A new mild procedure for the direct coupling of 1-trimethylsilyl acetylenes with vinyl triflates or aryl iodide

Article abstract of DOI:10.1016/S0040-4039(02)00209-5

1-Trimethylsilyl acetylenes can be directly coupled with vinyl triflates or aryl iodide in the presence of the appropriate amount of potassium carbonate and methanol and a catalytic amount of AgCl and Pd(PPh₃)₄. Functionalized enynes can thus be obtained in good to excellent yields without prior deprotection of the alkyne.

Full text of DOI:10.1016/S0040-4039(02)00209-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2039–2042
A new mild procedure for the direct coupling of 1-trimethylsilyl
acetylenes with vinyl triflates or aryl iodide
Ulla Halbes and Patrick Pale*
Laboratoire de synth e` se et r e´ activit e´ organique, associ e´ au CNRS, Institut Le Bel, Universit e´ L. Pasteur, 67000 Strasbourg,
France
Received 30 December 2001; revised 25 January 2002; accepted 28 January 2002
Abstract—1-Trimethylsilyl acetylenes can be directly coupled with vinyl triflates or aryl iodide in the presence of the appropriate
amount of potassium carbonate and methanol and a catalytic amount of AgCl and Pd(PPh ) . Functionalized enynes can thus be
3
4
obtained in good to excellent yields without prior deprotection of the alkyne. © 2002 Elsevier Science Ltd. All rights reserved.
The rapid construction of a polyunsaturated system is
of prime importance for material science as well as
natural products chemistry. The elaboration of regular
arrays of triple and double bonds is indeed often
required since such units are used as core or building
from a nucleophilic attack of in situ formed methylate
ion to the silicon atom. Based on this mechanism and
6,7
some of our recent results,
we reasoned that the
silicate in situ formed by addition of methylate to
8
1-trimethylsilyl alkynes should be displaced by the
1
,2
blocks for complex materials. Conjugated enyne units
are often encountered in various natural products, most
more electropositive silver ion, the release of volatile
methoxytrimethylsilane would favor this process. As we
demonstrated that silver acetylides are able to enter the
3
,4
of them exhibiting potent biological activities.
7
palladium catalytic cycle, silver ion would therefore be
Due to synthetic planning, an acetylene group often
ends up in multifunctional molecules as a trimethylsilyl
alkyne. Therefore, a deprotection step is required for a
released, allowing for another catalytic cycle, involving
silver ion, to take place (Scheme 2). Since silver
acetylides are efficiently prepared in protic solvents,
5
7,9
subsequent coupling reaction. From a practical as well
as economical point of view, it would be interesting to
avoid the deprotection step and to be able to directly
couple 1-trimethylsilyl-1-alkynes with activated alkenes.
and since Pd-catalyzed cross-coupling can be performed
10
in aqueous medium, running the coupling reaction in
methanol or in the presence of methanol would not be
a problem.
6d
To achieve that goal, we recently proposed a method
based on the concomitant use of nBu NF–3H O and
In order to check the above assumptions and to find the
4
2
Pd(PPh ) and AgI as catalysts. However, this method
more appropriate conditions, 4-tert-butylcyclohexenyl
3
4
11
cannot be applied to compounds bearing other silyl
groups without deprotecting them. To circumvent this
problem and enrich the panoply of synthetic tools, we
developed another route to perform such direct cou-
pling (Scheme 1).
triflate 1 and 1-trimethylsilyl hex-1-yne 2a were first
stirred in DMF together with various amounts of
potassium carbonate and methanol in the presence of
catalytic amounts of silver salt and tetra-
kis(triphenylphosphine) palladium (Scheme 3 and Table
1
).
One of the mildest methods to regenerate terminal
acetylenes from trimethylsilyl acetylenes uses a mixture
of potassium carbonate in methanol. In this deprotec-
tion, the cleavage of the CꢀSi bond probably results
Me3Si
R4
R1
R4
K2CO3 MeOH
R1
Ar-I or
OTf Pd° / AgX cat. R2
DMF
R2
R3
R3
*
0
Corresponding author. Tel./fax: +33 390 241 517; e-mail:
ppale@chimie.u-strasbg.fr
Scheme 1.
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00209-5

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040
U. Halbes, P. Pale / Tetrahedron Letters 43 (2002) 2039–2042
R1
R1
ever, the presence of silver ion is critical since no
R4
reaction was observed without silver salt whatever the
amount of potassium carbonate and methanol added
(entries 6, 7). Surprisingly, in the latter conditions, the
starting materials were recovered intact, indicating that
silver ion may play a role during the desilylation step.
Running the reaction in pure methanol or in a 1 to 1
mixture of methanol and DMF was less efficient than
doing it in pure DMF with just the required amount of
methanol (entries 8 or 9 versus 5). In the latter condi-
tions, 3a was obtained in quantitative yield (entry 5).
OTf
R2
R2
R3
Pd0
R3
R1
R1
PdOTf
Pd
R2
R2
R3
R3
R4
Various representative trimethylsilylated alkynes 2b–f
1
2,13
were then prepared by conventional methods
and
_
R4
Ag+ OTf-
submitted to the above conditions. The expected cou-
pling products 3b–f were obtained in good to excellent
yields, as shown in Table 2.
Ag
_
R4
The presence of a free hydroxyl group do not impart
the efficiency of this coupling as demonstrated by the
quantitative coupling of 5-trimethylsilyl-4-pentynol 2b
compared to the coupling of 1-trimethylsilyl-1-hexyne
Me3SiOMe
SiMe3OMe
K2CO3, MeOH
SiMe3
R4
2
a (entry 2 versus 1). However, if such functional group
is adjacent to the triple bond, a decrease in yield is
observed (entries 3, 4 versus 2). The electronic influence
of this functional group may be responsible for the
observed effect, and the presence of a second group
which also exhibits an electronic influence proved to
markedly diminish the yield (entry 4 versus 3). In the
latter case, the yield is nevertheless good and compara-
ble with those obtained through the common two-step
sequence usually required. Interestingly, really conju-
gated 1-trimethylsilyl-1-alkynes, with or without
hydroxyl group, 2f or 2e, respectively, gave the corre-
sponding dienynes in very good yield (entries 5, 6).
Scheme 2. Mechanistic hypothesis for a Pd/Ag-catalyzed cou-
pling of 1-trimethylsilylalkynes.
R
OTf
R
SiMe3
2a-f
K2CO3 MeOH
AgX - Pd(PPh3)4
DMF, rt
1
3a-f
Scheme 3.
We were pleased to observe the formation of the
expected enyne 3a. However, the coupling yield was
dramatically influenced by the amount of potassium
6
More complex vinyl triflates can also be involved in this
coupling reaction. Conjugated vinyl triflates proved to
be good partners and, as an example, the triflate
derived from tetralone 8 was reacted with 1-trimethyl-
silyl hex-1-yne 2a and 5-trimethylsilyl-4-pentynol 2b,
providing the corresponding enynes 9a–b in excellent
yields (Scheme 4). Aryl iodide could also be engaged in
this new coupling reaction. They however required a
slight heating (40°C instead of rt) and a further increase
of reagents (K CO , MeOH 8 equiv. each) to undergo
carbonate and methanol added to the reaction mixture
(
Table 1, entries 1–5). Less than 4 equiv. of each
reagent in DMF gave around 50% of conversion and
thus a modest overall yield of the expected coupling
product after purification (Table 1, entries 1–3). From
some of our previous results, we anticipated an effect
from the nature of silver salt and indeed, the chloride
proved more effective as cocatalyst in these conditions
than the iodide (entries 2 versus 1, 5 versus 4). How-
2
3
an efficient coupling, as illustrated with the coupling of
Table 1. Coupling of 1 and 1-trimethylsilyl-1-hexyne 2a in the presence of Pd(PPh ) (0.1 equiv.) and AgX (0.2 equiv.)
3
4
Entry
AgX
K CO (equiv.)
MeOH
DMF (mM)
Yieldb of 3a
2
3
1
2
3
4
5
6
7
8
9
AgI
AgCl
AgCl
AgI
AgCl
–
1.2
1.2
2
4
4
2
4
4
4
1.2 equiv.
1.2 equiv.
2 equiv.
4 equiv.
4 equiv.
2 equiv.
4 equiv.
33a
33
33
33
33
33
33
–
23
46
42
39
99
0
0
72
84
–
a
AgCl
AgCl
33 mM
a
a
16.5 mM
16.5
a
Concentration relative to the triflate.
Yield of isolated pure product.
b

U. Halbes, P. Pale / Tetrahedron Letters 43 (2002) 2039–2042
Table 2. Coupling of 1 with various 1-trimethylsilyl-1-alkynes 2b–f
2041
Entry
Alkyne
Time (h)
Yield (%)a
Product
1
2
3
4
5
R=nBu
R=-(CH ) OH
R=-C(CH ) OH
R=-CH(Ph)OH
2a
2b
2c
2d
2e
20
19
23
22
15
99
99
78
56
89
3a
3b
3c
3d
3e
2
3
3
2
6
2f
25
76
3f
a
Yield of isolated pure product.
phenyl iodide and 2a or 2b (Scheme 5). The expected
times with water to remove DMF, dried over MgSO4,
filtered and concentrated in vacuo. The crude product
was purified by silica gel column chromatography using
the appropriate mixture of hexane and ethyl acetate
yielding the corresponding pure enyne.
1
4
1
-phenyl-1-alkynes 10a–b were obtained with good
yields in these conditions.
In conclusion, we demonstrated here that 1-trimethylsil-
yl-1-alkynes can be directly coupled to vinyl triflates or
aryl iodide in the presence of potassium carbonate,
methanol and with tetrakis(triphenylphosphine)-
palladium and silver salt as catalysts. Various enynes
have thus been conveniently obtained in good to excellent
yields in a single step avoiding a preliminary deprotection
step. Further works in this area are now in progress.
Acknowledgements
The authors thank the CNRS for financial support. P.P.
thanks the ‘Institut Universitaire de France’ for support,
and U.H. the Daimler-Benz Foundation for a Ph.D.
fellowship.
Typical procedure for the methylate-induced coupling
reaction of 1-trimethylsilyl-1-alkynes with vinyl triflate
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