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3.4. (ꢀ)-4-(1-Acetoxyethyl)benzenesulfonamide 7
To a stirred and cooled (−10°C) solution of (ꢀ)-6 (1.806 g, 8.97 mmol) in pyridine (50 ml) was
added acetyl chloride (1.051 g, 13.39 mmol) and the whole mixture was stirred for 2 h at −10°C. This
was diluted with 2 M aqueous HCl and extracted with AcOEt. The organic layer was washed with satd
aqueous NaHCO3 and dried over MgSO4. Evaporation of the organic solvent gave a residue. It was
chromatographed on silica gel (60 g, n-hexane:AcOEt=3:1) to provide crystals of (ꢀ)-7 (1.918 g, 87%),
which were recrystallized from EtOH to give colorless needles of (ꢀ)-7. (ꢀ)-7: mp 135.5–136.5°C; IR
(Nujol): 3312, 3210 (NH2), 1714 cm−1 (c O); 1H NMR: δ 1.47 (3H, d, J=6.8 Hz), 2.06 (3H, s), 5.82 (1H,
q, J=6.8 Hz), 7.35 (2H, br, s), 7.55, 7.80 (each 2H, d, J=8.0 Hz). Anal. found: C, 49.51; H, 5.39; N, 5.83.
Calcd. for C10H13NO4S: C, 49.37; H, 5.39; N, 5.76%. The racemate (ꢀ)-7 was analyzed to provide well
separated peaks (22 and 26 min) of each enantiomer using a Chiralcel AS (4.6 mm×250 mm) under the
following analytical conditions [eluent, n-hexane:EtOH (5:1); detection, UV at 254 nm; flow rate, 1.0
ml/min].
3.5. (ꢀ)-4-(1-Acetoxyethyl)-N-(cyclohexylcarbamoyl)benzenesulfonamide 3
A mixture of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 2.211 g, 14.52 mmol) and (ꢀ)-7 (2.354 g,
9.68 mmol) in benzene (50 ml) was stirred for 30 min at room temperature, and cyclohexylisocyanate
(1.816 g, 14.51 mmol) was added and the whole mixture was stirred for 1 h at room temperature. This was
diluted with 6 M aqueous HCl, and extracted with AcOEt. The organic layer was dried over MgSO4 and
evaporated to give an oily product, which was chromatographed on silica gel (60 g, n-hexane:AcOEt=2:1)
to afford (ꢀ)-3 (3.474 g, 97%). Recrystallization of (ꢀ)-3 from AcOEt–Et2O gave colorless needles of
1
(ꢀ)-3. (ꢀ)-3: mp 137–138°C; IR (Nujol): 3309, 3251 (NH2), 1731, 1689 cm−1 (C_O); H NMR: δ
1.09–1.23 (5H, m), 1.48 (3H, d, J=6.4 Hz), 1.57–1.67 (5H, m), 2.07 (3H, s), 3.24–3.32 (1H, m), 5.84
(1H, q, J=6.4 HZ), 6.36 (1H, d, J=7.7 Hz), 7.58, 7.88 (each 2H, d, J=7.6 Hz), 10.36 (1H, br, s). Anal.
found: C, 55.59; H, 6.54; N, 7.67. Calcd. for C17H24N2O5S: C, 55.42; H, 6.57; N, 7.60%.
3.6. (ꢀ)-4-(1-Hydroxyethyl)-N-(cyclohexylcarbamoyl)benzenesulfonamide 2
To a solution of (ꢀ)-3 (2.884 g, 7.83 mmol) in MeOH (40 ml) was added K2CO3 (2.167 g, 15.6
mmol) and the whole mixture was stirred for 12 h at room temperature. The reaction mixture was
diluted with 6 M aqueous HCl, and extracted with AcOEt. The organic layer was dried over MgSO4
and evaporated to give a residue. This was diluted with substantial amounts of MeOH and evaporated
to give a residue, which was chromatographed on silica gel (60 g, n-hexane:AcOEt=1:2) to afford (ꢀ)-
2 (2.319 g, 90%). Recrystallization of (ꢀ)-2 from AcOEt gave colorless needles of (ꢀ)-2. (ꢀ)-2: mp
143–144°C; IR (Nujol): 3527 (OH), 3346, 3057 (NH2), 1658 cm−1 (C_O); 1H NMR: δ 1.07–1.28 (5H,
m), 1.33 (3H, d, J=6.4 Hz), 1.47–1.66 (5H, m), 3.25–3.34 (1H, m), 4.80 (1H, dq, J=6.4, 3.9 Hz), 5.39
(1H, d, J=3.9 Hz), 6.33 (1H, d, J=7.8 Hz), 7.55, 7.84 (each 2H, d, J=8.3 Hz), 10.30 (1H, br, s). Anal.
found: C, 54.94; H, 6.82; N, 8.49. Calcd. for C15H22N2O4S: C, 55.19; H, 6.79; N, 8.58%.
3.7. General procedure of enantioselective acetylation of (ꢀ)-6
A suspension of (ꢀ)-6 (100 mg) and lipase (100 mg) in vinyl acetate (20 ml) was incubated at 33°C
for an adequate time as shown in Table 1. After the reaction mixture was filtered, the precipitate was
washed with AcOEt. The combined organic layer was dried over MgSO4 and evaporated. The residue