Z.-C. Duan et al. / Tetrahedron: Asymmetry 20 (2009) 588–592
591
was diluted with ether and washed successively with HCl, NaHCO3,
and H2O. The organic layer was dried over Na2SO4, and then the ex-
cess methyl acrylate and solvent was removed. The crude product
was purified by flash chromatography to give the desired product
methyl 2-(1-hydroxybenzyl)acrylate 5a (23.1 g) in 85.1% yield.
Acetyl chloride (4.0 g, 3.72 mL, 52 mmol) was slowly dropped
into a solution of 5a (40 mmol) and pyridine (40 mL) in CH2Cl2
(20 mL), maintained at 0 °C and under nitrogen. After being stirred
overnight at room temperature, the solution was poured into ice-
water and extracted with ether (3 ꢁ 80 mL). The organic phase
was dried, and the solvent was evaporated. The crude product
was purified by column chromatography.
To a solution of the Baylis–Hillman acetate (16 mmol) in anhy-
drous benzene (80 mL) were added (methoxycarbonyl-methy-
lene)triphenylphosphorane (16 mmol) and Pd(OAc)2 (6 mol %)
and the solution was heated at reflux for 10–13 h (monitored by
TLC). After completion of the reaction, H2O (20 mL) was added to
the reaction mixture, which was extracted with EtOAc
(3 ꢁ 100 mL). The combined organic layer was washed with H2O
and brine, dried over anhydrous Na2SO4, concentrated in vacuum
and the crud product was purified by column chromatography.
meric excess was determined by GC or HPLC after purification on
silica gel.
4.4.1. Dimethyl 2-methylglutarate 2
Colorless oil. 92% ee, GC,
c
-DEX-225 column (0.25 mm ꢁ 30 m),
80 °C, t1 = 41.8 min, t2 = 43.6 min. ½a D25
ꢂ
¼ ꢀ8:1 (c 0.64, CHCl3); 1H
NMR (CDCl3): d 3.67–3.68 (m, 6H), 2.49 (m, 1H), 2.32–2.37 (m,
2H), 1.96 (m, 2H), 1.16–1.19 (m, 3H).
4.4.2. Dimethyl 2-benzylglutarate 7a
Colorless oil. 76% ee, HPLC (UV 260 nm, Chiralcel OJ-H
(0.46 cm ꢁ 25 cm), i-PrOH/hexane = 3/97, 1 mL/min), t1 = 16.7 min,
t2 = 18.7 min. ½a 2D0
ꢂ
¼ ꢀ4:8 (c 1.02, CHCl3); 1H NMR (400 MHz,
CDCl3): d 7.13–7.28 (m, 5H), 3.64 (s, 3H), 3.59 (s, 3H), 2.94–2.97
(m, 1H), 2.73–2.78 (m, 2H), 2.29–2.36 (m, 2H), 1.84–1.93 (m, 2H).
13C NMR (100 MHz, CDCl3): d 175.3, 173.2, 138.8, 128.9, 128.5,
126.5, 51.6, 51.6, 46.7, 38.4, 31.7, 26.8. HRMS (EI): calcd for
C14H18O4 [M+] 250.1205, found 250.1210.
4.4.3. Dimethyl 2-(4-chlorobenzyl)glutarate 7b
Colorless oil. 75% ee, HPLC (UV 260 nm, Chiralcel OJ-H
(0.46 cm ꢁ 25 cm), i-PrOH/hexane = 1/99, 0.8 mL/min), t1 = 37.6
min, t2 = 39.0 min. ½a D20
ꢂ
¼ ꢀ8:5 (c 1.18, CHCl3); 1H NMR (400 MHz,
4.3.1. Dimethyl (E)-2-benzylideneglutarate 4a
Colorless oil. 1H NMR (400 MHz, CDCl3): d 7.74 (s, 1H), 7.32–
7.39 (m, 5H), 3.81 (s, 3H), 3.64 (s, 3H), 2.86–2.90 (m, 2H), 2.54–
2.58 (m, 2H). 13C NMR (100 MHz, CDCl3): d 173.11, 168.25,
140.54, 135.21, 131.07, 129.14, 128.66, 52.09, 51.63, 33.28, 23.09.
HRMS (EI): calcd for C14H16O4 [M+] 248.1049, found 248.1049.
CDCl3): d 7.22–7.27 (m, 2H), 7.07–7.09 (m, 2H), 3.65 (s, 3H), 3.60
(s, 3H), 2.90–2.93 (m, 1H), 2.69–2.76 (m, 2H), 2.29–2.37 (m, 2H),
1.87–1.94 (m, 2H). 13C NMR (100 MHz, CDCl3): d 174.99, 173.16,
137.28, 132.31, 130.21, 128.58, 51.66, 46.54, 37.69, 31.62, 26.85.
HRMS (EI): calcd for C14H17ClO4 [M+] 284.0815, found 284.0816.
4.3.2. Dimethyl (E)-2-(4-chlorobenzylidene)glutarate 4b
Colorless oil. 1H NMR (400 MHz, CDCl3): d 7.67 (s, 1H), 7.36–
7.38 (m, 2H), 7.28–7.31 (m, 2H), 3.82 (s, 3H), 3.67 (s, 3H), 2.82–
2.86 (m, 2H), 2.53–2.57 (m, 2H). 13C NMR (100 MHz, CDCl3): d
172.97, 167.99, 139.14, 134.63, 131.69, 130.45, 129.52, 128.91,
52.17, 51.69, 33.12, 23.04. HRMS (EI): calcd for C14H15ClO4 [M+]
282.0659, found 282.0620.
4.4.4. Dimethyl 2-(4-methoxybenzyl)glutarate 7c
Colorless oil. 78% ee, HPLC (UV 254 nm, Chiralcel OD-H
(0.46 cm ꢁ 25 cm), i-PrOH/hexane = 1/99, 1 mL/min), t1 = 15.4
min, t2 = 16.6 min. ½a D20
ꢂ
¼ ꢀ8:6 (c 1.14, CHCl3); 1H NMR (400 MHz,
CDCl3): d 7.04–7.07 (m, 2H), 6.80–6.82 (m, 2H), 3.77 (s, 3H), 3.65
(s, 3H), 3.61 (s, 3H), 2.88–2.91 (m, 1H), 2.69–2.73 (m, 2H), 2.28–
2.36 (m, 2H), 1.87–1.91 (m, 2H). 13C NMR (100 MHz, CDCl3): d
175.3, 173.3, 158.2, 130.8, 129.8, 113.8, 55.2, 51.6, 51.6, 46.9, 37.6,
31.7, 26.7. HRMS (EI): calcd for C15H20O5 [M+] 280.1311, found
280.1309.
4.3.3. Dimethyl (E)-2-(4-methoxybenzylidene)glutarate 4c
Colorless oil. 1H NMR (400 MHz, CDCl3): d 7.68 (s, 1H), 7.34–
7.37 (m, 2H), 6.91–6.94 (m, 2H), 3.85 (s, 3H), 3.81 (s, 3H), 3.68 (s,
3H), 2.88–2.92 (m, 2H), 2.55–2.59 (m, 2H). 13C NMR (100 MHz,
CDCl3): d 173.29, 160.06, 140.16, 131.11, 128.77, 127.63, 114.16,
55.31, 52.02, 51.66, 33.19, 23.13. HRMS (EI): calcd for C15H18O5
[M+] 278.1154, found 278.1150.
4.4.5. Dimethyl 2-(3-methoxybenzyl)glutarate 7d
Colorless oil. 81% ee, HPLC (UV 254 nm, Chiralcel OJ-H
(0.46 cm ꢁ 25 cm), i-PrOH/hexane = 1/99, 0.8 mL/min), t1 = 45.0
min, t2 = 49.4 min. ½a D20
ꢂ
¼ ꢀ2:7 (c 1.16, CHCl3); 1H NMR (400 MHz,
CDCl3): d 7.17–7.21 (m, 1H), 6.70–6.75 (m, 3H), 3.80 (s, 3H), 3.65
(s, 3H), 3.62 (s, 3H), 2.92–2.96 (m, 1H), 2.69–2.76 (m, 2H), 2.29–
2.37 (m, 2H), 1.88–1.94 (m, 2H). 13C NMR (100 MHz, CDCl3): d
175.2, 173.2, 159.7, 140.4, 129.5, 121.2, 114.5, 111.9, 55.1, 51.6,
46.5, 38.4, 31.7, 26.8. HRMS (EI): calcd for C15H20O5 [M+] 280.1311,
found 280.1319.
4.3.4. Dimethyl (E)-2-(3-methoxybenzylidene)glutarate 4d
Colorless oil. 1H NMR (400 MHz, CDCl3): d 7.71 (s, 1H), 7.28–
7.32 (m, 1H), 6.88–6.95 (m, 3H), 3.83 (s, 3H), 3.81 (s, 3H), 3.66 (s,
3H), 2.86–2.90 (m, 2H), 2.54–2.58 (m, 2H). 13C NMR (100 MHz,
CDCl3): d 173.06, 168.18, 159.65, 140.42, 136.49, 131.28, 129.65,
121.51, 114.45, 55.20, 52.06, 51.59, 33.29, 23.20. HRMS (EI): calcd
for C15H18O5 [M+] 278.1154, found 278.1147.
Acknowledgments
4.4. General procedure for asymmetric hydrogenation
We are grateful for financial support from the National Natural
Science Foundation of China (20873145, 20802076) and the
Knowledge Innovation of the Chinese Academy of Sciences (DICP-
S200802).
In a nitrogen-filled glovebox, to a solution of [Rh(COD)2]BF4
(1.0 mg, 0.0025 mmol) in anhydrous and degassed CH2Cl2 (1 mL)
was added ligand (0.00275 mmol for bidentate ligands or
0.005 mmol for monodentate ligands). After stirring the mixture
for 30 min, a substrate (0.25 mmol) dissolved in CH2Cl2 (1 mL)
was added. The reaction mixture was transferred to a Par stainless
autoclave. The autoclave was purged three times with hydrogen
and the pressure was set to the desired pressure. The hydrogena-
tion was performed at room temperature for 24 h. After carefully
releasing the hydrogen, the solvent was removed. The enantio-
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