ORGANIC
LETTERS
2007
Vol. 9, No. 22
4607-4610
Preparation of
r-Haloacrylate
Derivatives via Dimethyl
Sulfoxide-Mediated Selective
Dehydrohalogenation
Wei Li,* Jianchang Li, Zhao-Kui Wan, Junjun Wu, and Walter Massefski
Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park DriVe,
Cambridge, Massachusetts 02140
Received August 28, 2007
ABSTRACT
Dimethyl sulfoxide causes
A variety of -halo Michael acceptors were prepared in dimethyl sulfoxide under mild, base-free conditions, including the preparation of
-bromoacrolein and -chloro- and bromoacrylonitriles. Synthesis of these molecules has been reported in the literature to be difficult. Among
all the existing dehydrohalogenation procedures, this protocol is the most facile, practical, and environmentally benign process.
r,â-dihalopropanoate derivatives to undergo efficient, selective dehydrohalogenation to form r-haloacrylate analogues.
r
r
r
Recent reports on new methods for the preparation of
R-haloacrylates reflect the renewed interest in the synthesis
of these useful building blocks1 and prompted the submission
of this communication. Acrylate derivatives are not only used
as Michael acceptors,2 but are also frequently employed as
dienophiles or dipolarophiles in cycloaddition reactions.3
With an additional vinyl halogen atom at the R-position to
the carbonyl, it is not surprising that R-haloacrylate analogues
have found more synthetic application due to this added
functional handle. For example, â,γ-unsaturated esters and
lactones can be easily obtained by reaction of the R-halo-
acrylate analogues with dialkyl phosphonates,4 and vinyl-
oxiranes can be prepared through reaction of aldehydes with
lithium dienolates.5 The halogen atom could also readily
undergo metal-halogen exchange,6 allowing for homologa-
tion of the parent structure through C-alkylation. The
R-haloacrylate analogues not only increase their utility as
Michael acceptors7 or dienophiles in cycloaddition chemis-
try,8 but they can also serve as the functionalized vinyl halide
in transition metal-mediated coupling reactions.9 With the
(5) Hudlicky, T.; Fleming, A.; Lovelace, T. C. Tetrahedron 1989, 45,
3021.
(6) (a) Grossman, G.; Poncioni, M.; Bornand, M.; Jolivet, B.; Neuburger,
M.; Sequin, U. Tetrahedron 2003, 59, 3237. (b) Thibonnet, J.; Vu, V. A.;
Berillon, L.; Knochel, P. Tetrahedron 2002, 58, 4787.
(7) Selected examples: (a) Saoudi, A.; Hamelin, J.; Benhaoua, H. J.
Chem. Res. Synop. 1996, 11, 491. (b) Chen, C.; Xi, C.; Jiang Y.; Hong, X.
Tetrahedron Lett. 2004, 45, 6067. (c) Gutke, H.; Braun, N. A.; Spitzner,
D. Tetrahedron 2004, 60, 8137. (d) Prostenic, M.; Salzman, N. P.; Carter,
H. E. J. Am. Chem. Soc. 1955, 77, 1856. (e) Martin, A. R.; Caputo, J. F. J.
Org. Chem. 1974, 39, 1811. (f) Martin, A. R.; Mallick, S. K.; Caputo, J. F.
J. Org. Chem. 1974, 39, 1808.
(8) (a) Corey, E. J.; Snider, B. B. J. Am. Chem. Soc. 1972, 94, 2549. (b)
Zhou, G.; Hu, Q.; Corey, E. J. Or. Lett. 2003, 5, 3979. (c) Sun, P.; Chang,
M.; Chiang M.; Chang, N. Org. Lett. 2003, 5, 1761.
(1) (a) Yin, J.; Gallis, C. E.; Chisholm, J. D. J. Org. Chem. 2007, 72,
7054. (b) Chen, S.; Wang, J. Org. Chem. 2007, 72, 4993. (c) J. Barma, D.
K.; Kundu, A.; Zhang, H.; Miokowski, C.; Falck, J. R. J. Am. Chem. Soc.
2003, 125, 3218.
(2) Richard, D. J.; Schiavi, B.; Joullie, M. M. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 11971.
(3) Chang, M.; Hsu, R.; Tseng, T.; Sun, P.; Chang, N. Tetrahedron 2004,
60, 5545.
(4) Hirao, T.; Fujihara, Y.; Kurokawa, K.; Ohshiro, Y.; Agawa, T. J.
Org. Chem. 1986, 51, 2830.
(9) Selected references: (a) Bellur, E.; Langer, P. Eur. J. Org. Chem.
2005, 22, 4815. (b) Sorg, A.; Blank, F.; Brueckner, R. Synlett 2005, 8,
1286. (c) Majo, V. J.; Prabhakaran, J.; Simpson, N. R.; Van Heertum, R.
L.; Mann, J. J.; Kumar, J. S. D. Bioorg. Med. Chem. Lett. 2005, 15, 4268.
10.1021/ol7021142 CCC: $37.00
© 2007 American Chemical Society
Published on Web 10/02/2007