The Journal of Organic Chemistry
Note
MHz, CDCl ) δ (ppm) 195.3, 171.0, 155.3, 153.2, 139.6, 139.4, 139.2,
H O. The organic layer was separated, and the aqueous layer was
2
3
1
1
0
1
39.1, 138.7, 133.8, 133.3, 131.4, 127.7, 127.1, 126.7, 126.0, 125.8,
23.8, 119.0, 118.1, 118.0, 107.4, 73.8, 73.1, 58.7, 58.5, 54.0, 52.3, 25.1,
.0, −0.7; IR (KBr) ν 742, 788, 835, 854, 1101, 1143, 1190, 1208,
extracted with Et O (100 mL × 2). The combined organic phase was
2
washed with saturated NaHCO solution (50 mL) and saturated NaCl
3
solution (50 mL), dried over Na SO , filtered, and concentrated under
2
4
−1
395, 1456, 1484, 1587, 1685, 1755, 2842, 2903, 2936, 2968 cm ;
reduced pressure. The residue was purified by flash column
+
HRMS (ESI) exact mass calcd for C H O Si [(M + H) ] requires
m/z 581.1990, found m/z 581.1995; mp (°C) 159−161; [α]
+
iPrOH, 1.0 mL/min, 254 nm; t (major) = 13.8 min, t (minor) = 15.5
min) gave the isomeric composition of the product, 89% ee.
chromatography on silica gel (eluent, petroleum ether/ethyl acetate
34
32
7
20
1
= 10:1) to afford 13 as a pale solid (2.75 g, 86% yield): H NMR (400
D
144.0 (c 0.1, CHCl ). HPLC analysis (Chiralpak IC, 95:5 hex/
MHz, CDCl ) δ (ppm) 8.09−7.96 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H),
3
3
7.42 (t, J = 7.7 Hz, 2H), 6.84 (s, 1H), 6.43 (d, J = 3.4 Hz, 1H), 5.80 (s,
1H), 4.89 (d, J = 2.8 Hz, 1H), 3.91 (s, 3H), 3.85 (s, 3H), 3.84 (s, 3H),
R
R
cis-9H-Fluoren-9-yl4-benzoyl-6,7,8-trimethoxy-1,1-dimeth-
0.55 (s, 3H), 0.49 (s, 3H); 13C NMR (100 MHz, CDCl ) δ (ppm)
3
1
yl-3,4-dihydro-1H-benzo[c][1,2]oxasiline-3-carboxylate (2′). H
192.1, 164.0, 155.3, 154.0, 139.8, 134.4, 131.6, 128.4, 128.2, 126.9,
NMR (400 MHz, CDCl ) δ (ppm) 7.81 (dd, J = 8.4, 1.2 Hz, 2H), 7.63
117.5, 108.7, 78.2, 71.5, 59.0, 58.9, 54.5, 52.4, 0.0; IR (KBr) ν 717,
3
−
1
(
d, J = 7.5 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.48−7.42 (m, 1H), 7.39
793, 843, 1019, 1113, 1195, 1262, 1321, 1357, 1627, 1713, 2110 cm ;
+
(
m, 2H), 7.33−7.27 (m, 3H), 7.21 (m, 2H), 7.00 (dt, J = 7.5, 1.0 Hz,
HRMS (ESI) exact mass calcd for C H N O Si [(M + H) ] requires
22
24
2
7
2
0
1
2
0
1
1
1
7
1
H), 6.63 (s, 1H), 6.33 (s, 1H), 5.08 (d, J = 2.6 Hz, 1H), 5.01 (d, J =
m/z 457.1426, found m/z 457.1433; mp (°C) 114−115; [α] +5.1
(c 0.1, CHCl ). HPLC analysis (Chiralpak IC, 95:5 hex/iPrOH, 1.0
D
.6 Hz, 1H), 3.92 (s, 3H), 3.80 (s, 3H), 3.65 (s, 3H), 0.58 (s, 3H),
3
.39 (s, 3H); 13C NMR (100 MHz, CDCl ) δ (ppm) 196.8, 171.2,
3
mL/min, 254 nm; t (major) = 28.3 min, t (minor) = 24.3 min) gave
R
R
57.2, 154.9, 141.1, 140.9, 140.8, 140.6, 140.0, 137.5, 137.1, 132.6,
29.3, 129.1, 128.4, 128.1, 127.6, 127.5, 126.2, 125.9, 119.6, 119.4,
19.3, 108.3, 75.9, 73.2, 60.3, 60.1, 55.6, 50.5, 0.0, −0.7; IR (KBr) ν
46, 792, 838, 856, 1103, 1145, 1195, 1392, 1456, 1488, 1557, 1594,
the isomeric composition of the product, 92% ee.
(3R,4S)-6,7,8-Trimethoxy-3-(2-methoxy-2-oxoethyl)-1,1-di-
methyl-3,4-dihydro-1H-benzo[c][1,2]oxasilin-4-yl benzoate
(6). To a solution of 13 (2.26 g, 5.0 mmol, 1.0 equiv) in methanol
−1
685, 1754, 2839, 2908, 2940, 2963 cm ; HRMS (ESI) exact mass
(70 mL) was added a solution of PhCO
Ag (0.34 g, 1.5 mmol, 0.3
2
+
calcd for C H O Si [(M + H) ] requires m/z 581.1990, found m/z
equiv) in Et N (3.5 mL, 25 mmol, 5.0 equiv). The mixture was stirred
3
34
32
7
5
81.1995; mp (°C) 138−140. HPLC analysis (Chiralpak IC, 95:5 hex/
in dark overnight. The mixture was concentrated and was purified by
flash column chromatography on silica gel (eluent, petroleum ether/
ethyl acetate = 12:1) to afford 6 as an oil with 6/1 dr (1.80 g, 78%
iPrOH, 1.0 mL/min, 254 nm; t (major) = 7.4 min, t (minor) = 6.6
R
R
min) gave the isomeric composition of the product, 40% ee.
3S,4S)-9H-Fluoren-9-yl 4-(benzoyloxy)-6,7,8-trimethoxy-
,1-dimethyl-3,4-dihydro-1H-benzo[c][1,2]oxasiline-3-carbox-
ylate (11). To a solution of 2 (6.66 g, 11.5 mmol, 1.0 equiv) in DCE
80 mL) was added m-CPBA (7.94 g, 46.0 mmol, 4.0 equiv) and
Na HPO ·12H O (8.9 g, 92.0 mmol, 8.0 equiv) at room temperature.
(
yield). The two diastereoisomers could not be separated at the step
1
1
(1.80 g, 78% yield): H NMR (400 MHz, CDCl
) δ (ppm) 8.07−8.04
3
(m, 2.30H), 7.58−7.53 (m, 1.15H), 7.45−7.40 (m, 2.30H), 6.88 (s,
0.15H), 6.71 (s, 1H), 6.01−5.97 (m, 1.15H), 4.79 (dt, J = 6.8, 4.8 Hz,
1H), 4.75−4.69 (m, 0.15H), 3.92 (s, 3H), 3.91 (s, 0.45H), 3.85 (s,
3H), 3.84 (s, 0.45H), 3.81 (s, 3H), 3.69 (s, 0.45H), 3.65 (s, 3H), 2.68
(ddd, J = 21.3, 15.8, 6.7 Hz, 0.30H), 2.56 (d, J = 6.9 Hz, 2H), 0.46 (s,
0.45H), 0.44 (s, 3H), 0.40 (s, 3H), 0.39 (s, 0.45H); 1 C NMR (100
(
2
4
2
The reaction was allowed to stir at reflux for 15 min. Cooled to room
temperature, the reaction was quenched with a saturated aqueous
solution of Na SO (120 mL) and extracted with Et O (150 mL × 3).
3
2
3
2
The combined organic layers were washed with a saturated aqueous
MHz, CDCl ) δ169.9, 164.8, 156.0, 154.6, 140.1, 136.1, 132.2, 128.8,
3
solution of NaHCO (150 mL), dried over Na SO , filtered, and
concentrated under reduced pressure. The residue was purified by
flash chromatography on basic aluminum oxide (eluent, petroleum
127.4, 118.2, 108.1, 73.1, 70.9, 59.5, 59.4, 55.1, 50.7, 39.0, 0.00, −0.6;
170.3, 165.0, 156.0, 154.4, 140.3, 137.3, 132.1, 128.9, 127.4, 118.2,
109.3, 71.8, 69.3, 59.5 55.0, 38.4, 28.7, −0.8, −1.6; IR (KBr) ν 710,
3
2
4
−1
ether/ethyl acetate = 10:1) to give compound 11 as a white solid (4.80
795, 840, 1019, 1119, 1199, 1263, 1318, 1592, 1712, 1742 cm ;
1
+
g, 70% yield): H NMR (400 MHz, CDCl ) δ (ppm) 8.00 (dd, J = 8.4,
HRMS (ESI) exact mass calcd for C H O Si [(M + H) ] requires
3
23 28
8
20
1
.2 Hz, 2H), 7.63 (dd, J = 7.6, 3.0 Hz, 2H), 7.56−7.49 (m, 1H), 7.43−
m/z 461.1632, found m/z 461.1630; [α]
+20.0 (c 0.1, CHCl3).
D
7.33 (m, 4H), 7.22 (ddd, J = 8.4, 6.8, 0.8 Hz, 2H), 7.10 (dt, J = 7.5, 1.0
HPLC analysis (Chiralpak AD-H, 75:25 hex/iPrOH, 1.0 mL/min, 254
nm; t (major) = 19.4 min, t (minor) = 25.0 min) gave the isomeric
Hz, 1H), 6.93 (d, J = 7.5 Hz, 1H), 6.77 (s, 1H), 6.64 (s, 1H), 6.21 (d, J
2.9 Hz, 1H), 5.21 (d, J = 2.9 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H),
R
R
=
composition of the product, 89% ee.
13
3.72 (s, 3H), 0.54 (s, 3H), 0.46 (s, 3H); C NMR (100 MHz, CDCl3)
(4R,5S)-4-Hydroxy-5-(3,4,5-trimethoxyphenyl)dihydrofuran-
2(3H)-one (5). To a solution of 6 (1.48 g, 3.2 mmol, 1.0 equiv) in
methanol (15 mL), NaOMe (0.35g, 6.4 mmol, 2.0 equiv) was added.
The reaction mixture was stirred for 3 h. 25 mL saturated aqueous of
NaCl and 100 mL of EtOAc were added. The organic layer was
separated, and the aqueous layer was extracted with EtOAc (100 mL ×
2). The combined organic phase was washed with saturated NaCl
δ (ppm) 170.2, 164.1, 155.7, 153.7, 140.5, 134.0, 139.7, 139.6, 139.5,
1
1
0
1
33.3, 131.7, 128.5, 128.3, 128.1, 128.0, 126.9, 126.4, 126.1, 124.3,
24.2, 118.8, 118.5, 118.4, 109.3, 74.1, 73.7, 72.2, 59.1, 59.0, 54.5, 25.5,
.4, 0.0; IR (KBr) ν 665, 712, 764, 791, 843, 970, 1031, 1101, 1148,
−1
251, 1321, 1435, 1481, 1584, 1720, 1748, 1831, 2906, 2939 cm ;
+
HRMS (ESI) exact mass calcd for C H O Si [(M + H) ] requires
34
32
8
20
m/z 597.1939, found m/z 597.1940; mp (°C) 118−120; [α] +59.0
solution (50 mL), dried over Na
reduced pressure. The residue was dissolved in CH
2
SO
4
, filtered, and concentrated under
Cl (15 mL), and
D
(c 0.1, CHCl ). HPLC analysis (Chiralpak IC, 95:5 hex/iPrOH, 1.0
2
2
3
mL/min, 254 nm; t (major) = 9.1 min, t (minor) = 7.9 min) gave
p-TsOH (61 mg, 0.32 mmol, 0.1 equiv) was added to the mixture. The
reaction mixture was stirred for 2 h and then was concentrated. The
residue was purified by flash column chromatography on silica gel
R
R
the isomeric composition of the product, 91% ee.
3S,4S)-3-(2-Diazoacetyl)-6,7,8-trimethoxy-1,1-dimethyl-3,4-
(
dihydro-1H-benzo[c][1,2]oxasilin-4-yl benzoate (13). To a
solution of 11 (4.2 g, 7 mmol) in EtOAc (120 mL) was added 10%
palladium on carbon (800 mg). The mixture was stirred at room
(eluent, petroleum ether/ethyl acetate = 1:1) to afford 5 as a white
1
solid (0.69 g, 80% yield): H NMR (400 MHz, CDCl ) δ (ppm) 6.52
3
(s, 2H), 5.23 (d, J = 4.3 Hz, 1H), 4.47 (m, 1H), 3.84 (s, 6H), 3.82 (s,
3H), 2.96 (brs, 1H), 2.89 (dd, J = 17.7, 6.8 Hz, 1H), 2.62 (dd, J = 17.7,
temperature overnight under 1 atm of H . The resulting mixture was
2
filtered through Celite, washed with EtOAc, and the combined filtrates
5.5 Hz, 1H); 13C NMR (100 MHz, CDCl ) δ (ppm) 174.6, 153.6,
3
were concentrated under reduced pressure. To the solution of the
137.9, 132.5, 102.0, 87.5, 74.5, 60.9, 56.2, 37.2, 29.7; IR (KBr) ν 941,
residue 12 in dry THF (30 mL) was added Et N (0.97 mL, 8.4 mmol,
1001, 1046, 1128, 1173, 1242, 1337, 1469, 1510, 1601, 1783, 1848,
3
−1
1
.2 equiv) and ClCO Et (0.73 mL, 7.7 mmol, 1.1 equiv) at 0 °C and
2925, 3012, 3467 cm ; HRMS (ESI) exact mass calcd for C H O
2
13 16 6
+
under an atmosphere of argon. The resulting mixture was stirred at the
same temperature for 15 min and then was added dropwise to a stirred
solution of diazomethane (ca. 3.0 equiv) in diethyl ether. The resulting
mixture was allowed to warm to room temperature and stirred for 2 h.
Excess diazomethane was destroyed by 0.5 M solution of AcOH in
[(M + H) ] requires m/z 269.1020, found m/z 269.1021; mp (°C)
20
D
99−101; [α] +4.2 (c 0.1, CHCl ). HPLC analysis (Chiralpak IC,
3
80:20 hex/iPrOH, 1.0 mL/min, 254 nm; t (major) = 25.8 min, t
R
R
(minor) = 30.0 min) gave the isomeric composition of the product,
90% ee.
4
23
dx.doi.org/10.1021/jo4024232 | J. Org. Chem. 2014, 79, 419−425