Cross-coupling of arylboronic acids with terminal alkynes in air

Article abstract of DOI:10.1016/j.tetlet.2003.09.173

A new procedure has been developed for constructing arylalkynes through cross-coupling of terminal alkynes with arylboronic acids catalyzed by a palladium-silver system under mild conditions.

Full text of DOI:10.1016/j.tetlet.2003.09.173

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8709–8711
Cross-coupling of arylboronic acids with terminal alkynes in air
Gang Zou,* Junru Zhu and Jie Tang
Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China
Received 22 April 2003; revised 7 August 2003; accepted 17 September 2003
Abstract—A new procedure has been developed for constructing arylalkynes through cross-coupling of terminal alkynes with
arylboronic acids catalyzed by a palladium–silver system under mild conditions.
© 2003 Elsevier Ltd. All rights reserved.
Alkyne moieties are widely found in natural products
and artificial organic materials.1 Sonogashira cross-cou-
pling has dominated the methodologies for construction
of aryl alkynes.2 There are some drawbacks with the
traditional Sonogashira coupling procedure. For exam-
ple, it does not work well for electron-deficient alkynes.
So, many efforts have been devoted to develop modifi-
cations or alternatives.3 Recently, an umpolung com-
plement to Sonogashira procedure has been reported
using thioalkynes and boronic acids under non-basic
condition.4 However, thioalkynes have to be prepared
separately. We report here a palladium-catalyzed, sil-
ver-assisted procedure for constructing arylalkynes by
direct cross-coupling of boronic acids with terminal
alkynes in air.
AgOAc failed to work without excess K2CO3, while
AgNO3 promoted only homo-coupling of PhB(OH)2.
However, in the presence of excess of K2CO3 both these
silver salts gave results similar to that obtainable from
Ag2O (Table 1, entries 2, 7 and 8). Non-oxidative silver
salt, such as Ag3PO4, displayed no activity regardless
whether there was K2CO3 or not. Ag2CO3 worked only
at elevated temperature (Table 1, entry 5). Ag2O (1
equiv.) with excess K2CO3 required much longer reac-
tion time and other metal oxides showed no reactivity
(Cu2O) or less efficiency (HgO). Palladium sources such
as (PPh3)2PdCl2 and PdCl2(Bmim)2 (Bmim=N-methyl-
N%-butylimidazol-2-ylidene) were also tested as cata-
lysts. The former was less efficient and the later
decomposed when exposed to Ag(I) salts. After much
experimentation,
a
combination of 5% equiv.
Pd(dppf)Cl2, 2 equiv. Ag2O and 5 equiv. K2CO3 was
Silver(I) oxide has been known to activate CꢀB bond,
thus accelerating the transmetalation between RB(OH)2
and palladium species.5 When octyne and PhB(OH)2
were subjected to treatment with Ag2O-Pd(dppf)Cl2 in
the presence of excess of K2CO3 in CH2Cl2 or toluene
under N2 the desired cross-coupling proceeded
smoothly. In fact, the above cross-coupling tolerated
air and water although protodeborylation of boronic
acids happened in some cases.
found to gave the best performance.6
Table 1. Cross-coupling of octyne with phenylboronic
acida
Entry
Catalyst
Additive
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
9
(PPh3)2PdCl2
(dppf)PdCl2
(dppf)PdCl2
(dppf)PdCl2
(dppf)PdCl2
(dppf)PdCl2
(dppf)PdCl2
(dppf)PdCl2
(dppf)PdCl2
Ag2O
Ag2O
Ag2O
Ag2O
CH2Cl2
CH2Cl2
THF
Toluene
Toluene
Toluene
CH2Cl2
CH2Cl2
CH2Cl2
56
89
60
87
70
49
80
85
c
Ag2CO3
HgOc
An initiation period was observed for the cross-cou-
pling, so no product was detected before a reddish–
brown color appeared. Oxidative silver salts and bases
were crucial for the success of the cross-coupling. Thus
AgOAcd
d
AgNO3
Ag3PO4
Trace
a Reactions were run with 1.1 equiv. PhB(OH)2 for 20–30 h in air and
at 25°C.
b Isolated yields.
Keywords: cross-coupling; alkyne; arylboronic acid; palladium; silver.
* Corresponding author. Tel.: +86-21-62232764; fax: +86-21-
62232100; e-mail: gzou@chem.ecnu.edu.cn
c Heated at 60°C.
d No cross-coupling without K2CO3.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.173

8710
G. Zou et al. / Tetrahedron Letters 44 (2003) 8709–8711
Table 2. Cross-coupling of alkynes with arylboronic acids
alkyne respectively, so they should be competitive.
When transmetalation from boron was much slower
than from alkyne, such as in the case of BuB(OH)2,
homo-coupling of the alkyne would occur. If they were
comparable the selectivity of both cross- and homo-
coupling would be low and a mixture of homo- and
cross-coupling products would be produced, such as in
the case of PhCꢁCH with PhB(OH)2.
Entry
RCꢁCH
R%-B(OH)2
Product
Yield (%)a
1
2
3
4
5
6
7
8
n-C6H13
n-C6H13
n-C6H13
Ph
1a
1b
1c
1d
1e
1f
90
81
87
87
86
78
30b
0c
In conclusion, an unprecedented generally efficient pro-
cedure catalyzed by a palladium–silver system for cross-
coupling of arylboronic acids with alkynes under mild
conditions has been developed. The umpolung proce-
dure to the traditional Sonogashira coupling worked
well for both electron-rich and -deficient alkynes. Inves-
tigation of the scope and utility of the procedure in
synthesis is in progress in our laboratory.
p-EtO2CC6H4
p-MeOC6H4
CH2OBn Ph
EtO2C
EtO2C
Ph
Ph
p-EtO2CC6H4
Ph
n-C4H9
1g
1h
n-C6H13
a Isolated yields.
b Biphenylbutadinye 2a (60%) and biphenyl (10%) were obtained.
c 7,9-Hexadecyldiyne 2b was isolated in 95% yield.
Acknowledgements
We thank Shanghai Science & Technology Council
(02QA14016, 02JG05040) and Ministry of Education,
PR China for financial support.
References
1. (a) Bunz, U. H. F. Chem. Rev. 2000, 100, 1605–1644; (b)
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sen, P.; Livingston, R. C.; Diederich, F. Angew. Chem.,
Int. Ed. 2000, 39, 2632–2657; (d) Martin, R. E.; Diederich,
F. Angew. Chem., Int. Ed. 1999, 38, 1350–1377.
2. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 16, 4467–4470; (b) Sonogashira, K. In Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F.; Stang,
P. J., Eds.; Wiley: Weinheim, 1997; Chapter 5, pp. 203–
229.
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Scheme 1. A plausible mechanism for the Pd–Ag catalyzed
cross-coupling of arylboronic acids with alkynes.
Typical electron donor (MeO) or withdrawing groups
(CO2Me) on the arylboronic acid component showed
little effect on the cross-coupling reaction (Table 2,
entries 2 and 3). It is noteworthy that the electron-
deficient alkyne, ethyl propiolate, also gave the desired
cross-coupling product in good yield since the tradi-
tional Sonogashira coupling procedure leads to low
yields for electron-deficient alkynes. However, PhCꢁCH
tended to self-couple during cross-coupling with
PhB(OH)2 (Table 2, entry 7). Alkylboronic acid, such
as BuB(OH)2, was inert under the condition. So only
homocoupling of the alkyne occurred for 1-octyne and
BuB(OH)2 (Table 2, entry 8).7
4. Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2001, 3,
91–93.
5. Zou, G.; Reddy, Y. K.; Falck, J. R. Tetrahedron Lett.
2001, 42, 7213–7215.
A plausible mechanism for the cross-coupling is shown
in Scheme 1. The precursor of catalytic species, palladi-
um(II) was first reduced to palladium(0) by arylboronic
acid or alkynylsilver (I) formed in situ. The key role of
Ag2O in the mechanism is probably to activate the
alkynylpalladium complex, thus facilitating the
transmetalation of aryl group from arylboronic acid.
Through the mechanism, cycle 1 provides cross-cou-
pling products while homo-coupling of alkynes takes
place through cycle 2. Both cycles 1 and 2 begin with
CꢀH oxidative addition of terminal alkyne to Pd(0)
species,8 followed by transmetalation from boron or
6. Representative procedure for the cross-coupling: To a solu-
tion of alkyne (1.0 mmol) and boronic acid (1.1 mmol) in
10 mL CH2Cl2 was added 0.05 equiv. (dppf)PdCl2 (35 mg,
0.05 mmol) followed by 5 equiv. K2CO3 (0.7 g, 5.0 mmol)
and 2.5 equiv. Ag2O (0.6 g, 2.5 mmol,). After the mixture
was stirred for 3–5 min a reddish–brown color developed.
The resulting deep brown mixture was stirred at room
temperature (25°C) until no starting material was detected
(20–30 h). Then the mixture was filtered and filtrate was
evaporated under reduced pressure. The crude products
were purified by flash chromatography or PTLC. All
1
known compounds were identified by comparing their H

G. Zou et al. / Tetrahedron Letters 44 (2003) 8709–8711
8711
NMR with those reported in the literature. The analyti-
cal data for new compounds are as follows:
(m, 10H, Ph); 4.71 (s, 2H, OCH2), 4.41 (s, 2H, OCH2).
13CNMR: 137.5, 131.7, 128.4, 128.2, 128.0, 127.8, 122.6,
86.4, 85.1, 71.6, 57.8. EI-MS, m/z (relative, %): 222 (2.0)
[M+], 221 (5.0) [M−1] +, 193 (29.0), 115 (100.0), 91
(39.0). Elemental analyses for C16H14O: Found: C, 86.13;
H, 6.27. Required: C, 86.45; H, 6.35.
1c: 1H NMR (500 MHz, CDCl3, 25°C) ppm: 7.30 (d,
2H, J=4.5 Hz); 6.80 (d, 2H, J=4.0 Hz,); 3.78 (s, 3H,
OCH3), 2.45 (t, 2H, J=3.5 Hz, CH2); 1.60–1.70 (m, 2H);
1.45–1.50 (m, 2H), 1.30–1.40 (m, 4H), 0.95 (t, J=
3.5 Hz, 3H, CH3). 13C NMR: 159.7, 133.5, 117.1,
114.5, 89.4, 81.0, 55.9, 32.1, 29.6, 29.3, 23.2, 20.1, 14.7.
EI-MS, m/z (relative, %): 216 (65.0) [M+], 187 (26.0)
[M−29]+, 173 (48.0), 145 (100.0). Elemental analyses for
C15H20O: Found: C, 83.60; H, 9.18. Required: C, 83.29;
H, 9.32.
7. For Pd-catalyzed homo-coupling of terminal alkynes,
see: (a) Liu, Q.; Burton, D. J. Tetrahedron Lett. 1997,
38, 4371–4374; (b) Lei, A.; Srivastava, M.; Zhang, X. J.
Org. Chem. 2002, 67, 1969–1971.
8. Oxidative addition of CꢀH of alkynes to Pd(0) is known.
See: Rubina, M.; Gevorgyan, V. J. Am. Chem Soc. 2001,
123, 11107–11108.
1d: 1H NMR (300 MHz, CDCl3, 25°C) ppm: 7.30–7.50