S. Serra / Tetrahedron: Asymmetry 22 (2011) 619–628
625
1.22 (d, J = 6.9 Hz, 3H), 1.72 (br t, J = 5.8 Hz, 1H), 2.34 (s, 3H), 3.16–
3.26 (m, 1H), 3.57–3.73 (m, 2H), 7.05–7.22 (m, 4H). 13C NMR
(100 MHz) d 17.4, 19.5, 37.2, 67.9, 125.4, 126.1, 126.2, 130.4,
136.2, 141.8. GC–MS m/z (rel intensity) 150 (M+, 33), 132 (1),
119 (100), 105 (9), 91 (26), 77 (8), 65 (5), 51 (2), 39 (2).
enzyme and evaporation of the solvent at reduced pressure. The
residue was then purified by chromatography using hexane–
diethyl ether (95:5–3:1) as eluent.
The general procedure afforded:
(Using PPL as catalyst): acetate (S)-(ꢀ)-12a as a colorless oil,
½
a 2D0
ꢃ
¼ ꢀ1:4 (c 3.5, CHCl3), 98% chemical purity by GC, 78% ee,
4.2.2.7. 2-(2-Ethyl-phenyl)-propan-1-ol 1h. Colorless oil, 89%
yield, 96% chemical purity by GC; 1H NMR (400 MHz, CDCl3) d
1.21 (t, J = 7.6 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H), 1.64 (br s, 1H),
2.59–2.80 (m, 2H), 3.20–3.30 (m, 1H), 3.63 (dd, J = 10.7, 6.8 Hz,
1H), 3.69 (dd, J = 10.7, 7.3 Hz, 1H), 7.09–7.21 (m, 4H). 13C NMR
(100 MHz) d 15.8, 18.1, 25.8, 36.5, 68.3, 125.6, 126.2, 126.3,
128.9, 141.3, 142.4. GC–MS m/z (rel intensity) 164 (M+, 24), 146
(2), 133 (100), 117 (10), 105 (48), 91 (16), 77 (7), 65 (3), 51 (2).
Ref. 18 [
a
]D: ꢀ2.8 (c 10.09, CHCl3). Alcohol (R)-(+)-1a as a colorless
oil, ½a 2D0
¼ þ8:7 (c 3.2, CHCl3), 98% chemical purity by GC, 66% ee,
ꢃ
Ref. 19 (for S-isomer) ½a D28
¼ ꢀ11:7 (c 1.2, CHCl3).
ꢃ
(Using PPL as catalyst): acetate (S)-(+)-12b as a colorless oil,
½
a 2D0
ꢃ
¼ þ24:1 (c 2, CHCl3), 98% chemical purity by GC, 88% ee by
chiral HPLC. 1H NMR (400 MHz, CDCl3) d 1.27 (d, J = 6.9 Hz, 3H),
2.02 (s, 3H), 2.35 (s, 3H), 3.43–3.55 (m, 1H), 3.82 (s, 3H), 4.14
(dd, J = 10.6, 7.4 Hz, 1H), 4.21 (dd, J = 10.6, 6.1 Hz, 1H), 6.70 (s,
1H), 6.75 (d, J = 7.4 Hz, 1H), 7.07 (d, J = 7.4 Hz, 1H). 13C NMR
(100 MHz) d 16.9, 20.9, 21.3, 31.9, 55.2, 68.5, 111.5, 121.1, 127.1,
128.2, 137.3, 157.0, 171.0. GC–MS m/z (rel intensity) 222 (M+, 4),
162 (38), 149 (100), 134 (6), 119 (20), 105 (7), 91 (17), 77 (5), 65
(3). According to Scheme 3, the procedure was repeated on a larger
scale (0.1 mol) allowing the acetylation reaction to reach a conver-
sion of about 60%. The alcohol obtained (R)-(ꢀ)-1b (7 g, 39 mmol)
showed the following analytical data: 97% chemical purity by GC,
4.2.2.8. 2-(2,6-Dimethoxy-4-methyl-phenyl)-propan-1-ol 1i. Col-
orless oil, 80% yield, 99% chemical purity by GC; 1H NMR (400 MHz,
CDCl3) d 1.25 (d, J = 7.1 Hz, 3H), 1.74 (br s, 1H), 2.32 (s, 3H), 3.58–
3.70 (m, 1H), 3.78 (s, 6H), 3.78 (dd, J = 10.1, 6.5 Hz, 1H), 3.88 (dd,
J = 10.1, 7.6 Hz, 1H), 6.38 (s, 2H). 13C NMR (100 MHz) d 15.4, 21.8,
32.5, 55.7, 66.7, 105.4, 116.8, 137.5, 158.7. GC–MS m/z (rel intensity)
210 (M+, 15), 192 (1), 179 (100), 164 (3), 149 (7), 134 (4), 119 (7),
105 (3), 91 (10), 77 (5), 65 (2).
95% ee by chiral HPLC; ½a D20
¼ ꢀ2:8 (c 2.5, CHCl3). The acetate ob-
ꢃ
tained (+)-12b was treated with NaOH (6 g, 0.25 mol) in MeOH
(80 mL) at reflux for 1 h. After a work-up procedure, the alcohol ob-
tained was again submitted to the resolution procedure allowing
the acetylation reaction reached a conversion of about 60%. The ob-
tained acetate (+)-12b (8.1 g, 36.5 mmol) showed the following
analytical data: 99% chemical purity by GC, 99% ee by chiral HPLC;
4.2.2.9. 2-(4-Methoxy-phenyl)-propan-1-ol 1j. Colorless oil, 90%
yield, 99% chemical purity by GC; 1H NMR (400 MHz, CDCl3) d 1.23
(d, J = 7.0 Hz, 3H), 1.65 (br s, 1H), 2.81–2.92 (m, 1H), 3.62 (d,
J = 6.9 Hz, 2H), 3.77 (s, 3H), 6.85 (dm, J = 8.7 Hz, 2H), 7.13 (dm,
J = 8.7 Hz, 2H). 13C NMR (100 MHz) d 17.6, 41.5, 55.1, 68.7, 114.0,
128.3, 135.7, 158.3. GC–MS m/z (rel intensity) 166 (M+, 19), 135
(100), 120 (6), 105 (15), 91 (10), 77 (7), 65 (3).
½
a 2D0
a 2D0
ꢃ
¼ þ27:2 (c 2.5, CHCl3).
(Using PPL as catalyst): acetate (S)-(+)-12c as a colorless oil,
½
ꢃ
¼ þ13:3 (c 3, CHCl3), 98% chemical purity by GC, 83% ee by
4.2.2.10. 2-(4-Methyl-phenyl)-propan-1-ol 1k. Colorless oil, 63%
yield from 10k, 97% chemical purity by GC; 1H NMR (400 MHz,
CDCl3) d 1.24 (d, J = 7.0 Hz, 3H), 1.56 (br s, 1H), 2.31 (s, 3H),
2.82–2.93 (m, 1H), 3.63 (d, J = 6.9 Hz, 2H), 7.11 (s, 4H). 13C NMR
(100 MHz) d 17.6, 20.9, 42.0, 68.6, 127.3, 129.2, 136.1, 140.6. GC–
MS m/z (rel intensity) 150 (M+, 18), 119 (100), 103 (4), 91 (17),
77 (5), 65 (4).
chiral GC. 1H NMR (400 MHz, CDCl3) d 1.27 (d, J = 7.0 Hz, 3H),
2.00 (s, 3H), 3.57–3.68 (m, 1H), 4.12–4.23 (m, 2H), 7.17–7.25 (m,
2H), 7.38 (d, J = 2.0 Hz, 1H). 13C NMR (100 MHz) d 17.1, 20.7,
34.5, 67.6, 127.3, 128.4, 129.4, 132.8, 134.7, 139.1, 170.7. GC–MS
m/z (rel intensity) 246 (M+, <1), 188 (72), 186 (100), 175 (37),
173 (56), 159 (8), 151 (7), 137 (16), 115 (9), 102 (19), 73 (10). Alco-
hol (R)-(ꢀ)-1c as a colorless oil, ½a D20
¼ ꢀ1:4 (c 3, CHCl3), 97%
ꢃ
chemical purity by GC, 52% ee by chiral GC.
4.2.2.11. 2-(3-Methoxy-4-methyl-phenyl)-propan-1-ol 1l. Col-
orless oil, 85% yield, 98% chemical purity by GC; 1H NMR
(400 MHz, CDCl3) d 1.26 (d, J = 6.9 Hz, 3H), 1.50 (br s, 1H), 2.18
(s, 3H), 2.84–2.95 (m, 1H), 3.62–3.70 (m, 2H), 3.82 (s, 3H), 6.69
(s, 1H), 6.72 (dm, J = 7.5 Hz, 1H), 7.07 (d, J = 7.5 Hz, 1H). 13C NMR
(100 MHz) d 15.7, 17.6, 42.5, 55.2, 68.7, 109.4, 118.9, 124.9,
130.7, 142.6, 157.9. GC–MS m/z (rel intensity) 180 (M+, 31), 162
(1), 149 (100), 134 (8), 119 (8), 117 (9), 103 (3), 91 (15), 77 (5),
65 (2).
(Using lipase PS as catalyst): acetate (S)-(+)-12d as a colorless
oil, ½a 2D0
¼ þ8:6 (c 8, CHCl3), 98% chemical purity by GC, 25% ee
ꢃ
by chiral HPLC. 1H NMR (400 MHz, CDCl3) d 1.29 (d, J = 7.0 Hz,
3H), 2.01 (s, 3H), 3.59–3.70 (m, 1H), 4.19 (d, J = 6.9 Hz, 2H), 7.05–
7.10 (m, 1H), 7.22–7.31 (m, 2H), 7.53–7.57 (m, 1H). 13C NMR
(100 MHz) d 17.4, 20.8, 37.5, 68.0, 124.8, 127.6, 127.6, 128.1,
133.0, 142.1, 170.9. GC–MS m/z (rel intensity) 258 (M++1, <1),
256 ((M+ꢀ1, <1), 198 (100), 196 (98), 185 (48), 183 (49), 171 (5),
169 (5), 147 (30), 117 (13), 115 (12), 104 (37), 91 (5), 77 (21), 63
(3), 51 (4). Alcohol (R)-(ꢀ)-1d as a colorless oil, ½a D20
¼ ꢀ2:5 (c
ꢃ
4.2.2.12.
2-(2,5-Dimethoxy-4-methyl-phenyl)-propan-1-ol
3.5, CHCl3), 97% chemical purity by GC, 22% ee by chiral HPLC.
1m. Colorless needles (hexane), mp 76–77 °C, 90% yield, 99%
chemical purity by GC; 1H NMR (400 MHz, CDCl3) d 1.25 (d,
J = 7.1 Hz, 3H), 1.64 (br s, 1H), 2.20 (s, 3H), 3.32–3.43 (m, 1H),
3.61–3.75 (m, 2H), 3.77 (s, 3H), 3.79 (s, 3H), 6.69 (s, 1H), 6.70 (s,
1H). 13C NMR (100 MHz) d 16.0, 16.6, 35.5, 56.1, 56.3, 68.0,
110.4, 114.4, 125.3, 129.7, 151.1, 152.0. GC–MS m/z (rel intensity)
210 (M+, 32), 192 (2), 179 (100), 164 (28), 149 (10), 134 (3), 117
(4), 103 (3), 91 (9), 77 (5), 65 (2), 53 (2).
(Using PPL as catalyst): acetate (S)-(+)-12e as a colorless oil,
½
a 2D0
ꢃ
¼ þ9:6 (c 3, CHCl3), 97% chemical purity by GC, 26% ee by chi-
ral HPLC. 1H NMR (400 MHz, CDCl3) d 1.26 (d, J = 7.0 Hz, 3H), 2.01
(s, 3H), 3.42–3.53 (m, 1H), 4.17 (d, J = 6.9 Hz, 2H), 6.87–6.94 (m,
1H), 7.20 (dd, J = 7.8, 1.6 Hz, 1H), 7.27–7.34 (m, 1H), 7.84 (dd,
J = 7.8, 1.2 Hz, 1H). 13C NMR (100 MHz) d 17.7, 20.8, 42.5, 68.1,
101.5, 126.8, 128.3, 128.4, 139.7, 145.2, 170.7. GC–MS m/z (rel
intensity) 304 (M+, 3), 244 (100), 231 (38), 217 (3), 177 (2), 147
(9), 135 (3), 115 (7), 104 (21), 91 (4), 77 (7). Alcohol (R)-(ꢀ)-1e
4.3. Lipase-mediated resolution of racemic 2-aryl-propan-1-
ol. General procedure. A solution of the suitable 2-aryl-propan-1-
ol derivative (30 mmol), lipase (5 g), vinyl acetate (15 mL) and
t-BuOMe (60 mL) was stirred at rt and the formation of the acety-
lated compounds was monitored by TLC analysis. The reaction was
stopped at the reported conversion (see Table 1) by filtration of the
as a colorless oil, ½a D20
¼ ꢀ1:8 (c 5, CHCl3), 97% chemical purity
ꢃ
by GC, 10% ee by chiral HPLC.
(Using CRL as catalyst): acetate (R)-(ꢀ)-12f as a colorless oil,
½
a 2D0
ꢃ
¼ ꢀ82:8 (c 6, CHCl3), 97% chemical purity by GC, 49% ee by
chiral HPLC. 1H NMR (400 MHz, CDCl3) d 1.36 (d, J = 6.9 Hz, 3H),
1.98 (s, 3H), 3.66–3.77 (m, 1H), 4.16 (dd, J = 10.8, 7.6 Hz, 1H),