General and Selective Synthesis of (Z)-3-Haloacrylates via
Palladium-Catalyzed Carbonylation of Terminal Alkynes
Jin-Heng Li,* Shi Tang, and Ye-Xiang Xie
Contribution from the Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research,
College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China
Received September 15, 2004
A general and selective palladium-catalyzed carbonylation of terminal alkynes method for the
synthesis of (Z)-3-haloacrylates is presented. In the presence of a catalytic amount of PdX2 and 5
equiv of CuX2 (X ) Cl and Br), terminal alkynes were carbonylated to afford the corresponding
(Z)-3-haloacrylates exclusively in moderate to good yields. The results showed that the effect of
solvent had a fundamental influence on the chemoselectivity and stereoselectivity of the palladium-
catalyzed carbonylation reaction.
Introduction
mations, palladium-catalyzed carbonylation is considered
to be one of the most effective strategies.6,7 However, few
reports on the palladium-catalyzed carbonylation of an
alkyne to a 3-haloacrylate have been described.7 Fur-
thermore, these reports focused on the PdCl2- and CuCl2-
catalyzed carbonylation of alkynes to synthesize 3-chlo-
roacrylates. Thus, the development of an effective
palladium-catalyzed carbonylation of alkynes procedure
to selectively construct 3-haloacrylate skeletons, includ-
ing 3-chloroacrylate and 3-bromoacrylate skeletons, would
be significant. Here, we report a general and selective
palladium-catalyzed carbonylation of alkynes method for
the synthesis of (Z)-3-haloacrylates.
3-Haloacrylates are valuable building blocks in organic
synthesis1,2 and a recurring functional group in many
natural products and bioactive compounds.3 Conse-
quently, a number of efficient and selective methods have
been developed for their synthesis.4-7 Of these transfor-
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Tetrahedron Lett. 1985, 26, 4419. (b) Bey, P.; Vevert, J. P. J. Org.
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19, 1267. (d) Larock, R. C.; Narayanan, K.; Hershberger, S. S. J. Org.
Chem. 1983, 48, 4377. (e) Zhang, C.; Lu, X. Synthesis 1996, 586. (f)
Crousse, B.; Alami, M.; Linstrumelle, G. Tetrahedron Lett. 1995, 36,
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67, 847.
(3) (a) Vanghn, T. H. Union Carbide Corp., Belg. 1963, 631, 355;
Chem. Abstr. 1964, 60, 11900h. (b) Herrett, R. A.; Kurtz, A. N. Science
1963, 141, 1192. (c) Kurtz, A. N.; Herret, R. A. Union Carbide Corp.,
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(4) (a) Winterfeldt, E. Angew. Chem., Int. Ed. Engl. 1967, 6, 423.
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3768.8
(5) (a) Kurtz, A. N.; Billups, W. E.; Greenlee, R. B.; Hamil, H. F.;
Pace, W. T. J. Org. Chem. 1965, 30, 3141. (b) Andersson, K. Chem.
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Shimada, S.; Tanaka, M. J. Am. Chem. Soc. 1998, 120, 12365.
(6) For reviews, see: (a) Colquhoun, H. M.; Thompson, D. J.; Twigg,
M. V. Carbonylation; Plenum Press: New York, 1991. (b) Tsuji, J.
Palladium Reagents and Catalysts; Wiley: New York, 1995. (c) In
Handbook of Organopalladium Chemistry for Organic Synthesis;
Negishi, E., Ed.; Wiley-Interscience: New York, 2002.
Results and Discussion
In 1999 we reported the PdCl2- and CuCl2-catalyzed
carbonylation of terminal alkynes to form (Z)-3-chlor-
oacrylates.7c In alcohol (0.6 mL)/benzene (10 mL), various
(Z)-3-chloroacrylates were obtained exclusively in moder-
ate to good yields using 5 mol % of PdCl2 as catalyst in
the presence of 3 equiv of CuCl2 as the catalytic system.
Thus, we expected that the use of PdBr2 and CuBr2
instead of PdCl2 and CuCl2 might afford 3-bromoacryl-
ates, but this attempt was unsuccessful (entry 1 in Table
(7) (a) Heck, R. F. J. Am. Chem. Soc. 1972, 94, 2712. (b) Larock, R.
C.; Riefling, B.; Fellows, C. A. J. Org. Chem. 1978, 43, 131. (c) Li, J.-
H.; Jiang, H.-F.; Feng, A.-Q.; Jia, L.-Q. J. Org. Chem. 1999, 64, 5984.
(d) Huang, X.; Sun, A. J. Org. Chem. 2000, 65, 6561. (e) Ma, S.; Wu,
B.; Zhao, S. Org. Lett. 2003, 5, 4429.
10.1021/jo048358r CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/10/2004
J. Org. Chem. 2005, 70, 477-479
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