Chiral quinolinyl-oxazolines as ligands for copper(I)-catalyzed asymmetric cyclopropanation

Article abstract of DOI:10.1016/S0957-4166(98)00455-8

Chiral quinolinyl-oxazoline compounds have been synthesized from enantiomerically pure amino alcohols and 8-quinoline-carboxylic acid using a convenient procedure. Asymmetric cyccopropanation of styrene with diazoacetates in the presence of 1 mol% of CuOTf and quinolinyl-oxazolines gave 2-phenylcyclopropane carboxylates in moderate enantiomeric excesses.

Full text of DOI:10.1016/S0957-4166(98)00455-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 4143–4150
Chiral quinolinyl-oxazolines as ligands for copper(I)-catalyzed
asymmetric cyclopropanation
Xin-Yan Wu, Xiang-Hong Li and Qi-Lin Zhou ∗
Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, People’s Republic of China
Received 14 September 1998; accepted 6 November 1998
Abstract
Chiral quinolinyl-oxazoline compounds have been synthesized from enantiomerically pure amino alcohols and
8-quinoline-carboxylic acid using a convenient procedure. Asymmetric cyclopropanation of styrene with diazo-
acetates in the presence of 1 mol% of CuOTf and quinolinyl-oxazolines gave 2-phenylcyclopropane carboxylates
in moderate enantiomeric excesses. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
Over the last decade the chiral oxazolines derived from readily available amino acids have emerged
as an efficient class of ligands in an increasing number of asymmetric transformations.1 In particular,
the oxazoline ligands with C2 symmetry have achieved extremely high enantioselectivities in various
catalytic processes.1c However, there have been few reports on applications of catalysts with unsymmetric
oxazoline ligands which also have two coordinating nitrogen atoms. Brunner has reported that pyridinyl-
oxazoline 1 is a good chiral ligand in asymmetric hydrosilylation reactions.2 Fujisawa has demonstrated
that the aminoaryl-oxazoline 2 has excellent asymmetric induction in cyclopropanation3 and Diels–Alder
reactions.4 During our studies on the design of new nitrogen-containing chiral reagents, we became
interested in the chiral quinolinyl-oxazoline ligands 3. Ligands 3 have similar electronic properties to
pyridinyl-oxazoline ligands, but they have a different size chelate ring in the metal complexes formed
in the reaction, which will influence the stability, stereochemistry and enantioselectivities of catalysts.5
Herein, we wish to report the preparation of 3 and their applications as ligands in copper(I)-catalyzed
asymmetric cyclopropanation.
∗
Corresponding author. E-mail: qlzhou@online.sh.cn
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00455-8

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2. Results and discussion
2.1. Synthesis of quinolinyl-oxazoline ligands
Quinolinyl-oxazolines 3 were synthesized from enantiomerically pure amino alcohols and 8-
quinolinecarboxylic acid in four steps as shown in Scheme 1. 8-Quinolinecarboxylic acids were
converted to the corresponding chlorides 5 with SOCl2. After evaporation of excess SOCl2, the chlorides
were reacted with the amino alcohols in the presence of triethylamine in chloroform to provide
8-quinolinecarboxamides 6 in 70–81% yield. The hydroxy groups of the 8-quinolinecarboxamides 6
were converted to chlorides in 52–85% yield by refluxing with SOCl2. The cyclization of chlorides 7
with NaOH in refluxing methanol gave the desired ligands 3 in 30–94% yield.
Scheme 1.
2.2. Copper(I)-catalyzed asymmetric cyclopropanation
Recently, copper(I)-catalyzed asymmetric cyclopropanation of olefins with diazoacetates, an important
synthetic reaction, has been investigated using various oxazoline compounds as chiral ligands, and very
high enantiomeric excesses have been achieved in some cases.6 To evaluate the new class of oxazoline
ligands 3, we first tested the copper(I)-catalyzed cyclopropanation of styrene with diazoacetates using
3 as chiral ligands (Eq. 1), and the results are reported in Table 1. The reaction was carried out in
CHCl3 by slow addition of the diazoacetate to a refluxing solution of styrene and copper(I)-oxazoline
catalyst prepared in situ from copper(I) triflate and ligands 3. It was found that almost the same yields

X.-Y. Wu et al. / Tetrahedron: Asymmetry 9 (1998) 4143–4150
4145
and selectivities were given in 1,2-dichloroethane and benzene as in chloroform. The reaction did not
occur in refluxing methylene chloride. In the reaction 1.0 mol% of catalyst was used, and no differences
in the chemical yield or enantioselectivity have been found when up to 2.5 mol% of catalyst was used.
As shown in Table 1, the R-group at the chiral center of the oxazoline ring has a significant effect on
the enantioselectivity. For all diazoacetates, ligand 3e, having the bulker tert-butyl group, provided
the highest enantioselectivities, whereas ligand 3a, having the small methyl group, gave the lowest
enantioselectivities. The low chemical yield using ligand 3a is due to decomposition of the catalyst during
reaction. Different substituents on the oxazoline ring of the ligand did not change the cis/trans ratio of
the cyclopropanation products, which only appears to depend on the ester group of the diazoacetate,
corresponding to the results reported by others.3,6,7
(1)
Table 1
Asymmetric cyclopropanation of styrene with diazoacetates catalyzed by copper(I)-ligands 3
In summary, new enantiomerically pure quinolinyl-oxazoline compounds have been synthesized and
were used as chiral ligands in asymmetric cyclopropanation. The scope and limitation of this type of

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X.-Y. Wu et al. / Tetrahedron: Asymmetry 9 (1998) 4143–4150
ligand in cyclopropanation and their applications in other metal-catalyzed asymmetric reactions are under
investigation in our laboratory.
3. Experimental
3.1. General
1,2-Dichloroethane was distilled from CaH2. C6H6 was distilled from Na. CHCl3 was distilled from
CaSO4. All optically pure amino alcohols were prepared by reduction of the corresponding commercially
available amino acids with NaBH4/I2 in THF.8 IR (film): selected bands in cm−1. 1H NMR (CDCl3, 300
MHz): δ in ppm (TMS), J in Hz. MS (EI): selected peaks, m/z (%).
3.2. Synthesis of 8-quinolinecarboxamides 6
3.2.1. (10S)-N-(10-Benzyl-20-hydroxyethyl)-8-quinolinecarboxamide (6b)
General procedure: 8-Quinoline-carboxylic acid (3.46 g, 20 mmol) was treated with SOCl2 (29 ml) at
reflux temperature for 8 h, and the excess SOCl2 was removed under reduced pressure. The residue was
dissolved in 65 ml of CHCl3, and 3.32 g (22 mmol) of L-phenylalaninol in CHCl3 (15 ml) was added
at −10°C, then 14 ml (100 mmol) of triethylamine in CHCl3 (20 ml) was added at −10°C over 2 h.
The resulting mixture was stirred at rt for 24 h and washed with water (2×50 ml), aqueous NaHCO3
(0.2 M, 2×50 ml) and saturated NaCl solution. After drying over anhydrous Na2SO4 and concentrating
under reduced pressure, the crude product was purified by column chromatography on silica gel with
20
PE:EtOAc (1:2) to give 4.28 g (14 mmol, 70%) of 6b as a pale yellow oil. [α]D −116 (c 0.4, EtOH).
IR: 1730w, 1641s, 1607m, 1592m, 1572s, 1546s, 1498m, 1456m, 1424w, 1382w, 1318w, 1280m, 1200w,
1146w, 1134w, 1097w, 1071w, 1044m, 914w. 1H NMR (CDCl3): δ 2.16 (s, 1H), 3.01 (m, 2H), 3.77 (m,
2H), 4.47 (m, 1H), 7.08–7.32 (m, 5H), 7.35 (dd, J=8.4 and 4.4 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.82 (dd,
J=8.1 and 1.3 Hz, 1H), 8.24 (dd, J=8.4 and 1.7 Hz, 1H), 8.69 (m, 2H), 11.48 (d, J=6.5 Hz, 1H). MS (EI):
274 (29), 260 (63), 244 (41), 243 (39), 157 (29), 156 (100), 155 (26), 128 (75), 101 (24), 89 (25). TLC
(PE:EtOAc 1:2): Rf=0.4. Anal. calcd for C19H18N2O2: C, 74.49; H, 5.92; N, 9.14. Found: C, 73.82; H,
5.82; N, 9.14.
3.2.2. (10S)-N-(10-Methyl-20-hydroxyethyl)-8-quinolinecarboxamide (6a)
Colorless oil, 80% yield. [α]D20 +22 (c 1.0, EtOH). IR: 1642s, 1608w, 1591m, 1571s, 1498w, 1455w,
1
1380w, 1289w, 1203w, 1130w, 1074w, 1060m, 947w, 885w. H NMR (CDCl3): δ 1.40 (d, J=6.8 Hz,
3H), 3.75 (dd, J=10.9 and 4.0 Hz, 1H), 3.86 (dd, J=10.9 and 3.5 Hz, 1H), 3.91 (s, 1H), 4.37–4.45 (m,
1H), 7.50 (dd, J=8.4 and 4.3 Hz, 1H), 7.67 (t, J=7.7 Hz, 1H), 7.97 (dd, J=8.1 and 1.5 Hz, 1H), 8.28 (dd,
J=8.4 and 1.8 Hz, 1H), 8.83 (dd, J=7.3 and 1.5 Hz, 1H), 8.93 (dd, J=4.3 and 1.8 Hz, 1H), 11.45 (s, 1H).
MS (EI): 213 (13), 200 (42), 199 (96), 157 (45), 155 (100), 128 (79), 102 (24), 101 (31). TLC (PE:EtOAc
1:1): Rf=0.29. Anal. calcd for C13H14N2O2: C, 67.81; H, 6.13; N, 12.17. Found: C, 67.49; H, 6.08; N,
12.00.
3.2.3. (10S)-N-(10-Isopropyl-20-hydroxylethyl)-8-quinolinecarboxamide (6c)
20
Pale yellow oil, 75% yield. [α]D −24 (c 0.4, EtOH). IR: 1730s, 1652s, 1609w, 1592m, 1573s, 1551s,
1499w, 1462w, 1384w, 1370w, 1342w, 1277m, 1199m, 1145m, 1073w, 1026w, 885w. 1H NMR (CDCl3):
δ 1.02 (dd, J=6.8 and 4.3 Hz, 6H), 2.07 (m, 1H), 3.78 (m, 2H), 4.04 (m, 2H), 7.40 (dd, J=8.4 and 4.2

X.-Y. Wu et al. / Tetrahedron: Asymmetry 9 (1998) 4143–4150
4147
Hz, 1H), 7.56 (t, J=7.8 Hz, 1H), 7.85 (dd, J=8.1 and 1.5 Hz, 1H), 8.18 (dd, J=8.4 and 1.7 Hz, 1H), 8.75
(dd, J=8.4 and 1.4 Hz, 1H), 8.84 (dd, J=4.2 and 1.7 Hz, 1H), 11.54 (d, J=5.9 Hz, 1H). MS (EI): 227 (8),
226 (31), 197 (10), 155(100), 128 (25), 127 (32), 101 (10). TLC (PE:EtOAc 1:2): Rf=0.2. Anal. calcd for
C15H18N2O2: C, 69.74; H, 7.02; N, 10.84. Found: C, 70.13; H, 6.74; N, 10.43.
3.2.4. (10S)-N-(10-Phenyl-20-hydroxyethyl)-8-quinolinecarboxamide (6d)
20
White solid, 70% yield, mp 152–155°C. [α]D −158 (c 0.24, EtOH). IR: 1644s, 1613w, 1586m,
1
1566s, 1497w, 1463w, 1453w, 1384w, 1333w, 1300w, 1202w, 1091w, 1070m, 1053m, 980w. H NMR
(CDCl3): δ 3.53 (s, 1H), 4.06 (m, 2H), 5.48 (m, 1H), 7.25–7.62 (m, 6H), 7.46 (t, J=7.7 Hz, 1H), 7.98 (d,
J=8.1 Hz, 1H), 8.30 (dd, J=8.3 and 1.2 Hz, 1H), 8.86 (d, J=7.3 Hz, 1H), 8.91 (d, J=4.1 Hz, 1H), 12.18
(d, J=5.9 Hz, 1H). MS (EI): 292 (67, M+), 275 (99), 261 (59), 157 (100), 155 (48), 129 (97), 128 (68),
106 (48), 102 (42), 101 (49). TLC (PE:EtOAc 1:1): Rf=0.2. Anal. calcd for C18H16N2O2: C, 73.96; H,
5.52; N, 9.58. Found: C, 74.29, H, 5.53; N, 9.58.
3.2.5. (10S)-N-(10-tert-Butyl-20-hydroxyethyl)-8-quinolinecarboxamide (6e)
20
White solid, 81% yield, mp 148–150°C. [α]D +4 (c 1.0, EtOH). IR: 1643s, 1610w, 1590m, 1572s,
1498w, 1462w, 1424w, 1382w, 1364w, 1298w, 1244w, 1200w, 1137w, 1099w, 1060m, 1018w, 944w. 1H
NMR (CDCl3) δ 1.16 (d, J=6.1 Hz, 9H), 3.70–3.80 (m, 2H), 4.00–4.20 (m, 2H), 7.52 (dd, J=8.3 and 4.3
Hz, 1H), 7.70 (t, J=7.8 Hz, 1H), 7.98 (dd, J=8.1 and 1.6 Hz, 1H), 8.32 (dd, J=8.3 and 1.8 Hz, 1H), 8.86
(dd, J=7.4 and 1.6 Hz, 1H), 8.93 (dd, J=4.3 and 1.8 Hz, 1H), 11.70 (d, J=5.5 Hz, 1H). MS (EI): 241(7),
215(12), 156(100), 129(25), 128(32). TLC (PE:EtOAc 1:1): Rf=0.2, Anal. calcd for C16H20N2O2: C,
70.56; H, 7.04; N, 10.29. Found: C, 70.31; H, 7.39; N, 10.24.
3.3. Synthesis of 8-quinolinecarboxamides 7
3.3.1. (10S)-N-(10-Benzyl-20-chloroethyl)-8-quinolinecarboxamide (7b)
General procedure: To a solution of 6b (3.06 g, 10 mmol) in chloroform (75 ml) was added a
solution of SOCl2 (3.7 ml, 50 mmol) in chloroform (25 ml) in 1 h, and the mixture was refluxed for
1 h. After cooling to rt, 20 ml of water was added slowly. The organic layer was separated, and the
aqueous layer was extracted with chloroform (2×20 ml). The combined organic layer was washed with
aqueous NaHCO3 and saturated NaCl solution, and dried over anhydrous Na2SO4. After filtration and
concentration under reduced pressure, the crude material was purified by column chromatography on
20
silica gel with PE:EtOAc (1:2) to give 2.47 g (7.6 mmol, 76%) of 7b as a pale yellow oil. [α]D −70
(c 0.4, EtOH). IR: 1652s, 1611w, 1592m, 1574s, 1538s, 1498s, 1455m, 1435w, 1382w, 1343w, 1281m,
1200w, 1134w, 1079w, 1030w. 1H NMR (CDCl3) δ 3.05 (dd, J=13.6 and 7.7 Hz, 1H), 3.15 (dd, J=13.6
and 6.3Hz, 1H), 3.70 (m, 2H), 4.72 (m, 1H), 7.08–7.40 (m, 5H), 7.46 (dd, J=8.0 and 4.3 Hz, 1H), 7.60
(t, J=7.8 Hz, 1H), 7.90 (d, J=7.4 Hz, 1H), 8.26 (d, J=8.0 Hz, 1H), 8.84 (d, J=7.4 Hz, 1H), 8.88 (d, J=3.0
Hz, 1H), 11.62 (d, J=7.0 Hz, 1H). MS (EI): 324 (34, M+), 289 (58), 235 (72), 233 (100), 198 (34), 197
(67), 157 (47), 142 (62), 129 (56), 128 (92), 91 (59). TLC (PE:EtOAc 1:2): Rf=0.79. Anal. calcd for
C19H17N2OCl: C, 70.26; H, 5.28; N, 8.62. Found: C, 69.83; H, 5.26; N, 8.60.
3.3.2. (10S)-N-(10-Methyl-20-chloroethyl)-8-quinolinecarboxamide (7a)
7a was prepared in 64% yield according to the general procedure described above except that the
aqueous layer was neutralized with solid NaHCO3 before extracting by chloroform. The product was
20
obtained as an oil after purification by column chromatography. [α]D +21 (c 1.0, EtOH). IR: 1652s,
1612w, 1593w, 1573m, 1552m, 1454w, 1438w, 1378m, 1344w, 1319w, 1277w, 1214w, 1200w, 1168w,

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1139w, 1090w, 1069w, 1039w. 1H NMR (CDCl3) δ 1.48(d, J=6.8 Hz, 3H), 3.80 (dd, J=10.9 and 3.8 Hz,
1H), 3.87 (dd, J=10.9 and 4.7 Hz, 1H), 4.70 (m, 1H), 7.50 (dd, J=8.4 and 4.2 Hz, 1H), 7.69 (t, J=7.9 Hz,
1H), 7.97 (dd, J=8.1 and 1.4 Hz, 1H), 8.29 (dd, J=8.4 and 1.8 Hz, 1H), 8.86 (dd, J=7.2 and 1.4 Hz, 1H),
8.96 (dd, J=4.2 and 1.7 Hz, 1H), 11.67 (d, J=3.8 Hz, 1H). MS (EI): 250 (16, M+2), 233 (16), 231 (49),
214 (100), 199 (32), 156 (25). TLC (PE:EtOAc 2:1): Rf=0.47. Anal. calcd for C13H13NOCl: C, 62.78; H,
5.27; N, 11.26. Found: C, 62.78; H, 5.42; N, 10.79.
3.3.3. (10S)-N-(10-Isopropyl-20-chloroethyl)-8-quinolinecarboxamide (7c)
20
Yellow oil, 65% yield. [α]D −8 (c 0.4, EtOH). IR: 1727m, 1656s, 1610m, 1574s, 1543s, 1500w,
1462w, 1438w, 1384w, 1318w, 1282w, 1198w, 1135w, 1075w, 1040w, 1028w, 1011w. 1H NMR (CDCl3)
δ 0.99 (d, J=6.8 Hz, 3H), 1.02 (d, J=6.9 Hz, 3H), 2.18 (m, 1H), 3.72 (dd, J=11.0 and 5.0 Hz, 1H), 3.80
(dd, J=11.0 and 4.0 Hz, 1H), 4.28 (m, 1H), 7.40 (dd, J=8.3 and 4.2 Hz, 1H), 7.57 (t, J=7.6 Hz, 1H), 7.86
(dd, J=8.1 and 1.5 Hz, 1H), 8.17 (dd, J=8.3 and 1.8 Hz,1H), 8.76 (dd, J=7.6 and 1.5 Hz, 1H), 8.83 (dd,
J=4.2 and 1.8 Hz, 1H), 11.54 (d, J=6.1 Hz, 1H). MS (EI): 235 (24), 232 (73), 226 (13), 197 (40), 157
(26), 156 (100), 142 (17), 129 (32), 128 (69), 102 (15), 101 (21). TLC (PE:EtOAc 1:1): Rf=0.73. Anal.
calcd for C15H17N2OCl: C, 65.10; H, 6.19; N, 10.12. Found: C, 64.70; H, 6.21; N, 10.18.
3.3.4. (10S)-N-(10-Phenyl-2-chloroethyl)-8-quinolinecarboxamide (7d)
20
White solid, 65% yield, mp 99–102°C. [α]D −102 (c 0.4, EtOH). IR: 1657s, 1612w, 1593w, 1575m,
1543s, 1497m, 1455w, 1442w, 1380w, 1353w, 1288w, 1254w, 1199w, 1148w, 1076w. 1H NMR (CDCl3)
δ 4.06 (m, 2H), 5.75 (m, 1H), 7.25–7.61 (m, 6H), 7.70 (t, J=7.8 Hz, 1H), 8.00 (dd, J=8.1 and 1.5 Hz,
1H), 8.33 (dd, J=8.4 and 1.8 Hz, 1H), 8.89 (dd, J=7.2 and 1.5 Hz, 1H), 9.00 (dd, J=4.3 and 1.8 Hz, 1H),
12.38 (d, J=6.0 Hz, 1H). MS (EI): 307 (15), 290 (22), 289 (100), 215 (24), 156 (15). TLC (PE:EtOAc
1:1): Rf=0.73. Anal. calcd for C18H15N2OCl: C, 69.57; H, 4.86; N, 9.01. Found: C, 69.69; H, 4.85; N,
8.99.
3.3.5. (10S)-N-(10-tert-Butyl-20-chloroethyl)-8-quinolinecarboxamide (7e)
20
White solid, 52% yield, mp 132–134°C. [α]D +8 (c 1.0, EtOH). IR: 1659s, 1610w, 1593w, 1573m,
1552s, 1496w, 1462w, 1434w, 1398w, 1380w, 1372w, 1316w, 1284w, 1271w, 1216w, 1134w, 1100w,
1068w, 995w. 1H NMR (CDCl3) δ 1.13 (d, J=4.5 Hz, 9H), 3.72 (dd, J=11.3 and 7.9 Hz, 1H), 4.00 (dd,
J=11.3 and 3.7 Hz, 1H), 4.52 (ddd, J=9.7, 7.9 and 3.6 Hz, 1H), 7.51 (dd, J=8.3 and 4.3 Hz, 1H), 7.70
(dd, J=7.9 and 7.5 Hz, 1H), 7.97 (dd, J=8.1 and 1.6 Hz, 1H), 8.30 (dd, J=8.3 and 1.8 Hz, 1H), 8.90 (dd,
J=7.5 and 1.6 Hz, 1H), 8.94 (dd, J=4.3 and 1.8 Hz, 1H), 11.74 (d, J=8.9 Hz,1H). MS (EI): 232 (34),
198 (17), 197 (92), 196 (13), 169 (14), 168 (12), 157 (12), 156 (100), 155 (17), 142 (34), 129 (12), 128
(34). TLC (PE:EtOAc 1:1): Rf=0.67. Anal. calcd for C16H19N2OCl: C, 66.09; H, 6.60; N, 9.63. Found:
C, 66.11; H, 6.64; N, 9.67.
3.4. Synthesis of quinolinyl-oxazoline ligands 3
3.4.1. (4S)-4,5-Dihydro-2-(80 -quinolinyl)-4-benzyl-oxazole (3b)
General procedure: A mixture of 7b (3.24 g, 10 mmol) and NaOH (0.6 g, 15 mmol) in methanol
(80 ml) was refluxed for 15 h. After removal of methanol, 20 ml of water and 20 ml of chloroform
were added to the residue, the organic layer was separated, and the aqueous layer was extracted with
chloroform (2×20 ml). The combined organic layer was dried over anhydrous K2CO3, and concentrated.
The pure product was obtained by column chromatography on silica gel with PE:EtOAc (1:2). Yield:
20
1.99 g (6.9 mmol, 69%), mp 94–98°C. [α]D −8 (c 0.8, EtOH). IR: 1656s, 1612w, 1602w, 1592m,

X.-Y. Wu et al. / Tetrahedron: Asymmetry 9 (1998) 4143–4150
4149
1578m, 1494s, 1471w, 1451w, 1389w, 1367w, 1356m, 1303w, 1286m, 1258m, 1194s, 1138w, 1017s,
1
1005s, 959s. H NMR (CDCl3) δ 2.80 (dd, J=13.7 and 9.0 Hz, 1H), 3.30 (dd, J=13.7 and 8.9 Hz, 1H),
4.22 (dd, J=8.5 and 7.5 Hz, 1H), 4.43 (dd, J=9.5 and 8.5 Hz, 1H), 4.65–4.80 (m, 1H), 7.10–7.32 (m, 5H),
7.38 (dd, J=8.3 and 4.2 Hz, 1H), 7.49 (dd, J=8.0 and 7.3 Hz, 1H), 7.85 (dd, J=8.3 and 1.3 Hz, 1H), 8.04
(dd, J=7.3 and 1.2 Hz, 1H), 8.11 (dd, J=8.3 and 1.8 Hz, 1H), 9.02 (dd, J=4.2 and 1.8 Hz, 1H). MS (EI):
289 (37, M+1), 198 (88), 197 (89), 169 (75), 168 (62), 155 (70), 144 (27), 143 (100), 128 (60), 91 (86),
77 (33), 65 (30). TLC (PE:EtOAc 2:1): Rf=0.16. Anal. calcd for C19H16N2O: C, 79.14; H, 5.59; N, 9.72.
Found: C, 78.70; H, 5.60; N, 9.44.
3.4.2. (4S)-4,5-Dihydro-2-(80 -quinolinyl)-4-methyl-oxazole (3a)
3a was prepared according to the general procedure described above except that aqueous NaHCO3 (0.2
20
M, 20 ml), instead of water, was added to the residue. White solid, 30% yield, mp 119–122°C. [α]D
−42 (c 0.6, EtOH). IR: 1650s, 1594m, 1574m, 1546w, 1499s, 1473w, 1451w, 1388w, 1374w, 1355m,
1342m, 1296m, 1262w, 1192s, 1142m, 1131w, 1061m. 1H NMR (CDCl3) δ 1.46 (d, J=6.3 Hz, 3H), 4.08
(t, J=7.6 Hz, 1H), 4.50–4.75 (m, 2H), 7.43 (dd, J=8.3 and 4.2 Hz, 1H), 7.56 (t, J=7.8 Hz, 1H), 7.91 (dd,
J=8.2 and 1.4 Hz, 1H), 8.16 (m, 2H), 9.07 (dd, J=4.2 and 1.8 Hz, 1H). MS (EI): 212 (61, M+), 197 (63),
181 (24), 171 (20), 156 (100), 155 (58), 154 (27), 142 (54), 129 (78), 128 (45), 127 (25), 101 (24). TLC
(PE:EtOAc 1:2): Rf=0.13. Anal. calcd for C13H12N2O: C, 73.56; H, 5.70; N, 13.20. Found: C, 73.77; H,
5.96; N, 13.24.
3.4.3. (4S)-4,5-Dihydro-2-(80 -quinolinyl)-4-isopropyl-oxazole (3c)
20
Dark yellow oil, 94% yield. [α]D −59 (c 0.8, EtOH). IR: 1657s, 1610w, 1594m, 1575m, 1498s,
1
1468m, 1387m, 1352m, 1298m, 1284m, 1256w, 1192s, 1140m, 1128m, 1066w. H NMR (CDCl3): δ
0.92 (d, J=6.8 Hz, 3H), 1.01 (d, J=6.8 Hz, 3H), 1.82–2.00 (m, 1H), 4.15–4.30 (m, 2H), 4.43–4.60 (m,
1H), 7.33 (dd, J=8.3 and 4.2 Hz, 1H), 7.46 (dd, J=8.0 and 1.3 Hz, 1H), 7.80 (dd, J=8.3 and 1.4 Hz, 1H),
8.02 (dd, J=7.2 and 1.3 Hz, 1H), 8.07 (dd, J=8.3 and 1.7 Hz, 1H), 8.96 (dd, J=4.2 and 1.7 Hz, 1H). MS
(EI): 197 (82), 198 (49), 168 (23), 156 (63), 155 (42), 144 (15), 143 (100), 128 (48), 101 (21). TLC
(PE:EtOAc 1:2): Rf=0.2. Anal. calcd for C15H16N2O: C, 74.97; H, 6.71; N, 11.66. Found: C, 75.19; H,
6.74; N, 11.73.
3.4.4. (4S)-4,5-Dihydro-2-(80 -quinolinyl)-4-phenyl-oxazole (3d)
20
White solid, 50% yield, mp 73–76°C. [α]D −50 (c 0.8, EtOH). IR: 1649s, 1611w, 1592w, 1577w,
1495m, 1472m, 1454w, 1387w, 1353m, 1320w, 1292m, 1277w, 1250w, 1191m, 1126m, 1011s, 938m.
1H NMR (CDCl3): δ 4.45 (t, J=8.3 Hz, 1H), 4.98 (dd, J=10.2 and 1.7 Hz, 1H), 5.58 (dd, J=10.2 and 8.1
Hz, 1H), 7.20–7.55 (m, 6H), 7.60 (t, J=7.8 Hz, 1H), 7.96 (dd, J=8.2 and 1.3 Hz, 1H), 8.21 (dd, J=8.3
and 1.7 Hz, 1H), 8.25 (dd, J=7.2 and 1.3 Hz, 1H), 9.11 (dd, J=4.3 and 1.7 Hz, 1H). MS (EI): 274 (16,
M+), 244 (57), 243 (67), 242 (15), 170 (24), 156 (100), 155 (27), 128 (22), 118 (16), 91 (23), 90 (26), 89
(44). TLC (PE:EtOAc 1:2): Rf=0.22. Anal. calcd for C18H14N2O: C, 78.81; H, 5.14; N, 10.21. Found: C,
78.80; H, 5.22; N, 10.10.
3.4.5. (4S)-4,5-Dihydro-2-(80 -quinolinyl)-4-tert-butyl-oxazole (3e)
24
White solid, 50% yield, mp 138–140°C. [α]D −72 (c 1.0, EtOH). IR: 1656s, 1610w, 1594m, 1574m,
1550w, 1499m, 1478m, 1393w, 1363m, 1354m, 1339w, 1297m, 1260m, 1208w, 1192m, 1139w, 1129w,
1066w, 1046w, 1012s, 957m. 1H NMR (CDCl3): δ 1.05 (d, J=3.4 Hz, 9H), 4.20 (dd, J=10.1 and 8.0 Hz,
1H), 4.39 (t, J=8.0 Hz, 1H), 4.57 (dd, J=10.1 and 8.6 Hz, 1H), 7.42 (dd, J=8.3 and 4.2 Hz, 1H), 7.56
(dd, J=8.2 and 7.2 Hz, 1H), 7.90 (dd, J=8.2 and 1.5 Hz, 1H), 8.08 (dd, J=7.1 and 1.5 Hz, 1H), 8.16 (dd,

4150
X.-Y. Wu et al. / Tetrahedron: Asymmetry 9 (1998) 4143–4150
J=8.3 and 1.8 Hz, 1H), 9.03 (dd, J=4.2 and 1.8 Hz, 1H). MS (EI): 256 (37, M+2), 254 (100, M+), 198
(15), 197 (84), 196 (11), 169 (31), 168 (18), 156 (29), 155 (14), 142 (35). TLC (PE:EtOAc 1:2): Rf=0.25.
Anal. calcd for: C16H18N2O: C, 75.56; H, 7.13; N, 11.02. Found: C, 75.33; H, 7.83; N, 11.01.
3.5. Copper(I)-catalyzed asymmetric cyclopropanation of styrene with diazoacetates
General procedure: To a suspension of 5.0 mg (0.02 mmol) of CuOTf(C6H6)0.5 in 10 ml of dry
chloroform, a solution of 10.2 mg (0.04 mmol) of ligand 3e in 10 ml of dry chloroform was added at
rt. The mixture was stirred for 1.5 h and filtered through a syringe-tip filter (0.45 µm). After addition
of 2.3 ml (20 mmol) of styrene, the solution was heated to reflux, and 228.2 mg (2 mmol) of ethyl
diazoacetate in 10 ml of dry chloroform was slowly added over 2 h at reflux temperature. The resulting
mixture was refluxed for an additional 6 h, and then was passed through a silica gel plug to remove
the catalyst. The filtrate was concentrated under reduced pressure, and the residue was chromatographed
on silica gel with petroleum ether:ethyl acetate (PE:EtOAc 95:5) to afford 298 mg (77%) of ethyl 2-
phenylcyclopropane carboxylate. The cis:trans ratio (35:65) was determined by GC analysis on a 30 m
capillary column (Supelco 2-4318) operated at 100°C for 5 min, then programmed at 4°C/min to 200°C
[TR=13.22 min (cis isomer) and 15.13 min (trans isomer)]. Enantiomeric excesses (26% ee for the cis
isomer and 45% ee for the trans isomer) were determined, after re-esterification with (−)-menthol,6c by
GC analysis on a 30 m capillary column (Supelco 2-4318) at 210°C constant [TR=7.82 and 8.04 min for
the cis isomer, and 8.98 and 9.31 min for the trans isomer].
Acknowledgements
Financial support from the National Science Foundation of China (29772008), Science Foundation for
Chinese Extraordinary Young Scientist and Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Science is gratefully acknowledged.
References
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