U. Halbes et al. / Tetrahedron Letters 42 (2001) 8641–8644
8643
and a solution of tetrabutylammonium fluoride trihy-
drate (1.5 equiv.) in anhydrous DMF (0.15 M) was
added. Once one of the starting materials disappeared,
diethyl ether (10 mL) and then water (10 mL) were
added. The mixture was then filtered over Celite and
the phases were separated. The aqueous layer was
extracted three times with diethyl ether and the com-
bined organic layers were washed three times with
water to remove DMF. The organic phases were dried
over MgSO4, filtered and concentrated in vacuo. The
crude product was purified by silica gel column chro-
matography yielding the expected pure enyne.
(Table 3 versus Tables 1 and 2). Nevertheless, the
fragile epoxyenyne moiety can easily and conveniently
be obtained in high yield owing to the mildness of the
present method. In this case, as in the case of 2a–d, the
bulkiness at the silyl group plays a significant role,
lowering the yield of coupling product (entries 2 and 3
versus 1). It is also worth mentioning that no protecting
group was required for the hydroxyl group in 6a–c. No
side reaction was detected despite the concomitant pres-
ence of a free alcohol and an acetylenic function.16
Control experiments exhibited unexpected results.
Indeed, experiments run without silver cocatalyst sur-
prisingly yielded the enynes 3, 5 and 7 although less
efficiently (Table 4). Under these conditions, the cou-
pling efficiency is clearly related to the structure of the
alkyne partner. However, the nature of the silyl group
carried by the alkyne, and most probably its size, seems
to be critical, dramatically reducing yields (entries 2, 4
and 6 versus 1, 3 and 5). For the sensitive trialkylsilyl-
epoxyalkynes 6, the presence of silver salt is always
critical, whatever the nature of the silyl group, in order
to achieve a efficient coupling (Table 4, entries 5 and 6
versus Table 3, entries 1 and 3). These preliminary
results raise interesting mechanistic questions, which
are now addressed.
Acknowledgements
The authors thank the CNRS for financial support.
P.P. thanks the ‘Institut Universitaire de France’ for
support. P.B. thanks the ‘Ministe`re de la Recherche et
de la Technologie’ and U.H. the Daimler-Benz Founda-
tion for PhD fellowships.
References
1. Christensen, L. P.; Lam, J. Phytochemistry 1991, 30, 11
and Phytochemistry 1990, 29, 2753.
In conclusion, functionalized enynes can be easily
obtained by a new fluoride-mediated coupling reaction
directly from their 1-trialkylsilyl-1-alkynes progenitors.
Further synthetic developments are underway in our
group.
2. (a) Faulkner, D. J. Nat. Prod. Rep. 1999, 16, 155–198; (b)
Faulkner, D. J. Nat. Prod. Rep. 2000, 17, 7–55.
3. Bohlmann, F.; Burkhardt, T.; Zdero, C. Naturally Occur-
ring Acetylenes; Academic Press: New York, 1973.
4. For an overview of the biological as well as chemical
aspects, see: Nicolaou, K. C.; Smith, A. L. In Modern
Acetylene Chemistry; Stang, P. J.; Diederich, F., Eds.;
VCH: Weinheim, 1995; pp. 203–283. For reviews dealing
with the synthesis of such enynes, see: Grissom, J. W.;
Gunawardena, G. U.; Klingberg, D.; Huang, D. Tetra-
hedron 1996, 52, 6453–6518; Lhermitte, H.; Grierson, D.
S. Parts 1 & 2, Contemporary Organic Synthesis 1996,
41–63 and 93–124.
Supplementary material
Typical procedure for the fluoride-induced coupling
reaction of 1-trialkylsilyl-1-alkynes with vinyl triflate:
To a triflate (1 equiv.) solution in anhydrous DMF
(0.17 M) were successively added under an argon atmo-
sphere
tetrakis(triphenylphosphine)palladium
(0.1
equiv.), silver iodide (0.2 equiv.) and 1-trialkylsilyl-1-
alkyne (1.1 equiv.) diluted in anhydrous DMF (0.27
M). The resulting mixture was then stirred for 5 min
5. Modern Acetylene Chemistry; Stang, P. J.; Diederich, F.,
Eds.; VCH: Weinheim, 1995.
6. (a) Sonogashira, K. In Comprehensive Organic Chemistry;
Fleming, I.; Trost, B. M., Eds.; Pergamon: Oxford, 1991;
Vol. 3, pp. 521–549; (b) Farina, V. In Comprehensive
Organometallic Chemistry II; Abel, E. W.; Stone, F. G.
A.; Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol.
12, pp. 222–225.
7. (a) Horn, K. Chem. Rev. 1995, 95, 1317–1350; (b)
Hiyama, T. In Metal-Catalyzed Cross-Coupling Reac-
tions; Diederich, F.; Stang, P. J., Eds.; Wiley: Weinheim,
1997; pp. 421–453.
Table 4. TBAF, 3H2O-promoted coupling of 1-trialkylsil-
yl-1-alkynes without AgI
R'
R'
SiR3
OTf
2,4,6
nBu4NF, 3H2O
Pd(PPh3)4
3, 5, 7
1
8. (a) Bertus, P.; Pale, P. Tetrahedron Lett. 1996, 37, 2019–
2022; (b) Bertus, P.; Pale, P. Tetrahedron Lett. 1997, 38,
8193–8196; (c) Bertus, P.; Pale, P. J. Organomet. Chem.
1998, 567, 173–180.
9. Pentacoordinated silanes bearing a vinyl or aryl group
have been postulated as intermediates in a few coupling
reactions. See: Kumada, M. Tetrahedron Lett. 1978, 19,
2161–2164; Hiyama, T.; Hatanaka, Y. Pure Appl. Chem.
1994, 66, 1471–1478; see also Ref. 7.
Entry
Alkyne
SiR3
Time (h)
Yield (%)
1
2
3
4
5
6
2a
2c
4a
4c
6a
6c
Me3Si–
Ph2tBuSi–
Me3Si–
Ph2tBuSi–
Me3Si–
Ph2tBuSi–
24
24
18
18
22
22
85
26
68
31
30
15
Halbes, Ulla
