Palladium-catalyzed cross-coupling reactions of 2-iodo-4- (phenylchalcogenyl)-1-butenes

Article abstract of DOI:10.1021/jo051709x

2-Iodo-4-(phenylchalcogenyl)-1-butenes 2 or 3, which are derived from the ring-opening reaction of methylenecyclopropanes (MCPs) 1 by iodine, can be applied to some palladium-catalyzed cross-coupling reactions such as the Sonogashira, Heck, Kumada, Suzuki

Full text of DOI:10.1021/jo051709x

Palladium-Catalyzed Cross-Coupling Reactions of
2-Iodo-4-(phenylchalcogenyl)-1-butenes
Min Shi,*,† Le-Ping Liu,‡ and Jie Tang‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China, and Department of Chemistry, East
China Normal University, 3663 Zhongshanbei Lu, Shanghai 200062, China
mshi@pub.sioc.ac.cn
Received August 11, 2005
2-Iodo-4-(phenylchalcogenyl)-1-butenes 2 or 3, which are derived from the ring-opening reaction of
methylenecyclopropanes (MCPs) 1 by iodine, can be applied to some palladium-catalyzed cross-
coupling reactions such as the Sonogashira, Heck, Kumada, Suzuki, and Negishi reactions under
mild conditions to give the corresponding coupling products in good yields. These reactions proceeded
smoothly at room temperature (20 °C) in most cases without any phosphine ligand and additive.
The phenylchalcogenyl group plays an important role in the reactions and a plausible reaction
mechanism has been proposed.
Introduction
as sulfur (S) and selenium (Se) atoms into the aromatic
and/or aliphatic group substituted methylenecyclopro-
panes.5 In fact, selenium- or sulfur-containing organic
molecules are extremely useful compounds in synthetic
organic chemistry,6 and selenium- or sulfur-ligated Pd-
(II) complexes are active catalysts for some coupling
reactions.7 For example, previously, we reported the
synthesis of 2-iodo-4-phenylchalcogenyl-1-butenes 2 (X
Metal-catalyzed cross-coupling reactions are an ex-
tremely useful synthetic method in current organic
chemistry and these reactions are primarily utilized for
the formation of the carbon-carbon bond as well as the
carbon-heteroatom bond.1 Among these reactions, the
Sonogashira, Heck, Kumada , Suzuki, and Negishi reac-
tions have been extensively investigated and have found
wide application in organic synthesis. On the other hand,
methylenecyclopropanes (MCPs) 1 are highly strained
but readily accessible molecules that have served as
useful building blocks in organic synthesis.2-4 Recently,
we have successfully introduced some heteroatoms such
(4) For selected recent articles on MCPs, see: (a) Nakamura, I.; Oh,
B. H.; Saito, S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2001, 40, 1298.
(b) Oh, B. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. Tetrahedron Lett.
2001, 42, 6203. (c) Yamago, S.; Nakamura, E. J. Org. Chem. 1990, 55,
5553. (d) Yamago, S.; Yanagawa, M.; Nakamura, E. Chem. Lett. 1999,
879. (e) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org.
Chem. 2001, 66, 270. (f) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J.
Org. Chem. 1998, 63, 6458. (g) Yamago, S.; Nakamura, E. J. Org.
Chem. 1990, 55, 5553. (h) Yamago, S.; Yanagawa, M.; Nakamura, E.
Chem. Lett. 1999, 879. (i) Lautens, M.; Han, W.; Liu, J. H.-C. J. Am.
Chem. Soc. 2003, 125, 4028. (j) Siriwardana, A. I.; Kamada, M.;
Nakamura, I.; Yamamoto, Y. J. Org. Chem. 2005, 70, 5932. (k) Scott,
M. E.; Lautens, M. Org. Lett. 2005, 7, 3045. (l) Scott, M. E.; Han, W.;
Lautens, M. Org. Lett. 2004, 6, 3309. (m) Lautens, M.; Han, W. J. Am.
Chem. Soc. 2002, 124, 6312. (n) Lautens, M.; Han, W.; Liu, J. H.-C. J.
Am. Chem. Soc. 2003, 125, 4028.
(5) (a) Liu, L.-P.; Shi, M. J. Org. Chem. 2004, 69, 2805. (b) Liu, L.-
P.; Shi, M. Chem. Commun. 2004, 2878. (c) Shi, M.; Wang, B.-Y.; Li,
J. Eur. J. Org. Chem. 2005, 759. (d) Wang, B.-Y.; Huang, J.-W.; Liu,
L.-P.; Shi, M. Synlett 2005, 421.
(6) For reviews on organoselenium and organosulfur compounds
see: (a) Paulmier, C. Selenium Reagents and Intermediates in Organic
Synthesis; Pergamon: Oxford, UK, 1986. (b) Organoselenium Chem-
istry; Back, T. G., Ed.; Oxford: New York, 1999. (c) Organoselenium
Chemistry; Wirth, T., Ed.; Springer: Berlin, Germany, 2000. (d) Oae,
S. Organic Chemistry of Sulfur; Plenum Press: New York, 1977; p
232. (e) Page, P. C. B., Vol. Ed. Top. Curr. Chem. 1999, 204, 205. (f)
Steudel, R., Vol. Ed. Top. Curr. Chem. 2003, 230, 231.
* Address correspondence to this author. Fax: 86-21-64166128.
† Chinese Academy of Sciences.
‡ East China Normal University.
(1) For recent reviews on metal-catalyzed cross-coupling reactions
see: (a) Diederich, F.; Stang, P. J., Eds. Metal-catalyzed Cross-coupling
Reactions; Wiley: New York, 1998. (b) de Meijere, A.; Diederich, F.,
Eds. Metal-catalyzed Cross-coupling Reactions, 2nd ed., 2 volumes;
Wiley: Weinheim, Germany, 2004. (c) Miyaura, N., Eds. Cross-coupling
Reactions, A Practical Guide; Top. Curr. Chem. Vol. 219; Springer:
Berlin, Germany, 2002. (d) Negishi, E.; de Meijere, A., Eds. Handbook
of Organo-palladium Chemistry for Organic Synthesis, 2 volumes;
Wiley: New York, 2002. (e) Tsuji, J. Palladium Reagents and Catalysts;
Wiley: Chichester, UK, 1995. (f) Tsuji, J. Palladium Reagents and
Catalysts; Wiley: Chichester, UK, 2004.
(2) For the synthesis of MCPs, see: Brandi, A.; Goti, A. Chem. Rev.
1998, 98, 589.
(3) For recent reviews on MCPs, see: (a) Nakamura, I.; Yamamoto,
Y. Adv. Synth. Catal. 2002, 344, 111. (b) Brandi, A.; Cicchi, S.; Cordero,
F. M.; Goti, A. Chem. Rev. 2003, 103, 1213. (c) Nakamura, E.; Yamago,
S. Acc. Chem. Res. 2002, 35, 867.
10.1021/jo051709x CCC: $30.25 © 2005 American Chemical Society
Published on Web 11/04/2005
10420
J. Org. Chem. 2005, 70, 10420-10425

Reactions of 2-Iodo-4-(phenylchalcogenyl)-1-butenes
TABLE 1. Heck Reaction of Compounds 2 or 3 (0.3
mmol)
SCHEME 1. Synthesis and Enynylation of
Compound 2 or 3 and Formation of Trienyne 6a
yield, %a E,Z/
entry
R1, R2
C6H5, C6H5 2a
R3
X
7 or 8
E,E
1
2
3
CO2CH3 Se 7a, 94
CO2CH3 Se 7b, 86
p-MeOC6H4, p-MeOC6H4 2c CO2CH3 Se 7c, 94
p-MeC6H4, p-MeC6H4 2b
4c p-MeC6H4, p-MeC6H4 2b
CO2CH3 Se 7d, 85
CO2CH3 Se 7e, 82
CO2CH3 Se 7f, 90
CO2CH3 Se 7g, 88
CO2CH3 Se 7h, 86
CO2CH3 Se 7i, 84
5c p-FC6H4, p-FC6H4 2e
6
7
8
9
10
11
12
13
14
p-MeOC6H4, H 2f
1.1:1b
0.7:1b
1.7:1b
1.8:1d
o,m-(MeO)2C6H3, H 2g
m,m,p-(MeO)3C6H2, H 2h
p-ClC6H4, H 2i
C6H5, C6H5 3a
p-MeC6H4, p-MeC6H4 3b
p-MeOC6H4, p-MeOC6H4 3c CO2CH3
C6H5, C6H5 2a
C6H5, C6H5 2a
CO2CH3
CO2CH3
S
S
S
8a, 86
8b, 82
8c, 90
CO2Ph
COCH3 Se 7k, 84
CN Se 7l, 82
Se 7j, 86
) Se) or 3 (X ) S) from MCPs 1 by a one-pot method
and the subsequent enynylation with alkynes (Sonogash-
ira reaction) to give the corresponding dienynes 4 (X )
Se) or 5 (X ) S) in good yields under mild conditions
(room temperature). The conjugated dienyne 5a, which
was obtained unexpectedly in this coupling reaction,
could be smoothly transformed to the corresponding
conjugated trienyne 6a in good yield (Scheme 1).8 In
addition, we further confirmed that the phenylchalcog-
enyl group plays an important role in this coupling
reaction. A plausible mechanism has been proposed on
the basis of the control experiments and 77Se NMR
spectroscopic investigation, indicating that the phenyl-
chalcogenyl group might be an intramolecular ligand to
the active Pd intermediate in the catalytic cycle.9 There-
fore, to extend the scope and limitations of this interest-
ing intramolecular phenylchalcogenyl group chelation
promoted coupling reaction, we attempted to further
investigate several other typical cross-coupling reactions
of 2-iodo-4-phenylchalcogenyl-1-butenes 2 (X ) Se) or 3
(X ) S) under similar conditions.
15c C6H5, C6H5 2a
a Isolated yields. b Determined by 1H NMR spectroscopic data.
c Conducted at 80 °C. d Determined by isolated yields.
phenylmagnesium bromide (Kumada reaction), phenyl-
boronic acid (Suzuki reaction), and benzylzinc bromide
(Negishi reaction) under mild conditions without any
phosphine ligand and additive.
Results and Discussion
First of all, we examined the Heck reaction10 of 2-iodo-
4-(phenylchalcogenyl)-1-butenes 2 and 3 (0.3 mmol) with
methyl acrylate (0.4 mmol) in dimethylformamide (DMF)
with use of palladium acetate [Pd(OAc)2] as a catalyst
and triethylamine (Et3N) as a base, typical Heck reaction
conditions. Using 1,1-diphenyl-2-iodo-4-(phenylselenyl)-
1-butene 2a as substrate, we found that the correspond-
ing coupling reaction product, methyl 5,5-diphenyl-4-(2-
phenylselenyl)ethyl-2,4-dientanoate 7a, was obtained in
good yield at room temperature (20 °C) (Table 1, entry
1). Next, we carried out the reactions of a variety of
compounds 2b-i or 3a-c with methyl acrylate (Table
1, entries 2-12) and other vinylic compounds such as
phenyl acrylate, methyl vinyl ketone, and acrylonitrile
(Table 1, entries 13-15) under the same conditions. As
can be seen from Table 1, most of these reactions
proceeded smoothly at room temperature without any
phosphine ligand and other additive to give the corre-
sponding coupling products 7 (X ) Se) and 8 (X ) S) in
good to high yields.
Herein, we wish to report the palladium-catalyzed
cross-coupling reactions of 2-iodo-4-(phenylchalcogenyl)-
1-butenes 2 or 3 with methyl acrylate (Heck reaction),
(7) For examples see: (a) Yao, Q.-W.; Kinney, E. P.; Zheng, C. Org.
Lett. 2004, 6, 2997. (b) Gruber, A. S.; Zim, D.; Ebeling, G.; Monteiro,
A. L.; Dupont, J. Org. Lett. 2000, 2, 1287. (c) Zim, D.; Gruber, A. S.;
Dupont, J.; Monteiro, A. L. Org. Lett. 2000, 2, 2881. (d) Zim, D.;
Monteiro, A. L.; Dupont, J. Tetrahedron Lett. 2000, 41, 8199. (e)
Silveira, P. B.; Lando, V. R.; Dupont, J.; Monteiro, A. L. Tetrahedron
Lett. 2002, 43, 2327. (f) Dupont, J.; Gruber, A. S.; Fonseca, G. S.;
Monteiro, A. L.; Ebeling, G.; Burrow, R. A. Organometallics 2001, 20,
171.
(8) Shi, M.; Liu, L.-P.; Tang, J. Org. Lett. 2005, 7, 3085.
For compounds 2d and 2e having an electron-with-
drawing group on the benzene rings, the reactions
proceeded slowly at room temperature. However, the
(9) (a) Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem. 2001,
1917. (b) Bedford, R. B. Chem. Commun. 2003, 1787. (c) Bergbreiter,
D. E.; Osburn, P. L.; Wilson, A.; Sink, E. M. J. Am. Chem. Soc. 2000,
122, 9058. There is a significant change of 77Se NMR spectra between
compound 2a and the mixture of compound 2a and Pd(OAc)2. The 77Se
NMR spectra (95.44 MHz, CDCl3) of PhSeSePh, compound 2a, and
compound 2a mixed with 1 equiv of Pd(OAc)2 were measured at 95.44
MHz on a BRUKER DRX 500 spectrometer at 300 K. Spectra were
recorded in CDCl3, with PhSeSePh as a 77Se external reference at δ
462.2 ppm. Typical parameters were as follows: 1 µs pulse (30° flip
angle) with a 2 s recycle time; spectral window of 1000 ppm; and line
broadening equal to 1.0 Hz. For compound 2a, δ 297.5 ppm; for a
solution of compound 2a and Pd(OAc)2 (1:1 mol ratio) in CDCl3, δ 347.5,
349.6, 353.1, 368.7 ppm (for detailed information see the Supporting
Information).
(10) For recent reviews on the Heck reaction, see: (a) Heck, R. F.
Palladium Reagents in Organic Synthesis; Academic Press: London,
UK, 1985. (b) Grisp, G. T. Chem. Soc. Rev. 1998, 24, 427. (c) Beletskaya,
I. P.; Cheprokov, A. Chem. Rev. 2000, 100, 3009. For some more recent
related papers, please see: (d) Gao, X.; Yu, W.; Mei, Y.; Jin, Z.
Tetrahedron Lett. 2004, 45, 8169. (e) Kondolff, I.; Doucet. H.; Santelli,
M. Tetrahedron Lett. 2003, 44, 8487. (f) Wang, A.-E.; Xie, J.-H.; Wang,
L.-X.; Zhou, Q.-L. Tetrahedron 2005, 61, 259. (g) Reddy, K. R.; Krishna,
G. G. Tetrahedron Lett. 2005, 46, 661. (h) Mo, J.; Xu, L.; Xiao, J. J.
Am. Chem. Soc. 2005, 127, 751.
J. Org. Chem, Vol. 70, No. 25, 2005 10421

Shi et al.
TABLE 2. Kumada Reaction of Compounds 2 (0.3 mmol)
SCHEME 2. Mechanism for Isomerization of the
Double Bond in the Coupling Products
entry
R
yield, %a
1
2
3
4
5
C6H5 2a
9a, 84
9b, 87
9c, 92
9d, 57
9e, 72
p-CH3C6H4 2b
p-CH3OC6H4 2c
p-ClC6H4 2d
p-FC6H4 2e
a Isolated yields.
As for the Heck reaction, it was usually performed at
high temperature except when using phase-transfer
catalyst at room temperature, known as Jeffery’s condi-
tions.13 We believe that the phenylchalcogenyl group in
compounds 2 or 3 contributes to this effective Heck
reaction at room temperature in most cases via an
intramolecular chelation promotion as we proposed in our
previous work.8
Next, we also examined the palladium-catalyzed Ku-
mada reaction14 of 2-iodo-4-(phenylchalcogenyl)-1-butenes
2a-e (0.3 mmol) with phenylmagnesium bromide (0.4
mmol) in diethyl ether at room temperature. In general,
these reactions proceeded smoothly under mild conditions
(room temperature) to afford the corresponding coupling
products 2-phenyl-4-(phenylchalcogenyl)-1-butenes 9 in
moderate or good to high yields in the presence of Pd-
(OAc)2 (1.5 mol %) within 3 h. The results are sum-
marized in Table 2.
In addition, using 1,1-diphenyl-2-iodo-4-(phenylsele-
nyl)-1-butene 2a (0.3 mmol) as substrate, we examined
the Suzuki reaction15 and the Negishi reaction16 with
phenylboronic acid (0.3 mmol) and benzylzinc bromide
(0.4 mmol) in THF, respectively, and the results are
corresponding coupling products 7d and 7e were obtained
in good yields at higher temperature (80 °C) (Table 1,
entries 4 and 5). According to the mechanism of oxidative
addition of vinyl halides to metal complex,11 the electron-
withdrawing group on the benzene rings decreased the
electron density of the carbon-carbon double bond, so
that the rate of the oxidative addition was reduced
relatively and a higher temperature was therefore re-
quired in the oxidative addition process. When acryloni-
trile, a weak nucleophilic compound, was utilized in this
reaction, higher temperature (80 °C) was also required
to give the corresponding product 7l in good yield (Table
1, entry 15).
For unsymmetrical compounds 2f-i, which are the
Z-isomers, the corresponding Heck reaction products 7f-i
were obtained as mixtures of E,Z- and E,E-isomers in
different ratios (Table 1, entries 8-11). The products of
E,Z- and E,E-isomeric mixtures of 7f-h are inseparable
by silica gel flash column chromatography although E,Z-
and E,E-7i could be separated by silica gel flash column
chromatography. The isomerization of the double bond
might be induced by the rearrangement of a certain
intermediate that has been proposed by Heck and co-
workers before (Scheme 2).12 The hydridopalladium
halide π complex A may form an allylic, σ derivative B,
which will go on to a π-allylic palladium complex C with
the allylic double bond. The π-allylic complex C, unfor-
tunately, rapidly equilibrates isomers C and D through
rotating σ forms. This causes loss of stereochemistry and
the product ultimately formed by the hydridopalladium
halide elimination and dissociation process will be the
isomer formed from the most stable π-allylic complex.
(13) (a) Jeffery, T. Chem. Commun. 1984, 1287. (b) Jeffery, T.
Tetrahedron Lett. 1985, 26, 2667. (c) Jeffery, T. Synthesis 1987, 70.
(14) (a) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.; Fujioka,
A.; Kodma, S.-I.; Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem.
Soc. Jpn. 1976, 49, 1958. For some more recent related papers, please
see: (b) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889
and references therein. (c) Li, G. Y. J. Organomet. Chem. 2002, 653,
63. (d) Anctil, E. J.-G.; Snieckus, V. J. Organomet. Chem. 2002, 653,
150. (e) Banno, T.; Hayakawa, Y.; Umeno, M. J. Organomet. Chem.
2002, 653, 288. (f) Tasler, S.; Lipshutz, B. H. J. Org. Chem. 2003, 68,
1190. (g) Yang, L.-M.; Huang, L.-F.; Luh, T.-Y. Org. Lett. 2004, 6, 1461.
(h) Horibe, H.; Fukuda, Y.; Kondo, K.; Okuno, H.; Murakami, Y.;
Aoyama, T. Tetrahedron 2004, 60, 10701. (i) Frisch, A. C.; Rataboul,
F.; Zapf, A.; Beller, M. J. Organomet. Chem. 2003, 687, 403.
(15) (a) Miyaura, N.; Suzuki,A. Chem. Rev. 1995, 95, 2457. (b)
Suzuki, A. J. Organomet. Chem. 1999, 576, 147. For some more recent
related papers, please see: (c) LeBlond, C. R.; Andrews, A. T.; Sun,
Y.; Sowa, J. R., Jr. Org. Lett. 2001, 3, 1555. (d) Collier, P. N.; Campbell,
A. D.; Patel, I.; Raynham, T. M.; Taylor, R. J. K. J. Org. Chem. 2002,
67, 1802. (e) Urawa, Y.; Ogura, K. Tetrahedron Lett. 2003, 44, 271. (f)
Byun, J.-W.; Lee, Y.-S. Tetrahedron Lett. 2004, 45, 1837. (g) Baleiza˜o,
C.; Corma, A.; Garc´ıa, H.; Leyva, A. J. Org. Chem. 2004, 69, 439. (h)
Dubbaka, S. R.; Vogel, P. Org. Lett. 2004, 6, 95. (i) Dai, M.-J.; Liang,
B.; Wang, C.-H.; Chen, J.-H.; Yang, Z. Org. Lett. 2004, 6, 221. (j)
Bedford, R. B.; Hazelwood, S. L.; Horton, P. N.; Hursthouse, M. B.
Dalton Trans. 2003, 4164. (k) McLachlan, F.; Mathews, C. J.; Smith,
P. J.; Welton, T. Organometallics 2003, 22, 5350. (l) Conlon, D. A.;
Pipik, B.; Ferdinand, S.; LeBlond, C. R.; Sowa, J. R., Jr.; Izzo, B.;
Collins, P.; Ho, G.-J.; Williams, J. M.; Shi, Y.-J.; Sun, Y.-K. Adv. Synth.
Catal. 2003, 345, 931. (m) Wang, A.-E.; Zhong, J.; Xie, J.-H.; Li, K.;
Zhou, Q.-L. Adv. Synth. Catal. 2004, 346, 595.
(11) Rajaram, J.; Pearson, R. G.; Ibers, J. A. J. Am. Chem. Soc. 1974,
96, 2103.
(12) The mechanism for the isomerization of the double bond in the
Heck coupling reaction has been proposed already by Heck and co-
workers (see Scheme 2). (a) Dieck, A.; Heck, R. F. J. Org. Chem. 1975,
40, 1083. (b) Kim, J. I.; Patel, B. A.; Heck, R. F. J. Org. Chem. 1981,
46, 1067.
(16) (a) Negishi, E.-I.; Baba, S. J. Chem. Soc., Chem. Commun. 1976,
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10422 J. Org. Chem., Vol. 70, No. 25, 2005

Reactions of 2-Iodo-4-(phenylchalcogenyl)-1-butenes
SCHEME 3. Suzuki and Negishi Reaction of
Compound 2a (0.3 mmol)
SCHEME 5. The Control Experiments
SCHEME 4. A Plausible Heck Reaction
Mechanism
a 95% of 11 was recovered. b92% isolated yield based on
compound 2a.
chelation is responsible for most of these coupling reac-
tions such as the Heck reaction to be fairly effective at
room temperature.
To further verify this mechanistic assumption of the
intramolecular chelation promoted effect on the coupling
reaction, three control experiments were performed under
identical conditions. We synthesized 1,1-diphenyl-2-iodo-
1-butene 11 and applied it to the Sonogashira reaction
with phenylacetylene8 and the Heck reaction with methyl
acrylate under the same conditions, respectively (Scheme
5). We found that no reactions occurred even at higher
temperature (80 °C) in both cases. Another control
experiment was conducted and the result was also
outlined in Scheme 5. We added compound 2a (2.0 equiv
to Pd(OAc)2) in the Heck reaction of compound 11 with
methyl acrylate. We found that compound 2a was simi-
larly transformed to compound 7a in good yield at room
temperature, but compound 11 was recovered mostly and
the corresponding compound 11a, derived from the Heck
reaction of 11 with methyl acrylate, was not formed at
room temperature. These results suggest that the phen-
ylchalcogenyl group is indeed necessary for these coup-
ling reactions such as the Heck reaction proceeding
smoothly at room or higher temperature (60-80 °C).
Moreover, we attempted to introduce a phenylselenyl
group into the substituted iodobenzene to examine
whether it has a promotion effect on the cross-coupling
reaction of aromatic iodide under similar reaction condi-
tions. We managed to synthesize the iodobenzene com-
pound 12 having a phenylselenyl group at the adjacent
position via the known synthetic method8 because a
similar intramolecular chelation of the phenylchalcogenyl
group to Pd center in compound 12 has been reported
before in some reactions (Scheme 6).19 This compound
was subjected to the Sonogashira and Heck reactions
under the same conditions (Scheme 6). The corresponding
normal Sonogashira reaction product 13 was obtained in
good yield (78%) at room temperature rather than the
shown in Scheme 2. The corresponding coupling products
9a and 10a were obtained in good yields. In the Suzuki
reaction, the palladium catalyst of Pd(PPh3)4 (5 mol %)
is more effective than Pd(OAc)2 under identical condi-
tions17 and higher temperature (65 °C) is required in THF
with Cs2CO3 as the base to afford the corresponding
product 9a in 82% yield (Scheme 2). On the other hand,
the Negishi reaction can be carried out at room temper-
ature to produce the product 10a in 79% yield (Scheme
3).
The mechanism for these palladium-catalyzed cross-
coupling reactions of 2-iodo-4-phenylchalcogenyl-1-butenes
2 or 3 was considered to proceed via an identical
intermediate E, having an intramolecular chelation of
selenium or sulfur atom to Pd metal center.8 Using the
Heck reaction as an example, the catalytic cycle is
described in Scheme 4. The in situ formed Pd(0) catalyst
inserts into the C-I bond of compounds 2 or 3 via an
oxidative addition to give the intermediate E, which is
chelated by the phenylchalcogenyl group on the basis of
77Se NMR spectroscopic investigation (see the Supporting
Information). The reaction of Pd complex E with a vinylic
molecule produces the intermediate F stereoselectively.
Afterward, the intermediate F turns into the intermedi-
ate G18 via a reductive elimination, which subsequently
produces the products 7 or 8 and regenerates the Pd(0)
catalyst in the presence of a base. The intramolecular
(18) The intramolecular chelation in the intermediate G obliges the
hydride to be cis at the iodine and this is important for the reductive
elimination, see: Hills, I. D.; Fu, G. C. J. Am. Chem. Soc. 2004, 126,
13178.
(19) (a) Dupont, J.; Beydoun, N.; Pfeffer, M. J. Chem. Soc., Dalton
Trans. 1989, 1715. (b) Spencer, J.; Pfeffer, M. J. Org. Chem. 1995, 60,
1005.
(17) The optimization of the reaction conditions is summarized in
the Supporting Information.
J. Org. Chem, Vol. 70, No. 25, 2005 10423

Shi et al.
SCHEME 6. Synthesis and Sonogashira-/
Heck-Type Reaction of Compound 12
plausible mechanism has been proposed based on the
control experiments and 77Se NMR spectroscopic inves-
tigation (see the Supporting Information). This is another
interesting case for the selenium- or sulfur-ligated Pd-
(II) complexes in the effective coupling reaction. Efforts
are underway to elucidate the mechanistic details and
the scope and limitations of these coupling reactions.
Experimental Section
General Methods. Melting points are uncorrected. 1H and
13C NMR spectra were recorded at 300 and 75 MHz, respec-
tively. Mass spectra were recorded by EI, MALDI, and ESI
methods, and HRMS was measured by the EI method. Organic
solvents used were dried by standard methods when necessary.
Commercially obtained reagents were used without further
purification. All reactions were monitored by TLC plates. Flash
column chromatography was carried out with silica gel or
Al2O3 at increased pressure.
Typical Reaction Procedure for the Heck Reaction of
2-Iodo-4-phenylchalcogenyl-1-butenes 2 or 3 with Meth-
yl Acrylate. To a solution of 1,1-diphenyl-2-iodo-4-phenylse-
lenyl-1-butene 2a (147 mg, 0.3 mmol) in DMF (2.0 mL) was
added methyl acrylate (35 mg, 0.4 mmol), Et3N (40 mg, 0.4
mmol), and Pd(OAc)2 (3 mg, 4 mol %). The mixture was stirred
for 10 h at room temperature (monitored by TLC) and then
quenched with the addition of water (5.0 mL). The mixture
was extracted with diethyl ether (5.0 mL). The organic layer
was washed with brine and dried over anhydrous Na2SO4, then
the solvent was removed under reduced pressure and the
residue was subjected to flash column chromatography to give
the product 7a (126 mg, 94%) as a white solid. Mp 83-84 °C;
IR (KBr) ν 3055, 2947, 1716, 1614, 1436, 1293, 1167, 861, 737,
701 cm-1; 1H NMR (CDCl3, 300 MHz, TMS) δ 2.77 (2H, t, J )
7.5 Hz, CH2), 3.00 (2H, t, J ) 7.5 Hz, CH2), 3.72 (3H, s, OCH3),
5.95 (1H, d, J ) 15.9 Hz, dCH), 7.10-7.23 (7H, m, Ar), 7.30-
7.34 (8H, m, Ar), 7.54 (1H, d, J ) 15.9 Hz, dCH); 13C NMR
(CDCl3, 75 MHz, TMS) δ 25.7, 31.5, 51.4, 117.9, 126.7, 127.5,
127.9, 128.0, 128.3, 128.8, 129.0, 129.5, 130.3, 132.3, 133.3,
140.6, 141.6, 144.0, 151.0, 167.6; MS (EI) m/e 448 (M+, 0.4),
291 (2), 231 (67), 215 (19), 202 (14), 188 (15), 174 (100), 144
(32), 91 (26). Anal. Calcd for C26H24O2Se requires C 69.79, H
5.41; found C 69.83, H 5.24.
Typical Reaction Procedure for the Kumada Reaction
of 2-Iodo-4-phenylselenyl-1-butenes 2 with Phenylmag-
nesium Bromide. To a solution of 1,1-diphenyl-2-iodo-4-
phenylselenyl-1-butene 2a (147 mg, 0.3 mmol) in diethyl ether
(2.0 mL) was added a solution of phenylmagnesium bromide
in diethyl ether (0.4 mL, 1.0 mol/L) and Pd(OAc)2 (1 mg, 1.5
mol %). The mixture was stirred for 3 h at room temperature
(monitored by TLC) and then quenched with water (5.0 mL).
The mixture was extracted with diethyl ether (5.0 mL). The
organic layer was washed with brine and dried over anhydrous
Na2SO4, then the solvent was removed under reduced pressure
and the residue was subjected to flash column chromatography
to give the product 9a (111 mg, 84%) as a white solid. Mp 98-
100 °C; IR (KBr) ν 3054, 3019, 1598, 1477, 1074, 762, 735,
699 cm-1; 1H NMR (CDCl3, 300 MHz, TMS) δ 2.85 (4H, t, J )
4.5 Hz, CH3), 6.87-6.90 (2H, m, Ar), 7.00-7.02 (3H, m, Ar),
7.08-7.30 (15H, m, Ar); 13C NMR (CDCl3, 75 MHz, TMS) δ
25.5, 36.7, 126.0, 126.4, 126.5, 126.8, 127.4, 128.0, 128.3, 128.9,
129.2, 129.6, 130.1, 130.5, 132.0, 138.9, 140.7, 141.2, 142.4,
142.7; MS (EI) m/e 440 (M+, 8), 269 (12), 205 (46), 191 (48),
167 (17), 91 (100). Anal. Calcd for C28H24Se requires C 76.53,
H 5.50; found C 76.58, H 5.61.
SCHEME 7. Oxidation of Seleno Compounds 7a
and 9a (0.3 mmol) with m-CPBA
corresponding dienyne product.8 On the other hand,
higher reaction temperature (80 °C) was required to
afford the corresponding product 14 in 75% yield in the
Heck reaction. These results suggest that the sterically
demanding position of the phenylchalcogenyl group in
2-iodo-4-(phenylchalcogenyl)-1-butenes is crucial in these
coupling reactions either to give different products from
compound 12 such as the Sonogashira reaction or under
milder conditions than compound 12 such as the Heck
reaction. The more flexible phenylchalcogenyl group in
2-iodo-4-(phenylchalcogenyl)-1-butenes might be able to
coordinate to the active Pd center in a more easy way.
Another reason for the distinction between the reactions
might be that the five-membered ring of palladacycle
from compound 12 is more stable than intermediate E
(Scheme 4), which might be less reactive under identical
conditions and therefore a higher temperature is neces-
sary for the insertion step.
Furthermore, as indicated in our previous work,8
oxidation of compounds 7a and 9a with m-CPBA in
dichloromethane furnishes the corresponding products 15
and 16 in moderate to good yields by a selenoxide
elimination process under mild conditions (Scheme 7).
Conclusion
We have found that several typical palladium-cata-
lyzed cross-coupling reactions of 2-iodo-4-phenylchalcog-
enyl-1-butenes 2 or 3 proceeded smoothly under mild
conditions (room temperature) to give the corresponding
coupling products in moderate or good to high yields in
most cases because of the existence of a sterically
demanding intramolecular chelation of the phenylchal-
cogenyl group in 2 or 3 to a certain palladium center. A
Acknowledgment. We thank the State Key Project
of Basic Research (Project 973) (No. G2000048007),
Shanghai Municipal Committee of Science and Technol-
ogy, Chinese Academy of Sciences (KGCX2-210-01), and
10424 J. Org. Chem., Vol. 70, No. 25, 2005

Reactions of 2-Iodo-4-(phenylchalcogenyl)-1-butenes
analytic data of the compounds shown in Tables 1 and 2 and
Schemes 1-6 and a detailed description of experimental
procedures. This material is available free of charge via the
Internet at http://pubs.acs.org.
the National Natural Science Foundation of China for
financial support (20472096, 203900502, and 20272069).
Supporting Information Available: The spectroscopic
data (1H, 13C, 77Se NMR and NOSEY spectroscopic data) and
JO051709X
J. Org. Chem, Vol. 70, No. 25, 2005 10425