Other fluoride ions and inorganic bases such as KF (0%),
CsF (0%), AgF (11%), and K2CO3 (0%) were used in the
coupling reaction of alkynes; however, such additives showed
little or no effect as a competent activator. The use of
tetrabutylammonium hydroxide (TBAOH; as a 40% aqueous
solution), in contrast, was also found to promote the coupling
under similar conditions, giving a >99% yield in the reaction
of 5b and 2a.
Table 2. Cross-Coupling of 1-Alkynes by the Activation of
TBAFa
R1
X-R2
time/h
yield/%
Although the coupling reactions using Ag2O or TBAF
were found to proceed smoothly, these reactivities seem
slightly inferior to that of the Sonogashira reaction under
similar conditions.3,14 However, worthy of note is the
procedural simplicity of the reactions despite stoichiometric
use of Ag2O or TBAF. The Sonogashira reactions generally
use excess amounts of amine as a solvent or cosolvent, which
might cause difficulties in procedures for removal of a high-
boiling solvent and of the thus formed ammonium salts. In
contrast, the workup procedure of the reaction using Ag2O
in THF could be carried out by easy filtration of the solid
residue followed by purification of the concentrated crude
material by simple column chromatography, distillation, and/
or recrystallization. The workup in the reaction with TBAF
was also similar. Thus, we consider that the present reactions
can be a viable alternative to the Sonogashira coupling with
a wide variety of organic electrophiles.
C6H5- (5b)
4-I-C6H4-OCH3 (2b)
I-C6H4-CN
6
5
6
48
24
24
6
24
5
83
86
76
54
75
81
59
59
64
64
5b
5b
5b
2b
4-Br-C6H4-COCH3
4-Br-C6H4-COCH3
n-C6H13- (5a )
5a
2b
5a
I-C6H5 (2a )
4-I-C6H4-COCH3 (2c)
HOCH2- (5e)
HO(CH2)2- (5f)
HO(CH3)2C- (5d )
2a
2a
24
a Reactions were carried out at 60 °C under the following reaction
conditions: THF (2 mL), alkyne (0.6 mmol), aryl halide (0.5 mmol),
Pd2(dba)3 (0.5 mol %)-PPh3 (2 mol %), TBAF (0.55-0.6 mmol).
Pd2(dba)3CHCl3 and 2 mol % of PPh3). Although the reaction
using a catalytic amount of TBAF was attempted, the
coupling product was obtained in a yield corresponding to
the employed amount of TBAF.9
As summarized in Table 2, aryl iodides with an electron-
donating or electron-withdrawing substituent similarly un-
derwent the reactions in good yields. In contrast to the results
using Ag2O, the reaction with an aryl bromide proceeded,
although relatively longer reaction periods than those of
iodides were necessary.10 In addition to 1-octyne (5a) and
phenylethyne (5b), terminal alkynes bearing a hydroxy
functional group (5d-5f) could effect the coupling reactions
in good yields.
In conclusion, the coupling reactions of terminal alkynes
with organic halides proceeded highly efficiently. Since
isolation and purification in these reactions can be performed
much more easily, the reactions could be used as an
alternative to the Sonogashira coupling. Further studies on
the optimization of reaction conditions to find highly reactive
catalyst systems are now in progress.
Acknowledgment. The authors thank Asahi Glass Foun-
dation for financial support.
TBAF has been recognized to be an effective desilylating
agent for a variety of organosilicon compound to convert a
X-Si bond to a X-H bond (X ) O, N, C, etc.).11 In addition,
TBAF has been utilized as an activating reagent of orga-
nosilanes for carbon-carbon bond-forming reactions such
as Sakurai-Hosomi reaction12 and palladium-catalyzed
cross-coupling reactions with various organic electrophiles.6
In a sharp contrast with numerous examples of such smooth
coupling of alkynyltrimethylsilane with aryl or alkenyl
halides, the coupling of terminal alkynes using TBAF as an
activator has not been reported so far to the best of our
knowledge.13
Supporting Information Available: Experimental pro-
cedures for typical palladium-catalyzed coupling reactions
using Ag2O and TBAF as activators and additional results
concerning optimization of the reaction conditions shown
in Table 2. This material is available free of charge via the
OL0061586
(13) Although several coupling reactions of terminal alkynes have been
shown to proceed without Cu(I), the use of highly reactive organic
electrophiles and/or excess amounts of amine as a (co)solvent are necessary.
For example: (a) Austin W. B.; Bilow, N.; Kelleghan, W. J.; Lau, K. S. Y.
J. Org. Chem. 1981, 46, 2280. (b) Alami, M.; Ferri, F.; Linstrumelle, G.
Tetrahedron Lett. 1993, 34, 6403. (c) Schaus, J.; Panek, J. S. Org. Lett.
2000, 2, 469. See also the use of AgI instead of CuI: (d) Bertus, P.; Pale
P. Tetrahedron Lett. 1996, 37, 2019.
(10) Attempted reaction with a triflate under similar conditions gave
unidentified products.
(11) For a review on the use of fluoride ion, see: Clark, J. H. Chem.
ReV. 1980, 429.
(12) (a) Pilcher, A. S.; DeShong, P J. Org. Chem. 1996, 61, 6901. (b)
Hosomi, A.; Shirahata, A.; Sakurai, H. Tetrahedron Lett. 1978, 3043.
(14) The reaction of 1-octyne and iodobenzene with 5 mol % of Pd
catalyst was compared using Ag2O (90%: 60 °C, 8 h), TBAF (82%: 60
°C, 3 h), and typical Sonogashira conditions (see ref 3b) (91%: rt, 1 h).
Org. Lett., Vol. 2, No. 19, 2000
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