ORGANIC
LETTERS
2010
Vol. 12, No. 5
1012-1014
Iron-Catalyzed Regio- and Stereoselective
Substitution of γ,δ-Epoxy-r,ꢀ-unsaturated
Esters and Amides with Grignard
Reagents
Takeshi Hata, Rie Bannai, Mamoru Otsuki, and Hirokazu Urabe*
Department of Biomolecular Engineering, Graduate School of Bioscience and
Biotechnology, Tokyo Institute of Technology, 4259-B-59 Nagatsuta-cho, Midori-ku,
Yokohama, Kanagawa 226-8501, Japan
Received January 5, 2010
ABSTRACT
When γ,δ-epoxy-r,ꢀ-unsaturated esters or amides were treated with 2 equiv of Grignard reagents in the presence of 10-24 mol % FeCl2,
regio- and stereoselective substitution of the epoxide moiety with the Grignard reagent occurred to give exclusively δ-hydroxy-γ-alkyl or
aryl-r,ꢀ-unsaturated esters or amides in good yields.
Diene monoepoxides are useful building blocks in organic
synthesis, and their utility has been explored by many
research groups.1 Although their functionalized counterparts,
such as γ,δ-epoxy-R,ꢀ-unsaturated carboxylic acid derivative
1 in eq 1, are often more useful than simple compounds,2
their reaction with organometallic reagents has not been
amply reported, probably because of the poor compatibility
of the functional group with metallic reagents.3,4 Here we
report that iron-catalyzed substitution of these diene monoe-
(3) With methyl- or ethylaluminum reagents: (a) Miyashita, M.; Hoshino,
M.; Yoshikoshi, A. J. Org. Chem. 1991, 56, 6483–6485. (b) Shanmugam,
P.; Miyashita, M. Org. Lett. 2003, 5, 3265–3268. For application to natural
product synthesis, see: (c) Komatsu, K.; Tanino, K.; Miyashita, M. Angew.
Chem., Int. Ed. 2004, 43, 4341–4353. (d) Nakamura, R.; Tanino, K.;
(1) (a) Olofsson, B.; Somfai, P. In Aziridines and Epoxides in Organic
Synthesis; Yudin, A. K., Ed.; Wiley-VCH: Weinheim, 2006; pp 315-347.
For substitution of epoxides with Grignard reagents, see: (b) Urabe, H.;
Sato, F. In Handbook of Grignard Reactions; Silverman, G. S., Rakita,
P. E., Eds.; Marcel Dekker: New York, 1996; pp 577-632.
Miyashita, M. Org. Lett. 2003, 5, 3579–3582
.
(4) With organocopper reagents (which shows different regioselection
to form allyl alcohols rather than homoallyl alcohols): Hirai, A.; Matsui,
A.; Komatsu, K.; Tanino, K.; Miyashita, M. Chem. Commun. 2002, 1970–
(2) Substitution of functionalized diene monoepoxides with various
nucleophiles has been reported. With oxygen or nitrogen nucleophiles: (a)
Yu, X.-Q.; Yoshimura, F.; Ito, F.; Sasaki, M.; Hirai, A.; Tanino, K.;
Miyashita, M. Angew. Chem., Int. Ed. 2008, 47, 750–754. (b) Miyashita,
M.; Mizutani, T.; Tadano, G.; Iwata, Y.; Miyazawa, M.; Tanino, K. Angew.
Chem., Int. Ed. 2005, 44, 5094–5097. (c) Fagnou, K.; Lautens, M. Org.
Lett. 2000, 2, 2319–2321. (d) Tsuda, T.; Horii, Y.; Nakagawa, Y.; Ishida,
T.; Saegusa, T. J. Org. Chem. 1989, 54, 977–979. With active methylene
compounds under Pd catalysis (which shows different regioselection to form
allyl alcohols rather than homoallyl alcohols): (e) Tsuji, J.; Kataoka, H.;
Kobayashi, Y. Tetrahedron Lett. 1981, 22, 2575–2578. (f) Nemoto, H.;
Ibaragi, T.; Bando, M.; Kido, M.; Shibuya, M. Tetrahedron Lett. 1999, 40,
1319–1322. With hydride under Pd catalysis: (g) Oshima, M.; Yamazaki,
H.; Shimizu, I.; Nisar, M.; Tsuji, J. J. Am. Chem. Soc. 1989, 111, 6280–
6287. With electron: (h) Molander, G. A.; Bella, B. E. L.; Hahn, G. J. Org.
Chem. 1986, 51, 5259–5264. (i) Yadav, J. S.; Shekharam, T.; Srinivas, D.
Tetrahedron Lett. 1992, 33, 7973–7976.
1971
.
(5) For reviews on iron-promoted organic reactions, see: (a) Correa, A.;
Manchen˜o, O. G.; Bolm, C. Chem. Soc. ReV. 2008, 37, 1108–1117. (b)
Enthaler, S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317–
3321. (c) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. ReV. 2004, 104,
6217–6254. For diene, enyne, and diyne cyclizations, see: (d) Michelet,
V.; Toullec, P. Y.; Geneˆt, J.-P. Angew. Chem.Int. Ed 2008, 47, 4268–4315.
For coupling reactions, see: (e) Sherry, B. D.; Fu¨rstner, A. Acc. Chem. Res.
2008, 41, 1500–1511. (f) Fu¨rstner, A.; Martin, R. Chem. Lett. 2005, 34,
624–629
.
(6) For iron-catalyzed or -mediated reactions from our laboratory, see:
(a) Okada, S.; Arayama, K.; Murayama, R.; Ishizuka, T.; Hara, K.; Hirone,
N.; Hata, T.; Urabe, H. Angew. Chem., Int. Ed. 2008, 47, 6860–6864. (b)
Hata, T.; Hirone, N.; Sujaku, S.; Nakano, K.; Urabe, H. Org. Lett. 2008,
10, 5051–5053. (c) Fukuhara, K.; Urabe, H. Tetrahedron Lett. 2005, 46,
603–606
.
10.1021/ol100022w 2010 American Chemical Society
Published on Web 02/09/2010