J.-C. Jung – O.-S. Park · Efficient Asymmetric Synthesis of Prostaglandin E1
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brine (5 mL). The organic layer was separated, dried over 1.6 M solution in hexane) at −78 ◦C under argon atmo-
◦
anhydrous MgSO4, filtered and concentrated under reduced sphere. The mixture was stirred at −78 C for 30 min, and
pressure. The crude product was purified by flash column a solution of ThCuCNLi (1.4 mL, 0.28 mmol; 0.2 M so-
chromatography (silica gel, 15 % EtOAc/hexanes) to afford lution in THF) in THF (0.5 mL) was added. The reaction
SEM-cyclopentenone 17 (0.15 g, 31 %) as a pale yellow oil. mixture was stirred at that temperature for 30 min, and a
Rf = 0.4 (15 % ethyl acetate in hexanes). – [α]2D5 = −4.0 solution of SEM-cyclopentenone 17 (0.1 g, 0.2 mmol) in
(c = 0.2, CHCl3). – IR (neat, NaCl): ν = 2951, 2898, 1740 THF (1 mL) was added. The resulting mixture was stirred
(CO), 1715 (COO), 1408, 1249, 1032, 837 cm−1. – 1H NMR at −78 ◦C for 30 min, and quenched with 10 % aqueous
(CDCl3, 500.14 MHz): δ = 7.18 (s, 1H, CH=CH), 5.27, (s, NH4OH solution (2 mL) and saturated aqueous NH4Cl so-
2H, OCH2O), 4.78 (d, J = 3.2 Hz, 1H, CH), 4.76 (s, 2H, lution (3 mL). The mixture was warmed to r. t., diluted with
OCH2O), 3.71 – 3.61 (m, 4H, 4 ×OCH2), 2.76 (dd, J = 6.0, ether (10 mL) and washed with brine (5 mL). The organic
18.8 Hz, 1H, CH2), 2.35 (dd, J = 1.6, 17.6 Hz, 1H, CH2),
3.23 (t, J = 7.6 Hz, 2H, CH2), 2.18 (t, J = 7.6 Hz, 2H, CH2),
1.67 – 1.59 (m, 2H CH2), 1.53 – 1.46 (m, 2H, CH2), 1.37 –
1.31 (m, 4H, 4×CH2), 0.96 (t, J = 8.4 Hz, 4H, 4×SiCH2),
0.03 (s, 9H, SiMe3), 0.02 (s, 9H, SiMe3). – 13C NMR
(CDCl3, 125.67 MHz): δ = 205.9 (CO), 173.3 (COO), 154.4
(CH), 148.3 (C), 94.5 (CH2), 88.7 (CH2), 73.6 (CH), 67.8
(CH2), 65.5 (CH2), 42.7 (CH2), 34.3 (CH2), 29.0 (CH2),
28.8 (CH2), 27.2 (CH2), 24.7 (CH2), 24.5 (CH2), 18.1
(CH2), 18.0 (CH2), −1.2 (SiMe3, 3C), −1.4 (SiMe3, 3C). –
HRMS: m/z = 487.2903 (calcd. 487.2911 for C24H47O6Si2,
[M+H]+).
layer was separated, dried over anhydrous MgSO4, filtered
and concentrated under reduced pressure. The crude prod-
uct was purified by flash column chromatography (silica gel,
20 % ether/hexanes) to afford fully protected SEM ester 18
(0.1 g, 67 %) as a pale yellow oil. Rf = 0.3 (20 % ether in
hexanes). – [α]2D5 = +30.7 (c = 1.2, CHCl3). – IR (neat,
NaCl): ν = 2951, 1740 (CO), 1716 (COO), 1463, 1249, 1105,
1031, 836 cm−1. – 1H NMR (CDCl3, 500.14 MHz): δ =
6.96 (dd, J = 5.0, 3.8 Hz, 1H, CH=CH), 6.80 (dd, J = 0.8,
3.4 Hz, 1H, CH=CH), 5.29 (s, 2H, OCH2O), 5.28 (s, 2H,
OCH2O), 4.80 (d, J = 2.4 Hz, 2H, OCH2O), 4.74 (d, J =
7.2 Hz, 1H, CH), 3.74 – 3.67 (m, 6H, 3 × CH2), 3.66 – 3.60
(m, 1H, CH), 2.81 (ddd, J = 6.8, 6.4, 6.0 Hz, 2H, CH2,
CH), 2.40 – 2.28 (m, 4H, CH2, CH), 2.03 (t, J = 11.5 Hz,
2H, CH2), 1.67 – 1.59 (m, 4H, 2×CH2), 1.56 – 1.47 (m, 4H,
2×CH2), 1.40 – 1.28 (m, 8H, 4×CH2), 1.01 – 0.93 (m, 9H,
3 × CH2, CH3), 0.05 (s, 3H, SiMe3), 0.04 (s, 6H, SiMe3),
0.04 (s, 9H, SiMe3), 0.03 (s, 9H, SiMe3). – 13C NMR
(CDCl3, 125.67 MHz): δ = 206.0 (CO), 173.5 (COO), 154.5
(CH=CH), 148.6 (CH=CH), 94.7 (CH2), 93.7 (CH2), 89.0
(CH2), 84.9 (CH), 78.7 (CH), 73.7 (CH), 68.0 (CH2), 65.8
(CH2), 65.4 (CH2), 51.6 (CH), 42.9 (CH2), 34.5 (2 × CH2,
2C), 29.3 (CH2), 29.2 (CH2), 29.1 (CH2), 29.0 (CH2), 27.7
(CH2), 27.5 (CH2), 26.2 (CH2), 24.9 (CH2), 24.7 (CH2),
18.3 (CH2), 18.2 (2 × CH2, 2C), −1.2 (3 × SiMe3, 9C). –
HRMS: m/z = 745.4932 (calcd. 745.4926 for C38H76O8Si3,
[M+H]+).
Preparation of 2-thienyl(cyano)copper lithium (12,
2-ThCuCNLi)
To a stirred solution of thiophene (1.56 g, 20.4 mmol) in
THF (10 mL) n-BuLi (12.5 mL, 20.0 mmol; 1.6 M solution in
◦
hexane) was added at −78 C under argon atmosphere, and
stirring was continued at −78 ◦C for 30 min. The mixture was
transferred to a slurry of copper cyanide (1.8 g, 20.0 mmol)
in THF (10 mL). The resulting reaction mixture was warmed
to −40 ◦C and diluted with THF (66 mL) to give a clear so-
lution (0.2 M solution in THF), which was stored in a freezer
at −22 ◦C.
(8R,11R,12R,15S)-11,15-Bis-(2-trimethylsilylethoxymeth-
oxy)-9-oxo-prost-13-en-1-oic acid 2-trimethylsilylethoxy-
methyl ester (18)
Acknowledgement
This work was supported by a Chungbuk National Uni-
versity Grant in 2005.
A solution of vinylstannane 14 (0.12 g, 0.22 mmol) in dry
THF (0.5 mL) was treated with n-BuLi (0.15 mL, 0.22 mmol;
[1] P. W. Collins, S. W. Djuric, Chem. Rev. 1993, 93,
1533 – 1564.
[4] F. S. Alvarez, D. Wren, A. Prince, J. Am. Chem. Soc.
1972, 94, 7823 – 7827.
[5] R. Noyori, M. Suzuki, A. Yangisawa, J. Am. Chem.
Soc. 1988, 110, 4718 – 4726.
[6] L. V. Hijfte, M. Kolb, Tetrahedron 1992, 48, 6393 –
6402; C. R. Johnson, M. P. Braun, J. Am. Chem. Soc.
1993, 115, 11014 – 11015.
[7] L. A. Arnold, R. Naasz, A. J. Minnaard, B. L. Feringa,
J. Am. Chem. Soc. 2001, 123, 5841 – 5842.
[2] C. J. Sih, P. Price, R. Sood, R. G. Salomon, G. Peruz-
zotti, M. Casey, J. Am. Chem. Soc. 1972, 94, 3642 –
3644; F. Sato, H. Tsujiyama, N. Ono, T. Yoshino,
S. Okamuko, Tetrahedron Lett. 1990, 31, 4481 – 4484;
O. W. Gooding, C. C. Beard, G. F. Cooper, D. Y. Jack-
son, J. Org. Chem. 1993, 58, 3681 – 3686.
[3] E. J. Corey, N. M. Weinshenker, T. K. Schaaf, W. Hu-
ber, J. Am. Chem. Soc. 1969, 91, 5675 – 5677.
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