.0ꢀ101.9; IR (KBr): 3076, 1807, 1590, 1340, 1102, 931, 717; H NMR (400
MHz, DMSO) δ 7.84 (s, 1H), 7.75 (s, 2H); 13C NMR (101 MHz, DMSO) δ 154.1,
151.6, 135.07, 130.7, 127.2, 123.7; MS (EI) m/z 109.05, 145.01, 173.05, 186.06,
188.04, 230.04.
5-(3,5-Bis(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2(3H)-one (2p)4: White solid
1
(39 mg, 65%); mp: 73.0ꢀ74.1; IR (KBr): 3082, 1772, 1397, 1281, 1137, 933, 701; H
13
NMR (400 MHz, DMSO) δ 8.32 (s, 1H), 8.29 (s, 2H); C NMR (101 MHz, DMSO)
δ 154.5, 152.0, 132.3, 132.0, 131.6, 131.3, 127.3, 127.1, 126.1, 126.0, 125.1, 124.6,
121.9, 119.1; MS (EI) m/z 163.09, 213.07, 241.05, 254.07, 279.08, 298.07.
5-(3,4,5-Trimethoxyphenyl)-1,3,4-oxadiazol-2(3H)-one (2q): White solid (35 mg,
70%); mp: 189.3ꢀ191.7; IR (KBr): 3744, 2923, 1800, 1274, 754; 1H NMR (400 MHz,
DMSO) δ 12.58 (s, 1H), 7.05 (s, 2H), 3.86 (s, 6H), 3.73 (s, 3H); 13C NMR (101 MHz,
DMSO) δ 154.4, 153.6, 153.3, 140.1, 119.1, 102.6, 60.2, 56.1; HRMS (ESI) m/z:
calcd for C11H13N2O5 [M+H]+, 253.0819; found, 253.0826.
ACS Paragon Plus Environment

Page 15 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
5-(Benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2(3H)-one (2r): White solid (21 mg,
50%); mp: 219.1ꢀ220.5; IR (KBr): 3302, 2923, 1570, 1411, 1029, 882; 1H NMR (400
MHz, DMSO) δ 12.48 (s, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.27 (s, 1H), 7.07 (d, J = 8.2
Hz, 1H), 6.14 (s, 2H); 13C NMR (101 MHz, DMSO) δ 154.4, 153.6, 150.0, 148.0,
120.4, 117.7, 108.9, 105.0, 102.0; HRMS (ESI) m/z: calcd for C9H6N2NaO4 [M+Na]+,
229.0220; found, 229.0223.
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-(Naphthalen-2-yl)-1,3,4-oxadiazol-2(3H)-one (2s): White solid (30 mg, 70%); mp:
1
189.5ꢀ190.7; IR (KBr): 2923, 1685, 1305, 897, 745; H NMR (400 MHz, DMSO) δ
12.65 (s, 1H), 8.39 (s, 1H), 8.11 (d, J = 7.6 Hz, 1H), 8.06 (d, J = 8.6 Hz, 1H), 7.98 (d,
J = 7.6 Hz, 1H), 7.88 (d, J = 8.6 Hz, 1H), 7.66ꢀ7.60 (m, 2H); 13C NMR (101 MHz,
DMSO) δ 154.5, 153.9, 133.9, 132.4, 129.0, 128.7, 127.9, 127.8, 127.2, 125.7, 121.5,
121.2; HRMS (ESI) m/z: calcd for C12H8N2NaO2 [M+Na]+, 235.0478; found,
235.0481.
5-(Furan-2-yl)-1,3,4-oxadiazol-2(3H)-one (2t): White solid (18 mg, 60%); mp:
110.4ꢀ111.7; IR (KBr): 3132, 1777, 1650, 1335, 1097, 920, 706; 1H NMR (400 MHz,
DMSO) δ 12.63 (s, 1H), 7.97 (s, 1H), 7.15 (d, J = 2.8 Hz, 1H), 6.74 (d, J = 1.6 Hz,
1H); 13C NMR (101 MHz, DMSO) δ 153.8, 147.3, 146.3, 138.7, 113.2, 112.2; HRMS
(ESI) m/z: calcd for C6H4N2NaO3 [M+Na]+, 175.0114; found, 175.0116.
3,5-Diphenyl-1,3,4-oxadiazol-2(3H)-one (4a): White solid (30 mg, 62%); mp:
1
136.7ꢀ137.9; IR (KBr): 3432, 1624, 1331, 1114, 748; H NMR (400 MHz, CDCl3) δ
8.52 (s, 1H), 7.85ꢀ7.80 (m, 3H), 7.61 (dd, J = 15.6, 7.6 Hz, 2H), 7.48 (t, J = 7.6 Hz,
13
2H), 7.24 – 7.15 (m, 2H); C NMR (101 MHz, CDCl3) δ 165.9, 160.6, 147.9, 135.3,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 21
1
2
3
4
5
6
133.0, 131.8, 129.9, 127.9, 125.7, 122.9, 117.9, 112.4. HRMS (ESI) m/z: calcd for
C14H10N2NaO2 [M+Na]+, 261.0634; found, 261.0637.
7
8
9
3-Phenyl-5-(p-tolyl)-1,3,4-oxadiazol-2(3H)-one (4b): White solid (41 mg, 82%); mp:
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
156.6ꢀ157.9; IR (KBr): 3290, 1725, 1658, 1339, 742; H NMR (400 MHz, CDCl3) δ
7.81 (d, J = 7.6 Hz, 1H), 7.77 (d, J = 7.6 Hz, 2H), 7.61 (t, J = 7.8 Hz, 1H), 7.28ꢀ7.26
(m, 3H), 7.23 – 7.14 (m, 2H), 2.45 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 166.0,
160.7, 147.8, 144.0, 135.1, 130.1, 128.9, 128.6, 125.6, 122.8, 118.0, 112.4, 21.8.
HRMS (ESI) m/z: calcd for C15H12N2NaO2 [M+Na]+, 275.0791; found, 275.0795.
5-(4-Methoxyphenyl)-3-phenyl-1,3,4-oxadiazol-2(3H)-one (4c): White solid (41 mg,
77%); mp: 137.1ꢀ138.4; IR (KBr): 3419, 1569, 1412, 1257, 1022, 750; 1H NMR (400
MHz, CDCl3) δ 8.52 (s, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 7.6 Hz, 1H), 7.62 (t,
J = 7.6 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 6.97 (d, J = 8.4 Hz,
2H), 3.89 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 165.4, 163.8, 160.8, 147.8, 135.0,
132.7, 125.6, 123.6, 122.8, 118.1, 113.3, 112.4, 55.5. HRMS (ESI) m/z: calcd for
C15H12N2NaO3 [M+Na]+, 291.0740; found, 291.0739.
3-Phenyl-5-(o-tolyl)-1,3,4-oxadiazol-2(3H)-one (4d): White solid (38 mg, 76%); mp:
1
82.7ꢀ84.4; IR (KBr): 2924, 1681, 1411, 1303, 978, 740, 654; H NMR (400 MHz,
CDCl3) δ 8.40 (s, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.42 (t, J
=7.0 Hz, 2H), 7.30 (d, J = 6.8 Hz, 2H), 7.23 (d, J = 8.4 Hz, 1H), 7.17 (t, J = 7.4 Hz,
1H), 2.43 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 165.5, 160.0, 147.6, 136.2, 135.4,
133.0, 131.0, 130.6, 127.9, 125.7, 125.6, 122.9, 117.8, 112.3, 19.4. HRMS (ESI) m/z:
calcd for C15H12N2NaO2 [M+Na]+, 275.0791; found, 275.0790.
ACS Paragon Plus Environment

Page 17 of 21
The Journal of Organic Chemistry
1
2
3
4
5-Mesityl-3-phenyl-1,3,4-oxadiazol-2(3H)-one (4e): White solid (45 mg, 80%); mp:
5
6
7
1
60.2ꢀ61.8; IR (KBr): 3212, 1683, 1618, 1339, 1301, 893, 752; H NMR (400 MHz,
8
9
CDCl3) δ 8.50 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.62 (t, J = 7.6 Hz, 1H), 7.21 (d, J =
8.4 Hz, 1H), 7.16 (t, J = 7.4 Hz, 1H), 6.90 (s, 2H), 2.31 (s, 3H), 2.23 (s, 6H); 13C
NMR (101 MHz, CDCl3) δ 165.8, 159.5, 147.5, 139.7, 135.3, 134.3, 131.3, 128.4,
125.6, 122.7, 117.5, 112.3, 21.3, 19.1. HRMS (ESI) m/z: calcd for C17H16N2NaO2
[M+Na]+, 303.1104; found, 303.1103.
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-(2-Chlorophenyl)-3-phenyloxazol-2(3H)-one (4f): White solid (44 mg, 80%); mp:
1
145.0ꢀ146.1; IR (KBr): 2923, 1670, 1413, 1189, 998, 772, 653; H NMR (400 MHz,
CDCl3) δ 8.34 (s, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.54 – 7.42
(m, 3H), 7.42 – 7.36 (m, 1H), 7.23 (s, 1H), 7.18 (t, J = 7.6 Hz, 1H); 13C NMR (101
MHz, CDCl3) δ 162.3, 160.0, 147. 8, 135.6, 133.4, 131.8, 131.5, 129.7, 128.6, 126.9,
125.7, 123.1, 117.5, 112.5. HRMS (ESI) m/z: calcd for C14H9ClN2NaO2 [M+Na]+,
295.0245; found, 295.0241.
3-(4-Bromophenyl)-5-phenyl-1,3,4-oxadiazol-2(3H)-one (4g): White solid (35 mg,
1
55%); mp: 146.0ꢀ147.9; IR (KBr): 2924, 1748, 1570, 1413, 1255, 1054, 751; H
NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 7.93 (s, 1H), 7.82 (d, J = 7.6 Hz, 2H), 7.71 (d,
J = 8.4 Hz, 1H), 7.62 (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.14 (d, J = 8.8 Hz,
1H); 13C NMR (101 MHz, CDCl3) δ 165.7, 159.1, 146.3, 138.2, 133.3, 131.4, 129.9,
128.2, 128.0, 119.6, 115.5, 114.0. HRMS (ESI) m/z: calcd for C14H9BrN2NaO2
[M+Na]+, 338.9740; found, 338.9735.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 21
1
2
3
4
5-(4-Fluorophenyl)-3-phenyl-1,3,4-oxadiazol-2(3H)-one (4h): White solid (40 mg,
5
6
7
1
78%); mp: 124.5ꢀ126.0; IR (KBr): 3074, 1747, 1623, 1506, 1242, 1153, 748; H
8
9
NMR (400 MHz, CDCl3) δ 7.88 (dd, J = 8.4, 5.6 Hz, 2H), 7.81 (d, J = 7.6 Hz, 1H),
7.61 (t, J = 7.6 Hz, 1H), 7.29 – 7.07 (m, 5H); 13C NMR (101 MHz, CDCl3) δ 167.0,
164.8, 164.4, 160.8, 147.9, 135.4, 132.8, 132.7, 127.8, 125.6, 122.9, 117.6, 115.3,
115.1, 112.4. HRMS (ESI) m/z: calcd for C14H9FN2NaO2 [M+Na]+, 279.0540; found,
279.0537.
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
BMS-191011: White solid (90 mg, 83%); mp: 216.7ꢀ217.8; IR (KBr): 2929, 2382,
1782, 1324, 1134, 1011, 848, 747; 1H NMR (400 MHz, DMSO) δ 10.12 (s, 1H), 7.95
(d, J = 8.0 Hz, 2H), 7.92 (d, J = 8.0 Hz, 2H), 7.29 (s, 1H), 7.20(dd, J = 8.7, 2.6 Hz,
1H), 6.87 (d, J = 8.4 Hz, 1H), 4.91 (s, 2H); 13C NMR (101 MHz, DMSO) δ 154.1,
152.7, 151.3, 131.3, 131.0, 128.8, 128.8, 127.2, 126.1, 125.0, 123.2, 122.4, 122.3,
116.7, 44.3. HRMS (ESI) m/z: calcd for C16H10ClF3N2NaO3 [M+Na]+, 393.0224;
found, 393.0222.
Acknowledgements
We are grateful to the National Basic Research Program of China (973 Program)
(2011CB808600), the National Natural Science Foundation of China (21172076 and
21420102003), the Guangdong Natural Science Foundation (10351064101000000),
and the Fundamental Research Funds for the Central Universities (2014ZP0004 and
2014ZZ0046).
ACS Paragon Plus Environment

Page 19 of 21
The Journal of Organic Chemistry
1
2
3
4
Supporting Information
5
6
7
8
1H and 13C NMR spectra of all synthesized compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
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
References
1. (a) Borg, S.; EstenneꢀBouhtou, G.; Luthman, K.; Csoeregh, I.; Hesselink, W.;
Hacksell, U. J. Org. Chem. 1995, 60, 3112. (b) Poulain, R. F.; Tartar, A. L.;
Deprez, B. P. Tetrahedron Lett. 2001, 42, 1495. (c) Poindexter, G. S.; Bruce, M. A.;
Breitenbucher, J. G.; Higgins, M. A.; Sit, S. Y.; Romine, J. L.; Martin, S. W.; Ward,
S. A.; McGovern, R. T.; Clarke, W.; Russell, J.; AntalꢀZimanyi, I. Bioorg. Med.
Chem. 2004, 12, 507. (d) Elzein, E.; Ibrahim, P.; Koltun, D. O.; Rehder, K.; Shenk,
K. D.; Marquart, T. A.; Jiang, B.; Li, X.; Natero, R.; Li, Y.; Nguyen, M.; Kerwar,
S.; Chu, N.; Soohoo, D.; Hao, J.; Maydanik, V. Y.; Lustig, D. A.; Zeng, D.; Leung,
K.; Zablocki, J. A. Bioorg. Med. Chem. Lett. 2004, 14, 6017.
2. Sherif, A. R.; Manal, A. S.; Maha, A. E. Eur. J. Med. Chem. 2003, 38, 959.
3. Jansen, M.; Rabe, H.; Strehle, A.; Dieler, S.; Debus, F.; Dannhardt, G.; Akabas, M.;
Luddens, H. J. Med. Chem. 2008, 51, 4430.
4. Romine, J. L.; Martin, S. W.; Meanwell, N. A.; Gribkoff, V. K.; Boissard, C. G.;
Dworetzky, S. I.; Natale, J.; Moon, S.; Ortiz, A.; Yeleswaram, S.; Pajor, L.; Gao,
Q.; Starrett, J. E. J. Med. Chem. 2007, 50, 528.
5. (a) Chen, H.; Li, Z.; Han, Y. J. Agric. Food Chem. 2000, 48, 5312. (b) Jiang, L.;
Tan, Y.; Zhu, X.; Wang, Z.; Zuo, Y.; Chen, Q.; Xi, Z.; Yang, G. J. Agric. Food
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 21
1
2
3
4
Chem. 2010, 58, 2643.
5
6
7
8
9
6. (a) Liu, Q.; Wu, P.; Yang, Y.; Zeng, Z.; Liu, J.; Yi, H.; Lei, A. Angew. Chem., Int.
Ed. 2012, 51, 4666. (b) Chu, W. J.; Yang, Y.; Chen, C. F. Org. Lett. 2010, 12, 3156.
(c) Mazouz, F.; Gueddari, S.; Burstein, C.; Mansuy, D.; Milcent, R. J. Med. Chem.
1993, 36, 1157. (d) Tong, Y.; Bouska, J. J.; Ellis, P. A.; Johnson, E. F.; Leverson, J.;
Liu, X.; Marcotte, P. A.; Olson, A. M.; Osterling, D. J.; Przytulinska, M.;
Rodriguez, L. E.; Shi, Y.; Soni, N.; Stavropoulos, J.; Thomas, S.; Donawho, C. K.;
Frost, D. J.; Luo, Y.; Giranda, V. L.; Penning, T. D. J. Med. Chem. 2009, 52, 6803.
(e) Zender, M.; Klein, T.; Henn, C.; Kirsch, B.; Maurer, C. K.; Kail, D.; Ritter, C.;
Dolezal, O.; Steinbach, A.; Hartman, R. W. J. Med. Chem. 2013, 56, 6761. (f)
Mullican, M. D.; Wilson, M. W.; Connor, D. T.; Kostlan, C. R.; Schrier, D. J.;
Dyer, R. D. J. Med. Chem. 1993, 36, 1090. (g) Levins, C. G.; Wan, Z. K. Org. Lett.
2008, 10, 1755.
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
7. (a) Andersen, T.ꢀL.; Friis, S.ꢀD.; Audrain, H.; Nordeman, P.; Antoni, G.;
Skrydstrup, T. J. Am. Chem. Soc. 2015, 137, 1548. (b) Burhardt, M.ꢀN.; Ahlburg,
A.; Skrydstrup, T. J. Org. Chem. 2014, 79, 11830. (c) Yin, H.; de Almeida, A.ꢀM.;
de Almeida, M.ꢀV.; Lindhardt, A.ꢀT.; Skrydstrup, T. Org. Lett. 2015, 17, 1248. (d)
Jusseau, X.; Yin, H.; Lindhardt, A.ꢀT.; Skrydstrup, T. Chem. Eur. J. 2014, 20,
15785. (e) Li, W.; Wu, X.ꢀF.; J. Org. Chem. 2014, 79, 10410. (f) Aubert, C.;
Fensterbank, L.; Garcia, P.; Malacria, M.; Simonneau, A. Chem. Rev. 2011, 111,
1954. (g) Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736. (h) Xu, Y.; Zhao, J.;
Chen, H.; Wu, W.; Jiang, H. Chem. Commun. 2014, 50, 2488. (i) Li, J.; Yang, S.;
ACS Paragon Plus Environment

Page 21 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
Wu, W.; Jiang, H. Chem. Commun. 2014, 50, 1381. (j) Chen, H.; Cai, C.; Liu, X.;
Li, X.; Jiang, H. Chem. Commun. 2011, 47, 12224.
7
8
9
8. (a) Liu, G.ꢀS.; Jia, L. J. Am. Chem. Soc. 2004, 126, 14716. (b) Liu, Q.; Zhang, H.;
Lei, A. Angew. Chem., Int. Ed. 2011, 50, 10788. (c) Guan, Z.ꢀH.; Chen, M.; Ren,
Z.ꢀH. J. Am. Chem. Soc. 2012, 134, 17490. (d) Gao, S.; Chen, M.; Zhao, M.ꢀN.;
Du, W.; Ren, Z.ꢀH.; Wang, Y.ꢀY.; Guan, Z.ꢀH. J. Org. Chem. 2014, 79, 4196.
(e)Wu, X.ꢀF.; Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 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
9. (a) Huang, H.; Ji, X.; Wu, W.; Jiang, H. Chem. Commun. 2013, 49, 3351. (b) Tang,
X.; Huang, L.; Qi, C.; Wu, W.; Jiang, H. Chem. Commun. 2013, 49, 9597. (c) Li,
Y.; Zhao, J.; Chen, H.; Liu, B.; Jiang, H. Chem. Commun. 2012, 48, 3545. (d) Wu,
X.ꢀF.; Schranck, J.; Neumann, H.; Beller. M. Chem. Eur. J. 2011, 17, 12246. (e)
Dai, G.; Larock, R. C. Org. Lett. 2002, 4, 193. (f) Lu, Y.; Leow, D.; Wang, X.;
Engle, K. M.; Yu, J.ꢀQ. Chem. Sci. 2011, 2, 967. (g) Zhang, Z.; Ouyang, L.; Wu,
W.; Li, J.; Zhang, Z.; Jiang, H. J. Org. Chem. 2014, 79, 10734.
10. The synthesis for BMSꢀ191011: (a) Luca, L. D.; Giacomelli, G.; Porcheddu, A.
Org. Lett. 2002, 4, 553 (b) Luca, L. D.; Giacomelli, G.; Nieddu, G. J. Comb.
Chem. 2008, 10, 517. (c) Hales, N. J.; Heaney, H.; Hollinshead, J. H.; Ley, S. V.
Tetrahedron 1995, 51, 7741.
11. Ji, F.; Li, X.; Wu, W.; Jiang, H. J. Org. Chem. 2014, 79, 11246.
12. Katane, M.; Osaka, N.; Matsuda, S.; Maeda, K.; Kawata, T.; Saitoh, Y.; Sekine, M.;
Furuchi, T.; Doi, I.; Hirono, S.; Homma, H. J. Comb. Chem. 2008, 10, 671.
13. Saegusa, Y.; Harada, S.; Nakamura, S. J. Heterocycl. Chem. 1990, 27, 739.
ACS Paragon Plus Environment