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A. Venkanna et al. / Tetrahedron: Asymmetry 24 (2013) 1010–1022
4.47–4.37 (m, 1H), 4.21–4.06 (m, 3H), 3.49 (t, J = 6.7 Hz, 1H), 3.37
(d, J = 7.1 Hz, 2H), 3.06–2.97 (m, 1H), 2.66–2.56 (m, 1H), 2.34 (q,
J = 14.3 Hz, 2H), 2.17 (t, J = 7.3 Hz, 2H), 1.83 (s, 3H), 1.69 (s, 3H),
1.37 (s, 3H), 1.32 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H) ppm. 13C NMR
(75 MHz, CDCl3): d = 196.8, 165.7, 158.0, 147.1, 135.6, 130.8,
122.6, 116.3, 168.4, 72.0, 59.3, 44.3, 38.1, 32.1, 30.9, 27.0, 25.5,
24.8, 23.3, 16.3, 14.5 ppm. HRMS (ESI): calcd for C21H32O5Na
[M+Na]+ 387.242; found 387.2123.
(0.092 g, 92%) as colourless oil. ½a D25
¼ þ56:8 (c = 0.64, CHCl3). IR
ꢂ
(KBr):
m = 2954, 2866, 2756, 1726, 1495, 1456, 1365, 1243, 1223,
821, 704 cmꢀ1 1H NMR (300 MHz, CDCl3): d = 5.67–5.56 (m, 2H),
.
5.39–5.24 (m, 1H), 5.13 (t, J = 6.9 Hz, 1H), 4.14 (q, J = 14.1 Hz, 2H),
3.98–3.86 (bs, 1H), 3.83–3.71 (m, 1H), 3.65–3.55 (m, 1H), 3.52–
3.42 (m, 1H), 3.40–3.30 (m, 3H), 3.24 (s, 3H), 2.81–2.62 (bs, 1H),
2.25–2.02 (m, 4H), 1.84 (s, 3H), 1.72–1.60 (m, 5H), 1.27 (t,
J = 7.17 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): d = 166.4, 159.0,
136.3, 133.9, 129.4, 121.1, 115.7, 79.8, 69.2, 66.7, 59.5, 55.8, 39.1,
4.22. (R,2Z,5Z,9E)-Ethyl 12-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-
11-methoxy-3,6-dimethyldodeca-2,5,9-trienoate 28
38.6, 31.9, 30.3, 24.7, 16.1, 14.2 ppm.
363.2142; found 363.2152.
C
19H32NaO5 [M+Na]+
To a stirred solution of the above diol (0.046 g, 0.13 mmol) in
dry DCM at 0 °C were added TrCl (0.041 g, 0.14 mmol) and pyridine
(0.01 mL, 0.14 mmol) and stirring was continued for 4 h at rt. After
completion, the reaction was quenched with sat. NH4Cl and the
aqueous phase was extracted with DCM (2 ꢃ 20 mL). The com-
bined organic layers were washed with brine, dried over anhy-
drous sodium sulfate and the organic layer concentrated to
afford the crude product. Purification by column chromatography
(10% ethyl acetate hexane) gave 29 (0.070 g, 89%) as a light yellow
A solution of (S)-(ꢀ)-2-methyl-CBS-oxazaborolidine (0.49 mL of
a 1 M solution in toluene, 4.9 mmol) in THF (5 mL) was treated with
BH3ꢁDMS (2.0 M solution in THF) (0.2 mL, 04.1 mmol) at 0 °C for
15 min. A solution of enone 27 (0.150 g, 4.1 mmol) in THF (8 mL)
was then added slowly at ꢀ78 °C and the reaction mixture was stir-
red for 1 h at the same temperature. After the addition of saturated
NH4Cl solution, the aqueous layer was extracted with EtOAc; the
combined organic phases were dried over Na2SO4 and concen-
trated. Purification of the residue by flash chromatography (10%
ethyl acetate hexane) gave (R,2Z,5Z,9E)-ethyl 12-((S)-2,2-di-
methyl-1,3-dioxolan-4-yl)-11-hydroxy-3,6-dimethyldodeca-2,5,9-
oil. ½a 2D5
ꢂ
¼ þ69:3 (c 0.5, CHCl3). IR (KBr):
m
= 3436, 2983, 2936,
2862, 1734, 1645, 1436, 1309, 1139, 859 cmꢀ1
.
1H NMR
(300 MHz, CDCl3): d = 7.47–7.41 (m, 6H), 7.33–7.17 (m, 9H), 5.63
(s, 1H), 5.61–5.49 (m, 1H), 5.31–5.20 (m, 1H), 5.14 (t, J = 7.3 Hz,
1H), 4.13 (q, J = 14.3 Hz, 2H), 4.06 (t, J = 5.6 Hz, 1H), 3.72–3.62
(m, 1H), 3.36 (d, J = 7.1 Hz, 2H), 3.15 (s, 3H), 3.09 (d, J = 5.6 Hz,
2H), 2.96–2.84 (bs, 1H), 2.20–2.03 (m, 4H), 1.81 (s, 3H), 1.68–
1.60 (m, 5H), 1.26 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (75 MHz,
CDCl3): d = 166.3, 158.9, 143.8 (3 C), 136.5, 133.6, 129.8, 128.6 (6
C), 127.7 (6 C), 126.9 (3 C), 121.0, 115.8, 86.4, 79.3, 67.9, 67.3,
59.4, 55.8, 39.2, 32.0, 30.6, 24.7, 16.2, 14.2 ppm. HRMS (ESI): calcd
for C38H46O5Na [M+Na]+ 605.3287; found 605.3236.
trienoate (0.128 g, 85%, dr >96:4) as a colourless oil. ½a D25
¼ þ37:2 (c
ꢂ
1.2, CHCl3). IR (KBr):
m = 2923, 2836, 1728, 1679, 1562, 1421, 1084,
752 cmꢀ1 1H NMR (300 MHz, CDCl3): d = 5.66–5.53 (m, 2H), 5.50–
.
5.39 (m, 1H), 5.09 (t, J = 6.6 Hz, 1H), 4.29–4.16 (m, 2H), 4.11 (q,
J = 14.1 Hz, 2H), 4.01 (t, J = 7.6 Hz, 1H), 3.50 (t, J = 7.5 Hz, 1H), 3.34
(t, J = 6.0 Hz, 1H), 2.30–2.25 (bs, 1H), 2.18–2.03 (m, 4H), 1.84 (s,
3H), 1.80–1.70 (m, 2H), 1.66 (s, 3H), 1.38 (s, 3H), 1.32 (s, 3H), 1.27
(t, J = 7.1 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3): d = 165.8, 158.6,
136.1, 133.3, 130.5, 121.5, 116.1, 108.5, 73.4, 69.7, 69.6, 59.2,
40.6, 39.2, 32.1, 30.5, 27.1, 25.9, 24.9, 16.3, 14.4 ppm. HRMS (ESI):
calcd for C18H30O5Na [M+Na]+ 389.1973; found 389.1942.
4.24. (2Z,5Z,9E,11R,13S)-13-Hydroxy-11-methoxy-3,6-dimethyl-
To a stirred solution of the above alcohol (0.120 g, 0.32 mmol) in
dry CH2Cl2 (10 mL) was added proton sponge™ (0.772 g, 3.6 mmol)
followed by trimethyloxonium tetrafluoroborate (0.436 g,
2.9 mmol) at 0 °C. The resulting solution was stirred at rt for 1 h
and then quenched by the addition of saturated aqueous NaHCO3
(5 mL). The phases were separated and the aqueous phase was ex-
tracted with CH2Cl2 (3 ꢃ 5 mL). The combined organic layers were
dried over Na2SO4, concentrated and purified by flash column chro-
matography (5% ethyl acetate hexane) to yield 28 (0.122 g, 98%) as a
14-(trityloxy)tetradeca-2,5,9-trienoic acid 32
To stirred solution of 29 (0.065 g, 0.11 mmol) in dry DCM (5 mL)
was added imidazole (0.019 g, 0.27 mmol) and stirred for 10 min.
The reaction mixture was then cooled to 0 °C, treated with TESCl
(0.03 mL, 0.16 mmol) and allowed to stir for an additional 5 h at
room temperature. After completion, the reaction was quenched
with sat. NaHCO3. The aqueous phase was extracted with Et2O
(2 ꢃ 10 mL), washed with brine and dried over Na2SO4. Removal
of the solvent gave the crude product, which was purified by flash
column chromatography (4% ethyl acetate hexane) to afford
(2Z,5Z,9E,11R,13S)-ethyl 11-methoxy-3,6-dimethyl-13-(triethylsi-
lyloxy)-14-(trityloxy)tetradeca-2,5,9-trienoate (0.071 g, 92%) as a
colourless oil. This compound was used for the next step.
To a stirred solution of the above TES protected compound
(0.068 g, 0.09 mmol) in dry DCM (20 mL) was added DIBAL-H
(25% in toluene, 0.14 mL, 0.24 mmol) dropwise at ꢀ15 °C. After
being stirred for 30 min, the reaction mixture was quenched with
sodium potassium tartarate, diluted with DCM and stirred until
the appearance of two clear layers. The organic layer was sepa-
rated, washed with brine and dried over sodium sulfate. Removal
of the solvent followed by purification of the crude product by col-
umn chromatography (12% ethyl acetate hexane) yielded the cor-
responding allylic alcohol 31 (0.059 g, 93%) as a colourless oil.
colourless oil. IR (KBr):
m = 3014, 2986, 2936, 2846, 1713, 1462,
1286, 1125, 1095, 742 cmꢀ1. ½a D25
ꢂ
¼ þ85:7 (c 0.8, CHCl3). 1H NMR
(300 MHz, CDCl3): d = 5.64 (s, 1H), 5.59 (t, J = 6.4 Hz, 1H), 5.30 (m,
1H), 5.15 (t, J = 6.9 Hz, 1H), 4.25–4.09 (m, 3H), 4.03 (t, J = 5.8 Hz,
1H), 3.65–3.56 (m, 1H), 3.51 (t, J = 7.5 Hz, 1H), 3.38 (d, J = 7.1 Hz,
2H), 3.22 (s, 3H), 2.22–2.04 (m, 4H), 1.84 (s, 3H), 1.80–1.71 (m,
2H), 1.68 (s, 3H), 1.39 (s, 3H), 1.36 (s, 3H), 1.27 (J = 6.9 Hz, 3H)
ppm. 13C NMR (75 MHz, CDCl3): d = 166.3, 158.9, 136.5, 133.6,
130.0, 121.0, 115.8, 108.2, 79.2, 73.4, 69.8, 59.4, 55.8, 40.3, 39.2,
32.0, 30.5, 26.9, 25.8, 24.7, 16.1, 14.2 ppm. HRMS (ESI): calcd for
C
22H36NaO5 [M+Na]+ 403.2455; found 403.2451.
4.23. (2Z,5Z,9E,11R,13S)-Ethyl 13-hydroxy-11-methoxy-3,6-dim
ethyl-14-(trityloxy) tetradeca-2,5,9-trienoate 29
To a solution of compound 28 (0.115 g, 0.30 mmol) in methanol
(5 mL) at 0 °C was added a catalytic amount of (–)-camphor-10-sul-
fonic acid. The reaction temperature was warmed to room temper-
ature and stirred for 4 h. The reaction mixture was concentrated to
remove methanol and diluted with ethyl acetate. The organic layer
was washed with sat. Na2CO3 solution and the organic layer was
concentrated to afford the crude product. Purification by column
chromatography (30% ethyl acetate in hexane) led the diol
To a suspension of the above primary alcohol (0.055 g,
0.08 mmol) and sodium bicarbonate (0.042 g, 0.54 mmol) in dry
DCM (5 mL) was added Dess–Martin periodinane (0.053 g,
0.12 mmol) at 0 °C. After being stirred for 1 h, the reaction mixture
was quenched with satd. sodium thiosulfate and stirred until the
appearance of a clear solution. The organic layer was separated
and the aq layer was extracted with diethyl ether (2 ꢃ 5 mL). The
combined organic layers were washed with sat. NaHCO3 and brine,