3.38 mmol) and Zn powder (442 mg, 6.76 mmol) with stirring under
a nitrogen atmosphere. After stirring for 0.5 h, the reaction mixture
developed a dark green color and was cooled to -20 °C. Then,
epoxy alcohol (1.13 mmol), dissolved in dry THF (4 mL), was
added to the reaction mixture followed by the addition of the dry
and freshly distilled radical quencher (20 equiv of the epoxy alcohol)
at the same temperature. The reaction was continued at -20 °C
for 2 h, allowed to warm slowly to room temperature, and stirred
for 14 h. It was then quenched with 1 N HCl (10 mL) and extracted
with diethyl ether. The combined organic extracts were washed
with H2O and brine, dried over Na2SO4, and concentrated in vacuo.
The residue was purified by silica gel column chromatography to
furnish the pure products, which were characterized by standard
spectroscopic methods.
1H NMR (200 MHz, CDCl3, major isomer 9): δ 7.34-7.18 (m,
5H), 4.53 (ABq, 2H), 3.81 (dd, J ) 7.5, 3.4 Hz, 1H), 3.66-3.34
(m, 5H), 1.8-1.4 (m, 4H), 1.37 (s, 3H), 1.32 (s, 3H), 1.06 (d, J )
6.7 Hz, 3H), 0.85 (s, 3H). 13C NMR (75 MHz, CDCl3, major isomer
9): δ 138.5, 128.2, 127.5, 127.4, 100.8, 73.5, 73.2, 72.0, 70.1, 63.7,
40.7, 30.0, 27.6, 24.3, 24.0, 17.3, 14.4. MS (LCMS): m/z (%) 345
(70) [M + Na]+. HRMS (ESI): calcd for C19H30O4Na [M + Na]+,
345.2041; found, 345.2035.
Synthesis of Acetonide 11. Ring opening of 4 using acrylonitrile
as the radical quencher gave an intermediate diol as a single isomer,
which was transformed into acetonide 11 following the same
procedure as that used in the synthesis of 7 in 40% overall yield
from 4. Rf ) 0.6 (silica gel, 20% EtOAc in hexane). IR (KBr):
1
νmax 2925, 2861, 2247, 1105 cm-1. H NMR (200 MHz, CDCl3):
Synthesis of 5 and 6. According to the general procedure of
epoxide opening described above, compound 4, using methyl
acrylate as a radical quencher, gave an inseparable mixture of
lactones 5 and 6 (in 2:1 ratio) in 75% yield. Rf ) 0.4 (silica gel,
50% EtOAc in hexane). IR (KBr): νmax 3447 (b), 2922, 1722, 1635,
δ 7.4-7.24 (m, 5H), 4.49 (ABq, 2H), 3.98-3.84 (m, 1H), 3.91 (q,
J ) 6.2 Hz, 1H), 3.55 (dd, J ) 10.2, 6.1 Hz, 1H), 3.33 (dd, J )
10.2, 4.2 Hz, 1H), 2.48-2.16 (m, 2H), 1.90-1.56 (m, 2H), 1.43
(s, 3H), 1.34 (s, 3H), 1.05 (d, J ) 6.2 Hz, 3H), 0.84 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 137.8, 128.5, 127.9, 127.7, 119.6, 98.6,
73.6, 70.2, 69.9, 37.7, 30.3, 29.8, 29.6, 19.5, 14.7, 12.7, 11.8. MS
(ESI): m/z (%) 318 (10) [M + H]+, 335 (100) [M + NH4]+. HRMS
(ESI): calcd for C19H28NO3 [M + H]+, 318.2069; found, 318.2063.
Synthesis of Acetonides 12 and 13. Acetonides 12 and 13 were
prepared as an inseparable mixture of diastereomers in a 2:1 ratio
and in 45% overall yield from 8 using acrylonitrile as the radical
quencher in the same way as that used for the synthesis of 11. Rf
) 0.6 (silica gel, 20% EtOAc in hexane). IR (KBr): νmax 2984,
2933, 2246, 1381, 1225, 1105 cm-1. 1H NMR (200 MHz, CDCl3,
mixture of 12 and 13): δ 7.40-7.24 (m, 5H), 4.64-4.40 (m, 2H),
3.78-3.40 (m, 4H), 2.52-2.32 (m, 2H), 1.82-1.60 (m, 2H), 1.33
and 1.30 (two s, total 9H), 1.07 (two d, J ) 6.1 Hz, total 3H), 0.87
and 0.79 (two s, total 3H). 13C NMR (75 MHz, CDCl3, mixture of
12 and 13): δ 137.9, 137.7, 128.4, 127.8, 127.76, 127.73, 127.6,
127.6, 120.1, 101.2, 101.1, 74.9, 73.5, 71.7, 71.4, 69.6, 68.9, 68.8,
41.4, 41.1, 30.1, 29.8, 29.6, 24.1, 24.0, 23.94, 23.90, 17.5, 17.3,
15.6, 14.3, 12.8, 12.6. MS (LCMS): m/z (%) 318 (60) [M + H]+.
HRMS (ESI): calcd for C19H28NO3 [M + H]+, 318.2069; found,
318.2060.
1
1379, 1215 cm-1. H NMR (300 MHz, CDCl3, major product 5):
δ 7.38-7.23 (m, 5H), 4.55 (ABq, 2H), 4.37 (q, J ) 6.7 Hz), 3.71
(dd, J ) 9.1, 2.3 Hz, 1H), 3.57 (dd, J ) 9.1, 2.3 Hz, 1H), 3.36 (t,
J ) 9.1 Hz, 1H), 2.51-2.42 (m, 2H), 1.97-1.82 and 1.52-1.41
(two m, 2H), 1.39 (d, J ) 6.7 Hz, 3H), 1.10 (s, 3H). 13C NMR (75
MHz, CDCl3, mixture of 5 and 6): δ 171.4, 171.1, 137.5, 137.4,
128.5, 127.9, 127.7, 85.06, 82.3, 74.0, 73.5, 73.0, 70.7, 70.4, 69.2,
29.6, 28.2, 26.5, 26.3, 25.7, 18.5, 17.6, 16.7, 16.4. MS (ESI): m/z
(%) 279 (10) [M + H]+, 296 (100) [M + NH4]+, 301 (60) [M +
Na]+. HRMS (ESI): calcd for C16H23O4 [M + H]+, 279.1596;
found, 279.1600.
Synthesis of Acetonide 7. The mixture of lactones 5 and 6 (200
mg, 0.72 mmol) was taken in dry Et2O (4 mL). It was cooled to 0
°C. Then, lithium aluminum hydride (54.6 mg, 1.44 mmol) was
added and stirred for 0.5 h at 0 °C. The reaction was quenched
carefully with saturated Na2SO4 solution (2 mL) at 0 °C and
extracted with EtOAc. The combined organic layer was washed
with H2O and brine, dried (Na2SO4), and concentrated in vacuo.
The residue was purified by column chromatography (SiO2, 90%
EtOAc in hexane as eluant) to afford the triol as a colorless oil,
which was used directly in the next step.
Synthesis of 15. Activated Zn powder (863 mg, 13.2 mmol),
freshly fused ZnCl2 (894 mg, 6.6 mmol). and Cp2TiCl2 (1.6 g, 6.6
mmol) were taken in dry THF (65 mL) and stirred for 0.5 h at
room temperature. The color of the reaction mixture turned into
deep green. Then, it was cooled to -20 °C and compound 14 (500
mg, 2.2 mmol) in dry THF (10 mL) was added. The reaction
mixture was allowed to come to room temperature slowly. Then,
it was stirred for 15 h. The reaction was quenched with 1 N HCl
and extracted with Et2O. The combined organic layer was washed
with H2O and brine, dried (Na2SO4), and concentrated in vacuo.
Purification by column chromatography (SiO2, 26% EtOAc in
hexane eluant) provided the 1,3-diol 15 as a pure colorless oil (252
The triol was dissolved in dry CH2Cl2 (3 mL) and cooled to 0
°C. Then, 2,2-dimethoxypropane (0.35 mL, 2.9 mmol) was added
to it followed by (()-camphor-10-sulfonic acid (16.7 mg, 0.07
mmol). The reaction was allowed to come to room temperature
and was stirred for 3 h. Then, it was cooled to 0 °C, quenched
with saturated NaHCO3 solution, and extracted with EtOAc. The
combined organic extracts were washed with H2O and brine, dried
(Na2SO4), and concentrated in vacuo. Chromatographic purification
(SiO2, 20% EtOAc in hexane as eluant) afforded pure 7 (162 mg,
80% from 5 and 6) as a colorless oil. Rf ) 0.4 (silica gel, 30%
EtOAc in hexane). IR (KBr): νmax 3445, 2987, 2925, 2857, 1632,
mg, 50% yield). Rf ) 0.65 (silica gel, 50% EtOAc in hexane). [R]27
D
1
1457 cm-1. H NMR (500 MHz, CDCl3): δ 7.38-7.24 (m, 5H),
) -7.54 (c 0.5 in CHCl3). IR (KBr): νmax 3387, 2229, 2857, 1731
1
4.54 (ABq, 2H), 4.04 (dd, J ) 6.0, 3.8 Hz, 1H), 3.93 (q, J ) 6.3
Hz, 1H), 3.62 (dd, J ) 10.6, 3.8 Hz, 1H), 3.53-3.43 (m, 2H),
3.36 (dd, J ) 10.6, 6.0 Hz, 1H), 1.66-1.22 (m, 2H), 1.45 (s, 3H),
1.37 (s, 3H), 1.04 (d, J ) 6.3 Hz, 3H), 0.85 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 138.4, 128.3, 127.8, 127.6, 98.4, 74.5, 73.2, 70.2,
70.0, 63.2, 37.2, 30.8, 30.0, 26.1, 19.6, 14.5, 13.5. MS (ESI): m/z
(%) 323 (20) [M + H]+, 340 (100) [M + NH4]+, 345 (10) [M +
Na]+. HRMS (ESI): calcd for C19H30O4Na [M + Na]+, 345.2041;
found, 345.2047.
cm-1. H NMR (300 MHz, CDCl3): δ 4.40-4.34 (m, 1H), 4.15
(q, J ) 7.1 Hz, 2H), 4.02-3.88 (m, 1H), 3.86-3.72 (bs, 2H), 2.54-
2.22 (m, 3H), 1.92-1.66 (m, 3H), 1.54-1.38 (m, 1H), 1.32-1.05
(m, 2H), 1.30 (t, J ) 7.1 Hz, 3H), 1.27 (d, J ) 6.7 Hz, 3H), 0.99-
0.87 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 175.0, 67.4, 66.3,
60.9, 50.9, 39.5, 33.6, 32.8, 29.1, 20.2, 19.9, 14.1. MS (ESI): m/z
(%) 231 (100) [M + H]+, 253 (10) [M + Na]+. HRMS (ESI):
calcd for C12H23O4 [M + H]+, 231.1596; found, 231.1603.
Synthesis of 16. Diol 15 (200 mg, 0.87 mmol) was dissolved in
dry CH2Cl2 (4 mL) and cooled to 0 °C. 2,2-Dimethoxypropane (0.43
mL, 3.48 mmol) was added to it, followed by the addition of (()-
camphor-10-sulfonic acid (21 mg, 0.09 mmol). The reaction was
allowed to come to room temperature slowly and was stirred for 1
h. Then, it was cooled to 0 °C, quenched with saturated NaHCO3
solution, and extracted with EtOAc. The combined organic extracts
were washed with H2O and brine, dried (Na2SO4), and concentrated
Synthesis of Acetonides 9 and 10. The mixture of four lactones
obtained from 8 using methyl acrylate as the radical quencher
following the general procedure of epoxide opening described above
was converted to an inseparable mixture of acetonides 9 and 10,
using the same protocol as that used for the synthesis of 7, in a 4:1
ratio and in 82% yield. Rf ) 0.4 (silica gel, 30% EtOAc in hexane).
IR (KBr): νmax 3453 (b), 2929, 1636, 1456, 1378, 1227, 1108 cm-1
.
J. Org. Chem, Vol. 71, No. 8, 2006 3323