K. Oh, J. Ryu / Tetrahedron Letters 49 (2008) 1935–1938
1937
Table 2
of Chemistry and Chemical Biology at IUPUI. The Bruker
500 MHz NMR was purchased via a NSF-MRI award
(CHE-0619254).
Asymmetric epoxidation of chalcone derivativesa
O
O
R1
R1
N
-oxide 2e
O
R2
Supplementary data
100 oC, 24 h
R2
1a-i
5a-i (α
Yieldb (%)
S
,β
R
)
Supplementary data associated with this article can be
Entry
R1
R2
eec (%)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
4-Me–Ph
4-Cl–Ph
4-F–Ph
4-NO2–Ph
4-F–Ph
53d
33f
53e
30d
42e
37e
43d
81e
32d
58
67
21
52
32
67
30
55
54
4-Me–Ph
4-Cl–Ph
4-F–Ph
Ph
References and notes
1. Berkessel, A.; Groger, H. Asymmetric Organocatalysis; Wiley-VCH:
Weinheim, Germany, 2005.
Ph
Ph
Ph
2. For recent reviews, see: (a) List, B. Chem. Commun. 2006, 819; (b)
Lelais, G.; MacMillan, D. W. C. Aldrichim. Acta 2006, 39, 79; (c)
Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138.
3. For recent reviews, see: (a) Masson, G.; Housseman, C.; Zhu, J.
Angew. Chem., Int. Ed. 2007, 46, 4614; (b) Marcelli, T.; van
Maarseveen, J. H.; Hiemstra, H. Angew. Chem., Int. Ed. 2006, 45,
7496; (c) Tian, S.-K.; Chen, Y.; Hang, J.; Tang, L.; Mcdaid, P.; Deng,
L. Acc. Chem. Res. 2004, 37, 621; (d) France, S.; Guerin, D.; Miller, S.
J.; Lectka, T. Chem. Rev. 2003, 103, 2985.
4. For recent review, see: Chelucci, G.; Murineddu, G.; Pinna, G. A.
Tetrahedron: Asymmetry 2004, 15, 1373.
5. For review on amine N-oxides, see: (a) Albini, A. Synthesis 1993, 263;
(b) Luh, T.-Y. Coord. Chem. Rev. 1984, 60, 255.
4-F–Ph
O
10
11
12
a
6a (n = 1)
6b (n = 2)
6c (n = 3)
14d
56d
69f
8
2
16
n
Ph
6a-c
Reaction performed with 1 (1 mmol), 2 (2 mmol) at 100 °C for 24 h.
Isolated after flash chromatography (not corrected with the recovery of
b
10–30% of starting materials).
c
Determined by chiral HPLC (absolute configuration of 5 was deter-
mined by comparison of the HPLC retention times with known data).
6. Anres, C. J.; Stetseris, N.; Norton, J. R.; Meyers, A. I. Tetrahedron
Lett. 1995, 36, 1613.
d
Reaction performed in 1,4-dioxane (0.6 mL).
Reaction performed in DME (1.2 mL).
Reaction performed in n-PrCN (0.6 mL).
e
7. (a) Armstrong, A.; Baxter, C. A.; Lamont, S. G.; Pape, A. R.;
Wincewicz, R. Org. Lett. 2007, 9, 351; (b) Shen, Y.-M.; Zhao, M.-X.;
Xu, J.; Shi, Y. Angew. Chem., Int. Ed. 2006, 45, 8005; (c) Armstrong,
A.; Carbery, D.; Lamont, S. G.; Pape, A.; Wincewicz, R. Synlett 2006,
2504; (d) Xu, J.; Jiao, P. J. Chem. Soc., Perkin Trans. 1 2002, 1491.
8. (a) Wang, X.; Shi, L.; Li, M.; Ding, K. Angew. Chem., Int. Ed. 2005,
44, 6362; (b) Kino, R.; Daikai, K.; Kawanami, T.; Furuno, H.;
Inanaga J. Org. Biomol. Chem. 2004, 2, 1822; (c) Yu, H.-B.; Zheng,
X.-F.; Lin, Z.-M.; Hu, Q.-S.; Huang, W.-S.; Pu, L. J. Org. Chem.
1999, 64, 8149 and references cited therein. For a review, see: (d)
Porter, M.; Skidmore, J. Chem. Commun. 2000, 1215.
f
presence of chiral tertiary amine could lower the reactivity
of carbonyl compounds. However, the reaction also failed
when non-enolizable ketones were used, indicating a subtle
steric bias upon the interaction between the N-oxide and
the carbonyl compounds.18
9. For representative a,b-unsaturated ketone examples, see: (a) Li, Y.;
Liu, X.; Yang, Y.; Zhao, G. J. Org. Chem. 2007, 72, 288; (b) Jew, S.-
S.; Lee, J.-H.; Jeong, B.-S.; Yoo, M.-S.; Kim, M.-J.; Lee, Y.-J.; Lee,
J.; Choi, S.-H.; Lee, K.; Lah, M. S.; Park, H.-G. Angew. Chem., Int.
Ed. 2005, 44, 1383; (c) Lattanzi, A. Org. Lett. 2005, 7, 2579; (d) Ooi,
T.; Ohara, D.; Tamura, M.; Maruoka, K. J. Am. Chem. Soc. 2004,
126, 6844; (e) Lattanzi, A.; Cocilova, M.; Iannece, P.; Scettri, A.
Tetrahedron: Asymmetry 2004, 15, 3751; (f) Aoki, M.; Seebach, D.
Helv. Chim. Acta 2001, 84, 187; (g) Adam, W.; Rao, P. B.; Degen, H.-
G.; Saha-Moller, C. R. J. Am. Chem. Soc. 2000, 122, 5654; (h) Arai, S.
S.; Shirai, Y.; Ishida, T.; Shioiri, T. Tetrahedron 1999, 55, 6375; (i)
Lygo, B.; Wainwright, P. G. Tetrahedron 1999, 55, 6289; (j) Corey, E.
J.; Zhang, F.-Y. Org. Lett. 1999, 1, 1287; (k) Ref. 8b.
10. Polonovski, M.; Polonovski, M. Bull. Soc. Chim. Fr. 1927, 41, 1190.
11. Kleinschmidt, R. F.; Cope, A. C. J. Am. Chem. Soc. 1944, 66, 1929.
12. (a) Ly, T.; Krout, M.; Pham, D. K.; Tani, K.; Stoltz, B. M.; Julian, R.
R. J. Am. Chem. Soc. 2007, 129, 1864; (b) Kubas, G. J.; Larson, A. C.;
Ryan, R. R. J. Org. Chem. 1979, 44, 3867.
13. (a) Hadden, C. E.; Kaluzny, B. D.; Robins, R. H.; Martin, G. E.
Magn. Reson. Chem. 1999, 37, 325; (b) Edward, J. T.; Whiting, J. Can.
J. Chem. 1971, 49, 3502.
In summary, we have demonstrated that the chiral ter-
tiary amine N-oxide 2e can promote the asymmetric epox-
idation of chalcone derivatives. Although the detailed
structural requirement of the chiral tertiary amine N-oxides
for asymmetric induction awaits further studies, our results
clearly show that the bridgehead amine N-oxides are capa-
ble of providing a sufficient stability for an asymmetric
induction. The present methodology utilizes a chiral
reagent 2e in excess; however, the recovery of brucine from
the reaction using 2 equiv of brucine N-oxide 2e can be
achieved without loss upon reaction work-up.19 Further-
more, our oxygen-transfer reaction is extremely simple
and convenient and can be performed in a highly concen-
trated organic medium (1.7 M).20 We are currently investi-
gating further applications of the chiral tertiary amine
N-oxides and our results will be reported in due course.
14. (a) Derdau, V.; Laschat, S. J. Organomet. Chem. 2002, 642, 131; (b)
Carpenter, N. E.; Nicholas, K. M. Polyhedron 1999, 18, 2027; (c)
Kerr, W. J.; Kirk, G. G.; Middlemiss, D. Synlett 1995, 1085.
15. (a) Derdau, V.; Laschat, S.; Jones, P. G. Heterocycles 1998, 48, 1445;
(b) Golebiewski, W. M.; Spenser, I. D. Can. J. Chem. 1985, 63, 716.
Acknowledgments
The authors gratefully acknowledge the financial sup-
port provided by the School of Science and the Department