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Bull. Chem. Soc. Jpn. Vol. 83, No. 2 (2010)
Enzymatic Reaction of Polymer-Bound Carbonate
70.65, 70.70, 71.8, 76.3, 114.5, 125.9, 127.4, 128.0, 128.4, 130.1,
140.9, 154.4, 158.9; ESI-TOF MS m/z 2479 Da (2477 Da calcd for
[CH3O(CH2CH2O)105C16H15O3¢2Na]2+).
1.78-2.01 (m, 2H), 2.89 (t, J = 7.5 Hz, 2H), 3.37 (s, 3H), 3.44-
3.80 (m, PEG-methylenes), 3.82 (t, J = 5.0 Hz, 2H), 4.09 (t,
J = 5.0 Hz, 2H), 4.26 (dt, J1 = 2.0 Hz, J2 = 7.0 Hz, 2H), 4.47 (s,
2H), 4.88-4.97 (m, 1H), 6.84 (d, J = 9.0 Hz, 2H), 7.10 (d, J =
8.5 Hz, 2H), 7.22-7.36 (m, 5H); 13C NMR (125 MHz, CDCl3): ¤
20.0, 34.1, 35.8, 58.9, 66.2, 67.2, 68.1, 69.6, 70.4 (PEG), 70.6,
70.7, 71.8, 72.6, 72.9, 114.5, 127.4, 127.5, 128.2, 129.3, 129.7,
138.1, 154.5, 157.4; ESI-TOF MS m/z 2515 Da (2514 Da calcd for
[CH3O(CH2CH2O)105C20H23O4¢2Na]2+).
Compound («)-5d: Yield 95% (purity, ca. 99%) from 9d; IR
(KBr): 2886, 1744, 1638, 1468, 1342, 1281, 1242, 1111, 962,
843 cm¹1; 1H NMR (500 MHz, CDCl3): ¤ 1.58 (d, J = 6.5 Hz, 3H),
2.89 (t, J = 7.0 Hz, 2H), 3.38 (s, 3H), 3.45-3.82 (m, PEG-
methylenes), 3.84 (t, J = 5.0 Hz, 2H), 4.10 (t, J = 5.0 Hz, 2H),
4.26 (dt, J1 = 2.5 Hz, J2 = 7.0 Hz, 2H), 5.70 (q, J = 6.5 Hz, 1H),
6.83 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 7.28-7.40 (m,
5H); 13C NMR (125 MHz, CDCl3): ¤ 22.2, 34.1, 58.9, 67.3, 68.3,
69.6, 70.4 (PEG), 70.6, 70.7, 71.8, 76.2, 114.5, 125.9, 128.0, 128.4,
129.2, 129.7, 140.9, 154.3, 157.4; ESI-TOF MS m/z 2486 Da
(2484 Da calcd for [CH3O(CH2CH2O)105C17H17O3¢2Na]2+).
Compound («)-5e: Yield 99% (purity, ca. 96%) from 9e; IR
(KBr): 2884, 1742, 1638, 1512, 1466, 1344, 1281, 1252, 1113,
953, 843 cm¹1; 1H NMR (500 MHz, CDCl3): ¤ 1.59 (d, J = 6.5 Hz,
3H), 1.89-1.98 (m, 2H), 2.61 (t, J = 7.5 Hz, 2H), 3.37 (s, 3H),
3.45-3.81 (m, PEG-methylenes), 3.83 (t, J = 5.0 Hz, 2H), 4.086
(dt, J1 = 6.5 Hz, J2 = 10.5 Hz, 1H), 4.088 (t, J = 5.0 Hz, 2H), 4.12
(dt, J1 = 6.5 Hz, J2 = 10.5 Hz, 1H), 5.72 (q, J = 6.5 Hz, 1H), 6.81
(d, J = 8.5 Hz, 2H), 7.04 (d, J = 8.5 Hz, 2H), 7.18-7.42 (m, 5H);
13C NMR (125 MHz, CDCl3): ¤ 22.2, 30.2, 30.8, 58.9, 67.0, 67.2,
69.6, 70.4 (PEG), 70.58, 70.62, 71.7, 76.1, 114.4, 125.8, 127.9,
128.4, 129.1, 133.0, 140.9, 154.4, 156.9; ESI-TOF MS m/z 2493
Da (2491 Da calcd for [CH3O(CH2CH2O)105C18H19O3¢2Na]2+).
Compound («)-12c: Yield 98% (purity, ca. 97%) from 9c; IR
(KBr): 2884, 1744, 1645, 1466, 1342, 1281, 1242, 1113, 962,
843 cm¹1; 1H NMR (500 MHz, CDCl3): ¤ 0.89 (t, J = 7.5 Hz, 3H),
1.77-2.03 (m, 2H), 3.37 (s, 3H), 3.44-3.87 (m, PEG-methylenes),
4.11 (t, J = 5.0 Hz, 2H), 5.02 (d, J = 12.0 Hz, 1H), 5.06 (d, J =
12.0 Hz, 1H), 5.49 (t, J = 6.5 Hz, 1H), 6.87 (d, J = 9.0 Hz, 2H),
7.25 (d, J = 9.0 Hz, 2H), 7.26-7.35 (m, 5H); 13C NMR (125 MHz,
CDCl3): ¤ 9.8, 29.3, 59.0, 67.3, 69.3, 69.6, 70.5 (PEG), 70.67,
70.72, 71.8, 81.5, 114.5, 126.4, 127.4, 128.0, 128.3, 130.1, 139.8,
154.6, 158.9; ESI-TOF MS m/z 2486 Da (2484 Da calcd for
[CH3O(CH2CH2O)105C17H17O3¢2Na]2+).
PEG4600-Supported Substrate Coupled with 1-Phenyletha-
nol ((«)-10): Yield 99% (purity, ca. 89%) from 11; IR (KBr):
¹1
2884, 1744, 1647, 1466, 1342, 1281, 1242, 1115, 964, 843 cm
;
1H NMR (500 MHz, CDCl3): ¤ 1.59 (d, J = 6.5 Hz, 6H), 3.45-3.82
(m, PEG-methylenes), 4.24 (td, J1 = 4.5 Hz, J2 = 12.0 Hz, 2H),
4.27 (td, J1 = 5.0 Hz, J2 = 11.5 Hz, 2H), 5.72 (q, J = 6.5 Hz,
2H), 7.17-7.45 (m, 10H); 13C NMR (125 MHz, CDCl3): ¤ 22.2,
66.7, 68.8, 70.4 (PEG), 70.5, 70.6, 76.4, 125.9, 128.0, 128.4,
140.8, 154.4; ESI-TOF MS m/z 2449 Da (2447 Da calcd for
[(CH2CH2O)103C18H18O5¢2Na]2+).
Typical Experimental Procedure for Enantioselective
Hydrolysis of PEG-Supported Substrates.
To a test tube
containing 125 mg of («)-1 (sub. concn., 5 mM) was added 4.5 mL
of hexane and 0.5 mL of 0.1 M phosphate buffer (pH 6.5). To the
mixture was added 10 mg of lipase from porcine pancreas (PPL;
Type II, Sigma) (187 U mg¹1, using olive oil at pH 7.7), and the
solution was stirred for 24 h at 0 °C. After the organic layer was
separated and evaporated in vacuo, the ee of the resulting (R)-
alcohol 3 (96% ee) in the residue was determined by GC analysis.
On the other hand, the aqueous layer was diluted with CH2Cl2, and
dried over Na2SO4. After evaporation, the residue was hydrolyzed
with 2 M NaOH aq. (1.0 mL) in MeOH (4.0 mL). The products
were extracted with hexane (©3), and the organic layer was dried
over Na2SO4. After evaporation, the ee of the corresponding (S)-3
(18% ee) was determined by GC analysis.
Other reactions were carried out by the same procedure.
Typical Preparative Scale Reaction of PEG-Supported
Substrates.
To a recovery flask containing 3.6 g of («)-5d
Compound («)-12d: Yield 89% (purity, ca. 61%) from 9d; IR
(KBr): 2886, 1748, 1638, 1466, 1342, 1281, 1242, 1115, 964,
843 cm¹1; 1H NMR (500 MHz, CDCl3): ¤ 0.90 (t, J = 7.5 Hz, 3H),
1.77-1.89 (m, 1H), 1.91-2.03 (m, 1H), 2.88 (t, J = 7.0 Hz, 2H),
3.37 (s, 3H), 3.44-3.88 (m, PEG-methylenes), 4.11 (t, J = 5.0 Hz,
2H), 4.25 (dt, J1 = 4.5 Hz, J2 = 7.5 Hz, 2H), 5.47 (t, J = 6.5 Hz,
1H), 6.82 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 7.21-7.36
(m, 5H); 13C NMR (125 MHz, CDCl3): ¤ 9.8, 29.2, 34.1, 58.9,
67.2, 68.3, 69.6, 70.4 (PEG), 70.6, 70.7, 71.8, 81.3, 126.3, 127.9,
128.3, 129.2, 129.7, 139.8, 154.5, 160.9; ESI-TOF MS m/z 2493
Da (2491 Da calcd for [CH3O(CH2CH2O)105C18H19O3¢2Na]2+).
Compound («)-13c: Yield 97% (purity, ca. 69%) from 9c; IR
(KBr): 2886, 1734, 1647, 1466, 1342, 1281, 1242, 1115, 964,
843 cm¹1; 1H NMR (500 MHz, CDCl3): ¤ 1.31 (d, J = 6.0 Hz, 3H),
3.38 (s, 3H), 3.42-3.93 (m, PEG-methylenes), 4.12 (t, J = 5.0 Hz,
2H), 4.46 (s, 2H), 4.98 (td, J1 = 1.5 Hz, J2 = 6.5 Hz, 1H), 5.05 (d,
J = 12.0 Hz, 1H), 5.06 (d, J = 12.0 Hz, 1H), 6.89 (d, J = 9.0 Hz,
2H), 7.22-7.37 (m, 5H), 7.30 (d, J = 8.5 Hz, 2H); 13C NMR (125
MHz, CDCl3): ¤ 20.0, 35.8, 58.9, 66.2, 67.3, 69.0, 69.5, 70.4
(PEG), 70.6, 70.7, 71.8, 72.7, 72.9, 114.4, 114.5, 127.4, 127.5,
128.2, 130.1, 138.1, 154.5, 158.9; ESI-TOF MS m/z 2508 Da
(2506 Da calcd for [CH3O(CH2CH2O)105C19H21O4¢2Na]2+).
Compound («)-13d: Yield 95% (purity, ca. 89%) from 9d;
IR (KBr): 2886, 1738, 1645, 1468, 1342, 1281, 1242, 1111, 962,
843 cm¹1; 1H NMR (500 MHz, CDCl3): ¤ 1.29 (d, J = 6.5 Hz, 3H),
(sub. concn., 5 mM) was added 130.5 mL of hexane and 14.5 mL
of 0.1 M phosphate buffer. To the mixture was added 290 mg of
PPL, and the solution was stirred for 48 h at 0 °C. After the organic
layer was separated and evaporated in vacuo, the residue was
purified by preparative TLC (hexane/AcOEt = 2/1) to give (R)-3
18
(9.6 mg, 12%, 98% ee, ½¡ꢀD = +32.8 (c 0.96, MeOH)). On the
other hand, the aqueous layer was diluted with CH2Cl2, and dried
over Na2SO4. After the solution was evaporated in vacuo, the
residue was precipitate into Et2O to afford the compound (S)-5d as
a white solid. To a solution of the solid in MeOH (120 mL) was
added 2 M NaOH aq. (30 mL), and the solution was stirred for 1 h
at rt. The products were extracted with ether (©3), and the organic
layer was washed with brine and dried over Na2SO4. After
evaporation, the residue was purified by column chromatography
(hexane/EtOAc = 2/1) on silica gel to give the corresponding (S)-
25
3 (37.9 mg, 46%, 58% ee, ½¡ꢀD = ¹21.0 (c 1.06, MeOH)).
Several data of alcohols are as follows.
1-Phenylethanol (3): The spectral data were in full agreement
with that of a commercial source. GLC conditions: column, CP-
Cyclodextrin-B-236-M19 (Chrompack), 0.25 mm © 50 m; injec-
tion, 160 °C; detection, 160 °C; oven, 140 °C; carrier gas, He; head
pressure, 2.4 kg cm¹2; retention time, 8.9 (R) and 9.2 (S) min.
1-Phenyl-1-propanol (15): The spectral data were in full
30
agreement with that of a commercial source. (S)-15, ½¡ꢀD = ¹38.3
30
(c 1.02, CHCl3) (86% ee); (R)-15, ½¡ꢀD = +41.4 (c 1.20, CHCl3)