Palladium-Catalyzed Synthesis of β,β-Diaryl α,β-Unsaturated Ketones

Article abstract of DOI:10.1055/s-0037-1611354

We herein describe a versatile palladium-catalyzed synthesis of β,β-diaryl α,β-unsaturated ketones. A broad range of aryl halides react with β-arylbutanones to afford biologically useful, symmetrical and unsymmetrical ketones. The use of 4,5-diazafluoren-9-one and oxygen makes this one-pot reaction more applicable. A plausible mechanism involving palladium-catalyzed oxidative Heck-type cross-coupling is also proposed.

Full text of DOI:10.1055/s-0037-1611354

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–K
paper
A
en
Y.-l. Zheng et al.
Paper
Synthesis
Palladium-Catalyzed Synthesis of β,β-Diaryl α,β-Unsaturated
Ketones
Yi-lin Zhenga
Li Xiaoa
Qiong Xiea
Li-ming Shao*a,b
H
Ar1
R1
Ar1
R1
Pd(OAc)2 (10 mol%), L1 (10 mol%), CsOAc
Ar2
X
+
Ar2
O
DMSO, O2, 100 °C, 4–24 h
O
O
Ar1 = C6H5, 4-CH3OC6H4,
4-ClC6H4, 4-FC6H4
R1 = CH3, C6H5, H
X = I, Br
37 examples
up to 88% yield
a Department of Medicinal Chemistry, School of Pharmacy, Fudan
University, 826 Zhangheng Road, Pudong New District, Shanghai
201203, P. R. of China
b State Key Laboratory of Medical Neurobiology, Fudan University,
138 Yixueyuan Road, Shanghai 200032, P. R. of China
limingshao@fudan.edu.cn
L1
N
N
Received: 27.07.2018
Accepted after revision: 23.10.2018
Published online: 03.12.2018
a subclass of β,β-diaryl α,β-unsaturated ketones with one
phenyl motif (Scheme 1, e).7 However, the strict substrate
restriction cannot be ignored. In 2014, Cheng and co-work-
ers reported a palladium-catalyzed dehydrogenative β,β-di-
arylation method for the synthesis of symmetrical β,β-di-
aryl α,β-unsaturated ketones (Scheme 1, f).8 While this
method is convenient, the synthesis of unsymmetrical
products is limited.
DOI: 10.1055/s-0037-1611354; Art ID: ss-2018-h0504-op
Abstract We herein describe a versatile palladium-catalyzed synthesis
of β,β-diaryl α,β-unsaturated ketones. A broad range of aryl halides re-
act with β-arylbutanones to afford biologically useful, symmetrical and
unsymmetrical ketones. The use of 4,5-diazafluoren-9-one and oxygen
makes this one-pot reaction more applicable. A plausible mechanism
involving palladium-catalyzed oxidative Heck-type cross-coupling is
also proposed.
Previous work
Ar1
Heck
Key words ketones, palladium, 4,5-diazafluoren-9-one, oxidation,
cross-coupling
Ar2
X
[a]
[b]
[c]
+
O
EtS
Liebeskind–Srogl
2 steps
H
SEt
O
Ar1
β,β-Diaryl α,β-unsaturated carbonyl compounds repre-
sent an important organic class with potential utility for
forming various biologically useful molecules.1 Recently,
methods for carbonyl compound synthesis have been wide-
ly explored,2 with approaches particularly suitable for β,β-
diaryl α,β-unsaturated ketone synthesis rather less so. Since
β,β-diaryl α,β-unsaturated ketones are stable and useful,
broadening synthetic methods for their preparation is nec-
essary.
Existing approaches for β,β-diaryl α,β-unsaturated ke-
tone synthesis are limited, particularly when wide varia-
tions of aryl groups are desired. Heck arylation of α,β-un-
saturated ketones is a major route to synthesize β,β-diaryl
α,β-unsaturated ketones (Scheme 1, a).3 α-Oxo ketene dith-
ioacetals give the desired products, via oxo-directing Lieb-
eskind–Srogl cross-coupling, after two steps (Scheme 1, b).4
Procedures such as diaryl-substituted tertiary alcohol OH-
directed Wacker oxidation–elimination (Scheme 1, c)5 and
oxidative palladium-catalyzed rearrangement (Scheme 1,
d)6 have also been reported. Arylacetylenes react with ben-
zene under acidic zeolite or superacid conditions, affording
OH
Ar2
Wacker oxidation
O
Ar1
Ar2
OH
PdCl2, CsOAc
[d]
Ar1
Ar2
DMA/MeCN, O2, 80 °C
H
zeolite H+ or superacid
Ar
[e]
[f]
+
Ar
O
Ph
O
Pd(OAc)2, Na2CO3
DMSO, 120 °C
Ar
+
Ar
X
O
Ar
O
This work
H
Ar1
R1
Ar1
R1
Pd(OAc)2, L1, CsOAc
Ar2
X
+
Ar2
O
DMSO, O2, 100 °C
16–24 h
O
Scheme 1 Strategies for β,β-diaryl α,β-unsaturated ketones synthesis
Considering the biological importance of β,β-diaryl α,β-
unsaturated ketones and synthetic difficulties, developing a
convenient method for both symmetrical and unsymmetri-
cal ketones continues to be valuable while challenging.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

B
Y.-l. Zheng et al.
Paper
Synthesis
Table 1 (continued)
Herein, we report a novel palladium-catalyzed oxidative
and Heck-type cross-coupling reaction to efficiently syn-
thesize β,β-diaryl α,β-unsaturated ketones.
Entry Catalystb
Additive
Ligand
Solvent (mL)e Yield
(%)f
(equiv)c
(mol%)d
28h,i Pd(OAc)2
CsOAc (4.0)
L1 (10)
DMSO (0.5)
66
Table 1 Optimization of the Reaction Conditionsa
29h,j Pd(OAc)2
CsOAc (4.0)
L1 (10)
DMSO (0.5)
62
a Reaction conditions: 1a (0.5 mmol), 2a (1.25 mmol, entries 1–7; 1.75
mmol, entries 8–29), stirred at 120 °C (entries 1–27), sealed 10 mL tube,
24 h.
catalyst
ligand
additive
CH3
I
b Catalyst loading: 10 mol%.
CH3
+
O
c 0.75 mmol (entry 1); 1 mmol (entry 2); 2 mmol (entries 3–29).
d L1 (10 mol%), L2 (20 mol%), L3 (20 mol%), L4 (10 mol%), L5 (10 mol%).
e 2 mL (entries 1–13); 1 mL (entry 14); 0.5 mL (entries 15, 17–29); 0.2 mL
(entry 16).
solvent, temp
O
3aa
1a
2a
O
Ph
OH
Ph
f Yield of isolated product, based on 1a.
g The mixture was purged with argon.
N
H
h The mixture was purged with O2.
N
N
L2
L1
i Reaction at 100 °C for 16 h.
OCH3
j Reaction at 80 °C for 24 h.
NH2
N
N
N
N
H3C
CH3
L3
L4
L5
Utilizing stable and readily available β-arylbutanones
and aryl halides, various symmetrical and unsymmetrical
β,β-diaryl α,β-unsaturated ketones were obtained, includ-
ing electron-withdrawing aryl products. Furthermore, the
method is also convenient for β,β-diaryl α,β-unsaturated al-
dehyde synthesis. However, this method fails to give rele-
vant dehydrogenative β-arylation products from β-alkylat-
ed ketones. Such an unsuccessful result was also reported
by Cheng and co-workers.8 We assume reaction at the
methylene site in β-alkylated ketones is more difficult than
that in β-aryl ketones or at the terminal methyl group.
We started our investigation by using benzylacetone
(1a) and iodobenzene (2a) as model substrates. Based on
our previously reported work with aldehydes2b the reaction
was initially performed in the presence of Pd(OAc)2 and
Ag2CO3 in HOAc at 120 °C for 24 hours (Table 1, entry 1).
Unfortunately, only a trace amount of the desired product
3aa was afforded. We hypothesized that the poor reactivity
of ketone 1a might relate to the higher pKa of the α-C–H
bond compared to aldehydes. We assumed that a basic en-
vironment may be superior for ketones. Inspired by Cheng’s
work,8 we carried out the reaction of 1a (0.5 mmol) and 2a
(1.25 mmol) using Pd(OAc)2 (10 mol%) and Na2CO3 (1
mmol) in DMSO (2 mL) at 120 °C for 24 hours (Table 1, en-
try 2), and 3aa was only obtained in 18% yield. To increase
the yield, we set out to optimize the reaction conditions.
Firstly, we doubled the amount of Na2CO3 (2 mmol), and the
yield increased to 25% (Table 1, entry 3). Then, various bases
(Table 1, entries 4–7) were screened, with CsOAc being the
most effective (30% yield; Table 1, entry 6). Considering the
low conversion rate of 1a, as well as the homocoupled by-
product from 2a,9 we increased the amount of 2a (3.5
equiv) which resulted in an elevated 37% yield (Table 1, en-
try 8). After further exploration, we found that DMSO was
the most suitable solvent and 0.5 mL was the best solvent
volume. Screening other palladium catalysts (Table 1, en-
tries 17–19) did not provide a better result. To our delight,
Entry Catalystb
Additive
(equiv)c
Ligand
Solvent (mL)e Yield
(%)f
(mol%)d
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Ag2CO3 (1.5)
Na2CO3 (2.0)
Na2CO3 (4.0)
NaOAc (4.0)
KOAc (4.0)
–
–
–
–
–
–
–
–
–
–
–
–
–
HOAc (2)
DMSO (2)
DMSO (2)
DMSO (2)
DMSO (2)
DMSO (2)
DMSO (2)
DMSO (2)
DMF (2)
trace
18
3
25
4
27
5
25
6
CsOAc (4.0)
AgOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
30
7
trace
37
8
9
24
10
11
12
13
1,4-dioxane (2) trace
toluene (2)
trace
trace
29
n-BuOH (2)
DMSO/H2O
(9:1, 2)
14
15
16
17
18
19
20
21
22
23
24
25g
26h
27h
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
PdCl2
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
CsOAc (4.0)
–
DMSO (1)
38
45
40
41
34
29
50
47
41
13
40
41
49
56
–
DMSO (0.5)
DMSO (0.2)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
DMSO (0.5)
–
–
–
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
–
L1 (10)
L2 (20)
L3 (20)
L4 (10)
L5 (10)
–
–
L1 (10)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

C
Y.-l. Zheng et al.
Paper
Synthesis
addition of 4,5-diazafluoren-9-one (L1, DAF) promoted
Pd(OAc)2 efficiency (50% yield; Table 1, entry 20),10 espe-
cially under oxygen atmosphere (56% yield; Table 1, entry
27). Subsequently, different temperature conditions (Table
1, entries 27–29) were examined, and 100 °C for 16 hours
turned out to give the highest yield (66%; Table 1, entry 28).
With the optimized conditions in hand, we further ex-
plored the scope and generality of the reaction. As shown in
Table 2, this method was practical for β-arylbutanones 1a–
d and aryl iodides 2 to obtain the desired β,β-diaryl α,β-un-
saturated ketones 3aa–dd under the standardized condi-
tions. The position of a substituent on the aryl iodide had a
huge impact on the reaction outcome. If an ortho-substitut-
ed iodobenzene was employed, the yield decreased signifi-
cantly because of steric effects (Table 2, 3ad and 3al). In
comparison, meta-substituted iodobenzenes (Table 2, 3ac
and 3ak) and para-substituted iodobenzenes (Table 2, 3ab
and 3aj) still delivered the products in moderate yields.
Electronic properties also influenced the results. An elec-
tron-donating group on the aryl iodide (Table 2, 3ab and
3ac) was more beneficial than an electron-withdrawing
group (Table 2; 3aj, 3ak, 3am, and 3an). Furthermore, com-
pounds with a terminal phenyl group resulted in 75–88%
yield (Table 2, 3da–dd), higher than the 59–71% yield for
compounds with a terminal methyl group (Table 2; 3aa,
3ab, 3ah, and 3aj), which may be attributed to a reduction
in the side reactions involving the terminal methyl group.
Because of separation difficulty, unsymmetrical β,β-diaryl
α,β-unsaturated ketones were obtained as a mixture of geo-
metric isomers (see Table 2). The ratio of stereoisomers was
calculated on the basis of NMR spectroscopy, and the
trans/cis configuration of 3ag (E/Z 1:0.1) was identified by
comparison with reported spectroscopic data.4
copy (see Supporting Information). Although the underly-
ing mechanism remains to be elucidated, taking the experi-
mental results obtained during optimization of the reaction
conditions together with mechanisms suggested in earlier
reports,11 a plausible oxidative Heck-type cross-coupling
mechanism for the formation of β,β-diaryl α,β-unsaturated
ketones is proposed (Scheme 3).
I
H
2
Cl
O
+
Pd(OAc)2, L1, CsOAc
O
O
DMSO, O2
100 °C, 1 h
1a
4
Cl
3am
Scheme 2 Mechanism exploration. Reagents and conditions: 1a (1.5
mmol), 2 (5.25 mmol), Pd(OAc)2 (10 mol%), L1 (10 mol%), CsOAc (6.0
mmol), DMSO (1.5 mL), O2 atmosphere, 100 °C, 1 h.
Ln
PdOAc
1
O
5
O
HOAc
H2O2
O
Oxidation
HOAc
LnHPdOAc
O
O
HOAc
Notably, using aryl bromides to synthesize the β,β-dia-
ryl α,β-unsaturated ketones (Table 3) was plausible, albeit
with relatively lower yields than the corresponding aryl io-
dides. For para-methyl substitution the yield of the unsepa-
rated geometric isomers reached 52% (Table 3, 3ab), while
para-fluoro substitution resulted in 58% yield (Table 3, 3aj).
The method was also convenient for the synthesis of
β,β-diaryl α,β-unsaturated aldehydes (Table 4). The reaction
time was shortened with comparable yields to the corre-
sponding methyl ketones. Also, the predominant trans/cis
configuration was consistent with the results under acidic
conditions.2b
LnPd0
O2
ArI
2
HOAc, CsI
CsOAc
Ln
I
Ar Pd
Heck-type cross-coupling
HPdILn
H
6
Ln
IPd
O
Ar
O
3
Ar
O
When we looked into the mechanism behind the reac-
tion, we found that oxidized intermediate 4 (Scheme 2) was
generated within 1 hour, as detected by H NMR spectros-
7
Scheme 3 Plausible mechanism
1
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

D
Y.-l. Zheng et al.
Paper
Synthesis
Table 2 Synthesis of β,β-Diaryl α,β-Unsaturated Ketones from β-Arylbutanones and Aryl Iodidesa
H
I
Ar1
R1
Ar1
R1
Pd(OAc)2 (10 mol%), L1 (10 mol%)
CsOAc (4 equiv)
R2
O
+
R2
O
DMSO (1.5 mL), O2, 100 °C, 16 h
1
2
1a: Ar1 = C6H5, R1 = CH3
3
1b: Ar1 = 4-CH3OC6H4, R1 = CH3
1c: Ar1 = 4-FC6H4, R1 = CH3
1c': Ar1 = 4-ClC6H4, R1 = CH3
1d: Ar1 = C6H5, R1 = C6H5
Entry
Compound
R2
Yield (%)b
Ratioc
1
3aa
3ab
3ac
3ad
3ae
3af
4-H
66
71
57
trace
55
57
53
59
57
60
42
15
38
26
60
78
–
H
2
4-CH3
3-CH3
2-CH3
4-Et
1:0.9
1:0.5
–
CH3
3
O
4
R2
5
1:0.3
1:0.3
1:0.1 (E/Z)
1:0.6
1:0.3
1:0.7
1:0.3
–
6
4-i-Pr
4-t-Bu
4-OCH3
3-OCH3
4-F
7
3ag
3ah
3ai
8
9
10
11
12
13
14
15
16
3aj
3ak
3al
3-F
2-F
3am
3an
3ao
3ap
4-Cl
1:0.2
1:0.1
1:0.4
1:0.7
4-Br
3,5-(CH3)2
3,4-(CH3)2
17
18
19
20
3ba
3bb
3bc
3bd
4-CH3
4-OCH3
4-t-Bu
4-F
85
56
64
57
1:0.9
–
H3CO
H
CH3
1:0.6
1:0.4
O
R2
21
22
23
24
3ca (X = F)
3cb (X = F)
3c′a (X = Cl)
3c′b (X = Cl)
4-CH3
4-Cl
60
24
55
50
1:0.4
1:0.3
1:0.6
1:0.3
X
H
CH3
4-CH3
3-CH3
O
R2
25
26
27
28
3da
3db
3dc
3dd
4-H
84
88
78
75
–
H
4-CH3
4-OCH3
4-F
1:0.9
1:0.8
–
O
R2
a Reaction conditions: 1 (1.5 mmol), 2 (5.25 mmol), Pd(OAc)2 (10 mol%), L1 (10 mol%), CsOAc (6.0 mmol), DMSO (1.5 mL), stirred under O2 atmosphere, 100 °C,
16 h.
b Yield of isolated product, based on 1.
c Mixture of geometric isomers; ratio of major versus minor isomer calculated on the basis of NMR spectroscopic data.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

E
Y.-l. Zheng et al.
Paper
Synthesis
Table 3 Synthesis of β,β-Diaryl α,β-Unsaturated Ketones from Benzyl-
In the catalytic cycle, DAF (L1) may have an influence on
all steps, which allows for the development of a more reac-
tive and robust catalyst. Also, by forming a complex with
palladium, DAF may reduce the aggregation of Pd0, decreas-
ing palladium precipitation.14d Recently, Campbell and
Stahl15 and Le Bras and co-workers16 proposed a PdIV reso-
nance contribution via π-backbonding formed by PdII and
DAF (Scheme 4). CsOAc is likely to serve as the OAc anion
provider13 and neutralizer, promoting the catalytic cycle.
The process is sensitive to the nature of the solvent and the
yields are highest in DMSO, which possibly contributes to
the regeneration of the active catalytic species.17
acetone and Aryl Bromidesa
H
Br
Pd(OAc)2 (10 mol%)
CH3
L1 (10 mol%)
CH3
CsOAc (4 equiv)
+
O
DMSO (1.5 mL)
O2, 100 °C, 24 h
O
R2
R2
1a
2'
3a
Entry
Compound
R2
Yield (%)b
Ratioc
–
1
2
3
4
3aa
3ab
3ac
3aj
4-H
33
52
34
58
4-CH3
3-CH3
4-F
1:0.2
1:1
O
O
1:0.1
a Reaction conditions: 1a (1.5 mmol), 2′ (5.25 mmol), Pd(OAc)2 (10 mol%),
L1 (10 mol%), CsOAc (6.0 mmol), DMSO (1.5 mL), stirred under O2 atmo-
sphere, 100 °C, 24 h.
N
N
N
N
PdIV
PdII
b Yield of isolated product, based on 1a.
Scheme 4 PdIV resonance contribution via π-backbonding
c Mixture of geometric isomers; ratio of major versus minor isomer calculat-
ed on the basis of NMR spectroscopic data.
Compound 3aa was obtained in 41% yield under argon
atmosphere (Table 1, entry 25). In addition to our proposed
mechanism, we assume that under oxygen-free conditions
ArI8,18 could form an Ar–PdII–I intermediate with palladium
and then conduct the β-H elimination as well as regenerate
active catalyst in the oxidation cycle, which may also func-
tion under oxygen atmosphere.
To summarize, we have developed a novel and efficient
strategy for the one-pot synthesis of symmetrical and un-
symmetrical β,β-diaryl α,β-unsaturated ketones and alde-
hydes. Through palladium catalysis with the help of the li-
gand 4,5-diazafluoren-9-one under oxygen atmosphere,
this reaction was made more applicable and versatile. Over-
all, 32 β,β-diaryl α,β-unsaturated ketones and aldehydes
were synthesized in up to 88% yield. Using aryl bromides
instead of aryl iodides to synthesize the β,β-diaryl α,β-un-
saturated ketones is also feasible. In addition, a plausible
palladium-catalyzed oxidative Heck-type cross-coupling
mechanism was proposed.
Table 4 Synthesis of β,β-Diaryl α,β-Unsaturated Aldehydes from Ben-
zenepropanal and Aryl Iodidesa
H
Pd(OAc)2 (10 mol%)
L1 (10 mol%)
I
H
CsOAc (3 equiv)
H
+
O
DMSO (1.5 mL)
O2, 100 °C, 4 h
O
R2
R2
1e
2
3e
Entry
Compound
R2
4-H
Yield (%)b
Ratioc
1
2
3
4
5
3ea
3eb
3ec
3ed
3ee
76
75
68
55
35
–
4-CH3
3-CH3
4-t-Bu
4-Cl
1:0.5
1:0.6
1:0.3
1:0.7
a Reaction conditions: 1e (1.5 mmol), 2 (3.75 mmol), Pd(OAc)2 (10 mol%),
L1 (10 mol%), CsOAc (4.5 mmol), DMSO (1.5 mL), stirred under O2 atmo-
sphere, 100 °C, 4 h.
b Yield of isolated product, based on 1e.
All commercially available reagents were used without further purifi-
cation unless otherwise stated. Compounds were purified using a
Smart Flash AI-580S system (Yamazen Co. Ltd.). 1H and 13C NMR spec-
tra were recorded on Varian 400 MHz and Bruker 600 MHz spectrom-
eters, respectively. Chemical shifts in 1H NMR spectra are reported in
parts per million (ppm) on the δ scale from an internal standard of
TMS (0.00 ppm). Data are reported as follows: chemical shift (δ), mul-
tiplicity (standard abbreviations), coupling constant(s) in hertz (Hz),
and integration. Chemical shifts in 13C NMR spectra are reported in
ppm from the central peak of TMS (0.0 ppm) on the δ scale. MS data
were recorded on an Agilent Technologies 6120 quadrupole mass
spectrometer. HRMS data were recorded on an AB Sciex 4000 quadru-
pole mass spectrometer.
c Mixture of geometric isomers; ratio of major versus minor isomer calcu-
lated on the basis of NMR spectroscopic data.
The reaction is initiated by activation of the α-C–H
bond, transforming 1 into intermediate 5.10a,12 Subsequent
fast β-H elimination from 5 affords the enone product 413
and a PdII–hydride intermediate. After loss of acetic acid,
the Pd0 can be oxidized by oxygen to regenerate the PdII cat-
alyst.14 Compound 4 undergoes a typical Heck reaction with
aryl iodide 2, catalyzed by palladium, to give the desired
β,β-diaryl α,β-unsaturated ketone 3.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

F
Y.-l. Zheng et al.
Paper
Synthesis
β-Arylbutanones 1c and 1c′; General Procedure19
1H NMR (400 MHz, CDCl3): δ = 7.42–7.28 (m, 7.3 H), 7.23–7.09 (m, 9.8
H), 6.58 (s, 1 H, major CH), 6.54 (s, 0.9 H, minor CH), 2.41 (s, 2.7 H,
minor CH3), 2.36 (s, 3 H, major CH3), 1.89 (s, 2.7 H, minor CH3), 1.86 (s,
3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.4, 200.2, 154.2, 154.1, 141.1,
139.8, 139.2, 138.9, 137.9, 136.0, 129.7, 129.6, 129.4, 129.2, 129.1,
128.7, 128.5, 128.4, 128.4, 127.6, 126.9, 30.3, 21.4, 21.3.
A mixture of pentane-2,4-dione (2 g, 20 mmol), a 4-substituted ben-
zyl halide (20 mmol), and anhydrous K2CO3 (20 mmol) in MeOH (60
mL) was heated at reflux temperature for 16 h. The mixture was then
cooled to room temperature, MeOH was removed under reduced
pressure, and the resulting residue was partitioned between EtOAc
(30 mL) and H2O (30 mL). The organic layer was separated, and the
aqueous layer was extracted further with EtOAc (3 × 30 mL). The com-
bined organic phase was dried over anhydrous Na2SO4 and concen-
trated under reduced pressure. The crude mixture was then purified
by column chromatography (silica gel; n-hexane/EtOAc) to afford the
desired product.
MS (ESI): m/z = 237.2 [M + H]+.
4-Phenyl-4-(m-tolyl)but-3-en-2-one (3ac)
Yellow oil; yield: 202 mg (57%); mixture of geometric isomers
(~1:0.5).
1H NMR (400 MHz, CDCl3): δ = 7.42–7.39 (m, 3 H), 7.35–7.30 (m, 2.5
H), 7.25–7.12 (m, 5 H), 7.13 (s, 1 H), 7.08 (d, J = 7.3 Hz, 1 H), 7.03 (s, 1
H), 6.58 (s, 1 H, major CH), 6.57 (s, 0.5 H, minor CH), 2.36 (s, 1.5 H,
minor CH3), 2.32 (s, 3 H, major CH3), 1.88 (s, 4.5 H).
13C NMR (151 MHz, CDCl3): δ = 200.2, 200.0, 154.0, 140.7, 138.9,
138.8, 138.0, 137.9, 130.1, 130.0, 129.5, 129.4, 129.3, 128.8, 128.6,
128.3, 128.2, 127.6, 127.5, 126.6, 125.6, 30.2, 30.1, 21.2, 21.2.
4-(4-Fluorophenyl)butan-2-one (1c)19
Colourless oil; yield: 1.43 g (43%).
1H NMR (400 MHz, CDCl3): δ = 7.19–7.05 (m, 2 H), 6.95 (t, J = 7.9 Hz, 2
H), 2.86 (t, J = 7.0 Hz, 2 H), 2.73 (t, J = 7.1 Hz, 2 H), 2.13 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 207.7, 161.5 (d, J = 234 Hz), 136.8 (d,
J = 2 Hz), 129.8 (d, J = 8 Hz), 115.3 (d, J = 21 Hz), 45.2, 30.2, 29.0.
MS (ESI): m/z = 167.2 [M + H]+.
HRMS (ESI): m/z calcd for
C17H16O
[M + H]+: 237.1274; found:
237.1268.
4-(4-Chlorophenyl)butan-2-one (1c′)20
Colourless oil; yield: 1.60 g (44%).
4-(4-Ethylphenyl)-4-phenylbut-3-en-2-one (3ae)
1H NMR (400 MHz, CDCl3): δ = 7.24 (d, J = 8.2 Hz, 2 H), 7.11 (d, J = 8.1
Hz, 2 H), 2.86 (t, J = 7.4 Hz, 2 H), 2.74 (t, J = 7.4 Hz, 2 H), 2.14 (s, 3 H).
Yellow oil; yield: 205 mg (55%); mixture of geometric isomers
(~1:0.3).
13C NMR (151 MHz, CDCl3): δ = 207.7, 139.6, 132.0, 129.9, 128.8, 45.1,
30.3, 29.2.
MS (ESI): m/z = 183.1 [M + H]+.
1H NMR (400 MHz, CDCl3): δ = 7.43–7.29 (m, 4.6 H), 7.24–7.11 (m, 7.1
H), 6.59 (s, 1 H, major CH), 6.54 (s, 0.3 H, minor CH), 2.72–2.63 (m, 2.6
H), 1.88 (s, 0.9 H, minor CH3), 1.86 (s, 3 H, major CH3), 1.31–1.26 (m,
0.9 H, minor CH3), 1.24 (t, J = 7.6 Hz, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.4, 200.1, 154.3, 154.1, 146.2,
145.2, 141.2, 139.3, 138.2, 136.3, 129.9, 129.7, 129.5, 128.8, 128.6,
128.5, 128.5, 128.1, 128.0, 127.7, 127.1, 30.4, 30.3, 28.8, 28.7, 15.4.
β,β-Diaryl α,β-Unsaturated Ketones 3aa–dd (Table 2); General Pro-
cedure
A tube (30 mL) equipped with a magnetic stirring bar was charged
with 1 (1.5 mmol), 2 (5.25 mmol), Pd(OAc)2 (10 mol%), L1 (10 mol%),
and CsOAc (6.0 mmol) in DMSO (1.5 mL), then the tube was sealed,
purged with O2, and the mixture was stirred at 100 °C for 16 h. At the
end of the reaction, the mixture was partitioned between EtOAc (30
mL) and H2O (30 mL). The organic layer was separated, and the aque-
ous layer was extracted further with EtOAc (3 × 30 mL). The combined
organic phase was dried over anhydrous Na2SO4 and concentrated un-
der reduced pressure. Then, the crude mixture was purified by col-
umn chromatography (silica gel; n-hexane/EtOAc) to afford the de-
sired product.
HRMS (ESI): m/z calcd for
C18H18O
[M + H]+: 251.1430; found:
251.1424.
4-(4-Isopropylphenyl)-4-phenylbut-3-en-2-one (3af)
Yellow oil; yield: 224 mg (57%); mixture of geometric isomers
(~1:0.3).
1H NMR (400 MHz, CDCl3): δ = 7.43–7.29 (m, 4.5 H), 7.25–7.12 (m, 7.2
H), 6.59 (s, 1 H, major CH), 6.54 (s, 0.3 H, minor CH), 2.99–2.87 (m, 1.3
H), 1.87 (d, J = 2.1 Hz, 0.9 H, minor CH3), 1.86 (s, 3 H, major CH3), 1.29
(d, J = 6.9 Hz, 1.8 H, minor CH3), 1.24 (d, J = 6.9 Hz, 6 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.5, 200.1, 154.2, 154.1, 150.7,
149.8, 141.1, 139.2, 138.2, 136.2, 129.7, 129.6, 129.4, 128.7, 128.5,
128.4, 128.4, 128.4, 127.7, 127.0, 126.5, 126.4, 33.9, 33.9, 30.3, 30.2,
23.9, 23.8.
4,4-Diphenylbut-3-en-2-one (3aa)6,21
Yellow oil; yield: 220 mg (66%).
1H NMR (400 MHz, CDCl3): δ = 7.42 (dd, J = 5.0, 1.9 Hz, 3 H), 7.32 (m,
J = 9.9, 8.2, 4.1 Hz, 5 H), 7.22 (dd, J = 6.4, 3.2 Hz, 2 H), 6.58 (s, 1 H), 1.88
(s, 3 H).
HRMS (ESI): m/z calcd for
C19H20O
[M + H]+: 265.1587; found:
265.1579.
13C NMR (151 MHz, CDCl3): δ = 200.3, 154.0, 140.8, 139.0, 129.6,
129.5, 128.8, 128.4, 127.7, 30.3.
MS (ESI): m/z = 223.1 [M + H]+.
4-(4-(tert-Butyl)phenyl)-4-phenylbut-3-en-2-one (3ag)4
Yellow oil; yield: 221 mg (53%); mixture of geometric isomers (~1:0.1,
E/Z).
4-Phenyl-4-(p-tolyl)but-3-en-2-one (3ab)
1H NMR (400 MHz, CDCl3): δ = 7.43–7.40 (m, 3 H), 7.36–7.21 (m, 6.6
H), 7.14 (d, J = 7.9 Hz, 0.3 H, Z-ArH), 6.60 (s, 1 H, E-CH), 6.54 (s, 0.1 H,
Z-CH), 1.87 (s, 0.3 H, Z-CH3), 1.86 (s, 3 H, E-CH3), 1.36 (s, 0.9 H, Z-tBu),
1.31 (s, 9 H, E-tBu).
Yellow oil; yield: 252 mg (71%); mixture of geometric isomers
(~1:0.9).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

G
Y.-l. Zheng et al.
Paper
Synthesis
13C NMR (151 MHz, CDCl3): δ = 200.5, 200.1, 154.2, 153.9, 152.9,
152.1, 141.1, 139.1, 137.7, 135.8, 129.6, 129.5, 129.4, 128.6, 128.5,
128.4, 128.1, 127.7, 127.0, 125.6, 125.4, 125.3, 34.7, 31.3, 31.2, 30.3,
30.2.
13C NMR (151 MHz, CDCl3): δ = 200.0, 199.3, 162.7 (d, J = 246 Hz),
162.7 (d, J = 248 Hz), 152.4, 152.3, 143.1 (d, J = 8 Hz), 141.1 (d, J = 8
Hz), 140.2, 138.4, 130.0 (d, J = 9 Hz), 129.9 (d, J = 9 Hz), 129.7, 129.5,
129.0, 128.6, 128.4, 128.3, 127.6, 125.4 (d, J = 2 Hz), 124.0 (d, J = 2 Hz),
116.6, 116.5, 116.3, 116.2, 115.7, 115.6, 115.4, 115.2, 30.6, 30.4.
HRMS (ESI): m/z calcd for
C20H22O
[M + H]+: 279.1743; found:
279.1746.
HRMS (ESI): m/z calcd for C16H13FO [M + H]+: 241.1023; found:
241.1013.
4-(4-Methoxyphenyl)-4-phenylbut-3-en-2-one (3ah)
4-(2-Fluorophenyl)-4-phenylbut-3-en-2-one (3al)
Yellow oil; yield: 222 mg (59%); mixture of geometric isomers
(~1:0.6).
Yellow oil; yield: 54 mg (15%).
1H NMR (400 MHz, CDCl3): δ = 7.45–7.28 (m, 6.2 H), 7.25–7.19 (m, 3.8
H), 7.15 (d, J = 8.4 Hz, 1.2 H, minor ArH), 6.93 (d, J = 8.4 Hz, 1.2 H,
minor ArH), 6.85 (d, J = 8.6 Hz, 2 H, major ArH), 6.56 (s, 1 H, major
CH), 6.50 (s, 0.6 H, minor CH), 3.86 (s, 1.8 H, minor OCH3), 3.82 (s, 3 H,
major OCH3), 1.92 (s, 1.8 H, minor CH3), 1.84 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.6, 200.1, 161.0, 160.4, 154.1,
154.0, 141.5, 139.4, 133.2, 131.5, 131.2, 130.0, 129.7, 129.5, 128.8,
128.8, 128.5, 128.5, 127.5, 126.1, 114.0, 114.0, 55.5, 55.4, 30.4.
1H NMR (400 MHz, CDCl3): δ = 7.40–7.30 (m, 4 H), 7.25–7.20 (m, 2 H),
7.12–7.05 (m, 3 H), 6.51 (s, 1 H), 1.94 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 200.1, 159.6 (d, J = 252 Hz), 147.0,
138.3, 130.9, 130.8 (d, J = 5 Hz), 129.95 (d, J = 9 Hz), 128.6, 128.5,
128.4, 128.3, 127.8, 123.4, 123.4, 115.7, 115.6, 29.8.
HRMS (ESI): m/z calcd for C16H13FO [M + H]+: 241.1023; found:
241.1023.
MS (ESI): m/z = 253.2 [M + H]+.
4-(4-Chlorophenyl)-4-phenylbut-3-en-2-one (3am)
Yellow oil; yield: 145 mg (38%); mixture of geometric isomers
(~1:0.2).
4-(3-Methoxyphenyl)-4-phenylbut-3-en-2-one (3ai)
Yellow oil; yield: 217 mg (57%); mixture of geometric isomers
(~1:0.3).
1H NMR (400 MHz, CDCl3): δ = 7.44–7.28 (m, 6.2 H), 7.24–7.14 (m, 4.6
H), 6.60 (s, 0.2 H, minor CH), 6.55 (s, 1 H, major CH), 2.00 (s, 0.6 H,
minor CH3), 1.88 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 199.8, 199.1, 152.5, 152.4, 140.3,
139.1, 138.3, 137.2, 135.4, 134.7, 130.8, 129.5, 129.5, 129.4, 128.9,
128.5, 128.4, 128.4, 128.2, 127.7, 127.2, 30.6, 30.2.
1H NMR (400 MHz, CDCl3): δ = 7.44–7.39 (m, 2.9 H), 7.36–7.30 (m, 2
H), 7.27–7.20 (m, 2.9 H), 6.96 (d, J = 8.2 Hz, 0.3 H, minor ArH), 6.89
(dd, J = 12.9, 8.1 Hz, 2 H), 6.85–6.79 (m, 1.3 H), 6.74 (s, 0.3 H, minor
ArH), 6.61–6.55 (m, 1.3 H), 3.79 (s, 0.9 H, minor OCH3), 3.77 (s, 3 H,
major OCH3), 1.91 (s, 0.9 H, minor CH3), 1.87 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.4, 159.7, 159.7, 153.9, 153.7,
142.4, 140.6, 140.4, 139.0, 129.7, 129.7, 129.6, 129.5, 128.9, 128.5,
128.4, 128.0, 127.9, 122.2, 121.1, 115.2, 115.0, 114.4, 114.2, 55.4, 30.4,
30.3.
HRMS (ESI): m/z calcd for C16H13ClO [M + H]+: 257.0728; found:
257.0717.
4-(4-Bromophenyl)-4-phenylbut-3-en-2-one (3an)
Yellow oil; yield: 116 mg (26%); mixture of geometric isomers
(~1:0.1).
HRMS (ESI): m/z calcd for C17H16O2 [M + H]+: 253.1223; found:
253.1225.
1H NMR (400 MHz, CDCl3): δ = 7.55 (d, J = 7.0 Hz, 0.2 H, minor ArH),
7.46 (dd, J = 8.4, 1.1 Hz, 2 H, major ArH), 7.44–7.32 (m, 3.3 H), 7.28 (s,
0.2 H, minor ArH), 7.20 (dd, J = 5.4, 1.9 Hz, 2 H, major ArH), 7.16 (dd,
J = 8.4, 1.1 Hz, 2 H, major ArH), 7.10 (d, J = 7.0 Hz, 0.2 H, minor ArH),
6.60 (s, 0.1 H, minor CH), 6.55 (s, 1 H, major CH), 2.00 (s, 0.3 H, minor
CH3), 1.88 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.0, 199.3, 152.7, 152.7, 140.6,
139.9, 138.6, 138.0, 131.8, 131.7, 131.4, 130.0, 129.8, 129.7, 129.1,
128.7, 128.7, 128.5, 128.0, 127.5, 124.1, 123.2, 30.9, 30.4.
4-(4-Fluorophenyl)-4-phenylbut-3-en-2-one (3aj)
Yellow oil; yield: 217 mg (60%); mixture of geometric isomers
(~1:0.7).
1H NMR (400 MHz, CDCl3): δ = 7.44–7.32 (m, 5.1 H), 7.31–7.26 (m, 3.4
H), 7.22–7.18 (m, 3.4 H), 7.10 (t, J = 8.6 Hz, 1.4 H, minor ArH), 7.02 (t,
J = 8.6 Hz, 2 H, major ArH), 6.59 (s, 0.7 H, minor CH), 6.53 (s, 1 H, ma-
jor CH), 1.97 (s, 2.1 H, minor CH3), 1.87 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.0, 199.6, 163.6 (d, J = 251 Hz),
163.1 (d, J = 249 Hz), 152.9, 152.9, 140.9, 138.9, 137.0 (d, J = 2 Hz),
134.9 (d, J = 3 Hz), 131.6 (d, J = 8 Hz), 130.4 (d, J = 8 Hz), 129.7, 129.7,
129.1, 128.7, 128.6, 128.5, 127.6, 115.6, 115.5, 30.8, 30.4.
HRMS (ESI): m/z calcd for C16H13FO [M + H]+: 241.1023; found:
241.1016.
HRMS (ESI): m/z calcd for C16H13BrO [M + H]+: 301.0223; found:
301.0212.
4-(3,5-Dimethylphenyl)-4-phenylbut-3-en-2-one (3ao)
Yellow oil; yield: 224 mg (60%); mixture of geometric isomers
(~1:0.4).
1H NMR (400 MHz, CDCl3): δ = 7.42–7.30 (m, 5.2 H), 7.23–7.20 (m, 1.8
H), 7.05 (s, 0.4 H, minor ArH), 7.00 (s, 1 H, major ArH), 6.90 (s, 2 H,
major ArH), 6.83 (s, 0.8 H, minor ArH), 6.56 (s, 1 H, major CH), 6.52 (s,
0.4 H, minor CH), 2.32 (s, 2.4 H, minor CH3), 2.27 (s, 6 H, major CH3),
1.86 (2s, 4.2 H).
13C NMR (151 MHz, CDCl3): δ = 200.7, 200.3, 154.6, 154.5, 141.1,
141.0, 139.3, 139.0, 138.1, 138.1, 131.3, 130.6, 129.7, 129.5, 128.8,
128.5, 128.5, 127.9, 127.7, 127.5, 126.4, 30.4, 30.3, 21.4, 21.4.
4-(3-Fluorophenyl)-4-phenylbut-3-en-2-one (3ak)
Yellow oil; yield: 150 mg (42%); mixture of geometric isomers
(~1:0.3).
1H NMR (400 MHz, CDCl3): δ = 7.45–7.28 (m, 5.8 H), 7.21 (d, J = 4.0 Hz,
2 H), 7.14–6.92 (m, 3.9 H), 6.61 (s, 0.3 H, minor CH), 6.57 (s, 1 H, major
CH), 1.95 (s, 0.9 H, minor CH3), 1.89 (s, 3 H, major CH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

H
Y.-l. Zheng et al.
Paper
Synthesis
HRMS (ESI): m/z calcd for C18H18
O
[M + H]+: 251.1430; found:
HRMS (ESI): m/z calcd for C21H24O2 [M + H]+: 309.1849; found:
251.1425.
309.1841.
4-(3,4-Dimethylphenyl)-4-phenylbut-3-en-2-one (3ap)
4-(4-Fluorophenyl)-4-(4-methoxyphenyl)but-3-en-2-one (3bd)
Yellow oil; yield: 292 mg (78%); mixture of geometric isomers
(~1:0.7).
Yellow oil; yield: 231 mg (57%); mixture of geometric isomers
(~1:0.4).
1H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 4.6 Hz, 3.4 H), 7.32–7.29 (m,
3.4 H), 7.20 (d, J = 4.7 Hz, 2 H), 7.15 (d, J = 7.5 Hz, 0.7 H), 7.10–7.05 (m,
2 H), 6.96 (dd, J = 13.1, 8.5 Hz, 2.1 H), 6.58 (s, 1 H, major CH), 6.52 (s,
0.7 H, minor CH), 2.30 (s, 2.1 H, minor CH3), 2.25 (s, 5.1 H, CH3), 2.21
(s, 3 H, major CH3), 1.88 (s, 2.1 H, minor CH3), 1.84 (s, 3 H, major CH3).
1H NMR (400 MHz, CDCl3): δ = 7.32–7.25 (m, 2.4 H), 7.24–7.18 (m, 1.4
H), 7.14–7.08 (m, 2.6 H), 7.02 (t, J = 7.7 Hz, 2 H), 6.94 (d, J = 7.7 Hz, 2
H), 6.86 (d, J = 7.9 Hz, 0.8 H, minor ArH), 6.56 (s, 0.4 H, minor CH),
6.45 (s, 1 H, major CH), 3.86 (s, 3 H, major OCH3), 3.82 (s, 1.2 H, minor
OCH3), 1.93–1.90 (m, 4.2 H).
13C NMR (151 MHz, CDCl3): δ = 200.6, 200.2, 154.5, 154.4, 141.3,
139.4, 138.6, 138.5, 137.6, 136.8, 136.6, 130.9, 129.9, 129.8, 129.8,
129.6, 129.5, 128.8, 128.7, 128.5, 127.7, 127.5, 127.0, 126.3, 30.4, 30.4,
20.0, 19.9, 19.8, 19.8.
13C NMR (151 MHz, CDCl3): δ = 200.3, 199.4, 163.6 (d, J = 251 Hz),
163.0 (d, J = 249 Hz), 161.0, 160.4, 152.9, 152.9, 137.4 (d, J = 3 Hz),
135.1 (d, J = 2 Hz), 133.0, 131.5 (d, J = 7 Hz), 131.3, 130.9, 130.5 (d, J =
9 Hz), 129.9, 127.2, 125.7, 115.5, 115.5, 115.4, 115.3, 113.9, 55.4, 55.3,
30.6, 30.2.
HRMS (ESI): m/z calcd for
C18H18O
[M + H]+: 251.1430; found:
251.1423.
HRMS (ESI): m/z calcd for C17H15FO2 [M + H]+: 271.1129; found:
271.1134.
4-(4-Methoxyphenyl)-4-(p-tolyl)but-3-en-2-one (3ba)
4-(4-Fluorophenyl)-4-(p-tolyl)but-3-en-2-one (3ca)
Yellow oil; yield: 338 mg (85%); mixture of geometric isomers
(~1:0.9).
Yellow oil; yield: 230 mg (60%); mixture of geometric isomers
(~1:0.4).
1H NMR (400 MHz, CDCl3): δ = 7.25–7.18 (m, 5.8 H), 7.14 (d, J = 3.5 Hz,
1.8 H, minor ArH), 7.12 (d, J = 3.0 Hz, 1.8 H, minor ArH), 7.09 (d, J = 7.7
Hz, 2 H, major ArH), 6.92 (d, J = 8.4 Hz, 1.8 H, minor ArH), 6.84 (d,
J = 8.7 Hz, 2 H, major ArH), 6.51 (s, 1 H, major CH), 6.49 (s, 0.9 H, mi-
nor CH), 3.84 (s, 2.7 H, minor OCH3), 3.80 (s, 3 H, major OCH3), 2.40 (s,
3 H, major CH3), 2.35 (s, 2.7 H, minor CH3), 1.89 (s, 2.7 H, minor CH3),
1.85 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.5, 200.3, 161.0, 160.4, 154.3,
154.3, 139.8, 138.9, 138.6, 136.4, 133.5, 131.4, 131.4, 130.1, 129.8,
129.2, 128.7, 126.8, 126.0, 113.9, 113.9, 55.5, 55.4, 30.4, 21.5, 21.4.
1H NMR (400 MHz, CDCl3): δ = 7.27 (dd, J = 8.8, 5.5 Hz, 0.8 H, minor
ArH), 7.24–7.06 (m, 9.6 H), 7.00 (t, J = 8.6 Hz, 0.8 H, minor ArH), 6.58
(s, 1 H, major CH), 6.49 (s, 0.4 H, minor CH), 2.41 (s, 1.2 H, minor CH3),
2.36 (s, 3 H, major CH3), 1.94 (s, 3 H, major CH3), 1.89 (s, 1.2 H, minor
CH3).
13C NMR (151 MHz, CDCl3): δ = 200.2, 199.5, 163.6 (d, J = 251 Hz),
163.1 (d, J = 249 Hz), 153.2, 153.1, 140.1, 139.2, 138.0, 137.3 (d, J = 2
Hz), 135.9, 135.1 (d, J = 3 Hz), 131.6 (d, J = 8 Hz), 130.6 (d, J = 9 Hz),
129.7, 129.4, 128.5, 127.5, 126.8, 115.6, 115.6, 115.5, 115.4, 30.7, 30.4,
21.5, 21.4.
MS (ESI): m/z = 267.2 [M + H]+.
HRMS (ESI): m/z calcd for C17H15FO [M + H]+: 255.1180; found:
4,4-Bis(4-methoxyphenyl)but-3-en-2-one (3bb)6
255.1177.
Yellow oil; yield: 236 mg (56%).
4-(4-Chlorophenyl)-4-(4-fluorophenyl)but-3-en-2-one (3cb)
1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.5 Hz, 2 H), 7.14 (d, J = 8.2
Hz, 2 H), 6.93 (d, J = 8.3 Hz, 2 H), 6.85 (d, J = 8.5 Hz, 2 H), 6.47 (s, 1 H),
3.86 (s, 3 H), 3.82 (s, 3 H), 1.87 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 200.3, 160.9, 160.3, 154.0, 133.6,
131.3, 130.1, 125.8, 113.8, 55.4, 55.3, 30.2.
Yellow oil; yield: 99 mg (24%); mixture of geometric isomers (~1:0.3).
1H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 8.2 Hz, 0.6 H, minor ArH),
7.31 (d, J = 8.5 Hz, 2 H, major ArH), 7.27 (d, J = 3.7 Hz, 0.3 H, minor
ArH), 7.24–7.15 (m, 4.6 H), 7.11 (t, J = 8.7 Hz, 2.3 H), 7.03 (t, J = 8.5 Hz,
0.6 H, minor ArH), 6.55 (s, 1.3 H), 1.99 (s, 0.9 H, minor CH3), 1.97 (s, 3
H, major CH3).
MS (ESI): m/z = 283.1 [M + H]+.
13C NMR (151 MHz, CDCl3): δ = 199.5, 199.2, 163.8 (d, J = 251 Hz),
163.3 (d, J = 251 Hz), 151.7, 151.7, 139.4, 137.3, 136.8 (d, J = 3 Hz),
135.9, 135.2, 134.5 (d, J = 3 Hz), 131.6 (d, J = 8 Hz), 131.1, 130.4 (d, J =
8 Hz), 129.8, 128.9, 127.8, 127.3, 115.9, 115.8, 115.7, 115.7, 30.9, 30.8.
HRMS (ESI): m/z calcd for C16H12ClFO [M + H]+: 275.0633; found:
275.0626.
4-(4-(tert-Butyl)phenyl)-4-(4-methoxyphenyl)but-3-en-2-one
(3bc)
Yellow oil; yield: 297 mg (64%); mixture of geometric isomers
(~1:0.6).
1H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 7.9 Hz, 1.2 H, minor ArH),
7.35 (d, J = 7.8 Hz, 2 H, major ArH), 7.25 (t, J = 7.0 Hz, 3.2 H), 7.15 (t,
J = 7.5 Hz, 3.2 H), 6.94 (d, J = 8.5 Hz, 2 H, major ArH), 6.86 (d, J = 8.6 Hz,
1.2 H, minor ArH), 6.52 (s, 1.6 H), 3.86 (s, 3 H, major OCH3), 3.82 (s, 1.8
H, minor OCH3), 1.89 (s, 3 H, major CH3), 1.83 (s, 1.8 H, minor CH3),
1.36 (s, 5.4 H, minor tBu), 1.32 (s, 9 H, major tBu).
4-(4-Chlorophenyl)-4-(p-tolyl)but-3-en-2-one (3c′a)
Yellow oil; yield: 224 mg (55%); mixture of geometric isomers
(~1:0.6).
1H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 8.1 Hz, 2 H, major ArH),
7.28 (d, J = 8.4 Hz, 1.2 H, minor ArH), 7.21 (d, J = 8.3 Hz, 2 H, major
ArH), 7.19–7.11 (m, 6.4 H), 7.07 (d, J = 7.6 Hz, 1.2 H, minor ArH), 6.58
(s, 1 H, major CH), 6.49 (s, 0.6 H, minor CH), 2.40 (s, 1.8 H, minor CH3),
2.35 (s, 3 H, major CH3), 1.97 (s, 3 H, major CH3), 1.88 (s, 1.8 H, minor
CH3).
13C NMR (151 MHz, CDCl3): δ = 200.6, 200.5, 160.9, 160.3, 154.3,
154.1, 153.0, 152.2, 138.3, 136.2, 133.5, 131.4, 130.1, 129.6, 128.5,
126.9, 126.1, 125.5, 125.4, 113.9, 55.5, 55.4, 34.8, 31.5, 31.3, 30.4,
30.3.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

I
Y.-l. Zheng et al.
Paper
Synthesis
13C NMR (151 MHz, CDCl3): δ = 199.9, 198.9, 152.5, 152.5, 139.8,
139.4, 138.9, 137.4, 137.3, 135.3, 134.5, 130.8, 129.5, 129.4, 129.1,
128.4, 128.1, 127.5, 126.3, 30.6, 30.1, 21.2, 21.0.
HRMS (ESI): m/z calcd for C17H15ClO [M + H]+: 271.0884; found:
271.0880.
3-(4-Fluorophenyl)-1,3-diphenylprop-2-en-1-one (3dd)
Yellow oil; yield: 338 mg (75%).
1H NMR (400 MHz, CDCl3): δ = 7.90 (s, 2 H), 7.49 (d, J = 7.0 Hz, 1 H),
7.38 (s, 5 H), 7.27 (s, 2 H), 7.19–7.04 (m, 4 H), 6.97 (t, J = 8.5 Hz, 1 H).
13C NMR (151 MHz, CDCl3): δ = 191.5, 191.5, 162.5 (d, J = 251 Hz),
161.7 (d, J = 249 Hz), 152.7, 152.6, 140.2, 137.8, 137.1, 136.4 (d, J = 3
Hz), 133.9 (d, J = 3 Hz), 131.8, 131.7, 130.6 (d, J = 8 Hz), 129.4 (d, J = 8
Hz), 128.7, 128.5, 127.7, 127.7, 127.5, 127.5, 127.4, 127.4, 127.1,
123.1, 122.8, 114.5, 114.4, 114.2, 114.0.
4-(4-Chlorophenyl)-4-(m-tolyl)but-3-en-2-one (3c′b)
Yellow oil; yield: 201 mg (50%); mixture of geometric isomers
(~1:0.3).
1H NMR (400 MHz, CDCl3): δ = 7.35 (d, J = 8.3 Hz, 2 H, major ArH),
7.29–7.25 (m, 0.6 H, minor ArH), 7.23–7.11 (m, 5.2 H), 7.07 (s, 1 H),
7.04 (d, J = 7.3 Hz, 1 H), 6.98 (s, 0.6 H), 6.57 (s, 1 H, major CH), 6.50 (s,
0.3 H, minor CH), 2.34 (s, 0.9 H, minor CH3), 2.30 (s, 3 H, major CH3),
1.96 (s, 3 H, major CH3), 1.85 (s, 0.9 H, minor CH3).
HRMS (ESI): m/z calcd for C21H15FO [M + H]+: 303.1180; found:
303.1182.
β,β-Diaryl α,β-Unsaturated Ketones 3a Using Aryl Bromides (Table
3); General Procedure
13C NMR (151 MHz, CDCl3): δ = 200.2, 199.3, 152.9, 152.9, 140.7,
139.5, 138.6, 138.4, 138.3, 137.6, 135.6, 134.8, 131.1, 130.6, 130.2,
129.9, 129.8, 129.1, 128.8, 128.7, 128.6, 128.6, 128.0, 127.4, 126.9,
125.8, 30.9, 30.4, 21.5.
HRMS (ESI): m/z calcd for C17H15ClO [M + H]+: 271.0884; found:
271.0882.
A tube (30 mL) equipped with a magnetic stirring bar was charged
with benzylacetone (1a; 1.5 mmol), 2′ (5.25 mmol), Pd(OAc)2 (10
mol%), L1 (10 mol%), and CsOAc (6.0 mmol) in DMSO (1.5 mL), then
the tube was sealed, purged with O2, and the mixture was stirred at
100 °C for 24 h. At the end of the reaction, the mixture was parti-
tioned between EtOAc (30 mL) and H2O (30 mL). The organic layer
was separated, and the aqueous layer was extracted further with EtO-
Ac (3 × 30 mL). The combined organic phase was dried over anhy-
drous Na2SO4 and concentrated under reduced pressure. Then, the
crude mixture was purified by column chromatography (silica gel; n-
hexane/EtOAc) to afford the desired product.
1,3,3-Triphenylprop-2-en-1-one (3da)22
Yellow oil; yield: 358 mg (84%).
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 7.4 Hz, 2 H), 7.45 (t, J = 7.3
Hz, 1 H), 7.40–7.33 (m, 7 H), 7.27–7.24 (m, 3 H), 7.21–7.16 (m, 2 H),
7.11 (s, 1 H).
13C NMR (151 MHz, CDCl3): δ = 192.5, 154.5, 141.2, 138.9, 138.1,
132.5, 129.6, 129.2, 128.6, 128.4, 128.3, 128.2, 127.9, 123.9.
4-Phenyl-4-(p-tolyl)but-3-en-2-one (3ab)
Yellow oil; yield: 184 mg (52%); mixture of geometric isomers
(~1:0.2).
1H NMR (400 MHz, CDCl3): δ = 7.42–7.29 (m, 4.2 H), 7.23–7.18 (m, 4.4
H), 7.15–7.09 (m, 2.2 H), 6.57 (s, 1 H, major CH), 6.54 (s, 0.2 H, minor
CH), 2.41 (s, 0.6 H, minor CH3), 2.36 (s, 3 H, major CH3), 1.89 (s, 0.6 H,
minor CH3), 1.86 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 200.5, 200.2, 154.2, 154.1, 141.1,
139.8, 139.1, 138.9, 137.9, 136.0, 129.7, 129.6, 129.4, 129.2, 129.1,
128.7, 128.5, 128.4, 128.4, 127.6, 126.9, 30.3, 21.4, 21.3.
MS (ESI): m/z = 285.1 [M + H]+.
1,3-Diphenyl-3-(p-tolyl)prop-2-en-1-one (3db)23
Yellow solid; yield: 393 mg (88%); mp 106–108 °C; mixture of geo-
metric isomers (~1:0.9).
1H NMR (400 MHz, CDCl3): δ = 7.79 (t, J = 8.8 Hz, 3.8 H), 7.35 (t, J = 7.0
Hz, 1.9 H), 7.30–7.20 (m, 7.9 H), 7.15 (t, J = 8.5 Hz, 5.4 H), 7.05 (d, J =
7.5 Hz, 3.8 H), 7.00 (s, 1 H), 6.98–6.93 (m, 4.7 H), 2.26 (s, 3 H, major
CH3), 2.20 (s, 2.7 H, minor CH3).
MS (ESI): m/z = 237.2 [M + H]+.
13C NMR (151 MHz, CDCl3): δ = 192.5, 192.4, 154.9, 154.8, 141.5,
139.5, 139.0, 138.4, 138.3, 138.2, 138.2, 135.9, 132.4, 132.4, 129.6,
129.1, 129.0, 128.6, 128.6, 128.5, 128.4, 128.2, 128.2, 128.2, 128.1,
127.8, 123.5, 122.9, 21.2, 21.1.
4-Phenyl-4-(m-tolyl)but-3-en-2-one (3ac)
Yellow oil; yield: 120 mg (34%); mixture of geometric isomers (~1:1).
1H NMR (400 MHz, CDCl3): δ = 7.43–7.28 (m, 9 H), 7.25–7.17 (m, 5 H),
7.12 (s, 1 H), 7.07 (d, J = 7.4 Hz, 1 H), 7.02 (s, 2 H), 6.57 (s, 1 H), 6.55 (s,
1 H), 2.37 (s, 3 H), 2.32 (s, 3 H), 1.87 (s, 6 H).
13C NMR (151 MHz, CDCl3): δ = 200.5, 200.3, 154.2, 140.9, 140.8,
139.1, 138.9, 138.2, 138.1, 130.3, 130.1, 129.6, 129.6, 129.4, 129.0,
128.7, 128.6, 128.4, 128.3, 128.3, 127.8, 127.7, 127.6, 126.8, 125.7,
30.3, 30.2, 21.4, 21.4.
HRMS (ESI): m/z calcd for
C22H18O
[M + H]+: 299.1430; found:
299.1439.
3-(4-Methoxyphenyl)-1,3-diphenylprop-2-en-1-one (3dc)23
Yellow oil; yield: 369 mg (78%); mixture of geometric isomers
(~1:0.8).
1H NMR (400 MHz, CDCl3): δ = 7.95–7.87 (m, 3.6 H), 7.47 (t, J = 7.3 Hz,
2 H), 7.39–7.27 (m, 12.4 H), 7.18 (d, J = 5.3 Hz, 2 H), 7.14–7.09 (m, 2.6
H), 7.01 (s, 0.8 H), 6.88 (d, J = 7.4 Hz, 2 H), 6.78 (d, J = 8.2 Hz, 1.6 H),
3.83 (s, 3 H, major OCH3), 3.77 (s, 2.4 H, minor OCH3).
13C NMR (151 MHz, CDCl3): δ = 192.8, 192.1, 160.7, 159.7, 154.8,
154.6, 141.8, 139.2, 138.5, 138.3, 133.6, 132.4, 132.3, 131.4, 131.1,
129.9, 129.6, 129.1, 128.7, 128.6, 128.5, 128.4, 128.2, 128.2, 128.2,
127.9, 123.3, 121.8, 113.7, 113.3, 55.2, 55.0.
MS (ESI): m/z = 237.2 [M + H]+.
4-(4-Fluorophenyl)-4-phenylbut-3-en-2-one (3aj)
Yellow oil; yield: 209 mg (58%); mixture of geometric isomers
(~1:0.1).
1H NMR (400 MHz, CDCl3): δ = 7.45–7.39 (m, 3.1 H), 7.35 (d, J = 7.9 Hz,
0.2 H), 7.30–7.26 (m, 2.2 H), 7.23–7.18 (m, 2.2 H), 7.10 (t, J = 8.5 Hz,
0.2 H), 7.02 (t, J = 8.5 Hz, 2 H), 6.58 (s, 0.1 H), 6.53 (s, 1 H), 1.97 (s, 0.3
H), 1.87 (s, 3 H).
HRMS (ESI): m/z calcd for C22H18O2 [M + H]+: 315.1380; found:
315.1380.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

J
Y.-l. Zheng et al.
Paper
Synthesis
13C NMR (151 MHz, CDCl3): δ = 200.0, 199.6, 163.5 (d, J = 251 Hz),
163.0 (d, J = 249 Hz), 152.9, 152.9, 140.7, 138.8, 136.9 (d, J = 1.51 Hz),
134.8 (d, J = 1.51 Hz), 131.5 (d, J = 7.55 Hz), 130.3 (d, J = 7.55 Hz),
129.6, 129.6, 128.8, 128.5, 128.5, 128.4, 127.5, 115.5, 115.4, 30.7, 30.3.
1H NMR (400 MHz, CDCl3): δ = 9.55 (d, J = 7.9 Hz, 0.3 H, minor CHO),
9.50 (d, J = 7.9 Hz, 0.9 H, major CHO), 7.47–7.37 (m, 7.2 H), 7.31 (s, 3.9
H), 7.24 (d, J = 7.4 Hz, 0.6 H, minor ArH), 6.62 (d, J = 7.7 Hz, 1 H, major
CH), 6.57 (d, J = 8.0 Hz, 0.3 H, minor CH), 1.37 (s, 2.7 H, minor CH3),
1.33 (s, 9 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 193.8, 193.7, 162.5, 162.2, 154.2,
152.9, 140.0, 136.8, 136.6, 133.7, 130.7, 130.4, 129.3, 128.8, 128.6,
128.5, 128.3, 127.2, 126.6, 125.6, 125.2, 34.8, 31.3, 31.1.
MS (ESI): m/z = 241.1 [M + H]+.
β,β-Diaryl α,β-Unsaturated Aldehydes 3ea–ee (Table 4); General
Procedure
MS (ESI): m/z = 265.2 [M + H]+.
A tube (30 mL) equipped with a magnetic stirring bar was charged
with benzenepropanal (1e; 201 mg, 1.5 mmol), 2 (3.75 mmol),
Pd(OAc)2 (10 mol%), L1 (10 mol%), and CsOAc (4.5 mmol) in DMSO
(1.5 mL), then the tube was sealed, purged with O2, and the mixture
was stirred at 100 °C for 4 h. At the end of the reaction, the mixture
was partitioned between EtOAc (30 mL) and H2O (30 mL). The organic
layer was separated, and the aqueous layer was extracted further
with EtOAc (3 × 30 mL). The combined organic phase was dried over
anhydrous Na2SO4 and concentrated under reduced pressure. Then,
the crude mixture was purified by column chromatography (silica
gel; n-hexane/EtOAc) to afford the desired product.
3-(4-Chlorophenyl)-3-phenylacrylaldehyde (3ee)
Yellow oil; yield: 126 mg (35%); mixture of geometric isomers
(~1:0.7).
1H NMR (400 MHz, CDCl3): δ = 9.52 (dd, J = 8.0, 5.3 Hz, 1.7 H), 7.50–
7.43 (m, 5.1 H), 7.42–7.36 (m, 2.4 H), 7.35 (s, 2 H), 7.34–7.32 (m, 0.7
H), 7.30 (s, 2 H), 7.29–7.28 (m, 1.4 H), 7.27 (d, J = 2.7 Hz, 1 H), 7.26–
7.24 (m, 0.7 H), 6.60 (d, J = 8.0 Hz, 0.7 H, minor CH), 6.58–6.55 (m, 1 H,
major CH).
13C NMR (151 MHz, CDCl3): δ = 193.3, 192.9, 160.9, 139.3, 138.2,
136.7, 136.2, 135.8, 135.1, 132.0, 130.7, 130.7, 129.9, 129.7, 128.9,
128.8, 128.7, 128.6, 128.5, 127.6, 127.4.
3,3-Diphenylacrylaldehyde (3ea)
Yellow oil; yield: 237 mg (76%).
1H NMR (400 MHz, CDCl3): δ = 9.53 (d, J = 8.0 Hz, 1 H), 7.49–7.35 (m, 8
H), 7.31 (d, J = 7.6 Hz, 2 H), 6.60 (d, J = 8.0 Hz, 1 H).
MS (ESI): m/z = 243.1 [M + H]+.
13C NMR (151 MHz, CDCl3): δ = 194.0, 162.7, 140.2, 137.1, 131.2,
131.0, 129.9, 129.1, 129.1, 128.8, 127.8.
Funding Information
MS (ESI): m/z = 209.1 [M + H]+.
Financial support from the National Natural Science Foundation of
China (No. 81473076 and 81673292), the National Basic Research
Program of China (973 Program, 2015CB931804), and the Science and
3-Phenyl-3-(p-tolyl)acrylaldehyde (3eb)
Technology
Commission
of
Shanghai
Municipality
(No.
Yellow oil; yield: 249 mg (75%); mixture of geometric isomers
(~1:0.5).
15431900100) is gratefully acknowledged.
N
ati
o
n
a
lNaturalS
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a
(8
1
4
7
3
0
7
6)Nati
o
n
a
lNaturalS
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a
(8
1
6
7
3
2
9
2)Nati
o
n
a
lBasi
c
R
esearc
h
Progra
m
of
C
h
i
n
a
(2
0
1
5
C
B
9
3
1
8
0
4)S
c
i
e
n
c
e
a
n
d
T
e
c
h
n
o
l
o
g
y
C
o
m
m
i
si
o
n
of
S
h
a
n
g
h
a
iM
u
n
i
c
i
p
a
l
i
ty(1
5
4
3
1
9
0
0
1
0
0)
1H NMR (400 MHz, CDCl3): δ = 9.43 (d, J = 8.0 Hz, 0.5 H, minor CHO),
9.38 (d, J = 8.0 Hz, 1 H, major CHO), 7.38–7.30 (m, 3.5 H), 7.27–7.23
(m, 2 H), 7.18 (d, J = 7.6 Hz, 2 H), 7.15–7.12 (m, 3 H), 7.07 (t, J = 6.7 Hz,
3 H), 6.47 (d, J = 8.0 Hz, 1 H, major CH), 6.44 (d, J = 8.0 Hz, 0.5 H, minor
CH), 2.31 (s, 1.5 H, minor CH3), 2.26 (s, 3 H, major CH3).
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611354.
S
u
p
p
orit
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
13C NMR (151 MHz, CDCl3): δ = 193.5, 162.4, 162.2, 140.9, 139.9,
139.6, 136.7, 133.6, 130.7, 130.6, 130.3, 129.2, 128.9, 128.6, 128.5,
128.4, 128.1, 127.0, 126.4, 21.2.
References
MS (ESI): m/z = 223.1 [M + H]+.
(1) (a) Welch, W. M.; Kraska, A. R.; Sarges, R.; Koe, B. K. J. Med.
Chem. 1984, 27, 1508. (b) Murdoch, D.; McTavish, D. Drugs
1992, 44, 604. (c) Chen, G.; Xia, H.; Cai, Y.; Ma, D.; Yuan, J.; Yuan,
C. Bioorg. Med. Chem. Lett. 2011, 21, 234. (d) Shen, Q.; Qian, Y.;
Huang, X.; Xu, X.; Li, W.; Liu, J.; Fu, W. ACS Med. Chem. Lett.
2016, 7, 391. (e) Saku, O.; Ishida, H.; Atsumi, E.; Sugimoto, Y.;
Kodaira, H.; Kato, Y.; Shirakura, S.; Nakasato, Y. J. Med. Chem.
2012, 55, 3436.
(2) (a) Tiwari, P. K.; Aidhen, I. S. Eur. J. Org. Chem. 2016, 2637.
(b) Xiao, L.; Zheng, Y.; Xie, Q.; Shao, L. Eur. J. Org. Chem. 2017,
5880. (c) Zhu, Z. Q.; He, J. S.; Wang, H. J.; Huang, Z. Z. J. Org.
Chem. 2015, 80, 9354. (d) Le Bras, J.; Muzart, J. Adv. Synth. Catal.
2018, 360, 2411.
3-Phenyl-3-(m-tolyl)acrylaldehyde (3ec)
Yellow oil; yield: 227 mg (68%); mixture of geometric isomers
(~1:0.6).
1H NMR (400 MHz, CDCl3): δ = 9.52 (dd, J = 7.9, 6.9 Hz, 1.6 H), 7.48–
7.41 (m, 3.2 H), 7.38–7.35 (m, 2.6 H), 7.33–7.28 (m, 3.2 H), 7.27–7.22
(m, 2.2 H), 7.17 (s, 1 H), 7.15–7.09 (m, 2.2 H), 6.58 (dd, J = 8.0, 2.6 Hz,
1.6 H), 2.39 (s, 1.8 H, minor CH3), 2.34 (s, 3 H, major CH3).
13C NMR (151 MHz, CDCl3): δ = 193.8, 193.7, 162.6, 162.6, 139.9,
139.9, 138.5, 138.2, 136.9, 136.8, 131.4, 131.4, 130.9, 130.6, 130.3,
129.5, 129.4, 128.8, 128.7, 128.6, 128.4, 128.3, 128.1, 127.4, 127.3,
126.1, 21.5, 21.5.
(3) (a) Kondolff, I.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2003,
44, 8487. (b) Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y. J. Am.
Chem. Soc. 2003, 125, 1476. (c) Tani, M.; Sakaguchi, S.; Ishii, Y. J.
Org. Chem. 2004, 69, 1221. (d) Botella, L.; Nájera, C. J. Org. Chem.
2005, 70, 4360.
MS (ESI): m/z = 223.1 [M + H]+.
3-(4-(tert-Butyl)phenyl)-3-phenylacrylaldehyde (3ed)
Yellow oil; yield: 217 mg (55%); mixture of geometric isomers
(~1:0.3).
(4) Jin, W.; Du, W.; Yang, Q.; Yu, H.; Chen, J.; Yu, Z. Org. Lett. 2011,
13, 4272.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

K
Y.-l. Zheng et al.
Paper
Synthesis
(5) Bethi, V.; Fernandes, R. A. J. Org. Chem. 2016, 81, 8577.
(6) Rosa, D.; Orellana, A. Org. Lett. 2011, 13, 3648.
(7) Ryabukhin, D. S.; Vasilyev, A. V. Mendeleev Commun. 2016, 26,
500.
(8) Gandeepan, P.; Rajamalli, P.; Cheng, C.-H. ACS Catal. 2014, 4,
4485.
(9) (a) Qi, C.; Sun, X.; Lu, C.; Yang, J.; Du, Y.; Wu, H.; Zhang, X.-M.
J. Organomet. Chem. 2009, 694, 2912. (b) Wang, L.; Lu, W. Org.
Lett. 2009, 11, 10792. (c) Hajipour, A. R.; Rafiee, F. Synth.
Commun. 2013, 43, 1314. (d) Afsaneh, F.; Ayoob, B.; Balu, A. M.;
Rafael, L. Sci. Rep. 2016, 6, 32719. (e) Lane, B. S.; Sames, D. Org.
Lett. 2004, 6, 2897.
(10) (a) Diao, T.; Wadzinski, T. J.; Stahl, S. S. Chem. Sci. 2012, 3, 887.
(b) Gao, W.; He, Z.; Qian, Y.; Zhao, J.; Huang, Y. Chem. Sci. 2012,
3, 883.
(14) (a) Konnick, M. M.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 5753.
(b) Decharin, N.; Popp, B. V.; Stahl, S. S. J. Am. Chem. Soc. 2011,
133, 13268. (c) Iosub, A. V.; Stahl, S. S. ACS Catal. 2016, 6, 8201.
(d) Gligorich, K. M.; Sigman, M. S. Angew. Chem. Int. Ed. 2006, 45,
6612. (e) Muzart, J. Chem. Asian J. 2006, 1, 508.
(f) Scheuermann, M. L.; Goldberg, K. I. Chem. Eur. J. 2014, 20,
14556.
(15) Campbell, A. N.; Stahl, S. S. Acc. Chem. Res. 2012, 45, 851.
(16) Vasseur, A.; Laugel, C.; Harakat, D.; Muzart, J.; Le Bras, J. Eur.
J. Org. Chem. 2015, 944.
(17) Larock, R. C.; Hightower, T. R. J. Org. Chem. 1993, 58, 5298.
(18) Tamaru, Y.; Yamamoto, Y.; Yamada, Y.; Yoshida, Z. I. Tetrahedron
Lett. 1979, 1401.
(19) Roman, G.; Riley, J. G.; Vlahakis, J. Z.; Kinobe, R. T.; Brien, J. F.;
Nakatsu, K.; Szarek, W. A. Bioorg. Med. Chem. 2007, 15, 3225.
(20) Cao, J. J.; Zhou, F.; Zhou, J. Angew. Chem. Int. Ed. 2010, 49, 4976.
(21) Shchukin, A. O.; Vasilyev, A. V. Appl. Catal., A 2008, 336, 140.
(22) (a) Engel, D. A.; Dudley, G. B. Org. Lett. 2006, 8, 4027. (b) Uyanik,
M.; Fukatsu, R.; Ishihara, K. Org. Lett. 2009, 11, 3470.
(23) Singh, G.; Purkayastha, M. L.; Ila, H.; Junjappa, H. J. Chem. Soc.,
Perkin Trans. 1 1985, 1289.
(11) (a) Shang, Y.; Jie, X.; Zhou, J.; Hu, P.; Huang, S.; Su, W. Angew.
Chem. Int. Ed. 2013, 52, 1299. (b) Yip, K.-T.; Nimje, R. Y.;
Leskinen, M. V.; Pihko, P. M. Chem. Eur. J. 2012, 18, 12590.
(12) Izawa, Y.; Pun, D.; Stahl, S. S. Science 2011, 333, 209.
(13) Muzart, J. Eur. J. Org. Chem. 2010, 3779.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K