Tin(II) chloride mediated coupling reactions between alkynes and aldehydes

Article abstract of DOI:10.1002/ejoc.201301189

Tin(II) chloride, which is insensitive to water and air, mediated the coupling reaction between alkynes and aldehydes as a Lewis acid in nitromethane to produce (E)-α,β-unsaturated ketones by a skeletal transformation in which one alkynic carbon atom changed into an oxo carbon atom accompanied by the cleavage of a C=O bond in the starting aldehydes. This coupling reaction was promoted by a catalytic amount of a primary or secondary alkanol. The coupling reaction between 1-deuterio-2-phenylethyne and benzaldehyde with BuOH afforded 1,3-diphenyl-2-deuterio-2-propenone (2-deuteriation: 94 % D), whereas the coupling reaction between phenylethyne and benzaldehyde with BuOD afforded 1,3-diphenyl-2-propenone (2-deuteriation: 0 % D). Because almost no exchange between hydrogen and deuterium at the 2-position of 1,3-diphenyl-2-propenone occurs in either of the reactions, the coupling reaction between alkynes and aldehydes with tin(II) chloride is presumed to proceed by nucleophilic addition of alkynes to aldehydes. The cleavage of the C-O single bond generated by the nucleophilic addition might be induced by the strong oxophilicity of tin. Coupling reactions occur between alkynes and aldehydes mediated by tin(II) chloride as a Lewis acid to produce (E)-α,β-unsaturated ketones by a skeletal transformation in which an alkynic carbon atom changes into an oxo carbon atom accompanied by cleavage of the C=O bond in the starting aldehydes. This coupling reaction is promoted by a catalytic amount of a primary or secondary alkanol. Copyright

Full text of DOI:10.1002/ejoc.201301189

FULL PAPER
DOI: 10.1002/ejoc.201301189
Tin(II) Chloride Mediated Coupling Reactions between Alkynes and Aldehydes
[a]
[a]
[a]
Yoshiro Masuyama,* Wataru Takamura, and Noriyuki Suzuki
Keywords: Aldehydes / Alkynes / Cross-coupling / Enones / Lewis acids / Tin
Tin(II) chloride, which is insensitive to water and air, medi-
ated the coupling reaction between alkynes and aldehydes
as a Lewis acid in nitromethane to produce (E)-α,β-unsatu-
rated ketones by a skeletal transformation in which one
alkynic carbon atom changed into an oxo carbon atom ac-
companied by the cleavage of a C=O bond in the starting
aldehydes. This coupling reaction was promoted by a cata-
lytic amount of a primary or secondary alkanol. The coupling
tion between phenylethyne and benzaldehyde with BuOD
afforded 1,3-diphenyl-2-propenone (2-deuteriation: 0% D).
Because almost no exchange between hydrogen and deuter-
ium at the 2-position of 1,3-diphenyl-2-propenone occurs in
either of the reactions, the coupling reaction between alk-
ynes and aldehydes with tin(II) chloride is presumed to pro-
ceed by nucleophilic addition of alkynes to aldehydes. The
cleavage of the C–O single bond generated by the nucleo-
reaction between 1-deuterio-2-phenylethyne and benzalde- philic addition might be induced by the strong oxophilicity
hyde with BuOH afforded 1,3-diphenyl-2-deuterio-2-pro-
penone (2-deuteriation: 94% D), whereas the coupling reac-
of tin.
Introduction
ide cleaves the propargylic C–O bond leading to propargylic
substitution. We envisioned that tin(II) chloride could be
used to activate aldehydes and subsequently cleave the C=O
bond, similarly to the Lewis acids described above in the
coupling reactions between alkynes and Lewis acid acti-
vated aldehydes.
Carbon skeleton constructions with alkynes have made
considerable progress since the reactions of directly acti-
vated alkynes were discovered, namely hydrometalation and
[
1]
carbometalation to alkynes, terminal C–H bond acti-
[
2]
vation of terminal alkynes, and nucleophilic addition to
[
3]
alkynes, which have been recognized as versatile method-
ologies because of their easy manipulation and high effi-
ciency (atom economy). In comparison with the methodol-
ogies described above, the electrophilic addition to alkynes
would be unsuitable for carbon skeleton construction be-
cause of the poor availability of carbon electrophiles. Nev-
ertheless, the coupling reactions between alkynes and Lewis
acid activated aldehydes provide one example of the ad-
dition of carbon electrophiles to alkynes. Such coupling re-
Results and Discussion
The coupling reactions between alkynes and aldehydes
with tin(II) halides were investigated by using phenylethyne
(1a) and benzaldehyde (2a) under various reaction condi-
tions (Table 1). Tin(II) chloride mediated the coupling reac-
tion in CH NO2 at 80 °C for 24 h to afford (E)-1,3-di-
3
phenyl-2-propen-1-one (3aa) stereoselectively in 34% yield
(Entries 1 and 2). The addition of butanol (20 mol-% with
[4]
[5]
actions have been carried out with SbF ,
GaCl3,
[9]
5
[
5,6]
[7]
[8]
In(OTf)3,
Yb(OTf)3,
FeCl3,
or TMSOTf as the
respect to SnCl ) promoted the coupling reaction at 80 °C
2
Lewis acid, and form a remarkable methodology for the
[4b,6]
for 3 h to give 3aa in 71% yield (Entry 5),
which is the
production of (E)-α,β-unsaturated ketones accompanied by
same yield as that obtained with 100 mol-% of butanol (En-
try 7). The yield was lower at 70 °C and remained un-
changed at 90 °C (Entries 4 and 6). The use of 20 mol-%
skeletal transformation.[
10–13]
We have studied the possible
applications of the relatively weak Lewis acid, tin(II) chlor-
ide, which is insensitive to water and air, in organic syn-
thetic reactions, and found that it catalyzes the propargylic
substitution of propargylic alcohols with carbon and nitro-
gen nucleophiles in nitromethane;[ oxophilic tin(II) chlor-
SnCl with respect to 1a afforded 3aa in 41% yield (En-
2
try 8). Increasing the amount of 2a improved the yield (En-
tries 5 and 9–12), but increasing the amount of 1a did not
14]
(Entries 12–14). SnCl2 is a superior activating agent to
SnBr and SnI (Entries 5, 16, and 17), and SnF could not
2
2
2
be used in the coupling reaction, because it is insoluble in
CH NO (Entry 15). Primary alcohols, such as methanol,
ethanol, and propanol, and secondary alcohols, such as 2-
butanol, can also be used to promote the coupling reaction
[
a] Department of Materials and Life Sciences, Faculty of Science
3
2
and Technology, Sophia University,
7
-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan
E-mail: y-masuya@sophia.ac.jp
www.mls.sophia.ac.jp/~orgsynth/
(Entries 5 and 18–21). However, both tert-butyl alcohol and
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301189.
water inhibited the coupling reaction (Entries 22 and 24).
Eur. J. Org. Chem. 2013, 8033–8038
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8033

Y. Masuyama, W. Takamura, N. Suzuki
FULL PAPER
Table 1. Coupling reactions between 1a and 2a.
Entry 1a [mmol] 2a [mmol] SnX
2
/quantity [mmol] ROH/quantity [mmol] Solvent[a] Temp. [°C] Time [h][b] Yield of 3aa [%][c]
1
2
3
4
5
6
7
8
9
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
3.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
5.0
3.0
2.0
1.0
1.0
1.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
–
–
–
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
NO
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
80
80
r.t.
70
80
90
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
reflux
24
24
24
4
3
3
3
24
3
3
3
3
3
3
24
8
24
3
3
3
3
–[d]
34
–
SnCl
2
2
2
2
2
2
2
2
2
2
2
2
2
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
/0.2
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
[d]
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/1.0
BuOH/0.1
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
MeOH/0.2
EtOH/0.2
PrOH/0.2
sBuOH/0.2
tBuOH/0.2
PhOH/0.2
60
71
68
70
41
68
54
48
27
27
31
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
[d]
SnF
SnBr
2
/1.0
–
2
/1.0
/1.0
21
31
65
68
65
65
SnI
2
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
SnCl
2
2
2
2
2
2
2
2
2
2
2
2
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
/1.0
[d]
24
3
24
8
24
24
24
24
–
20
[d]
H
2
O/1.0
–
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
BuOH/0.2
CH
toluene
DCE
dioxane
THF
3
CN
52
38
31
[
[
d]
–
–
d]
[a] 1 mL of solvent was used. [b] The reactions were discontinued after the specified times. [c] Isolated yields. [d] The reactions did not
occur.
CH NO is superior as solvent to CH CN, toluene, or DCE 3fa, respectively, stereoselectively, accompanied by the same
3
2
3
(
Entries 5 and 25–27), and the coupling reaction failed with skeletal transformation as that of 1a (Entries 14 and 15).[4b]
dioxane and THF (Entries 28 and 29).
To confirm the skeletal transformation in the synthesis
The coupling reaction of phenylethyne (1a) with substi- of the α,β-unsaturated ketone products, an X-ray diffrac-
tuted benzaldehydes 2b–i under the same conditions as tion study was performed on colorless crystals of 3bf ob-
those of Entry 5 in Table 1 afforded the corresponding (E)- tained by the slow diffusion of hexane into a chloroform
α,β-unsaturated ketones stereoselectively (Entries 1–8 in solution (Entry 11). The ORTEP drawing of the molecular
Table 2). 4-Methoxybenzaldehyde (2e) was relatively unre- structure of 3bf is shown in Figure 1. Thus, one alkynic car-
active (Entry 4), and the reaction with 4-nitrobenzaldehyde bon atom changes into an oxo carbon atom accompanied
(2i) gave undetermined byproducts (Entry 8). The α- by the cleavage of the C=O bond in the starting aldehyde.
branched aliphatic aldehyde cyclohexanecarbaldehyde (2j) To investigate the reaction mechanism, deuteriation ex-
reacted with 1a to produce (E)-3-cyclohexyl-1-phenyl-2- periments were performed; the coupling reaction between 1-
propen-1-one (3aj; Entry 9), whereas the straight-chain ali- deuterio-2-phenylethyne (1a-d, 99% D) and 2a with BuOH
phatic aldehyde heptanal did not afford the corresponding afforded 3aa-d [2-deuteriation: 94% D; Equation (1)],
coupling product. 4-Ethynyltoluene (1b) and 1-ethynyl-4- whereas the coupling reaction between 1a and 2a with
fluorobenzene (1c) exhibited almost the same reactivity as BuOD (97% D) afforded 3aa [2-deuteriation: 0% D; Equa-
1
a (Entries 10–12), whereas the straight-chain terminal tion (2)]. In contrast to the coupling reaction with
[
6]
alkyne 1-octyne (1d) was less reactive under the same condi- In(OTf)3, almost no exchange between hydrogen and deu-
tions as those of Entry 5 in Table 1, the corresponding α,β- terium at the 2-position of 3aa occurred. It is known that
unsaturated ketone, (E)-1-phenyl-1-nonen-3-one (3da), be- π-acids, such as gold complexes, catalyze the nucleophilic
ing obtained in 15% yield (Entry 13). Internal alkynes, addition of alcohols to alkynes to prepare enol ethers or
[
15]
namely 1-phenyl-1-propyne (1e) and 1-phenyl-1-pentyne ketones. Thus, we investigated whether alkynes activated
1f) readily underwent the coupling reaction with 2a to by tin(II) chloride, similarly to gold complexes, could be
form 2-alkylated (E)-2-propen-1-one derivatives 3ea and used to prepare enol ethers or ketones for application in
(
8034
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 8033–8038

Coupling Reactions between Alkynes and Aldehydes
Table 2. Coupling reactions between alkynes 1 and aldehydes 2.[a]
with aqueous HCl scarcely produced acetophen-
one. In the light of this result and the result of Entry 24
in Table 1, the coupling reaction between 1a and 2a is not
considered to be a simple aldol condensation of 2a with α-
butoxystyrene or its hydrolysate, acetophenone, derived
from 1a. If tin(II) chloride assisted nucleophilic addition
of BuOH to 1a, similarly to gold complexes, led to the prep-
aration of α-butoxystyrene and subsequent aldol-type con-
densation with 2a, the coupling reaction between 1a and 2a
with BuOD would afford [D]3aa with a high 2-deuteriation
rate.
[
12]
1
2
2: R3
2b: 2-ClC
2c: 3-BrC
2d: 4-MeC
2e: 4-MeOC
2f: 4-ClC
2g: 4-FC
2h: 4-NCC
2i: 4-O NC
2j: c-C
2a: Ph
Time [h][b] 3, yield [%][c]
Entry
1: R , R
1
2
3
4
5
6
7
8
9
1a: Ph, H
1a: Ph, H
1a: Ph, H
1a: Ph, H
1a: Ph, H
1a: Ph, H
1a: Ph, H
1a: Ph, H
1a: Ph, H
6
H
H
6 4
6
H
4
3
3
3ab, 70
3ac, 57
3ad, 77
3ae, 32
3af, 60
3ag, 54
3ah, 62
3ai, 38
3aj, 48
3ba, 70
3bf, 58
3ca, 68
3da, 15
4
3
24
3
3
3
6
H
4
6
H
4
H
4
6
H
6
H
On the basis of these experimental results and the X-
ray diffraction study, plausible mechanisms without ROH
6
4
(path a) and with ROH (path b) are illustrated in Scheme 1.
2
4
3
4
3
3
An aldehyde activated by coordination to SnCl reacts by
H
11
2
6
1
0
1b: 4-MeC
1b: 4-MeC
1c: 4-FC
1d: C
6
H
H
4
4
, H
, H
, H
1
1
6
2f: 4-ClC
2a: Ph
2a: Ph
2a: Ph
2a: Ph
6
H
4
1
2
6
H
4
3
13
6
H
13, H
24
3
[d]
1
15
4
1e: Ph, Me
1f: Ph, Pr
3ea, 75
3fa, 70
5
[
a] The coupling reactions between 1 (1.0 mmol) and 2 (4.0 mmol)
were performed with SnCl (1.0 mmol) and BuOH (0.2 mmol) at
0 °C in CH NO (1.0 mL). [b] The reactions were discontinued
2
8
3
2
after the specified times. [c] Isolated yields of the (E) isomers. [d]
The (E)/(Z) ratio was 93:7.
Figure 1. ORTEP drawing of the molecular structure of 3bf with
ellipsoids drawn at the 50% probability level.
aldol condensation reactions with aldehydes. The reaction
of 1a (1 mmol) and BuOH (1 mmol) with tin(II) chloride
(
1 mmol) at 80 °C for 24 h in CH NO (1 mL) in the ab-
3 2
sence of 2a followed by hydrolysis of the reaction mixture
(
1)
Scheme 1. Plausible mechanisms without ROH (path a) and with
2) ROH (path b).
(
Eur. J. Org. Chem. 2013, 8033–8038
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
8035

Y. Masuyama, W. Takamura, N. Suzuki
electrophilic addition to an alkyne to generate zwitterion A chased from Tokyo Chemical Industry Co. 4-Chlorobenzaldehyde
FULL PAPER
(
2f) was purchased from Wako Pure Chemical Industries. All pur-
and subsequently oxametallacyclopentene B, which is trans-
formed into oxetene-like intermediate C in the absence of
ROH (path a). The intermediate C undergoes ring-opening
chased organic reagents were used as received. TLC analysis was
carried out on silica gel plates (Merck 105735), and column
chromatography on silica gel (Kanto Chemical Co., Inc. Cat. No.
to form the relatively stable ketone–SnCl adduct D, from
2
3
7564). HPLC purification was performed with a Japan Analysis
which SnCl is released to produce α,β-unsaturated ketone
2
Industry LC-908 or LC-9201 instrument (JAIGEL-2 H, CHCl ).
NMR spectra were recorded with a JEOL ECX-300 spectrometer,
and EI-MS data were recorded with a JEOL JMS-700 spectrome-
3
3. On the other hand, in the presence of ROH (path b),
ROH undergoes S 2Ј reaction with oxametallacyclopentene
N
B with O-protonation to generate alcohol adduct E, from ter.
–
which dichlorohydroxystannate [ Sn(OH)Cl ] is eliminated
2
Typical Reaction Procedure: Tin(II) chloride (1.0 mmol, 0.19 g) was
added to a solution of phenylethyne (1a; 1.0 mmol, 0.10 g), benzal-
dehyde (2a; 4.0 mmol, 0.42 g), and butanol (0.2 mmol, 0.015 g) in
to form oxycarbenium intermediate F. The formation of B
and subsequent cleavage of the C–O bond might be quite
rapid because of the strong oxophilicity of tin.[
14,16]
Next, nitromethane (1.0 mL). The mixture was stirred at 80 °C for 3 h,
the intermediate F reacts with the dichlorohydroxystannate being monitored by TLC (Merck silica gel 60 F254, 105735; hexane/
to generate hemiacetal G and SnCl . Finally, ROH is re- EtOAc, 3:1) and then extracted with diethyl ether/dichloromethane
2
(
1:1, 150 mL). The extracted mixture was washed with water and a
leased from hemiacetal G to produce α,β-unsaturated
ketone 3.
saturated solution of aqueous NaCl and then dried with anhydrous
MgSO . After evaporation of the volatiles, purification by column
4
chromatography (Kanto Chemical Co., silica gel 60, 37564; hexane/
EtOAc, 8:1) and GPC (Japan Analytical Industry Co., LC-908,
Conclusions
3
JAIGEL-2 H; CHCl ) afforded 0.15 g (71%) of (E)-1,3-diphenyl-
2
-propen-1-one (3aa).
A weak Lewis acid, tin(II) chloride, which is insensitive
to water and air, mediated the coupling reactions between (E)-1,3-Diphenyl-2-propen-1-one (3aa):[6] 1H NMR (300 MHz,
3
alkynes and aldehydes to afford (E)-α,β-unsaturated CDCl ): δ = 7.34–7.63 (m, 9 H), 7.79 (d, J = 15.5 Hz, 1 H), 7.98–
1
3
8
1
1
2
.03 (m, 2 H) ppm. C NMR (75.6 MHz, CDCl
3
): δ = 121.9,
ketones by a skeletal transformation in which one alkynic
carbon atom changes into an oxo carbon atom ac-
companied by the cleavage of the C=O bond in the starting
aldehydes. The coupling reaction is promoted by a catalytic
amount of primary or secondary alkanol. Tin(II) chloride
was the most effective mediator among all tin(II) halides
for the coupling reaction. The coupling reaction between 1-
deuterio-2-phenylethyne and benzaldehyde with BuOH af-
forded 1,3-diphenyl-2-deuterio-2-propenone (2-deuter-
iation: 94% D), whereas the coupling reaction between
phenylethyne and benzaldehyde with BuOD afforded 1,3-
diphenyl-2-propenone (2-deuteriation: 0% D). Because al-
most no exchange between hydrogen and deuterium at the
28.27, 128.32, 128.4, 128.8, 130.4, 132.6, 134.7, 138.0, 144.6,
90.2 ppm. HRMS (EI): calcd. for C15
08.0864.
E)-2-Deuterio-1,3-diphenyl-2-propen-1-one (3aa-d): 1H NMR
300 MHz, CDCl ): δ = 7.36–7.64 (m, 8 H), 7.79 (s, 1 H), 7.98–
.04 (m, 2 H) ppm. C NMR (75.6 MHz, CDCl
H12O 208.0888; found
(
(
8
3
1
3
3
): δ = 121.6 (JC-
D
= 24 Hz), 128.3, 128.4, 128.5, 128.8, 130.4, 132.7, 134.7, 138.1,
1
44.6, 190.3 ppm.
E)-3-(2-Chlorophenyl)-1-phenyl-2-propen-1-one (3ab): 1H NMR
300 MHz, CDCl ): δ = 7.28–7.37 (m, 2 H), 7.41–7.55 (m, 4 H),
.56–7.63 (m, 1 H), 7.71–7.78 (m, 1 H), 7.99–8.05 (m, 2 H), 8.18
(
(
7
(
1
1
C
3
1
3
d, J = 15.8 Hz, 1 H) ppm. C NMR (75.6 MHz, CDCl
3
): δ =
24.8, 127.1, 127.8, 128.60, 128.64, 130.3, 131.1, 132.9, 133.2,
35.5, 137.9, 140.6, 190.4 ppm. HRMS (EI): calcd. for
2-position of 1,3-diphenyl-2-propenone occurs in either re-
action, the coupling reactions between alkynes and alde-
hydes with tin(II) chloride are presumed to proceed by nu-
cleophilic addition of the alkynes to aldehydes. The cleavage
of the C–O single bond generated by the nucleophilic ad-
dition might be induced by the strong oxophilicity of tin
and has potential for further functionalization in organic
synthetic reactions.
35
15
H
11 ClO 242.0498; found 242.0490.
E)-3-(3-Bromophenyl)-1-phenyl-2-propen-1-one (3ac): 1H NMR
300 MHz, CDCl ): δ = 7.26 (t, J = 7.7 Hz, 1 H), 7.45–7.62 (m, 6
H), 7.70 (d, J = 15.8 Hz, 1 H), 7.76 (br., 1 H), 8.01 (d, J = 6.9 Hz,
H) ppm. C NMR (75.6 MHz, CDCl
(
(
3
13
2
1
3
): δ = 122.96, 123.02,
27.1, 128.4, 128.6, 130.3, 130.7, 132.9, 133.1, 136.8, 137.7, 142.8,
189.8 ppm. HRMS (EI): calcd. for C H BrO 285.9993; found
7
9
1
5
11
2
85.9972.
E)-3-(4-Methylphenyl)-1-phenyl-2-propen-1-one (3ad): 1H NMR
300 MHz, CDCl ): δ = 2.35 (s, 3 H), 7.18 (d, J = 8.3 Hz, 2 H),
.43–7.57 (m, 6 H), 7.78 (d, J = 15.8 Hz, 1 H), 7.97–8.02 (m, 2 H)
(
(
7
Experimental Section
3
General Methods: Tin(II) chloride (Wako first-grade, over 97%)
was purchased from Wako Pure Chemical Industries and used after
being dried at 120 °C under vacuum for 5 h. Phenylethyne (1a), 1-
deuterio-2-phenylethyne (1a-d), and 1-ethynyl-4-fluorobenzene (1c)
were purchased from Sigma–Aldrich. 1-Octyne (1d), 1-phenyl-1-
propyne (1e), and 1-phenyl-1-pentyne (1f) were purchased from
Kanto Chemical Co. [D]Butanol (BuOD, 97% D), 4-ethynyltoluene
1
3
ppm. C NMR (75.6 MHz, CDCl
3
): δ = 21.4, 120.9, 128.30,
1
28.33, 128.4, 129.5, 131.0, 132.5, 138.2, 140.9, 144.7, 190.3 ppm.
HRMS (EI): calcd. for C16
H
14O 222.1045; found 222.1022.
(3ae):[6]
): δ = 3.85 (s, 3 H), 6.93 (d, J = 8.9 Hz, 2
H), 7.41 (d, J = 15.5 Hz, 1 H), 7.45–7.63 (m, 5 H), 7.79 (d, J =
(E)-3-(4-Methoxyphenyl)-1-phenyl-2-propen-1-one
NMR (300 MHz, CDCl
1H
3
1
3
(
1b), benzaldehyde (2a), 2-chlorobenzaldehyde (2b), 3-bromobenz-
aldehyde (2c), 4-cyanobenzaldehyde (2h), 4-fluorobenzaldehyde
2g), 4-methoxybenzaldehyde (2e), 4-methylbenzaldehyde (2d), 4-
nitrobenzaldehyde (2i), and cyclohexanecarbaldehyde (2j) were pur-
15.5 Hz, 1 H), 7.98–8.03 (m, 2 H) ppm. C NMR (75.6 MHz,
CDCl ): δ = 55.4, 114.4, 119.7, 127.6, 128.4, 128.5, 130.2, 132.5,
138.5, 144.7, 161.6, 190.5 ppm. HRMS (EI): calcd. for C16
238.0994; found 238.0989.
3
(
14 2
H O
8036
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 8033–8038

Coupling Reactions between Alkynes and Aldehydes
(
(
7
(
1
C
E)-3-(4-Chlorophenyl)-1-phenyl-2-propen-1-one (3af): 1H NMR δ = 14.0, 22.5, 24.3, 29.0, 31.6, 41.0, 126.2, 128.2, 128.9, 130.4,
300 MHz, CDCl ): δ = 7.31–7.36 (m, 2 H), 7.43–7.59 (m, 6 H), 134.6, 142.3, 200.7 ppm. HRMS (EI): calcd. for C15 20O 216.1514;
.72 (d, J = 15.8 Hz, 1 H), 7.97–8.02 (m, 2 H) ppm. C NMR
75.6 MHz, CDCl ): δ = 122.2, 128.3, 128.5, 129.0, 129.4, 132.8,
3
H
13
found 216.1497.
3
E)-2-Methyl-1,3-diphenyl-2-propen-1-one (3ea):[4b] 1H NMR
(
33.2, 136.2, 137.8, 143.0, 189.9 ppm. HRMS (EI): calcd. for
15
H11 ClO 242.0498; found 242.0490.
(
1
300 MHz, CDCl
.4 Hz, 2.8 H), 7.17 (d, J = 1.4 Hz, 0.93 H), 7.26–7.54 (m, 8 H),
3
): δ = 2.15 (d, J = 1.7 Hz, 0.2 H), 2.26 (d, J =
35
E)-3-(4-Fluorophenyl)-1-phenyl-2-propen-1-one (3ag): 1H NMR
300 MHz, CDCl ): δ = 7.11 (t, J = 8.6 Hz, 2 H), 7.46 (d, J =
5.8 Hz, 1 H), 7.46–7.67 (m, 5 H), 7.78 (d, J = 15.8 Hz, 1 H), 8.02
13
(
(
1
7.72–7.75 (m, 1.9 H), 7.86–7.89 (0.1 H) ppm. C NMR (75.6 MHz,
CDCl ): δ = 14.3, 128.0, 128.3, 128.4, 129.3, 129.5, 131.5, 135.6,
3
3
136.7, 138.3, 142.0, 199.2 ppm. HRMS (EI): calcd. for C16
222.1045; found 222.1022.
14
H O
1
3
(
(
(
d, J = 7.9 Hz, 2 H) ppm. C NMR (75.6 MHz, CDCl
3
): δ = 116.1
2
C-F = 22 Hz), 121.7, 128.4, 128.6, 130.3 (3JC-F = 9 Hz), 131.1
J
1H
(
E)-2-Propyl-1,3-diphenyl-2-propen-1-one
(3fa):
NMR
4JC-F = 4 Hz), 132.8, 138.1, 143.5, 164.0 ( JC-F = 251 Hz),
1
(
300 MHz, CDCl
3
): δ = 1.00 (t, J = 7.2 Hz, 3 H), 1.53–1.67 (m, 2
1
2
90.3 ppm. HRMS (EI): calcd. for C15
26.0784.
H11FO 226.0794; found
H), 2.69–2.76 (m, 2 H), 7.06 (s, 1 H), 7.29–7.58 (m, 8 H), 7.77–7.82
13
(m, 2 H) ppm. C NMR (75.6 MHz, CDCl
3
): δ = 14.3, 22.1, 29.7,
E)-3-(4-Cyanophenyl)-1-phenyl-2-propen-1-one (3ah): 1H NMR
128.2, 128.4, 128.5, 129.1, 129.6, 131.9, 135.7, 138.6, 140.8, 142.2,
(
(
1
2
99.4 ppm. HRMS (EI): calcd. for C18
50.1343.
H18O 250.1358; found
300 MHz, CDCl
3
): δ = 7.46–7.53 (m, 2 H), 7.56–7.63 (m, 1 H),
7
1
1
1
.58 (d, J = 15.8 Hz, 1 H), 7.68–7.70 (br., 4 H), 7.75 (d, J = 15.8 Hz,
13
H), 7.97–8.02 (m, 2 H) ppm. C NMR (75.6 MHz, CDCl
13.5, 118.4, 125.0, 128.6, 128.7, 128.8, 132.9, 133.3, 137.6, 139.2,
42.1, 189.7 ppm. HRMS (EI): calcd. for C16 11NO 233.0841;
3
): δ =
X-ray Diffraction Analyses of 3bf: Single crystals were obtained by
recrystallization by slow diffusion of hexane into a chloroform
H
solution. A colorless crystal (0.30ϫ0.15ϫ0.03 mm) was mounted
found 233.0833.
TM
on a MicroMount
(MiTeGen) and coated with liquid paraffin.
E)-3-(4-Nitrophenyl)-1-phenyl-2-propen-1-one (3ai): 1H NMR
All measurements were made with a Rigaku Mercury CCD area
(
(
α
detector with graphite-monochromated Mo-K radiation at 93 K.
300 MHz, CDCl
3
): δ = 7.51–7.58 (m, 2 H), 7.60–7.69 (m, 2 H),
The structure was solved by direct methods[ and expanded by
using Fourier techniques. Non-hydrogen atoms were refined aniso-
tropically, and hydrogen atoms were refined by using the riding
17]
7
.77–7.87 (m, 3 H), 8.02–8.07 (m, 2 H), 8.26–8.31 (m, 2 H) ppm.
13
C NMR (75.6 MHz, CDCl
28.9, 133.4, 137.5, 141.0, 141.5, 148.5, 189.6 ppm. HRMS (EI):
253.0739; found 253.0740.
3
): δ = 124.2, 125.7, 128.6, 128.8,
1
2
model. The final cycle of full-matrix least-squares refinement on F
calcd. for C15H11NO
3
was based on 2860 observed reflections and 164 variable param-
eters. All calculations were performed by using the CrystalStruc-
(
E)-3-Cyclohexyl-1-phenyl-2-propen-1-one (3aj):
300 MHz, CDCl ): δ = 1.11–1.46 (m, 6 H), 1.57–1.89 (m, 4 H),
.17–2.32 (m, 1 H), 6.82 (dd, J = 15.5, 1.3 Hz, 1 H), 7.01 (dd, J =
5.5, 6.5 Hz, 1 H), 7.41–7.49 (m, 2 H), 7.50–7.57 (m, 1 H), 7.89–
1H
NMR
(
3
[18]
ture crystallographic software package except for the refinement,
2
1
7
3
[19]
which was performed by using SHELXL-97.
The crystallo-
graphic data are presented in Table S1 in the Supporting Infor-
mation. CCDC-933560 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
.95 (m, 2 H) ppm. 1 C NMR (75.6 MHz, CDCl
1.8, 41.0, 123.3, 128.4, 128.5, 132.5, 138.1, 154.8, 191.2 ppm.
18O 214.1358; found 214.1333.
3
): δ = 25.7, 25.9,
3
HRMS (EI): calcd. for C15
H
(
E)-1-(4-Methylphenyl)-3-phenyl-2-propen-1-one (3ba):[6] 1H NMR
300 MHz, CDCl ): δ = 2.41 (s, 3 H), 7.24–7.7.30 (m, 2 H), 7.38– Supporting Information (see footnote on the first page of this arti-
(
3
1
13
7
.7.40 (m, 3 H), 7.53 (d, J = 15.5 Hz, 1 H), 7.61–7.63 (m, 2 H), cle): H and C NMR spectra and HRMS (EI) data of all com-
3
7
.80 (d, J = 15.8 Hz, 1 H), 7.92–7.95 (m, 2 H) ppm. 1 C NMR
): δ = 21.6, 121.9, 128.3, 128.6, 128.8, 129.2,
30.3, 134.9, 135.5, 143.5, 144.3, 189.8 ppm. HRMS (EI): calcd.
14O 222.1045; found 222.1044.
pounds, X-ray crystallographic analysis of 3bf.
(75.6 MHz, CDCl
3
1
Acknowledgments
for C16
H
1
(
E)-3-(4-Chlorophenyl)-1-(4-methylphenyl)-2-propen-1-one (3bf): H
We thank the Sophia Research Organization for an Intra-Univer-
sity Collaborative Research Grant.
NMR (300 MHz, CDCl
3
): δ = 2.42 (s, 3 H), 7.28 (d, J = 7.9 Hz, 2
H), 7.36 (d, J = 8.6 Hz, 2 H), 7.49 (d, J = 15.8 Hz, 1 H), 7.54 (d,
J = 8.3 Hz, 2 H), 7.73 (d, J = 15.8 Hz, 1 H), 7.92 (d, J = 8.2 Hz,
H) ppm. 1 C NMR (75.6 MHz, CDCl
3
[1] For selected reviews, see: a) H. C. Brown, J. B. Cambell Jr., Ald-
richim. Acta 1981, 14, 3–11; b) J. K. Stille, Angew. Chem. 1986,
2
3
): δ = 21.6, 122.4, 128.6,
1
29.1, 129.3, 129.5, 133.4, 135.4, 136.2, 142.7, 143.7, 189.5 ppm.
9
8, 504; Angew. Chem. Int. Ed. Engl. 1986, 25, 508–524; c)
35
HRMS (EI): calcd. for C16H13 ClO 256.0655; found 256.0651.
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E)-1-(4-Fluorophenyl)-3-phenyl-2-propen-1-one (3ca): 1H NMR
(
(300 MHz, CDCl
3
): δ = 7.11–7.20 (m, 2 H), 7.38–7.44 (m, 3 H),
7
1
1
1
1
2
.49 (d, J = 15.8 Hz, 1 H), 7.58–7.67 (m, 2 H), 7.81 (d, J = 15.5 Hz,
13
3
H), 8.01–8.09 (m, 2 H) ppm. C NMR (75.6 MHz, CDCl ): δ =
2
3
15.6 ( JC-F = 22 Hz), 121.5, 128.4, 128.9, 130.6, 131.0 ( JC-F
=
4
1
0 Hz), 134.4 ( JC-F = 3 Hz), 134.7, 144.9, 166.5 ( JC-F = 255 Hz),
(
Eds.: L. E. Overman), Wiley, 2007, vol. 68, pp. 1–302; i) J. C.
88.7 ppm. HRMS (EI): calcd. for C15
26.0775.
H11FO 226.0794; found
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(
E)-1-Phenyl-1-nonen-3-one (3da): H NMR (300 MHz, CDCl
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=
0.89 (t, J = 6.9 Hz, 3 H), 1.25–1.42 (m, 6 H), 1.61–1.74 (m, 2
2010, 43, 581–590.
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Eur. J. Org. Chem. 2013, 8033–8038
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
8037

Y. Masuyama, W. Takamura, N. Suzuki
FULL PAPER
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Published Online: October 9, 2013
8038
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 8033–8038