T. Onishi et al. / Tetrahedron 60 (2004) 9503–9515
9511
10 mL of ethyl acetate, washed with 1 M HCl (2!2.5 mL),
H2O (1!2.5 mL), 5% NaHCO3 (2!2.5 mL), sat. brine sol.
(1!1 mL), dried over Na2SO4, filtered and evaporated to
yield the crude dipeptide as a brown foam which was
taken on crude. To the foam was added a stir bar and
ethanol (10 mL). Argon was bubbled through for 5 min
and 10% Pd/C (0.04 g) was added. The system was
flushed with H2 and a balloon of H2 was attached. The
solution was stirred vigorously for 1.5 h and then
filtered through celite, evaporated and placed on high
vacuum overnight. To the crude mixture was added a
stir bar, BOP reagent (0.27 g, 0.62 mmol) and aceto-
nitrile (5 mL). Triethylamine (0.086 mL, 0.62 mmol)
was added dropwise and the reaction was allowed to
stir for 8 h at which time the solvent was evaporated.
Purification via column chromatography with 75:20:5
CH2Cl2/AcOEt/iPrOH afforded 7 (127 mg, 39%) as a
white amorphous solid.
[1H]pyrrolo[2,1-c][1,4]oxazine], 1,2,30,40,80,80a-hexahy-
dro-6-methoxy-60-(2-methyl-1-propenyl)-10,2-dioxo-30-
40-diphenyl-, (3S,30S,40R,60S,80aR) (22). To a suspension
of oxyindole 21 (199 mg, 0.750 mmol) in toluene (10 mL)
was added trifluoroacetic acid (97 ml, 1.25 mmol) at once
at 0 8C. After stirring for 15 min at 0 8C, triethylamine
(174 ml, 1.25 mmol) was added at once. After stirring for
additional 5 min at 0 8C, water (6.1 mL) and toluene
(10 mL) were added and the mixture was filtrated through
celite. The residue was washed by toluene (2.5 mL). The
organic layer was separated by phase separation and was
dried over anhydrous sodium sulfate (2.5 g) and anhy-
drous magnesium sulfate (2.5 g) for 20 min. The drying
reagents were removed by filtration and the residue was
washed with toluene (1 mL). To the combined toluene
˚
solution were added 0.5 g of activated 3 A molecular
sieves, (5R,6S)-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-
2-one (127 mg, 0.5 mmol), 3-methyl-3-methoxybutanal
(70 mg, 0.6 mmol) and toluene (4 mL) at K15 8C. After
stirring for 25 h at 0 8C, the mixture was filtrated through
celite to remove the sieves and concentrated in vacuo. The
product was purified by thin layer chromatography (eluted
with 1:2 hexane/AcOEt) to give 17 (115 mg, 44%) and 22
(51 mg, 20%).
[a]2D5ZK57.3 (CH2Cl2, cZ1.1); 1H NMR (400 MHz,
CDCl3) d CHCl3: 1.05 (s, 3H), 1.15 (s, 3H), 1.21 (s, 9H),
1.70 (dd, JZ4.0, 18.4 Hz, 2H), 1.78 (quint, JZ8.4 Hz, 1H),
1.85–1.96 (m, 1H), 1.96–2.08 (m, 1H), 2.15 (dd, JZ9.6,
14.0 Hz, 1H), 2.49 (quint, JZ6.0 Hz, 1H), 2.95 (s, 3H), 3.43
(d, JZ9.6 Hz, 1H), 3.39 (ddd, JZ3.6, 10.0, 13.6 Hz, 1H),
3.76 (s, 3H), 3.89 (dt, JZ8.0, 12.4 Hz, 1H), 4.24 (dd, JZ
6.0, 11.6 Hz, 1H), 4.80 (dd, JZ4.4, 9.6 Hz, 1H), 4.96 (d,
JZ10.0 Hz, 1H), 6.45 (d, JZ2.0 Hz, 1H), 6.47 (dd, JZ2.0,
8.4 Hz, 1H), 7.13 (d, JZ8.4 Hz, 1H), 8.01 (brs, 1H); 13C
NMR (75 MHz, CDCl3) d CHCl3: 12.9, 20.7, 23.1, 23.7,
29.1, 38.4, 43.8, 47.9, 53.3, 56.1, 59.3, 59.6, 60.1, 60.6,
73.5, 109.6, 121.1, 123.6, 126.3, 128.5, 141.0, 161.8, 165.2,
Compound 17.
A pale yellow amorphous solid:
[a]2D4ZK46.0 (CHCl3, cZ1); 1H NMR (400 MHz,
CDCl3) d CHCl3: 1.02 (s, 3H), 1.09 (s, 3H), 1.36 (dd,
JZ5.6, 15.6 Hz, 1H), 1.61 (dd, JZ2.1, 15.6 Hz, 1H), 2.44
(dd, JZ8.0, 12.6 Hz, 1H), 2.69 (dd, JZ10.4, 12.6 Hz, 1H),
3.04 (s, 3H), 3.81 (s, 3H), 4.01 (dd, JZ2.1, 5.6 Hz, 1H),
4.46 (dd, JZ8.0, 10.4 Hz, 1H), 4.85 (d, JZ2.6 Hz, 1H),
6.29 (d, JZ2.6 Hz, 1H), 6.55 (d, JZ2.1 Hz, 1H), 6.57 (dd,
JZ2.1, 8.4 Hz, 1H), 6.99–7.05 (m, 2H), 7.13–7.33 (m, 9H),
8.35 (brs, 1H); 13C NMR (100 MHz, CDCl3) d CHCl3: 23.5,
25.0, 41.4, 44.5, 49.1, 55.5, 56.5, 56.7, 59.2, 64.6, 73.3,
76.4, 97.3, 107.4, 122.6, 125.5, 125.7, 127.2, 127.6, 128.0,
128.3, 128.8, 136.8, 136.8, 141.6, 160.2, 172.2, 179.2; IR
(NaCl/neat) 1726, 1631, 1505, 1271, 1238, 1193, 1148, 755,
698 cmK1; HRMS (FABC) calcd for C32H35O5N2 (m/z)
527.2546, found (m/z) 527.2540.
168.8, 179.5; IR (NaCl/neat) 3244, 1763, 1667, 1665 cmK1
;
HRMS (FABC) calcd for C28H38O7N3 (m/z) 528.2710,
found (m/z) 528.2714.
4.1.5. 3-Hydroxy-6-methoxy-3-trimethylsilyl-1,3-dihy-
droindole-2-one (21). To a suspension of 6-methoxy-1H-
indole-2,3-dione (3.22 g, 20 mmol) in tetrahydrofuran
(200 mL) was gradually added a 1.0 M solution of
(trimethylsilyl)methyllithium in pentane (50 mL,
50 mmol) at K78 8C. After stirring for 3 h at K78 8C,
saturated aqueous ammonium chloride solution was added.
The product was extracted with ethyl acetate and dichlor-
omethane. The combined organic layer was dried over
anhydrous sulfate and concentrated to give 21 (4.49 g, 85%)
as a white solid. The compound 21 was used for the next
reaction without further purification.
Compound 22.
A pale yellow amorphous solid:
[a]2D4ZK36.4 (CHCl3, cZ0.55); 1H NMR (400 MHz,
CDCl3) d CHCl3: 1.54 (s, 3H), 1.74 (s, 3H), 2.48 (dd, JZ
8.4, 13.0 Hz, 1H), 2.75 (dd, JZ9.6, 13.0 Hz, 1H), 3.80 (s,
3H), 4.27 (d, JZ3.0 Hz, 1H), 4.52 (d, JZ9.4 Hz, 1H), 4.54
(dd, JZ8.4, 9.6 Hz, 1H), 4.70 (d, JZ9.4 Hz, 1H), 6.18 (d,
JZ3.0 Hz, 1H), 6.48 (d, JZ2.3 Hz, 1H), 6.56 (dd, JZ2.3,
8.4 Hz, 1H), 7.02–7.07 (m, 2H), 7.15–7.33 (m, 9H), 7.75
(brs, 1H); 13C NMR (100 MHz, CDCl3) d CHCl3: 18.6,
26.2, 40.0, 55.5, 56.3, 56.6, 60.2, 67.5, 97.2, 107.2, 120.8,
122.1, 125.6, 125.7, 127.4, 127.9, 128.0, 128.4, 128.9,
136.2, 136.4, 139.9, 141.2, 160.1, 168.5, 171.9, 178.3; IR
(NaCl/neat) 3261, 1723, 1631, 1504, 1453, 1193, 1153, 755,
698 cm-1; HRMS (FABC) calcd for C31H31O4N2 (m/z)
495.2284, found (m/z) 495.2267.
1H NMR (400 MHz, CDCl3) d CHCl3: K0.22 (s, 9H), 1.49
(d, JZ10.2 Hz, 1H), 1.53 (d, JZ10.2 Hz, 1H), 2.65 (s, 1H),
3.79 (s, 3H), 6.45 (d, JZ1.8 Hz, 1H), 6.56 (dd, JZ1.8,
6.3 Hz, 1H), 7.23 (d, JZ6.3 Hz, 1H), 7.88 (brs, 1H); 13C
NMR (100 MHz, CDCl3) d CHCl3: K1.1, 28.3, 55.5, 75.5,
97.5, 107.5, 123.4, 125.4, 141.1, 161.2, 180.6; IR (NaCl/
neat) 3388, 1714, 1634, 1507, 1351, 1251, 1151, 1125,
840 cm-1; HRMS (FABC) calcd for C13H19O3NSi (m/z)
265.1134, found (m/z) 265.1132.
4.2. Confirmation of the relative configuration of 17 by
NOESY
4.1.6.
Spiro[3H-indole-3,70(60H)-[1H]pyrrolo[2,1-
c][1,4]oxazine], 1,2,30,40,80,80a-hexahydro-6-methoxy-60-
(2-methoxy-2-methylpropyl)-10,2-dioxo-30-40-diphenyl-,
(3S,30S,40R,60S,80aR) (17) and Spiro[3H-indole-3,70(60H)-
NOE’s were obrserved between 0the proton at position 4 of
the oxyindole and the proton at 8 a, between the proton at 60