Asymmetric reduction of 2-chloro-3-oxo esters by transfer hydrogenation

Article abstract of DOI:10.1002/cjoc.201180419

Asymmetric reduction of 2-chloro-3-oxo esters was achieved by catalytic transfer hydrogenation using [RuCl₂(p-cymene)](S,S)-TsDPEN as the chiral catalyst and HCOOH-Et₃N as the hydrogen source. Moderate to good yields (up to 85%) and

Full text of DOI:10.1002/cjoc.201180419

FULL PAPER
Asymmetric Reduction of 2-Chloro-3-oxo Esters by Transfer
Hydrogenation
Bai, Jinjin(白进进)
Miao, Shifeng(缪世峰)
Wu, Yun(吴云)
Zhang, Yawen*(张雅文)
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Mate-
rials Science, Soochow University, Suzhou, Jiangsu 215123, China
Asymmetric reduction of 2-chloro-3-oxo esters was achieved by catalytic transfer hydrogenation using
[RuCl2(p-cymene)](S,S)-TsDPEN as the chiral catalyst and HCOOH-Et3N as the hydrogen source. Moderate to
good yields (up to 85%) and good enantioselectivities (up to 98% ee) were obtained.
Keywords asymmetric catalysis, transfer, hydrogenation, 2-chloro-3-oxo esters, ruthenium
Introduction
3-phenyl-propanoate 1a as a research mode. We first
investigated the effects of the solvent on the reaction.
As shown by the data listed in Table 1, it can be seen
that the reaction proceeded well in various kinds of sol-
vents, providing the desired product in moder-
ate-to-good yield with about 90% ee for the major di-
astereomer, except in methanol, when ester exchange
Optically active 2-chroro-3-hydroxy esters are an
extremely important class of compounds in modern or-
ganic synthetic chemistry.1 They can be converted into a
variety of synthons or key intermediates for the prepara-
tion of many biologically active products such as Dilti-
azem,2,3 Taxol4 which are the most exciting compounds
in cancer chemotherapy and 2,3-epoxyesters5-9 that are
another kind of key intermediates for synthesizing other
drugs and natural products as well. In addition, they can
be converted into α-amino-β-hydroxy acids with a direct
nucleophilic substitution of the chlorine atom.10-12 Now
many methods have been developed for the enantioslec-
tive synthesis of them, including hydride reduction,13
catalytic hydrogenation14,3 or biocatalytic reduc-
tions1,15,16 of the corresponding 2-chloro-3-oxo esters,
nitrous halogeno-deamination of natural α-amino-β-
hydroxy acids,17,18 and so on.
Table 1 Influence of the solvent on ATH of 1aa
Asymmetric transfer hydrogenation (ATH) is a mild
methodology for the catalytic asymmetric reduction of
C＝ O or C＝ N double bonds.19-22 In recent years, be-
cause of the operational simplicity and the easy avail-
ability of hydrogen source, hydrogen transfer reduction
has gained a prominent position. Its importance is gen-
erally considered just behind asymmetric hydrogenation
with molecular hydrogen.23,24
To the best of our knowledge, however, no paper has
ever been reported on the asymmetric synthesis of
2-chroro-3-hydroxy esters via ATH reaction to date.
Herein, we report the asymmetric synthesis of these
important compounds using asymmetric transfer hydro-
genation reaction of 2-chloro-3-oxo esters.
Entry Solvent
S/C Yieldb/% drc/%
eec/% major
1
2
3
4
5
6
7
8
9
THF
80
80
80
80
80
80
80
80
82
79
79
70
89
81
50
88
72
66∶ 34
72∶ 28
64∶ 36
71∶ 29
72∶ 28
65∶ 35
54∶ 46
62∶ 38
71∶ 29
89
92
92
86
86
82
85
90
91
(iPr)2O
Toluene
CH2Cl2
DMF
CH3CN
CH3OH
EtOH
Slovent-free 80
a All the reactions were processed under argon at room tempera-
ture for 12 h. b Isolated yields after column chromatography. c The
enantiomeric excess and diastereomeric ratio were determined by
chiral HPLC analysis on a Chiralcel OJ-H column.
Results and discussion
We chose the reduction of ethyl 2-chloro-3-oxo-
*
E-mail: zhangyw@suda.edu.cn; Tel.: 0086-0512-65880340; Fax: 0086-0512-65880305
Received April 17, 2011; revised July 26, 2011; accepted August 15, 2011.
2476
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2476— 2480

Asymmetric Reduction of 2-Chloro-3-oxo Esters by Transfer Hydrogenation
occurred which resulted in lower yield (50%), and very
poor dr was found (Entry 7). The reaction can also pro-
ceed under solvent-free conditions (Entry 9). Taking
consideration of easy work up and the solvent effects on
both dr and ee, methylene chloride was chosen as the
solvent in the subsequent investigation. The influence of
the catalyst/substrate ratio on the reduction was exam-
ined in methylene chloride at room temperature (Table
2). The best results were obtained when a S/C＝ 80 was
employed, although the catalyst loading effect was
found not very significant.
Table 3 Transfer hydrogention of various 2-chloro-3-oxo-
estersa
Table 2 Influence of the S/C ratio on ATH of 1aa
eec/%
major
Entry R1
R2 Product Yieldb/%
drc/%
Entry
S/C T/h
Yielda/%
drb/% eeb/% major
1
2
3
4
40
80
10
12
15
15
96
70
70
78
65∶ 35
71∶ 29
65∶ 35
60∶ 40
83
86
87
86
1
C6H5
Et
p-MeOC6H4 Et
p-MeOC6H4 Me
2a
2b
2c
2d
2e
2f
70
77
65
78
80
62
50
75
70
80
85
85
71∶ 29
67∶ 33
82∶ 18
52∶ 48
66∶ 34
74∶ 26
67∶ 33
51∶ 49
76∶ 24
59∶ 41
78∶ 22
88∶ 12
86
86
90
76
69
77
59
82
91
83
93
98
2
120
160
3
4
p-FC6H4
Et
Et
a
b
Isolated yield. The enantiomeric excess and diastereomeric
ratio were determined by chiral HPLC analysis on a Chiralcel
OJ-H column.
5
p-BrC6H4
6
2,4-Cl2C6H3 Et
7
o-MeC6H4
m-MeC6H4
1-Naphthyl
2-Naphthyl
2-Furyl
Et
Et
Et
Et
Et
2g
2h
2i
8
With the optimized reaction conditions in hand, the
scope of substrates was investigated, as shown in Table
3. Data showed that (1) for R1＝ substituted phenyl
group, halogen atom at para-position accelerates the
reaction and make the reaction less selective (Entries 4
and 5); (2) ortho-substitution decreases the yield and
enantioselectivity (Entry 7); (3) replacement of the
benzene ring with a 2-furyl or 2-thiophenyl group im-
proves the yield and the selectivity significantly (Entries
11 and 12).
9
10
11
2j
2k
2l
12
a
2-thiophenyl Et
All the reactions were processed under argon at room tempera-
b
c
ture for 12 h. Isolated yield. The enantiomeric excess and di-
astereomeric ratio were determined by chiral HPLC analysis on a
Chiralcel IA , OD-H or OJ-H column.
In summary, we have demonstrated a new stereose-
lective approach to 2-chroro-3-hydroxy esters. The
asymmetric transfer hydrogenation of the corresponding
2-chroro-3-oxo-esters by using Noyori’s Ru(cymene)-
TsDPEN catalyst and HCOOH-Et3N as the hydrogen
source selectively affords the desired compounds for a
variety of substrates. The desired 2-chroro-3-hydroxy
esters were obtained in moderate to good yields (up to
85%) and enantio-selectivities (up to 98% ee, 88∶ 12
dr).
mobile phase at a flow rate of 1 cm3•min－ 1 on a Waters
1525 HPLC instrument and a waters 2996 Photodiode
Array Detector. Optical rotations were measured with
an Autopol IV automatic polarimeter. IR spectra were
recorded on a Varian 1000 FT-IR Spectrometer.
General procedure of asymmetric transfer hydro-
genation of 2-chloro-3-oxo esters
A suspension of [RuCl2(p-cymene)]2 (3.75 mg,
0.00625 mmol) and (1S,2S)-TsDPEN (4.58 mg, 0.0125
mmol) in CH2Cl2 (0.5 mL) was degassed three times,
and then stirred at room temperature for 2 h. 5∶ 2 (V∶
V) HCOOH-Et3N (0.2 mL) was then added, followed by
addition of 2-chloro-3-oxo ester (0.5 mmol). The
reaction was stirred at room temperature until
completion according to TLC detection. Water (15.0
mL) was added to the reaction, the mixture was then
extracted with EtOAc (10 mL × 3), dried over
anhydrous sodium sulfate and concentrated under
vacuum. After removal of the solvent, the residue was
purified by column chromatography to give the desired
product, which was then characterized.
Experimental
All reactions were carried out under argon and
monitored by thin layer chromatography (TLC). All
2-chloro-3-oxo esters were prepared by optimizing the
previously described methods.25,26 [RuCl2(p-cymene)]2
was prepared following the reported procedure.27 NMR
spectra were recorded in CDCl3 on a Varian Inova-400
or Varian System-300 NMR spectrometer at 400 or 300
1
MHz for H and 100 or 75 MHz for 13C NMR with
TMS as an internal reference. Enantiomeric excess (ee)
and diastereomeric ratio (dr) determination were carried
out using HPLC analysis with a Daicel Chiralcel OD-H,
IA or OJ-H column using hexane/isopropanol as the
Ethyl
2-chloro-3-hydroxy-3-phenylpropanoate
(2a) 70% yield, dr＝ 71∶ 29, ee＝ 86% and 50% for
Chin. J. Chem. 2011, 29, 2476— 2480
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2477

Bai et al.
FULL PAPER
the major and minor diastereomer, respectively, as
detemined by HPLC analysis (Daicel Chiralcel OJ-H
5.4 Hz, 2H), 7.05 (t, J＝ 8.6 Hz, 2H), 5.11 (dd, J＝ 6.1,
2.9 Hz, 1H), 4.39 (d, J＝ 6.5 Hz, 1H), 4.12 (q, J＝ 7.1 Hz,
2H), 3.20 (s, 1H), 1.16 (t, J＝ 7.1 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ: 168.03, 162.87 (d, J＝ 247.3 Hz),
134.08 (d, J＝ 3.1 Hz), 128.64 (d, J＝ 8.3 Hz), 115.53 (d,
J＝ 21.6 Hz), 74.03, 62.83 (d, J＝ 0.8 Hz), 62.46, 13.87.
The minor diastereomer, [α]2D1 26.04 (c 1.1, abs
EtOH). 1H NMR (300 MHz, CDCl3) δ: 7.38 (dd, J＝ 8.4,
5.4 Hz, 2H), 7.06 (t, J＝ 8.6 Hz, 2H), 5.03 (dd, J＝ 7.6,
4.7 Hz, 1H), 4.32 (d, J＝ 7.8 Hz, 1H), 4.25 (q, J＝ 7.1 Hz,
2H), 3.23 (d, J＝ 4.4 Hz, 1H), 1.28 (t, J＝ 7.1 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ: 168.94, 162.91 (d, J＝
247.3 Hz), 134.71 (d, J＝ 3.1 Hz), 128.83 (d, J＝ 8.3 Hz),
115.51 (d, J＝ 21.6 Hz), 74.68, 62.59, 59.32, 14.00.
Ethyl 3-(4-bromophenyl)-2-chloro-3-hydroxy-
propanoate (2e) 80% yield; dr＝ 66∶ 34, ee＝ 69%
and 71% for the major and the minor diastereomer,
respectively, as detemined by HPLC analysis (Daicel
Chiralcel OJ-H column; hexane/i-PrOH＝ 90/10); IR
column; hexane/i-PrOH＝ 90/10, V∶ V); IR (KBr) ν
:
max
－
1
3495, 2984, 2938, 1729, 1456, 1373, 870 cm ; HRMS
(EI) calcd for C11H1335ClO3 228.0553, found 228.0550.
The major diastereomer, [α]2D1 13.4 (c 2.2, abs
1
EtOH). H NMR (300 MHz, CDCl3) δ: 7.49— 7.28 (m,
5H), 5.13 (dd, J＝ 6.2, 3.8 Hz, 1H), 4.45 (d, J＝ 6.4 Hz,
1H), 4.12 (q, J＝ 7.1 Hz, 2H), 3.01 (d, J＝ 3.6 Hz, 1H),
1.14 (t, J＝ 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
168.05, 138.28, 128.74, 128.54, 126.75, 74.67, 63.03,
62.31, 13.80; The minor diastereomer, [α]2D1 15.4 (c
1
1.1, abs EtOH). H NMR (300 MHz, CDCl3) δ: 7.44—
7.30 (m, 5H), 5.04 (dd, J＝ 7.6, 5.0 Hz, 1H), 4.37 (d,
J＝ 7.8 Hz, 1H), 4.24 (q, J＝ 7.1 Hz, 2H), 3.18 (d, J＝
4.9 Hz, 1H), 1.26 (t, J＝ 7.1 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ: 169.01, 138.87, 128.85, 128.62, 127.03,
75.40, 62.50, 59.28, 14.02.
Ethyl 2-chloro-3-hydroxy-3-(4-methoxyphenyl)-pro-
panoate (2b) 77% yield, dr＝ 67∶ 33, ee＝ 86% and
55% for the major and the minor diastereomer,
respectively, as detemined by HPLC analysis (Daicel
Chiralcel OJ-H column; hexane/i-PrOH＝ 90/10, V∶ V);
(KBr) νmax: 3446, 2938, 2983, 2906, 1733, 1594, 1489,
－
1011, 826, 715) cm 1; HRMS (EI) calcd for
C11H10O2ClBr (M－ H2O) 287.9553, found 287.9550.
The major diastereomer, [α]2D1 13.57 (c 0.6, abs
1
IR (KBr) νmax: 3502, 2983, 2938, 2839, 1743, 1613,
EtOH). H NMR (300 MHz, CDCl3) δ: 7.50 (d, J＝ 8.4
－
1516, 1372, 836 cm 1; HRMS (EI) calcd for
Hz, 2H), 7.27 (d, J＝ 8.3 Hz, 2H), 5.12 (d, J＝ 5.7 Hz,
1H), 4.39 (d, J＝ 6.0 Hz, 1H), 4.16 (qd, J＝ 7.1, 1.7 Hz,
2H), 3.12 (s, 1H), 1.19 (t, J＝ 7.1 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ: 168.04, 137.30, 131.81, 128.53, 122.87,
73.95, 62.64, 62.62, 13.98.
Ethyl 2-chloro-3-(2,4-dichlorophenyl)-3-hydroxy-
propanoate (2f) 62% yield; dr＝ 74∶ 26, ee＝ 77%
and 29% for the major and the minor diastereomer,
respectively, as detemined by HPLC analysis (Daicel
Chiralcel OJ-H; column hexane/i-PrOH＝ 95/5, V∶ V);
C12H15ClO4 258.0659, found 258.0659.
The major diastereomer, [α]2D1 10.69 (c 2.0, abs
1
EtOH). H NMR (300 MHz, CDCl3) δ: 7.29 (d, J＝ 8.6
Hz, 2H), 6.87 (d, J＝ 8.7 Hz, 2H), 5.04 (d, J＝ 6.9 Hz,
1H), 4.40 (d, J＝ 6.9 Hz, 1H), 4.10 (dq, J＝ 7.1, 3.7 Hz,
2H), 3.79 (s, 3H), 3.09 (s, 1H), 1.13 (t, J＝ 7.1 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ: 168.00, 159.85, 130.31,
128.09, 113.91, 74.38, 63.00, 62.21, 55.30, 13.84.
Methyl 2-chloro-3-hydroxy-3-(4-methoxyphenyl)-
propanoate (2c) 65% yield; dr＝ 82∶ 18, ee＝ 90%
and 21% for the major and the minor diastereomer,
respectively, as detemined by HPLC analysis (Daicel
Chiralcel OJ-H column; hexane/i-PrOH＝ 70/30, V∶ V);
IR (KBr) νmax: 3517, 3004, 2937, 2956, 2840, 1729,
IR (KBr) νmax: 3509, 3096 , 2984, 2939, 1747, 1591,
－
1472, 869, 825 cm 1; HRMS (EI) calcd for
C11H11O335Cl3: 295.9774, found 295.9775.
The major diastereomer, [α]2D1 31.76 (c 0.6, abs
1
EtOH). H NMR (300 MHz, CDCl3) δ: 7.47 (d, J＝ 8.4
－
1
1613, 1516, 1031, 838 cm ; HRMS (EI) calcd for
C11H1137ClO3 (M－ H2O): 228.0367, found 228.0346.
The major diastereomer, [α]2D1 15.63 (c 2.1, abs
Hz, 1H), 7.41 (d, J＝ 2.0 Hz, 1H), 7.30 (dd, J＝ 8.4, 2.0
Hz, 1H), 5.44 (d, J＝ 3.1 Hz, 1H), 4.59 (d, J＝ 5.8 Hz,
1H), 4.28— 4.05 (m, 2H), 3.52 (s, 1H), 1.21 (t, J＝ 7.1
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ: 168.21, 135.07,
134.96, 133.54, 129.56, 129.19, 127.60, 72.04, 62.64,
57.88, 14.01.
1
EtOH). H NMR (300 MHz, CDCl3) δ: 7.29 (d, J＝ 8.7
Hz, 2H), 6.88 (d, J＝ 8.7 Hz, 2H), 5.06 (d, J＝ 6.6 Hz,
1H), 4.42 (d, J＝ 6.7 Hz, 1H), 3.79 (s, 3H), 3.65 (s, 3H),
3.06 (s, 1H); 13C NMR (101 MHz, CDCl3) δ: 168.51,
159.88, 130.26, 127.98, 114.00, 74.30, 62.87, 55.33,
53.08.
Ethyl 2-chloro-3-(4-fluorophenyl)-3-hydroxy-pro-
panoate (2d) 78% yield; dr＝ 52∶ 48, ee＝ 76% and
69% for the major and minor diastereomer, respectively,
as detemined by HPLC analysis (Daicel Chiralcel IA
Ethyl
2-chloro-3-hydroxy-3-o-tolyl-propanoate
(2g) 50% yield; dr＝ 67∶ 33, ee＝ 59% and 17% for
the major and the minor diastereomer, respectively, as
detemined by HPLC analysis (Chiralcel OD-H column,
hexane/i-PrOH＝ 2/98); IR (KBr) νmax: 3487, 3066,
－
1
2934, 2982, 1829, 1747, 1025, 763 cm ; HRMS (EI)
calcd for C12H13O235Cl (M－ H2O) 224.0604, found
224.0605.
column; hexane/i-PrOH＝ 98/2, V∶ V); IR (KBr) ν
:
max
－
1
3466, 2986, 2940, 2908, 1729, 1606, 1516, 840 cm ;
HRMS (EI) calcd for C11H12O335ClF 246.0459, found
246.0466.
The major diastereomer, [α]2D1 26.2 (c 1.2, abs
1
EtOH). H NMR (300 MHz, CDCl3) δ: 7.51— 7.34 (m,
1H), 7.26— 7.14 (m, 3H), 5.33 (dd, J＝ 7.9, 4.5 Hz, 1H),
4.42 (d, J＝ 8.0 Hz, 1H), 4.26 (q, J＝ 7.1 Hz, 2H), 3.00
(d, J＝ 4.7 Hz, 1H), 2.43 (s, 3H), 1.28 (t, J＝ 7.1 Hz, 3H);
The major diastereomer, [α]2D1 19.7 (c 0.7, abs
EtOH). 1H NMR (300 MHz, CDCl3) δ: 7.36 (dd, J＝ 8.4,
2478
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2476— 2480

Asymmetric Reduction of 2-Chloro-3-oxo Esters by Transfer Hydrogenation
13C NMR (101 MHz, CDCl3) δ: 169.19, 137.19, 136.28,
130.71, 128.56, 126.50, 125.96, 71.49, 62.48, 58.59,
19.59, 14.01.
for the major and the minor diastereomer, respectively,
as detemined by HPLC analysis (Daicel Chiralcel OJ-H
column, i-PrOH/hexane＝ 10/90, V∶ V); IR (KBr) ν
:
max
Ethyl
2-chloro-3-hydroxy-3-m-tolylpropanoate
3501.7, 2984.8, 2938.9, 1747.2, 1505.6, 1372.9, 1304.7,
1013.3, 743.6, 598.5 cm－ 1; HRMS (EI) calcd for
C9H11O335Cl 218.0346, found 218.0327.
(2h) 75% yield; dr＝ 51∶ 49, ee＝ 59% and 82% for
the major and the minor diastereomer, respectively, as
detemined by HPLC analysis (Chiralcel OD-H column;
hexane/i-PrOH＝ 98/2, V∶ V); IR (KBr) νmax: 3499,
2984, 2924, 1822, 1747, 1609, 1467, 1373, 1178, 959,
The major diastereomer, [α]2D1 － 0.72 (c 2.1, abs
EtOH). 1H NMR (300 MHz, CDCl3) δ: 7.43 (dd, J＝ 1.7,
0.7 Hz, 1H), 6.53 (d, J＝ 3.3 Hz, 1H), 6.40 (dd, J＝ 3.3,
1.8 Hz, 1H), 5.44 (s, 1H), 4.37 (q, J＝ 7.1 Hz, 2H), 3.53
(s, 1H), 1.35 (t, J＝ 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ: 165.47, 149.52, 143.15, 110.87, 110.46,
85.39, 74.33, 64.61, 14.07.
－
1
862 cm ; HRMS (EI) calcd for C12H15O337Cl 242.0710,
found 242.0708.
The major diastereomer, [α]2D1 8.94 (c 1.5, abs
1
EtOH). H NMR (300 MHz, CDCl3) δ: 7.35— 7.02 (m,
Ethyl 2-chloro-3-hydroxy-3-(thiophen-2-yl)-pro-
panoate (2l) 85% yield; dr＝ 88∶ 12, ee＝ 98% and
5% for the major and the minor diastereomer,
respectively, as detemined by HPLC analysis (Daicel
Chiralcel OJ-H column; hexane/i-PrOH＝ 90/10, V∶ V);
IR (KBr) νmax: 3502, 3109, 2984, 1733, 1373, 1179,
4H), 5.08 (d, J＝ 6.4 Hz, 1H), 4.44 (d, J＝ 6.5 Hz, 1H),
4.12 (q, J＝ 7.1 Hz, 2H), 3.05 (s, 1H), 2.35 (s, 3H), 1.14
(t, J＝ 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ:
168.09, 138.32, 138.16, 129.56, 128.50, 127.35, 123.83,
74.71, 63.13, 62.34, 21.51, 13.88.
Ethyl 2-chloro-3-hydroxy-3-(naphthalen-1-yl)-
propanoate (2i) 70% yield; dr＝ 76∶ 24, ee＝ 91%
and 29% for the major and the minor diastereomer,
respectively, as detemined by HPLC analysis (Daicel
Chiralcel OJ-H column, hexane/i-PrOH＝ 90/10, V∶ V);
IR (KBr) νmax: 3479, 3052, 2982, 2937, 1831, 1743,
－
1
1025, 708 cm ; HRMS (EI) calcd for C9H11O335ClS
234.0117, found 234.0116.
The maajor diastereomer, [α]2D1 28.2 (c 2.0, abs
1
EtOH). H NMR (300 MHz, CDCl3) δ: 7.31 (d, J＝ 4.6
Hz, 1H), 7.08— 6.92 (m, 2H), 5.39 (d, J＝ 6.3 Hz, 1H),
4.49 (d, J＝ 6.4 Hz, 1H), 4.16 (q, J＝ 7.1 Hz, 2H), 3.34
(s, 1H), 1.20 (t, J＝ 7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ: 167.75, 141.39, 126.82, 126.06, 125.82,
71.12, 62.57, 29.76, 13.91.
－
1
1598, 1466, 1095, 801, 778 cm ; HRMS (EI) calcd for
C15H15O335Cl 278.0710, found 278.0709.
Diastereomeric mixture, 1H NMR (300 MHz, CDCl3)
δ: 8.12/8.04 (d/d, J＝ 8.2/8.3 Hz, 1H), 7.90— 7.79 (m,
2H), 7.68/7.62 (d/d, J＝ 7.1/7.1 Hz, 1H), 7.58— 7.42 (m,
3H), 5.95/5.81 (t/t, J＝ 4.6/6.0 Hz, 1H), 4.71/4.77 (d/d,
J＝ 5.2/7.1 Hz, 1H), 4.19/4.05 (q/qd, J＝ 7.1/7.1, 2.2 Hz,
2H), 3.53/3.29 (d/d, J＝ 5.2/4.5 Hz, 1H), 1.19/1.05 (t/t,
J＝ 7.1/7.1 Hz, 3H).
Determination of the absolute configuration of the
products
The absolute configuration of the major of 2c was
assigned as (2S,3R), by comparison of its retention time
with the literature data.3 The absolute configurations of
the major diastereomers of 2a, 2b, 2j, 2k, and 2l were
also assigned as (2S,3R) by analogy.
Ethyl
2-chloro-3-hydroxy-3-(naphthalen-2-yl)-
propanoate (2j) 80% yield; dr＝ 59∶ 41; ee＝ 83%
and 55%% for the major and the minor diastereomer,
respectively, as detemined by HPLC analysis (Daicel
Chiralcel OD-H column hexane/i-PrOH＝ 90/10, V∶ V);
IR (KBr) νmax: 3502, 3057, 2982, 2936, 1729, 1508,
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1373, 1162, 1020, 861, 819 cm ; HRMS (EI) calcd for
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Chin. J. Chem. 2011, 29, 2476— 2480