benzenes2f,4e,9 and five-membered aromatic heterocycles.2e,4e,10
In contrast, the asymmetric Friedel-Crafts reaction of furan
derivatives with electron-deficient olefins has not been fully
developed. In 2004, Terada et al. reported the first asym-
metric Friedel-Crafts reaction of 2-methoxyfuran with
tosylimines.10d In 2005, Evans et al. reported the reaction of
2-methoxyfuran with 2-acyl imidazoles.2e Since (1) the
nitroalkenes are important Michael-acceptors in different
asymmetric reactions,11 (2) the nitro group has diverse
transformations,12 and (3) the furan is an important bioactive
heterocycle, we speculate that it will be important to
investigate the asymmetric Friedel-Crafts reaction of furan
derivative with nitroalkenes. Herein, we would like to
document our recent results about the diphenylamine-tethered
bis(oxazoline)-metal complexes13 catalyzed asymmetric
Friedel-Crafts reaction of 2-methoxyfuran with nitroalkenes.
Our research began with the optimization of the model
reaction between 2-methoxyfuran 1 and â-nitrostyrene 2a.
The results are summarized in Tables 1 and 2.
After the screening of metal salts, it was found that
Zn(OTf)2 is the suitable choice. Rare earth triflates and
Cu(I/II) triflates led to both low yields and low enantio-
selectivities, while no formation of desired product 3a was
observed when other metal triflates were used (Table 1,
entries 1-8). Under the catalysis of 4a-Zn(II) complex, a
significant solvent effect was observed. Xylene gave better
results than toluene and dipolar solvents, while coordinative
solvents inhibited the reactivity of the catalyst (Table 1,
entries 9-14).
Table 1. Effect of Metal Sources and Solventsa
entry
metal salt
solvent
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
AgOTf
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
xylene
THF
0
0
20
20
0
19
5
64
65
0
n.d.
n.d.
0
5
n.d.
2
24
85
87
n.d.
1
38
36
21
Sc(OTf)3
La(OTf)3
Yb(OTf)3
In(OTf)3
CuOTf
Cu(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
9
10
11
12
13
14
CH3CN
DCM
DCE
14
34
20
28
hexane
a All data were obtained using 0.25 mmol substrates under the catalysis
of 10 mol % ligand-metal triflate complex in 3 mL of solvent for 24 h.
b Isolated yields. c Determined by HPLC using a Chiracel OD-H column
with hexane/isopropanol, 90:10, as eluent.
1),13a variable enantioselectivities were obtained in the
reaction in catalyzing the asymmetric Friedel-Crafts alkyl-
ation reaction of 2-methoxyfuran with â-nitrostyrene. BOX
ligands 4a-4c and BTH ligands 5a-5c gave comparable
enantioselectivities (Table 2, entries 1-3 vs entries 9-11),
whereas BOX 4d is more active than the corresponding BTH
5d. The new ligand 4f with trans-diphenyl substitution on
the oxazoline ring gave better results than its anomer 4e
formerly developed by our group,6e as well as other bis-
In order to improve the enantioselectivity of the asym-
metric alkyaltion, we further optimized the ligands. Utilizing
diphenylamine-tethered bis(oxazoline) (BOX) ligands (4a-
4d) originally prepared by Guiry14a and bis(thiazoline) (BTH)
ligands (5a-5d) originally developed by our group (Figure
(6) (a) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem.,
Int. Ed. 2005, 44 6576. (b) Zhuang, W.; Hazell, R. G.; Jorgensen, A. K.
Org. Biomol. Chem. 2005, 3, 2566. (c) Jia, Y.-X.; Zhu, S.-F.; Yang, Y.;
Zhou, Q.-L. J. Org. Chem. 2006, 71, 75. (d) Bandini, M.; Garelli, A.;
Rovinetti, M.; Tommasi, M.; Umani-Ronchi, A. Chirality 2005, 17, 522.
(e) Lu, S.-F.; Du, D.-M.; Xu, J. Org. Lett. 2006, 8, 2115. (f) Fleming, E.
M.; McCabe, T.; Connon, S. J. Tetrahedron Lett. 2006, 47, 7037. (g) Singh,
P. K.; Bisai, A.; Singh, V. K. Tetrahedron Lett. 2007, 48, 1127.
(7) (a) Zhuang, W; Hansen, T.; Jorgensen, K. A. Chem. Commun. 2001,
347. (b) Zhou, J.; Tang, Y. J. Am. Chem. Soc. 2002, 124, 9030. (c) Zhou,
J.; Ye, M.-C.; Tang, Y. J. Comb. Chem. 2004, 6, 301. (d) Zhou, J.; Tang,
Y. Chem. Commun. 2004, 432.
(8) Yamazaki, S.; Iwata, Y. J. Org. Chem. 2006, 71, 739.
(9) For some recent examples, see: (a) Ishii, A.; Soloshonok, V. A.;
Mikami, K. J. Org. Chem. 2000, 65, 1597. (b) Yuan, Y.; Wang, X.; Li, X.;
Ding, K. J. Org. Chem. 2004, 69, 146.
(10) (a) Paras, N. A.; MacMillan, D. W. C. J. Am. Chem. Soc. 2001,
123, 4370. (b) Palomo, C.; Oiarbide, M.; Kardak, B. G.; Garcia, J. M.;
Linden, A. J. Am. Chem. Soc. 2005, 127, 4154. (c) Evans, D. A.; Fandrick,
K. R. Org. Lett. 2006, 8, 2249. (d) Uraguchi, D.; Sorimachi, K.; Terada,
M. J. Am. Chem. Soc. 2004, 126, 11804. (e) Li, G.; Rowland, G. B.;
Rowland, E. B.; Antilla, J. C. Org. Lett. 2007, 9, 4065.
Table 2. Effect of Chiral Ligandsa
entry
ligand
yield (%)b
ee (%)c
1
2
3
4
5
6
4a
4b
4c
4d
4e
4f
65
64
31
73
70
85
74
54
66
78
15
6
87
92
78
92
94
94
94d
94e
84
93
67
3
7
4f
8
4f
9
5a
5b
5c
5d
(11) For recent reviews, see: Berner, O. M.; Tedeschi, L.; Enders, D.
Eur. J. Org. Chem. 2002, 1877 and refs therein.
(12) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH: New
York, 2001.
10
11
12
(13) (a) Lu, S.-F.; Du, D.-M.; Zhang, S.-W.; Xu, J. Tetrahedron:
Asymmetry 2004, 15, 3433. (b) Du, D.-M.; Lu, S.-F.; Fang, T.; Xu, J. J.
Org. Chem. 2005, 70, 3712. (c) Lu, S.-F.; Du, D.-M.; Xu, J.; Zhang, S.-W.
J. Am. Chem. Soc. 2006, 128, 7418.
(14) (a) McManus, H. A.; Guiry, P. J. J. Org. Chem. 2002, 67, 8566.
(b) McManus, H. A.; Cozzi, P. G.; Guiry, P. J. AdV. Synth. Catal. 2006,
348, 551.
a All data were obtained using 0.25 mmol substrates under the catalysis
of 10 mol % ligand-Zn(OTf)2 complex in 3 mL of xylene for 24 h.
b Isolated yields. c Determined by HPLC using a Chiracel OD-H column
with hexane/isopropanol, 90:10, as eluent. d Reaction performed at 0 °C.
e Reaction performed at 30 °C.
4726
Org. Lett., Vol. 9, No. 23, 2007