Metal-Free Synthesis of Fully Substituted Pyridines via Ring Construction Based on the Domino Reactions of Enaminones and Aldehydes

Article abstract of DOI:10.1021/acs.joc.6b01149

An unprecedented domino reaction involving primary enaminones/enaminoesters and aldehydes has been developed for the synthesis of fully substituted pyridines. The construction of the products has been accomplished via the cascade generation of two C-C and

Full text of DOI:10.1021/acs.joc.6b01149

Subscriber access provided by The University of British Columbia Library
Note
Metal-free synthesis of fully substituted pyridines via ring construction
based on the domino reactions of enaminones and aldehydes
Jie-Ping Wan, Yanfeng Jing, Changfeng Hu, and Shouri Sheng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01149 • Publication Date (Web): 01 Jul 2016
Downloaded from http://pubs.acs.org on July 2, 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 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Metal-free synthesis of fully substituted pyridines via ring
construction based on the domino reactions of enaminones
and aldehydes
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
,
†
†
‡
,†
JieꢀPing Wan,* Yanfeng Jing, Changfeng Hu, Shouri Sheng*
†
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022,
P.R. China. Email: wanjieping@jxnu.edu.cn; shengsr@jxnu.edu.cn
‡
College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang
3
10053, China. Hangzhou, Zhejiang 310014, P.R. China
Abstract
An unprecedented domino reaction involving primary enaminones/enaminoesters and
aldehydes has been developed for the synthesis of fully substituted pyridines. The
construction of the products has been accomplished via the cascade generation of two
CꢀC and one CꢀN bonds by simply using TfOH as a promoter.
Throughout the history of synthetic science, the synthesis of pyridines occupies
significant position as a fundamental heterocyclic entity. The widespread applications
of pyridines in pharmaceutical, agricultural, materials and synthetic organic fields
1
have revealed the irreplaceable merits of these compounds. Classically, the Hantzsch
reaction involving the condensation annulations of aldehydes, methylene dicarbonyl
2
compounds and ammonia combining a subsequent oxidation, the Kröhnke pyridine
synthesis using phenacyl isoquinolinium bromides, benzalacetophenone and
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 19
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
4
ammonium, the multimolecular Chichibabin reactions and the [2+2+2]
5
cycloadditionꢀbased ring formation have been predominantly utilized for pyridine
synthesis. During the past decades, impressive advances have occurred in the
chemistry of pyridine synthesis and a large number of alternative tactics have been
successfully established to access pyridine with unprecedentedly high molecular
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
6
7
diversity. The protocols of metalꢀcatalyzed cycloaddition reactions, the
8
multicomponent assemblies of acetophenone, aldehyde and ammonium, the
9
transition metalꢀcatalyzed reactions of ketoxime actates with carbon electrophiles,
10
among others, have constituted the representative model of new pyridine synthesis.
In despite the enriched availability on the synthetic methodologies, however, one or
more of the restrictions such as reliance on transition metal catalyst, stepwise
operation and/or utilization of sensitive reactants remain as challenges in pyridine
synthesis. In this context, extensive efforts in devising new synthetic routes of high
6,11
sustainability such as metalꢀfree methods for the synthesis of pyridine, especially
those densely or fully substituted pyridines, is present an issue of high desirability.
Enaminones are useful synthons showing prevalent application in organic
12
synthesis.
Particularly, enaminones have been discovered with widespread
13
application in the construction of heterocyclic molecules of different types,
14
including the known protocols for pyridines synthesis. However, the survey on
related known literatures indicates that most enaminoneꢀbased heterocycle syntheses
employ tertiary or secondary enaminones. The reactions employing primary
enaminones containing free NH
2
group, on the other hand, have been much less
2
ACS Paragon Plus Environment

Page 3 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
explored. Recently, Yan, Huang and coꢀworkers have reported an interesting
dimerization reactions of primary enaminones which lead to the synthesis of various
1
5
pyridine fused heterocyclic products (A in Scheme 1). On the other hand, Pal, Iqbal
and coꢀworkers have reported that the reactions of primary enaminones with allylic
alcohols provides 1,2,5,6ꢀtertrasubstituted pyridines with the catalysis of IBX (B in
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
16
Scheme 1). During our continuous research in designing new synthetic approaches
using enaminones and related electron deficient enamines, we report herein a
metalꢀfree, primary enaminoneꢀbased reaction for the synthesis of fully substituted
pyridines via cascade formation of two CꢀC and one C=N bonds (C in Scheme 1).
Scheme 1 Synthesis of pyridines and ring fused pyridines using enaminones
Prevous: Metal-free synthesis of fused pyridiens
R2
O
NH2
O
NH2
I2
O
R1
A)
R1
MeCN, 80 o
C
R1
R1
N
R2
R2
R2
one C=C, one C-O and one C-N bond formation
Prevous: Metal-free synthesis of tetra-substituted pyridines
O
R2
R2
R3
O
NH2
R1
one C-C and one C=N bond formation
Present: Metal-free, multicomponent synthesis of full substituted pyridines
IBX/DMSO EtO
30 or 50 o
B)
OH
C
R1
N
EtO
R3
O
O
O
NH2
R1
R1
TfOH
R2 CHO
2
C)
o
R1
DMF, 90 C
R2
N
two C-C and one C=N bond formation
The investigation started from the condition optimization on the model reaction
of primary enaminone 1a and pꢀchlorobenzaldehyde 2a. The reaction conducted in the
presence of different Brønsted and Lewis acids was found to be capable of providing
pyridine 3a, and TfOH displayed amongst the best effect (entries 1ꢀ7, Table 1). On the
other hand, the examination on entries using different media suggested that DMF was
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 19
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 most proper polar organic solvent (entries 8ꢀ13, Table 1). Subsequent investigation
on the effect of the reaction temperature disclosed that heightening or lowering the
temperature was neither positive to the result (entries 14ꢀ15, Table 1). Finally,
reducing the loading of TfOH led to the decrease on the product yield although
increasing the amount of TfOH didn’t gave further enhancement of the yield (entries
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
6ꢀ18, Table 1). The requirement of stoichiometric acid in the reaction might be
attributed to the generation of the ammonium side product in the reaction which
deactivated part of acid (See also the reaction mechanism in Scheme 2). Finally, a
control experiment performed under argon showed the formation only trace product
(entry 19, Table 1), indicating the indispensable function of air for the reaction.
a
Table 1 Optimization of reaction conditions
o
Entry Catalyst
Solvent
DMF
T ( C) Yield (%)b
1
2
3
4
5
6
7
8
9
10
TMSCl
TfOH
90
90
90
90
90
90
90
90
90
52
81
38
45
55
43
50
55
DMF
PhCOOH DMF
FeCl
3
DMF
DMF
DMF
DMF
DMSO
AlCl3
AcOH
TsOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
c
H
2
O
nr
EtOH
CH CN
THF
reflux 46
reflux 37
reflux nr
11
3
12
13
1,4ꢀdioxane 90
34
4
ACS Paragon Plus Environment

Page 5 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
4
5
6
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
DMF
DMF
DMF
DMF
DMF
DMF
80
100
90
90
90
90
67
75
c
d
e
f
45
17
58
1
8
9
80
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
trace
a
General conditions:1a (0.6 mmol), 2a (0.3 mmol), acid promoter (0.3 mmol), stirred for 8 h. NR
b
c
d
=
no reaction. Yield of isolated product. The TfOH was 0.15 mmol. The TfOH was 0.21 mmol.
e
f
The TfOH was 0.39 mmol. Reaction under argon.
Based on the in hand results from the optimization experiments, the scope of the
pyridine synthesis was then investigated. The results in the synthesis of various full
substituted pyridines were provided in Table 2. Based on these synthesized products,
it was demonstrated that the present synthetic approach was generally applicable for
the synthesis of these full substituted pyridines. The tolerance of the reaction to
diverse aryl aldehydes (3aꢀl, Table 2) vinyl aldehydes (3nꢀo, Table 2) and alkyl
aldehyde (3m, Table 2) demonstrated the broad application scope of the present
method in the preparation of pyridines with flexible C2ꢀsubstitution. As for the
enaminone component, the alkyl functionalized enaminone also exhibited practical
application in the synthesis of corresponding pyridine product (3p, Table 2). However,
the entry employing two different enaminones 1a and 1b (the alkylꢀbased enaminone)
proved that complex mixture was formed.
All the products were obtained in generally good yield, and no substantial effect
of the functional group to yield of products was indicated with the present data. The
structure of the novel pyridine products were clearly assigned by full spectroscopic
17
analysis and Xꢀray single crystal of 3i (see SI).
a
Table 2 Scope for the synthesis of fully substituted pyridines
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 19
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
Yield of isolated product based on 2 was reported.
Interestingly, when enaminoesters 4 were subjected as alternative substrates of
enaminones to the catalytic system, unexpected production of symmetrical pyridines 5
were observed, revealing the novel application of the present catalytic method for the
synthesis of diverse pyridines (Scheme 2). According to the structure of the products,
it was possible the Hantzschꢀtype reaction pathway was selectively involved to
provide the symmetrical pyridines with the promotion of TfOH. Based on our
previous works on the switchable relative nucleophilicity of the amino group and the
18
αꢀcarbon in the enaminones and enaminoesters, the outcome of the selective
formation of symmetrical pyridines 5 might be ascribed to the electron withdrawing
6
ACS Paragon Plus Environment

Page 7 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
effect produced by the conjugate styrene fragment, which reduced the nucleophilic
strength of the amino group in 4, and thereafter prevented its direct condensation with
the aldehyde (see also Scheme 3). Instead, the nucleophilic αꢀcarbon in 4 acted as the
initial site to incorporate the aldehyde and finally led to the formation of products 5
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).
Scheme 2 Formation of symmetrical pyridines with enaminoester
R
R
NH2
O
O
OEt
TfOH
2
OEt
DMF, 90 o
C
EtO
O
4
CHO
N
R = Cl,
5a, 72%
OMe, 5b, 73%
5
R
NH2
O
OH
R
NH
Ph
OEt
EtO2C
CHO
H+
NH
O
4
OEt
OH
R
NH2
R
NH2
Ph
-
H2O
EtO2C
Ph
EtO2C
H+
EtO2CPh NH
NH2
Ph
EtO CPh NH2
TfOH
2
R
R
NH
+
-
EtO2C
EtO C
NH4 TfO
2
EtO2C
Ph
NH
Ph
EtO C
Ph
N
2
aromatisation
air
R
R
EtO2C
EtO C
Ph
2
To further illustrate the application potential of the method, we attempted the
scaled up synthesis of pyridine 3a, and it was found that the gram scale synthesis
provided practical result with 51% yield (Eq 1). On the other hand, a control
experiment using aldehyde 2a, 1ꢀphenylbutaneꢀ1,3ꢀdione 6 and ammonium acetate 7
failed to afforded pyridine product 3a under standard reaction conditions, instead, the
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 19
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
NH
2
ꢀenaminone 1a was acquired as the main product (Eq 2), suggesting the
irreplaceable role of enaminones 1 in the synthesis of these unprecedented pyridines.
O
NH2
TfOH (1 equiv)
DMF (3 mL), 90 o
Cl
CHO
3a
(1)
Ph
C
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
51%, 1.08g
2a, 5 mmol
1a, 10 mmol
O
O
standard condition
3
a
1a (2)
2a
0.3 mmol
NH OAc
4
Ph
6
trace 56%
7, 0.6 mmol
, 0.6 mmol
According to the reaction results, a mechanism for the formation of these
pyridines has been tentatively proposed in Scheme 3. Firstly, the activation of TfOH
to the enaminone 1 promoted the condensation of the amino group with the aldehyde
and yield imine intermediate 8, and the nucleophilic addition of 1’, the isomeric
version of 1, to the imine gives intermediate 9. The tautomerization of 9 gives 10
which subsequently incorporate TfOH to access ammonium intermediate 11. The
intramolecular annulation on 11 initiated by a nucleophilic substitution yields
4
dihydropyridine intermediate 12 and TfONH . The pyridine products 3 were then
generated via the aromatization of 12 via the aerobic oxidation.
Scheme 3 The postulated reaction mechanism
8
ACS Paragon Plus Environment

Page 9 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
In conclusion, we have established an unprecedented cascade reaction involving
the dimerization of primary enaminones for the synthesis of full substituted pyridines
with unprecedented pattern. Without using any metal catalyst, the construction of
pyridine has been achieved through the generation of two new CꢀC and a C=N bonds.
The easy availability and high stability of the starting materials, simple operation and
novelty in both the reaction model as well as products features the high application
potential of the present method.
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
Experimental section
General procedure for the synthesis of pyridines 3 and 5. In a 25 mL round
bottom flask were charged with enaminone 1 or enaminoester 4 (0.6 mmol), aldehyde
2 (0.3 mmol), triflic acid (TfOH) (0.3 mmol) and DMF (2.0 mL). The vessel was then
o
heated at 90 C for 8 h (TLC) under air atmosphere. Upon completion, 10 mL water
was added, and resulting mixture was extracted with ethyl acetate (3×10 mL). The
organic phase was collected and dried with anhydrous Na SO . After filteration, the
2
4
solution was evaporated at reduced pressure to remove the solvent, and the residue
was subjected to silica gel column chromatography to give pure product using mixed
petroleum ether / ethyl acetate as eluent (v / v = 15:1).
(2-(4-Chlorophenyl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone) (3a). Yield:
o
1
103 mg; 81%; white solid; mp 189ꢀ190 C; H NMR (400 MHz, CDCl ): δ 7.89 (d, J
3
=
7.2 Hz, 2 H), 7.65 (d, J = 8.0 Hz, 3 H), 7.55ꢀ7.47 (m, 5 H), 7.33 (t, J = 8.0 Hz, 2 H),
13
7.22 (d, J = 8.8 Hz, 2 H), 2.49 (s, 3 H), 2.04 (s, 3 H); C NMR (100 MHz, CDCl
3
): δ
1
97.8, 197.7, 154.7, 154.3, 142.7, 137.7, 136.8, 136.4, 135.0, 134.5, 134.2, 134.0,
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 19
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
32.4, 130.5, 129.5, 129.4, 129.3, 128.8, 128.5, 23.1, 16.9; ESIꢀHRMS: Calcd for
+
C
27
H
21ClNO
2
[M + H] 426.1255, found 426.1259.
(2-(4-Bromophenyl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone) (3b). Yield:
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
1
1
08 mg; 77%; white solid; mp 198ꢀ199 C; H NMR (400 MHz, CDCl ): δ 7.89 (d, J
3
=
7.2 Hz, 2 H), 7.66ꢀ7.63 (m, 3 H), 7.55ꢀ7.47 (m, 3 H), 7.43ꢀ7.32 (m, 6 H), 2.48 (s, 3
13
H), 2.03 (s, 3 H); C NMR (100 MHz, CDCl
3
): δ 197.8, 197.7, 154.7, 154.3, 142.7,
1
1
38.1, 136.8, 136.3, 134.6, 134.2, 134.1, 132.3, 131.5, 130.8, 129.5, 129.4, 129.3,
+
2
28.8, 123.4, 23.1, 16.9; ESIꢀHRMS: Calcd for C27H21BrNO [M + H] 470.0750,
found 470.0750.
2,4-Dimethyl-6-(p-tolyl)pyridine-3,5-diyl)bis(phenylmethanone) (3c). Yield: 95 mg;
(
o
1
78%; white solid; mp 223ꢀ224 C; H NMR (400 MHz, CDCl
3
): δ 7.90 (d, J = 7.2 Hz,
2
H), 7.65 (t, J = 8.0 Hz, 3 H), 7.52 (t, J = 8.0 Hz, 2 H), 7.43 (t, J = 8.0 Hz, 3 H), 7.31
(t, J = 8.0 Hz, 2 H), 7.03 (d, J = 8.0 Hz, 2 H), 2.48 (s, 3 H), 2.24 (s, 3 H), 2.02 (s, 3 H);
13
C NMR (100 MHz, CDCl ): δ 198.1, 198.0, 155.7, 154.4, 142.4, 138.6, 137.0, 136.5,
3
136.4, 134.4, 133.6, 132.6, 132.2, 129.5, 129.4, 129.2, 129.1, 129.0, 128.6, 23.2, 21.2,
+
1
6.9. ESIꢀHRMS: Calcd for C28
H
24NO
2
[M + H] 406.1802, found 406.1805.
(2-(4-Methoxyphenyl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone)
(3d).
o
1
Yield: 99 mg; 78%; white solid; mp 195ꢀ196 C; H NMR (400 MHz, CDCl
3
): δ 7.90
(d, J = 7.6 Hz, 2 H), 7.65 (t, J = 7.6 Hz, 3 H), 7.54 ꢀ 7.43 (m, 5 H), 7.31 (t, J = 7.6 Hz,
13
2
H), 6.76 (d, J = 8.8 Hz, 2 H), 3.71 (s, 3 H), 2.48 (s, 3 H), 2.03 (s, 3 H); C NMR
(100 MHz, CDCl
3
): δ 198.1 (2C), 160.1, 155.2, 154.4, 142.4, 137.0, 136.6, 134.4,
1
33.7, 133.4, 131.9, 131.8, 130.6, 129.5, 129.3, 129.2, 128.6, 113.8, 55.1, 23.2, 16.9.
10
ACS Paragon Plus Environment

Page 11 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
+
ESIꢀHRMS: Calcd for C28
H
24NO
3
[M + H] 422.1751, found,422.1755.
4
-(3,5-Dibenzoyl-4,6-dimethylpyridin-2-yl)benzonitrile (3e). Yield: 100 mg; 80%;
o
1
white solid; mp 203ꢀ204 C; H NMR (400 MHz, CDCl
3
): δ 7.90 (d, J = 7.6 Hz, 2 H),
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
3
1
2
.70ꢀ7.63 (m, 5 H), 7.57ꢀ7.49 (m, 5 H), 7.35 (d, J = 8.0 Hz, 2 H), 2.50 (s, 3 H), 2.05 (s,
13
3
H); C NMR (100 MHz, CDCl ): δ 197.5, 197.3, 155.1, 153.5, 143.5, 143.0, 138.6,
36.1, 134.9, 134.7, 134.3, 132.7, 132.0, 129.8, 129.5, 129.4, 128.9, 118.5, 112.4,
+
3.1, 17.0; ESIꢀHRMS: Calcd for C28
H
21
N
2
O
2
[M + H] 417.1598, found 417.1596.
(2,4-Dimethyl-6-(3-nitrophenyl)pyridine-3,5-diyl)bis(phenylmethanone) (3f). Yield:
1
9
9
7 mg; 74%; yellow liquid; H NMR (400 MHz, CDCl ): δ 8.47 (s, 1 H), 8.09 (d, J =
3
.6 Hz, 1 H), 7.91 (d, J = 7.2 Hz, 2 H), 7.86 (d, J = 7.6 Hz, 1 H), 7.67 (d, J = 7.6 Hz, 3
H), 7.56 (t, J = 7.6 Hz, 2 H), 7.52 ꢀ 7.41 (m, 2 H), 7.36 (t, J = 7.6 Hz, 2 H), 2.52 (s, 3
13
H), 2.08 (s, 3 H); C NMR (100 MHz, CDCl
3
): δ 197.5 , 197.3, 155.2, 152.9, 148.1,
143.1, 140.7, 136.6, 136.2, 134.9, 134.8, 134.4, 132.7, 130.0, 129.5, 129.4, 129.3,
+
1
29.0, 128.4, 124.3, 123.5, 23.1, 17.0; ESIꢀHRMS: Calcd for C H N O [M + H]
27 21 2 4
437.1496, found, 437.1498.
(2-(3,4-Dichlorophenyl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone)
(3g).
1
Yield: 105 mg; 76%; yellow liquid; H NMR (400 MHz, CDCl
3
): δ 7.88 (d, J = 7.6
Hz, 2 H), 7.70 (s, 1 H), 7.66 (d, J = 7.6 Hz, 3 H), 7.53 (q, J = 7.6 Hz, 3 H), 7.39 ꢀ 7.33
13
(m, 3 H), 7.29 (d, J = 8.8 Hz, 1 H), 2.49 (s, 3 H), 2.04 (s, 3 H); C NMR (100 MHz,
CDCl ): δ 197.6, 197.4, 154.9, 152.9, 142.9, 139.0, 136.8, 136.3, 134.62, 134.57,
3
134.2, 133.2, 132.6, 132.5, 131.2, 130.2, 129.4, 129.32, 129.29, 128.9, 128.3, 23.1,
+
1
6.9; ESIꢀHRMS: Calcd for C27
H
20Cl
2
NO
2
[M + H] 460.0866, found 460.0869.
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 19
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
2-(2-Chlorophenyl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone) (3h). Yield:
o
1
9
7 mg; 76%; white solid; mp 121ꢀ122 C; H NMR (400 MHz, CDCl
3
): δ 7.92 (d, J =
7
.2 Hz, 2 H), 7.60 (d, J = 7.6 Hz, 3 H), 7.54 (t, J = 7.2 Hz, 2 H), 7.46 (t, J = 7.6 Hz, 1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
H), 7.32 (d, J = 7.2 Hz, 2 H), 7.24 (d, J = 7.6 Hz, 2 H), 7.11 (brs, 2 H), 2.49 (s, 3 H),
1
3
2
1
1
4
3
.07 (s, 3 H); C NMR (100 MHz, CDCl ): δ 197.7, 196.6, 154.3, 153.9, 142.5, 137.2,
36.8, 136.2, 134.62, 134.58, 133.8, 133.6, 132.9, 131.4, 129.9, 129.8, 129.5, 129.3,
+
29.2, 128.5, 126.2, 23.0, 17.0; ESIꢀHRMS: Calcd for C27
26.1255, found 426.1257.
2
H21ClNO [M + H]
(2,4-Dimethyl-6-phenylpyridine-3,5-diyl)bis(phenylmethanone) (3i). Yield: 87 mg;
o
1
7
3
4%; white solid; mp 154ꢀ155 C; H NMR (400 MHz, CDCl ): δ 7.91 (d, J = 8.0 Hz,
2 H), 7.64 (d, J = 7.2 Hz, 3 H), 7.52 (t, J = 7.6 Hz, 4 H), 7.42 (t, J = 7.6 Hz, 1 H), 7.29
13
(t, J = 7.6 Hz, 2 H), 7.22 (d, J = 7.2 Hz, 3 H), 2.50 (s, 3 H), 2.05 (s, 3 H); C NMR
(100 MHz, CDCl
3
): δ 198.1, 197.9, 155.7, 154.6, 142.6, 139.2, 136.9, 136.4, 134.6,
1
33.9, 133.8, 132.3, 129.5, 129.4, 129.3, 129.2, 128.8, 128.6, 128.3, 23.2, 17.0;
+
ESIꢀHRMS: Calcd for C27
2
H22NO [M + H] 392.1645, found 392.1650.
(2-(2-Bromophenyl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone) (3j). Yield:
o
1
108 mg; 77%; yellow solid; mp 76ꢀ77 C; H NMR (400 MHz, CDCl
3
): δ 7.91 (d, J =
7
.6 Hz, 2 H), 7.67 (d, J = 7.6 Hz, 3 H), 7.55 (t, J = 7.2 Hz, 2 H), 7.47ꢀ7.41 (m, 2 H),
7.33 (t, J = 7.6 Hz, 2 H), 7.25 (d, J = 7.2 Hz, 1 H), 7.16 (t, J = 7.2 Hz, 1 H), 7.04 (d, J
13
=
7.6 Hz, 1 H), 2.49 (s, 3 H), 2.07 (s, 3 H); C NMR (100 MHz, CDCl
3
): δ 197.8,
196.7, 155.0, 154.2, 142.4, 138.9, 136.9, 136.3, 134.6, 134.5, 133.8, 133.4, 133.1,
1
31.4, 129.9, 129.5, 129.29, 129.27, 128.5, 126.7, 122.8, 23.0, 17.0; ESIꢀHRMS:
12
ACS Paragon Plus Environment

Page 13 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
+
Calcd for C27
H
21BrNO
2
[M + H] 470.0750, found, 470.0754.
(
2-(2-Hydroxyphenyl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone)
(3k).
Yield: 94 mg; 77%; white solid; mp 164ꢀ165 C; H NMR (400 MHz, CDCl ): δ
2.43 (brs, 1 H), 7.87 (d, J = 8.0 Hz, 2 H), 7.70 ꢀ 7.65 (m, 3 H), 7.55 ꢀ 7.47 (m, 3 H),
.40 ꢀ 7.32 (m, 3 H), 7.13 (t, J = 8.0 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 6.61 (d, J =
o
1
3
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
7
7
1
1
13
3
.6 Hz, 1 H), 2.49 (s, 3 H), 2.06 (s, 3 H); C NMR (100 MHz, CDCl ): δ 197.6, 197.0,
57.9, 154.4, 152.4, 144.9, 136.6, 136.2, 134.7, 134.1, 133.9, 132.0, 131.6, 129.9,
29.5, 129.34, 129.29, 128.9, 120.3, 119.1, 118.0, 22.6, 17.4; ESIꢀHRMS: Calcd for
+
C H NO [M + H] 408.1594, found, 408.1597.
27 22
3
(
4,6-Dimethyl-[2,3'-bipyridine]-3,5-diyl)bis(phenylmethanone) (3l). Yield: 84 mg;
1
71%; yellow liquid; H NMR (400 MHz, CDCl
3
): δ 8.80 (brs, 1 H), 8.47 (brs, 1 H),
7
.89 (q, J = 8.4 Hz, 3 H), 7.67 (d, J = 7.6 Hz, 3 H), 7.57 ꢀ 7,.47 (m, 3 H), 7.34 (d, J =
1
3
7.6 Hz, 2 H), 7.19 (d, J = 6.8 Hz, 1 H), 2.51 (s, 3 H), 2.07 (s, 3 H); C NMR (100
MHz, CDCl ): δ 197.6, 197.3, 155.0, 152.4, 149.6, 149.4, 142.8, 136.7, 136.5, 136.2,
3
135.0, 134.65, 134.56, 134.2, 132.8, 129.4, 129.35, 129.30, 128.9, 123.0, 23.0, 16.9;
+
ESIꢀHRMS: Calcd for C26
H
21
N
2
O
2
[M + H] 393.1598, found, 393.1601.
(2-Ethyl-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone) (3m). Yield: 74 mg;
1
7
2%; yellow liquid; H NMR (400 MHz, CDCl
3
): δ 7.86 (d, J = 8.0 Hz, 4 H),
7.66ꢀ7.62 (m, 2 H), 7.53ꢀ7.49 (m, 4 H), 2.65 (q, J = 7.6 Hz, 2 H), 2.42 (s, 3 H), 1.92 (s,
13
3
H) 1.22 (t, J = 7.6 Hz, 3 H); C NMR (100 MHz, CDCl
3
): δ 198.1, 198.0, 158.9,
154.1, 141.3, 136.8, 136.5, 134.4, 132.9, 132.4, 130.0, 129.5, 129.2, 129.1, 128.3,
+
2
9.6, 22.8, 16.8, 14.1; ESIꢀHRMS Calcd: for C23
H22NO
2
[M + H] 344.1645, found
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 19
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
44.1655.
(E)-(2-(4-Methoxystyryl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone) (3n).
1
Yield: 98 mg; 73%; yellow liquid; H NMR (400 MHz, CDCl
3
): δ 8.16 (d, J = 15.6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Hz, 1 H), 7.88 (t, J = 7.6 Hz, 4 H), 7.63 (q, J = 7.6 Hz, 2 H), 7.50 (q, J = 7.6 Hz, 4 H),
.31 (d, J = 7.2 Hz, 1 H), 7.21 (t, J = 7.2 Hz, 1 H), 6.95 (d, J = 15.2 Hz, 1 H), 6.84 (q,
7
13
J = 8.0 Hz, 2 H), 3.75 (s, 3 H), 2.46 (s, 3 H), 1.94 (s, 3 H); C NMR (100 MHz,
CDCl ): δ 198.3 , 198.1, 160.1, 154.4, 151.4, 141.7, 137.1, 136.6, 135.2, 134.4, 133.3,
31.7, 130.4, 129.7, 129.5, 129.2, 128.9, 126.5, 121.8, 114.6, 114.1, 55.3, 23.3, 16.8;
3
1
+
ESIꢀHRMS: Calcd for C H NO [M + H] 448.1907, found 448.1915.
30 26
3
(E)-(2-(2-Methoxystyryl)-4,6-dimethylpyridine-3,5-diyl)bis(phenylmethanone) (3o).
1
Yield: 106 mg; 79%; yellow liquid; H NMR (400 MHz, CDCl
3
): δ 7.89ꢀ7.85 (m, 5
H), 7.63 (q, J = 8.0 Hz, 2 H), 7.50 (q, J = 7.6 Hz, 4 H), 7.33 (d, J = 7.6 Hz, 2 H), 6.81
(d, J = 8.8 Hz, 2 H), 6.69 (d, J = 15.2 Hz, 1 H), 3.79 (s, 3 H), 2.46 (s, 3 H), 1.93 (s, 3
13
H); C NMR (100 MHz, CDCl ): δ 198.3, 198.2, 157.8, 154.5, 151.7, 141.7, 137.1,
3
136.6, 134.4, 134.3, 133.4, 132.0, 130.9, 129.7, 129.5, 129.2, 129.1, 128.3, 125.4,
+
1
25.1, 120.5, 110.9, 55.3, 23.3, 16.8; ESIꢀHRMS: Calcd for C30
3
H26NO [M + H]
448.1907, found, 448.1915.
2
,4-Dimethyl-3,5-diacetyl-6-(4-chlorophenyl) pyridine (3p). Yield: 62 mg; 69%;
1
yellow liquid; H NMR (400 MHz, CDCl ): δ 7.42 (d, J = 8.4 Hz, 2H), 7.33 (d, J =
3
13
8
.0 Hz, 2 H), 2.47 (s, 3 H), 2.45 (s, 3 H), 2.11 (s, 3 H), 1,94 (s, 3 H); C NMR (100
MHz, CDCl
3
): δ 205.5, 205.3, 153.0,. 152.6, 139.3, 137.5, 136.8, 135.6, 134.8, 130.4,
+
1
29.0, 32.3, 32.2, 22.6, 16.1; ESIꢀHRMS: Calcd for C17
H
17ClNO
2
[M + H] 302.0942,
14
ACS Paragon Plus Environment

Page 15 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
found, 302.0942.
Diethyl 4-(4-chlorophenyl)-2,6-diphenylpyridine-3,5-dicarboxylate (5a). Yield: 105
1
mg; 72%; yellow liquid; H NMR (400 MHz, CDCl
3
): δ 7.73ꢀ7.70 (m, 4 H), 7.44ꢀ7.38
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
(
m, 8 H), 7.32 (d, J = 8.4 Hz, 2 H), 3.90 (q, J = 7.2 Hz, 4 H), 0.86 (t, J = 7.2 Hz, 6 H);
1
3
C NMR (100 MHz, CDCl
3
): δ 167.4, 156.4, 146.3, 139.1, 135.0, 134.1, 130.0, 129.3,
+
1
28.7, 128.5, 128.4, 127.6, 61.7, 13.5; ESIꢀHRMS: Calcd for C29
86.1467, found 486.1471.
4
H25ClNO [M + H]
4
Diethyl 4-(4-methoxyphenyl)-2,6-diphenylpyridine-3,5-dicarboxylate (5b). Yield: 106
1
mg; 73%; yellow liquid; H NMR (400 MHz, CDCl ): δ 7.73ꢀ7.70 (m, 4 H), 7.44ꢀ7.40
3
(m, 6 H), 7.31 (d, J = 8.8 Hz, 2 H), 6.92 (d, J = 8.8 Hz, 2 H), 3.90 (q, J = 7.2 Hz, 4 H),
13
3.82 (s, 3 H), 0.86 (t, J = 7.2 Hz, 6 H); C NMR (100 MHz, CDCl
3
): δ 167.8 , 159.9,
1
56.1, 147.2, 139.3, 129.8, 129.1, 128.7, 128.4, 128.1, 127.8, 113.5, 61.5, 55.3, 13.5;
+
5
ESIꢀHRMS: Calcd for C30H28NO [M + H] 482.1962, found 482.1964.
Supporting Information
1
13
General experimental information, H/ C NMR spectra for all products and the
crystallographic data of 3i. This material is available free of charge via the Internet at
http:
AUTHOR INFORMATION
Corresponding Author
wanjieping@jxnu.edu.cn; shengsr@jxnu.edu.cn
Notes
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 19
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 authors declare no competing financial interests.
ACKNOWLEDGMENTs
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
The work is financially supported by the National Natural and Science Foundation of
China (21562025) and National Natural and Science Foundation of Jiangxi Province
(20151BAB203008).
REFERENCES
1
. (a) Gibson, V. C.; Redshaw, C.; Solan, G. A. Chem. Rev. 2007, 107, 1745. (b)
Michael, J. P. Nat. Prod. Rep. 2005, 22, 627. (c) Fan, Y.; Weinstein, J. N.; Kohn, K.
W.; Shi , L. M.; Pommier, Y. J. J. Med. Chem. 1998, 41, 2216. (d) Redinbo, M. R.;
Stewart, L.; Kuhn, P.; Champoux, J. J.; Hol, W. G. J. Science 1998, 279, 1504. (e)
Basnet, A.; Thapa, P.; Karki, R.; Na, Y.; Jahng, Y.; Jeong, B.ꢀS.; Jeong, T. C.; Lee
,
C.ꢀS.; Lee, E.ꢀS. Bioorg. Med. Chem. 2007, 15, 4351.
2. (a) Stout, D. M.; Meyers, A. I. Chem. Rev. 1982, 82, 223. (b) Pfister, J. R. Synthesis
1990, 689. (c) AbdelꢀMohsen, H. T.; Conrad, J.; Beifuss, U. Green Chem. 2012, 14,
2686. (d) Ray, S.; Brown, M.; Bhaumik, A.; Dutta , A.; Mukhopadhyay, C. Green
Chem. 2013, 15, 1910.
. (a) Kröhnke, F.; Synthesis 1976, 1. (b) Zecher, W.; Kröhnke, F. Chem. Ber. 1962,
94, 698. (c) Jiang, B.; Hao, W.ꢀJ.; Wang, X.; Shi, F.; Tu, S.ꢀJ. J. Comb. Chem. 2009,
1, 846.
3
1
16
ACS Paragon Plus Environment

Page 17 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
4
. (a) Usuki, T.; Sugimura, T.; Komatsu ,A.; Koseki, Y. Org. Lett. 2014, 16, 1672. (b)
Dagorn, F.; Yan, L.ꢀH.; Gravel, E.; Leblanc, K.; Maciuk , A.; Poupon, E. Tetrahedron
Lett. 2011, 52, 3523.
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
. (a) Varela, J. A.; Saá, C. Chem. Rev. 2003, 103, 3787. (b) Varela, J. A. Saá, C.
Synlett 2008, 17, 2571. (c) Heller, B.; Hapke, M. Chem. Soc. Rev. 2007, 36, 1085. (d)
Nakamura, I. Yamamoto, Y. Chem. Rev. 2004, 104, 2127.
6
1
7
. Allais, C.; Grassot, J.ꢀM.; Rodriguez, J. Constantieux, T. Chem. Rev. 2014, 114,
0829.
. (a) Wu, J.; Xu, W.; Yu, Z.ꢀX.; Wang, J. J. Am. Chem. Soc. 2015, 137, 9489. (b)
Bachollet, S. P. J. T.; Vivat, J. F.; Cocker, D. C.; Adams, H.; Harrity, J. P. A. Chem.
Eur. J. 2014, 20, 12889. (c) Lei, C.ꢀH.; Wang, D.ꢀX.; Zhao, L.; Zhu, J.; Wang, M.ꢀX.
J. Am. Chem. Soc. 2013, 135, 4708. (d) Barluenga, J.; Á, M.; GaríaꢀGaría, P.; Aguilar,
E. J. Am. Chem. Soc. 2008, 130, 2746.
8
. (a) Yin, G.; Liu, Q.; Ma, J.; She, N. Green Chem. 2012, 14, 1796. (b) Yasmin, L.;
Eqqers, P. K.; Skelton, B. W.; Stubbs, K. A.; Raston, C. L. Green Chem. 2014, 16,
450. (c) Bai, Y.; Tang, L. Huang, H.; Deng, G.ꢀJ. Org. Biomol. Chem. 2015, 13,
4404.
. (a) Ren, Z.ꢀH.; Zhang, Z.ꢀY.; Yang, B.ꢀQ.; Wang, Y.ꢀY.; Guan, Z.ꢀH. Org. Lett.
3
9
2011, 13, 5394. (b) Zhao, M.ꢀN.; Hui, R.ꢀR.; Ren, Z.ꢀH.; Wang, Y.ꢀY.; Guan, Z.ꢀH.
Org. Lett. 2014, 16, 3082. (c) Jiang, H.; Yang, J.; Tang, X.; Li, J.; Wu, W. J. Org.
Chem. 2015, 89, 8763. (d) Wei, Y.; Yoshikai, N. J. Am. Chem. Soc. 2013, 135, 3756.
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 19
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
(
e) Huang, H.; Cai, J.; Tang, L.; Wang, Z.; Li, F.; Deng, G.ꢀJ. J. Org. Chem. 2016, 81,
1
1
5
1
1
499.
0. (a) Li, Z.; Huang, X.; Chen, F.; Zhang, C.; Wang, X.; Jiao, N. Org. Lett. 2015, 17,
84. (b) Yoshida, M.; Mizuguchi, T.; Namba, K. Angew. Chem. Int. Ed. 2014, 53,
4550. (c) Xi, L.ꢀY.; Zhang, R.ꢀY.; Liang, S.; Chen, S.ꢀY.; Yu, X.ꢀQ. Org. Lett. 2014,
6, 5269. (d) Rieckhoff, S.; Hellmuth, T.; Peters, R. J. Org. Chem. 2015, 80, 6822. (e)
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
Reddy, C. R.; Panda, S. A.; Reddy, M. D. Org. Lett. 2015, 17, 896. (f) Jiang, H.; An,
X.; Tong, K.; Zheng, T.; Zhang, Y. Yu, S. Angew. Chem. Int. Ed. 2015, 54, 4055.
1
1. For some recent examples on metalꢀfree pyridine synthesis, see: (a) Shi, Z.; Loh,
T.ꢀP. Angew. Chem. Int. Ed. 2013, 52, 8584. (b) Kral, K.; Hapke, M. Angew. Chem.
Int. Ed. 2011, 50, 2434. (c) Stark, D. G.; Morrill, L. C.; Yeh, P.ꢀP.; Slawin, A. M. Z.;
O’Riordan, T. J. C.; Smith, A. D. Angew. Chem. Int. Ed. 2013, 52, 11642. (d)
LiébyꢀMuller, F.; Allais, C.; Constantieux, T.; Rodriguez, J. Chem. Commun. 2008,
4
207. (e) Jiang, Y.; Park, C.ꢀM.; Loh, T.ꢀP. Org. Lett. 2014, 16, 3432. (f) Yan, R.;
Zhou, X.; Li, M.; Li, X.; Kang, X.; Liu, X.; Huo, X.; Huang, G. RSC Adv. 2014, 4,
0369. (g) Xiang, J.ꢀC.; Wang, M.; Cheng, Y.; Wu, A.ꢀX. Org. Lett. 2016, 18, 14. (h)
Wei, H.; Li, Y.; Xiao, K.; Cheng, B.; Wang, H.; Hu, L.; Zhai, H. Org. Lett. 2015, 17,
974.
5
5
12. For reviews, see (a) Stanovnik, B.; Svete, J. Chem. Rev. 2004, 104, 2433. (b)
Elassar, A.ꢀZ. A.; ElꢀKhair, A. A. Tetrahedron 2003, 59, 8463. (c) Cao, S.; Jing, Y.;
Liu, Y.; Wan, J. Chin. J. Org. Chem. 2014, 34, 876. (d) Wan, J.ꢀP.; Gao, Y. Chem. Rec.
2
016, 16, 1164.
18
ACS Paragon Plus Environment

Page 19 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
3. (a) Würtz, S.; Rakshit, S.; Neumann, J. J.; Dröge, T.; Glorius, F. Angew. Chem.
Int. Ed. 2008, 47, 7230. (b) Goutham, K.; Kumar, D. A.; Suresh, S.; Sridhar, B.;
Narender, R.; Karunakar, G. V. J. Org. Chem. 2015, 80, 11162. (c) Cao, C.ꢀP.; Lin, W.;
Hu, M.; Huang, Z.ꢀB.; Shi, D.ꢀQ. Chem. Commun. 2013, 49, 6983. (d) Gu, Z.ꢀY.; Zhu,
T.ꢀH.; Cao, J.ꢀJ.; Xu, X.ꢀP.; Wang, S.ꢀY.; Ji, S.ꢀJ. ACS Catal. 2014, 4, 49. (e) Jiang, B.;
Yi, M.ꢀS.; Shi, F.; Tu, S.ꢀJ.; Pindi, S.; McDowell, P.; Li, G. Chem. Commun. 2012, 48,
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
08. (f) Zhao, F.; Liu, X.; Qi, R.; ZhangꢀNegrerie, D.; Huang, J.; Du Y.; Zhao, K. J.
Org. Chem. 2011, 76, 10338.
4. (a) Wan, J.ꢀP.; Zhou, Y.; Cao, S. J. Org. Chem. 2014, 79, 9872. (b) Shen, J.; Cai,
1
D.; Kuai, C.; Liu, Y.; Wei, M.; Cheng, G.; Cui, X. J. Org. Chem. 2015, 80, 6584. (c)
Wan, J.ꢀP.; Zhou, Y.; Jiang, K.; Ye, H. Synthesis 2014, 46, 3256.
1
5. Yan, R.; Li, X.; Yang, X.; Kang, X.; Xiang, L.; Huang, G. Chem. Commun. 2015,
51, 2573.
6. Gade, N. R.; Devendram, V.; Pal, M.; Iqbal, J. Chem. Commun. 2013, 49, 7926.
17. CCDC 1464635 contains the supplementary crystallographic data for this paper
3i).These data can be obtained free of charge from the Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
8. (a) Wan, J.ꢀP.; Gan, S.ꢀF.; Sun, G.ꢀL.; Pan, Y.ꢀJ. J. Org. Chem. 2009, 74, 2862. (b)
1
(
1
Wan, J.ꢀP.; Lin, Y.; Jing, Y.; Xu, M.; Liu, Y. Tetrahedron 2014, 70, 7874. (c) Cao, S.;
Xin, L.; Liu, Y.; Wan, J.ꢀP.; Wen, C. RSC Adv. 2015, 5, 27372.
19
ACS Paragon Plus Environment