Palladium-Catalyzed One-Pot Highly Regioselective 6- Endo Cyclization and Alkylation of Enynoates: Synthesis of 2-Alkanone Pyrones

Article abstract of DOI:10.1021/acs.joc.8b02198

The Pd(II)-catalyzed one-pot tandem cyclization/alkylation reactions of enynoates with allylic alcohols have been demonstrated. In this reaction, an innovative protocol proceeded well through Pd-catalyzed intramolecular selective 6-endo cyclization, inser

Full text of DOI:10.1021/acs.joc.8b02198

Subscriber access provided by UNIV OF NEW ENGLAND
Article
Palladium-Catalyzed One-pot Highly Regioselective 6-Endo Cyclization
and Alkylation of Enynoates: Synthesis of 2-Alkanone Pyrones
Tanveer Ahmad, Sheng-Qi Qiu, Yun-He Xu, and Teck-Peng Loh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02198 • Publication Date (Web): 15 Oct 2018
Downloaded from http://pubs.acs.org on October 16, 2018
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 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 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.
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 15
The Journal of Organic Chemistry
1
2
3
4
5
6
Palladium-Catalyzed One-pot Highly Regioselective 6-Endo Cyclization and Alkylation of
Enynoates: Synthesis of 2-Alkanone Pyrones
Tanveer Ahmad,†Sheng-Qi Qiu,† Yun-He Xu*,† and Teck-PengLoh*,†,‡
7
8
9
†Department of Chemistry, University of Science and Technology of China, Hefei, China, 230026.
‡Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological
University, Singapore 637371.
10
11
12
13
14
15
16
17
18
19
20
21
Supporting Information
R3
O
R2
Pd(PhCN)2Cl2 (5 mol %)
Cu(OAc)2 (20 mol %)
R
OH
R
R2
+
R3
Cyclohexanone, O2, 30 °C
24-60 h
R1O2C
R = Alkyl, Aryl,
O
R3 = H, Me, Et, iPr, nBu, Ph
O
Cycloalkyl, Cycloalkenyl
R1 = Me, Et, nBu
R2 = H, Me, nPr, Ph, Ph-4-Cl
CH2-Ph, Ph-4-Br
ABSTRACT:Pd(II)-catalyzed one-pot tandem cyclization/alkylation reactions of enyanoates with allylic alcohols has been
demonstrated. In this reaction, an innovative protocol proceeded well through Pd-catalyzed intramolecular selective 6-endo
cyclization, insertion of allylic alcohols into the Pd-C bond of vinylpalladium species generated in situ, and β-hydrogen
elimination processes. This conversion provides a convenient and efficient methodology for the synthesis of 2-alkanone
pyronesin moderate to good yields.
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
coupling reactions between internal alkynes and allylic
alcohols have been developed (Scheme 1).17,13a,18Inspired by
the previous work, we became interested to discover the
INTRODUCTION
Pyrones are fundamental structural motifs in numerous
natural products and also versatile building blocks for the
application of vinyl-Pd species produced in situ during cross
1
coupling reaction19 for the synthesis of 2-alkanonepyrone
synthesis of various biologically active heterocyclic
compounds.2 As a result, considerable attention has been
devoted to preparing diverse pyrone compounds by employing
differentmethods.3 Owing to the limitation of traditional
methods, thegroupsof Rossi,4 Larock,5 and Burton, et al.6 have
developed more convenient approaches4b, 7by using different
electrophiles such as I2, NIS, ICl, PhSeCletcfor the cyclization
of enynoates to form pyrone derivatives. Recently,
Loh,8Pardasani, et al.9 studied the palladium-catalyzed
difunctionalization reaction of internal alkynes of
enynoatesvia6-endo cyclization and using different coupling
partners such as electron-deficient olefins to capture the
vinylpalladium species generated in situ.10Despite the fact
these methods made processes more facile and efficient, there
still need to develop a new methodology to broaden the
diversity of the pyrone compounds.11Therefore, we selected
allylic alcohol as an alkylating agent in order to develop a
convenient and dominant protocol for the synthesis of
multisubstitutedpyrones through the Heck-type C-C bond
formation.12Allylic alcohols exhibiting several advantages like
abundant in nature, easy preparation, inexpensive and as a
simple starting material offer synthetic applications.13 It has
been extensively utilized in transition metal catalyzed
reactions in three different ways such as nucleophilic
substitution of –OH groups,14formations of C=C bonds15 and
as a carbonyl alkylating agent.16 To the best of our knowledge,
rare examples of the palladium-catalyzed oxidative cross
compounds using enynoate.
Previous work:
DG
O
DG
OH
[Ru] or [Rh]/[O]
R'
R
R'
R
Me
DG
= directing group (CO2NR2, NHAc, Pyridine, Pyrazole)
Ph
O
[Pd]/[O]
OH
Me
R
R
N
H
NH2
O
O
OH
[Pd]/[O]
O
X
R
n
R1
O
R1
X= OH, OEt, OtBu
n = 0, 1, 2
R
n
R3
O
This work:
R2
R
OH
[Pd]/[O]
R
R2
+
R3
R1O2C
O
R = Alkyl, Aryl,
R3 = H, Me, Et, iPr, nBu, Ph
CH2-Ph, Ph-4-Br
O
Cycloalkyl, Cycloalkenyl
R1 = Me, Et, nBu
R2 = H, Me, nPr, Ph, Ph-4-Cl
Scheme 1.Reported Methods forAlkylationwith Allylic
Alcohols.
RESULTS AND DISCUSSION
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 15
d
The Z-enynoate1a and allylic alcohol 2a were employed as
model substrates. Recently, we found that the combination of
ofmethyl (Z)-5-phenylpent-2-en-4-ynoate(1a'). With use ofn-
butyl (Z)-5-phenylpent-2-en-4-ynoate (1a″).
1
2
Pd(II)
catalyst
with
an
oxidant
favored
such
cyclization/coupling reactions. So our investigation began
with 5 mol % of PdCl2, 10 mol % Cu(OAc)2 and O2 in DMSO
at 30°C (Chart 1). Pleasingly, the desired 5-(3-oxobutyl)-6-
phenyl-2H-pyran-2-one 3a could be obtained but in a low
yield (25%).For the optimization of the reaction condition, an
extensive screening of solvents, to our delight, the desired
product 3a was obtained in 62% yield in 2-butanone (Chart 1,
entry 7). Cyclohexanone was also an
effective solvent as compared to the other tested solvents, and
the product 3a was obtained in 68 % yield (entry 8). The
reaction was also run with various Pd(II) catalysts, except for
Pd(OAc)2 and Pd(dba)2 (entries 13, 14), other Pd(II) catalysts
gave comparable results. Next screening the combined oxidant
system such as Cu(OAc)2 with oxygen, CuCl2 with oxygen and
Cu(OAc)2 in the air could afford the desired product in
acceptable yield, while the silver salt, BQ, and K2S2O8 with
oxygen were not effective.After screening the reaction
conditions it was revealed that chlorine anion, oxidant acetate
anion, O2 (atm) and solvent as well had a significant influence
on the yield and efficiency of the reaction. Especially, a good
yield of the desired product was obtained when Pd(PhCN)2Cl2
and Cu(OAc)2 as an oxidant with O2 (atm) were applied in this
reaction. Moreover, it was found that higher temperature
decreased the product yield (entries 21).Finally, it was found
that increasing the oxidant loading to 20 mol% could afford
the desired product 3a in 76% yield (entry 9).
3
4
5
6
7
8
9
Chart 1. Optimization of Reaction Conditions.a,b
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
Me
Pd(PhCN)2Cl2 (5 mol %)
Cu(OAc)2 (20 mol %)
Ph
OH
Ph
O
+
Me
2a
EtO2C
1a
O
Cyclohexanone, O2, 30 °C
3a
O
entry catalyst (05 mol %)
oxidant (20 mol %)
solvent
temp (°C) time (h) yield (%)
25
PdCl2
Cu(OAc)2 (10) + O2 (1 atm) DMSO
24
30
32
30
36
24
32
36
24
26
36
32
36
36
36
30
30
30
24
24
24
1
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
50
40
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
PdCl2
Cu(OAc)2 (10) + O2 (1 atm) DMSO
2
<5
28
Cu(OAc)2 (10) + O2 (1 atm) CH3CN
3
Cu(OAc)2 (10) + O2 (1 atm) 1,4-Dioxane
Cu(OAc)2 (10) + O2 (1 atm) DCE
4
34
5
58
Cu(OAc)2 (10) + O2 (1 atm) Acetone
Cu(OAc)2 (10) + O2 (1 atm) 2-Butanone
Cu(OAc)2 (10) + O2 (1 atm) Cyclohexanone
Cu(OAc)2 (20) + O2 (1 atm) Cyclohexanone
Cu(OAc)2 (30) + O2 (1 atm) Cyclohexanone
Cu(OAc)2 (20) + O2 (1 atm) Cyclohexanone
Cu(OAc)2 (20) + O2 (1 atm) Cyclohexanone
Cu(OAc)2 (20) + O2 (1 atm) Cyclohexanone
Cu(OAc)2 (20) + O2 (1 atm) Cyclohexanone
6
Chart 3. Substrate Scope of Enynoate.a,b
62
7
68
8
Me
76
9
Pd(PhCN)2Cl2 (5 mol %)
Cu(OAc)2 (20 mol %)
R
R
O
OH
71
10
11
12
13
14
15
16
17
18
19
20
21
O
EtO2C
1a-1t
Me
2a
Cyclohexanone, O2, 30 °C
24-40 h
72
4a-4s
O
60
Pd(MeCN)2Cl2
Pd(OAc)2
Me Me
Me
Me
Me
N.R
N.R
17
O
O
O
O
Pd(dba)2
Me
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
BQ (20) + O2 (1 atm)
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
Cyclohexanone
O
O
O
Me
4c
71 % (40h)
O
4a
4b
3a
10
K2S2O8 (20) + O2 (1 atm)
CuCl2 (20) + O2 (1 atm)
Ag2O(20) + O2 (1 atm)
AgOAc(20) + O2 (1 atm)
O
O
O
O
O
74 % (28h)
70 % (30h)c
72 % (26h)
76 % (24h)
74 % (30h)c
53
MeO
Me
Me
Cl
N.R
N.R
49
Me
O
Me
O
O
O
O
4f
67 % (28h)
Cu(OAc)2 (20) + Air (1 atm) Cyclohexanone
Cu(OAc)2 (20) + O2 (1 atm) Cyclohexanone
O
O
4d
4g
O
53 % (36h)
64
4e
O
65 % (36h)
O
O
50 % (40h)
aReaction conditions: A mixture of1a (0.2 mmol), 2a (0.6
mmol, 3 equiv), Pd(PhCN)2Cl2 (0.01 mmol, 0.05 equiv),
Cu(OAc)2 (0.04 mmol, 0.2 equiv), and oxidant in solvent
(1mL) were stirred at 30 °C for 24 h. bIsolated yields.
MeO2C
Me
Me
Br
Me
Me
O
O
O
O
O
O
O
O
4i
4h
4j
4k
O
71 % (32h)
O
50 % (40h)
49 % (40h)
O
O
64 % (32h)
Chart 2. Scope of Allylic Alcohol
Me
Me
Me
BnO
Me
R3
n-Bu
O
O
O
O
O
Pd(PhCN)2Cl2 (5 mol %)
Cl
NC
Ph
OH
Ph
O
Cu(OAc)2 (20 mol %)
O
4l
O
O
O
+
4o
54 % (32h)
4n
4m
R3
EtO2C
Cyclohexanone, O2, 30 °C
67 % (30h)
O
56 % (32h)
O
O
O
O
O
61 % (32h)
3a-3h
2
1a
Me
Me
Me
Me
O
R3 = H, Me, Et, iPr, nBu, Ph
CH2-Ph, Ph-4-Br
AcO
O
O
O
S
N
Me
4s
61 % (36h)
O
O
O
O
4p
4q
46 % (34h)
4r
48 % (30h)
iPr
nBu
O
Et
58 % (32h)
Me
O
O
O
Ph
O
Ph
O
Ph
O
Ph
O
O
O
aReaction conditions: Unless otherwise specified, all the
reactions were carried out with 1 (0.2 mmol), 2a (0.6 mmol, 3
equiv),Pd(PhCN)2Cl2 (0.01 mmol, 0.05 equiv), Cu(OAc)2
(0.04 mmol, 0.2 equiv), and O2 (1 atm) in cyclohexanone(1
O
O
O
3b
3c
3a
3d
O
O
65 % (30h)
55 % (36h)
72 % (24h)
76 % (24h)
72 % (36h)c
74 % (40h)d
Br
Ph
Bn
H
b
mL) were stirred at 30 °C for 24-40 h. Isolated yields.cThe
Ph
O
Ph
O
Ph
O
Ph
O
reaction was run on 0.5 mmol scale.
O
O
O
O
3e
64 % (38h)
O
3g
O
42 % (40h)
3f
O
3h
O
After concluding optimization of the reaction conditions, we
next probed the generality of different allylic alcohols as
coupling partner and the results are summarized in Chart 2.
The but-3-en-2-ol (2a) was first investigated with
differentenynoates(1a, 1a' and 1a″).Among them, the
enynoate1agave the corresponding product (3a) in good yield
50 % (32h)
55 % (40h)
aReaction conditions: Unlessotherwise specified, the reactions
were performed with1a (0.2 mmol), 2 (0.6 mmol, 3 equiv),
Pd(PhCN)2Cl2 (0.01 mmol, 0.05 equiv), Cu(OAc)2 (0.04 mmol,
0.2 equiv), and O2 (1 atm) in cyclohexanone(1 mL) were
c
stirred at 30 °C for 24-40 h. bIsolated yields. With use
2
ACS Paragon Plus Environment

Page 3 of 15
The Journal of Organic Chemistry
with short reaction time.Then the enynoate1awas selected as Pd(PhCN)2Cl2 (0.01 mmol, 0.05 equiv), Cu(OAc)2 (0.04
1
2
3
4
5
6
7
8
substrate for the synthesis of products(3b-3h).When an alkyl
chain was increased and/or branched on allylic alcohols,the
corresponding products were obtained (3b-3d) in moderate to
good yield. Additionally, the phenyl and benzyl group were
well tolerated to afford the desired products3e and 3f in good
yields, respectively. Furthermore, the bromo substituted
phenyl group was transformed into the product (3g) in 42%
yield. It shows that the steric effect is very significant as it
prolongs the reaction time to obtain the desired products
(Chart 2, 3e-3f, 3g). Finally, the simplest allyl alcohols were
successfully converted into an active aldehyde (3h) in 50 %
yield.
We next tested the substrate scope of this highly
regioselective 6-endo cyclization and alkylation (Chart 3). In
general, the phenyl ring bearing methyl group at meta and
para-position could afford the desired product in moderate to
good yield (4a-4b). However, the presence of a methyl group
at the ortho-position of the aryl ring prolonged the reaction
time due to steric effect (4c). The electron-donating group
substituted phenyl ring and bulky substituents such as
naphthyl and fluorenyl all favored this transformation under
the standard conditions (Chart 3, 4d-4f). The substrates with
the electron-withdrawing group or halides on the phenyl ring
were also compatible with the reaction system by prolonging
the reaction time (4g-4i). Additionally, the cyclohexyl,
cyclohexenyl, and aliphatic substituted enynoates were all well
tolerated. The corresponding products obtained in moderate to
good yields (4j-4q). Moreover, thioenyl and indole-substituted
enynoate were utilized with the allylic alcohols, the desired
products 4r and 4s could be obtained in 58% and 61% yield,
respectively.
mmol, 0.2 equiv), and O2 (1 atm) in cyclohexanone(1mL)
c
were stirred at 30 °C for 32-60 h. bIsolated yields. The
reaction was run on 0.5 mmol scale.
Finally, we proceeded to examine the substrates with β-
substituent of enynoates achieving good to excellent yield
(Chart 4). It was observed that the substrates with methyl or
propyl at β-position led to the corresponding product in
highyield (70%-82%, 5a-5f).The structure 5a was clearly
confirmed by the X-ray crystallography (CCDC: 1836656,
Chart 4). In addition, a series of substrates with a phenyl group
at β-position were also converted to the desired products in
moderate to good yields (5g-5l). In this case, due to the
bulkiness of the phenyl group at theβ-position, prolonging the
reaction time is necessary.
The proposed reaction mechanism for the Pd(II)-
catalyzed regioselective 6-endo cyclization and alkylation of
enynoate is illustrated in Scheme 2.20 First, the carbonyl
oxygen of ester moiety attacks the Pd(II) activated alkyne of
enyanoate to afford the vinylpalladium intermediate A, via6-
endo cyclization. Subsequently, an allylic alcohol will insert
into the C-Pd bond of vinylpalladium species to form
thealkylpalladium species C, which is followed by β-hydrogen
elimination to form the enol product D and then produces the
final product 3a. The released Pd(0) species will be oxidized
into Pd(II) in the presence of the oxidants Cu(OAc)2, O2 and
utilized in the next catalytic cycle.
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
R
O
R3
1
O2
EtO2C
Cu(I)
3a
PdX2
R
O
Cu(II)
PdX2
O
Chart 4. Scope of β-substituted Enynoate.a,b
O
O
Me
R
HPdX
Pd(0)
R2
Pd(PhCN)2Cl2 (5 mol%)
Cu(OAc)2 (20 mol%)
R
OH
HO
R3
O
Et
R
R2
+
Me
2a
Cyclohexanone, O2, 30 °C
32-60 h
EtO2C
O
O
5a-5l
1aa-1al
R2 = H, Me, nPr, Ph, Ph-4-Cl
R
H
H
O
-H elimination
O
D
O
R3
O
Me
O
O
Me
Me
EtOH
+
HX
HO
H
PdX
PdX
Me
R
R
O
O
R3
5b
81 % (36h)
5a
O
O
OH
O
82 % (32h)
79 % (32h)c
A
O
O
C
R3
PdX
O
O
O
Me
Me
O
Me
O
Me
Me
O
O
Me
Me
OH
R
Cl
MeO
MeOC
O
B
n-Bu
5c
Me
O
O
O
O
5e
5f
5d
O
O
O
72 % (36h)
74 % (40h)
75 % (45h)
70 % (45h)
Scheme 2. Proposed Mechanism
O
Me
Ph
Me
Ph
O
Me
O
Me
Ph
Cl
MeO
CONCLUSION
n-Bu
Ph
In conclusion, we have reportedthepalladium catalyzed
highly regioselective 6-endo cyclization and alkylation. The
corresponding products were obtained in good yields. This
work provides a simple and general approach for the synthesis
of highly substituted pyronealkanones from readily available
nonbiased allylic alcoholsunder mild and efficient reaction
condition.
O
O
O
5i
O
5j
5h
5g
O
78 % (46h)
75 % (46h)
Me
55 % (60h)
O
O
79 % (46h)
O
O
Me
5l
O
Cl
MeOC
Ph
Ph
O
O
5k
60 % (60h)
63 % (60h)
O
O
aReaction conditions: Unless otherwise specified, the reacions
were performed with1(0.2 mmol), 2a (0.6 mmol, 3 equiv),
EXPERIMENTAL SECTION
General Information
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 15
Pd(PhCN)2Cl2, Cu(OAc)2 and some of allylic alcohols were room temperature and diluted with Et2O(10 mL). Then the
1
2
3
4
5
6
7
8
purchased from commercial suppliers used as received unless
otherwise noted. All Commercial solvents and reagents were
employed without further purification. Reactions were
monitored through analytical thin layer chromatography (SiO2
60 F-254 plates). The spots visualization were performed
under UV radiation (254 nm), further visualization was
possible using a basic solution of potassium permanganate.
Flash chromatography was carried out using 200-300 mesh
silica gel (SiO2 60) with distilled solvents. Proton nuclear
magnetic resonance (1H NMR) and Carbon nuclear magnetic
resonance (13C NMR) spectra were recorded at 25 ºC on
Bruker Advance 400M NMR spectrometers. Chloroform-d
was used as the solvent and Si(CH3)4(TMS) as an internal
solution was washed with saturated NH4Cl (10 mL) twice. The
aqueous phase was extracted with Et2O (10 mL). The
combined organic phase was dried over anhydrous Na2SO4
and concentrated under reduced pressure to give the crude
product which was purified by flash column chromatography
using petroleum ether/ethyl acetate (97:3 - 95:5) as eluent
afforded the desired products (1aa and 1ac-1af).The ethyl (Z)-
3-iodohex-2-enoate (P5) was used to synthesis the 1ab.The
1ag-1ak were synthesized by using ethyl (Z)-3-iodo-3-
phenylacrylate(P6) while the ethyl (Z)-3-(4-chlorophenyl)-3-
iodoacrylate (P7)was used to prepare the 1al.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
The H NMR, 13C NMR, HRMS and FTIRcharacterization
dataof newly synthesized β-substituted(Z) enynoates (1ad,
1ae, 1af, 1ai, 1aj, 1ak, 1al) are given below (for spectral data
see supporting information), while the β-substituted(Z)
enynoates (1aa-1ac, 1agand1ah) are previously reported in
literatures. The P4, P5, P6 and P7 were prepared according to
the reported literature.All the Allylic alcohols wereprepared
according to the reported literatures.22(2c-2h).
1
standard. Chemical shifts for H NMR spectra are reported as
δ in units of parts per million (ppm) downfield from TMS (δ
0.00 ppm) and relative to the signal of chloroform-d (δ 7.260
ppm, singlet). Multiplicities are recorded as: s (singlet); d
(doublet); t (triplet); q (quartet); dd(doublets of doublet); m
(multiplets). Coupling constants are expressed as a J value in
Hz. 13C NMR are reported as δ in units of parts per million
(ppm) downfield from TMS (δ 0.00 ppm) and relative to the
signal of chloroform-d (δ 77.03 ppm, triplet). Notable,
splitting signals of the 13C nucleus was difficult to differentiate
and 13C NMR signals were reported as a singlet. High
resolution mass spectral analysis (HRMS) spectra were
recorded on Water XEVO-G2 Q-TOF (Waters Corporation).
IR spectra were recorded on a FTIR spectrophotometer.
Preparation of (Z)-Enynoates:
Ethyl(Z)-5-(4-chlorophenyl)-3-methylpent-2-en-4-
ynoate (1ad). To a mixture of ethyl (Z)-3-iodobut-2-enoate
(P4) (1.2 g, 5 mmol, 1.0 eq.), Pd(PPh3)2Cl2 (35.6 mg, 0.05
mmol, 1.0 mol%), CuI (4.9 mg, 0.025 mmol, 0.5 mol%), and
Et3N (20 mL) was added the 1-chloro-4-ethynylbenzene (0.75
g, 5.5 mmol, 1.1 equiv.). The mixture was stirred for 18 h at
50 °C under an inert argon atmosphere and dealt with
according to the similar Method B to give the product 1ad
(0.87 g, 3.5 mmol, 70 % yield) as light green oil;Rf= 0.45
(petroleum ether/ethyl acetate = 95:5);FTIR (KBr neat)
υmax2204, 1722, 1620, 1489,1188 cm-1;1H NMR (400 MHz,
CDCl3): δ 7.47 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H),
6.05 (s, 1H), 4.22 (q, J = 7.2 Hz, 2H), 2.13 (s, 3H), 1.30 (t, J =
7.1 Hz, 3H) ppm;13C{1H}NMR (101 MHz, CDCl3):δ165.0,
135.1, 134.3, 133.2, 128.7, 124.7, 121.2, 98.8, 89.2, 60.1,
25.1, 14.3 ppm;HRMS (EI): m/z Calcd. for C14H13ClO2Na
[M+Na]+: 271.0502, found: 271.0499.
(Z)-Enynoates1a-1t were prepared according to the reported
literature .2, 4a, 8, 21
MethodA: In an oven dried 50 mL round bottom flask with a
mixture of (Z)-ethyl 3-iodoacrylate(P1)(1.13 g, 5 mmol, 1.0
eq.), Pd(PPh3)2Cl2 (35.6 mg, 0.05 mmol, 1.0 mol%), CuI (4.9
mg, 0.025 mmol, 0.5 mol%), and Et3N (20 mL) was added the
corresponding alkyne (5.5 mmol, 1.1 equiv.). The mixture was
stirred at 50 °C under an inert argon atmosphere until the
starting material was completely disappeared (monitored by
TLC). Then the reaction mixture was cooled to room
temperature and diluted with diethyl ether (Et2O, 10 mL).
Then the solution was washed with saturated ammonium
chloride (NH4Cl, 10 mL) twice. The aqueous phase was
extracted with Et2O (10 mL). The combined organic phase
was dried over anhydrous sodium sulfate (Na2SO4) and
concentrated under reduced pressure to give the crude product,
which was purifiedby flash column chromatography using
petroleum ether/ethyl acetate (97:3) as eluent afforded the
desired products (1a-1t).
Ethyl(Z)-5-(4-methoxyphenyl)-3-methylpent-2-en-4-
ynoate (1ae).To a mixture of ethyl (Z)-3-iodobut-2-enoate (P4)
(1.2 g, 5 mmol, 1.0 eq.), Pd(PPh3)2Cl2 (35.6 mg, 0.05 mmol,
1.0 mol%), CuI (4.9 mg, 0.025 mmol, 0.5 mol%), and Et3N
(20 mL) was added the 1-ethynyl-4-methoxybenzene (0.73 g,
5.5 mmol, 1.1 equiv.). The mixture was stirred for 18 h at
50 °C under an inert argon atmosphere and dealt with
according to the similar Method B to give the product
(1ae)(0.91 g, 3.7 mmol, 74% yield) as light brown oil;Rf=
0.44(petroleum ether/ethyl acetate = 95:5);FTIR (KBr neat)
υmax2197, 1719, 1616, 1511, 1194, 825 cm-1;1H NMR (400
MHz, CDCl3): δ 7.49 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.4 Hz,
2H), 5.99 (s, 1H), 4.23 (q, J = 7.1 Hz, 2H), 3.83 (s, 3H), 2.13
(s, 3H), 1.31 (t, J = 7.0 Hz, 3H) ppm; 13C{1H}NMR (101
MHz, CDCl3): δ 165.3, 160.3, 135.0, 133.5, 123.5, 114.9,
114.0, 100.8, 87.6, 60.0, 55.3, 25.3, 14.4 ppm; HRMS (EI):
m/z Calcd. for C15H17O3 [M+H]+: 245.1178, found: 245.1182.
Ethyl(Z)-5-(4-acetylphenyl)-3-methylpent-2-en-4-
ynoate (1af).To a mixture of ethyl (Z)-3-iodobut-2-enoate (P4)
(1.2 g, 5 mmol, 1.0 eq.), Pd(PPh3)2Cl2 (35.6 mg, 0.05 mmol,
1.0 mol%), CuI (4.9 mg, 0.025 mmol, 0.5 mol%), and Et3N
(20 mL) was added the 1-(4-ethynylphenyl)ethan-1-one (0.79
g, 5.5 mmol, 1.1 equiv.). The mixture was stirred for 18 h at
50 °C under an inert argon atmosphere and dealt with
according to the similar Method B to give the product
The Enynoate1a' and 1a″were prepared by using (Z)-methyl
3-iodoacrylate (P2) and(Z)-n-butyl 3-iodoacrylate (P3)
respectivelyaccording to theMethod A.The P1, P2andP3 were
also prepared according to the reported literatures.2
Preparation of β-substituted(Z)-Enynoates:
Theβ-substituted(Z) enynoates(1aa-1al) were prepared
according tothe reported literatures.2, 4a, 8, 21
Method B:In an oven dried 50 mL round bottom flask with a
mixture of ethyl (Z)-3-iodobut-2-enoate (P4),(1.13 g, 5 mmol,
1.0 eq.), Pd(PPh3)2Cl2 (35.6 mg, 0.05 mmol, 1.0 mol%), CuI
(4.9 mg, 0.025 mmol, 0.5 mol%), and Et3N (20 mL) was
added the corresponding alkyne (5.5 mmol, 1.1 equiv.). The
mixture was stirred at 50 °C under an inert argon atmosphere
until the starting material was completely disappeared
(monitored by TLC). Then the reaction mixture was cooled to
4
ACS Paragon Plus Environment

Page 5 of 15
The Journal of Organic Chemistry
(1af)(0.92 g, 3.6mmol, 72 %yield) as light yellow solid;Rf=
ppm; HRMS (EI): m/z Calcd. for C21H19O3 [M+H]+: 319.1334,
found: 319.1335.
Ethyl(Z)-3-(4-chlorophenyl)-5-phenylpent-2-en-4-
1
2
3
4
5
6
7
8
0.40 (petroleum ether/ethyl acetate = 95:5); FTIR (KBr neat)
υmax2204, 1720, 1684, 1616, 1556, cm-1;1H NMR (400 MHz,
CDCl3): δ 7.93 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 8.1 Hz, 2H),
6.08 (s, 1H), 4.23 (q, J = 7.1 Hz, 2H), 2.61 (s, 3H), 2.15 (s,
3H), 1.31 (t, J = 7.1 Hz, 3H) ppm; 13C{1H}NMR (101 MHz,
CDCl3): δ 197.3, 164.9, 136.7, 134.0, 132.1, 128.2, 127.6,
125.5, 98.7, 91.1, 60.2, 26.7, 25.0, 14.3 ppm;HRMS (EI): m/z
Calcd. for C16H16O3Na [M+Na]+: 279.0997, found: 279.1001.
Ethyl(Z)-5-(4-chlorophenyl)-3-phenylpent-2-en-4-
ynoate (1al).To a mixture of ethyl (Z)-3-(4-chlorophenyl)-3-
iodoacrylate (P7) (1.7 g, 5 mmol, 1.0 eq.), Pd(PPh3)2Cl2 (35.6
mg, 0.05 mmol, 1.0 mol%), CuI (4.9 mg, 0.025 mmol, 0.5
mol%), and Et3N (20 mL) was added the ethynylbenzene (0.56
g, 5.5 mmol, 1.1 equiv.). The mixture was stirred for 24 h at
50 °C under an inert argon atmosphere and dealt with
according to theMethod B to give the product1al(0.90 g, 2.90
mmol, 58 % yield) as brown solid;Rf= 0.39(petroleum
ether/ethyl acetate = 95:5);FTIR (KBr neat) υmax2202, 1719,
1601, 1563, 1490, 1093 cm-1;1H NMR (400 MHz, CDCl3): δ
7.74-7.71 (m, 2H), 7.64-7.60 (m, 2H), 7.41-7.37 (m, 5H), 6.56
(s, 1H), 4.30 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H) ppm;
13C{1H} NMR (101 MHz, CDCl3): δ 165.2, 136.0, 135.6,
135.1, 132.1, 131.5, 130.5, 129.4, 129.1, 128.9, 128.5, 128.3,
127.9, 122.9,122.5, 102.4,86.5, 60.5, 14.4 ppm; HRMS (EI):
m/z Calcd. for C19H16ClO2 [M+H]+: 311.0839, found:
311.0836.
Procedure forthe synthesis of2-alkanone pyrones(3a-3h),
(4a-4s), (5a-5l). An oven dried 10 mL schlenk tube charged
with a stir bar, cyclohexanone (1.0 mL) was added to a
mixture of Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) under O2
atmosphere. The mixture was stirred for 5 minutes and then
enynoate1(0.2 mmol, 1.0 equiv.) and corresponding allylic
alcohols2 (0.6 mmol, 3.0 equiv.) were subsequently added to
the mixture. The reaction mixture was stirred at 30 °C until the
starting material 1 was completely disappeared (Monitored by
TLC). The reaction mixture was diluted with ethyl acetate and
washed with water (10 mL × 2) and brine (5 mL). The organic
layer was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column chromatography on
silica gel using as eluent petroleum ether/ethyl acetate (8:2 -
7:3) to afford the corresponding 2-alkanones pyrone.
9
ynoate (1ai).To
a
mixture of ethyl (Z)-3-iodo-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
phenylacrylate(P6) (1.5 g, 5 mmol, 1.0 eq.), Pd(PPh3)2Cl2 (35.6
mg, 0.05 mmol, 1.0 mol%), CuI (4.9 mg, 0.025 mmol, 0.5
mol%), and Et3N (20 mL) was added the 1-chloro-4-
ethynylbenzene (0.75 g, 5.5 mmol, 1.1 equiv.). The mixture
was stirred for 24 h at 50 °C under an inert argon atmosphere
and dealt with according to the similar Method Bto give the
product (1ai) (0.93 g, 2.96 mmol, 62 % yield) as brown
solid;Rf=0.39(petroleum ether/ethyl acetate = 95:5);FTIR
(KBr neat) υmax2192, 1720, 1609,1559, 1497, 1101 cm-1;1H
NMR (400 MHz, CDCl3): δ 7.79-7.74 (m, 2H), 7.56 (d, J = 8.4
Hz, 2H), 7.44-7.41 (m, 3H), 7.35 (d, J = 8.4 Hz, 2H), 6.60 (s,
1H), 4.30 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H) ppm;
13C{1H}NMR (101 MHz, CDCl3): δ 165.3, 137.0, 136.1,
135.4, 133.3, 130.0, 128.8, 128.7, 127.2, 123.1, 121.2, 100.7,
87.8, 60.5, 14.4 ppm; HRMS (EI): m/z Calcd. for C19H15ClO2
[M+H]+: 311.0839, found: 311.0840.
Ethyl(Z)-5-(4-methoxyphenyl)-3-phenylpent-2-en-4-
ynoate (1aj). To
a
mixture of ethyl (Z)-3-iodo-3-
phenylacrylate(P6) (1.5 g, 5 mmol, 1.0 eq.), Pd(PPh3)2Cl2 (35.6
mg, 0.05 mmol, 1.0 mol%), CuI (4.9 mg, 0.025 mmol, 0.5
mol%), and Et3N (20 mL) was added the 1-ethynyl-4-
methoxybenzene (0.73 g, 5.5 mmol, 1.1 equiv.). The mixture
was stirred for 24 h at 50 °C under an inert argon atmosphere
and dealt with according to the similar Method B to give the
product(1aj) (1.03 g, 3.36mmol, 7% yield) as light brown
solid;Rf = 0.39(petroleum ether/ethyl acetate = 95:5);FTIR
(KBr neat) υmax2191, 1715, 1608, 1561, 1511, 1160, 771 cm-
1;1H NMR (400 MHz, CDCl3): δ 7.81-7.77 (m, 2H), 7.58 (d, J
= 8.4 Hz, 2H), 7.43-7.40 (m, 3H), 6.90 (d, J = 8.5 Hz, 2H),
6.54 (s, 1H), 4.30 (q, J = 7.1 Hz, 2H), 3.84 (s, 3H), 1.36 (t, J =
7.1 Hz, 3H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ 165.6,
160.5, 137.4, 136.7, 133.8, 129.8, 128.6, 127.2, 121.8, 114.8,
114.1, 102.8, 86.2, 60.3, 55.4, 14.4 ppm; HRMS (EI): m/z
Calcd. for C20H19O3 [M+H]+: 307.1334, found: 307.1337.
Ethyl(Z)-5-(4-acetylphenyl)-3-phenylpent-2-en-4-
5-(3-oxobutyl)-6-phenyl-2H-pyran-2-one(3a)
Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) andPd(PhCN)2Cl2
(3.8 mg, 0.01 mmol, 5 mol%) wereadded in cyclohexanone
(1.0 mL) under O2 atmosphere.Afterstirring for5 minutes,1a
(40 mg, 0.2 mmol, 1.0 equiv.) and 3-buten-2-ol2a (43 mg, 0.6
mmol, 3.0 equiv.) were subsequently added to the mixture.
The system was stirring at 30 °Cfor 24 h.The reaction mixture
was diluted with ethyl acetate washed with water and brine.
The organic layer was dried over Na2SO4, filtered,
concentrated in vacuo. The residue was purified by flash
column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2- 7:3) to afford the pure
product(3a)as a light green oil (37 mg, 0.15 mmol, Yield:
76%);Rf= 0.44(petroleum ether/ethyl acetate = 7:3);FTIR (KBr
neat) υmax1725, 1706,1631, 1540cm-1;1H NMR (400 MHz,
CDCl3): δ 7.54-7.50 (m, 2H), 7.44-7.48 (m, 3H), 7.35 (d, J =
9.5 Hz, 1H), 6.30 (d, J = 9.5 Hz, 1H), 2.74 (t, J = 7.3 Hz, 2H),
2.63 (t, J = 7.3 Hz, 2H), 2.12 (s, 3H) ppm, 13C{1H}NMR (101
MHz, CDCl3): δ 206.7, 161.9, 158.6, 146.8, 132.2, 130.1,
128.6, 114.9, 114.8, 43.4, 29.9, 23.4 ppm; HRMS (EI): m/z
Calcd. for C15H14O3Na [M+Na]+: 265.0841, found: 265.0858.
5-(3-oxopentyl)-6-phenyl-2H-pyran-2-one
ynoate (1ak). To
a
mixture of ethyl (Z)-3-iodo-3-
phenylacrylate(P6) (1.5 g, 5 mmol, 1.0 eq.), Pd(PPh3)2Cl2 (35.6
mg, 0.05 mmol, 1.0 mol%), CuI (4.9 mg, 0.025 mmol, 0.5
mol%), and Et3N (20 mL) was added the 1-(4-
ethynylphenyl)ethan-1-one (0.79 g, 5.5 mmol, 1.1 equiv.). The
mixture was stirred for 24 h at 50 °C under an inert argon
atmosphere and dealt with according to the similar Method B
to give the product (1ak) (1.0 g, 3.14mmol, 63 % yield) as
light yellow solid;Rf= value 0.36(petroleum ether/ethyl acetate
= 95:5);FTIR (KBr neat) υmax2192, 1715, 1687,1605, 1510,
1462, 771 cm-1;1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.9
Hz, 2H), 7.80-7.76 (m, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.46-
7.42 (m, 3H), 6.64 (s, 1H), 4.31 (q, J = 7.2 Hz, 2H), 2.63 (s,
3H), 1.36 (t, J = 7.0 Hz, 3H) ppm; 13C{1H}NMR (101 MHz,
CDCl3): δ 197.3, 165.2, 136.9, 136.8, 135.9, 132.2, 130.1,
128.8, 128.3, 127.5, 127.2, 123.8, 100.6, 89.6, 60.6, 26.7, 14.4
(3b)Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
for 5 minutes,1a (40 mg, 0.2 mmol, 1.0 equiv.) and pent-1-en-
Page 6 of 15
130.1, 128.6, 115.0, 114.8, 42.6, 42.4, 25.9, 23.4, 22.3,
13.8ppm;HRMS (EI): m/z Calcd. for C18H20O3 [M+H]+:
285.1491, found: 285.1488.
1
2
3
4
5
6
7
8
3-ol 2b (52 mg, 0.6 mmol, 3.0 equiv.)were subsequently added
to the mixture. The system was stirring at 30 °C for 24 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2- 7:3) to afford the pure
product(3b)as a light green oil (37 mg, 0.14 mmol, Yield:
72%); Rf= 0.44(petroleum ether/ethyl acetate = 7:3); FTIR
(KBr neat) υmax 1735, 1713,1633, 1545cm-1;1H NMR (400
MHz, CDCl3): δ 7.50-7.54 (m, 2H), 7.44-7.49 (m, 3H), 7.36 (d,
J = 9.5 Hz, 1H), 6.30 (d, J = 9.5 Hz, 1H), 2.75 (t, J = 7.3 Hz,
2H), 2.60 (t, J = 7.4 Hz, 2H), 2.39 (q, J = 7.2 Hz, 2H), 1.03 (t,
J = 7.3 Hz, 3H) ppm; 13C{1H}NMR (101 MHz, CDCl3): δ
209.5, 162.0, 158.5, 146.9, 132.2, 130.1, 128.6, 115.0, 114.9,
42.1, 36.0, 23.5, 7.7 ppm; HRMS (EI): m/z Calcd. for
C16H16O3Na [M+Na]+: 279.0997, found: 279.0999.
5-(3-oxo-3-phenylpropyl)-6-phenyl-2H-pyran-2-one
(3e). Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1a (40 mg, 0.2 mmol, 1.0 equiv.) and 1-
phenylprop-2-en-1-ol 2e (80 mg, 0.6 mmol, 3.0 equiv.) were
subsequently added to the mixture. The system was stirring at
30 °Cfor 38 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer was
dried over Na2SO4, filtered, concentrated in vacuo. The residue
was purified by flash column chromatography on silica gel
using as eluent petroleum ether/ethyl acetate (8:2 - 7:3) to
afford the pure product (3e) as a brown solid (39 mg, 0.13
mmol, Yield: 64%);Rf= 0.42(petroleum ether/ethyl acetate =
7:3);mp 60-61°C; FTIR (KBr neat) υmax1731, 1685, 1636,1590,
1548 cm-1;1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 7.9 Hz,
2H), 7.59-7.53 (m, 3H), 7.48 – 7.40 (m, 6H), 6.32 (d, J = 9.5
Hz, 1H), 3.16 (t, J = 7.5 Hz, 2H), 2.93 (t, J = 7.5 Hz, 2H) ppm;
13C{1H} NMR (101 MHz, CDCl3): δ 198.2, 162.0, 158.7,
147.0, 136.3, 133.45, 132.2, 130.1, 128.7, 128.6, 128.0, 115.0,
114.9, 38.6, 24.0 ppm; HRMS (EI): m/z Calcd. for C20H17O3
[M+H]+: 305.1178, found: 305.1184.
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
5-(4-methyl-3-oxopentyl)-6-phenyl-2H-pyran-2-one
(3c).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere.After stirringfor
5 minutes1a (40 mg, 0.2 mmol, 1.0 equiv.) and 4-methylpent-
1-en-3-ol2c (60 mg, 0.6 mmol, 3.0 equiv.) were subsequently
added to the mixture.The system was stirring at 30 °Cfor 30
h.The reaction mixture was diluted with ethyl acetate washed
with water and brine. The organic layer was dried over
Na2SO4, filtered, concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel using
as eluent petroleum ether/ethyl acetate (8:2 - 7:3) to afford the
pure product(3c) as a light green oil (35 mg, 0.13 mmol, Yield:
65%);Rf= 0.45(petroleum ether/ethyl acetate = 7:3); FTIR
(KBr neat) υmax 1730, 1709,1628, 1545 cm-1;1H NMR (400
MHz, CDCl3): δ 7.50-7.55 (m, 2H), 7.43-7.48 (m, 3H), 7.36 (d,
J = 9.5 Hz, 1H), 6.30 (d, J = 9.5 Hz, 1H), 2.75 (t, J = 7.3 Hz,
2H), 2.63 (t, J = 7.3 Hz, 2H), 2.57-2.50 (m, 1H), 1.06 (d, J =
6.9 Hz, 6H) ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 212.8,
162.0, 158.5, 147.0, 132.2, 130.1, 128.6, 115.1, 114.8, 41.0,
40.0, 23.5, 18.1 ppm; HRMS (EI): m/z Calcd. for C17H19O3
[M+H]+: 271.1334, found: 271.1321.
5-(3-oxo-4-phenylbutyl)-6-phenyl-2H-pyran-2-one
(3f). Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After
stirringfor 5 minutes1a (40 mg, 0.2 mmol, 1.0 equiv.) and 1-
phenylbut-3-en-2-ol 2f (88 mg, 0.6 mmol, 3.0 equiv.) were
subsequently added to the mixture.The system was stirring at
30 °Cfor 40 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer was
dried over Na2SO4, filtered, concentrated in vacuo. The residue
was purified by flash column chromatography on silica gel
using as eluent petroleum ether/ethyl acetate (8:2 - 7:3) to
afford the pure product(3f) as a white solid (35 mg, 0.11 mmol,
Yield: 55%);Rf = 0.41(petroleum ether/ethyl acetate = 7:3);mp
63-64°C; FTIR (KBr neat) υmax 1735, 1709, 1636,1560, 1540
cm-1;1H NMR (400 MHz, CDCl3): δ 7.42 (s, 5H), 7.35-7.27 (m,
3H), 7.25 (d, J = 7.2 Hz, 1H), 7.13 (d, J = 7.0 Hz, 2H), 6.23 (d,
J = 9.5 Hz, 1H), 3.64 (s, 2H), 2.70 (t, J = 7.1 Hz, 2H), 2.62 (t,
J = 7.0 Hz, 2H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ
206.4, 161.9, 158.5, 146.8, 133.6, 132.1, 130.1, 129.3, 128.9,
128.6, 128.6, 127.3, 114.7, 50.3, 41.4, 23.5 ppm; HRMS (EI):
m/z Calcd. for C21H19O3 [M+H]+: 319.1334, found: 319.1336.
5-(3-(4-bromophenyl)-3-oxopropyl)-6-phenyl-2H-
pyran-2-one (3g).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%)
and Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1a (40 mg, 0.2 mmol, 1.0 equiv.) and 1-(4-
bromophenyl)prop-2-en-1-ol 2g (127 mg, 0.6 mmol, 3.0
equiv.) were subsequently added to the mixture. The system
was stirring at 30 °Cfor 40 h.The reaction mixture was diluted
with ethyl acetate washed with water and brine. The organic
layer was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column chromatography on
silica gel using as eluent petroleum ether/ethyl acetate (8:2 -
7:3) to afford the pure product (3g) as a light green solid (32
5-(3-oxoheptyl)-6-phenyl-2H-pyran-2-one
(3d).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1a (40 mg, 0.2 mmol, 1.0 equiv.) and hept-1-en-
3-ol 2d (68 mg, 0.6 mmol, 3.0 equiv.) were subsequently
added to the mixture. The system was stirring at 30 °Cfor 36
h.The reaction mixture was diluted with ethyl acetate washed
with water and brine. The organic layer was dried over
Na2SO4, filtered, concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel using
as eluent petroleum ether/ethyl acetate (8:2 -7:3) to afford the
pure product(3d)as a light brown oil (31.5 mg, 0.11 mmol,
Yield: 55%);Rf= 0.46(petroleum ether/ethyl acetate = 7:3);
FTIR (KBr neat) υmax 1732, 1709, 1630, 1541 cm-1;1H NMR
(400 MHz, CDCl3): δ 7.53-7.44 (m, 5H), 7.35 (d, J = 9.5 Hz,
1H), 6.30 (d, J = 9.5 Hz, 1H), 2.74 (t, J = 7.4 Hz, 2H), 2.59 (t,
J = 7.4 Hz, 2H), 2.36 (t, J = 7.5 Hz, 2H), 1.56-1.47 (m, 2H),
1.32-1.22 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H) ppm; 13C{1H}
NMR (101 MHz, CDCl3): δ 209.2, 162.0, 158.5, 146.9, 132.2,
6
ACS Paragon Plus Environment

Page 7 of 15
The Journal of Organic Chemistry
5-(3-oxobutyl)-6-(m-tolyl)-2H-pyran-2-one
mg, 0.08 mmol, Yield: 42%);Rf= 0.40(petroleum ether/ethyl
1
2
3
4
5
6
7
8
acetate = 7:3);mp77-78°C; FTIR (KBr neat) υmax1729, 1681,
1635, 1582, 1550 cm-1; 1H NMR (400 MHz, CDCl3): δ 7.73 (d,
J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.55-7.51 (m, 2H),
7.46 (d, J = 5.0 Hz, 3H), 7.41 (d, J = 9.5 Hz, 1H), 6.33 (d, J =
9.5 Hz, 1H), 3.11 (t, J = 7.4 Hz, 2H), 2.92 (t, J = 7.4 Hz, 2H)
ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 197.1, 161.9, 158.8,
146.8, 135.0, 132.2, 132.1, 130.2, 129.5, 128.7, 128.6, 115.0,
114.8, 38.6, 23.9 ppm; HRMS (EI): m/z Calcd. for C20H16BrO3
[M+H]+: 383.0283, found: 383.0294.
(4b).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1c (43
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 26 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4b) as a light brown oil (37 mg, 0.14 mmol, Yield:
9
5-(3-oxopropyl)-6-phenyl-2H-pyran-2-one
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
(3h).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1a (35 mg, 0.2 mmol, 1.0 equiv.) and prop-2-en-
1-ol 2h (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently
added to the mixture.The system was stirring at 30 °Cfor 32
h.The reaction mixture was diluted with ethyl acetate washed
with water and brine. The organic layer was dried over
Na2SO4, filtered, concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel using
as eluent petroleumether/ethyl acetate (8:2) to afford the pure
product 3h as a light brown oil (23 mg, 0.10 mmol, Yield:
50%);Rf= 0.36(petroleum ether/ethyl acetate = 8:2);FTIR (KBr
neat) υmax1738, 1730, 1627, 1544 cm-1;1H NMR (400
MHz,CDCl3): δ 9.75 (s, 1H), 7.52-7.45 (m, 5H), 7.35 (d, J =
9.5 Hz, 1H), 6.32 (d, J = 9.5 Hz, 1H), 2.80 (t, J = 7.3 Hz, 2H),
2.68 (t, J = 7.4 Hz, 2H) ppm; 13C{1H}NMR (101 MHz,
CDCl3):δ 200.0, 161.8, 158.8, 146.5, 132.1, 130.2, 128.7,
128.6, 115.1, 114.3, 43.8, 21.9 ppm; HRMS (EI): m/z Calcd.
for C14H12O3Na [M+Na]+: 251.0684, found: 251.0688.
72%);Rf= 0.44 (petroleum ether/ethyl acetate = 7:3);FTIR
(KBr neat) υmax 1733, 1712, 1636, 1553 cm-1;1H NMR (400
MHz, CDCl3): δ 7.36-7.25 (m, 5H), 6.29 (d, J = 9.4 Hz, 1H),
2.74 (t, J = 7.2 Hz, 2H), 2.62 (t, J = 7.4 Hz, 2H), 2.40 (s, 3H),
2.12 (s, 3H) ppm; 13C{1H}(101 MHz, CDCl3): δ 207.2, 162.5,
159.3, 147.4, 139.0, 132.6, 131.4, 129.8, 128.9, 126.1, 115.2,
44.0, 30.5, 23.9, 21.9 ppm; HRMS (EI): m/z Calcd. for
C16H17O3 [M+H]+: 257.1178, found: 257.1174.
5-(3-oxobutyl)-6-(o-tolyl)-2H-pyran-2-one
(4c).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1d (43
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 40 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to obtaine the pure
product(4c)as a light brown oil (36.5 mg, 0.14 mmol, Yield:
71%);Rf=0.44 (petroleum ether/ethyl acetate = 7:3);FTIR
(KBr neat) υmax 1734, 1711, 1634, 1551 cm-1;1H NMR
5-(3-oxobutyl)-6-(p-tolyl)-2H-pyran-2-one
(4a)Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1b (43
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol2a (43 mg, 0.6
mmol, 3.0 equiv.). The system was stirring at 30 °C for
28 h.The reaction mixture was diluted with ethyl acetate
washed with water and brine. The organic layer was
dried over Na2SO4, filtered, concentrated in vacuo. The
residue was purified by flash column chromatography on
silica gel using as eluent petroleum ether/ethyl acetate
(8:2 - 7:3) to isolate the pure product (4a) as a light brown
oil (38 mg, 0.15 mmol, Yield: 74%);Rf=0.44 (petroleum
ether/ethyl acetate = 7:3);FTIR (KBr neat) υmax 1728, 1713,
(400 MHz, CDCl3): δ 7.38-7.33 (m, 2H), 7.31-7.18 (m, 3H),
6.30 (d, J = 9.5 Hz, 1H), 2.53-2.43 (m, 4H), 2.27 (s, 3H), 2.07
(s, 3H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ 206.8,
162.2, 159.4, 146.5, 137.2, 131.7, 130.8, 130.2, 129.4, 125.9,
115.7, 115.2, 43.2, 30.0, 23.3, 19.6 ppm; HRMS (EI): m/z
Calcd. for C16H17O3 [M+H]+: 257.1178, found: 257.1183.
6-(naphthalen-2-yl)-5-(3-oxobutyl)-2H-pyran-2-one
1632, 1550, cm-1;1H NMR (400 MHz, CDCl3): δ 7.41 (d, J =
7.9 Hz, 2H), 7.34 (d, J = 9.5 Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H),
6.27 (d, J = 9.4 Hz, 1H), 2.74 (t, J = 7.3 Hz, 2H), 2.62 (t, J =
7.4 Hz, 2H), 2.41 (s, 3H), 2.12 (s, 3H) ppm; 13C{1H} NMR
(101 MHz, CDCl3): δ 206.8, 162.1, 158.8, 146.9, 140.4, 129.4,
129.3, 128.5, 114.5, 114.5, 43.5, 30.1, 23.5, 21.4 ppm; HRMS
(EI): m/z Calcd. for C16H17O3 [M+H]+: 257.1178, found:
257.1183.
(4d).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
6-(4-methoxyphenyl)-5-(3-oxobutyl)-2H-pyran-2-
Page 8 of 15
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1e (50
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 36 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4d) as a brown solid (38 mg, 0.13 mmol, Yield:
65%);Rf=0.40 (petroleum ether/ethyl acetate = 7:3);mp 70-
71°C; FTIR (KBr neat) υmax1727, 1710, 1628, 1535,
1169,828 cm-1;1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H),
1
2
3
4
5
6
7
8
one (4f).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1g (46
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 28 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolated the pure
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
product(4f) was obtained as a brown oil (36 mg, 0.13 mmol,
Yield: 67%);Rf= 0.43 (petroleum ether/ethyl acetate =
7:3);FTIR (KBr neat) υmax1726, 1708, 1635, 1545 cm-1;1H
7.89 (m, 3H), 7.57 (m, 3H), 7.39 (d, J = 9.5 Hz, 1H), 6.33 (d, J
= 9.5 Hz, 1H), 2.82 (t, J = 7.4 Hz, 2H), 2.65 (t, J = 7.4 Hz,
2H), 2.10 (s, 3H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ
206.7, 162.0, 158.5, 147.0, 133.7, 132.7, 129.5, 128.9, 128.6,
128.4, 127.8, 127.6, 126.9, 125.2, 115.2, 114.9, 43.4, 30.0,
23.5 ppm; HRMS (EI): m/z Calcd. for C19H17O3 [M+H]+:
293.1178, found: 293.1180.
NMR (400 MHz, CDCl3): δ 7.48 (d, J = 8.5 Hz, 2H), 7.33 (d, J
= 9.5 Hz, 1H), 6.96 (d, J = 8.5 Hz, 2H), 6.25 (d, J = 9.5 Hz,
1H), 3.86 (s, 3H), 2.75 (t, J = 7.3 Hz, 2H), 2.63 (t, J = 7.3 Hz,
2H), 2.13 (s, 3H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ
206.8, 162.2, 160.9, 158.56, 147.0, 130.1, 124.6, 114.2, 114.1,
114.0, 55.4, 43.4, 30.0, 23.5 ppm; HRMS (EI): m/z Calcd. for
C16H17O4 [M+H]+: 273.1127, found: 273.1125.
6-(9H-fluoren-2-yl)-5-(3-oxobutyl)-2H-pyran-2-one
(4e).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1f (57
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 40 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4e) as a light yellow solid (33 mg, 0.10 mmol, Yield:
50%);Rf= 0.36 (petroleum ether/ethyl acetate = 7:3);mp 128-
129°C; FTIR (KBr neat) υmax1730, 1701, 1633, 1549,
1056 cm-1;1H NMR (400 MHz, CDCl3): δ 7.83-7.81 (m, 2H),
6-(4-chlorophenyl)-5-(3-oxobutyl)-2H-pyran-2-one
(4g).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1h (47
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 36 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure product
(4g) as a light brown oil (29.5 mg, 0.11 mmol, Yield:
53%);Rf= 0.43 (petroleum ether/ethyl acetate = 7:3);FTIR
(KBr neat) υmax1724, 1700, 1630, 1540, 1090 cm-1;1H NMR
(400 MHz, CDCl3): δ 7.48 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4
Hz, 2H), 7.34 (d, J = 9.5 Hz, 1H), 6.31 (d, J = 9.5 Hz, 1H),
2.72 (t, J = 7.1 Hz, 2H), 2.63 (t, J = 7.2 Hz, 2H), 2.13 (s, 3H)
ppm; 13C{1H} NMR (101 MHz, CDCl3): δ 206.5, 161.6,
157.3, 146.6, 136.3, 130.6, 130.0, 128.9, 115.2, 115.1, 43.2,
30.0, 23.3 ppm; HRMS (EI): m/z Calcd. for C15H14O3Cl
[M+H]+: 277.0631, found: 277.0631.
7.73 (s, 1H), 7.58 (d, J = 7.1 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H),
7.43-7.34 (m, 3H), 6.30 (d, J = 9.4 Hz, 1H), 3.95 (s, 2H), 2.82
(t, J = 7.3 Hz, 2H), 2.65 (t, J = 7.3 Hz, 2H), 2.12 (s, 3H) ppm;
13C{1H} NMR (101 MHz, CDCl3): δ 206.7, 162.1, 159.0,
147.0, 143.8, 143.6, 143.5, 140.6, 130.3, 127.7, 127.4, 127.0,
125.4, 125.2, 120.5, 119.8, 114.7, 114.5, 43.4, 37.0, 30.0, 23.6
ppm; HRMS (EI): m/z Calcd. for C22H19O3 [M+H]+: 331.1334,
found: 331.1335.
6-(4-bromophenyl)-5-(3-oxobutyl)-2H-pyran-2-one
(4h).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
8
ACS Paragon Plus Environment

Page 9 of 15
The Journal of Organic Chemistry
in cyclohexanone (1.0 mL) under O2 atmosphere. After stirring for 5 minutes followed by the addition of 1k (41
1
stirring for 5 minutes followed by the addition of 1i (56
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 40 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4h) as a light brown oil (31.5 mg, 0.10 mmol, Yield:
49%);Rf= 0.40 (petroleum ether/ethyl acetate = 7:3); FTIR
(KBr neat) υmax1728, 1701, 1628, 1542, 1060 cm-1;1H NMR
(400 MHz, CDCl3): δ 7.60 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.4
Hz, 2H), 7.34 (d, J = 9.5 Hz, 1H), 6.31 (d, J = 9.5 Hz, 1H),
2.72 (t, J = 7.2 Hz, 2H), 2.63 (t, J = 7.3 Hz, 2H), 2.13 (s, 3H)
ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 206.5, 161.6, 157.3,
146.6, 131.9, 131.0, 130.2, 124.7, 115.3, 115.1, 43.2, 30.0,
23.3 ppm; HRMS (EI): m/z Calcd. for C15H13O3BrNa
[M+Na]+: 342.9946, found: 342.9946.
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 32 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
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
ether/ethyl acetate (8:2 - 7:3) to isolate the pure product
(4j) as a light green oil (26 mg, 0.13 mmol, Yield: 64%);Rf=
0.37(petroleum ether/ethyl acetate = 8:2);FTIR (KBr neat)
υmax1719, 1706, 1630, 1610, 1531 cm-1;1H NMR (400
MHz, CDCl3): δ 7.25-7.23 (d, J = 9.5 Hz, 1H), 6.17 (d, J = 9.5
Hz, 1H), 5.97 (s, 1H), 2.69-2.61 (m, 4H), 2.68-2.61 (m, 4H),
2.17 (s, 3H), 1.78-1.65 (m, 4H) ppm; 13C{1H} NMR (101
MHz, CDCl3): δ 206.9, 162.1, 161.4, 146.9, 132.9, 130.8,
114.0, 113.5, 43.9, 30.0, 26.6, 25.3, 23.6, 22.2, 21.5 ppm;
HRMS (EI): m/z Calcd. for C15H19O3 [M+H]+: 247.1334,
found: 247.1338.
6-cyclohexyl-5-(3-oxobutyl)-2H-pyran-2-one
6-(4-methoxycarbonyl)phenyl-5-(3-oxobutyl)-2H-
(4k).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1l (36
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 32 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4k) as a light green oil (29 mg, 0.14 mmol, Yield:
71%);Rf= 0.39(petroleum ether/ethyl acetate = 8:2); FTIR
(KBr neat) υmax1721, 1703, 1628, 1549, 1463 cm-1;1H NMR
(400 MHz, CDCl3): δ 7.19 (d, J = 9.5 Hz, 1H), 6.12 (d, J = 9.4
Hz, 1H), 2.65 – 2.56 (m, 5H), 2.17 (s, 3H), 1.88-1.81 (m, 2H),
1.75 – 1.64 (m, 5H), 1.36 – 1.24 (m, 3H) ppm; 13C{1H} NMR
(101 MHz, CDCl3): δ 206.8, 165.8, 162.7, 147.1, 113.3, 112.5,
43.9, 39.6, 30.2, 26.0, 25.5, 22.9 ppm; HRMS (EI): m/z Calcd.
for C15H21O3 [M+H]+: 249.1491, found: 249.1500.
pyran-2-one (4i).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%)
and Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were
added in cyclohexanone (1.0 mL) under O2 atmosphere.
After stirring for 5 minutes followed by the addition of 1j
(41 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43
mg, 0.6 mmol, 3.0 equiv.). The system was stirring at 30
°C for 40 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4i)as a white solid (30 mg, 0.10 mmol, Yield:
50%);Rf= 0.38 (petroleum ether/ethyl acetate = 7:3); mp 68-
69°C; FTIR (KBr neat) υmax1738, 1723, 1703, 1634, 1546
cm-1;1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 8.1 Hz, 2H),
7.61 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 9.5 Hz, 1H), 6.34 (d, J =
9.5 Hz, 1H), 3.95 (s, 3H), 2.74 (t, J = 6.9 Hz, 2H), 2.64 (t, J =
7.1 Hz, 2H), 2.13 (s, 3H) ppm; 13C{1H} NMR (101 MHz,
CDCl3): δ 206.3, 166.2, 161.4, 157.2, 146.6, 136.2, 131.5,
129.8, 128.7, 115.7, 115.6, 52.4, 43.2, 30.0, 23.3 ppm; HRMS
(EI): m/z Calcd. for C17H17O5 [M+H]+: 301.1076, found:
301.1081.
6-butyl-5-(3-oxobutyl)-2H-pyran-2-one
(4l).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1m (36
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
6-(cyclohex-1-en-1-yl)-5-(3-oxobutyl)-2H-pyran-2-
one (4j). Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 15
for 30 h.The reaction mixture was diluted with ethyl chromatography on silica gel using as eluent petroleum
1
2
3
4
5
6
7
8
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2)to isolatethe pure product, (4l) as
a light green oil (30 mg, 0.13 mmol, Yield: 67%);Rf= 0.40
(petroleum ether/ethyl acetate = 8:2); FTIR (KBr neat)
υmax1723, 1707, 1630, 1373, 821cm-1;1H NMR (400 MHz,
CDCl3): δ 7.20 (d, J = 9.3 Hz, 1H), 6.14 (d, J = 9.5 Hz, 1H),
2.65-2.56 (m, 4H), 2.51 (t, J = 7.7 Hz, 2H), 2.17 (s, 3 H), 1.68-
1.60 (m, 2H), 1.42-1.34 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H) ppm;
13C NMR (101 MHz, CDCl3): δ 206.8, 162.6, 162.5, 146.8,
113.8, 113.5, 43.5, 30.6, 30.1, 29.7, 22.9, 22.4, 13.8 ppm;
HRMS (EI): m/z Calcd. for C13H19O3 [M+H]+: 223.1334,
found: 223.1339.
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4n) as a white solid (26 mg, 0.11 mmol, Yield:
56%);mp 54-55°C;Rf= 0.36(petroleum ether/ethyl acetate =
7:3);FTIR (KBr neat) υmax2245, 1724, 1702, 1634cm-1;1H
NMR (400 MHz, CDCl3): δ 7.22 (d, J = 9.5 Hz, 1H), 6.19 (d, J
= 9.5 Hz, 1H), 2.75 (t, J = 7.5 Hz, 2H), 2.68 (t, J = 6.7 Hz,
2H), 2.61 (t, J = 6.8 Hz, 2H), 2.46 (t, J = 6.9 Hz, 2H), 2.17 (s,
3H), 2.11-2.04 (m, 2H) ppm; 13C{1H}NMR (101 MHz,
CDCl3): δ 206.6, 161.9, 159.2, 146.6, 118.9, 115.0, 114.5,
43.0, 30.1, 29.1, 22.8, 22.7, 16.7 ppm; HRMS (EI): m/z Calcd.
for C13H15NO3Na [M+Na]+: 256.0950, found: 256.0953.
6-(2-(benzyloxy)ethyl)-5-(3-oxobutyl)-2H-pyran-2-
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
one(4o).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1p (52
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 32 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4o)was obtained as a light green oil (34.5 mg, 0.11
mmol, Yield: 54%);Rf= 0.38(petroleum ether/ethyl acetate =
7:3);IR (KBr neat) υmax1726, 1708, 1631, 1540, 1250 cm-1;1H
NMR (400 MHz, CDCl3): δ 7.34 -7.25 (m, 5H), 7.21 (d, J =
9.5 Hz, 1H), 6.16 (d, J = 9.5 Hz, 1H), 4.48 (s, 2H), 3.79 (t, J =
6.1 Hz, 2H), 2.80 (t, J = 6.0 Hz, 2H), 2.64-2.52 (m, 4H), 1.96
(s, 3H) ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 207.2,
162.5, 159.2, 147.0, 137.9, 128.4, 127.8, 127.8, 115.7, 113.9,
73.3, 67.1, 43.6, 31.8, 29.9, 23.1 ppm, HRMS (EI): m/z Calcd.
for C19H22O4Na [M+Na]+: 337.1416., found: 337.1411.
6-(3-chloropropyl)-5-(3-oxobutyl)-2H-pyran-2-one
(4m).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1n (40
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 32 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4m) was obtained as a light brown oil (29 mg, 0.12
mmol, Yield: 61%);Rf= 0.37(petroleum ether/ethyl acetate =
7:3);FTIR (KBr neat) υmax1725, 1708, 1628, 1173,678 cm-1;1H
NMR (400 MHz, CDCl3): δ 7.22 (d, J = 9.5 Hz, 1H), 6.17 (d, J
= 9.4 Hz, 1H), 3.59 (t, J = 6.0 Hz, 2H), 2.74 (t, J = 7.3 Hz,
2H), 2.69-2.59 (m, 4H), 2.21-2.13 (m, 5H) ppm; 13C{1H}
NMR (101 MHz, CDCl3): δ 206.7, 162.2, 160.3, 146.7, 114.8,
114.1, 44.0, 43.3, 30.1, 29.8, 27.7, 22.9 ppm; HRMS (EI): m/z
Calcd. for C12H16ClO3 [M+H]+: 243.0788, found: 243.0793.
6-(3-cyanopropyl)-5-(3-oxobutyl)-2H-pyran-2-one
6-(2-acetoxyethyl)-5-(3-oxobutyl)-2H-pyran-2-
one(4p).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1q (42
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 30 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
(4n).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1o (38
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 32 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
product(4p) as a light brown oil (24 mg, 0.09 mmol, Yield:
48%);Rf= 0.29 (petroleum ether/ethyl acetate = 7:3);FTIR
10
ACS Paragon Plus Environment

Page 11 of 15
The Journal of Organic Chemistry
(KBr neat) υmax1740, 1723, 1703, 1633 cm-1;1H NMR (400 2.18 (s, 3H) ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 206.7,
1
2
3
4
5
6
7
8
MHz, CDCl3): δ 7.22 (d, J = 9.5 Hz, 1H), 6.19 (d, J = 9.5 Hz,
1H), 4.35 (t, J = 6.5 Hz, 2H), 2.88 (t, J = 6.6 Hz, 2H), 2.67 (t,
J = 6.9 Hz, 2H), 2.59 (t, J = 7.1 Hz, 2H), 2.17 (s, 3H), 2.05 (s,
3H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ 206.5, 170.7,
162.0, 157.8, 146.5, 115.5, 114.6, 61.2, 43.3, 30.4, 30.1, 22.8,
20.8 ppm; HRMS (EI): m/z Calcd. for C13H16O5Na [M+Na]+:
275.0895, found: 275.0900.
161.1, 152.6, 148.1, 133.9, 129.2, 129.1, 127.8, 114.0, 42.7,
30.1, 24.3 ppm; HRMS (EI): m/z Calcd. for
C13H12O3SNa[M+Na]+: 271.0405, found: 271.0408.
6-(1-methyl-1H-indol-2-yl)-5-(3-oxobutyl)-2H-
pyran-2-one (4s).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%)
and Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were
added in cyclohexanone (1.0 mL) under O2 atmosphere.
After stirring for 5 minutes followed by the addition of
1t(51 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43
mg, 0.6 mmol, 3.0 equiv.). The system was stirring at 30
°C for 36 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
5-(3-oxobutyl)-6-phenethyl-2H-pyran-2-one
(4q)Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1r (45
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 34 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
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
product(4s)as
a red oil (36 mg, 0.12 mmol, Yield:
61%);%);Rf= 0.41(petroleum ether/ethyl acetate = 7:3);FTIR
(KBr neat) υmax 1727, 1706, 1627, 1550, 1101 cm-1;1H NMR
(400 MHz, CDCl3) δ 7.65 (d, J = 8.0 Hz, 1H), 7.43-7.37 (m,
2H), 7.36-7.30 (m, 1H), 7.19-7.14 (m, 1H), 6.70 (s, 1H), 6.33
(d, J = 9.5 Hz, 1H), 3.81 (s, 3H), 2.80 (t, J = 7.2 Hz, 2H), 2.65
(t, J = 7.2 Hz, 2H), 2.12 (s, 3H) ppm; 13C{1H}NMR (101
MHz, CDCl3) δ 206.6, 161.4, 151.3, 146.4, 138.2, 129.5,
126.8, 123.7, 121.5, 120.4, 118.2, 115.4, 109.9, 105.9, 43.4,
31.5, 30.0, 23.8 ppm; HRMS (EI): m/z Calcd. for C18H18NO3
[M+H]+: 296.1287, found: 296 .1291.
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
product(4q)as a light green oil (25 mg, 0.09 mmol, Yield:
46%);Rf= 0.41(petroleum ether/ethyl acetate = 7:3);FTIR
(KBr neat) υmax 1725,1703, 1632, 1549, 1460 cm-1;1H
NMR (400 MHz, CDCl3): δ 7.30-7.19 (m, 3H), 7.16-7.10 (m,
3H), 6.15 (d, J = 9.5 Hz, 1H), 3.00 (t, J = 7.3 Hz, 2H), 2.81 (t,
J = 7.4 Hz, 2H), 2.35 (t, J = 7.3 Hz, 2H), 2.15 (t, J = 7.3 Hz,
2H), 2.03 (s, 3H) ppm; 13C{1H}NMR (101 MHz, CDCl3):
δ206.8, 162.5, 160.6, 146.7, 140.3, 128.6, 126.5, 114.8, 113.8,
43.1, 33.4, 32.9, 29.9, 22.7 ppm; HRMS (EI): m/z Calcd. for
C17H19O3 [M+H]+: 271.1334, found: 271.1334.
4-methyl-5-(3-oxobutyl)-6-phenyl-2H-pyran-2-one
(5a).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1aa (43 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 32 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5a) as a white solid crystal (42 mg, 0.16 mmol, Yield:
82%);Rf= 0.46(petroleum ether/ethyl acetate = 7:3);mp 47-
48°C; FTIR (KBr neat) υmax 1721, 1705, 1628, 1546 cm-1;1H
NMR (400 MHz, CDCl3): δ 7.45 (s, 5H), 6.18 (s, 1H), 2.70 (t,
J = 7.8 Hz, 2H), 2.50 (t, J = 7.8 Hz, 2H), 2.23 (s, 3H), 2.07 (s,
3H) ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 206.5, 161.8,
158.4, 156.7, 132.7, 130.0, 128.6, 128.6, 115.7, 113.8, 43.4,
29.8, 20.8, 20.2 ppm; HRMS (EI): m/z Calcd. for C16H17O3
[M+H]+: 257.1178, found: 257.1180.
5-(3-oxobutyl)-6-(thiophen-2-yl)-2H-pyran-2-one
(4r).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After
stirring for 5 minutes followed by the addition of 1s (41
mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-ol 2a (43 mg,
0.6 mmol, 3.0 equiv.). The system was stirring at 30 °C
for 32 h.The reaction mixture was diluted with ethyl
acetate washed with water and brine. The organic layer
was dried over Na2SO4, filtered, concentrated in vacuo.
The residue was purified by flash column
chromatography on silica gel using as eluent petroleum
ether/ethyl acetate (8:2 - 7:3) to isolate the pure
5-(3-oxobutyl)-6-phenyl-4-propyl-2H-pyran-2-one
(5b).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1ab (48 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 36 h.The
reaction mixture was diluted with ethyl acetate washed with
product(4r)as a red oil (29 mg, 0.12 mmol, Yield: 58%);Rf=
0.46(petroleum ether/ethyl acetate = 7:3); FTIR (KBr neat)
υmax 3094, 1730, 1701, 1625cm-1;1H NMR (400 MHz, CDCl3):
δ 7.58 (d, J = 3.5 Hz, 1H), 7.52 (d, J = 5.0 Hz, 1H), 7.36 (d, J
= 9.4 Hz, 1H), 7.16-7.14 (dd, J = 4.5, 4.3 Hz, 1H), 6.23 (d, J =
9.4 Hz, 1H), 2.93 (t, J = 7.3 Hz, 2H), 2.77 (t, J = 7.3 Hz, 2H),
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 15
water and brine. The organic layer was dried over Na2SO4, to the mixture. The system was stirring at 30 °C for 40 h.The
1
2
3
4
5
6
7
8
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5b) as a white solid crystal (46 mg, 0.16 mmol, Yield:
81%);Rf= 0.47(petroleum ether/ethyl acetate = 7:3);mp 48-
49°C; FTIR (KBr neat) υmax1723, 1706, 1628, 1547, 1370 cm-
1;1H NMR (400 MHz, CDCl3): δ 7.45 (s, 5H), 6.17 (s, 1H),
2.70 (t, J = 7.8 Hz, 2H), 2.50-2.41 (m, 4H), 2.05 (s, 3H), 1.69-
1.60 (m, 2H), 1.05 (t, J = 7.3 Hz, 3H) ppm; 13C{1H} NMR
(101 MHz, CDCl3): δ 206.6, 162.2, 160.4, 158.5, 132.8, 130.0,
128.7, 128.6, 115.4, 112.4, 43.7, 34.5, 29.8, 21.8, 20.3, 13.9
ppm; HRMS (EI): m/z Calcd. for C18H21O3 [M+H]+: 285.1491,
found: 285.1490.
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5e)as a brown solid (42 mg, 0.15 mmol, Yield:
74%);Rf= 0.43(petroleum ether/ethyl acetate = 7:3);mp 68-
69°C; FTIR (KBr neat) υmax1727, 1711, 1633, 1565, 1163 cm-
1 1
; H NMR (400 MHz, CDCl3): δ 7.41 (d, J = 8.3 Hz, 2H), 6.95
9
(d, J = 8.3 Hz, 2H), 6.14 (s, 1H), 3.85 (s, 3H), 2.72 (t, J = 7.8
Hz, 2H), 2.51 (t, J = 7.9 Hz, 2H), 2.22 (s, 3H), 2.09 (s, 3H)
ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 206.6, 162.0, 160.7,
158.3, 156.8, 130.1, 125.0, 115.2, 114.0, 113.3, 55.4, 43.4,
29.8, 20.9, 20.2 ppm; HRMS (EI): m/z Calcd. for C17H19O4
[M+H]+: 287.1283, found: 287.1289.
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
6-butyl-4-methyl-5-(3-oxobutyl)-2H-pyran-2-one
(5c).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1ac (39 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 36 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2) to afford the pure
product(5c)as a light brown oil (34 mg, 0.14 mmol, Yield:
72%);Rf= 0.41(petroleum ether/ethyl acetate = 8:2);mp 53-
54°C; FTIR (KBr neat) υmax1730, 1710, 1631, 1372, cm-1;1H
NMR (400 MHz, CDCl3): δ 6.01 (s, 1H), 2.64-2.54 (m, 4H),
2.49 (t, J = 7.6 Hz, 2H), 2.19 (s, 3H), 2.14 (s, 3H), 1.68-1.60
(m, 2H), 1.42-1.32 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H) ppm;
13C{1H}NMR (101 MHz, CDCl3): δ 206.8, 162.6, 161.7,
156.6, 114.4, 112.3, 43.4, 30.7, 30.0, 29.8, 22.5, 20.2, 20.1,
13.8 ppm; HRMS (EI): m/z Calcd. for C14H21O3 [M+H]+:
237.1491, found: 237.1493.
6-(4-acetylphenyl)-4-methyl-5-(3-oxobutyl)-2H-
pyran-2-one (5f).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1af (51 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 45 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5f)was obtained as a white solid (45 mg, 0.15 mmol,
Yield: 75%); Rf= 0.40(petroleum ether/ethyl acetate = 7:3);mp
77-78°C; FTIR (KBr neat) υmax1730, 1703, 1683, 1629, 1542
cm-1;1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.1 Hz, 2H),
7.58 (d, J = 8.1 Hz, 2H), 6.21 (s, 1H), 2.71 (t, J = 7.8 Hz, 2H),
2.65 (s, 3H), 2.52 (t, J = 7.8 Hz, 2H), 2.25 (s, 3H), 2.09 (s, 3H)
ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 206.1, 197.2, 161.3,
156.9, 156.5, 137.9, 136.8, 129.0, 128.5, 116.5, 114.4, 43.2,
29.8, 26.7, 20.7, 20.1 ppm; HRMS (EI): m/z Calcd. for
C18H19O4 [M+H]+: 299.1283, found: 299.1291.
6-(4-chlorophenyl)-4-methyl-5-(3-oxobutyl)-2H-
pyran-2-one (5d).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%)
and Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1ad (50 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 45 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5d) as a white solid (40.5 mg, 0.14 mmol, Yield:
70%);Rf= 0.44(petroleum ether/ethyl acetate = 7:3);mp 64-
65°C; FTIR (KBr neat) υmax 1725, 1706, 1631, 1540, 1092 cm-
1;1H NMR (400 MHz, CDCl3): δ 7.45-7.38 (m, 4H), 6.18 (s,
1H), 2.69 (t, J = 7.8 Hz, 2H), 2.50 (t, J = 7.9 Hz, 2H), 2.23 (s,
3H), 2.10 (s, 3H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ
206.2, 161.5, 157.0, 156.6, 136.2, 131.0, 130.0, 129.0, 116.0,
114.1, 43.2, 29.9, 20.8, 20.2 ppm; HRMS (EI): m/z Calcd. for
C16H16ClO3 [M+H]+: 291.0788, found: 291.0791.
5-(3-oxobutyl)-4,6-diphenyl-2H-pyran-2-one
(5g).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1ag (55 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 46 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5g)was obtained as a light brown solid (50 mg, 0.16
mmol, Yield: 78%);Rf= 0.43(petroleum ether/ethyl acetate =
7:3);mp 95-96°C; FTIR (KBr neat) υmax1722, 1705, 1613,
1523, 1485 cm-1;1H NMR (400 MHz, CDCl3): δ 7.56-7.52
(m, 2H), 7.49-7.44 (m, 6H), 7.37-7.33 (m, 2H), 6.22 (s,
1H),2.74 (t, J = 7.9 Hz, 2H), 2.09 (t, J = 8.0 Hz, 2H), 1.77 (s,
3H) ppm; 13C{1H} NMR (101 MHz, CDCl3): δ 206.5, 161.7,
159.5, 159.2, 137.1, 132.7, 130.2, 129.2, 128.9, 128.8, 128.6,
127.4, 114.6, 114.5, 42.8, 29.4, 21.5 ppm; HRMS (EI): m/z
Calcd. for C21H19O3 [M+H]+: 319.1334, found: 319.1335.
6-butyl-5-(3-oxobutyl)-4-phenyl-2H-pyran-2-one
6-(4-methoxyphenyl)-4-methyl-5-(3-oxobutyl)-2H-
pyran-2-one (5e).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%)
and Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1ae (49 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
(5h).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
12
ACS Paragon Plus Environment

Page 13 of 15
The Journal of Organic Chemistry
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
125.0, 114.0, 114.0, 55.4, 42.8, 29.4, 21.6 ppm; HRMS (EI):
m/z Calcd. for C22H21O4 [M+H]+: 349.1440, found: 349.1441.
6-(4-acetylphenyl)-5-(3-oxobutyl)-4-phenyl-2H-
1
2
3
4
5
6
7
8
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1ah (51 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 46 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5h)was obtained as a white solid (45 mg, 0.15 mmol,
Yield: 75%);Rf= 0.39(petroleum ether/ethyl acetate = 7:3);mp
88-89°C; FTIR (KBr neat) υmax 1725, 1707, 1626, 1540, 1363
cm-1;1H NMR (400 MHz, CDCl3): δ 7.46-7.42 (m, 3H), 7.26-
7.23 (m, 2H), 6.05 (s, 1H), 2.61-2.55 (m, 4H), 2.20 (t, J = 7.9
Hz, 2H), 1.92 (s, 3H), 1.74-1.65 (m, 2H), 1.46-1.36 (m, 2H),
0.96 (t, J = 7.3 Hz, 3H) ppm; 13C{1H}NMR (101 MHz,
CDCl3): δ 206.7, 162.7, 162.3, 159.5, 137.2, 129.0, 128.7,
127.3, 113.4, 113.2, 43.3, 31.1, 29.9, 29.7, 22.5, 20.7, 13.8
ppm; HRMS (EI): m/z Calcd. for C19H23O3 [M+H]+: 299.1647,
found: 299.1647.
pyran-2-one (5k).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%)
and Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added
in cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for5 minutes1ak (64 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-
ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 60 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5k)as a white solid (45 mg, 0.13 mmol, Yield:
63%);Rf= 0.31(petroleum ether/ethyl acetate = 7:3);mp 127-
128°C; FTIR (KBr neat) υmax1723, 1708, 1684, 1603 1550,
1525 cm-1;1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.2 Hz,
2H), 7.66 (d, J = 8.2 Hz, 2H), 7.50-7.46 (m, 3H), 7.38-7.33
(m, 2H), 6.26 (s, 1H), 2.78-2.71 (m, 2H), 2.65 (s, 3H), 2.12-
2.07 (m, 2H), 1.79 (s, 3H) ppm; 13C{1H}NMR (101 MHz,
CDCl3): δ 206.1, 197.2, 161.3, 159.3, 157.7, 138.0, 136.9,
136.8, 129.3, 129.3, 128.9, 128.5, 127.4, 115.3, 115.2, 42.5,
29.5, 26.8, 21.4 ppm; HRMS (EI): m/z Calcd. for C23H21O4
[M+H]+: 361.1440, found: 361.1438.
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
6-(4-chlorophenyl)-5-(3-oxobutyl)-4-phenyl-2H-
pyran-2-one (5i).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1ai (62 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-
ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 60 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5i)as a light green solid (39 mg, 0.11 mmol, Yield:
55%);Rf= 0.38(petroleum ether/ethyl acetate = 7:3);mp 110-
111°C; FTIR (KBr neat) υmax1721, 1706, 1620, 1540, 1532,
4-(4-chlorophenyl)-5-(3-oxobutyl)-6-phenyl-2H-
pyran-2-one (5l).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1al (62 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-2-
ol 2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 60 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 - 7:3) to afford the pure
product(5l) as a white solid (42.5 mg, 0.12 mmol, Yield:
60%);Rf= 0.38(petroleum ether/ethyl acetate = 7:3);mp 112-
113°C; FTIR (KBr neat) υmax1723, 1705, 1622, 1550, 1530,
1085 cm-1;1H NMR (400 MHz, CDCl3): δ 7.54-7.45 (m, 7H),
7.31 (d, J = 8.0 Hz, 2H), 6.19 (s, 1H), 2.73 (t, J = 8.0 Hz, 2H),
2.10 (t, J = 8.0 Hz, 2H), 1.82 (s, 3H) ppm; 13C{1H}NMR (101
MHz, CDCl3): δ 206.2, 161.4, 159.5, 158.4, 135.5, 132.6,
130.3, 129.3, 128.9, 128.7, 114.7, 114.2, 42.7, 29.5, 21.3 ppm;
HRMS (EI): m/z Calcd. for C21H18ClO3 [M+H]+: 353.0944,
found: 353.0949.
1489, 1100 cm-1;1H NMR (400 MHz, CDCl3): δ 7.51-7.44 (m,
7H), 7.36-7.33 (m, 2H), 6.23 (s, 1H), 2.73 (t, J = 8.0 Hz, 2H),
2.08 (t, J = 8.0 Hz, 2H), 1.79 (s, 3H) ppm; 13C{1H} NMR (101
MHz, CDCl3): δ 206.2, 161.4, 159.4, 157.9, 136.9, 136.4,
131.1, 130.3, 129.3, 129.0, 128.9, 127.4, 114.9, 114.8, 42.6,
29.5, 21.4 ppm; HRMS (EI): m/z Calcd. for C21H18ClO3
[M+H]+: 353.0944, found: 353.0940.
6-(4-methoxyphenyl)-5-(3-oxobutyl)-4-phenyl-2H-
pyran-2-one (5j).Cu(OAc)2 (7.2 mg, 0.04 mmol, 20 mol%) and
Pd(PhCN)2Cl2 (3.8 mg, 0.01 mmol, 5 mol%) were added in
cyclohexanone (1.0 mL) under O2 atmosphere. After stirring
for 5 minutes1aj (61 mg, 0.2 mmol, 1.0 equiv.) and 3-Buten-
2-ol2a (43 mg, 0.6 mmol, 3.0 equiv.) were subsequently added
to the mixture. The system was stirring at 30 °C for 46 h.The
reaction mixture was diluted with ethyl acetate washed with
water and brine. The organic layer was dried over Na2SO4,
filtered, concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel using as eluent
petroleum ether/ethyl acetate (8:2 -7:3) to afford the pure
product(5j) as a white solid (55 mg, 0.16 mmol, Yield:
79%);Rf= 0.36(petroleum ether/ethyl acetate = 7:3);mp 117-
118°C; FTIR (KBr neat) υmax1729, 1706, 1624, 1572 1540,
1165 cm-1;1H NMR (400 MHz, CDCl3): δ 7.51-7.44 (m, 5H),
7.35 (d, J = 6.8 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 6.18 (s, 1H),
3.86 (s, 3H), 2.76 (t, J = 8.0 Hz, 2H), 2.10 (t, J = 8.0 Hz, 2H),
1.78 (s, 3H)ppm; 13C{1H}NMR (101 MHz, CDCl3): δ 206.6,
161.9, 160.9, 159.7, 159.2, 137.2, 130.5, 129.1, 128.8, 127.4,
Supporting Information
Single crystaldata of 5a andspectral data for all novel compounds
(1H NMR, 13C NMR).
AUTHOR INFORMATION
Corresponding Author
xyh0709@ustc.edu.cn;teckpeng@ntu.edu.sg
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge the funding support of Anhui Provincial
Natural Science Foundation (1708085MB29), the National Natural
Science Foundation of China (21672198) and the State Key Program
of National Natural Science Foundation of China (21432009).T.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 15
Ahmad acknowledges the China Scholarship Council (CSC) for
M.Synthesis of Functionalized α-Pyrone and Butenolide
supporting him for the Ph.D. degree from University of Science and
Technology of China in the category of 2015 CSC Fellowship
Awardee (CSC No. 2015GXZQ17).
1
2
3
4
5
6
7
8
Derivatives by Rhodium-Catalyzed Oxidative Coupling of
Substituted Acrylic Acids with Alkynes and Alkenes.J. Org.
Chem. 2009,74, 6295-6298.(c) Fukuyama, T.; Higashibeppu, Y.;
Yamaura, R.; Ryu, I.Ru-Catalyzed intermolecular [3+2+1]
cycloaddition of α, β-unsaturated ketones with silylacetylenes and
carbon monoxide leading to α-pyrones.Org. Lett. 2007,9, 587-
589.(d) Anastasia, L.; Xu, C.; Negishi, E.-i.Catalytic and selective
conversion of (Z)-2-en-4-ynoic acids to either 2H-pyran-2-ones in
the presence of ZnBr2 or (Z)-5-alkylidenefuran-2 (5H)-ones in the
presence of Ag2CO3.Tetrahedron Lett. 2002,43, 5673-5676.
(8) Tian, P.-P.; Cai, S.-H.; Liang, Q.-J.; Zhou, X.-Y.; Xu, Y.-H.;
Loh, T.-P.Palladium-Catalyzed Difunctionalization of Internal
Alkynes via Highly Regioselective 6-Endo Cyclization and
Alkenylation of Enynoates: Synthesis of Multisubstituted
PyronesOrg. Lett.2015,17, 1636-1639.
REFERENCES
(1) (a) Kamano, Y.; Nogawa, T.; Yamashita, A.; Hayashi, M.;
Inoue, M.; Drašar, P.; Pettit, G. R. Isolation and structure of a 20,
21-epoxybufenolide series from “Ch'an Su”.J. Nat. Prod.
2002,65, 1001-1005.(b) McGlacken, G. P.; Fairlamb, I. 2-Pyrone
natural products and mimetics: isolation, characterisation and
biological activity. J.Nat. Prod. Rep. 2005,22, 369-385.(c) Blunt,
J. W.; Copp, B. R.; Keyzers, R. A.; Munro, M. H.; Prinsep, M.
R.Marine natural products.Nat. Prod. Rep 2013,30, 237-323.(d)
Yokoe, H.; Mitsuhashi, C.; Matsuoka, Y.; Yoshimura, T.;
Yoshida, M.; Shishido, K.Enantiocontrolled total syntheses of
breviones A, B, and C.J. Am. Chem. Soc. 2011,133, 8854-8857.(e)
Sunazuka, T.; Ōmura, S. Total synthesis of α-pyrone
meroterpenoids, novel bioactive microbial metabolites.Chem. Rev.
2005,105, 4559-4580.
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
(9) Pathare, R. S.; Sharma, S.; Gopal, K.; Sawant, D. M.;
Pardasani, R. T.Palladium-catalyzed convenient one-pot synthesis
of multi-substituted 2-pyrones via transesterification and
alkenylation of enynoates. Tetrahedron Lett. 2017,58, 1387-1389.
(10) (a) Wang, H.; Han, X.; Lu, X.Palladium (II)-catalyzed
tandem annulation reaction of o-alkynylbenzoates with methyl
(2) (a) Gan, P.; Smith, M. W.; Braffman, N. R.; Snyder, S.
A.Pyrone Diels–Alder Routes to Indolines and Hydroindolines:
vinyl
ketone
for
the
synthesis
of
isocoumarins.
Syntheses
of
Gracilamine,
Mesembrine,
and
Tetrahedron.2013,69, 8626-8631.(b) Negishi, E.-i.; Kotora,
M.Regio-and stereoselective synthesis of γ-alkylidenebutenolides
and related compounds.Tetrahedron.1997,53, 6707-6738.
Δ7‐Mesembrenone.Angew. Chem. 2016,128, 3689-3694.(b) Sun,
C. L.; Fürstner, A.Formal Ring‐Opening/Cross‐Coupling
Reactions of 2‐Pyrones: Iron‐Catalyzed Entry into Stereodefined
Dienyl Carboxylates.Angew. Chem. Int. Ed. 2013,52, 13071-
13075.(c) Požgan, F.; Kranjc, K.; Kepe, V.; Polanc, S.; Kočevar,
M.Synthesis of 2H-pyran-2-ones and fused pyran-2-ones as useful
building blocks. Arkivoc.2007,2007, 97-111.(d) Posner, G. H.;
Nelson, T. D.; Kinter, C. M.; Johnson, N.Diels-Alder
cycloadditions using nucleophilic 3-(p-tolylthio)-2-pyrone.
Regiocontrolled and stereocontrolled synthesis of unsaturated,
bridged, bicyclic lactones. J. Org. Chem. 1992,57, 4083-4088.(e)
Larsson, R.; Sterner, O.; Johansson, M.Biomimetic synthesis
toward the transtaganolides/basiliolides. Org. Lett. 2009,11, 657-
660.(f) Vara Prasad, J.; Para, K. S.; Lunney, E. A.; Ortwine, D. F.;
Dunbar Jr, J. B.; Ferguson, D.; Tummino, P. J.; Hupe, D.; Tait, B.
D.Novel series of achiral, low molecular weight, and potent HIV-
1 protease inhibitors. J. Am. Chem. Soc. 1994,116, 6989-6990.(g)
Nelson, H. M.; Gordon, J. R.; Virgil, S. C.; Stoltz, B. M.Total
(11) (a) Yoshikawa, T.; Shindo, M.Stereoselective Synthesis of
(E)-2-En-4-ynoic Acids with Ynolates: Catalytic Conversion to
Tetronic Acids and 2-Pyrones.Org. Lett. 2009,11, 5378-5381.(b)
Rossi, R.; Bellina, F.; Biagetti, M.; Catanese, A.; Mannina,
L.Palladium-catalyzed synthesis of stereodefined 3-[(1, 1-
unsymmetrically disubstituted) methylidene] isobenzofuran-1
(3H)-ones and stereodefined 5-[(1, 1-unsymmetrically
disubstituted) methylidene] furan-2 (5H)-ones, Tetrahedron Lett.
2000,41, 5281-5286.(c) Liang, Y.; Xie, Y.-X.; Li, J.-H.Cy2NH·
HX-promoted cyclizations of o-(alk-1-ynyl) benzoates and (Z)-
alk-2-en-4-ynoate with copper halides to synthesize isocoumarins
and α-pyrone.Synthesis.2007,2007, 400-406.(d) Huang, J.; Li, L.;
Chen, H.; Xiao, T.; He, Y.; Zhou, L.Synthesis of 3-Aryl-2-
pyrones by Palladium-Catalyzed Cross-Coupling of Aryl Iodides
with Cyclic Vinyldiazo Ester.J. Org. Chem. 2017,82, 9204-9209.
(12) (a) Pankajakshan, S.; Xu, Y. H.; Cheng, J. K.; Low, M. T.;
Loh, T. P.Palladium‐Catalyzed Direct C-H Arylation of Enamides
with Simple Arene.Angew. Chem. Int. Ed. 2012,51, 5701-5705.(b)
Syntheses
of
(−)‐Transtaganolide
A,(+)‐Transtaganolide
and
B,(+)‐Transtaganolide C, and (−)‐Transtaganolide
D
Biosynthetic Implications.Angew. Chem. Int. Ed. 2013,52, 6699-
6703.
(3) (a) Lee, J. S. Recent Advances in the Synthesis of 2-
Pyrones.Marine drugs.2015,13, 1581-1620.(b) Goel, A.; Ram, V.
J.Natural and synthetic 2H-pyran-2-ones and their versatility in
organic synthesis.Tetrahedron.2009,65, 7865-7913.
(4) (a) Bellina, F.; Biagetti, M.; Carpita, A.; Rossi, R.Selective
synthesis of natural and unnatural 5, 6-disubstituted 2 (2H)-
pyranones via iodolactonization of 5-substituted (Z)-2-en-4-ynoic
acids. Tetrahedron.2001,57, 2857-2870.(b) Biagetti, M.; Bellina,
F.; Carpita, A.; Rossi, R.6-Chloro-2 (2H)-pyranone: a new 2
(2H)-pyranone synthon.Tetrahedron Lett. 2003,44, 607-610.
(5) (a) Yao, T.; Larock, R. C.Synthesis of isocoumarins and α-
pyrones via iodocyclization. Tetrahedron Lett. 2002,43, 7401-
7404.(b) Yao, T.; Larock, R. C.Synthesis of isocoumarins and α-
pyrones via electrophilic cyclization.J. Org. Chem. 2003,68,
5936-5942.
Feng,
trifluoromethylation
temperature.Chem.Sci.2012,3, 3458-3462.(c) Xu, Y.-H.; Chok, Y.
K.; Loh, T.-P.Synthesis and characterization of cyclic
C.;
Loh,
T.-P.Copper-catalyzed
enamides at
olefinic
room
of
a
vinylpalladium (II) complex: vinylpalladium species as the
possible intermediate in the catalytic direct olefination reaction of
enamide.Chem. Sci.2011,2, 1822-1825.(d) Xu, Y.-H.; He, T.;
Zhang, Q.-C.; Loh, T.-P.Synthesis of multi-substituted pyrroles
using enamides and alkynes catalyzed by Pd(OAc)2 with
molecular oxygen as an oxidant.Chem. Commun. 2014,50, 2784-
2786.(e) Zhang, X.; Wang, M.; Zhang, M.-X.; Xu, Y.-H.; Loh, T.-
P.Synthesis of Dienyl Ketones via Palladium (II)-Catalyzed
Direct Cross-Coupling Reactions between Simple Alkenes and
Vinyl Ketones: Application to the Synthesis of Vitamin A1 and
Bornelone.Org. Lett. 2013,15, 5531-5533.(f) Zhou, H.; Chung,
W.-J.; Xu, Y.-H.; Loh, T.-P.Direct arylation of cyclic enamides
via Pd (II)-catalyzed C–H activation.Chem. Commun. 2009, 3472-
3474.(g) Zhou, H.; Xu, Y. H.; Chung, W. J.; Loh, T.
P.Palladium‐Catalyzed Direct Arylation of Cyclic Enamides with
Aryl Silanes by sp2 C- H Activation.Angew. Chem. 2009,121,
5459-5461.(h) Shang, X.; Liu, Z.-Q.Transition metal-catalyzed C
vinyl–C vinyl bond formation via double C vinyl–H bond
activation.Chem. Soc. Rev. 2013,42, 3253-3260.(i) Li, Z.; Zhang,
(6) Wang, Y.; Burton, D. J.A facile, general synthesis of 3, 4-
difluoro-6-substituted-2-pyrones.J. Org. Chem. 2006,71, 3859-
3862.
(7) (a)Luo, T.; Dai, M.; Zheng, S.-L.; Schreiber, S. L.Syntheses of
α-Pyrones Using Gold-Catalyzed Coupling Reactions.Org. Lett.
2011,13, 2834-2836.(b)Mochida, S.; Hirano, K.; Satoh, T.; Miura,
14
ACS Paragon Plus Environment

Page 15 of 15
The Journal of Organic Chemistry
Y.; Liu, Z.-Q.Pd-catalyzed olefination of perfluoroarenes with
Huang, L.; Wu, X.; Jiang, H.Nucleopalladation Triggering the
1
2
3
4
5
6
7
allyl esters.Org. Lett. 2011,14, 74-77.
Oxidative Heck Reaction: A General Strategy to Diverse β-Indole
Ketones. Org. Lett. 2013,15, 5940-5943.
(13) (a) Zheng, M.; Huang, L.; Tong, Q.; Wu, W.; Jiang,
H.Oxypalladation Initiating the Oxidative Heck Reaction with
Alkenyl Alcohols: Synthesis of Isocoumarin–Alkanones.Eur. J.
Org. Chem. 2016,2016, 663-667.(b) Huang, W.-Y.; Nishikawa,
T.; Nakazaki, A.Palladium-Catalyzed Cascade Wacker/Allylation
Sequence with Allylic Alcohols Leading to Allylated
Dihydropyrones.ACS Omega.2017,2, 487-495.
(19) (a) Liang, Q. J.; Yang, C.; Meng, F. F.; Jiang, B.; Xu, Y. H.;
Loh, T. P.Chelation versus Non‐Chelation Control in the
Stereoselective Alkenyl sp2 C−H Bond Functionalization
Reaction.Angew. Chem. 2017,129, 5173-5177.(b) Zhang, D.; Liu,
J.; Córdova, A.; Liao, W.-W.Recent Developments in Palladium-
Catalyzed
Oxidative
Cascade
Carbocyclization.ACS
(14) (a) Roggen, M.; Carreira, E. M.Enantioselective Allylic
Etherification: Selective Coupling of Two Unactivated
Alcohols.Angew. Chem. Int. Ed. 2011,50, 5568-5571.(b) Roggen,
M.; Carreira, E. M.Enantioselektive Allylethersynthese: selektive
Kupplung von zwei Alkoholen.Angew. Chem. 2011,123, 5683-
5686.(c) Banerjee, D.; Junge, K.; Beller, M.Cooperative catalysis
by palladium and a chiral phosphoric acid: enantioselective
amination of racemic allylic alcohols.Angew. Chem. Int. Ed.
2014,53, 13049-13053.(d) Krautwald, S.; Schafroth, M. A.;
Sarlah, D.; Carreira, E. M.Stereodivergent α-allylation of linear
aldehydes with dual iridium and amine catalysis.J. Am. Chem.
Soc. 2014,136, 3020-3023.(e) Hamilton, J. Y.; Sarlah, D.;
Carreira, E. M.Iridium-catalyzed enantioselective allyl–alkene
coupling.J. Am. Chem. Soc. 2014,136, 3006-3009.
(15) (a) Hoye, T. R.; Zhao, H.Some allylic substituent effects in
ring-closing metathesis reactions: Allylic alcohol activation.Org.
Lett. 1999,1, 1123-1125.(b) Colbon, P.; Ruan, J.; Purdie, M.;
Mulholland, K.; Xiao, J.Double arylation of allyl alcohol via a
one-pot Heck arylation–isomerization–acylation cascade.Org. Lett
2011,13, 5456-5459.(c) Ahlsten, N.; Bermejo Gómez, A.;
Catalysis.2017,7, 7051-7063.(c)Zhang, Z.; Ouyang, L.; Wu, W.;
Li, J.; Zhang, Z.; Jiang, H.Palladium-catalyzed intermolecular
oxyvinylcyclization of alkenes with alkynes: An approach to 3-
methylene γ-lactones and tetrahydrofurans.J. Org. Chem.
2014,79, 10734-10742.(d)Yeung, C. S.; Dong, V. M.Catalytic
dehydrogenative cross-coupling: forming carbon− carbon bonds
by oxidizing two carbon− hydrogen bonds.Chem. Rev. 2011,111,
1215-1292.(e) Yu, H.; Jin,W.; Sun, C.; Chen, J.; Du, W.; He, S.;
Yu, Z.Palladium‐Catalyzed Cross‐Coupling of Internal Alkenes
with Terminal Alkenes to Functionalized 1, 3‐Butadienes Using
C-H Bond Activation: Efficient Synthesis of Bicyclic
Pyridones.Angew. Chem. 2010,122, 5928-5933.
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
(20) (a) Faizi, D. J.; Issaian, A.; Davis, A. J.; Blum, S. A.Catalyst-
Free Synthesis of Borylated Lactones from Esters via
Electrophilic Oxyboratio.J. Am. Chem. Soc. 2016,138, 2126-
2129.(b) Huang, Q.; Larock, R. C.Synthesis of 4-(1-alkenyl)
isoquinolines
by
palladium
(II)-catalyzed
cyclization/olefination.J. Org. Chem. 2003,68, 980-988.(c) Zhao,
P.; Chen, D.; Song, G.; Han, K.; Li, X.Palladium-Catalyzed
Cascade Cyclization–Oxidative Olefination of tert-Butyl 2-
AlkynylbenozatesJ. Org. Chem. 2012,77, 1579-1584.
(21) Paterson, I.; Paquet, T. Total synthesis and configurational
validation of (+)-phorbaside A. Org. Lett. 2010, 12, 2158-2161.
(22) (a) .Lin,H.; Liu, Y.; Wu. Z-L.Highly diastereo-and enantio-
selective epoxidation of secondary allylic alcohols catalyzed by
styrene monooxygenase. Chem. Commun. 2011, 47, 2610-2612.
(b) Lehmann, J.; Lloyd-Jones, G. C. Regiocontrol and
stereoselectivity in tungsten-bipyridine catalysed allylic alkylation
Tetrahedron.1995, 51, 8863-8874.
Martín‐Matute,
B.Iridium‐Catalyzed
1,
3‐Hydrogen
Shift/Chlorination of Allylic Alcohols.Angew. Chem. Int. Ed.
2013,52, 6273-6276.(d) Shibuya, G. M.; Kanady, J. S.;
Vanderwal, C. D.Stereoselective dichlorination of allylic alcohol
derivatives to access key stereochemical arrays of the
chlorosulfolipids.J. Am. Chem. Soc. 2008,130, 12514-12518.
(16) (a) Vellakkaran, M.; Andappan, M. M.; Kommu,
N.Replacing a stoichiometric silver oxidant with air: ligated Pd
(II)-catalysis to β-aryl carbonyl derivatives with improved
chemoselectivity.Green Chem. 2014,16, 2788-2797.(b) Bunescu,
A.; Wang, Q.; Zhu, J.Copper‐Catalyzed Cyanomethylation of
Allylic Alcohols with Concomitant 1, 2‐Aryl Migration: Efficient
Synthesis of Functionalized Ketones Containing an α‐Quaternary
Center.Angew. Chem. Int. Ed. 2015,54, 3132-3135.(c) Werner, E.
W.; Mei, T.-S.; Burckle, A. J.; Sigman, M. S.Enantioselective
Heck arylations of acyclic alkenyl alcohols using a redox-relay
strategy.Science.2012,338, 1455-1458.
(17) (a) Xia, Y.; Qu, S.; Xiao, Q.; Wang, Z.-X.; Qu, P.; Chen, L.;
Liu, Z.; Tian, L.; Huang, Z.; Zhang, Y.Palladium-Catalyzed
Carbene Migratory Insertion Using Conjugated Ene–Yne–
Ketones as Carbene Precursors.J. Am. Chem. Soc. 2013,135,
13502-13511.(b) Cai, Z.-J.; Yang, C.; Wang, S.-Y.; Ji, S.-
J.Palladium-catalyzed highly regioselective 6-exo-dig cyclization
and alkenylation of ortho-ethynylanilides: the synthesis of
polyene-substituted benzo [d][1, 3].Chem. Commun. 2015,51,
14267-14270.
(18) (a) Huang, L.; Wang, Q.; Qi, J.; Wu, X.; Huang, K.; Jiang,
H.Rh (III)-catalyzed ortho-oxidative alkylation of unactivated
arenes with allylic alcohols.Chem. Sci.2013,4, 2665-2669.(b) Qi,
J.; Huang, L.; Wang, Z.; Jiang, H.Ruthenium and rhodium-
catalyzed oxidative alkylation of C–H bonds: efficient access to β-
aryl ketones.Org. Biomol. Chem. 2013,11, 8009-8013.(c) Weiss,
M.; Peters, R.Catalytic direct dehydrogenative cross-couplings of
C–H (Pro) nucleophiles and allylic alcohols without an additional
oxidant.ACS Catalysis.2014,5, 310-316.(d) Wen, Y.; Huang, L.;
Jiang, H.; Chen, H.Synthesis of δ-Bromo γ, δ-Unsaturated
Carbonyl Compounds via Palladium-Catalyzed Bromoalkylation
of Alkynoates.J. Org. Chem. 2012,77, 2029-2034.(e) Wang, Q.;
15
ACS Paragon Plus Environment