1695
H. Zhou et al.
Letter
Synlett
The plausible mechanism of this SnCl4-promoted formal
[3+2] cycloaddition reaction is outlined in Scheme 1. We
believe that the reaction may go through an oxocarbenium
intermediate, which is similar to the mechanism of the for-
mal [3+2] cycloaddition of donor–acceptor oxiranes with al-
dehydes8b,c or alkynes.8d The Lewis acid is supposed to coor-
dinate the two carbonyl groups of oxirane 1, forming an en-
ergetically favorable six-membered-ring structure 4 which
then gives oxocarbenium intermediate 5 (the zwitterionic
intermediate) via C–C bond cleavage. The lone pair on the
nitrogen atom of the nitriles attacks oxocarbenium to gen-
erate the 1,5-dipole 6, which is followed by nucleophilic at-
tack of the malonate carbanion on the nitrile carbenium, af-
fording cycloadduct 3. The ring structure of 3 was deter-
mined by X-ray crystallographic analysis13 of 7, which was
obtained from the reduction of 3aa (see Scheme 2 and the
Supporting Information).
Acknowledgment
Financial support from National Natural Science Foundation of China
(21373073), Zhejiang Provincial Natural Science Foundation of China
(LY14B020015), Scientific Research Fund of Zhejiang Provincial Edu-
cation Department (Y201329747), and Program for Changjiang Schol-
ars and Innovative Research Team in Chinese University (IRT-1231) is
gratefully acknowledged. G.Z. gratefully acknowledges a Qianjiang
scholarship from Zhejiang Province in China.
Supporting Information
Supporting information for this article is available online at
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References and Notes
(1) (a) 1,3-Dipolar Cycloaddition Chemistry; Vol. 1; Padwa, A., Ed.;
Wiley: New York, 1984. (b) 1,3-Dipolar Cycloaddition Chemistry;
Vol. 2; Padwa, A., Ed.; Wiley: New York, 1984. (c) Huisgen, R. In
Advances in Cycloaddition; Vol. 1; Curran, D. P., Ed.; JAI Press:
Greenwich, 1988, 1–32. (d) Deshong, P.; Lander, S. W.; Leginus,
J. M. Jr.; Dicken, C. M. In Advances in Cycloaddition; Vol. 1;
Curran, D. P., Ed.; JAI Press: Greenwich, 1988, 87–128.
(e) Gothelf, K. V.; Jørgensen, K. A. Chem. Rev. 1998, 98, 863.
(f) Kanemasa, S. Synlett 2002, 1371. (g) The Chemistry of Hetero-
cyclic Compounds: Synthetic Applications of 1,3-Dipolar Cycload-
dition Chemistry Toward Heterocycles and Natural Products; Vol.
59; Padwa, A.; Pearson, W. H., Eds.; Wiley and Sons: New York,
2002. (h) Topics in Heterocyclic Chemistry: Synthesis of Heterocy-
cles via Cycloadditions I; Vol. 12; Hassner, A., Ed.; Springer: Ber-
lin/Heidelberg, 2008.
OMe
O
MeO
O+
R
N:
O
2
O–
O
O
CO2Me
CO2Me
+ LA
LA
Ar
MeO
Ar
Ar
LA
O
MeO
1
4
5
Ar
O
CO2Me
OMe
CO2Me
O
CO2Me
R
N
R
– LA
Ar
O
N
LA
6
3
(2) (a) Huisgen, R. Angew. Chem., Int. Ed. Engl. 1977, 16, 572; and
references cited therein. (b) Bemaus, C.; Font, J.; de March, P.
Tetrahedron 1991, 47, 7713. (c) Wang, G.-W.; Yang, H.-T.; Wu, P.;
Miao, C. B.; Xu, Y. J. Org. Chem. 2006, 71, 4346.
Scheme 1 Plausible mechanism of [3+2] cycloaddition of donor–
acceptor oxiranes with nitriles
(3) (a) Hojo, M.; Ohkuma, M.; Ishibashi, N.; Hosomi, A. Tetrahedron
Lett. 1993, 34, 5943. (b) Hojo, M.; Aihara, H.; Suginohara, Y.;
Sakata, K.; Nakamura, S.-Y.; Murakami, C.; Hosomi, A. J. Org.
Chem. 1997, 62, 8610.
(4) (a) Shimizu, N.; Bartlett, P. D. J. Am. Chem. Soc. 1978, 100, 4260.
(b) Bekhazi, M.; Warkentin, J. J. Am. Chem. Soc. 1983, 105, 1289.
(c) Bekhazi, M.; Risbood, P. A.; Warkentin, J. J. Am. Chem. Soc.
1983, 105, 5675. (d) Couture, P.; Terlouw, J. K.; Warkentin, J.
J. Am. Chem. Soc. 1996, 118, 4214. (e) Warkentin, J. J. Chem.
Soc., Perkin Trans. 1 2000, 2161.
In addition, the products are resourceful intermediates
and could be used for further transformation into a variety
of other compounds. For example, further reduction of
compound 3aa with NaBH4 afforded a 3-oxazoline 7 in 97%
yield (Scheme 2).
HOH2C
MeO2C
NaBH4
O
HOH2C
Ph
O
MeO2C
Ph
THF–H2O (9:1)
0 °C to r.t., 97%
C6H4-4-Me
C6H4-4-Me
N
(5) (a) Gill, H. S.; Landgrebe, J. A. Tetrahedron Lett. 1982, 23, 5099.
(b) Gill, H. S.; Landgrebe, J. A. J. Org. Chem. 1983, 48, 1051.
(6) Hojo, M.; Aihara, H.; Hosomi, A. J. Am. Chem. Soc. 1996, 118,
3533.
N
3aa
Scheme 2 Reduction of 3-oxazoline 3aa with NaBH4
7
(7) (a) De March, P.; Huisgen, R. J. Am. Chem. Soc. 1982, 104, 4952.
(b) Huisgen, R.; De March, P. J. Am. Chem. Soc. 1982, 104, 4953.
(c) Doyle, M. P.; Forbes, D. C.; Protopopova, M. N.; Stanley, S. A.;
Vasbinder, M. M.; Xavier, K. R. J. Org. Chem. 1997, 62, 7210.
(d) Jiang, B.; Zhang, X.-B.; Luo, Z.-H. Org. Lett. 2002, 4, 2453.
(e) Mehta, G.; Muthusamy, S. Tetrahedron 2002, 58, 9477. (f) Lu,
C.-Y.; Chen, Z.-Y.; Liu, H.; Hu, W. H.; Mi, A.-Q. J. Org. Chem. 2004,
69, 4856. (g) Russell, A. E.; Brekan, J.; Gronenberg, L.; Doyle, M.
P. J. Org. Chem. 2004, 69, 5269. (h) Suga, H.; Ebiura, Y.;
Fukushima, K.; Kakehi, A.; Baba, T. J. Org. Chem. 2005, 70, 10782.
(i) Padwa, A. Helv. Chim. Acta 2005, 88, 1357. (j) Torssell, S.;
In conclusion, we have developed a SnCl4-promoted for-
mal [3+2] cycloaddition of donor–acceptor oxiranes with
nitriles, which provides an efficient and practical method to
produce a wide variety of 3-oxazolines under mild condi-
tions. Future studies will focus on its potential application
and understanding of the mechanism of this formal [3+2]-
cycloaddition reaction.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1693–1696