1470
B. M. Nestl et al. / Tetrahedron: Asymmetry 18 (2007) 1465–1474
20
1
(30 mg, 80%, ee >99%). ½aꢁD ¼ þ50:0 (c 1.0, CHCl3); H
NMR (360 MHz, CDCl3) d = 1.53 (3H, d, J = 7.0 Hz,
CH3), 2.53 (1H, s, OH), 5.80 (1H, q, J = 7.1 Hz, CH–
OH), 7.32 (1H, t, J = 6.1 Hz), 7.60 (2H, d, J = 5.7 Hz);
13C NMR (90 MHz, CDCl3) d = 32.0, 71.2, 108.4, 110.8,
139.8, 164.5, 198.1.
7 mmol) in n-hexane (30 mL). The mixture was vigorously
shaken at 30 ꢁC and after 24 h, the enzyme was removed by
filtration and the solvent was evaporated under reduced
pressure. Column chromatography on silica gel afforded
optically active (R)-3 (332 mg, 32%, ee >99%).
½aꢁD ¼ ꢂ13:8 (c 0.5, CHCl3); H NMR (360 MHz, CDCl3)
d = 0.91–0.95 (6H, m, CH3), 1.37–1.44 (2H, m), 1.56–1.66
(2H, m), 1.67–1.74 (2H, m), 2.13 (1H, s, OH), 2.38–2.49
(2H, m), 4.15 (1H, q, J = 3.1 Hz, CH–OH), 13C NMR
(90 MHz, CDCl3) d = 13.2, 13.8, 17.1, 18.1, 35.8, 39.7,
76.2, 212.4.
20
1
4.3.6. rac-3-Hydroxychroman-4-one acetate rac-13a was
obtained as previously described.49 (R)-3-Hydroxychro-
man-4-one (R)-13: was obtained from rac-13a by PPL cat-
alyzed hydrolysis using xylene as co-solvent as described
in literature.49,50 Under these conditions, (R)-13a was
20
20
obtained in 82% ee ½aꢁD ¼ þ72:9 (c 0.82, CHCl3); ½aꢁD
¼
4.3.9.2. (R)-a-Furoin (R)-8. Vinyl acetate (6 mL) and
lipase powder (Lipase Amano TL, 2.5 g) were added to a
solution of rac-a-furoin (1 g, 4 mmol) in THF (50 mL).
The mixture was vigorously shaken at 30 ꢁC and after
24 h, the enzyme was removed by filtration and the solvent
evaporated under reduced pressure. Column chromato-
þ54:0 (c 2, CHCl3).49
4.3.7. Synthesis of rac-3,3,3-trifluoro-2-hydroxy-1-phenyl-
propan-1-one rac-7. rac-3,3,3-Trifluoro-2-hydroxy-1-phen-
ylpropan-1-one rac-7 was obtained from the corresponding
a-hydroxycarboxylic acid using the following procedure
adapted from the literature.51 Trifluoroacetic anhydride
(3.6 mL, 24 mmol) was added to a stirred solution of phen-
yllactic acid (1 g, 6 mmol) and pyridine (2.92 mL, 36 mmol)
in dry benzene (21 mL) at room temperature under an inert
atmosphere and the mixture refluxed for 4 h. HCl (5%) was
then added to the mixture and the solution was stirred at
60 ꢁC for 15 min. After standard workup, the crude product
was purified by column chromatography on silica gel elut-
ing with dichloromethane to give the product rac-7 as a
white solid (1.02 g, 78%). 1H NMR (360 MHz, CDCl3)
d = 2.20 (1H, s), 5.44 (1H, q, J = 6.6 Hz, CH–OH), 7.56
(2H, t, J = 7.8 Hz), 7.71 (1H, t, J = 7.4 Hz), 8.0 (2H, d,
J = 7.6 Hz), 13C NMR (90 MHz, CDCl3) d = 94.3, 116.1,
128.9, 129.5, 133.4, 135.3, 193.1.
graphy on silica gel afforded optically active (R)-8
20
(450 mg, 45%, ee >99%). ½aꢁD ¼ þ62:7 (c 0.9, CHCl3);
1
mp = 128 ꢁC; H NMR (360 MHz, CDCl3) d = 2.18 (1H,
s, OH), 5.81 (1H, s, CH–OH), 6.35–6.41 (2H, dd,
J1 = 3.2 Hz, J2 = 14.4 Hz), 6.54 (1H, t, J = 2.0 Hz), 7.26
(1H, d, J = 3.6 Hz), 7.38 (1H, d, J = 1.0 Hz), 7.62 (1H, d,
J = 1.0 Hz), 13C NMR (90 MHz, CDCl3) d = 69.3, 109.2,
110.8, 112.6, 120.2, 143.2, 147.7, 149.3, 151.2, 184.5.
4.3.9.3. (R)-a-Pyridoin (R)-9. Vinyl acetate (6 mL) and
lipase powder (Lipase Amano TL, 2.5 g) were added to a
solution of rac-a-pyridoin (1 g, 4 mmol) in THF (50 mL).
The mixture was vigorously stirred at 30 ꢁC and after
24 h, the enzyme was removed by filtration and the solvent
was evaporated under reduced pressure. Column chroma-
tography on silica gel afforded optically active (R)-9
4.3.8. Synthesis of (S)-3,3,3-trifluoro-2-hydroxy-1-phenyl-
propan-1-one (S)-7. Vinyl acetate (5 mL) and lipase pow-
der (lipase CAL-B Novozyme 435, 0.5 g) were added to a
solution of rac-3,3,3-trifluoro-2-hydroxy-1-phenylpropan-
1-one rac-7 (1 g, 6.6 mmol) in t-BuOMe (60 mL). The mix-
ture was vigorously stirred at 30 ꢁC and after 24 h, the en-
zyme was removed by filtration and the solvent evaporated
under reduced pressure. Column chromatography on silica
20
(356 mg, 36%, ee >99%). ½aꢁD ¼ þ78:8 (c 0.8, CHCl3);
1
mp = 138 ꢁC; H NMR (360 MHz, CDCl3) d = 2.18 (1H,
s), 7.49–7.52 (2H, m), 7.92–7.97 (2H, ddd, J1 = J2 =
1.6 Hz, J3 = 6.1 Hz), 8.23 (2H, d, J = 7.8 Hz), 8.61 (2H,
d, J = 4.2 Hz), 13C NMR (90 MHz, CDCl3) d = 30.9,
119.4, 121.1, 127.4, 135.9, 137.5, 145.6, 156.6, 206.9.
4.3.9.4. (R)-2,20-Dimethoxybenzoin (R)-10. Vinyl ace-
tate (6 mL) and lipase powder (Lipase Amano TL, 2.5 g)
were added to a solution of rac-2,20-dimethoxybenzoin
(1 g, 4 mmol) in THF (50 mL). The mixture was vigorously
stirred at 30 ꢁC and after 96 h, the enzyme was removed by
filtration and the solvent evaporated under reduced pres-
gel afforded optically active (S)-7 (267 mg, 27%, ee >99%).
20
½aꢁD ¼ þ8:6 (c 0.2, CHCl3); mp = 81 ꢁC; 1H NMR
(360 MHz, CDCl3) d = 2.20 (1H, s), 5.44 (1H, q,
J = 6.6 Hz, CH–OH), 7.56 (2H, t, J = 7.8 Hz), 7.71 (1H,
t, J = 7.4 Hz), 8.0 (2H, d, J = 7.6 Hz), 13C NMR
(90 MHz, CDCl3) d = 94.3, 116.1, 128.9, 129.5, 133.4,
135.3, 193.1.
sure. Column chromatography on silica gel afforded opti-
20
cally active (R)-10 (110 mg, 11%, ee >99%). ½aꢁD ¼ ꢂ70:4
20
(c 1.0, CHCl3), ½aꢁ ¼ ꢂ125 (c 0.9, CHCl3);53 1H NMR
4.3.9. General procedure for lipase mediated kinetic resolu-
tion.46,52 The acyl donor (6 mL) and lipase powder
(2.5 g) were added to a solution of rac-3, rac-8 and rac-9
(1 g) in solvent (30 mL). The mixture was vigorously sha-
ken at 30 ꢁC and after 24 h, the enzyme was removed by fil-
tration and the solvent evaporated under reduced pressure.
Column chromatography on silica gel afforded optically
active a-hydroxyketones (R)-3 and (R)-8–(R)-12.
(360 MHz, CDCl3)Dd = 2.84 (1H, s, OH), 3.69 (3H, s, O–
CH3), 3.83 (3H, s, O–CH3), 6.12 (1H, s, CH–OH), 6.84–
6.86 (2H, m), 6.93–6.99 (2H, m), 7.16–7.22 (2H, m),
7.50–7.53 (1H, m), 8.12 (1H, d, J = 3.1 Hz); 13C NMR
(90 MHz, CDCl3) d = 54.7, 54.9, 75.2, 110.8, 111.4,
120.1, 120.2, 128.2, 129.2, 129.5, 130.0, 133.3, 157.3,
158.0, 205.2.
4.3.9.1. (R)-5-Hydroxyoctan-4-one (R)-3. Vinyl acetate
(6 mL) and lipase powder (Lipase Amano PS, 2.5 g) were
added to a solution of rac-5-hydroxyoctan-4-one (1 g,
4.3.9.5. (R)-4,40-Dimethoxybenzoin (R)-11. Vinyl ace-
tate (6 mL) and lipase powder (Lipase Amano TL, 2.5 g)
were added to a solution of rac-4,40-dimethoxybenzoin