Enynylation of 2-iodo-4-(phenylchalcogenyl)-1-butenes via intramolecular chelation: Approach to the synthesis of conjugated dienynes or trienynes

Article abstract of DOI:10.1021/ol051101a

(Chemical Equation Presented) 2-Iodo-4-(phenylchalcogenyl)-1 -butenes 3 and 4, which are derived from methylenecyclopropanes 1, can be enynylated with alkynes catalyzed by Pd(OAc)₂ to give conjugated dienynes 5 and 6 in the absence of any phosp

Full text of DOI:10.1021/ol051101a

ORGANIC
LETTERS
2005
Vol. 7, No. 14
3085-3088
Enynylation of
2-Iodo-4-(phenylchalcogenyl)-1-butenes
via Intramolecular Chelation: Approach
to the Synthesis of Conjugated
Dienynes or Trienynes
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 May 12, 2005
ABSTRACT
2-Iodo-4-(phenylchalcogenyl)-1-butenes 3 and 4, which are derived from methylenecyclopropanes 1, can be enynylated with alkynes catalyzed
by Pd(OAc)2 to give conjugated dienynes 5 and 6 in the absence of any phosphine ligand and copper salt, and trienyne 9a can be obtained
by oxidation of compound 5a. A plausible reaction mechanism has been proposed.
Methylenecyclopropanes (MCPs) 1 are highly strained but
readily accessible molecules that have served as useful
building blocks in organic synthesis.1,2 Recently, we have
been investigating the dihalogenation of MCPs 1 and the
coupling reactions of the resulting products 2,4-diiodo-1-
butenes 2 under mild conditions.3,4 To explore the further
transformation of 1, we investigated the reactions of 1 with
a variety of reactants having selenium or sulfur heteroatoms,5
because selenium- or sulfur-containing organic molecules are
extremely useful compounds in synthetic organic chemistry6
and selenium or sulfur-ligated Pd(II) complexes are active
catalysts for some coupling reactions.7 Herein, we wish to
report the synthesis of 2-iodo-4-(phenylchalcogenyl)-1-
† Chinese Academy of Sciences.
‡ East China Normal University.
(1) For synthesis of MCPs: Brandi, A.; Goti, A. Chem. ReV. 1998, 98,
589.
(2) For recent reviews, 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. See also: (d) Nakamura, I.; Oh, B. H.; Saito, S.;
Yamamoto, Y. Angew. Chem., Int. Ed. 2001, 40, 1298. (e) Oh, B. H.;
Nakamura, I.; Saito, S.; Yamamoto, Y. Tetrahedron Lett. 2001, 42, 6203.
(f) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org. Chem.
2001, 66, 270. (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) Shi, M.; Chen, Y.; Xu, B. Org. Lett. 2003, 5, 1225. (k) Shi, M.;
Xu, B. Tetrahedron Lett. 2003, 44, 3839. (l) Chen, Y.; Shi, M. J. Org.
Chem. 2004, 69, 426.
(3) Shi, M.; Shao, L.-X. Synlett 2004, 807.
(4) Zhou, H.-W.; Huang, X.; Chen, W.-L. Synlett 2003, 2080.
(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, 759-765.
(6) For reviews on organoselenium and organosulfur compounds: (a)
Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis;
Pergamon: Oxford, 1986. (b) Organoselenium Chemistry; Back, T. G., Ed.;
Oxford: New York, 1999. (c) Organoselenium Chemistry; Wirth, T., Ed.;
Springer: Berlin, 2000. (d) Oae, S. Organic Chemistry of Sulfur; Plenum
Press: New York, 1977; p 232. (e) Top. Curr. Chem. 1999, 204, 205 (Vol.
Ed. Page, P. C. B.). (f) Top. Curr. Chem. 2003, 230, 231 (Vol. Ed. Steudel,
R.).
10.1021/ol051101a CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/08/2005

Table 1. Synthesis of 2-Iodo-4-(phenylchalcogenyl)-1-butenes
3 and 4 from MCPs 1 in a One-Pot Manner
Table 2. Enynylation of the Compounds 3 or 4 (1.0 Equiv)
entry
R1, R2
C6H5, C6H5 (1a)
p-MeC6H4, p-MeC6H4 (1b)
X
yielda of 3 or 4 (%)
yielda of
entry
R1, R2
C6H5, C6H5 (3a)
X
R3
5 or 6 (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Se
Se
3a, 88
3b, 88
3c, 92
3d, 78
3e, 86
3f, 89
3g, 79
3h, 73
3i, 62
3j, 83b
3k, 55b
4a, 87
4c, 90
4d, 82
1
2
3
4
5
6
7
8
9
Se C6H5
Se C6H5
5a, 82
5b, 72
5c, 78
5d, 77
5e, 74
5f, 58
p-MeC6H4, p-MeC6H4 (3b)
p-MeOC6H4, p-MeOC6H4 (1c) Se
p-MeOC6H4, p-MeOC6H4 (3c) Se C6H5
p-ClC6H4, p-ClC6H4 (1d)
p-FC6H4, p-FC6H4 (1e)
p-MeOC6H4, H (1f)
o,p-(MeO)2C6H3, H (1g)
m,m,p-(MeO)3C6H2, H (1h)
p-ClC6H4, H (1i)
p-MeOC6H4, C6H5 (1j)
o-ClC6H4, C6H5 (1k)
C6H5, C6H5 (1a)
Se
Se
Se
Se
Se
Se
Se
Se
S
p-ClC6H4, p-ClC6H4 (3d)
p-FC6H4, p-FC6H4 (3e)
p-MeOC6H4, H (3f)
Se C6H5
Se C6H5
Se C6H5
Se C6H5
Se C6H5
Se C6H5
Se C6H5
Se C6H5
o,p-(MeO)2C6H3, H (3g)
m,m,p-(MeO)3C6H2, H (3h)
p-ClC6H4, H (3i)
5g, 55
5h, 60
5i, 64
10 p-MeOC6H4, C6H5 (3j)b
11 o-ClC6H4, C6H5 (3k)b
12 C6H5, C6H5 (3a)
13 C6H5, C6H5 (3a)
14 C6H5, C6H5 (3a)
15 C6H5, C6H5 (3a)
16 C6H5, C6H5 (3a)
17 C6H5, C6H5 (3a)
18 C6H5, C6H5 (3a)
19 C6H5, C6H5 (4a)
5j, 69b
5k, 73b
5l, 42c
5m, 38c
5n, 78
Se n-C4H9
Se CH2OH
Se p-CH3C6H4
p-MeOC6H4, p-MeOC6H4 (1c)
p-ClC6H4, p-ClC6H4 (1d)
S
S
Se p-CH3OC6H4 5o, 86
Se p-ClC6H4
Se p-BrC6H4
Se o-CF3C6H4
5p, 84
5q, 85
5r, 78
6a, 78
6c, 74
6d, 72
a Isolated yields. b Mixtures of Z and E isomers in a 1:1 ratio, determined
1
by H NMR spectroscopic data.
S
C6H5
20 p-MeOC6H4, p-MeOC6H4 (4c) S C6H5
21 p-ClC6H4, p-ClC6H4 (4d) C6H5
S
butenes 3 and 4 from MCPs 1 and subsequent enynylation
with alkynes under mild conditions. In this coupling reaction,
neither a phosphine ligand nor a copper salt was used, and
the reaction proceeded smoothly at room temperature (20
°C) in most cases. A plausible reaction mechanism has been
proposed on the basis of a 77Se NMR spectroscopic inves-
tigation.
Compounds 3 and 4, which have a vinylic iodine atom
and a phenylchalcogenyl group, were synthesized from
MCPs 1a-k in a one-pot manner in THF at room temper-
ature (Table 1). After the starting materials 1 were consumed,
the in situ formed products 2 were sequentially treated with
diphenyl diselenide or diphenyl disulfide, sodium borohy-
dride, and methanol to give the compounds 3 and 4 in good
to high yields (for experimental details, see the Supporting
Information). The results are summarized in Table 1 (entries
1-14). For the unsymmetrical MCPs 1j,k, the corresponding
products 3j,k were obtained as mixtures of Z and E isomers
in a 1:1 ratio (Table 1, entries 10 and 11). For the
unsymmetrical MCPs 1f-i, the corresponding products 3f-i
were obtained as a single Z isomer (Table 1, entries 6-9).
Their configurations were determined by NOESY spectro-
scopic data (see the Supporting Information).
a Isolated yields. b Mixtures of Z and E isomers in a 1:1 ratio, determined
1
by H NMR spectroscopic data. c Conducted at 80 °C.
corresponding conjugated dienynes 5 and 6,8 derived from
the enynylation of 3 and 4, respectively, were obtained in
moderate to good yields under mild conditions rather than
the normal Sonogashira-type coupling reaction product
(Table 2).9,10
1
Their structures were determined by H and 13C NMR
spectroscopic data, HRMS, and microanalysis. The X-ray
crystal structure of 5d is provided in the Supporting
Information.11
Using phenylacetylene and other arylacetylenes as cou-
pling reagents, the reactions were conducted at room
temperature and the corresponding dienynes were obtained
(8) Conjugated dienynes are found to be integral parts in some medicinal
molecules: (a) Olivo, H. F.; Velazquez, F.; Trevisam, H. C. Org. Lett. 2000,
2, 4055. (b) Lipshutz, B. H.; Lindsley, C. J. Am. Chem. Soc. 1997, 119,
4555. (c) Fiandanese, V.; Babudvi, F.; Marchese, G.; Punzi, A. Tetrahedron
2002, 58, 9547.
(9) There are very few examples of enynylation with alkynes; see: (a)
Pal, M.; Parasuraman, K.; Subramanian, V.; Dakarapu, R.; Yeleswarapu,
K. R. Tetrahedron Lett. 2004, 45, 2305. (b) Pottier, L. R.; Peyrat, J. F.;
Alami, M.; Brion, J. D. Synlett 2004, 1503.
(10) This reaction also can be performed in toluene, tetrahydrofuran
(THF), dichloromethane, acetonitrile, and dimethylacetamide as well, but
5a was obtained in lower yields or a prolonged reaction time was required.
Other bases such as sodium hydrogen carbonate, potassium carbonate, and
cesium carbonate were not as effective as Et3N (see the Supporting
Information).
Next we carried out the Sonogashira-type coupling reaction
of compounds 3 and 4 with arylacetylenes or other alkynes
catalyzed by Pd(OAc)2 in DMF without any phosphine
ligand, copper salt, or other additives. We found that the
(7) For examples: (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.
(11) The crystal data of 5d have been deposited in the CCDC with the
file number 246799: empirical formula, C38H28Cl2Se; formula weight,
634.46; crystal color, habit, yellow, prismatic; crystal dimensions, 0.505 ×
0.278 × 0.093 mm; crystal system, monoclinic; lattice type, primitive; lattice
parameters, a ) 9.322(3) Å, b ) 28.033(10) Å, c ) 25.438(9) Å, R ) 90°,
â ) 92.491(8)o, γ ) 90°, V ) 6642(4) Å3; space group, P21/c; Z ) 8;
Dcalcd ) 1.269 g/cm3; F000 ) 2592; diffractometer, Rigaku AFC7R; residuals,
R ) 0.0850, Rw ) 0.2072.
3086
Org. Lett., Vol. 7, No. 14, 2005

Scheme 1. Effect of Copper(I) Iodide in the Reaction
Scheme 3. Plausible Reaction Mechanism
in moderate to good yields (Table 2, entries 1-11 and 14-
21). The substituents on the benzene rings of compounds 3,
4, and arylacetylenes did not significantly affect the yields
of 5 and 6 (Table 2, entries 1-11 and 14-21). Using other
alkynes such as n-hexyne and propynol as coupling reagents,
the reactions were conducted at 80 °C and the products were
obtained in moderate yields (Table 2, entries 12 and 13).
The normal Sonogashira-type coupling reaction12 product 7a
can be obtained in low yield along with the formation of
dienyne 5a in the presence of copper(I) iodide (10 mol %)
in the reaction of compound 3a with phenylacetylene. When
the employed amount of copper(I) iodide was increased to
150 or 250 mol %, compound 7a was formed as a single
product in moderate yields without the formation of dienyne
5a (Scheme 1).
confirmed on the basis of a 77Se NMR spectroscopic
investigation (see the Supporting Information). The Pd
intermediate A inserts into an alkyne molecule to produce
the intermediate B regioselectively. Intermediate B adds into
another alkyne molecule to afford intermediate C, which
produces the dienynes 5 and 6 via a reductive elimination
in the presence of base and regenerates the Pd(0) catalyst.
These coordinating groups might retard the direct transmeta-
lation of intermediate A with an alkyne (Scheme 3), and
carbopalladation across an alkyne would be operative to give
the intermediate B, in which a rather labile seven-membered
chelate would enable its transmetalation with another alkyne,
giving an alkenyl(alkynyl)palladium(II) species (intermediate
C), a product-forming intermediate. Addition of CuI would
facilitate the direct transmetalation of intermediate A with
an alkyne, resulting in the normal Sonogashira product.
Furthermore, oxidation of the dienyne 5a with m-CPBA
furnishes the corresponding trienyne 9a by a selenoxide elim-
ination15 in 58% yield under mild conditions (Scheme 4).
The control experiment showed that the selenium or sulfur
atom in 3 or 4 is crucial for this coupling reaction because
no reaction occurred using compound 8a, 1,1-diphenyl-2-
iodo-1-butene, as a starting material under identical condi-
tions (Scheme 2). Compound 7a cannot be transformed into
Scheme 2. Control Experiments in This Reaction
Scheme 4. Transformation of Dienyne 5a to Trienyne 9a
compound 5a with phenylacetylene under the same condi-
tions (Scheme 2).
The mechanism for this unusual enynylation of 2-iodo-
4-(phenylchalcogenyl)-1-butenes 3 and 4 with alkynes is
described in Scheme 3 on the basis of the above results. The
in situ formed Pd(0) catalyst inserts into compounds 3 and
4 via an oxidative addition to afford the Pd intermediate A,
which was chelated by the intramolecular phenylchalcogenyl
group.13,14 The evidence for this intramolecular chelation was
In conclusion, we have found a one-pot method for the
synthesis of 2-iodo-4-(phenylchalcogenyl)-1-butenes 3 and
4 from MCPs 1 and a synthetic approach to the formation
(12) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
16, 4467. See also: (b) Sonogashira, K. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998;
Chapter 5. (c) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse, H. D.
Application of Transition Metal Catalysts in Organic Synthesis; Springer-
Verlag: Berlin, 1998; Chapter 10. (d) Rossi, R.; Carpita, A.; Bellina, F.
Org. Prep. Proced. Int. 1995, 27, 127. (e) Sonogashira, K. In ComprehensiVe
Organic Synthesis; Trost, B. M. Ed.; Pergamon: New York, 1991; Vol. 3,
Chapter 2.4. There have been a few Sonogashira-type coupling reactions
performed without copper salts; see: (f) Liang, B.; Dai, M.; Chen, J.; Yang,
Z. J. Org. Chem. 2005, 70, 391 and references therein.
(13) (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.
(14) There is a significant chemical shift change of the 77Se NMR
spectrum between compound 3a and the mixture of compounds 3a and
Pd(OAc)2 (see the Supporting Information).
Org. Lett., Vol. 7, No. 14, 2005
3087

of dienynes 5 and 6 and trienyne 9a by the subsequent Pd-
catalyzed enynylation of the products with alkynes under
mild conditions. To the best of our knowledge, this is a good
example of intramolecular phenylchalcogenyl group chelation
promoted enynylation of vinylic iodides with alkynes.
Shanghai Municipal Committee of Science and Technology,
the Chinese Academy of Sciences (No. KGCX2-210-01), and
the National Natural Science Foundation of China for
financial support (Nos. 20025206, 203900502, and 20272069).
Supporting Information Available: Spectroscopic data
(1H, 13C, 77Se and NOESY NMR spectroscopic data), HRMS,
analytical data, and X-ray crystal structures of the compounds
shown in Tables 1 and 2 and Schemes 1, 2, and 4 and a
detailed description of experimental procedures. This material
is available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. We thank the State Key Project of
Basic Research (Project 973) (No. G2000048007), the
(15) For recent reviews, see: (a) Reich, H. J.; Wollowitz, S. Org. React.
1993, 44, 1-296. (b) Back, T. G. In Organoselenium Chemistry, Back, T.
G., Ed.; Oxford University Press: Oxford, U.K., 1999; pp 7-33. (c)
Nishibayashi, Y.; Uemura, S. Top. Curr. Chem. 2000, 208, 201-235 (Vol.
Ed. Wirth, T.).
OL051101A
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