(
dd, J = 9.9 Hz and J = 7.0 Hz, 1H), 2.24 (ttapp, J = 6.7 Hz and
silica gel (Petroleum ether–Et O: 90 : 10) furnished dienic ester
12 (63 mg, 86%) as a viscous dark yellow oil; IR (neat): 2930,
2
13
J = 1.2 Hz, 2H), 2.12 (br s, 1H), 0.90 (s, 9H), 0.07 (s, 6H);
C
NMR (75 MHz, CDCl ): δ 134.5 (d), 117.4 (t), 71.1 (d), 66.5
2857, 1707, 1471, 1369, 1303, 1253, 1179, 1096, 1030, 979,
3
1 1
834, 777 cm− ; H NMR (300 MHz, CDCl ): δ 7.29 (dd, J =
(
t), 37.6 (t), 25.9 (q, 3C), 18.3 (s), −5.4 (q, 2C); MS (EI, 70 eV)
3
+
m/z (%): 175 (4), 159 (M − tBu , 8), 141 (8), 117 (16), 105
(
15.4 Hz and J = 11.3 Hz, 1H), 6.39 (m, 1H), 6.16 (dt, J = 15.2
Hz and J = 4.2 Hz, 1H), 5.86 (d, J = 15.3 Hz, 1H), 4.29 (br dd,
J = 4.2 Hz and J = 1.7 Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H), 1.28
27), 89 (8), 76 (9), 75 (100), 73 (24), 67 (29), 59 (8).
Ethyl (E)-6-(tert-butyldimethylsilyloxy)-5-hydroxy-2-hexenoate
13
(
t, J = 7.1 Hz, 3H), 0.91 (s, 9H), 0.07 (s, 6H); C NMR
(10). To a solution of alkene 9 (2.41 g, 11.16 mmol, 1.0 equiv)
(
100 MHz, CDCl ): δ 168.7 (s), 140.3 (d), 139.5 (d), 135.4 (d),
3
in CH Cl2 (60 mL) were successively added ethyl acrylate
2
1
32.8 (d), 61.8 (t), 61.6 (t), 25.6 (q, 3C), 18.0 (s), 14.1 (q), −4.7
(3.6 mL, 33.47 mmol, 3.0 equiv) and the second generation
+
(q, 2C); MS (EI, 70 eV) m/z (%): 270 (M ˙, 20), 213 (33), 185
Grubbs-catalyst [Ru]-II (285 mg, 0.33 mmol, 0.03 equiv). The
mixture was refluxed and after 4 h the reaction mixture was con-
centrated under reduced pressure. Purification of the residue by
flash chromatography on silica gel (gradient Petroleum ether–
(28), 167 (22), 157 (18), 141 (26), 139 (10), 131 (25), 115 (7),
1
03 (78), 75 (100), 73 (49), 66 (17), 65 (10), 59 (10), 57 (8).
Ethyl (2E,4E)-6-hydroxy-2,4-hexadienoate (13). To a solution
of silyl ether 12 (552 mg, 2.04 mmol, 1.0 equiv) in THF
EtOAc: 90 : 10 then 70 : 30) furnished α,β-unsaturated ester 10
1
(
2.99 g, 93%) as a brown oil; H NMR (300 MHz, CDCl ): δ
3
(55 mL) at 0 °C was added n-Bu NF (1 M in THF, 2.25 mL,
4
6
.98 (dt, J = 15.7 Hz and J = 7.3 Hz, 1H), 5.91 (dt, J = 15.6 Hz
and J = 1.4 Hz, 1H), 4.19 (q, J = 7.1 Hz, 2H), 3.79 (m, 1H),
.64 (dd, J = 9.9 Hz and J = 3.6 Hz, 1H), 3.46 (dd, J = 9.9 Hz
2
.25 mmol, 1.1 equiv) and the mixture was stirred for 1 h at rt.
The reaction mixture was poured in water (50 mL) and the layers
3
were separated. The aqueous phase was extracted with Et O
2
and J = 3.6 Hz, 1H), 2.37 (br tapp, J = 7.4 Hz, 2H), 1.28 (t,
(3 × 50 mL) and the combined organic layers were washed with
J = 7.1 Hz, 3H), 0.90 (s, 9H), 0.07 (s, 6H); MS (EI, 70 eV) m/z
brine (50 mL), dried over MgSO , filtered and concentrated
4
+
(
1
%): 243 (2), 231 (M − tBu , 4), 186 (10), 185 (70), 157 (15),
in vacuo. Purification of the residue by flash chromatography on
silica gel (Petroleum ether–EtOAc: 60 : 40) furnished alcohol 13
17 (77), 114 (15), 111 (31), 105 (15), 103 (14), 89 (13),
8
3 (29), 75 (100), 73 (40), 55 (12).
(258 mg, 81%) as a viscous colorless oil which crystallized
upon standing in the freezer at −20 °C; IR (neat): 3400, 2980,
Ethyl (E)-5-acetoxy-6-(tert-butyldimethylsilyloxy)-2-hexenoate
11). To a solution of alcohol 10 (218 mg, 0.756 mmol, 1.0
equiv) in pyridine (61 μL, 0.756 mmol, 1.0 equiv) at 0 °C were
successively added acetic anhydride (286 μL, 3.02 mmol, 4.0
equiv) dropwise then 4-dimethylaminopyridine (19 mg,
2
7
860, 1710, 1650, 1620, 1370, 1180, 1135, 1090, 1000, 875,
(
95 cm− ; H NMR (300 MHz, CDCl ): δ 7.28 (dd, J = 15.4 Hz
1
1
3
and J = 10.9 Hz, 1H), 6.40 (br dd, J = 15.3 Hz and J = 10.9 Hz,
H), 6.21 (dt, J = 15.4 Hz and J = 4.9 Hz, 1H), 5.87 (d, J = 15.5
Hz, 1H), 4.28 (br d, J = 4.2 Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H),
1
0
.15 mmol, 0.2 equiv). After stirring for 15 h at rt, the reaction
mixture was hydrolyzed upon addition of a saturated aqueous
13
1
.93 (br s, 1H), 1.28 (t, J = 7.1 Hz, 3H); C NMR (75 MHz,
CDCl ): δ 167.1 (s), 143.7 (d), 141.1 (d), 127.8 (d), 121.4 (d),
solution of NaHCO (15 mL). Diethyl ether was added (30 mL)
3
3
+
62.6 (t), 60.4 (t), 14.2 (q); MS (EI, 70 eV) m/z (%): 156 (M ˙,
23), 128 (12), 127 (73), 111 (43), 110 (46), 109 (19), 99 (98),
97 (28), 88 (8), 84 (22), 83 (83), 82 (67), 81 (100), 79 (17),
71 (11), 69 (10), 67 (10), 66 (24), 65 (16), 56 (11), 55 (99),
54 (19), 53 (54), 52 (11), 51 (16).
and the layers were separated. The aqueous phase was extracted
with Et O (3 × 30 mL) and the combined organic layers were
2
washed with brine, dried over MgSO , filtered then concentrated
4
under reduced pressure to give acetate 11 (261 mg, 100%) as a
pale yellow oil. This compound was used in the following step
without further purification; IR (neat): 2940, 2925, 2850, 1740,
Ethyl
(2E,4E,6E)-8-(tert-butyldimethylsilyloxy)-2,4,6-octa-
1
8
1
720, 1660, 1460, 1470, 1370, 1320, 1235, 1175, 1040, 980,
trienoate (16). To a solution of alkene 9 (3.0 g, 13.86 mmol, 1.0
−
1 1
40, 780 cm ; H NMR (300 MHz, CDCl ): δ 6.88 (dt, J =
3
equiv) in an acetone–H O mixture (9 : 1, 70 mL) at 0 °C were
2
5.6 Hz and J = 7.4 Hz, 1H), 5.87 (dt, J = 15.6 Hz and J = 1.4
successively added N-methylmorpholine N-oxide (1.62 g,
Hz, 1H), 4.94 (br quintapp, J = 6.0 Hz, 1H), 4.17 (q, J = 7.1 Hz,
H), 3.68–3.58 (m, 2H), 2.62–2.42 (m, 2H), 2.04 (s, 3H), 1.27
1
3.86 mmol, 1.0 equiv) followed by OsO4 (4 wt% in H O,
2
2
(
(
7
1
8
52 μL, 0.01 equiv) dropwise. After 15 h at rt, water (30 mL)
1
3
t, J = 7.1 Hz, 3H), 0.87 (s, 9H), 0.04 (s, 6H); C NMR
and NaIO4 (12 g, 55.4 mmol, 4.0 equiv) were successively
added to the reaction mixture. After 30 min at rt, solid Na S O
2 3
75 MHz, CDCl ): δ 170.4 (s), 166.2 (s), 143.5 (d), 124.1 (d),
3
2
2.7 (d), 63.5 (t), 60.3 (t), 33.3 (t), 25.8 (q, 3C), 21.1 (q),
(3 g) and Florisil® (10 g) were added and the resulting suspen-
8.2 (s), 14.2 (q), −5.5 (q, 2C); MS (EI, 70 eV) m/z (%): 285
sion was stirred for 30 min, then filtered over a plug of cotton to
remove osmium salts. The filtrate was concentrated in vacuo,
Et O was added (75 mL) and the layers were separated. The
2
+
+
(
1
M − OEt , 4), 273 (M − tBu , 5), 231 (8), 185 (12), 118 (9),
17 (100), 111 (10), 75 (27), 73 (12).
Ethyl (2E,4E)-6-(tert-butyldimethylsilyloxy)-2,4-hexadienoate
12). To a solution of acetate 11 (90 mg, 0.272 mmol, 1.0 equiv)
aqueous phase was extracted with Et O (3 × 75 mL) and the
2
(
combined organic layers were successively washed with a satu-
rated aqueous solution of Na S O (50 mL), brine (75 mL) then
in THF (1 mL) at 0 °C was added DBU (90 μL, 0.60 mmol, 2.2
equiv) dropwise. After stirring for 36 h at rt, the reaction mixture
was hydrolyzed by addition of a saturated aqueous solution
of NH Cl (5 mL). The aqueous layer was extracted with Et O
2
2 3
dried over MgSO , filtered and concentrated under reduced
4
pressure. The obtained crude aldehyde thus obtained was not
purified but directly used in the following step.
4
2
(
3 × 10 mL) and the combined organic layers were washed
To a solution of the afore-mentioned aldehyde (13.86 mmol,
1.0 equiv) in THF (45 mL) at −20 °C was added allylmagne-
sium chloride (2 M in THF, 20.8 mL, 41.6 mmol, 3.0 equiv)
with brine (10 mL), dried over MgSO , filtered and concentrated
in vacuo. Purification of the residue by flash chromatography on
4
6178 | Org. Biomol. Chem., 2012, 10, 6169–6185
This journal is © The Royal Society of Chemistry 2012