Synthesis of chiral 2-alkyl-8-quinolinyl-oxazoline ligands: Reversal of enantioselectivity in the asymmetric palladium-catalyzed allylic alkylation

Article abstract of DOI:10.1016/S0022-328X(01)01172-X

New chiral 2-alkyl-8-quinolinyl-oxazolines were synthesized from 2-alkyl-8-quinolinecarboxylic acids and enantiomerically pure amino alcohols using a convenient procedure. Enantioselective palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl

Full text of DOI:10.1016/S0022-328X(01)01172-X

Journal of Organometallic Chemistry 640 (2001) 65–71
www.elsevier.com/locate/jorganchem
Synthesis of chiral 2-alkyl-8-quinolinyl-oxazoline ligands: reversal
of enantioselectivity in the asymmetric palladium-catalyzed allylic
alkylation
Xiao-Guang Li a, Xu Cheng a, Jun-An Ma a, Qi-Lin Zhou a,b,
*
a The State Key Laboratory and the Institute of Elemento-organic Chemistry, Nankai Uni6ersity, Weijin Road 94,
Tianjin 300071, People’s Republic of China
b The Open Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, People’s Republic of China
Received 15 May 2001; accepted 28 July 2001
Abstract
New chiral 2-alkyl-8-quinolinyl-oxazolines were synthesized from 2-alkyl-8-quinolinecarboxylic acids and enantiomerically pure
amino alcohols using a convenient procedure. Enantioselective palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl
acetate with dimethyl malonate in the presence of 2-alkyl-8-quinolinyl-oxazolines provided an alkylation product with an opposite
configuration compared to those obtained from unsubstituted quinolinyl-oxazoline ligands. © 2001 Elsevier Science B.V. All
rights reserved.
Keywords: Palladium complexes; Asymmetric catalysis; Chiral ligands; Allylic alkylation
1. Introduction
2. Results and discussion
Chiral heteroaryl-oxazolines have been used as lig-
ands in a number of catalytic enantioselective reactions
[1]. Recently, we synthesized 8-quinolinyl-oxazolines 1
as ligands in the copper-catalyzed cyclopropanation of
styrene with diazoacetates [2], palladium-catalyzed
Heck-type hydroarylation of norbornene with phenyl
iodides [3] and the copper-catalyzed allylic oxidation of
cyclic olefins with tert-butyl perbenzoate [4]. In 1999,
Chelucci used ligands 1 in the palladium-catalyzed al-
lylic alkylation of 1,3-diphenyl-2-propenyl acetate with
dimethyl malonate, and moderate to good enantioselec-
tivities have been achieved [5]. Later, he reported that
4-acridininyl-oxazoline ligands, 2,3-benzo-fused deriva-
tives of 1, have much lower activities and enantioselec-
tivities in this reaction [6]. These promoted us to report
our results in the investigation of 2-alkyl-8-quinolinyl-
oxazoline ligands 2 in the palladium-catalyzed allylic
alkylation reaction.
2-Alkyl-8-quinolinyl-oxazolines were synthesized
from 2-alkyl-8-quinolinecarboxylic acids 3 and enan-
tiomerically pure amino alcohols according to the pro-
cedure shown in Scheme 1. Thus, the 2-alkyl-8-
quinolinecarboxylic acids 3 were converted to the esters
4 in 70–81% yield. The ester exchange of 4 with amino
alcohols provided amides 5 in 51–88% yield. The cy-
clization of amides 5 with MsCl–Et3N–DMAP in a
mild condition afforded the ligands 2 in 54–88% yield
[7].
To investigate the chiral discrimination of ligands 2,
asymmetric palladium-catalyzed allylic alkylation of
1,3-diphenyl-2-propenyl acetate (6) was performed. The
alkylation reaction was carried out in CH2Cl2 using
[Pd(h3-C3H5)Cl]2 as precatalyst and the N,O-
bis(trimethylsilyl)-acetamide (BSA) as the base accord-
ing to Trost’s procedure [8]. The results are summarized
in Table 1.
Compared to ligands 1, ligands 2 provided a slightly
higher level of enantiocontrol, although the reactions
using ligands 2 needed longer reaction time. In contrast,
* Corresponding author. Fax: +86-22-2350-0011.
E-mail address: qlzhou@public.tpt.tj.cn (Q.-L. Zhou).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)01172-X

66
X.-G. Li et al. / Journal of Organometallic Chemistry 640 (2001) 65–71
the 4-acridininyl-oxazoline ligands gave much lower
enantioselectivities (less than 34% ee) than those ob-
tained with ligands 1 [6]. The effect of the 2-alkyl group
(R%) in ligands 2 on the enantioselectivity was exam-
ined. When the R group in ligands 2 is benzyl, the
influence of the R% group on the enantioselectivity of
the reaction is very limited, resulting in enantiomeric
excesses ranging from 66 to 74% (Table 1, entries 7, 11
and 12). However, when R is tert-butyl, R% has a
significant effect on the enantioselectivity of the reac-
tion. For example, ligand 2d (R%=CH3) gave 78% ee,
whereas ligand 2g (R%=i-Bu) afforded only 53% ee. It
is unexpected and interesting that ligands 2 with S
configuration yielded the alkylation product 7 with R
configuration, which is opposite to the configuration of
the product given by ligands 1. This reversal of enan-
tioselectivity was also observed in the reaction with
acridininyl-oxazoline ligands [6].
According to the generally accepted mechanism of
palladium-catalyzed allylic alkylation, the enantioselec-
tivity of the reaction is determined by the regioselectiv-
ity in the attack of nucleophile to one of the two allylic
termini in the 1,3-diphenyl-h3-allylpalladium(II) inter-
mediate [9]. There are a number of possible allylpalla-
dium complex intermediates in the solution. Among
them, the intermediate 8 is the most predominant one,
and has been demonstrated by 1H-NMR [10]. As shown
in Scheme 2, there are two pathways, a and b, for the
nucleophile to attack the allylic termini giving the alky-
lation products with S and R configuration individu-
ally. From the absolute configuration of the product
Scheme 1.
Table 1
Enantioselectively allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate a
Entry
Ligand
Time (h) b
Yield (%) c
ee (%) d
Conf. e
1
2
3
4
7
8
9
10
11
12
13
1a (R%=H, R=Bn)
1b (R%=H, R=i-Pr)
1c (R%=H, R=Ph)
3
0.5
1
98
96
88
94
95
86
96
79
96
67
99
69 f
42 g
59 g
77 g
66
76
64
78
73
S
S
S
S
R
R
R
R
R
R
R
1d (R%=H, R=t-Bu)
2a (R%=CH3, R=Bn)
2b (R%=CH3, R=i-Pr)
2c (R%=CH3, R=Ph)
2d (R%=CH3, R=t-Bu)
2e (R%=n-Bu, R=Bn)
2f (R%=i-Bu, R=Bn)
2g (R%=i-Bu, R=t-Bu)
2
41
60
64
50
51
60
46
74
53
a Reaction condition: [Pd(h3-C3H5)Cl]2 (2.5 mol%), ligand (10 mol%), 1,3-diphenyl-2-propenyl acetate (0.4 mmol), CH2(CO2Me)2 (1.2 mmol),
BSA (1.2 mmol) and KOAc (3.5 mol%) in dichloromethane (4 ml) at room temperature.
b Time for completion of reaction.
c Isolated yields.
d Determined by HPLC using a chiral column (DIACEL Chiracel OD, at 254 nm, n-hexane–2-propanol=99:1, 0.9 ml min−1, tR=15.3 min,
tS=16.8 min).
e Assigned by comparison of specific rotation with that in the literature (Ref. [12]).
f Data are taken from literature (Ref. [10]).
g Data are taken from literature (Ref. [5]).

X.-G. Li et al. / Journal of Organometallic Chemistry 640 (2001) 65–71
67
Scheme 2.
obtained with ligands 2, we know that the nucleophile
3.2. Synthesis of ethyl 2-alkyl-8-quinolinecarboxylate 4
preferentially attacks the allylic terminus trans to the
quinoline nitrogen, i.e. pathway b. This selectivity can
be explained by a late transition state related to the
steric interaction between ligand and allyl in a product
like the Pd(0)–olefin complex [6,9d,11]. According to
this model, the pathway of the nucleophile depends on
the relative strength of steric interactions A and B.
When R% is hydrogen, the steric interaction B is
stronger than A, and the Pd(0)–olefin complex 9a is
more stable than 9b, providing the alkylation product
with S configuration (pathway a). However, when R% is
an alkyl group, the steric interaction A is stronger than
B, and the complex 9b becomes more stable than 9a,
giving the product with R configuration (pathway b). In
the case of ligand 2g, the bulk tert-butyl on the oxazo-
line ring decreased the difference between the steric
interactions A and B, leading to a lower enantio-
selectivity.
3.2.1. Synthesis of ethyl
2-methyl-8-quinolinecarboxylate (4a)
3.2.1.1. General procedure. A mixture of 2-methyl-8-
quinolinecarboxylic acid (3a) (2.0 g, 10.7 mmol), anhy-
drous EtOH (35 ml) and concentrated sulfuric acid (0.8
ml) was heated under reflux for 3 days. After the
solvent was evaporated under reduced pressure, the
residue was dissolved in CHCl3 (50 ml) and washed
with saturated NaHCO3 (3×20 ml) and brine. The
organic phase was dried over Na2SO4 and concentrated
under reduced pressure to give 1.86 g (8.65 mmol, 81%)
of 4a as a pale orange solid, which was used directly for
the next step without further purification. M.p. 56–
1
58 °C. H-NMR (CDCl3, 200 MHz): l 8.00 (d, J=8.4
Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.83 (d, J=7.3 Hz,
1H), 7.44 (t, J=7.8 Hz, 1H), 7.26 (d, J=8.7 Hz, 1H),
4.49 (q, J=7.1 Hz, 2H), 2.72 (s, 3H), 1.42 (t, J=7.2
Hz, 3H). TLC (PE–EtOAc=2:1): Rf=0.50.
In conclusion, 2-alkyl-quinolinyl-oxazoline ligands
have been synthesized, and the substituents on position
2 of the quinoline ring can tune the configuration of
product in the palladium-catalyzed alkylation reaction,
which could be explained by a late transition state.
3.2.2. Synthesis of ethyl 2-butyl-8-quinolinecarboxylate
(4b)
Pale yellow oil, 70% yield. 1H-NMR (CDCl3, 300
MHz): l 8.03 (d, J=8.4 Hz, 1H), 8.00–7.80 (m, 2H),
7.48 (t, J=8.1 Hz, 1H), 7.30 (d, J=9.0 Hz, 1H), 4.51
(q, J=7.2 Hz, 2H), 2.96 (t, J=7.8 Hz, 2H), 1.95–1.75
(m, 2H), 1.60–1.35 (m, 5H), 0.96 (t, J=7.8 Hz, 3H).
TLC (PE–EtOAc=6:1): Rf=0.55.
3. Experimental
3.1. General
Dichloromethane was distilled from CaH2. Chloro-
form was distilled from anhydrous CaSO4. The 2-alkyl-
8-quinolinylcarboxylic acids were prepared according to
the Doebner–Miller method [13]. All optically pure
amino alcohols were prepared by reduction of the
corresponding commercially available amino acids with
NaBH4/H2SO4 in THF [14]. IR (film): selected bands in
3.2.3. Synthesis of ethyl
2-isobutyl-8-quinolinecarboxylate (4c)
Pale yellow oil, 81% yield. 1H-NMR (CDCl3, 300
MHz): l 8.03 (d, J=7.8 Hz, 1H), 7.91 (d, J=7.2 Hz,
1H), 7.85 (d, J=7.5 Hz, 1H), 7.46 (t, J=7.8 Hz, 1H),
7.27 (d, J=7.2 Hz, 1H), 4.51 (q, J=7.2 Hz, 2H), 2.84
(d, J=6.9 Hz, 2H), 2.38–2.20 (m, 1H), 1.44 (t, J=7.2
Hz, 3H), 0.97 (d, J=6.9 Hz, 6H). TLC (PE–EtOAc=
6:1): Rf=0.55.
1
cm−1. H-NMR (CDCl3, 200 or 300 Hz): l in ppm
(TMS), J in Hz. EIMS: selected peaks, m/z (%).

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X.-G. Li et al. / Journal of Organometallic Chemistry 640 (2001) 65–71
3.3. Synthesis of 2-alkyl-8-quinolinecarboxamides 5
Hz, 1H), 8.79 (d, J=6.3 Hz, 1H), 8.14 (d, J=8.5 Hz,
1H), 7.91 (d, J=5.2 Hz, 1H), 7.60–7.24 (m, 7H),
5.55–5.30 (m, 1H), 4.20–4.00 (m, 2H), 3.90–3.70 (m,
1H), 2.65 (s, 3H). EIMS: 276 (20), 275 (48), 171 (13),
170 (100), 143 (22), 142 (13), 115 (23). TLC (PE–
EtOAc=1:1): Rf=0.40. Anal. Calc. for C19H18N2O2:
C, 74.49; H, 5.92; N, 9.14. Found: C, 73.98; H, 5.52; N,
9.14%.
3.3.1. (1%S)-N-(1%-Benzyl-2%-hydroxyethyl)-2-
methyl-8-quinolinecarboxamide (5a)
3.3.1.1. General procedure. A mixture of ethyl 2-methyl-
8-quinolinecarboxylate (4a) (3.01 g, 14 mmol), L-pheny-
lalaninol (2.75 g, 18.2 mmol) and KCN (303 mg, 4.67
mmol) in toluene (50 ml) was heated under reflux until
the ester disappeared. After cooling to room tempera-
ture (r.t.), water (20 ml) was added. The organic layer
was separated, and the aqueous layer was extracted
with chloroform (2×30 ml). The combined organic
layer was washed with brine and dried over anhydrous
Na2SO4. After filtration and concentration under re-
duced pressure, the crude product was purified by flash
column chromatography on silica gel with PE–EtOAc
(1:2) to give 3.94 g (12.3 mmol, 88%) of 5a as a white
solid. M.p. 96–98 °C. [h]2D0 −142.0 (c 0.4, EtOH). IR:
3355m, 3158w, 3064w, 2940m, 2875w, 1952w, 1883w,
1732w, 1631s, 1563s, 1496w, 1384m, 1358m, 1278w,
3.3.4. (1%S)-N-(1%-tert-Butyl-2%-hydroxyethyl)-2-
methyl-8-quinolinecarboxamide (5d)
White solid, 72% yield. M.p. 138–139.5 °C. [h]D20
−10.8 (c 0.4, EtOH). IR: 3354m, 3165w, 3035w,
2962w, 2919w, 2868w, 1947w, 1908w, 1869w, 1777w,
1639s, 1590m, 1563s, 1431m, 1394w, 1369m, 1221w,
1
1084m. H-NMR (CDCl3, 200 Hz): l 11.83 (d, J=6.3
Hz, 1H), 8.80 (d, J=7.3 Hz, 1H), 8.16 (d, J=8.5 Hz,
1H), 7.92 (d, J=8.4 Hz, 1H), 7.60 (t, J=7.3 Hz, 1H),
7.36 (d, J=8.4 Hz, 1H), 4.20–3.90 (m, 2H), 3.80–3.60
(m, 2H), 2.77 (s, 3H), 1.14 (s, 9H). EIMS: 256 (9), 255
(32), 229 (48), 211 (6), 171 (19), 170 (100), 143 (24), 142
(17), 115 (28). TLC (PE–EtOAc=1:1): Rf=0.40.
Anal. Calc. for C17H22N2O2: C, 71.30; H, 7.74; N, 9.78.
Found: C, 70.77; H, 7.61; N, 9.70%.
1
1235w, 1078m, 1037m. H-NMR (CDCl3, 200 Hz): l
11.87 (d, J=6.7 Hz, 1H), 8.74 (d, J=7.3 Hz, 1H), 8.10
(d, J=8.5 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.55 (t,
J=7.8 Hz, 1H), 7.32–7.15 (m, 6H), 4.60–4.40 (m, 1H),
3.90–3.70 (m, 2H), 3.39 (broad, 1H), 3.20–3.05 (m,
2H), 2.64 (s, 3H). EIMS: 320 (1, M+), 289 (13), 230
(15), 229 (75), 211 (9), 171 (25), 170 (100), 143 (28), 115
(39), 91 (10). TLC (PE–EtOAc=1:2): Rf=0.49. Anal.
Calc. for C20H20N2O2: C, 74.98; H, 6.29; N, 8.74.
Found: C, 74.78; H, 6.76; N, 8.99%.
3.3.5. (1%S)-N-(1%-Benzyl-2%-hydroxyethyl)-2-
butyl-8-quinolinecarboxamide (5e)
White solid, 73% yield. M.p. 114–117 °C. [h]D20
−115.8 (c 0.4, EtOH). IR: 3352m, 3151w, 3027w,
2955w, 2926w, 2860w, 1953w, 1911w, 1743w, 1627s,
1588m, 1563s, 1539s, 1496m, 1360m, 1135m, 1093m,
1
1046m. H-NMR (CDCl3, 300 Hz): l 11.97 (d, J=6.6
3.3.2. (1%S)-N-(1%-Isopropyl-2%-hydroxyethyl)-2-
methyl-8-quinolinecarboxamide (5b)
Hz, 1H), 8.80 (dd, J=7.2 and 1.5 Hz, 1H), 8.16 (d,
J=8.4 Hz, 1H), 7.92 (dd, J=8.1 and 1.5 Hz, 1H), 7.61
(t, J=7.8 Hz, 1H), 7.37–7.18 (m, 6H), 4.65–4.50 (m,
1H), 4.00–3.80 (m, 2H), 3.80–3.65 (m, 1H), 3.30–3.05
(m, 2H), 2.94 (t, J=7.8 Hz, 2H), 1.90–1.70 (m, 2H),
1.50–1.30 (m, 2H), 0.97 (t, J=7.5 Hz, 3H). EIMS: 362
(1, M+) 331 (21), 271 (87), 253 (9), 213 (26), 212 (100),
185 (7), 169 (8), 142 (10), 115 (19), 91 (11). TLC
(PE–EtOAc=1:1): Rf=0.40. Anal. Calc. for
C23H26N2O2: C, 76.21; H, 7.23; N, 7.73. Found: C,
75.86; H, 7.25; N, 7.70%.
White solid, 56% yield. M.p. 115–117 °C. [h]D20
−21.0 (c 0.4, EtOH). IR: 3345m, 3180w, 3035w,
2958w, 2926w, 2875w, 1953w, 1911w, 1864w, 1644s,
1617m, 1594m, 1548s, 1460m, 1386w, 1369m, 1285m,
1
1080m. H-NMR (CDCl3, 200 Hz): l 11.78 (d, J=6.3
Hz, 1H), 8.78 (d, J=7.3 Hz, 1H), 8.16 (d, J=8.4 Hz,
1H), 7.91 (d, J=7.3 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H),
7.36 (d, J=8.5 Hz, 1H), 4.25–4.00 (m, 1H), 3.90–3.70
(m, 3H), 2.77 (s, 3H), 2.30–2.10 (m, 1H), 1.13 (d,
J=6.7 Hz, 3H), 1.10 (d, J=6.3 Hz, 3H). EIMS: 241
(35), 170 (100), 143 (26), 142 (16), 115 (39), 43 (18), 41
(17), 31 (27), 27 (13). TLC (PE–EtOAc=1:2): Rf=
0.40. Anal. Calc. for C16H20N2O2: C, 70.56; H, 7.40; N,
10.29. Found: C, 70.70; H, 7.38; N, 10.26%.
3.3.6. (1%S)-N-(1%-Benzyl-2%-hydroxyethyl)-2-
isobutyl-8-quinolinecarboxamide (5f)
White solid, 54% yield. M.p. 129–131 °C. [h]D20
−116.8 (c 0.4, EtOH). IR: 3353m, 3136m, 3013w,
2955m, 2917m, 2866m, 1965w, 1910w, 1869w, 1776w,
1627s, 1563s, 1489m, 1454m, 1358m, 1336m, 1198w,
3.3.3. (1%S)-N-(1%-Phenyl-2%-hydroxyethyl)-2-
1
methyl-8-quinolinecarboxamide (5c)
1136m, 1092m, 1046m. H-NMR (CDCl3, 300 Hz): l
White solid, 60% yield. M.p. 149–150 °C. [h]D20
−147.5 (c 0.4, EtOH). IR: 3372m, 3209w, 3027w,
2998w, 2926w, 2875w, 1950w, 1870w, 1732w, 1643s,
1605m, 1594m, 1546s, 1489m, 1455m, 1431m, 1278w,
11.97 (d, J=6.6 Hz, 1H), 8.80 (d, J=7.2 Hz, 1H), 8.16
(d, J=8.4 Hz, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.61 (t,
J=7.8 Hz, 1H), 7.37–7.18 (m, 6H), 4.60–4.45 (m, 1H),
3.90 (d, J=11.1 Hz, 1H), 3.77 (d, J=4.8 Hz, 1H),
3.20–3.00 (m, 3H), 2.77 (d, J=6.9 Hz, 2H), 2.20–2.00
1
1070m. H-NMR (CDCl3, 200 Hz): l 12.46 (d, J=5.2

X.-G. Li et al. / Journal of Organometallic Chemistry 640 (2001) 65–71
69
(m, 1H), 0.95 (d, J=6.6 Hz, 6H). EIMS: 362 (0.7,
M+), 331 (11), 271 (73), 213 (22), 212 (100), 185 (16),
169 (20), 142 (22), 115 (24), 91 (35). TLC (PE–
EtOAc=1:1): Rf=0.57. Anal. Calc. for C23H26N2O2:
C, 76.21; H, 7.23; N, 7.73. Found: C, 76.35; H, 7.06; N,
7.53%.
EIMS: 302 (2, M+), 301 (2, M−1), 212 (32), 211 (100),
182 (18), 170 (9), 156 (50), 115 (18), 91 (12). TLC
(PE–EtOAc=1:2): Rf=0.30. Anal. Calc. for
C20H18N2O: C, 79.44; H, 6.00; N, 9.26. Found: C,
78.78; H, 6.30; N, 9.26%.
3.4.2. (4S)-4,5-Dihydro-2-(2%-methyl-8%-quinolinyl)-4-
isopropyloxazole (2b)
3.3.7. (1%S)-N-(1%-tert-Butyl-2%-hydroxyethyl)-2-
isobutyl-8-quinolinecarboxamide (5g)
Orange yellow oil, 81% yield. [h]2D0 −83.5 (c 0.8,
EtOH). IR: 3050w, 2958s, 2926m, 2900m, 2872m,
2721w, 1942w, 1898w, 1830w, 1667s, 1614s, 1600s,
1570m, 1500s, 1465m, 1384w, 1357s, 1326m, 1188s,
1129s, 1024s. 1H-NMR (CDCl3, 200 Hz): l 7.97 (d,
J=8.7 Hz, 1H), 7.94 (d, J=7.3 Hz, 1H), 7.82 (d,
J=8.3 Hz, 1H), 7.45 (t, J=7.3 Hz, 1H), 7.24 (d,
J=8.4 Hz, 1H), 4.60–4.40 (m, 1H), 4.40–4.15 (m, 2H),
2.69 (s, 3H), 2.05–1.90 (m, 1H), 1.07 (d, J=7.0 Hz,
3H), 1.01 (d, J=7.1 Hz, 3H). EIMS: 255 (1, M+1),
254 (5, M+), 212 (15), 211 (100), 183 (11), 182 (10), 170
(13), 156 (53), 115 (19), 43(19), 41(25). TLC (PE–
EtOAc=1:1): Rf=0.40. Anal. Calc. for C16H18N2O: C,
75.79; H, 7.13; N, 11.01. Found: C, 75.15; H, 7.43; N,
10.64%.
White solid, 51% yield. M.p. 114–116 °C. [h]D20
−31.3 (c 0.4, EtOH). IR: 3317m, 3158m, 3027w,
2958m, 2911w, 2875w, 1961w, 1917w, 1872w, 1637s,
1591m, 1567s, 1543s, 1460m, 1393w, 1382w, 1362m,
1
1220w, 1084s. H-NMR (CDCl3, 300 Hz): l 11.62 (s,
1H), 8.94 (s, 1H), 8.27 (d, J=7.5 Hz, 1H), 7.98 (d,
J=8.1 Hz, 1H), 7.68 (t, J=7.8 Hz, 1H), 7.41 (d,
J=8.1 Hz, 1H), 4.65–4.45 (m, 1H), 4.28–4.10 (m, 1H),
4.05 (dd, J=10.8 and 2.4 Hz, 1H), 3.80 (t, J=9.6 Hz,
1H), 2.91 (d, J=6.9 Hz, 2H), 2.30–2.10 (m, 1H), 1.14
(s, 9H), 0.99 (t, J=7.5 Hz, 6H). EIMS: 298 (15), 297
(47), 271 (67), 213 (28), 212 (100), 185 (27), 169 (24),
142 (22), 115 (25), 41 (12). TLC (PE–EtOAc=1:1):
Rf=0.40. Anal. Calc. for C20H28N2O2: C, 73.13; H,
8.59; N, 8.53. Found: C, 72.33; H, 8.38; N, 8.24%.
3.4.3. (4S)-4,5-Dihydro-2-(2%-methyl-8%-quinolinyl)-4-
phenyloxazole (2c)
3.4. Synthesis of 2-alkyl-8-quinolinyl-oxazoline
ligands 2
Orange yellow oil, 80% yield. [h]2D0 −71.5 (c 0.8,
EtOH). IR: 3054w, 3028w, 2964w, 2917w, 1952w,
1891w, 1822w, 1733w, 1667s, 1614s, 1600s, 1571m,
1498s, 1472w, 1453m, 1433m, 1356s, 1324m, 1185s,
1130s, 1022s. 1H-NMR (CDCl3, 300 Hz): l 8.07 (t,
J=8.7 Hz, 1H), 8.06 (dd, J=7.5 and 1.5 Hz, 1H), 7.90
(dd, J=8.4 and 1.5 Hz, 1H), 7.64–7.56 (m, 2H), 7.52
(t, J=7.8 Hz, 1H), 5.53 (dd, J=10.2 and 7.5 Hz, 1H),
4.94 (dd, J=9.9 and 8.1 Hz, 1H), 4.45 (t, J=7.8 Hz,
1H), 2.82 (s, 3H). EIMS: 289 (8, M+1), 288 (43, M+),
287 (6, M−1), 258 (58), 257 (44), 184 (65), 170 (100),
115 (17), 91 (41), 89 (34). TLC (PE–EtOAc=1:1):
Rf=0.50.
3.4.1. (4S)-4,5-Dihydro-2-(2%-methyl-8%-quinolinyl)-4-
benzyloxazole (2a)
3.4.1.1. General procedure. To a mixture of 5a (3.2 g, 10
mmol), 4-dimethylaminopyridine (50 mg, 0.4 mmol)
and Et3N (5.39 ml, 39.1 mmol) in CH2Cl2 (85 ml) was
added methanesulfonyl chloride (4.44 g, 3 ml, 38.7
mmol) at −5 to 0 °C, and the solution was stirred for
40 min at this temperature. Another portion of Et3N
(24.54 ml, 175.6 mmol) was added to the solution, and
it was refluxed until the initially formed mesylate disap-
peared (checked by TLC). After cooling to r.t., the
reaction mixture was diluted with CHCl3 and washed
with saturated NaHCO3 solution. The organic layer
was dried over anhydrous NaSO4. After filtration and
concentration under reduced pressure, the crude
product was purified by flash chromatography on silica
gel (elution with PE–EtOAc=1:2) to give 2.68 g (8.87
mmol, 88%) of 2a as a pale yellow solid. M.p. 101–
102 °C. [h]2D0 −8.0 (c 0.8, EtOH). IR: 3020w, 2970w,
2926w, 1947w, 1901w, 1729w, 1671s, 1606m, 1598s,
1569m, 1493m, 1431w, 1355m, 1255m, 1189m, 1129m,
3.4.4. (4S)-4,5-Dihydro-2-(2%-methyl-8%-quinolinyl)-4-
tert-butyloxazole (2d)
Pale purple oil, 80% yield. [h]2D0 −114.3 (c 0.8,
EtOH). IR: 3054w, 2955w, 2897w, 2860w, 1947w,
1905w, 1840w, 1670s, 1614m, 1598m, 1564m, 1497m,
1392w, 1360m, 1292m, 1256m, 1185m, 1129m. 1H-
NMR (CDCl3, 300 Hz): l 8.02 (d, J=8.7 Hz, 1H), 7.95
(dd, J=7.2 and 1.5 Hz, 1H), 7.84 (dd, J=8.1 and 1.8
Hz, 1H), 7.47 (dd, J=8.1 and 7.2 Hz, 1H), 7.28 (d,
J=8.1 Hz, 1H), 4.51 (dd, J=10.5 and 8.7 Hz, 1H),
4.39 (t, J=8.1 Hz, 1H), 4.19 (dd, J=10.2 and 7.8 Hz,
1H), 2.73 (s, 3H), 1.08 (s, 9H). EIMS: 269 (1, M+1),
268 (3, M+), 211 (100), 170 (13), 156 (36), 115 (14), 41
(24), 29 (27). TLC (PE–EtOAc=1:1): Rf=0.50. Anal.
Calc. for C17H20N2O: C, 76.08; H, 7.51; N, 10.43.
Found: C, 75.69; H, 7.78; N, 9.68%.
1
1020m. H-NMR (CDCl3, 300 Hz): l 8.04 (d, J=8.6
Hz, 1H), 8.01 (d, J=7.8 Hz, 1H), 7.86 (d, J=8.1 Hz,
1H), 7.49 (t, J=7.8 Hz, 1H), 7.35–7.24 (m, 6H),
4.80–4.65 (m, 1H), 4.50 (dd, J=9.4 and 8.3 Hz, 1H),
4.26 (t, J=7.8 Hz, 1H), 3.34 (dd, J=13.6 and 5.2 Hz,
1H), 2.90 (dd, J=13.6 and 8.4 Hz, 1H), 2.76 (s, 3H).

70
X.-G. Li et al. / Journal of Organometallic Chemistry 640 (2001) 65–71
3.4.5. (4S)-4,5-Dihydro-2-(2%-butyl-8%-quinolinyl)-4-
benzyloxazole (2e)
3.5. Allylic alkylation of 1,3-diphenyl-2-propenyl
acetate with dimethyl malonate
Orange yellow oil, 78% yield. [h]2D0 −22.6 (c 0.8,
EtOH). IR: 3058w, 2955s, 2928s, 2870m, 2859m,
1946w, 1887w, 1810w, 1658s, 1612s, 1600s, 1570m,
1498s, 1464m, 1454m, 1358s, 1181m, 1129s, 1005m.
1H-NMR (CDCl3, 200 Hz): l 8.02 (d, J=8.6 Hz, 1H),
7.93 (dd, J=7.7 Hz, 1H), 7.81 (t, J=8.3 Hz, 1H), 7.45
(t, J=7.2 Hz, 1H), 7.35–7.23 (m, 6H), 4.80–4.60 (m,
1H), 4.48 (t, J=8.9 Hz, 1H), 4.26 (t, J=7.8 Hz, 1H),
3.33 (dd, J=13.6 and 5.2 Hz, 1H), 3.05–2.90 (m, 3H),
1.95–1.70 (m, 2H), 1.45–1.25 (m, 2H), 0.95 (t, J=7.2
Hz, 3H). EIMS: 344 (1, M+), 343 (0.8, M−1), 302
(16), 254 (24), 253 (100), 181 (11), 168 (14), 156 (16), 91
(47). TLC (PE–EtOAc=1:1): Rf=0.60. Anal. Calc.
for C23H24N2O: C, 79.48; H, 7.02; N, 8.13. Found: C,
79.48; H, 7.54; N, 7.85%.
3.5.1. General procedure
[Pd (h3-C3H5) Cl]2 (4 mg, 2.5 mol%) and the ligand
(0.04 mmol, 10 mol%) were added into a Shlenck tube
containing 2 ml CH2Cl2 under nitrogen and the mixture
was stirred at 25 °C for 30 min. To this solution,
rac-(E)-1,3-diphenyl-2-propenyl acetate (0.4 mmol,
100.8 mg) in 2 ml CH2Cl2, CH2(CO2Me)2 (0.14 ml, 1.2
mmol), BSA (0.3 ml, 1.2 mmol) and KOAc (1.4 mg, 3.5
mol%) were added successively. The resulting mixture
was stirred at 25 °C for an appropriate time. After the
reaction was completed (determined by TLC), the reac-
tion mixture was diluted with ether (25 ml) and washed
with ice-cold saturated aqueous ammonium chloride.
The organic phase was dried over anhydrous Na2SO4
and concentrated under reduced pressure. The crude
product was purified by flash chromatography (PE–
EtOAc=6:1) to give dimethyl 1,3-diphenyl-2-propenyl-
malonate. The enantiomeric excess was determined by
HPLC with DAICEL Chiracel OD (hexane–2-
propanol=99:1).
3.4.6. (4S)-4,5-Dihydro-2-(2%-isobutyl-8%-quinolinyl)-4-
benzyloxazole (2f)
Orange yellow oil, 54% yield. [h]2D0 −27.3 (c 0.8,
EtOH). IR: 3058w, 3026w, 2954s, 2928m, 2895m,
2867m, 1946w, 1884w, 1814w, 1658s, 1612m, 1600m,
1570m, 1498s, 1464m, 1454m, 1384w, 1359m, 1183m,
1
1130m, 1005m. H-NMR (CDCl3, 300 Hz): l 8.04 (d,
Acknowledgements
J=8.4 Hz, 1H), 7.95 (dd, J=7.2 and 1.2 Hz, 1H), 7.86
(dd, J=8.1 and 1.2 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H),
7.35–7.24 (m, 6 H), 4.850–4.65 (m, 1 H), 4.50 (t,
J=9.0 Hz, 1H), 4.28 (t, J=7.8 Hz, 1H), 3.33 (dd,
J=13.8 and 5.1 Hz, 1H), 2.95–2.85 (m, 3H), 2.40–2.20
(m, 1H), 1.01 (d, J=6.9 Hz, 6H). EIMS: 345 (1,
M+1), 344 (4, M+), 343 (2, M−1), 302 (26), 254 (35),
253 (100), 225 (16), 198 (24), 181 (16), 168 (25), 115
(10), 91 (27). TLC (PE–EtOAc=1:1): Rf=0.40. Anal.
Calc. for C23H24N2O: C, 79.48; H, 7.02; N, 8.13.
Found: C, 78.64; H, 7.03; N, 7.77%.
Financial supports from the National Natural Sci-
ence Foundation of China, the Major State Basic
Research
Development
Program
(grant
No.
G2000077506), the Education Department of China
and the Tianjin Municipal Committee of Science and
Technology are gratefully acknowledged.
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EtOH). IR: 3049w, 2954s, 2902m, 2868s, 1935w, 1884w,
1826w, 1667s, 1613m, 1599m, 1572w, 1499s, 1478m,
1464m, 1393w, 1384w, 1356s, 1183m, 1129m, 1013s.
1H-NMR (CDCl3, 300 Hz): l 8.02 (d, J=8.7 Hz, 1H),
7.92 (dd, J=6.9 and 1.5 Hz, 1H), 7.84 (dd, J=8.1 and
1.5 Hz, 1H), 7.46 (dd, J=8.4 and 7.5 Hz, 1H), 7.25 (d,
J=8.4 Hz, 1H), 4.48 (dd, J=10.2 and 8.7 Hz, 1H),
4.38 (t, J=8.4 Hz, 1H), 4.17 (dd, J=10.2 and 7.8 Hz,
1H), 2.82 (d, J=7.2 Hz, 2H), 2.35–2.15 (m, 1H), 1.06
(d, J=4.8 Hz, 9H), 0.95 (d, J=6.9 Hz, 3H), 0.94 (d,
J=6.9 Hz, 3H). EIMS: 311(1, M+1), 310 (6, M+),
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168 (14), 156 (11), 41 (9). TLC (PE–EtOAc=1:1):
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