Synthesis of 3-Aryl-2-pyrones by Palladium-Catalyzed Cross-Coupling of Aryl Iodides with Cyclic Vinyldiazo Ester

Article abstract of DOI:10.1021/acs.joc.7b01470

A palladium-catalyzed cross-coupling reaction of aryl iodides with cyclic vinyldiazo ester was developed. The reaction provides various 3-aryl-2-pyrones in good yields with high functional group tolerance. The synthetic application of the resulting 3-aryl-2-pyrones as the diene component in a Diels-Alder reaction was also described.

Full text of DOI:10.1021/acs.joc.7b01470

Subscriber access provided by UNIVERSITY OF ADELAIDE LIBRARIES
Note
Synthesis of 3-Aryl-2-pyrones by Palladium-catalyzed
Cross-coupling of Aryl Iodides with Cyclic Vinyldiazo Ester
Jun Huang, Linyong Li, Haoguo Chen, Tiebo Xiao, Yuwei He, and Lei Zhou
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01470 • Publication Date (Web): 08 Aug 2017
Downloaded from http://pubs.acs.org on August 8, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 23
The Journal of Organic Chemistry
1
2
3
4
5
Synthesis of 3ꢀArylꢀ2ꢀpyrones by Palladiumꢀcatalyzed
6
7
Crossꢀcoupling of Aryl Iodides with Cyclic Vinyldiazo Ester
8
9
Jun Huang,†,‡ Linyong Li,† Haoguo Chen,† Tiebo Xiao,† Yuwei He,† and Lei Zhou†,*
†
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
School of Chemistry, Sun YatꢀSen University, 135 Xingang West Road, Guangzhou, 510275, China.
College of Chemistry and Materials Science, Guangxi Teachers Education University, 175 Mingxiu
‡
East Road, Nanning, 530001, China.
Eꢀmail: zhoul39@mail.sysu.edu.cn
ABSTRACT: A palladiumꢀcatalyzed crossꢀcoupling reaction of aryl iodides with
cyclic vinyldiazo ester was developed. The reaction provides various 3ꢀarylꢀ2ꢀpyrones
in good yields with high functional group tolerance. The synthetic application of the
resulting 3ꢀarylꢀ2ꢀpyrones as the diene component in a Diels–Alder reaction was also
described.
2ꢀPyrone is an important class of lactones present in many natural products and
pharmaceuticals.1 Compounds with different substitutions on the 2ꢀpyrone skeleton
possess a wide range of biological activities, such as antiꢀHIV,2 antimicrobial,3
antiꢀinflammatory,4 anticancer,5 and antifungal.6 Owing to its unique unsaturated
sixꢀmembered lactone structure, 2ꢀpyrone has been commonly utilized as a diene
component in Diels–Alder reactions,7 and as an attractive building block for the
synthesis of heterocycles.8 Consequently, the synthesis of various substituted
2ꢀpyrones has been widely covered in the literature and inspired significantly different
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 23
1
2
3
4
5
6
7
8
9
strategies.9 In particular, 3ꢀsubstituted 2ꢀpyrones without any additional activating
functional groups are typical substrates for exploring photochemical isomerization of
2ꢀpyrones.10 To our surprise, the current methods for substituted 2ꢀpyrones synthesis
can hardly be suitable to access such simple derivatives.11 Although the direct
coupling of organometallic reagents with halogenated 2ꢀpyrones has been developed
for their synthesis,12 the prefunctionalized 3ꢀhaloꢀ2ꢀpyrone has to been prepared from
commercially available dihydropyranꢀ2ꢀone by three steps with low yield and poor
regionselectivity.13 Therefore, the development of novel approaches for the efficient
synthesis of 3ꢀsubstituted 2ꢀpyrones is still highly desirable.
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
Palladiumꢀcatalyzed crossꢀcoupling reaction involving diazo compounds as the
nucleophilic partner has been demonstrated to be a highly valuable tool for CꢀC bond
formation.14 The characteristic step for this new type of reaction is the migratory
insertion of Pd carbene species, which has been found to be quite general in terms of
various migratory groups.14b With regard to the synthesis of conjugated dienes by this
transformation, Wang and coꢀworkers reported a Pdꢀcatalyzed crossꢀcoupling of diazo
compounds with allyl halides, in which the allyl migratory insertion of Pd carbene is
involved.15 Barluenga and Valdés developed an elegant migratory
insertion/palladatropic rearrangement/βꢀhydride elimination cascade to produce
dienes.16 Migration insertion was also employed for the generation of transient
cyclopropyl carbinyl palladium species, leading to 1,3ꢀbutadiene products through a
sequential βꢀcarbon elimination/ βꢀhydride elimination process.17 Using this strategy,
our group recently disclosed a regioselective ringꢀenlargement of strained bicyclic
ACS Paragon Plus Environment

Page 3 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
cyclopropane derivatives to access benzoxepines.18 Despite these progresses, the
conversion of vinyldiazo compounds into conjugated dienes is notably absent from
the literature.19 Herein, we reported a Pdꢀcatalyzed crossꢀcoupling reaction of aryl
iodides and cyclic vinyldiazo esters, which affords various 3ꢀarylꢀ2ꢀprones in good
yields. Moreover, an oxidative coupling of terminal alkynes with cyclic vinyldiazo
esters for the synthesis of 3ꢀalkynylꢀ2ꢀprones was also demonstrated, albeit with low
efficiency.
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. Synthesis of vinyldiazo ester 2
Initially, vinyldiazo ester 2 was prepared in 63% yield on 0.78 g scale by the
treatment of commercially available 3,5ꢀdihydropyranꢀ2ꢀone with pꢀABSA in the
presence of DBU (scheme 1).20 Then its coupling with 4ꢀiodotoluene 1a was
investigated. When the reaction was carried out in the presence of Pd2(dba)3/Xphos,
which is a general catalytic system for Pdꢀcatalyzed crossꢀcoupling reactions of diazo
compounds, product 3a was detected in 10% yield (table 1, entry 1). Switching the
ligand from Xphos to tri(2ꢀfuryl)phosphine in 1,4ꢀdioxane at room temperature led
to 3a in 22% yield (table 1, entry 2). However, the combination of Pd2(dba)3 with
strong electronꢀrich ligand such as PCy3 or P(tBu)3·HBF4 was ineffective (table 1,
entries 3 and 4). Pd(PPh3)2Cl2 was effective catalyst for the reaction, providing
2ꢀpyrone 3a in the yield of 35% (table 1, entry 5). Pleasingly, we found that the yield
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 23
1
2
3
4
5
6
7
8
9
was further increased to 90% when 5 mol% of Pd(PPh3)4 was employed (table 1,
entry 6). Reducing the catalytic loading to 2.5% started to have a negative impact on
the reactivity, resulting in an incomplete reaction (table 1, entry 7). The yield of 3a
decreased sharply when the reaction was carried out at higher temperature (table 1,
entries 8 and 9), which might be attributed to the fast decomposition of vinyldiazo
ester 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
Table 1. Cross-coupling reaction of 4-iodotoluene 1a and vinyldiazo ester 2 catalyzed by
various palladium catalysta
O
O
O
O
cat., base
H3C
I
H3C
+
N2
solvent, Ar, rt
1a
3a
2
entry
cat. (mol%)/ligand (mol%)
Pd2(dba)3 (2.5)/Xphos (10)
Pd2(dba)3 (2.5)/P(2ꢀfuryl)3 (10)
Pd2(dba)3 (2.5)/PCy3 (10)
T/oC
25
25
25
25
25
25
25
40
80
yield (%)b
10
1
2
3
4
5
6
7
8
9
22
trace
trace
35
Pd2(dba)3 (2.5)/P(tBu)3·HBF4 (10)
Pd(PPh3)2Cl2 (5)
Pd(PPh3)4 (5)
90
Pd(PPh3)4 (2.5)
65
Pd(PPh3)4 (5)
67
Pd(PPh3)4 (5)
31
i
a Reaction conditions: 4ꢀiodotoluene 1a (0.2 mmol), vinyldiazo ester 2 (1.3 equiv.), Pr2NH (3
equiv.) and catalyst in dry 1,4ꢀdioxane (2 mL) under argon for 24 h. b Yields were determined by
1H NMR using 1,3,5ꢀtrimethoxybenzene as the internal standard.
ACS Paragon Plus Environment

Page 5 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
The optimized conditions were then applied to the crossꢀcoupling of vinyldiazo
ester 2 with a series of aryl iodides. As shown in scheme 2, a number of functional
groups, including methyl (3a, 3m, 3n), tertꢀbutyl (3c), methoxy (3d),
trifluoromethoxy (3e), dioxyethylene (3k), ether (3j), F (3g), Cl (3h), Br (3i, 3p),
phenyl (3f), free amino (3o) and hydroxyl (3l), on the aryl moiety were tolerated well
under the standard conditions. The electronic properties of the substituents on the
paraꢀposition do not affect the efficacy of the reaction, for instance, both
4ꢀiodoanisole and ethyl 4ꢀiodobenzoate underwent the coupling with vinyldiazo ester
2 smoothly, affording the corresponding 2ꢀpyrones 3d and 3j in the yields of 79% and
90% respectively. Good yield was also achieved from the crossꢀcoupling of
metaꢀiodotoluene with vinyldiazo ester 2. Substrates bearing methyl, free amino, and
bormo group on the orthoꢀposition were effective, albeit generating the corresponding
products 3n-p with moderately high yields. It is noteworthy that a bromo substituent
on the aromatic ring, which usually undergoes oxidative addition with Pd(0) catalyst,
could survive under the standard conditions. The preservation of the bromo group in
2ꢀpyrones 3i and 3p might be attributed to the lower reactivity of bromobenzene, as
well as the low temperature of this reaction. It is also worth mentioning that
4ꢀiodophenol and 2ꢀiodoaniline could be employed to react with vinyldiazo ester 2
directly without the need of functional group protection. The reaction is not limited to
aryl iodides, as exemplified by the use of 1ꢀiodonaphthalene to generate
3ꢀnaphthylꢀ2ꢀpyrone 3q. We were pleased to find that 2ꢀiodothiophene was also
suitable for the reaction, providing the desire product 3r in 76% yield. However, the
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
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 23
1
2
3
4
5
6
7
8
9
coupling partner under present reaction conditions is limited to aryl iodides. When
aryl bromides or aryl triflates were employed, no coupling product was detected and
both starting materials remained unchanged.21
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. Pd-catalyzed cross-coupling of vinyldiazo ester with aryl iodidesa
a The reaction was carried out using aryl iodide 1 (0.2 mmol), vinyl diazo ester 2 (0.26 mmol), and
iPr2NH (3 equiv.) in the presence of Pd(PPh3)4 (5 mol%) in 2 mL of dry 1,4ꢀdioxane under argon
at room temperature. b Isolated yield.
ACS Paragon Plus Environment

Page 7 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
To demonstrate the practical usefulness of this reaction, the Pdꢀcatalyzed
crossꢀcoupling reaction of iodobenzene and vinyldiazo ester 2 has been carried out on
5 mmol scale. As shown in scheme 3, 0.594 g of desired 3ꢀphenylꢀ2ꢀpyrone 3b was
obtained in slightly diminished yield (69%) after 48 hours of reaction at room
temperature.
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. Gram-Scale Reaction
In 2011, Wang and coꢀworkers developed a palladiumꢀcatalyzed oxidative
crossꢀcoupling of terminal alkynes and diazo compounds for the synthesis of
conjugated enynes.22 However, vinyl diazo compounds have never been examined as
the substrates for this reaction. We thus sought to further investigate the formation of
3ꢀalkynylꢀ2ꢀpyrones by a similar Pdꢀcatalyzed oxidative coupling of terminal alkynes
and vinyldiazo ester 2. Our initial efforts to realize the transformation commenced
with the reaction of 2 with phenylacetylene using the optimized conditions in Wang’s
report, and the desired 3ꢀphenylethynylꢀ2ꢀpyrone 4a was isolated in 20% yield. To
improve the efficiency of the reaction, the effects of various ligands, bases, oxidants
and solvents were evaluated (see Table S1 in the Supporting Information). The yield
of 4a was increased to 39% with 1,4ꢀdioxane as the solvent in the presence of
iꢀ
Pd(OAc)2, P(tBu)3, BQ, and Pr2NEt. Unfortunately, the effort to further improve the
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 23
1
2
3
4
5
6
7
8
9
yield was unsuccessful. Different from Wang’s reaction that was carried out at 80 oC,
we found room temperature favored the formation of 4a, owing to the lower stability
of vinyl diazo ester 2. Next, other terminal alkynes including 4ꢀchlorophenylacetylene
and 4ꢀethynylanisole were examined, and their oxidative coupling with vinyldiazo
ester 2 gave the corresponding 3ꢀalkynylꢀ2ꢀpyrones 4b and 4c in the yields of 37%
and 32%, respectively (scheme 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
Scheme 4. Pd-catalyzed oxidative coupling of terminal alkynes with vinyldiazo
ester 1.
To demonstrate the synthetic application of 3ꢀsubstituted 2ꢀpyrones obtained by
present method, 3a was employed as the diene component in a Diels–Alder reaction
with diethyl maleate in the presence of 10% Pd/C. We were pleased to find that the
reaction gave the desired biphenyl 5 in 64% yield. The DꢀA reaction of 3j with
benzyne also occurred smoothly, providing naphthalene 6 in the yield of 78%
(scheme 5).
Scheme 5. Synthetic applications of 3-aryl-2-pyrones.
ACS Paragon Plus Environment

Page 9 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
EtO2C
CO2Et
CO2Et
CO2Et
10% Pd/C (2.5 equiv.)
3a
+
+
Me
dodecane, 200 oC
5, 64%
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
TMS
CsF (5 equiv.)
3j
EtO2C
MeCN, 100 oC
OTf
6, 78%
A plausible mechanism for this palladiumꢀcatalyzed crossꢀcoupling of aryl iodides
and vinyldiazo ester is shown in scheme 6. The oxidative addition of Pd(0) to
iodobenzene affords Pd(II) intermediate A, which would react with vinyldiazo ester to
give the palladium–carbene intermediate B. Migratory insertion of the phenyl group
into the carbenic carbon leads to η1ꢀallylpalladium complex C.14 Palladatropic
rearrangement of C to η3ꢀallylpalladium intermeidated D followed by
βꢀhydride
elimination regenerate the Pd(0) catalyst and give the 3ꢀphenylꢀ2ꢀpyrone product.16
Scheme 6. A plausible mechanism
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 23
1
2
3
4
5
6
7
8
9
In conclusion, we have developed an efficient synthetic method for the synthesis of
3ꢀarylꢀ2ꢀpyrones via Pdꢀcatalyzed crossꢀcoupling reactions of aryl iodides and vinyl
diazo ester. A wide range of functional groups were found that are able to tolerate the
reaction conditions. The synthetic applications of resulting 3ꢀarylꢀ2ꢀpyrones, as a
diene component in the Diels–Alder reactions, were demonstrated. Moreover, the
conversion of vinyl diazo ester to 3ꢀalkynylꢀ2ꢀpyrones by a palladiumꢀcatalyzed
oxidative coupling with terminal alkynes was also investigated. Because vinyl diazo
ester can be easily prepared from commercially available 3,5ꢀdihydropyranꢀ2ꢀone in
only one simple step, the present protocol provides a valuable synthetic route to
3ꢀsubstituted 2ꢀpyrones, suppressing the stoichiometric organometallic reagents that
used in previous methods.
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: Except for the synthesis of the starting materials, all reactions were
performed under argon atmosphere in a 10 mL microwave tube. 1,4ꢀDioxane was
dried over CaH2 before use. For chromatography, 200ꢀ300 mesh silica gel was
1
employed. H NMR and 13C NMR spectra were measured in CDCl3 on 400 MHz
nuclear magnetic resonance spectrometer. Chemical shifts (δ) were given in ppm,
referenced to the residual proton resonance of CDCl3 (7.26), to the carbon resonance
of CDCl3 (77.16). HRMS spectra were recorded on an electrospray ionization
quadrupole timeꢀofꢀflight (ESIꢀQꢀTOF) mass spectrometer. IR spectra are reported in
wave numbers, cm−1. Melting points were measured with a heating speed of 4 °C/min.
ACS Paragon Plus Environment

Page 11 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
Unless otherwise noted, materials obtained from commercial suppliers were used
without further purification.
7
8
9
General procedure for Pd-catalyzed cross-coupling reaction of aryl iodides and
vinyl diazo ester. A 10 mL microwave tube was charged with Pd(PPh3)4 (5 mol%),
aryl iodides (0.2 mmol) and vinyl diazo ester 2 (0.26 mmol) under argon atmosphere.
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
i
Then 2 mL of 1, 4ꢀdioxane and Pr2NH (3 equiv., 0.6 mmol) were added via syringe,
and the resulting solution was stirred at room temperature. After the reaction was
completed as monitored by TLC, the mixture was filtered through a short path of
silica gel, eluting with ethyl acetate. The volatile compounds were removed in vacuo
and the residue was purified by column chromatography to give the coupling
products.
12a
3-(p-tolyl)-2H-pyran-2-one (3a)
.
White solid (85%, 32 mg, eluent: petroleum
o
ether/ethyl acetate = 10/1), mp 116–117 C; IR (KBr, cmꢀ1) 3091, 2942, 1709, 1626,
1
1554, 1312, 1114, 824, 788, 551; H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 7.9 Hz,
2H), 7.47 (d, J = 3.6 Hz, 1H), 7.40 (d, J = 6.6 Hz, 1H), 7.22 (d, J = 7.8 Hz, 2H), 6.31
13
(t, J = 5.8 Hz, 1H), 2.37 (s, 3H). C NMR (101 MHz, CDCl3) δ 161.7, 150.5, 138.7,
138.7, 131.8, 129.2, 128.5, 128.1, 106.8, 21.3; EIꢀMS (m/z, relative intensity): 186
(M+, 75), 171 (17), 158 (30), 129 (100), 115 (80), 91 (7).
3-phenyl-2H-pyran-2-one (3b). 12a White solid (81%, 28 mg, eluent: petroleum
o
ether/ethyl acetate = 10/1), mp 104–105 C; IR (KBr, cmꢀ1) 3089, 2932, 1709, 1694,
1
1552, 1316, 1113, 783, 696, 550; H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 7.4 Hz,
2H), 7.53 – 7.47 (m, 1H), 7.47 – 7.33 (m, 4H), 6.34 (t, J = 5.8 Hz, 1H); 13C NMR
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 23
1
2
3
4
5
6
7
8
9
(101 MHz, CDCl3) δ 161.6, 150.9, 139.4, 134.7, 128.8, 128.7, 128.5, 128.3, 106.8;
EIꢀMS (m/z, relative intensity): 172 (M+, 34), 144 (30), 115 (100), 89 (23), 77 (2).
3-(4-(tert-butyl)phenyl)-2H-pyran-2-one (3c). White solid (84%, 38 mg, eluent:
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
petroleum ether/ethyl acetate = 10/1), mp 102–103 C; IR (KBr, cmꢀ1) 3088, 2966,
1
1700, 1624, 1556, 1342, 1111, 967, 783, 735, 568; H NMR (400 MHz, CDCl3) δ
7.60 (d, J = 8.0 Hz, 2H), 7.50 – 7.40 (m, 4H),, 6.33 (t, J = 5.8 Hz, 1H), 1.34 (s, 9H).
13C NMR (101 MHz, CDCl3) δ 161.7, 151.9, 150.5, 138.8, 131.8, 128.6, 127.9, 125.5,
106.9, 34.7, 31.3; HRMS (ESI) calcd. for C15H17O2 [(M + H)+] 229.1223, found:
229.1222.
3-(4-methoxyphenyl)-2H-pyran-2-one (3d). 12a White solid (79%, 32 mg, eluent:
petroleum ether/ethyl acetate = 10/1), mp 94–95 oC; IR (KBr, cmꢀ1) 3095, 2964, 1706,
1
1625, 1557, 1513, 1299, 1034, 834, 777, 553; H NMR (400 MHz, CDCl3) δ 7.61 (d,
J = 8.3 Hz, 2H), 7.46 (d, J = 4.4 Hz, 1H), 7.37 (d, J = 6.6 Hz, 1H), 6.93 (d, J = 8.3 Hz,
2H), 6.31 (t, J = 5.8 Hz, 1H), 3.82 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 161.8,
160.1, 150.2, 138.0, 129.5, 128.2, 127.1, 113.9, 106.9, 55.4; EIꢀMS (m/z, relative
intensity): 202 (M+, 100), 174 (13), 159 (74), 145 (25), 131 (65), 102 (43), 51 (20).
3-(4-(trifluoromethoxy)phenyl)-2H-pyran-2-one (3e). Pale yellow solid (86%, 44
mg, eluent: petroleum ether/ethyl acetate = 5/1), mp 76–77 C; IR (KBr, cmꢀ1) 3088,
o
1
2927, 1694, 1626, 1557, 1506, 1258, 1161, 849, 792, 558; H NMR (400 MHz,
CDCl3) δ 7.72 – 7.66 (m, 2H), 7.53 (dd, J = 5.1, 2.1 Hz, 1H), 7.45 (dd, J = 6.7, 2.1 Hz,
1H), 7.28 – 7.23 (m, 2H), 6.36 (dd, J = 6.7, 5.1 Hz, 1H); 19F NMR (377 MHz, CDCl3)
δ ꢀ57.77; 13C NMR (101 MHz, CDCl3) δ 161.4, 151.3, 149.5, 139.7, 133.3, 129.9,
ACS Paragon Plus Environment

Page 13 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
127.4, 120.9, 110.6 (q, JCꢀF = 257.6 Hz), 106.8; HRMS (ESI) calcd. for C12H8O3F3
[(M + H)+] 257.0420, found: 257.0418.
7
8
9
3-([1,1'-biphenyl]-4-yl)-2H-pyran-2-one (3f). White solid (83%, 41 mg, eluent:
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
petroleum ether/ethyl acetate = 10/1), mp 153–154 C; IR (KBr, cmꢀ1) 3091, 2923,
1
1695, 1626, 1552, 1405, 1344, 1094, 843, 780, 527; H NMR (400 MHz, CDCl3) δ
7.75 (d, J = 8.0 Hz, 2H), 7.64 (dd, J = 10.9, 8.5 Hz, 4H), 7.55 – 7.41 (m, 4H), 7.37 (t,
J = 7.2 Hz, 1H), 6.35 (t, J = 5.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 161.6, 150.8,
141.6, 140.5, 139.1, 133.6, 128.9, 128.7, 128.2, 127.7, 127.2, 127.2, 106.9; HRMS
(ESI) calcd. for C17H13O2 [(M + H)+] 249.0910, found: 249.0908.
3-(4-fluorophenyl)-2H-pyran-2-one (3g). Pale yellow solid (76%, 29 mg, eluent:
o
petroleum ether/ethyl acetate = 10/1), mp 123–124 C; IR (KBr, cmꢀ1) 3109, 3090,
1
1709, 1624, 1557, 1510, 1304, 1232, 845, 792, 553; H NMR (400 MHz, CDCl3) δ
7.63 (dd, J = 7.9, 5.7 Hz, 2H), 7.50 (d, J = 4.9 Hz, 1H), 7.41 (d, J = 6.6 Hz, 1H), 7.09
(t, J = 8.5 Hz, 2H), 6.34 (t, J = 5.8 Hz, 1H); 19F NMR (377 MHz, CDCl3) δ ꢀ112.61
(s); 13C NMR (101 MHz, CDCl3) δ 164.3, 161.7 (d, JCꢀF = 26.3 Hz), 150.9, 139.2,
130.7 (d, JCꢀF = 3.2 Hz), 130.2 (d, JCꢀF = 8.2 Hz), 127.7, 115.5 (d, JCꢀF = 21.6 Hz),
106.8; HRMS (ESI) calcd. for C11H8O2F [(M + H)+] 191.0503, found: 191.0502.
3-(4-chlorophenyl)-2H-pyran-2-one (3h). White solid (83%, 34 mg, eluent:
o
petroleum ether/ethyl acetate = 10/1), mp 117–118 C; IR (KBr, cmꢀ1) 3110, 3090,
1
1694, 1625, 1554, 1339, 1231, 1096, 837, 790, 550; H NMR (400 MHz, CDCl3) δ
7.59 (d, J = 8.4 Hz, 2H), 7.51 (dd, J = 4.9, 1.5 Hz, 1H), 7.43 (dd, J = 6.7, 1.3 Hz, 1H),
7.37 (d, J = 8.4 Hz, 2H), 6.38 – 6.30 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 161.3,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 23
1
2
3
4
5
6
151.2, 139.4, 134.8, 133.1, 129.6, 128.7, 127.5, 106.8; HRMS (ESI) calcd. for
C11H8O2Cl [(M + H)+] 207.0207, found: 207.0206.
7
8
9
3-(4-bromophenyl)-2H-pyran-2-one (3i).12a White solid (84%, 42 mg, eluent:
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
petroleum ether/ethyl acetate = 10/1), mp 114–115 C; IR (KBr, cmꢀ1) 3089, 1705,
1
1625, 1553, 1489, 1338, 1230, 1114, 1090, 830, 776, 550; H NMR (500 MHz,
CDCl3) δ 7.52 (s, 4H), 7.50 (dd, J = 5.1, 2.0 Hz, 1H), 7.43 (dd, J = 6.7, 2.1 Hz, 1H),
6.33 (d, J = 6.7, 5.1 Hz, 1H)；13C NMR (126 MHz, CDCl3) δ 161.2, 151.2, 139.4,
133.5, 131.6, 129.8, 127.4, 123.0, 106.8；EIꢀMS (m/z, relative intensity): 250 (M+, 28),
224 (15), 193 (28), 171 (69), 115 (100), 51 (9).
3-ethyl 4-(2-oxo-2H-pyran-3-yl)benzoate (3j). Pale yellow solid (90%, 44 mg,
eluent: petroleum ether/ethyl acetate = 5/1), mp 72–73 oC; IR (KBr, cmꢀ1) 3104, 2983,
1
1718, 1626, 1555, 1341, 1273, 1110, 1022, 784, 549; H NMR (400 MHz, CDCl3) δ
8.08 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.58 – 7.47 (m, 2H), 6.37 (dd, J =
6.6, 5.2 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 166.3, 161.1, 151.7, 140.2, 139.0, 130.6, 129.7, 128.2, 127.7, 106.8,
61.2, 14.4; HRMS (ESI) calcd. for C14H13O4 [(M + H)+] 245.0808, found: 245.0805.
3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2H-pyran-2-one (3k). White solid (70%,
32 mg, eluent: petroleum ether/ethyl acetate = 5/1), mp 147–148 C; IR (KBr, cmꢀ1)
o
3089, 2938, 2887, 1709, 1624, 1556, 1501, 1315, 1282, 1063, 885, 781, 700, 564; 1H
NMR (500 MHz, CDCl3) δ 7.46 (dd, J = 5.1, 2.0 Hz, 1H), 7.36 (dd, J = 6.7, 2.0 Hz,
1H), 7.22 (d, J = 2.2 Hz, 1H), 7.14 (dd, J = 8.4, 2.2 Hz, 1H), 6.88 (d, J = 8.5 Hz, 1H),
6.30 (dd, J = 6.7, 5.1 Hz, 1H), 4.28 – 4.24 (m, 4H); 13C NMR (126 MHz, CDCl3) δ
ACS Paragon Plus Environment

Page 15 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
161.6, 150.3, 144.3, 143.4, 138.3, 128.0, 128.0, 121.6, 117.3, 117.3, 106.8, 64.6, 64.4;
HRMS (ESI) calcd. for C13H11O4 [(M + H)+] 231.0652, found: 231.0648.
7
8
9
3-(4-hydroxyphenyl)-2H-pyran-2-one (3l). Pale yellow solid (75%, 28 mg, eluent:
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
petroleum ether/ethyl acetate = 3/1), mp 134–135 C; IR (KBr, cmꢀ1) 3400, 2921,
2851, 2361, 2343, 1691, 1611, 1556, 1513, 1270, 1121, 838, 778, 553; 1H NMR (500
MHz, Acetoneꢀd6) δ 8.60 (s, 1H), 7.64 (dd, J = 5.1, 2.0 Hz, 1H), 7.61 – 7.58 (m, 2H),
7.56 (dd, J = 6.7, 2.0 Hz, 1H), 6.90 – 6.86 (m, 2H), 6.45 (dd, J = 6.7, 5.1 Hz, 1H); 13C
NMR (126 MHz, Acetoneꢀd6) δ 161.9, 158.7, 151.4, 138.8, 130.4, 128.3, 127.1, 115.9,
107.6; HRMS (ESI) calcd. for C11H9O3 [(M + H)+] 189.0546, found: 189.0545.
3-(m-tolyl)-2H-pyran-2-one (3m). White solid (78%, 29 mg, eluent: petroleum
ether/ethyl acetate = 10/1), mp 89–90 C; IR (KBr, cmꢀ1) 3110, 3089, 2948, 1709,
o
1
1626, 1553, 1451, 1337, 1112, 785, 704, 585; H NMR (400 MHz, CDCl3) δ 7.52 –
7.39 (m, 4H), 7.30 (t, J = 7.6 Hz, 1H), 7.19 (d, J = 7.5 Hz, 1H), 6.33 (t, J = 5.8 Hz,
1H), 2.39 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 161.6, 150.7, 139.3, 138.1, 134.7,
129.6, 128.9, 128.8, 128.4, 125.4, 106.8, 21.6; HRMS (ESI) calcd. for C12H11O2 [(M
+ H)+] 187.0754, found: 187.0751.
12a
3-(o-tolyl)-2H-pyran-2-one (3n).
Pale yellow oil (51%, 19 mg, eluent:
petroleum ether/ethyl acetate = 10/1); IR (KBr, cmꢀ1) 3060, 2926, 1723, 1629, 1560,
1457, 1339, 1233, 967, 785, 754, 616; 1H NMR (400 MHz, CDCl3) δ 7.57 – 7.51 (m,
1H), 7.32 – 7.16 (m, 5H), 6.32 (t, J = 5.8 Hz, 1H), 2.27 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 161.3, 151.3, 141.4, 136.8, 134.8, 130.4, 130.3, 129.8, 128.8, 126.0, 106.4,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 23
1
2
3
4
5
6
20.0; EIꢀMS (m/z, relative intensity): 186 (M+, 45), 158 (29), 129 (100), 115 (54), 91
(6), 51 (26).
7
8
9
3-(2-aminophenyl)-2H-pyran-2-one (3o). Pale yellow solid (44%, 16 mg, eluent:
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
petroleum ether/ethyl acetate = 1/1), mp 145–146 C; IR (KBr, cmꢀ1) 3370, 2922,
1
2851, 1703, 1624, 1552, 1494, 1453, 967, 749, 617; H NMR (400 MHz, CDCl3) δ
7.57 (dd, J = 5.1, 2.1 Hz, 1H), 7.43 (dd, J = 6.7, 2.1 Hz, 1H), 7.20 (td, J = 8.0, 1.6 Hz,
1H), 7.09 (dd, J = 7.6, 1.4 Hz, 1H), 6.83 (td, J = 7.5, 1.1 Hz, 1H), 6.76 (dd, J = 8.0,
0.8 Hz, 1H), 6.37 (dd, J = 6.6, 5.1 Hz, 1H), 3.98 (s, 2H); 13C NMR (101 MHz, CDCl3)
δ 161.5, 151.2, 145.3, 142.8, 131.1, 130.1, 129.0, 122.0, 119.2, 117.5, 106.9; HRMS
(ESI) calcd. for C11H10O2N [(M + H)+] 188.0706, found: 188.0701.
3-(2-bromophenyl)-2H-pyran-2-one (3p). Pale yellow oil (69%, 35 mg, eluent:
petroleum ether/ethyl acetate = 10/1); IR (KBr, cmꢀ1) 3100, 2921, 1725, 1631, 1561,
1
1
1089, 968, 852, 781, 756, 658; H NMR (400 MHz, CDCl3) δ H NMR (400 MHz,
CDCl3) δ 7.68 – 7.61 (m, 1H), 7.56 (dd, J = 5.1, 2.1 Hz, 1H), 7.39 – 7.29 (m, 3H),
7.28 – 7.21 (m, 1H), 6.34 (dd, J = 6.6, 5.2 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ
160.7, 151.9, 142.3, 135.8, 133.2, 131.3, 130.2, 129.2, 127.5, 123.5, 106.2; HRMS
(ESI) calcd. for C11H8O2Br [(M + H)+] 250.9702, found: 250.9700.
3-(naphthalen-1-yl)-2H-pyran-2-one (3q). White solid (78%, 35 mg, eluent:
o
petroleum ether/ethyl acetate = 10/1), mp 144–145 C; IR (KBr, cmꢀ1) 3058, 1716,
1630, 1558, 1508, 1234, 1096, 951, 774, 550; 1H NMR (400 MHz, CDCl3) δ 1H NMR
(400 MHz, CDCl3) δ 7.92 – 7.87 (m, 2H), 7.75 – 7.69 (m, 1H), 7.61 (dd, J = 5.1, 2.1
Hz, 1H), 7.54 – 7.47 (m, 3H), 7.46 – 7.38 (m, 2H), 6.38 (dd, J = 6.5, 5.2 Hz, 1H); 13C
ACS Paragon Plus Environment

Page 17 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
NMR (101 MHz, CDCl3) δ 161.8, 151.6, 142.5, 133.7, 132.8, 131.4, 129.3, 128.8,
128.6, 127.6, 126.5, 126.1, 125.3, 125.2, 106.5; HRMS (ESI) calcd. for C15H11O2 [(M
+ H)+] 223.0754, found: 223.0750.
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-(thiophen-2-yl)-2H-pyran-2-one (3r). 12a Pale yellow oil (76%, 27 mg, eluent:
petroleum ether/ethyl acetate = 20/1); IR (KBr, cmꢀ1) 3103, 2921, 1710, 1617, 1543,
1425, 1236, 1086, 841, 771, 704, 687, 526; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J =
3.3 Hz, 1H), 7.66 – 7.60 (m, 1H), 7.50 – 7.43 (m, 1H), 7.38 (d, J = 5.0 Hz, 1H), 7.09
(t, J = 4.4 Hz, 1H), 6.38 – 6.30 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 160.4, 149.6
135.9, 135.1, 127.6, 126.7, 122.6, 106.8; EIꢀMS (m/z, relative intensity): 178 (M+, 96),
150 (29), 121 (100), 95 (6), 51 (10).
General procedure for Pd-catalyzed oxidative coupling reaction of terminal
alkynes and vinyl diaoester 1. A 10 mL microwave tube was charged with Pd(OAc)2
(5 mol%), P(tBu)3·HBF4 (20 mol%), BQ (0.4 mmol) and vinyl diaoester 2 (0.2 mmol)
i
under argon atmosphere. Then 2 mL of 1, 4ꢀdioxane, Pr2NEt (0.6 mmol) and
phenylacetylenes (0.3 mmol) were added via syringe. After the resulting solution was
stirred at room temperature for 24 h, the mixture was filtered through a short path of
silica gel, eluting with ethyl acetate. The volatile compounds were removed in vacuo
and the residue was purified by column chromatography to give the coupling
products.
3-(phenylethynyl)-2H-pyran-2-one (4a). Pale yellow solid (39%, 15.4 mg, eluent:
petroleum ether/ethyl acetate = 10/1), mp 83–84 oC; IR (KBr, cmꢀ1) 3405, 3108, 2921,
1
2217, 1725, 1615, 1543, 1489, 1333, 1110, 1037, 834, 755, 587, 526; H NMR (400
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 23
1
2
3
4
5
6
7
8
9
MHz, CDCl3) δ 7.61 – 7.48 (m, 4H), 7.39 – 7.31 (m, 3H), 6.28 (dd, J = 6.7, 5.2 Hz,
1H); 13C NMR (126 MHz, CDCl3) δ 160.6, 151.3, 144.5, 132.0, 129.2, 128.5, 122.3,
114.0, 106.4, 96.3, 83.2; HRMS (ESI) calcd. for C13H9O2 [(M + H)+] 197.0597, found:
197.0595.
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-chlorophenyl)ethynyl)-2H-pyran-2-one (4b). White solid (37%, 17 mg,
o
eluent: petroleum ether/ethyl acetate = 5/1), mp 154–155 C; IR (KBr, cmꢀ1) 3414,
3112, 2919, 1719, 1707, 1620, 1544, 1487, 1333, 1089, 1086, 824, 771, 604, 550; 1H
NMR (400 MHz, CDCl3) δ 7.57 – 7.50 (m, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.32 (d, J =
8.4 Hz, 2H), 6.29 (dd, J = 6.5, 5.4 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 160.4,
151.5, 144.7, 135.3, 133.2, 128.9, 120.8, 113.7, 106.4, 95.1, 84.1; HRMS (ESI) calcd.
for C13H8O2Cl [(M + H)+] 231.0207, found: 231.0213.
3-((4-methoxyphenyl)ethynyl)-2H-pyran-2-one (4c). Pale yellow oil (32%, 14.5
mg, eluent: petroleum ether/ethyl acetate = 5/1); IR (KBr, cmꢀ1) 3397, 3104, 2921,
2850, 2201, 1727, 1604, 1508, 1290, 1251, 1098, 1038, 833, 771, 546; 1H NMR (400
MHz, CDCl3) δ 7.52 – 7.46 (m, 4H), 6.90 – 6.85 (m, 2H), 6.26 (dd, J = 6.7, 5.2 Hz,
1H), 3.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 160.8, 160.4, 150.9, 143.8, 133.6,
114.4, 114.3, 114.2, 106.5, 96.6, 82.1, 55.5; HRMS (ESI) calcd. for C14H11O3 [(M +
H)+] 227.0703, found: 227.0703.
Synthesis of biphenyl 5. A mixture of 3a (0.2 mmol, 37 mg), diethyl maleate (1
mmol) and 10% Pd/C (93 mg) in 2 mL of dodecane was heated to 200 oC under argon.
After the reaction was completed, the mixture was filtered through a short path of
silica gel and eluted with petroleum ether to remove most of dodecane. Then the
ACS Paragon Plus Environment

Page 19 of 23
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
filtrate was collected by eluting with ethyl acetate. Biphenyl 5 was obtained as
colorless oil (64%, 40 mg) through purification by column chromatography with
petroleum ether/ethyl acetate (40/1) as the eluent. IR (KBr, cmꢀ1) 3438, 2983, 2927,
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
1720, 1516, 1450, 1366, 1266, 1149, 1064, 1016, 814, 761, 743, 563; H NMR (400
MHz, CDCl3) δ 7.97 (dd, J = 6.9, 2.2 Hz, 1H), 7.53 – 7.46 (m, 2H), 7.27 – 7.24 (m,
2H), 7.19 (d, J = 7.9 Hz, 2H), 4.36 (q, J = 7.1 Hz, 2H), 4.14 (q, J = 7.2 Hz, 2H), 2.38
(s, 3H), 1.37 (t, J = 7.1 Hz, 3H), 1.07 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ 168.9, 166.0, 140.7, 137.6, 136.6, 134.9, 134.1, 129.0, 129.0, 128.8, 128.7, 128.6,
61.6, 61.3, 21.3, 14.2, 13.8; HRMS (ESI) calcd. for C19H20O4Na [(M + Na)+]
335.1254, found: 335.1256.
Synthesis of ethyl 4-(naphthalen-1-yl)benzoate 6. A solution of 3j (0.2 mmol),
CsF (1 mmol) and 2ꢀ(trimethylsilyl)phenyl trifluoromethanesulfonate (1 mmol) in
anhydrous MeCN (2.0 mL) was heated to 100 °C. After the reaction was completed,
the mixture was cooled to room temperature and the solvent removed in vacuo. The
residue was purified by column chromatography to give product 6 as pale yellow oil
(78%, 43 mg). IR (KBr, cmꢀ1) 3435, 3044, 2980, 2929, 1716, 1609, 1396, 1367, 1271,
1177, 1100, 1021, 862, 802, 779, 705, 642, 569; 1H NMR (400 MHz, CDCl3) δ 8.26 –
8.15 (m, 2H), 7.97 – 7.84 (m, 3H), 7.63 – 7.58 (m, 2H), 7.57 – 7.50 (m, 2H), 7.49 –
7.42 (m, 2H), 4.47 (q, J = 7.1 Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 166.7, 145.6, 139.3, 133.9, 131.3, 130.2, 129.6, 129.5, 128.5, 128.4, 127.0,
126.4, 126.1, 125.7, 125.4, 61.1, 14.5; EIꢀMS (m/z, relative intensity): 276 (M+, 100),
231 (52), 202 (80), 176 (2), 101 (20), 88 (2).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 23
1
2
3
4
ASSOCIATED CONTENT
5
6
7
Supporting Information
8
9
Table S1, 1H and 13C NMR spectra of all products. This material is available free of
charge via the Internet at http://pubs.acs.org.
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
AUTHOR INFORMATION
Corresponding Author
Eꢀmail: zhoul39@mail.sysu.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to the funds from the National Basic Research Program of China
(2016YFA0602900), and the Natural Science Funds of Guangdong Province for
Distinguished Young Scholar (2016A030306029).
REFERENCES
1. a) Goel, A.; Ram, V. J. Tetrahedron 2009, 65, 7865. b) McGlacken, G. P.;
Fairlamb, I. J. S. J. Nat. Prod. 2005, 22, 369.
2. a) Turner, S. R.; Strohbach, J. W.; Tommasi, R. A.; Aristoff, P. A.; Johnson, P. D.;
Skulnick, H. I.; Dolak, L. A.; Seest, E. P.; Tomich, P. K.; Bohanon, M. J.; Horng,
M.ꢀM.; Lynn, J. C.; Chong, K.ꢀT.; Hinshaw, R. R.; Watenpaugh, K. D.; Janakiraman,
M. N.; Thaisrivongs, S. J. Med. Chem. 1998, 41, 3467. b) Thaisrivongs, S.;
Janakiraman, M. N.; Chong, K.ꢀT.; Tomich, P. K.; Dolak, L. A.; Turner, S. R.;
Strohach, J. W.; Lynn, J. C.; Horng, M.ꢀM.; Hinshaw, R. R.; Watenpaugh, K. D. J.
ACS Paragon Plus Environment

Page 21 of 23
The Journal of Organic Chemistry
1
2
3
4
Med. Chem. 1996, 39, 2400.
5
6
7
8
9
3. Fairlamb, I. J. S.; Marrison, L. R.; Dickinson, J. M.; Lu, F.ꢀJ.; Schmidt, J. P. Bioorg.
Med. Chem. 2004, 12, 4285.
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. Rao, P. N. P.; Amini, M.; Li, H.; Habeeb, A. G.; Knaus, E. E. J. Med. Chem. 2003,
46, 4872.
5. Marrison, L. R.; Dickinson, J. M.; Fairlamb, I. J. S. Bioorg. Med. Chem. Lett. 2002,
12, 3509.
6. Evidente, A.; Cabras, A.; Maddau, L.; Serra, S.; Andolfi, A.; Motta, A. J. Agric.
Food Chem. 2003, 51, 6957.
7. For reviews of DA cycloadditions of 2ꢀpyrones, see: a) Afarinkia, K.; Vinader, V.;
Nelson, T. D.; Posner, G. H. Tetrahedron 1992, 48, 9111. b) Komiyama, T.;
Takaguchi, Y.; Tsuboi, S. Synlett 2006, 124.
8. a) Kim, W.ꢀS.; Kim, H.ꢀJ.; Cho, C.ꢀG. Tetrahedron Lett. 2002, 43, 9015. b) Chung,
S.ꢀI.; Seo, J.; Cho, C.ꢀG. J. Org. Chem. 2006, 71, 6701. c) Tam, N. T.; Chang, J.; Jung,
E.ꢀJ.; Cho, C.ꢀG. J. Org. Chem. 2008, 73, 6258. d) Rueping, M.; Merino, E.; Sugiono,
E. Adv. Synth. Catal., 2008, 350, 2127. e) Tam, N. T.; Cho, C.ꢀG. Org. Lett. 2008, 10,
601. f) Tam, N. T.; Jung, E.ꢀJ.; Cho, C.ꢀG. Org. Lett. 2010, 12, 2012. g) Shin, H.ꢀS.;
Jung, Y.ꢀG.; Cho, H.ꢀK.; Park, Y.ꢀG.; Cho, C.ꢀG. Org. Lett. 2014, 16, 5718. h) Lee,
J.ꢀH.; Cho, C.ꢀG. Org. Lett. 2016, 18, 5126.
9. For recent reviews on the synthesis of substituted 2ꢀpyrones, see: a) Pratap, R.;
Ram, V. J. Tetrahedron 2017, 73, 2529. b) Lee, J. S. Mar. Drugs 2015, 13, 1581.
10. a) Niyomchon, S.; Audisio, D.; Luparia, M.; Maulide, N. Org. Lett. 2013, 15,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 23
1
2
3
4
5
6
2318. b) Souris, C.; Luparia, M.; Frébault, F.; Audisio, D.; Farès, C.; Goddard, R.;
Maulide, N. Chem. Eur. J. 2013, 19, 6566.
7
8
9
11. a) Rosen, J. D.; Nelson, T. D.; Huffman, M. A.; McNamara, J. M. Tetrahedron
Lett. 2003, 44, 365. b) Shi, X.; Leal, W. S.; Liu, Z.; Schrader, E.; Meinwald, J.
Tetrahedron Lett. 1995, 36, 71. c) Boulanger, W. A.; Katzenellenbogen, J. A. J. Med.
Chem. 1986, 29, 1159.
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
12. a) Frébault, F.; Oliveira, M. T.; Wöstefeld, E.; Maulide, N. J. Org. Chem. 2010,
75, 7962. b) Orimoto, K.; Tomizawa, T.; Namera, Y.; Oyama, H.; Niwa, T.; Nakada,
M. Heterocycles 2013, 87, 827. c) Liu, Z.; Meinwald, J. J. Org. Chem. 1996, 61, 6693.
d) Posner, G. H.; Harrison, W.; Wettlaufer, D. G. J. Org. Chem. 1985, 50, 5041. e)
Lee, J.ꢀH.; Kim, W.ꢀS.; Lee, Y. Y.; Cho, C.ꢀG. Tetrahedron Lett. 2002, 43, 5779. f)
Kim, W.ꢀS.; Kim, H.ꢀJ.; Cho, C.ꢀG. Tetrahedron Lett. 2002, 43, 9015.
13. Vijgen, S.; Nauwelaerts, K.; Wang, J.; Van Aerschot, A.; Lagoja, I.; Herdewijn, P.
J. Org. Chem. 2005, 70, 4591.
14. For some reviews, see: a) Barluenga, J.; Valdés, C. Angew. Chem. Int. Ed. 2011,
50, 7486. b) Xiao, Q.; Zhang, Y.; Wang, J. Acc. Chem. Res. 2013, 46, 236. c) Liu, Z.;
Wang, J. J. Org. Chem. 2013, 78, 10024. d) Xia, Y.; Zhang, Y.; Wang, J. ACS Catal.
2013, 3, 2586. e) Xia, Y.; Wang, J. Chem. Soc. Rev. 2017, 46, 2306.
15. a) Chen, S.; Wang, J. Chem. Commun. 2008, 4198. b) Xiao, Q.; Wang, B.; Tian,
L.; Yang, Y.; Ma, J.; Zhang, Y.; Chen, S.; Wang, J. Angew. Chem. Int. Ed. 2013, 52,
9305.
16. Barluenga, J.; TomásꢀGamasa, M.; Aznar, F.; Valdés, C. Adv. Synth. Catal. 2010,
ACS Paragon Plus Environment

Page 23 of 23
The Journal of Organic Chemistry
1
2
3
4
352, 3235.
5
6
7
8
9
17. Zhou, L.; Ye, F.; Zhang, Y.; Wang, J. Org. Lett. 2012, 14, 922.
18. Xie, Y.; Zhang, P.; Zhou, L. J. Org. Chem. 2016, 81, 2128.
19. For interception of η3ꢀallylpalladium intermediate by nucleophiles, see: a) Devine,
S. K. J.; Van Vranken, D. L. Org. Lett. 2008, 10, 1909. b) Zhou, P.ꢀX.; Luo, J.ꢀY.;
Zhao, L.ꢀB.; Ye, Y.ꢀY.; Liang, Y.ꢀM. Chem. Commun. 2013, 49, 3254. c) Ye, Y.ꢀY.;
Zhou, P.ꢀX.; Luo, J.ꢀY.; Zhong, M.ꢀJ.; Liang, Y.ꢀM. Chem. Commun. 2013, 49,
10190.
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
20. Bykowski, D.; Wu, K.ꢀH.; Doyle, M. P. J. Am. Chem. Soc. 2006, 128, 16038.
21. Aryl triflate can hardly be activated by Pd(PPh3)4 in dioxane at room temperature:
Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987, 109, 5478.
22. Zhou, L.; Ye, F.; Ma, J.; Zhang, Y.; Wang, J. Angew. Chem. Int. Ed. 2011, 50,
3510.
ACS Paragon Plus Environment