ORGANIC
LETTERS
2003
Vol. 5, No. 9
1579-1582
An Efficient, Regio- and Stereoselective
Palladium-Catalyzed Route to
Tetrasubstituted Olefins
Chengxiang Zhou, Daniel E. Emrich, and Richard C. Larock*
Department of Chemistry, Iowa State UniVersity, Ames, Iowa 50011
Received March 12, 2003
ABSTRACT
An efficient, regio- and stereoselective palladium-catalyzed route to tetrasubstituted olefins has been developed, which involves the intermolecular
coupling of an aryl iodide, an internal alkyne, and an arylboronic acid. The reaction involves cis-addition of the aryl group from the aryl halide
to the less hindered or less electron-poor end of the alkyne, while the aryl group from the arylboronic acid adds to the other end.
The expeditious, regio- and stereoselective synthesis of
tetrasubstituted olefins has provided a challenge for synthetic
organic chemists for years.1 Although tetrasubstituted olefins
can be obtained by the McMurry reaction2 or Wittig
olefination,3 the generality, as well as the regio- and
stereoselectivity, of these procedures are major problems.
Recent approaches to tetrasubstituted olefins involve alkyne
carbolithiation4 and reactions employing CF3-containing
oxiranes,5 organosilanes,6 electrotelluration,7 and ynolate
anions.8 However, these approaches do not generally employ
readily available starting materials, sometimes lack regio-
and stereoselectivity, and are fairly limited in scope.
and ability to tolerate a wide range of important organic
functional groups.9 For example, palladium has provided
useful synthetic approaches to specific tetrasubstituted olefins
by the intramolecular addition of arylpalladium intermediates
to internal alkynes, followed by cross-coupling with boron,
tin, and zinc organometallics.10 The intermolecular carbo-
palladation of alkynes has interested organic chemists for
years.11 Recently, the intermolecular Rh-,12 Ni-,13 and Pd-
catalyzed14 addition of arylboronic acids to alkynes has been
reported to produce di- and trisubstituted alkenes. Rawal et
(9) (a) Trost, B. Science 1991, 234, 1471. (b) Tsuji J. Palladium Reagents
and Catalysis: InnoVations in Organic Synthesis; Wiley: New York, 1995.
(c) Handbook of Organopalladium Chemistry for Organic Synthesis;
Negishi, E., Ed.; John Wiley & Sons: New York, 2002.
(10) (a) Burns, B.; Grigg, R.; Sridharan, V.; Stevenson, P.; Sukirthal-
ingam, S.; Worakun, T. Tetrahedron Lett. 1989, 30, 1135. (b) Grigg, R.;
Sandano, J. M.; Santhakumar, V.; Sridharan, V.; Thangavelanthum, R.;
Thornton, P. M.; Wilson, D. Tetrahedron 1997, 53, 11803. (c) Grigg, R.;
Sridharan, V. Pure Appl. Chem. 1998, 70, 1047. (d) Grigg, R.; Sridharan,
V. J. Organomet. Chem. 1999, 576, 65. (e) Poli, G.; Giambastiani, G.;
Heumann, A. Tetrahedron 2000, 56, 5959. (f) Fretwell, P.; Grigg, R.;
Sansano, J. M.; Sridharan, V.; Sukirthalingam, S.; Wilson, D.; Redpath, J.
Tetrahedron 2000, 56, 7525.
(11) For representative examples, see: (a) Sugihara, T.; Cope´ret, C.;
Owczarczyk, Z.; Harring, L.; Negishi, E. J. Am. Chem. Soc. 1994, 116,
7923. (b) Gevorgyan, V.; Quan, L.; Yamamoto, Y. Tetrahedron Lett. 1999,
40, 4089. (c) Yoshikawa, E.; Yamamoto, Y. Angew. Chem., Int. Ed. 2000,
39, 173. (d) Larock, R. C.; Reddy, C. J. Org. Chem. 2002, 67, 2027.
(12) (a) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem.
Soc. 2000, 122, 10464. (b) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou,
K.; Martin-Matute, B. J. Am. Chem. Soc. 2001, 123, 5358. (c) Hayashi, T.;
Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem. Soc. 2001, 123,
9918. (d) Lautens, M.; Yoshida, M. Org. Lett. 2002, 4, 123.
Palladium-catalyzed reactions are versatile methods for
carbon-carbon bond formation as a result of their generality
(1) (a) Denmark, S. E.; Amburgey, J. J. Am. Chem. Soc. 1993, 115,
10386. (b) Creton, I.; Marek, I.; Normant, J. F. Synthesis 1996, 1499. (c)
Brown, S. D.; Armstrong, R. W. J. Am. Chem. Soc. 1996, 118, 6331. (d)
Organ, M. G.; Cooper, J. T.; Rogers, L. R.; Soleymanzadeh, F.; Paul, T. J.
Org. Chem. 2000, 65, 7959.
(2) (a) Ephritikhine, M. Chem. Commun. 1998, 2549. (b) Detsi, A.;
Koufaki, M.; Calogeropoulou, T. J. Org. Chem. 2002, 67, 4608. (c) Sabelle,
S.; Hydrio, J.; Leclerc, E.; Mioslowshi, C.; Renard, P. Y. Tetrahedron Lett.
2002, 43, 3645 and references therein.
(3) For a representative review for Wittig olefination, see: Maryanoff,
B. E.; Reitz, A. B. Chem. ReV. 1989, 89, 863.
(4) Hojo, M.; Murakami, Y.; Aihara, H.; Sakuragi, R.; Baba, Y.; Hosomi,
A. Angew. Chem., Int. Ed. 2001, 40, 621 and references therein.
(5) Shimizu, M.; Fujimoto, T.; Minezaki, H.; Hata, T.; Hiyama, T. J.
Am. Chem. Soc. 2001, 123, 6947.
(6) Itami, K.; Nokami, T.; Ishimura, Y.; Mitsudo, K.; Kamei, T.; Yoshida,
J. J. Am. Chem. Soc. 2001, 123, 11577.
(7) Marino, J. P.; Nguyen, H. N. J. Org. Chem. 2002, 67, 6291.
(8) Shindo, M.; Matsumoto, K.; Mori, S.; Shishido, K. J. Am. Chem.
Soc. 2002, 124, 6840.
(13) Shirakawa, E.; Takahashi, G.; Tsuchimoto, T.; Kawakami, Y. Chem.
Commun. 2001, 2688.
10.1021/ol034435d CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/05/2003