1676
Vol. 54, No. 12
1
(473.9 mg, 66%) as an amorphous powder. H-NMR (400 MHz, CDCl3) d:
0.74 (3H, d, Jꢄ6.8 Hz), 0.91 (3H, d, Jꢄ7.0 Hz), 1.70 (2H, br), 2.03—2.10
(1H, m), 2.46—2.68 (3H, m), 3.56 (1H, br s), 3.79—3.86 (1H, m), 3.92 (3H,
s), 5.04 (1H, br s), 5.11 (4H, s, 2ꢆOCH2O), 6.43 (2H, s), 6.73 (2H, d,
Jꢄ8.4 Hz), 6.91 (2H, d, Jꢄ8.4Hz), 7.28—7.43 (10H, m). 13C-NMR
(100 MHz, CDCl3) d: 16.2, 19.4, 30.8, 32.5, 41.4, 60.9, 63.6, 71.1 (2C),
76.7, 106.2 (2C), 115.4 (2C), 127.3 (4C), 128.0 (2C), 128.6 (4C), 129.7
(2H, d, Jꢄ8.5 Hz), 6.87 and 6.90 (2H, d, Jꢄ8.6 Hz), 7.26—7.41 (10H, m).
13C-NMR (100 MHz, CDCl3) d: 14.9, 15.9, 18.1, 18.6, 28.2, 32.4, 32.8,
34.2, 40.9, 40.9, 60.9, 61.1, 63.9, 64.2, 71.1, 71.4, 76.1, 107.5, 115.5, 127.2,
128.0, 128.3, 128.6, 128.7, 129.4, 129.7, 129.8, 130.2, 131.5, 136.3, 136.6,
140.5, 141.3, 152.7, 154.8, 154.8, 166.4, 166.8. IR (CHCl3) cmꢀ1: 3325,
2936, 1697, 1597, 1516, 1504, 1445, 1420, 1371, 1346, 1327, 1292, 1259,
1238, 1167, 1115, 1078, 1003, 826. FAB-MS m/z: 662 (Mꢃ). HR-MS m/z:
662.2608 (Calcd for C37H37F3N2O6: 662.2604).
(2C), 134.9, 136.7 (2C), 140.1, 152.9 (2C), 154.9, 174.4. IR (CHCl3) cmꢀ1
:
3327, 2964, 1682, 1595, 1516, 1445, 1369, 1352, 1327, 1259, 1240, 1113,
1078, 1003, 827. EI-MS m/z: 566 (Mꢃ). HR-MS m/z: 566.2784 (Calcd for
C35H38N2O5: 566.2780).
(2S,5R)-5-Benzyl-3-(4-hydroxyphenethyl)-1-(2,2,2-trifluoroacetyl)-2-
(3,4,5-trimethoxyphenyl)-imidazolin-4-one (30c) Trifluoroacetic anhy-
dride (0.23 ml, 1.62 mmol) was added to a solution of 29c (311.6 mg,
0.67 mmol) in pyridine (3.0 ml) at 0 °C and the mixture was stirred for
60 min. After the reaction, methanol (3 ml) was added to the mixture, which
was concentrated in vacuo. The residue was partitioned between ethyl ac-
etate and 1 M hydrochloric acid. The organic layer was washed with a satu-
rated aqueous solution of sodium bicarbonate, dried over sodium sulfate,
and concentrated in vacuo. The residue was purified by silica gel chromatog-
raphy (hexane : ethyl acetateꢄ1 : 1) to give 30c (358 mg, 95%) as colorless
(2S,5R)-5-Benzyl-3-(4-hydroxyphenethyl)-2-(3,4,5-trimethoxy-
phenyl)imidazolidin-4-one (29c) A mixture of 3,4,5-trimethoxybenzalde-
hyde (9) (2.6 g, 13.2 mmol) and 28a (2.5 g, 8.8 mmol) in dioxane (30 ml)
was stirred at room temperature for 12 h. And then, 4.0 M HCl in dioxane
(20 ml) was added to the reaction mixture at 0 °C, which was stirred at room
temperature for another 12 h. The reaction mixture was then concentrated in
vacuo and an aqueous solution of sodium bicarbonate was added and ex-
tracted with ethyl acetate. The organic layer was washed with a saturated
aqueous solution of sodium chloride, dried over sodium sulfate, and concen-
trated in vacuo. The residue was purified by silica gel column chromatogra-
phy (hexane : ethyl acetateꢄ2 : 1) to give 29c (1.75 g, 43%) as an amorphous
1
crystals. H-NMR (400 MHz, CDCl3) d: 2.17 (1H, br t, Jꢄ8.8 Hz), 2.26—
2.50 (3H, m), 3.34 (0.5H, dd, Jꢄ14.5, 4.6 Hz, A part of AB), 3.46 (0.5 H,
dd, Jꢄ14.5, 2.2 Hz, B part of AB), 3.36 (0.5H, dd, Jꢄ14.0, 2.2 Hz, Aꢂ part
of AB), 3.58 and 3.73 (1H, m), 3.72 (0.5H, dd, Jꢄ14.0, 4.9 Hz, Bꢂ part of
AꢂBꢂ), 3.76 (3H, s), 3.77 (3H, s), 3.82 (3H, s), 5.01 and 5.08 (1H, m), 5.52
and 5.59 (1H, br s), 6.04 and 6.21 (2H, s), 6.57 and 6.61 (2H, d, Jꢄ8.4 Hz),
6.67 (2H, d, Jꢄ8.4 Hz), 7.17 and 7.23 (2H, dd, Jꢄ7.4, 1.9 Hz), 7.36—7.40
(3H, m). 13C-NMR (100 MHz, CDCl3) d: 32.5, 33.1, 33.3, 38.7, 41.7, 41.8,
56.2, 56.3, 60.8, 60.9, 61.3, 76.2, 76.3, 104.2, 115.4, 127.6, 127.9, 128.7,
129.0, 129.6, 129.8, 130.15, 130.23, 130.3, 130.4, 131.6, 133.6, 134.7,
1
powder. H-NMR (400 MHz, CDCl3) d: 2.48—2.61 (2H, m), 2.78 (1H, m),
2.85 (1H, dd, Jꢄ13.8, 7.2 Hz, A part of AB), 3.05 (1H, dd, Jꢄ13.8, 3.9 Hz,
B part of AB type), 3.67 (1H, s), 3.80 (6H, s), 3.81 (3H, s), 3.74—3.93 (1H,
m), 4.02—4.05 (1H, m), 4.85 (1H, d, Jꢄ1.5 Hz), 6.34 (2H, s), 6.75 (2H, d,
Jꢄ8.6 Hz), 6.86 (2H, d, Jꢄ8.6 Hz), 7.22—7.38 (5H, m). 13C-NMR
(100 MHz, CDCl3) d: 32.7, 38.1, 42.1, 56.1 (2C), 59.9, 60.8, 76.3, 106.2
(2C), 115.5 (2C), 126.8, 128.5 (2C), 129.6 (2C), 129.66, 129.70 (2C), 134.5,
136.7, 138.5, 153.7 (2C), 155.1, 174.4. IR (CHCl3) cmꢀ1: 1686, 1597, 1516,
1447, 1425, 1329, 1238, 1130. EI-MS m/z: 462 (Mꢃ). HR-MS m/z:
462.2158 (Calcd for C27H30N2O5: 462.2154).
138.9, 139.6, 153.5, 153.7, 154.6, 154.7, 166.5, 167.1. IR (CHCl3) cmꢀ1
:
3323, 1701, 1597, 1516, 1466, 1425, 1350, 1329, 1240, 1169, 1130. EI-MS
m/z: 558 (Mꢃ). HR-MS m/z: 558.1977 (Calcd for C29H29F3N2O6: 558.1975).
Anal. Calcd for C29H29F3N2O6: C, 62.36; H, 5.23; N, 5.02. Found: C, 62.27;
H, 5.14; N, 4.90.
(2S,5R)-5-Benzyl-2-(3,5-dibenzyloxy-4-methoxyphenyl)-3-(4-hydroxy-
phenethyl)-1-(2,2,2-trifluoroacetyl)imidazolidin-4-one (30a) s-cis and s-
transꢃ2 : 1 Trifluoroacetic anhydride (0.89 ml, 6.33 mmol) was added to a
solution of 29a (1.63 g, 2.64 mmol) in pyridine (10 ml) at 0 °C and the mix-
ture was stirred for 15 min. After the reaction, methanol (10 ml) was added
to the mixture, which was concentrated in vacuo. The residue was parti-
tioned between ethyl acetate and 1 M hydrochloric acid. The organic layer
was washed with a saturated aqueous solution of sodium bicarbonate, dried
over sodium sulfate, and concentrated in vacuo. The residue was purified by
silica gel chromatography (hexane : ethyl acetateꢄ2 : 1) to give 30a (1.77 g,
94%) as colorless crystals; mp 118—135 °C. 1H-NMR (400 MHz, CDCl3) d:
1.96—2.09 (1H, m), 2.14—2.32 (2H, m), 3.25—3.33 (1H, m), 3.39—3.46
(1H, m), 3.53—3.60 (1H, m), 3.65 and 3.68 (1H, d, Jꢄ5.2 Hz), 3.86 and
3.87 (3H, s, OMe), 4.85 and 4.91 (1H, br s), 4.97—5.07 (4H, m,
2ꢆPhCH2O), 5.47 and 5.53 (1H, br s, –OH), 6.02 and 6.24 (2H, s), 6.47
(1H, d, Jꢄ8.5 Hz), 6.54 (1H, d, Jꢄ8.5 Hz), 6.63 and 6.65 (2H, d, Jꢄ8.5 Hz),
7.11—7.13 (1H, m), 7.18—7.20 (1H, m), 7.27—7.38 (13H, m). 13C-NMR
(100 MHz, CDCl3) d: 32.3, 33.0, 33.2, 38.6, 41.6, 60.8, 60.9, 61.0, 61.2,
71.2, 71.3, 76.0, 107.4, 113.5, 114.1, 115.4, 116.4, 116.7, 127.2, 127.2,
127.5, 127.9, 128.0, 128.1, 128.6, 128.6, 128.9, 129.6, 129.8, 130.0, 130.1,
130.2, 130.3, 131.2, 133.6, 134.6, 136.2, 136.6, 140.4, 141.2, 152.6, 154.6,
154.7, 155.2, 155.7, 156.1, 166.4, 167.0. IR (CHCl3) cmꢀ1: 3314, 1701,
1597, 1454, 1443, 1327, 1169, 1115. FAB-MS m/z: 711 (MꢃHꢃ). HR-MS
m/z: 711.2690 (Calcd for C41H38F3N2O6: 711.2682). Anal. Calcd for
C41H37F3N2O6: C, 69.29; H, 5.25; N, 3.94. Found: C, 69.13; H, 5.20; N,
3.82.
(2S,5R)-2-(3,5-Benzyloxy-4-methoxyphenyl)-3-(4-hydroxyphenethyl)-
5-isopropyl-1-(2,2,2-trifluoroacetyl)imidazolin-4-one (30b) Trifluoro-
acetic anhydride (0.02 ml, 0.147 mmol) was added to an ice-cooled solution
of 29b (34.8 mg, 0.06 mmol) in pyridine (1.0 ml) at 0 °C and the mixture was
stirred for 3 h. After the reaction, methanol (1.0 ml) was added to the mix-
ture, which was concentrated in vacuo. The residue was partitioned between
ethyl acetate and 1 M hydrochloric acid. The organic layer was washed with a
saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate,
and concentrated in vacuo. The residue was purified by silica gel chromatog-
raphy (chloroform : methanolꢄ10 : 1) to give 30b (30.5 mg, 77%) as color-
less crystals. 1H-NMR (400 MHz, CDCl3) d: 0.66 and 0.73 (3H, d,
Jꢄ6.9 Hz), 1.19 and 1.23 (3H, d, Jꢄ7.1 Hz), 2.13 and 2.43 (1H, m), 2.35—
2.49 (1H, m), 2.50—2.60 (1H, m), 3.71—3.82 (2H, m), 3.91 and 3.92 (3H,
s, OMe), 4.43 and 4.52 (1H, br s), 5.10 (2H, s, OCH2Ph), 5.06 (1H, d,
Jꢄ12.4 Hz, A part of AB type, OCH2Ph), 5.14 (1H, d, Jꢄ12.4 Hz, B part of
AB, OCH2Ph), 5.56 and 5.68 (1H, br s), 6.25 and 6.40 (2H, s), 6.72 and 6.75
Oxidative Coupling Reaction of 30a with PIFA PIFA (57.8 mg,
0.13 mmol) in 2,2,2-trifluoroethanol (3 ml) was added to a solution of 30a
(86.8 mg, 0.12 mmol) in 2,2,2-trifluoroethanol (3.0 ml) at ꢀ40 °C and the
mixture was stirred for 10 min. After the reaction, the mixture was concen-
trated in vacuo and the residue was purified by silica gel colum chromatog-
raphy (hexane : ethyl acetateꢄ2 : 1) to give 31a (51.8 mg, 61%) as an amor-
phous powder; 1H-NMR (400 MHz, CDCl3) d: 1.47 (0.5H, dd, Jꢄ16.5,
12.3 Hz, A part of AB type), 1.75 (0.5H, dd, Jꢄ16.5, 5.7 Hz, B part of AB
type), 1.88 (0.5H, dd, Jꢄ16.5, 5.5 Hz, Aꢂ part of AꢂBꢂ), 2.10 (0.5H, dd,
Jꢄ15.7, 12.6 Hz, Bꢂ part of AꢂBꢂ), 2.90 and 3.15 (1H, t, Jꢄ13.2 Hz), 3.27—
3.45 (1H, m), 3.57 (1H, dd, Jꢄ13.2, 5.2 Hz), 3.76 and 3.80 (3H, s, OMe),
3.75—3.85 (1H, m), 4.47 and 4.90 (1H, br s), 4.61 and 4.70 (1H, d,
Jꢄ10.6 Hz), 4.82 and 4.89 (1H, d, Jꢄ10.6 Hz), 4.99 and 5.04 (1H, d,
Jꢄ12.1 Hz), 5.08 and 5.21 (1H, d, Jꢄ12.1 Hz), 5.91 and 5.96 (1H, dd,
Jꢄ10.1, 1.7 Hz), 5.60 and 6.06 (1H, s), 6.14 and 6.15 (1H, d, Jꢄ10.1 Hz),
6.29 and 6.36 (1H, s), 6.69 and 6.78 (1H, dd, Jꢄ9.9, 3.0 Hz), 7.08—7.52
(15H, m). 13C-NMR (100 MHz, CDCl3) d: 32.6, 36.7, 37.2, 37.3, 39.1, 46.1,
46.5, 60.9, 62.7, 62.8, 70.4, 70.7, 70.9, 71.0, 75.8, 77.2, 104.4, 104.5, 121.4,
121.9, 122.6, 123.4, 126.0, 127.1, 127.2, 127.4, 127.5, 128.0, 128.1, 128.3,
128.4, 128.7, 128.9, 129.6, 129.8, 130.3, 133.2, 134.1, 136.0, 136.0, 136.2,
136.4, 143.7, 150.9, 152.5, 152.6, 153.4, 153.7, 155.9, 156.3, 156.8, 157.2,
164.7, 165.5, 184.6, 184.9. IR (CHCl3) cmꢀ1: 1707, 1660, 1456, 1333, 1184,
1171, 1117. FAB-MS m/z: 709 (MꢃHꢃ). HR-MS m/z: 709.2530 (Calcd for
C41H36F3N2O6: 709.2525).
Oxidative Coupling Reaction of 30b with PIFA PIFA (7.14 mg,
0.017 mmol) in 2,2,2-trifluoroethanol (0.5 ml) was added to a solution of
30b (10.0 mg, 0.015 mmol) in 2,2,2-trifluoroethanol (0.5 ml) at ꢀ40 °C and
the mixture was stirred for 15 min. After the reaction, the mixture was con-
centrated in vacuo and the residue was purified by silica gel column chro-
matography (chloroform : methanolꢄ1 : 1) to give 31b (4.5 mg, 45%) as an
amorphous powder; 1H-NMR (400 MHz, CDCl3) d: 0.86 and 0.94 (3H, d,
Jꢄ6.8 Hz), 1.23 and 1.30 (3H, d, Jꢄ7.0 Hz), 2.09 (1H, td, Jꢄ16.0, 5.5 Hz),
2.33 and 2.96 (1H, m), 2.59 (1H, dt, Jꢄ16.0, 5.5 Hz) , 3.17 and 3.20 (1H, t,
Jꢄ13.0 Hz), 3.74 and 3.90 (2H, dd, Jꢄ14.0, 5.5 Hz) 3.79 and 3.82 (3H, s),
4.06 and 4.41 (1H, br s), 4.72 and 4.73 (1H, d, Jꢄ10.5 Hz), 4.89 and 4.92
(1H, d, Jꢄ10.5 Hz), 5.01 and 5.03 (1H, d, Jꢄ12.5 Hz), 5.10 and 5.23 (1H, d,
Jꢄ12.5 Hz), 6.02 (1H, dd, Jꢄ10.1, 1.8 Hz), 6.22 and 6.24 (1H, dd, Jꢄ9.1,
1.8 Hz), 6.31 and 6.32 (1H, s), 6.71 and 6.75 (1H, s), 6.90 and 7.13 (1H, dd,
Jꢄ10.0, 3.0 Hz), 7.20—7.43 (10H, m). 13C-NMR (100 MHz, CDCl3) d:
15.0, 15.4, 17.9, 18.4, 25.8, 34.1, 36.9, 37.3, 37.4, 37.6, 46.7, 46.7, 60.9,
61.0, 65.6, 65.8, 70.5, 70.7, 70.8, 70.9, 75.8, 75.9, 104.3, 104.6, 121.6,