ORGANIC
LETTERS
2003
Vol. 5, No. 26
4991-4993
Gallium(III) Chloride-Catalyzed Double
Insertion of Isocyanides into Epoxides†
Ghanashyam Bez and Cong-Gui Zhao*
Department of Chemistry, UniVersity of Texas at San Antonio, 6900 N. Loop 1604 W.,
San Antonio, Texas 78249-0698
Received October 7, 2003
ABSTRACT
Gallium(III) chloride-catalyzed double insertion of aryl isocyanides into terminal and disubstituted epoxides leads to r,â-unsaturated r-amino
iminolactones (3-amino-2-iminio-2,5-dihydrofurans).
Epoxides are very useful building blocks in organic synthesis
due to the high reactivity of their three-membered ring.1
Because of our ongoing research in epoxidation chemistry,2
we became interested in the reaction of epoxide and
isocyanide. Although isocyanides are very reactive toward
cations, anions, and radicals,3 they do not react with epoxides
without a promoter. A careful literature search reveals that
the reaction of isocyanides and epoxides has not been studied
in detail. Only one paper briefly mentioned a Lewis acid
(BF3‚Et2O and AlCl3)-catalyzed reaction of isocyanides with
isobutene oxide. This reaction operates through an SN1
mechanism, producing 2,3-diiminofurans in low yields
(Scheme 1).4 The authors also tried some other types of
ring-opening reactions has been well documented in the
literature. For example, Shibasaki et al. reported that gallium
bis(binaphthoxide) complexes are good catalysts for highly
enantioselective ring-opening of epoxides with p-methoxy-
phenol6 and thiols7 as nucleophiles. Similarly, Li et al.
reported that GaCl3 catalyzes ring-opening reaction of
epoxides by alkynes.8 Since GaCl3 promotes carbocation
formation from epoxides in the latter reaction8 and it is also
reported that GaCl3 may be used together with isocyanides,9
we envisaged that GaCl3 should be a good catalyst for the
(1) For reviews, see: (a) Jacobsen, E. N.; Wu, M. H. In ComprehensiVe
Asymmetric Catalysis I-III; Jacobsen, E. N., Pfaltz, A., Yamamoto, H.,
Eds.; Springer-Verlag: Berlin, Germany, 1999; Vol. 3, pp 1309-1326. (b)
Fringuelli, F.; Piermatti, O.; Pizzo, F. Trends Org. Chem. 1997, 6, 181-
195. (c) Chemla, F.; Ferreira, F. Curr. Org. Chem. 2002, 6, 539-570. (d)
Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421-433.
(2) (a) Bez, G.; Zhao, C.-G. Tetrahedron Lett. 2003, 44, 7403-7406.
(b) Adam, W.; Saha-Mo¨ller, C. R.; Zhao, C.-G. Tetrahedron: Asymmetry
1999, 10, 2749-2755. (c) Adam, W.; Zhao, C.-G. Tetrahedron: Asymmetry
1997, 8, 3995-3998.
Scheme 1. Lewis Acid (BF3‚Et2O and AlCl3)-Catalyzed
Reaction of Isocoyanides with Isobutene Oxide4
(3) For reviews on isocyanides in organic synthesis, see: (a) Do¨mling,
A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168-3120. (b) Josien, H.;
Ko, S.-B.; Bom, D.; Curran, D. P. Chem.sEur. J. 1998, 4, 67-83. (c)
Saegusa, T.; Ito, Y. Synthesis 1975, 291-300.
(4) Saegusa, T.; Takaishi, N.; Takami, M.; Ito, Y. Synth. Commun. 1971,
1, 99-102.
epoxides for this reaction but without success and concluded
that only 2,2-dialkyl epoxides are suitable for such cyclo-
addition.4
(5) For reviews, see: (a) Kellogg, R. M. Chemtracts 2003, 16, 79-92.
(b) Yamaguchi, M.; Tsukagoshi, T.; Arisawa, M. Chemtracts 2000, 13,
431-434.
(6) Iida, T.; Yamamoto, N.; Matsunaga, S.; Woo, H.-G.; Shibasaki, M.
Angew. Chem., Int. Ed. 1998, 37, 2223-2226.
GaCl3 is a versatile catalyst for many organic reactions.5
The use of GaCl3 or its derivatives as catalysts for epoxide
(7) Iida, T.; Yamamoto, N.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc.
1997, 118, 4783-4784.
(8) Viswanathan, G. S.; Li, C.-J. Synlett 2002, 1553-1555.
(9) Chatani, N.; Oshita, M.; Tobisu, M.; Ishii, Y.; Murai, S. J. Am. Chem.
Soc. 2003, 125, 7812-7813.
† Dedicated to Professor Waldemar Adam on the occasion of his 66th
birthday.
10.1021/ol0359618 CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/21/2003