ORGANIC
LETTERS
2000
Vol. 2, No. 5
651-653
Formation of Organomagnesium
Compounds via EtMgBr-Mediated
Radical Cyclization of Allyl
â-Iodoacetals
Atsushi Inoue, Hiroshi Shinokubo, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto 606-8501, Japan
Received December 25, 1999
ABSTRACT
Treatment of allyl â-iodoacetals with ethylmagnesium bromide in THF provided tetrahydrofuran derivatives in good yields. On the other hand,
the reaction in DME provided tetrahydrofuranylmethylmagnesium compounds in good yields.
Since the Grignard reagent was discovered in 1900, it has
been widely used for the construction of organic molecules.
It is the most basic and indispensable tool for organic
chemists.1 Grignard reagents have some common reaction
patterns: (1) nucleophilic addition or substitution, (2) proton
abstraction as a base, (3) magnesium-halogen exchange
reactions.2 There have been reports of some radical reactions
using Grignard reagents in the presence or absence of a
transition metal catalyst.3 Synthetic applications of this type
of reaction, however, have been quite limited so far.4 Herein
we wish to disclose an ethylmagnesium bromide5-mediated
radical cyclization reaction of allyl â-iodoacetals.6 This type
of radical cyclization by means of tin hydride has been
extensively explored during the past two decades.7 Currently,
however, it is desirable to avoid the use of tin compounds
due to their neurotoxicity as well as the difficulty of com-
pletely eliminating them from the reaction products. On the
contrary, organomagnesium reagents have few toxic prob-
lems. Moreover, they are easily prepared or are commercially
available. From this point of view, this facile radical
cyclization reaction using Grignard reagents has significant
advantages over tin-mediated radical cyclization reactions.
(1) (a) Wakefield, B. J. Organomagnesium Methods in Organic Synthesis;
Academic Press: London, 1995. (b) Handbook of Grignard-Reagents;
Silverman, G. S., Rakita, P. E., Eds.; Marcel Dekker: New York, 1996.
(2) (a) Boymond, L.; Rottla¨nder, M.; Cahiez, G.; Knochel, P. Angew.
Chem. 1998, 110, 1801; Angew. Chem., Int. Ed. 1998, 37, 1701. (b)
Rottla¨nder, M.; Boymond, L.; Cahiez, G.; Knochel, P. J. Org. Chem. 1999,
64, 1080 and references therein.
(3) (a) Ashby, E. C.; Laemmle, J.; Neumann, H. M. Acc. Chem. Res.
1974, 7, 272. (b) Ashby, E. C. Pure Appl. Chem. 1980, 52, 545. (c)
Maruyama, K.; Katagiri, T. J. Phys. Org. Chem. 1989, 2, 205. (d) Ward,
H. R.; Lawler, R. G.; Narzilli, T. A. Tetrahedron Lett. 1970, 521. (e) Maeda,
K.; Shinokubo, H.; Oshima, K. J. Org. Chem. 1996, 61, 6770. (f) Inoue,
A.; Shinokubo, H.; Oshima, K. Synlett 1999, 1582.
(4) Recently, synthetic applications of a transition metal-catalyzed radical
reaction involving Grignard reagents have been reported. (a) Terao, J.; Saito,
K.; Nii, S.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1998, 120, 11822.
(b) Nakao, J.; Inoue, R.; Shinokubo, H.; Oshima, K. J. Org. Chem. 1997,
62, 1910. (c) Inoue, R.; Nakao, J.; Shinokubo, H.; Oshima, K. Bull. Chem.
Soc. Jpn. 1997, 70, 2039. (d) Hayashi, Y.; Shinokubo, H.; Oshima, K.
Tetrahedron Lett. 1998, 39, 63.
(5) Muceniece, D. Ethylmagnesium Bromide. In Encyclopedia of Re-
agents for Organic Synthesis; Paquette, L., Ed.; Wiley: Chichester, 1995;
p 2486.
(6) (a) Stork, G.; Sher, P. M.; Chen, H.-L. J. Am. Chem. Soc. 1986,
108, 6384. (b) Stork, G.; Mook, R., Jr.; Biller, S. A.; Rychnovsky, S. D. J.
Am. Chem. Soc. 1983, 105, 3741. (c) Ueno, Y.; Moriya, O.; Chino, K.;
Watanabe, M.; Okawara, M. J. Chem. Soc., Perkin Trans. 1 1986, 108,
1351. (d) Ueno, Y.; Chino, K.; Watanabe, M.; Moriya, O.; Okawara, M. J.
Am. Chem. Soc. 1982, 104, 5564.
(7) (a) Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical
Reactions; VCH Verlagsgesellschaft mbH: Weinheim, 1996. (b) Giese, B.;
Kopping, B.; Go¨bel, T.; Dickhaut, J.; Thoma, G.; Kulicke, K. J.; Trach, F.
Org. React. 1996, 48, 301. (c) Giese, B. Radicals in Organic Synthesis:
Formation of Carbon-Carbon Bonds; Baldwin, J. E., Ed.; Pergamon
Press: Oxford, 1986. (d) Giese, B. Angew. Chem., Int. Ed. Engl. 1989, 28,
969. (e) Curran, D. P.; Shen, W.; Zhang, J.; Heffner, T. A. J. Am. Chem.
Soc. 1990, 112, 6738. (f) Porter, N. A.; Scott, D. M.; Rosenstein, I. J.;
Giese, B.; Veit, A.; Zeitz, H. G. J. Am. Chem. Soc. 1991, 113, 1791. (g)
Curran, D. P. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, Chapter 4.2, p 779.
10.1021/ol991403a CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/08/2000