5716
J . Org. Chem. 1996, 61, 5716-5717
P a lla d iu m -Ca ta lyzed Ster eoselective
Hyd r ogen olysis of Con ju ga ted
1,1-Dibr om o-1-a lk en es to
(Z)-1-Br om o-1-a lk en es. An Ap p lica tion to
Step w ise a n d On e-P ot Syn th esis of
En ed iyn es a n d Dien yn es
F igu r e 1.
Sch em e 1
J un’ichi Uenishi,* Reiko Kawahama, and
Osamu Yonemitsu
Department of Chemistry, Okayama University of Science,
Ridaicho, Okayama 700, J apan
J iro Tsuji
homologation of the aldehydes by the standard pr-
ocedure.10 The stereoselective hydrogenolysis was car-
ried out in benzene with a slight excess of Bu3SnH in
the presence of Pd(PPh3)4 (4 mol %).11 Results of the
bromo dienes, trienes, and enynes syntheses are listed
in Table 1.
Department of Chemical Technology, Kurashiki University
of Science and the Arts, Tsurajima-cho, Kurashiki 712,
J apan
Received May 30, 1996
Palladium-catalyzed coupling reactions of alkenyl ha-
lides with alkenyl or alkynyl metals have been used
widely in organic synthesis.1 For this reason, alkenyl
halides have become increasingly important. Particu-
larly, geometrically pure alkenyl halides have been
required in the stereospecific preparation of conjugated
polyenes and enynes.2 A number of important natural
products possess a (Z)-olefin unit in conjugated structures
(e.g., rhodopsins,3 eicosanoids,4 and enediyne antibiot-
ics5), all of which exhibit significant biological activities.
For the synthesis of such a unique structural moiety,
geometrically pure (Z)-1-halo dienes or (Z)-1-halo enynes
(Figure 1) are essential. In fact, some (Z)-(chloroethenyl)-
acetylenes have been employed for the preparation of
enediynes.6 Several methods were reported on stereo-
selective preparation of (Z)-1-halo alkenes.7 However,
they could not be used in conjugated systems.8 Herein,
we disclose a new and reliable procedure for preparing
geometrically pure (Z)-1-bromo dienes and (Z)-1-bromo
enynes based on Pd-catalyzed hydrogenolysis of 1,1-
dibromo dienes or 1,1-dibromo enynes with Bu3SnH.
These are then used for either stepwise or one-pot
construction of dienynes and enediynes by the Sonogash-
ira-Castro reaction.9
The hydrogenolysis proceeded very cleanly with high
stereoselectivity to give the geometrically pure (Z)-
bromoalkenes in good yields.12 The reactions were mostly
complete within 1 h at room temperature, and rate
enhancement was observed in the conjugated systems.13
For example, the reaction of 1,1-dibromo triene 1b was
approximately 4 times faster than that of 1,1-dibromo
diene 1a , while conjugation with a phenyl ring also
accelerated the reaction (compare entries 5 and 6). When
the reactions of (E)- and (Z)-1,1-dibromo 1,3-dienes 1c
and 1d were examined under the above reaction condi-
tions, the conjugated alkenyl moiety retained its stere-
ochemistry completely. 1,1-Dibromoalkenes 1e and 1f,
conjugated with an alkynyl group, gave (Z)-bromo enynes
2e and 2f in 69 and 63% yields. It was confirmed that a
hydride source for the hydrogenolysis was provided from
Bu3SnH by the fact that the use of Bu3SnD afforded the
deuterogenolysis product fully incorporated with deute-
rium at the terminal olefinic position.14
The palladium catalyst was essential for the reactions
and the selectivity.15 The reaction was complete when
an approximately equal molar amount of the Bu3SnH was
consumed. On the other hand, when a large excess of
Bu3SnH was employed, over hydrogenolysis took place
leading to terminal alkenes. The differentiation of the
gem-dibromide is quite interesting,16 because the at-
The typical reaction sequence is described in Scheme
1. First 1,1-dibromo-1-alkenes were prepared by C-1
(1) (a) Tsuji, J . Palladium Reagents and Catalysts; J ohn Wiley &
Sons Ltd.: New York, 1995.
(10) Ramirez, F.; Desai, N. B.; McKelvie, N. J . Am. Chem. Soc. 1962,
84, 1745. The conjugated 1,1-dibromoalkenes were obtained in 60-
95% yields.
(2) (a) Knight, D. W. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, p
481. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (c) Stille,
J . K. Angew. Chem. Int. Ed. Engl. 1986, 25, 508. (d) Sonogashira, K.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: New York, 1991; Vol. 3, p 521.
(3) Balogh-Nair, V.; Nakanishi, K. In Method in Enzymalogy;
Packer, L. Ed.; Academic Press: New York, 1982; Vol. 88.
(4) Nicolaou, K. C.; Ramphal, J . Y.; Petasis, N. A.; Serhan, C. N.
Angew. Chem. Int. Ed. Engl. 1991, 30, 1100.
(11) A typical procedure consists of the following: To a mixture of
1,1-dibromoalkene (1 mmol) and Pd(PPh3)4 (4 mol %) in benzene (9
mL) was added Bu3SnH (1.05-1.1 mmol) in benzene (3 mL), and the
mixture was stirrred for 15-60 min at room temperature. Although
(Z)-1-bromoalkene was isolated at this stage, the successive coupling
reaction with alkyne was carried out. To the reaction mixture were
added alkyne (1.5 mmol), CuI (30 mol %), and diisopropylamine (6
mmol), and the reaction was conducted at room temperature for 15-
60 min.
(5) (a) Danishefsky, S. J .; Shair, M. D. J . Org. Chem. 1996, 61, 16.
(b) Grissom, J . W.; Gunawardena, G. U.; Klingberg, D.; Huang, D.
Tetrahedron 1996, 52, 6453. (c) Wang, K. K. Chem. Rev. 1996, 96, 207.
(d) Maier, M. E. Synlett. 1995, 13.
(6) (a) Nicolaou, K. C.; Maligres, P.; Suzuki, T.; Wendeborn, S. V.;
Dai, W.-M.; Chadha, R. K. J . Am. Chem. Soc. 1992, 114, 8890. (b)
Magnus, P.; Carter, P.; Elliott, J .; Lewis, R.; Harlin, J .; Pitterna, T.;
Bauta, W. E.; Fortt, S. J . Am. Chem. Soc. 1992, 114, 2544.
(7) (a) Kluge, A. F.; Untch, K. G.; Fried, J . H. J . Am. Chem. Soc.
1972, 94, 9256. (b) Miller, R. B.; McGarvey, G. J . Org. Chem. 1978,
43, 4424. (c) Brown, H. C.; Hamaoka, T.; Ravindran, N. J . Am. Chem.
Soc. 1973, 95, 6456.
(8) Although some (Z)-1-halo-1,3-dienes have been prepared, the
geometrical purities were not satisfactory. (a) Bestmann, H. J .; Rippel,
H. C.; Dostalek, R. Tetrahedron Lett. 1989, 30, 5261. (b) Matsumoto,
M.; Kuroda, K. Tetrahedron Lett. 1980, 21, 4021.
(9) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4467. Stephens, R. D.; Castro, C. E. J . Org. Chem. 1963, 28, 3313.
(12) The (E)-isomer could not be detected by NMR in the crude
mixture. The Pd-catalyzed hydrogenolysis of simple 1-iodo-1-alkenes
was reported by Utimoto et al. Although it was highly stereospecific,
the reaction of 1-bromo-1-alkenes was reported to be sluggish (see:
Taniguchi, M.; Takeyama, Y.; Fugami, K.; Oshima, K.; Utimoto, K.
Bull. Chem. Soc. J pn. 1991, 64, 2593).
(13) The hydrogenolysis of simple 1,1-dibromo-1-alkenes also worked
well.
(14) Other reducing reagents such as triethylsilane, tris(trimeth-
ylsilyl)silane, and formic acid were ineffective.
(15) In the absence of the palladium catalyst, the reaction was very
slow and the yield was very poor. The hydrogenolysis under the radical
conditions (e.g., catalytic Et3B and Bu3SnH) gave complex mixtures
including (E)- and (Z)-isomers.
(16) For differentiation of the two bromo groups of the 1,1-dibromo-
1-alkene, a successful Suzuki coupling was reported by Roush et al.
(see: Roush, W. R.; Brown, B. B.; Drozda, S. E. Tetrahedron Lett. 1988,
29, 3541).
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