Palladium-catalyzed coupling of two alkynes and an alkenyl iodide: Formation of pentasubstituted fulvenes

Article abstract of DOI:10.1021/ol016472f

(matrix presented) Disubstituted alkynes reacted with alkenyl iodide in the presence of a catalytic amount of Pd(OAc)₂ and Ag₂CO₃ to give pentasubstituted fulvene derivatives in excellent yields. Other Ag salts such as AgNO₃, AgBF₄, and AgOTf are not effective, whereas a combination of AgNO₃ and K₂CO₃ has a remarkable effect on the formation of fulvene.

Full text of DOI:10.1021/ol016472f

ORGANIC
LETTERS
2001
Vol. 3, No. 22
3467-3470
Palladium-Catalyzed Coupling of Two
Alkynes and an Alkenyl Iodide:
Formation of Pentasubstituted Fulvenes
Martin Kotora,* Hiroshi Matsumura, Guohua Gao, and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences,
Hokkaido UniVersity, Kita-ku, Sapporo 060 -0811, and CREST, Science and
Technology Corporation (JST), Sapporo 060-0811, Japan
tamotsu@cat.hokudai.ac.jp
Received July 21, 2001
ABSTRACT
Disubstituted alkynes reacted with alkenyl iodide in the presence of a catalytic amount of Pd(OAc)2 and Ag2CO3 to give pentasubstituted
fulvene derivatives in excellent yields. Other Ag salts such as AgNO3, AgBF4, and AgOTf are not effective, whereas a combination of AgNO3
and K CO3 has a remarkable effect on the formation of fulvene.
2
Transition metal catalyzed [2 + 2 + 1] cycloaddition of
alkene-alkene, alkene-alkyne, or alkyne-alkynes with
carbenoids (CO, RNC) is well-known and eventually results
in the formation of five-membered ring ketones or their
derivatives.1 On the other hand, [2 + 2 + 1] cycloaddition
reactions of vinyl halides with alkynes have been reported
of alkynes with some other unsaturated compound to
to give fulvenes, there are some limitations, such as (i)
cyclopentadienes2-5 or fulvenes6-10 has so far received only
reaction conditions requiring elevated temperatures (100
marginal attention (eq 1). Although several Pd-catalyzed
(1) (a) Brummond, K. M.; Kent, J. L. Tetrahedron 2000, 56, 3263. (b)
Dell, C. P. J. Chem Soc., Perkin Trans. 1 1998, 3873. (c) Fruhauf, H.-W.
Chem. ReV. 1997, 97, 523. (d) Schore, N. E. ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds; Pergamon Press Ltd: Oxford,
1991; Vol. 5, p 1037. (e) Negishi, E. ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds; Pergamon Press Ltd: Oxford, 1991; Vol. 5,
p 1163.
(2) Pd-catalyzed preparation of hexasubstituted cyclopentadienes: (a)
Reinheimer, H.; Moffat, J., Maitlis, P. M. J. Am. Chem. Soc. 1970, 92,
2285. (b) Maitlis, P. M. Acc. Chem. Res. 1976, 9, 93. (c) Kong, K.-C.;
Cheung, C.-H. Organometallics 1992, 11, 1972.
Ji. H.-L.; Hiibner, K. J. Am. Chem. Soc. 1995, 117, 8029. (c) O’Connor, J.
M.; Hiibner, K.; Merwin, R.; Gantzel, P. K.; Fong, B. S.; Adams, M.;
Rheingold, A. L. J. Am. Chem. Soc. 1997, 119, 3631. For reactions of
alkynes with a stoichiometric amount of a Rh complex, see also: (d) Moran,
G.; Green, M.; Orpen, A. G. J. Organomet. Chem. 1983, 250, C15.
(5) For a stoichiometric reaction between a Ru π-allyl complexes with
alkynes, see: Older, C. M.; Stryker, J. M. Organometallics 1998, 17, 5596.
(6) Ti-catalyzed trimerization of tert-butylacetylene: Johnson, E. S.;
Balaich, G. J.; Fanwick, P. E.; Rothwell, I. J. Am. Chem. Soc. 1997, 119,
11086.
(7) Pd-catalyzed trimerization of alkynes: Radhakrishnan, U.; Gevorgyan,
V.; Yamamoto, Y. Tetrahedron Lett. 2000, 41, 1971.
(8) (a) Wu, G.; Rheigold, A. L.; Geib, S. J.; Heck, R. F. Organometallics
1987, 6, 1941. (b) Silverberg, L. J.; Wu, G.; Rheigold, A. L.; Heck, R. F.
J. Organomet. Chem. 1991, 409, 411.
(3) Ni-catalyzed preparation of hexasubstituted cyclopentadienes: (a)
Inoue, Y.; Itoh, Y.; Hashimoto, H. Chem. Lett. 1978, 633. (b) Inoue, Y.;
Itoh, Y.; Kazama, H.; Hashimoto, H. Bull. Chem. Soc. Jpn. 1980, 53, 3329.
(c) See ref 2.
(4) For reactions of alkynes or carbenes with a stoichiometric amount
of Co or Ir-metallacycles to afford cyclopentadienes coordinated to the
transition metal, see: (a) O’Connor, J. M.; Pu, L.; Uhrhammer, R.; Jonhson,
J. A. J. Am. Chem. Soc. 1989, 111, 1889. (b) O’Connor, J. M.; Fong, B. S.;
(9) Lee, G. C. M.; Tobias, B.; Holmes, J. M.; Harcourt, D. A.; Garst,
M. E. J. Am. Chem. Soc. 1990, 112, 9330.
(10) Dyker, G.; Siemsen, P.; Sostmann, S.; Wiegand, A.; Dix, I.; Jones,
P. G. Chem. Ber. 1997, 130, 261.
10.1021/ol016472f CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/02/2001

Table 1. Pd-Catalyzed Reaction of (Z)-3-Iodopropenoate 1a with Alkynes to Give Fulvenes 2a-f
a MeCN was used as a solvent unless otherwise noted. b MeCN/benzene, 1/1. c 1H NMR yields. Isolated yields are in parentheses.
°C),8,10 (ii) the reaction being specific to a certain alkyne,9
(iii) a migration of double bonds in the products,8 and (iv)
moderate yields.8-10 This prompted us to investigate the
palladium cation system using Ag salts11 for the catalytic
formation of fulvenes. In this paper we would like to report
novel catalytic coupling reaction of two alkynes with one
alkenyl halide using the combination of cat. Pd(OAc)2 and
1 equiv of Ag2CO3, giving highly substituted fulvene
derivatives in excellent yields.
Recently, we have concentrated our efforts on the study
of [2 + 2 + 1] cycloadditions of alkynes with unsaturated
compounds with the aim of synthesizing cyclopentadiene
derivatives by the means of both stoichiometric and catalytic
protocols. This resulted in the development of new proce-
dures for the preparation of pentasubstituted cyclopentadienes
by the reaction of zirconacyclopentadienes with pro-
pynoates12 or 3-halopropenoates13 in the presence of a
stoichiometric amount of CuCl. Our further studies in this
area resulted in the development of the first catalytic
procedure for the preparation of pentasubstituted cyclopen-
tadienes by the reaction of alkynes with 3-bromopropenoates
in the presence of NiBr2(cat.)/Zn.14 Surprisingly, the use of
palladium salts (e.g., PdCl2) under the identical conditions
(11) For the coupling of alkenyl halides with the carbon-carbon double
bond or triple bond moieties, see: (a) Karabelas, K.; Hallberg, A.
Tetrahedron Lett. 1985, 26, 3131-3132. (b) Karabelas, K.; Westerlund,
C.; Hallberg, A. J. Org. Chem. 1985, 50, 3896-3900. (c) Abelman, M.
M.; Overman, T. O. L. E. J. Org. Chem. 1987, 52, 4133-4135. (d)
Karabelas, K.; Hallberg, A. J. Org. Chem. 1988, 53, 4909-4919. (e) Sato,
Y.; Sodeoka, M.; Shibasaki, M. Chem. Lett. 1990, 1953-1954. (f) Meyer,
F. E.; Parsons, P. J.; Meijere, A. J. Org. Chem. 1991, 56, 6487-6488. (g)
Sato, Y.; Watanabe, S.; Shibasaki, M. Tetrahedron Lett. 1992, 18, 2589-
2592. (h) Nukui, S.; Sodeoka, M.; Shibasaki, M. Tetrahedron Lett. 1993,
34, 4965-4968. (i) Meyer, F. E.; Ang, K. H.; Steinig, A. G.; Meijere, A.
Synlett 1994, 191. (j) Ohrai, K.; Kondo, K.; Sodeoka, M.; Shibasaki, M. J.
Am. Chem. Soc. 1994, 116, 11737-11748. (k) Sato, Y.; Nukui, S.; Sodeoka,
M.; Shibasaki, M. Tetrahedron 1994, 50, 371-382. (l) Henniges, H.; Meyer,
F. E.; Schick, U.; Funke, F.; Parsons, P. J.; Meijere, A. Tetrahedron 1996,
52, 11545. (m) Bengoa, E. G.; Cuerva, J. M.; Echavarren, A. M.; Martorell,
G. Angew. Chem., Int. Ed. Engl. 1997, 36, 767. (n) Ludwig, M.; Stromberg,
S.; Svensson, M.; Akermark, B. Organometallics 1999, 18, 970-975.
(12) Takahashi, T.; Sun, W.-H.; Xi, C.; Kotora, M. Chem. Commun. 1997,
2069.
(13) Kotora, M.; Xi, C.; Takahashi, T. Tetrahedron Lett. 1998, 39, 4321.
(14) Kotora, M.; Ishikawa, M.; Tsai, F.-Y.; Takahashi, T. Tetrahedron
1999, 55, 4969.
3468
Org. Lett., Vol. 3, No. 22, 2001

Table 2. Pd-Catalyzed Reaction of Variously Substituted Vinyl Iodides with Alkynes to Give Fulvenes 2g-l
a MeCN was used as a solvent unless otherwise noted. b MeCN/benzene, 1/1. c 1H NMR yields. Isolated yields are in parentheses.
did not result in the formation of any major products.
However, after considerable experimentation we found that
alkynes and alkenyl iodides 1a-g15,16 could react in the
presence of a catalytic amount of Pd(OAc)2 (5 mol %) and
1 equiv of Ag2CO3 in MeCN to give fulvenes as shown in
Scheme 1.
various disubstituted alkynes proceeded very cleanly with
full conversion of the starting material under mild reaction
conditions (Table 1). The reaction of 3-hexyne with 1a
afforded the desired product 2a in 98% NMR yield (isolated
yield 85%). The reaction with diphenylacetylene required
using a mixture of MeCN/benzene (1/1) as solvent and
heating of the reaction mixture to 50 °C. In pure MeCN the
product precipitated from the reaction mixture and caused
the reaction to stop at about 50% conversion of the starting
material. However, in a mixture of MeCN and benzene, the
corresponding product 2c was obtained in an excellent yield.
The reaction proceeded well with para-substituted diphenyl-
acetylenes with both electron-donating as well as electron-
withdrawing groups (mixture of MeCN/benzene was used
Scheme 1
Our initial interest focused on the reactions with 3-iodo-
propenoates. Reaction of methyl (Z)-iodopropenoate 1a with
(15) Piers, E.; Wong, T.; Coish, P. D.; Rogers, C. Can. J. Chem. 1994,
72, 1816. See also: (a) Ma, S.; Lu, X.; Li, Z. J. Org. Chem. 1992, 57, 709.
(b) Marek, I.; Alexakis, A.; Normat, J.-F. Tetrahedron Lett. 1991, 32, 5329-
5332. (c) Ma, S.; Lu, X. J. Chem. Soc., Chem. Commun. 1990, 1643.
(16) Zweifel, G.; Steele, R. B. J. Am. Chem. Soc. 1967, 89, 2753-2755.
Figure 1.
Org. Lett., Vol. 3, No. 22, 2001
3469

as a solvent). Thus the reaction of 1a with bis(4-methoxy-
phenyl)- or bis(4-fluorophenyl)acetylene afforded 2d and 2e
in 96%, and 93% yields, respectively. The use of bis(thienyl)-
acetylene gave fulvene 2f in good yield (82%).
To investigate the scope of the reaction various vinyl
iodides were checked. The use of (E)-iodopropenoate 1e
instead of Z-isomer in the reaction with 3-hexyne and
diphenylacetylene furnished 2g and 2h in 97% and 85%
yields, respectively. Reactions of (Z)-4-iodo-2-butenone 1b
with diphenylacetylene and bis(4-methoxyphenyl)acetylene
gave fulvenes 2i and 2j in high yields (95% and 95%). On
the other hand, reaction of methyl and dimethyl (Z)-
iodopropenamide 1c and 1d was disappointing.
halide from a halopalladium species to generate palladium
cationic species that are more reactive.11m The counteranion
CO32- plays an role of removal of the acid generated in the
reaction. The higher reactivity enables one to conduct the
reaction at low temperature,11m which is essential for the
successful course of the reaction.
As far as the reaction mechanism of this process is
concerned, it is reasonable to assume that it proceeds, after
initial oxidative addition of vinyl iodide to Pd to give 5, via
2-fold carbopalladation (5 f 6 f 7) followed by intramo-
lecular Heck reaction (7 f 8 f 2) as is outlined in Scheme
2.
The reaction conditions were also suitable for utilization
of nonactivated vinyl iodides. The reaction of 1f with
diphenylacetylene afforded 2k in 50% isolated yield after
24 h at 50 °C. Less reactive vinyl iodide such as 1g reacted
with diphenylacetylene and gave fulvene 2l in 66% isolated
yield.
Scheme 2
As far as choice of solvent was concerned, the best yields
were obtained in MeCN (for alkyl-substituted alkynes) or a
mixture of MeCN/benzene (for phenyl-substituted alkynes).
Nonetheless, the reaction of 1a with 3-hexyne also proceeded
in other solvents: DMF (6 h, 98%), DMSO (24 h, 88%),
THF (24 h, 81%), benzene (24 h, 84%). The use of AgOAc
has an effect similar to that of Ag2CO3. The product 2a was
formed in 99% yield. It is interesting to note that the other
silver salts such as AgBF4, AgOTf, and AgNO3 did not give
2a under the same conditions. As for carbonates, the use of
Na2CO3, K2CO3, and Cs2CO3 did not give 2a at all. However,
surprisingly, the combination of the silver salts and carbon-
ates such as AgBF4 + K2CO3, AgNO3 + K2CO3, and AgNO3
+ Na2CO3 had a remarkable effect, and 2a was obtained in
86%, 94%, and 82% yields, respectively. The combination
of AgNO3 + Et3N also gave 2a in 67% yield. In the case of
acetates, the same phenomena were observed. The use of
NaOAc instead of AgOAc did not give the product 2a,
whereas the combination of AgNO3 and NaOAc gave 2a in
75% yield. These results clearly indicated that both Ag+ and
Further investigations to clarify the reaction mechanism
are now in progress.
Supporting Information Available: Experimental details
and spectroscopic characterization of new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
2-
CO3 (or OAc-) have an important role in the catalytic
reaction. Silver carbonate is a mild base (halide scavenger),
and it is widely accepted as an agent for the abstraction of
OL016472F
3470
Org. Lett., Vol. 3, No. 22, 2001