COMMUNICATIONS
5.0, 12.3, 17.2, 18.4, 19.7, 21.9, 26.1 (2C), 29.1, 33.2, 34.5, 39.9, 60.4, 125.2,
tert-butyldimethylsilyl propargyl ether in the presence of
[Pd(PPh3)4] (5 mol%), CuI, and diisopropylamine in benzene
under the standard Sonogashira conditions[14] to give 10 in
88% yield. The reaction proceeded without isomerization of
the (11Z)-double bond. After the TBDMS group was
quantitatively removed with Bu4NF, the primary alcohol
obtained was oxidized with BaMnO4 to give 3 (68% yield
over two steps).[15]
We have demonstrated an efficient and concise synthesis of
geometrically pure (11Z)-retinals, in which a construction of
the conjugated pentaene system involving the (Z)-alkenyl
unit is achieved. (11Z)-Retinals prepared by this method
exhibit perfect purity in their geometry. An advantage of this
method is that it can be used to prepare a wide range of (11Z)-
retinals and thus offers a further development in the research
of vision.
127.0, 127.4, 129.1, 132.4, 133.4, 134.3, 136.8, 138.3, 138.9; MS (70 eV): m/z
(%): 400 (M , 100), 385 (9), 343 (8), 269 (8), 254 (12), 199 (9); HR-MS calcd
for C26H44OSi (M ): 400.3162; found: 400.3167.
10: A mixture of 5 (100 mg, 0.34 mmol), tert-butyldimethylsilyl propargyl
ether (115 mg, 0.68 mmol), diisopropylamine (95 mL, 0.68 mmol),
[Pd(PPh3)4] (20 mg, 0.017 mmol), and CuI (6.5 mg, 0.034 mmol) in de-
gassed benzene (3.4 mL) was stirred at room temperature for 30 min. The
reaction mixture was diluted with hexane and washed with water (2 mL Â
2) and brine (2 mL). The organic layer was dried over MgSO4 and
evaporated under reduced pressure below 108C. The crude mixture was
purified by column chromatography (silica gel, diethyl ether/hexane, 2/98)
to give 10 (115 mg) in 88% yield. The material is very light-sensitive, and
should be handled in the dark. Oil; Rf 0.17 (hexane); UV (hexane):
lmax 324, 252 nm; 1H NMR (300 MHz, CDCl3): d 0.15 (6H, s), 0.93 (9H,
s), 1.03 (6H, s), 1.44 ± 1.49 (2H, m), 1.57 ± 1.66 (2H, m), 1.72 (3H, d, J
0.9 Hz), 1.95 (3H, d, J 0.9 Hz), 2.02 (2H, br t, J 6.0 Hz), 4.53 (2H, d, J
2.5 Hz), 5.46 (1H, d, J 10.6 Hz), 6.17 (1H, d, J 16.0 Hz), 6.27 (1H, d,
J 16.0 Hz), 6.56 (1H, d, J 12.1 Hz), 6.76 (1H, dd, J 12.1, 10.6 Hz); 13
C
NMR (75 MHz, CDCl3): d 5.0, 12.7, 18.3, 19.2, 21.7, 25.9 (2C), 28.9, 33.1,
34.2, 39.6, 52.5, 82.6, 95.2, 107.6, 126.9, 128.7, 129.8, 136.2, 137.4, 137.7, 139.1;
MS (70 eV): m/z (%): 384 (M , 31), 369 (3), 327 (2), 149 (100); HR-MS
Experimental Section
calcd for C25H40OSi (M ): 384.2849; found: 384.2838.
8: PPh3 (1.92 g, 7.32 mmol) was added all at once to an ice-cooled, stirred
solution of 4 (400 mg, 1.83 mmol) and CBr4 (912 mg, 2.75 mmol) in CH2Cl2
(30 mL). The mixture was stirred for 5 min at the same temperature and
then purified by column chromatography (silica gel, hexane) to give a
mixture of 8 and retroionylidene bromide (638 mg, 8.8:1 ratio) in a
combined yield of 98%. Oil; Rf 0.62 (hexane); 1H NMR (300 MHz,
CDCl3): d 1.03 (6H, s), 1.44 ± 1.50 (2H, m), 1.57 ± 1.66 (2H, m), 1.71 (3H,
d, J 0.9 Hz), 1.91 (3H, d, J 1.2 Hz), 2.01 (2H, br t, J 6.2 Hz), 6.01 (1H,
d, J 10.9 Hz), 6.13 (1H, d, J 16.1 Hz), 6.33 (1H, dd, J 16.1, 0.8 Hz),
7.27 (1H, d, J 10.9 Hz); 13C NMR (75 MHz, CDCl3): d 13.5, 19.2, 21.7,
28.9 (2C), 33.1, 34.2, 39.6, 90.7, 125.7, 129.6, 130.0, 133.6, 136.8, 137.6, 139.5;
Received: August 5, 1997 [Z10782IE]
German version: Angew. Chem. 1998, 110, 334 ± 336
Keywords: alkenes ´ bioorganic chemistry ´ cross-coupling ´
palladium ´ retinoids
[1] R. R. Birge, Annu. Rev. Biophys. Bioeng. 1981, 10, 315 ± 354; J. E.
Dowling, The Retina, Harvard University Press, Cambridge, 1987.
[2] K. Nakanishi, R. Crouch, Isr. J. Chem. 1995, 35, 235 ± 272; R. R.
Rando, Angew. Chem. 1990, 102, 507 ± 526; Angew. Chem. Int. Ed.
Engl. 1990, 29, 461 ± 480; J. C. Saari, The Retinoids, Biology, Chemistry
and Medicine, 2nd ed. (Eds.: M. B. Sporn, A. B. Roberts, D. S.
Goodmann), Raven, New York, 1994, chap. 9, pp. 351 ± 395.
[3] Reviews: R. S. H. Liu, A. E. Asato, Tetrahedron 1984, 40, 1931 ± 1969;
M. Dawson, P. D. Hobbs, The Retinoids, Biology, Chemistry and
Medicine, 2nd ed. (Eds.: M. B. Sporn, A. B. Roberts, D. S. Good-
mann), Raven, New York, 1994, chap. 2, pp. 5 ± 178; recent synthesis
of (11Z)-retinals: B. Borhan, R. Kunz, A. Y. Wang, K. Nakanishi, N.
Bojkova, K. Yoshihara, J. Am. Chem. Soc. 1997, 119, 5758 ± 5759; A.
Wada, Y. Tanaka, N. Fujioka, M. Ito, Bioorg. Med. Chem. Lett. 1996, 6,
2049 ± 2052, and references therein.
[4] J. Uenishi, R. Kawahama, O. Yonemitsu, J. Tsuji, J. Org. Chem. 1996,
61, 5716 ± 5717; J. Uenishi, R. Kawahama, Y. Shiga, O. Yonemitsu, J.
Tsuji, Tetrahedron Lett. 1996, 37, 6759 ± 6762.
[5] R. W. Dugger, C. H. Heathcock, Syn. Commun. 1980, 10, 509 ± 515;
J. A. Pardoen, P. P. Mulder, E. M. M. van Den Berg, J. Lugtenburg,
Can. J. Chem. 1985, 63, 1431 ± 1435; A. Wada, S. Hiraishi, M. Ito,
Chem. Pharm. Bull. 1994, 42, 757 ± 759.
MS (70 eV): m/z (%): 376 (M , 52), 374 (M , 100), 372 (M , 50), 361 (19),
359 (34), 357 (20), 295 (11), 293 (11), 214 (29), 199 (38); HR-MS calcd for
C16H22Br2 (M ): 376.0047, 374.0068, 372.0088; found: 376.0043, 374.0089,
372.0089.
5: A solution of Bu3SnH (0.84 mmol, 2.27 mL, 0.37m in benzene) was
added to a mixture of 8 (298 mg, 0.8 mmol) and [Pd(PPh3)4] (37 mg,
0.032 mmol) in benzene (5.7 mL) at room temperature. The mixture was
stirred for 20 min, diluted with hexane (30 mL), washed with water (2 mL)
and brine (2 mL), and dried over MgSO4. The extract was concentrated
under reduced pressure below 108C and purified by column chromatog-
raphy (alumina, hexane) to give 5 (203 mg) in 86% yield. After addition of
PPh3 (30 mg), the mixture was frozen in benzene at 208C for storage. Oil;
Rf 0.59 (hexane); UV (hexane): lmax 301, 239 nm; 1H NMR (300 MHz,
CDCl3): d 1.03 (6H, s), 1.44 ± 1.49 (2H, m), 1.57 ± 1.67 (2H, m), 1.72 (3H,
d, J 0.8 Hz), 1.94 (3H, d, J 1.0 Hz), 2.02 (2H, br t, J 6.2 Hz), 6.18 (1H,
d, J 16.2 Hz), 6.20 (1H, d, J 7.1 Hz), 6.30 (1H, d, J 16.2 Hz), 6.33 (1H,
d, J 11.0 Hz), 6.98 (1H, dd, J 11.0, 7.1 Hz); 13C NMR (75 MHz, CDCl3):
d 13.3, 19.2, 21.7, 28.9 (2C), 33.0, 34.2, 39.6, 108.2, 124.8, 128.9 (2C), 129.8,
137.2, 137.6, 139.7; MS (70 eV): m/z (%): 296 (M , 85), 294 (M , 99), 281
(21), 279 (18), 215 (100), 199 (35); HR-MS calcd for C16H23Br (M ):
296.0963, 294.0983; found: 296.0958, 294.0979.
[6] J.-F. Betzer, J. Ardisson, J. -Y. Lallemand, A. Pancrazi, Tetrahedron
9: [Pd(PPh3)4] (42 mg, 0.036 mmol), an aqueous solution of KOH (7.2 mL,
2n), and Ag2CO3 (398 mg, 1.44 mmol) were successively added at room
temperature to a mixture of 5 (104 mg, 0.36 mmol) and 7 (268 mg,
0.88 mmol) in degassed THF (2.6 mL). The reaction mixture was stirred for
3 h at the same temperature, diluted with 10% ether in hexane (40 mL),
washed with water (3 Â 5 mL) and brine (5 mL), and dried over MgSO4.
The organic extract was condensed under reduced pressure below 108C,
and the oily residue purified by column chromatography (silica gel, diethyl
ether/hexane, 2/98) to give 9 (111 mg) in 77% yield. The material is very
light-sensitive, and should be handled in the dark. Oil; Rf 0.18 (hexane);
UV (hexane): lmax 322, 236 nm; 1H NMR (300 MHz, C6D6): d 0.08 (6H,
s), 0.99 (9H, s), 1.11 (6H, s), 1.44 ± 1.51 (2H, m), 1.54 ± 1.63 (2H, m), 1.73
(3H, s), 1.76 (3H, d, J 0.8 Hz), 1.85 (3H, d, J 1.1 Hz), 1.95 (2H, br t, J
6.2 Hz), 4.26 (2H, d, J 6.6 Hz), 5.88 (1H, t, J 6.6 Hz), 5.90 (1H, d, J
11.8 Hz), 6.28 (1H, d, J 16.0 Hz), 6.38 (1H, d, J 16.0 Hz), 6.38 (1H, dd,
J 12.0, 11.8 Hz), 6.88 (1H, d, J 12.0 Hz); 13C NMR (75 MHz, C6D6): d
Lett. 1997, 38, 2279 ± 2282.
1
[7] 6: Oil; Rf 0.21 (EtOAc/hexane, 1/9); IR (neat): nÄ 3326 cm
;
1H
NMR (300 MHz, CDCl3): d 0.86 ± 0.93 (15H, m), 1.24 ± 1.38 (6H,
m), 1.41 ± 1.55 (6H, m), 1.70 (1H, br s), 1.88 (3H, s), 4.26 (2H, d, J
6.0 Hz), 5.75 (1H, tq, J 6.0, 1.8 Hz); 13C NMR (75 MHz, CDCl3):
d 9.0, 13.6, 19.3, 27.3, 29.1, 58.8, 139.3, 142.3.
[8] H. C. Brown, T. E. Cole, Organometallics 1983, 2, 1316 ± 1319.
[9] F. Ramirez, N. B. Desai, N. McKelvie, J. Am. Chem. Soc. 1962, 84,
1745 ± 1747.
[10] This yield was determined by 1H NMR spectroscopy for a mixture of 8
and the unseparable by-product 10-bromo-3,5,7,9-tetraene (retroio-
nylidene bromide), which results from direct bromination of 4 under
the reaction conditions. However, the by-product decomposed easily
within several hours at room temperature.
[11] Y. Katsuta, M. Sakai, M. Ito, J. Chem. Soc. Perkin Trans. 1 1993, 2185 ±
2192.
322
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Angew. Chem. Int. Ed. 1998, 37, No. 3