J. Yamazaki et al. / Tetrahedron: Asymmetry 13 (2002) 729–734
733
1
8
the same temperature. A solution of 8 (106 mg, 0.28
mmol) in DMF (5 mL) was added and the mixture was
stirred for 48 h at an ambient temperature. The reac-
tion mixture was poured into water and extracted with
Et O. The Et O layer was successively washed with
water and brine, and then dried. Evaporation of the
solvent under reduced pressure left a residue, which was
purified by p-TLC on silica gel with hexane/AcOEt
Compound 4: amorphous; [h]D +306 (c 0.34, CHCl ,
1
3
H
inseparable mixture of diastereomers (ca. 1:1));
NMR (270 MHz, CDCl ) l 7.99–7.86 (m, 8H), 7.52–
7.37 (m, 8H), 7.30–7.08 (m, 8H), 3.65 (s, 3H), 3.49 (s,
3H), 3.13–2.91 (m, 2H), 2.74–2.60 (m, 8H), 2.10–1.84
(m, 4H), 1.60–1.48 (m, 4H), 1.60–0.97 (m, 4H, over-
lapped), 1.03 (s, 3H), 0.97 (s, 3H); IR (CHCl ) 3021,
2960, 2880, 1725, 1590, 1465, 1435, 1288, 1225, 1194,
1072, 963 cm ; MS (m/z) 556 (M ); HRMS (m/z)
calcd for C H O P (M ) 556.1651, found: 556.1630.
3
2
2
3
−
1
+
(
1/1) to afford 9 as an amorphous solid (97.1 mg, 53%).
1
8
+
9
: [h] +236 (c 0.75, CHCl , inseparable mixture of
D
3
23 29
7
1
diastereomers (ca. 1:1)); H NMR (200 MHz, CDCl ) l
3
8
8
3
2
1
1
.15–7.96 (m, 8H), 7.64–7.49 (m, 8H), 7.36–7.28 (m,
H), 4.00–3.79 (m, 16H), 3.84 (s, 3H), 3.61 (s, 3H),
.31–3.08 (m, 2H), 2.39–1.88 (m, 4H), 1.73–1.49 (m,
0H), 1.12 (s, 3H), 1.05 (s, 3H); IR (KBr) 2960, 2880,
740, 1590, 1510, 1465, 1435, 1325, 1290, 1225, 1155,
4.8. Cyclization of 4 and 10 to 11 and 12
A solution of 10 (19.5 mg, 0.03 mmol) in THF (4.0 mL)
was treated with a solution of Et Zn (0.05 mL, 1.0 M in
2
−
1
+
065, 1035 cm ; MS (m/z) 658 (M ); HRMS (m/z)
hexane, 0.05 mmol, 1.4 equiv.) at −78°C and the mix-
ture was initially stirred at −78°C and then allowed to
warm to room temperature over 17 h under Ar with
stirring. The mixture was poured into cold saturated
+
calcd for C H O P (M ) 658.2331, found: 658.2361.
3
7
39
9
In the same way as above for the preparation of 9, 3
was provided from 2 and (S)-1 as an inseparable mix-
ture of diastereomers in 48% yield after purification by
p-TLC on silica gel with hexane/AcOEt (1/2).
aq. NH Cl solution and extracted with AcOEt. The
4
extracts were washed with water and brine. Drying and
successive evaporation of the solvent gave the residue,
which was subjected to p-TLC (hexane/AcOEt, 3/1).
The cyclized compound 12 was obtained as an oil (6.2
mg, 82%). The optical purity of the sample was ana-
lyzed by HPLC.
1
8
Compound 3: amorphous; [h] +229 (c 0.46, CHCl ,
inseparable mixture of diastereomers (ca. 1:1));
NMR (270 MHz, CDCl ) l 8.57–7.28 (m, 24H), 4.00–
D
3
H
1
3
3
2
3
1
1
.75 (m, 16H), 3.72 (s, 3H), 3.62 (s, 3H), 3.54–3.30 (m,
H), 2.27–1.84 (m, 12H), 1.53–1.17 (m, 8H), 1.13 (s,
1
8
Compound 12: colorless oil; [h] +114 (c 0.40, CHCl3,
D
1
H), 1.07 (s, 3H); IR (CHCl ) 3002, 2982, 2957, 1759,
81% e.e.); H NMR (200 MHz, CDCl ) l 3.68 (s, 3H),
3.05 (brd, 1H, J=14.6 Hz), 2.70–2.52 (m, 1H), 2.43–
2.16 (m, 4H), 2.06–1.82 (m, 2H), 1.69–1.55 (m, 4H),
1.29 (s, 3H); IR (CHCl ) 3020, 2935, 1705, 1435, 1230,
1085, 1010 cm ; CD (MeOH) see Fig. 1; UV (MeOH)
3
3
747, 1743, 1739, 1728, 1722, 1512, 1504, 1462, 1435,
−
1
323, 1286, 1240, 1161, 1074, 1039 cm . Anal. calcd
for C H O P: C, 67.87; H, 5.78. Found: C, 66.78; H,
3
6
37
9
3
−
1
6.03%.
umax 228.6 nm (m 5850). Anal. calcd for C H O : C,
13
18
3
7
0.25; H, 8.16. Found: C, 69.96; H, 8.27%.
4.7. Acidic hydrolysis of 3 and 9 to 4 and 10
A solution of 9 (183 mg, 0.28 mmol) and HClO (0.3
In the same way as above for the cyclization of 10,
compound 11 was formed as an oil in 49% yield after
purification by p-TLC on silica gel with hexane/AcOEt
(3/1).
4
mL, 70% in H O) in MeOH/H O (4/1, 5 mL) was
2
2
stirred for 1 h at 40°C, and then poured into satd aq.
NaHCO solution at 0°C. The mixture was extracted
3
with AcOEt and the extracts were washed with water
and brine. Drying and following evaporation of the
solvent gave the residue, which was subjected to p-TLC
1
8
Compound 11: colorless oil; [h]
+251 (c 0.60, CHCl
,
3
D
1
80% e.e.); H NMR (270 MHz, CDCl ) l 3.75 (s, 3H),
3.45 (dd, 1H, J=15.8, 9.9 Hz), 2.92–2.82 (m, 1H),
2.76–2.64 (m, 1H), 2.35–1.18 (m, 3H), 1.85–1.64 (m,
3H), 1.41–1.25 (m, 1H), 1.20 (s, 3H); IR (CHCl
950, 1738, 1705, 1651, 1437, 1271, 1114, 1024 cm ;
CD (MeOH) see Fig. 1; UV (MeOH) umax 232.6 nm (m
900); MS (m/z) 208 (M ); HRMS (m/z) calcd for
3
(
hexane/AcOEt, 1/2). Compound 10 was obtained as an
inseparable mixture of diastereomers (100 mg, 63%
yield)
) 3025,
3
−1
2
1
8
Compound 10: amorphous; [h] +244 (c 0.77, CHCl ,
D
3
H
1
+
inseparable mixture of diastereomers (ca. 1:1));
+
NMR (200 MHz, CDCl ) l 8.09–7.98 (m, 8H), 7.63–
C
12
H
16
O
3
(M ) 208.1100. Found: 208.1096.
3
7
3
.49 (m, 8H), 7.37–7.28 (m, 8H), 3.75 (s, 3H), 3.59 (s,
H), 3.29–3.00 (m, 2H), 2.64 (dd, 8H, J=15.0, 6.7,
overlapped), 2.34–1.73 (m, 16H), 1.40–1.00 (m, 4H,
4.9. Dibenzoate 14
overlapped), 1.20 (s, 3H); IR (CHCl ) 3010, 2960, 2880,
3
1
1
730, 1695, 1590, 1510, 1465, 1435, 1325, 1290, 1225,
To a stirred solution of 12 (12.0 mg, 0.05 mmol) in
THF (5.0 mL) was added a solution of DIBAL-H (0.14
mL, 1.5 M in toluene, 0.21 mmol, 4.0 equiv.) at −78°C
and the mixture was further stirred for 1.5 h at the
same temperature and for 1 h at 0°C. The mixture was
−
1
+
155, 1065, 1035 cm ; MS (m/z) 570 (M ); HRMS
+
(
m/z) calcd for C H O P (M ) 570.1784, found:
33 31 7
5
70.1838. Anal. calcd for C H O P: C, 69.47; H, 5.48.
33 31 7
Found: C, 69.75; H, 5.53%.
poured into cold sat. aqueous NH Cl solution and
4
Similarly, 4 was obtained from 3 as an inseparable
mixture of diastereomers in 47% yield.
extracted with AcOEt. Washing with water and brine,
drying and evaporation left the residue (10.6 mg) con-