Synthesis of Hydroxytetradecatrienic Acid
935
(
9S,5Z)-Decen-1,9-diol (7; C10H20O2)
2
6
2
.4 ml of a 1.6 N solution of BuLi in hexane were added dropwise to a solution of 858 mg (2.0 mmol)
in 20 ml abs. THF under argon. The mixture was stirred for 30 min, and 204 mg (2.0 mmol) 3 in
ml abs. THF were added slowly. After stirring for another hour, the reaction mixture was
evaporated under reduced pressure, diluted with 30 ml of H2O, and extracted with 4Â50 ml CH2Cl2.
The combined organic phases were washed with 15 ml brine, dried over Na2SO4, and evaporated. CC
over 100 g silica with EtOAc afforded 160 mg (47%) of 7 as a colourless oil.
D
ꢀ
Rf 0.33 (EtOAc); ꢀ 7:24 (c 0.46 in CH2Cl2); IR (neat): ꢁ 3335 (s), 2932 (s), 1457
2
0
�
1 1
(
m), 1437 (m), 1374 (m), 1121 (m), 1069 (m), 723 (m) cm ; H NMR (400 MHz, ꢂ, CDCl3): 1.14
d, J 6.1 Hz, 3H, 10-H), 1.39 (quint, J 7.7 Hz, 2H, 3-H), 1.46 (m, 2H, 8-H), 1.52 (m, 2H, 2-H),
(
2
.04 (m, 2H, 4-H), 2.09 (m, 3H, 7-H), 2.09 (s br, 2H, OH), 3.58 (t, J 6.5 Hz, 2H, 1-H), 3.75 (sext,
13
J 6.1 Hz, 1H, 9-H), 5.35 (m, 2H, 5-H, 6-H) ppm; C NMR (100 MHz, ꢂ, CDCl3): 23.5 (q, C-10),
2
3.6 (t, C-7), 25.7 (t, C-3), 26.7 (t, C-4), 32.1 (t, C-2), 39.0 (t, C-8), 62.5 (t, C-1), 67.6 (d, C-9), 129.5
(
(
d, C-6*), 130.1 (d, C-7*) ppm; MS (70 eV): m/z (%) 172 (1.5) [M ], 154 (1.5) [M -H2O], 139
1.3) [154-CH3], 136 (1.5) [M -2 H2O], 121 (3.1) [136-CH3], 107 (7.0) [136-C2H5], 95 (12.8) [136-
C3H5], 93 (12.3) [136-C3H7], 81 (20.8), 79 (100) [136-C4H9], 67 (49.8) [136-C5H7], 31 (7.6)
[
CH2OH].
(
9S,5Z)-9-Hydroxy-5-decenal (8; C10H18O2)
1
40 mg (0.81 mmol) 7, 25 mg (0.16 mmol) 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), 221 mg
1.65 mmol) dry CuCl2, and 102 mg (2.43 mmol) CaH2 in 5 ml abs. CH3CN were stirred vigorously
(
under O2 in a 25 ml round bottom ¯ask overnight. The reaction mixture was evaporated under
reduced pressure, diluted with 8 ml of water, and extracted with 4Â25 ml CH2Cl2. The combined
organic phases were washed with 5 ml brine, dried over Na2SO4, evaporated to 2 ml and ®ltered over
2
g alumina. The alumina was washed with CH2Cl2, and the product containing fractions were
combined and evaporated. CC over 50 g silica (EtOAc) gave 90 mg (65%) of 8 as a colourless oil.
D
ꢀ
Rf 0.50 (EtOAc); ꢀ 14:4 (c 2.0 in CH2Cl2); IR (neat): ꢁ 3422 (s), 3007 (m), 2929
2
0
�
1 1
(
s), 2721 (m), 1719 (s), 1651 (w), 1457 (m), 1374 (m), 1129 (m), 723 (m) cm ; H NMR (400 MHz,
ꢂ, CDCl3): 1.18 (d, J 6.3 Hz, 3H, 10-H), 1.51 (m, 2H, 8-H), 1.67 (quint, J 7.3 Hz, 2H, 3-H), 1.74
(
s br, 1H, OH), 2.08 (m, 4H, 2-H, 4-H), 2.42 (t, J 7.3 Hz, 2H, 2-H), 3.79 (sext, J 6.3 Hz, 1H, 9-
13
H), 5.33 (m, 1H, 5-H), 5.38 (m, 1H, 6-H), 9.74 (t, J 1.5 Hz, 1H, 1-H) ppm; C NMR (100 MHz, ꢂ,
CDCl3): 21.2 (t, C-3), 22.8 (q, C-10), 22.9 (t, C-7), 25.7 (t, C-4), 38.2 (t, C-8), 42.5 (t, C-2), 66.8 (d,
+
C-9), 128.1 (d, C-5), 129.8 (d, C-6), 201.9 (d, C-1) ppm; MS (70 eV): m/z (%) 152 (0.9) [M -
H2O], 137 (1.1) [152-CH3], 123 (3.7) [152-CHO], 108 (13.3) [152-C2H4O], 93 (17.0) [108-CH3], 79
(
100) [C6H , 31 (2.1) [CH2OH].
7
(
S)-Ethyl-13-hydroxy-2,4,9-tetradecatrienoate (mixture of (4Z)- and (4E)-isomer; 910)
2
28 mg (0.50 mmol) 3-ethoxycarbonyl-2-propenyl-triphenylphosphonium bromide and 300 mg
ꢀ
K2CO3 were heated to 120 C in 10 ml abs. DMF under Ar. A solution of 85 mg (0.50 mmol) 8 in
ꢀ
1
ml abs. DMF was added, and stirring at 120 C was continued for 1.5 hours. After cooling to room
temp., the reaction mixture was poured into 20 ml of water and extracted with 4Â25 ml Et2O. The
combined extracts were washed with 20 ml brine, dried over Na2SO4, and evaporated under reduced
pressure. CC over 50 g silica with EtOAc afforded 95 mg (71%) of a (Z/E)-mixture of 9 as a
colourless oil.
Rf 0.63 (EtOAc); IR (neat): ꢁ 3420 (s), 2930 (s), 2860 (s), 1718 (s), 1641 (s), 1617 (m), 1456
(
s), 1368 (s), 1304 (s), 1269 (s), 1183 (s), 1136 (s), 1095 (m), 1039 (s), 1001 (s), 872 (m), 714 (m)
�
1
cm ; UV (CH2Cl2): ꢃmax (lg") 262.5 (4.28) nm.