GaCl3-catalyzed chloroacylation of alkynes: A simple, convenient and efficient method to β-chlorovinyl ketones

Article abstract of DOI:10.1055/s-2006-956478

Gallium chloride catalyzed acylation of alkynes was studied to afford one of the most atom-economic and efficient methodologies for the preparation of β-chlorovinyl ketones. In contrast to the Friedel-Crafts acylation, only a catalytic amount of GaCl

Full text of DOI:10.1055/s-2006-956478

3504
LETTER
GaCl3-Catalyzed Chloroacylation of Alkynes: A Simple, Convenient and
Efficient Method to b-Chlorovinyl Ketones
G
aCl -Catalyzed
C
o
hloroacylati
n
on of
A
lkyne
g
s
wei Zhou,*a Changying Zeng,a Lianjun Ren,a Wenhui Liao,a Xian Huang*a,b
3
a
Department of Chemistry, Zhejiang University (Campus Xixi), Hangzhou 310028, P. R. of China
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. of China
Fax +86(571)88212531; E-mail: zhouhw@zju.edu.cn
Received 27 August 2006
1
observe the trans isomer even in the H NMR spectra of
Abstract: Gallium chloride catalyzed acylation of alkynes was
studied to afford one of the most atom-economic and efficient meth-
odologies for the preparation of b-chlorovinyl ketones. In contrast
to the Friedel–Crafts acylation, only a catalytic amount of GaCl3
crude products, demonstrating that this reaction took a
different reaction route from the AlCl3-promoted Friedel–
Crafts addition. Considering the moisture-sensitivity and
was needed to produce the target products in high stereoselectivity. low turnover number (TON) of the catalyst GaCl3,5 we
tried the experiment under nitrogen atmosphere using 0.2
equivalent of GaCl3. To our delight, the reaction was com-
plete in two hours and compound 3a was obtained in 65%
yield (Scheme 1).
Key words: gallium trichloride, acylation, alkyne, b-chlorovinyl
ketone
In the past decade, gallium chloride (GaCl3), for a long
time considered to be analogous to aluminum chloride
(AlCl3) but with a lower reactivity, has been revealed to be
a reagent used for generating organogallium compounds,
which can carbometalate unactivated unsaturated bonds.1
Recently, Yamaguchi and co-workers reported many in-
teresting GaCl3-promoted reactions, such as the insertion
of Ga(III) complexes into alkynes to produce vinylgalli-
ums as important synthetic intermediates.2
O
O
GaCl3
C5H11
Cl
Ph
C5H11
+
r.t., CH2Cl2
Cl
H
Ph
1a
2a
3a
0.1 equiv GaCl3: 3 h, 25%
0.2 equiv GaCl3: 2 h, 65%
Scheme 1
b-Chlorovinyl ketones are very useful intermediates
for the synthesis of a variety of compounds.3 Although
b-chlorovinyl ketones are a class of simple com-
pounds, there are not many synthetic routes to these
compounds.3b–3g In the early 1970s, the Friedel–Crafts
addition of acid chloride–AlCl3 complexes to acetylenes
leading to b-chlorovinyl ketones had been reported.4 The
major products from the Friedel–Crafts addition, which
requires equimolar amounts of acid chloride–AlCl3 com-
plex, have the chlorine and the carbonyl groups config-
ured in a trans relationship.4b Herein we wish to report a
GaCl3-catalyzed acylation of alkynes for the synthesis of
b-chlorovinyl ketones in which the major products con-
tain a cis configuration.
Encouraged by this result, we turned our attention to other
acid chlorides and alkynes (Table 1). However, we ob-
served that the trans isomers could be isolated in cases
when the acid chlorides used were sterically non-hindered
or aromatic acid chlorides (entries 6–11, Table 1). More-
over, to our surprise, in those cases prolonging the reac-
tion time also changed the cis/trans ratio (entries 12–16,
Table 1), indicating that this type of b-chlorovinyl ke-
tones was sensitive to cis/trans isomerization in the pres-
ence of GaCl3.4c
Recently, Yadav et al. reported a stereoselective conden-
sation of phenylacetylene with benzaldehyde in the pres-
ence of gallium trihalides but no mechanism was
proposed.7 Yamaguchi et al. has also developed an inter-
esting GaCl3-promoted C2-olefination of aromatic hydro-
As a first attempt, we examined the reaction of hexanoyl
chloride (1a) with phenylacetylene (2a) using 0.1 equiva-
lent of GaCl3 as catalyst and dichloromethane as solvent
at room temperature. 1-Chloro-1-phenyloct-1-en-3-one
(3a) was isolated in 25% yield together with 42% of re-
covered phenylacetylene. The stereochemistry of the
product 3a was established by 2D NOE experiment which
clearly showed an NOE effect between the aromatic pro-
tons and the vinyl proton. It was notable that we did not
carbons with silylacetylene, in which
a
novel
organogallium intermediate was reported.8 Considering
the absence of b-silicon-stabilization to vinyl cation, we
suggested the possibility of a C1-vinyl cation intermediate
mechanism for the reaction (Scheme 2).
At first a GaCl3-complexed alkyne is formed, generating
a vinyl cation intermediate A.8 The intermediate A is at-
tacked by a chloride anion to afford vinylgallium interme-
diate B. The vinylgallium intermediate B reacts with acid
chloride to give 3. Due to the sensitivity to cis/trans
isomerization,4c 3 may rearrange to give a mixture.
SYNLETT 2006, No. 20, pp 3504–3506
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.1
2
.2
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Advanced online publication: 08.12.2006
DOI: 10.1055/s-2006-956478; Art ID: W17606ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
GaCl3-Catalyzed Chloroacylation of Alkynes
3505
of unsaturated bonds by GaCl3, synthetic applications of
organogallium compounds, and the reaction mechanism
are being studied further in our laboratory.
Table 1 Synthesis of b-Chlorovinyl Ketones via the GaCl3-Cata-
lyzed Chloroacylation of Alkynesa,6
O
O
0.2 equiv GaCl3
r.t., CH2Cl2
R1
Cl
R2
R1
+
Cl
H
R2
Acknowledgment
1
2
3
Financial support was received from the Natural Science Foundati-
on of Zhejiang Province (No. 107305-N20501).
Entry R1
R2
Time (h) Yield (%)b of 3
cis/trans ratioc
References and Notes
1
2
n-Pent
n-Pent
Ph
2
3a (65)
(1) For a review, see: Amemiya, R.; Yamaguchi, M. Eur. J. Org.
Chem. 2005, 5145.
n-Pent
n-Pent
n-Pent
Ph
2
3b (61)
(2) (a) Yamaguchi, M.; Tsukagoshi, T.; Arisawa, M. J. Am.
Chem. Soc. 1999, 121, 4074. (b) Arisawa, M.; Akamatsu,
K.; Yamaguchi, M. Org. Lett. 2001, 3, 789. (c) Arisawa,
M.; Amemiya, R.; Yamaguchi, M. Org. Lett. 2002, 4, 2209.
(d) Kobayashi, K.; Arisawa, M.; Yamaguchi, M. J. Am.
Chem. Soc. 2002, 124, 8528. (e) Yonehara, F.; Kido, Y.;
Morita, S.; Yamaguchi, M. J. Am. Chem. Soc. 2001, 123,
11310. (f) Arisawa, M.; Akamatsu, K.; Yamaguchi, M. Org.
Lett. 2001, 3, 789.
(3) (a) Pohland, A. E.; Benson, W. R. Chem. Rev. 1966, 66,
161. (b) Luo, F. T.; Lai, J. H.; Shaeh, J. C. Acad. Sin. 1987,
34, 23. (c) Martin, G. J.; Kirschleger, B. Sci. Chim. 1974,
279, 363. (d) Luo, F. T.; Hsieh, L. C. Tetrahedron Lett.
1994, 35, 9585. (e) Hua, R.; Onozawa, S.; Tanaka, M.
Chem. Eur. J. 2005, 3621. (f) Doyle, M. P.; Devia, A. H.;
Bassett, K. E.; Terpstra, J. W.; Mahapatro, S. N. J. Org.
Chem. 1987, 52, 1619. (g) Badrieh, Y.; Kayyal, A.; Blum, J.
J. Mol. Catal. 1992, 75, 161.
(4) (a) Martens, H.; Janssens, F.; Hoornaert, G. Tetrahedron
1975, 31, 177. (b) Benson, W. R.; Pohland, A. E. J. Org.
Chem. 1964, 29, 385. (c) Cavalchi, B.; Landini, D.;
Montanari, F. J. Chem. Soc. C 1969, 9, 1204.
(d) Sandermann, W.; Bruns, K. Chem. Ber. 1962, 95, 1863.
(5) (a) Amemiya, R.; Suwa, K.; Toriyama, J.; Nishimura, Y.;
Yamaguchi, M. J. Am. Chem. Soc. 2005, 127, 8252.
(b) Yonehara, F.; Kido, Y.; Sugimoto, H.; Morita, S.;
Yamaguchi, M. J. Org. Chem. 2003, 68, 6752.
3
n-Pent
n-Hex
n-Hex
Med
Etd
2
3c (58)
4
2
3d (62)
5
2
3e (66)
6
n-Pent
n-Pent
n-Bu
BrCH2CH2
Ph
2.5
2.5
2.5
1.5
1.5
1.5
5
3f (62) (50:50)
3g (57) (69:31)
3h (55) (55:45)
3i (52) (88:12)
3j (61) (89:11)
3k (62) (87:13)
3g (55) (62:38)
3h (59) (52:48)
3i (58) (83:17)
3j (58) (82:18)
3k (55) (84:16)
7
8
Etd
9
Ph
10
11
12
13
14
15
16
Ph
p-Tol
Etd
Ph
n-Pent
n-Bu
BrCH2CH2
Ph
Etd
5
Ph
5
Ph
5
p-Tol
Ph
5
a All reactions were carried out using 1 (0.6 mmol), 2 (0.5 mmol) and
GaCl3 (0.1 mmol) in CH2Cl2 (5 mL) at r.t.
b Isolated product yield after chromatography.
(6) All reagents were obtained commercially except GaCl3. The
GaCl3 used was prepared as follows: Gallium (3.5 g) was
dissolved in concd HCl (100 mL) under reflux and excessive
HCl was removed under reduced pressure. To the reaction
mixture was added SOCl2 (35 mL) and excessive SOCl2 was
removed under reduced pressure (ca. 20 mm Hg by rotary
evaporation then 5 mm Hg by a pump). The residue was used
directly for our reaction with 80% purity.
c The cis/trans ratios of 3 were determined by NMR spectroscopy.
d Acid chloride (1 mmol) was used.
R
GaCl3
R
R = Alkyl or Aryl
GaCl3-Catalyzed Acylation of Alkynes; General
Procedure: To a solution of GaCl3 (20 mol%) and acid
chloride (0.6 mmol) in CH2Cl2 (5 mL) was added alkyne (0.5
mmol) under nitrogen. The reaction was stirred at r.t. and
filtered through a short celite pad, washed with Et2O,
concentrated by vacuo, and purified by chromatography on
silica gel with n-hexane–EtOAc (10:1) as the eluent.
(Z)-1-Chloro-1-phenyloct-1-en-3-one (3a): 1H NMR (400
MHz, CDCl3): d = 7.66–7.69 (m, 2 H), 7.38–7.44 (m, 3 H),
6.79 (s, 1 H), 2.67–2.71 (t, J = 7.2 Hz, 2 H), 1.66–1.70 (t,
J = 7.4 Hz, 2 H), 1.31–1.37 (m, 4 H), 0.89–0.92 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 199.0, 142.3, 137.4, 130.5,
128.6, 127.2, 123.8, 44.4, 31.3, 23.6, 22.4, 13.9. MS (EI):
m/z = 239 (7.2) [M + 3], 238 (4.6) [M + 2], 237 (21.6)
[M + 1], 236 (3.85) [M+]. IR (neat): 1695, 1591 cm–1.
(Z)-4-Chloronon-3-en-2-one (Z-3f): 1H NMR (400 MHz,
CDCl3): d = 6.24 (s, 1 H), 2.42–2.45 (t, J = 7.8 Hz, 2 H), 2.37
(s, 3 H), 1.61–1.64 (m, 2 H), 1.30–1.35 (m, 4 H), 0.89–0.92
H
R
R = Si
ref. 7
R
+
+
Ga
Cl3
Ga
Cl
+
Cl
A
–
Cl
GaCl3
–
O
R'
R
R
R
GaCl3
Cl
GaCl2
Cl
COR'
COR'
Cl
Cl
GaCl3
B
3
cis/trans-3
Scheme 2
In summary, we have reported a simple and efficient pro-
tocol for the synthesis of b-chlorovinyl ketones. The catal-
ysis of GaCl3 may produce organogallium intermediates,
which have received much less attention in organic syn-
thesis than organoaluminum compounds.1 The activation
Synlett 2006, No. 20, 3504–3506 © Thieme Stuttgart · New York

3506
H. Zhou et al.
LETTER
(m, 3 H). 13C NMR (100 MHz, CDCl3): d = 196.6, 147.4,
125.0, 41.2, 31.4, 30.6, 26.9, 22.2, 13.8. MS (EI): m/z = 176
(1.25) [M + 2], 174 (2.68) [M+]. IR (neat): 1710, 1610 cm–1.
(E)-4-Chloronon-3-en-2-one (E-3f): 1H NMR (400 MHz,
CDCl3): d = 6.44 (s, 1 H), 2.90–2.94 (t, J = 7.8 Hz, 2 H), 2.20
(s, 3 H), 1.59–1.62 (m, 2 H), 1.30–1.34 (m, 4 H), 0.87–0.91
(m, 3 H). 13C NMR (100 MHz, CDCl3): d = 195.5, 157.0,
125.7, 35.8, 31.9, 30.9, 27.3, 22.3, 13.9. MS (EI): m/z = 176
(0.96) [M + 2], 174 (1.33) [M+]. IR (neat): 1697, 1600 cm–1.
(7) Yadav, J. S.; Reddy, B. V. S.; Eeshwaraiah, B.; Gupta, K.
M.; Biswas, K. S. Tetrahedron Lett. 2005, 46, 1161.
(8) Yamaguchi, M.; Kido, Y.; Hayashi, A.; Hirama, M. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1313.
Synlett 2006, No. 20, 3504–3506 © Thieme Stuttgart · New York