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J. Matsubara et al. / Tetrahedron 56 (2000) 4667±4682
stirred at room temperature for overnight. The reaction
mixture was poured into 10% Na2CO3 aqueous solution
and extracted with CH2Cl2. The extract was dried over
MgSO4 and concentrated in vacuo. The residue was puri®ed
by preparative thin layer chromatography (silica gel; eluent,
CH2Cl2±MeOH8:1) and recrystallized from EtOH±H2O
to give 4a (0.18 g, 75%) as white powder, which was
.99% ee by HPLC analysis using ULTRON ES-CD
(CH3CN±20 mM KH2PO4 aq15:85), mp 126±1288C.
7.68 (1H, d, J8.2 Hz). Anal. Calcd for C17H19NO4S: C,
61.24; H, 5.74; N, 4.20. Found: C, 61.29; H, 5.69; N, 4.11.
(4S,5R)-4,5-Dihydroxy-1-(p-toluenesulfonyl)-2,3,4,5-tetra-
hydro-1H-1-benzazepine (19a). A mixture of (^)-19
(5.52 g, 16.5 mmol), vinyl acetate (860 mL) and lipase QL
(6.5 g) was stirred at room temperature for 6 h. The reaction
mixture was ®ltered and lipase was washed with CH2Cl2.
The ®ltrate was evaporated and the residue was puri®ed
by column chromatography (silica gel; eluent, hexane±
AcOEt4:1) to give the unreacted alcohol 19a (2.90 g,
53%, 76% ee) and the acetate 20b (2.48 g, 40%). The
crude alcohol 19a (76% ee) was recrystallized from
hexane±AcOEt to give 19a (2.27 g, 93% ee) from mother
liquid. Next, a mixture of 19a (2.27 g, 93% ee), vinyl
acetate (350 mL) and lipase QL (2.0 g) was stirred at
room temperature for 24 h. The reaction mixture was
®ltered and the ®ltrate was concentrated in vacuo. The
residual oil was puri®ed by column chromatography (silica
gel; eluent, hexane±AcOEt4:1) and the crystalline powder
was washed with iso-PrOH to give pure 19a (2.05 g, 90%)
as white powder, which was .99% ee by HPLC analysis
1
[a]2D622808 (c 0.1, MeOH). H NMR (CDCl3) d: 1.40±
1.90 (2H, m), 1.90±2.25 (2H, m), 2.46 (3H, s), 2.80±3.00
(1H, m), 4.10±5.25 (2H, m), 6.67 (1H, d, J8.2 Hz), 6.95±
7.25 (9H, m), 7.69 (1H, d, J7.7 Hz). IR (KBr): 3362, 1631,
1597, 1409, 1321 cm21. Anal. Calcd for C25H25N3O2´1/
2H2O: C, 73.51; H, 6.42; N, 10.29. Found: C, 73.09; H,
6.29; N, 10.65.
(R)-5-Amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,
4,5-tetrahydro-1H-1-benzazepine (4b). The title com-
pound was prepared from 17b and tri¯uoroacetic acid by
the procedure described for the preparation of 4a. The
product was recrystallized from EtOH±H2O to give 4b
(81%, .99% ee) as white powder, mp 125±1268C.
[a]2D312788 (c 0.1, MeOH). IR (KBr): 3362, 1629, 1598,
1409, 1321 cm21. Anal. Calcd for C25H25N3O2´3/4H2O: C,
72.71; H, 6.47; N, 10.17. Found: C, 72.91; H, 6.19; N, 10.48.
using
CHIRALCEL
OJ
(hexane±EtOH±Et2NH
700:300:1), mp 140±1428C. [a]2D5224.58 (c 0.2,
MeOH). Anal. Calcd for C17H19NO4S: C, 61.24; H, 5.74;
N, 4.20. Found: C, 61.35; H, 5.75; N, 4.07.
1-(p-Toluenesulfonyl)-2,3-dihydro-1H-1-benzazepine (18).
A solution of (^)-7 (25.0 g, 78.8 mmol) and p-TsOH
(3.15 g, 15.8 mmol) in toluene (800 mL) was re¯uxed
under Dean±Stark apparatus for 6 h. The mixture was
poured into water and the whole was extracted with
AcOEt. The extract was dried over Na2SO4 and concen-
trated in vacuo. The residue was recrystallized from
AcOEt±hexane to give 18 (22 g, 93%) as white powder,
(4R,5S)-4,5-Dihydroxy-1-(p-toluenesulfonyl)-2,3,4,5-tetra-
hydro-1H-1-benzazepine (19b). A solution of 20b (2.48 g,
6.61 mmol) and 1 N NaOH aqueous solution (72 mL) in
MeOH (80 mL) was stirred at room temperature for 3 h.
The reaction mixture was adjusted to pH 4±5 with 2 N
HCl and the solution was extracted with CH2Cl2. The extract
was dried over MgSO4 and concentrated in vacuo. The crys-
talline residue was washed with iso-PrOH to give 19b
(1.89 g, 86%, 99% ee), mp 139±1418C. [a]2D4123.88 (c
0.2, MeOH). Anal. Calcd for C17H19NO4S: C, 61.24; H,
5.74; N, 4.20. Found: C, 61.19; H, 5.61; N, 4.24.
1
mp 106±1088C. H NMR (CDCl3) d: 2.34 (3H, s), 2.60
(2H, d, J5.6 Hz), 3.83 (2H, t, J5.4 Hz), 5.63 (1H, dt,
J4.1, 12.3 Hz), 6.07 (1H, d, J12.3 Hz), 7.09±7.23 (5H,
m), 7.42 (2H, d, J8.2 Hz), 7.56±7.60 (1H, m). Anal. Calcd
for C17H17NO2S: C, 68.20; H, 5.72; N, 4.68. Found: C,
68.15; H, 5.64; N, 4.64.
(4S,5R)-4,5-Dimethylmethylenedioxy-1-( p-toluenesul-
fonyl)-2,3,4,5-tetrahydro-1H-1-benzazepine (21a).
A
solution of 19a (2.0 g, 6.0 mmol), 2,2-dimethoxypropane
(1.1 mL, 8.94 mmol) and p-TsOH (48 mg, 0.25 mmol) in
acetone (50 mL) was re¯uxed for 2 h, and the mixture was
concentrated in vacuo. The residue was puri®ed by column
chromatography (silica gel; eluent, CH2Cl2±AcOEt18:1)
to give 21a (2.5 g, quant.) as colorless oil. [a]2D4258.88 (c
0.03, MeOH). 1H NMR (CDCl3) d: 1.20±1.25 (1H, m), 1.39
(3H, s), 1.52 (3H, s), 2.10 (1H, t, J3.3 Hz), 2.44 (3H, s),
3.29 (1H, d, J4.1, 11.7 Hz), 4.05 (1H, dt, J4.7, 16.8 Hz),
4.34±4.43 (1H, m), 5.08 (1H, d, J7.5 Hz), 7.09 (1H, d,
J7.6 Hz), 7.22±7.38 (4H, m), 7.50 (1H, d, J7.6 Hz), 7.71
(2H, d, J8.2 Hz). Anal. Calcd for C20H23NO4S: C, 64.32;
H, 6.21; N, 3.75. Found: C, 64.07; H, 6.15; N, 3.70.
cis-4,5-Dihydroxy-1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-
1H-1-benzazepine ((^)-19). N-Methylmorpholine N-oxide
(7.83 g, 66.8 mmol) and osmium tetroxide (4 wt% solution
in water, 5.0 mL, 23.8 mmol) were added to a solution of 18
(10.0 g, 33.4 mmol) in acetone (200 mL), t-BuOH (50 mL)
and water (50 mL) and the mixture was stirred at room
temperature for 14 h. Osmium tetroxide (5 mL) was added
to the reaction mixture and the mixture was stirred for 60 h.
Saturated NaHSO3 aqueous solution was added to the
mixture and the solution was stirred for 5 min. The reaction
mixture was extracted with AcOEt. The extract was washed
with 1N HCl and water, dried over Na2SO4 and concentrated
in vacuo. The residue was puri®ed by column chromato-
graphy (silica gel; eluent, hexane±AcOEt3:1) and recrys-
tallized from AcOEt±hexane to give 19 (7.7 g, 69%), as
(4R,5S)-4,5-Dimethylmethylenedioxy-1-( p-toluenesul-
fonyl)-2,3,4,5-tetrahydro-1H-1-benzazepine (21b). The title
compound was prepared from 19b, 2,2-dimethoxypropane
and p-TsOH by the procedure described for the preparation
of 21a. The product was puri®ed by column chromato-
graphy to give 21b (quant.) as colorless oil. [a]2D4158.08
(c 0.1, MeOH). Anal. Calcd for C20H23NO4S: C, 64.32; H,
6.21; N, 3.75. Found: C, 64.25; H, 6.06; N, 3.79.
1
white powder, mp 153±1558C. H NMR (DMSO-d6) d:
1.60±1.80 (1H, m), 1.95±2.10 (1H, m), 2.39 (3H, s),
3.05±3.20 (1H, m), 3.85±4.00 (2H, m), 4.52 (1H, d, J
5.2 Hz), 4.57 (1H, d, J3.9 Hz), 5.34 (1H, d, J5.2 Hz),
6.96 (1H, d, J7.7 Hz), 7.17 (1H, t, J1.4 Hz), 7.27 (1H, t,
J6.5 Hz), 7.40 (2H, d, J8.1 Hz), 7.52 (1H, d, J7.4 Hz),