6120
K. Tanaka et al. / Tetrahedron 65 (2009) 6115–6122
(hexane/EtOAc¼100:1) to give 17 (FW: 479.29, 454 mg,
0.724 mmol, 46%) as a colorless oil. This compound was very un-
stable. Rf¼0.71 (hexane/EtOAc¼10:1). 1H NMR (CDCl3, 300 MHz):
was dried with MgSO4 and concentrated in vacuo. The residue was
chromatographed on silica gel. Elusion with hexane/EtOAc (100:1)
gave 23 (FW: 430.98, 1.85 g, 4.29 mmol, 69%) as a colorless oil. This
oil was pure enough for the further reaction.
d¼0.91 (t, J¼7.2 Hz, 9H, CH2CH3), 0.92–1.00 (m, 6H), 1.34 (sext, 6H,
CH2CH3), 1.48–1.61 (m, 6H), 1.54 (s, 3H, Me2C), 1.56 (s, 3H, Me2C),
4.93 (s, 2H, H-4), 6.72 (dd, J¼8.1, 1.2 Hz, 1H), 6.76 (s, 2H, H-10, 20),
7.07 (pseudo d, J¼8.1 Hz, 1H), 7.15 (t, J¼8.1 Hz, 1H, H-7). FABMS: m/
z¼479 [MþH]þ, 423, 365, 291, 251, 235, 179, 177, 115. HRFABMS:
calcd for C24H41O2Sn [MþH]þ 479.2123; found 479.2123.
4.14. (10E,30Z,50R)-5-(50-tert-Butyldimethylsilyloxyhexa-10,30-
dienyl)-2,2-dimethyl-4H-benzo[e][1,3]dioxin [(R)-24]
To a solution of (R)-21 (FW: 312.05, 55.6 mg, 0.178 mmol),
Pd2dba3 (FW: 915.72, 5.3 mg, 0.0058 mmol), AsPh3 (FW: 306.24,
3.6 mg, 0.012 mmol) and CuI (FW: 190.45, 2.2 mg, 0.012 mmol) in
DMF (0.5 mL) was added dropwise 17 (FW: 479.29, 55.6 mg,
0.116 mmol) in DMF (1.5 mL) at 22 ꢁC, and the mixture was stirred
for 2 days, before poured into satd aq NH4Cl soln and extracted with
Et2O. The organic layer was washed with satd aq NaHCO3 soln and
brine, dried with MgSO4, and concentrated in vacuo. The residue
was chromatographed on SiO2. Elution with hexane/EtOAc (100:1)
(b) Radical-mediated hydrostannylation. To a solution of 13
(52.8 mg, 0.293 mmol) in dry toluene (5 mL) were added AIBN (FW:
164.22, 9.3 mg, 0.057 mmol) and Bu3SnH (124 mg, 0.426 mmol),
and the mixture was stirred at reflux for 3 h. Then, the mixture was
diluted with EtOAc and washed with water and brine, dried with
MgSO4, and concentrated in vacuo to give 17 (ca. 94%, E/Z¼89:11) as
a crude yellow oil. Compound (Z)-17 was assigned by 1H NMR
(CDCl3, 300 MHz):
(d, 1H, J¼13.5 Hz).
d
¼4.76 (s, 2H, H-4), 6.27 (d, 1H, J¼13.5 Hz), 6.32
gave (R)-24 (FW: 374.59, 34 mg, 0.091 mmol, 78.4%) as a colorless
24
(c) Palladium-catalyzed hydrostannylation. To a solution of 14
(FW: 267.11, 147 mg, 0.550 mmol), PPh3 (FW: 262.29, 6.0 mg,
0.023 mmol), and Pd2dba3 (FW: 915.7, 3.1 mg, 0.0034 mmol) in
dry THF (4 mL) was added dropwise Bu3SnH (FW: 291.06,
0.33 mL, 360 mg, 1.2 mmol) over 0.5 h. After being stirred at 20 ꢁC
for 2 h, the mixture was filtrated through a Celite pad and the pad
was washed with EtOAc. The combined filtrate was concentrated
oil, [
a]
ꢂ100 (c 0.20, Et2O). Rf¼0.59 (hexane/EtOAc¼10:1), 0.58
D
(hexane/Et2O¼5:1). UV (Et2O, 1.7ꢄ10ꢂ5 mol/l):
l
(log
3
)¼288 (4.32),
237 (4.18), 219 (4.23) nm. FTIR (Zn/Se):
n
¼1579 (m), 1283 (m), 1253
(m, Si–C), 1079 (m), 834 (m) cmꢂ1
.
1H NMR (CDCl3, 300 MHz):
d
¼0.063 (s, 3H, MeSi), 0.082 (s, 3H, MeSi), 0.89 (s, 9H, t-Bu), 1.27 (d,
J¼6.3 Hz, 3H, H-60),1.54 (s, 6H, Me2C), 4.84 (m,1H, H-50), 4.90 (s, 2H,
H-4), 5.55 (dd, J¼11.2, 8.5 Hz, 1H, H-40), 6.05 (t, J¼11.2 Hz, 1H, H-30),
6.39 (d, J¼15.3 Hz, 1H, H-10), 6.74 (dd, J¼8.0, 1.2 Hz, 1H, Ar), 6.95
(ddd, J¼15.3, 11.2, 1.2 Hz, 1H, H-20), 7.09 (dd, J¼7.4, 1.1 Hz, 1H, Ar),
in vacuo to give
a crude brown oil containing [(E)-17/18/
19¼21:21:42]. Compound 18: 1H NMR (CDCl3, 300 MHz):
¼4.67
d
(s, 2H, H-4), 5.52 (d, 1H, J¼3.0 Hz, vinyl), 5.77 (d, 1H, J¼3.0 Hz,
vinyl), 6.47 (d, J¼7.7 Hz), 6.64 (d, J¼8.2 Hz), 7.07 (dd, J¼8.2,
7.16 (dd, J¼8.0, 7.4 Hz, 1H, H-7). EIMS: m/z¼374 (Mþ), 316 [MþHꢂt-
ꢃ
Bu]þ, 259 [MꢂHOTBS]þ. HREIMS: calcd for C22H34O3Si (Mþ
)
7.7 Hz).Compound 19: 1H NMR (CDCl3, 300 MHz):
d
¼1.55 (s, 6H,
374.2277; found 374.2279.
25
Me2C), 4.90 (s, 2H, 4–H), 5.3 5(dd, 1H, J¼10.8, 1.2 Hz, Z-vinyl), 5.69
(dd, 1H, J¼17.4, 1.2 Hz, E-vinyl), 6.66 (dd, 1H, J¼17.4, 10.8 Hz), 6.77
(dd, 1H, J¼7.8, 2.0 Hz), 7.09 (dd, 1H, J¼7.8, 1.5 Hz), 7.16 (t, 1H,
J¼7.8 Hz).
Compound (S)-24: A colorless oil, [
a
]
þ119 (c 1.53, Et2O).
D
HREIMS: calcd for C22H34O3Si (Mþ) 374.2277; found 374.2284.
4.15. (10E,30Z,50R)-5-(50-Hydroxyhexa-10,30-dienyl)-2,2-
dimethyl-4H-benzo[e][1,3]dioxin [(R)-11]
4.12. (1Z,3R)-3-tert-Butyldimethylsilyloxy-1-iodobut-1-ene
(R)-21
A solution of (R)-24 (FW: 374.59, 12.9 mg, 0.0344 mmol) in
a 0.25 M solution of TBAF in THF (0.8 mL, 0.2 mmol) was stirred at
20 ꢁC for 3 h. The mixture was diluted with EtOAc and washed with
water, a satd aq NaHCO3 soln and brine, dried with MgSO4, and
concentrated in vacuo. The residue was chromatographed on silica
gel (hexane/EtOAc¼10:1 to 5:1) to give unreacted (R)-24 (2.1 mg,
0.0056 mmol, 16%) and (R)-11 [FW: 260.33, 7.1 mg, 0.027 mmol,
After a mixture of iodomethyltriphenylphoshonium iodide (FW:
530.12, 5.70 g, 10.8 mmol) and NaN(TMS)2 (1.0
M in THF, 10.8 mL,
10.8 mmol) in THF (15 mL) being stirred at 20 ꢁC for 5 min under
nitrogen, HMPA (FW: 179.20, 0.48 g, 2.7 mmol), was added and the
resulting mixture was cooled to ꢂ78 ꢁC. Then to this was added
aldehyde (R)-2020 (FW: 188.34, 50.6 mg, 2.69 mmol) in THF
(15 mL), and the resulting mixture being stirred at ꢂ78 ꢁC for
20 min before poured into satd aq NH4Cl soln, and extracted with
Et2O. The organic layer was washed with H2O and brine, dried with
MgSO4, and concentrated in vacuo to give crude product (Z/
E¼25:1). This was chromatographed on silica gel (hexane/
79%; 94% taking into account the recovered (R)-24] as a colorless oil,
25
[
n
a
]
ꢂ15 (c 0.36, Et2O). Rf¼0.17 (hexane/EtOAc¼4:1). FTIR (Zn/Se):
D
¼3380 (s, O–H), 1578 (s), 1283 (s), 1144 (s), 1117 (s), 872 (m), 785
(m) cmꢂ1. 1H NMR (CDCl3, 300 MHz):
d
¼1.33 (d, J¼6.3 Hz, 3H, H-60),
1.54 (s, 6H, Me2C), 1.71 (br s, 1H, OH), 4.89 (m, 1H, H-50), 4.89 (s, 2H,
H-4), 5.57 (ddd, J¼9.9, 8.7, 0.9 Hz, 1H, H-40), 6.16 (t, J¼11.1 Hz, 1H, H-
30), 6.43 (d, J¼15.3 Hz, 1H, H-10), 6.74 (dd, J¼7.5, 1.8 Hz, 1H, Ar), 7.00
(ddd, J¼15.3, 11.1, 1.2 Hz, 1H, H-20), 7.11 (dd, J¼8.1, 1.8 Hz, 1H, Ar),
Et2O¼75:1) to give (R)-21 (FW: 312.05, 337 mg, 1.08 mmol, 40.1%)
24
as a colorless oil, [
a
]
D
ꢂ62 (c 0.86, CHCl3). Rf¼0.75 (hexane/
ꢃ
Et2O¼10:1). The 1H NMR datum was identical with the that
7.15 (t, J¼7.4 Hz, 1H, H-7). EIMS: m/z¼260 (Mþ ), 242, 218, 202, 192,
ꢃ
reported for (S)-21.18HREIMS: calcd for C10H21OISi (Mþ ) 312.0406;
184, 144. HREIMS: calcd for C16H20O3 (Mþ) 260.1412; found
260.1418.
found 312.0410.
Compound (S)-21: Compound (S)-20 (0.54 g, 2.3 mmol) afforded
Compound (S)-11: Compound 13 (692 mg, 3.68 mmol) was
24
(S)-21 (0.30 g, 0.97 mmol, 41% in two steps), [
a
]
D
þ60 (c 0.62,
converted to (S)-11 (192 mg, 0.738 mmol, 20.1% from 13 in three
23
24
CHCl3) {lit.18
[
a
]
þ68.1 (c 0.79, CHCl3)}.
steps) as a colorless oil, [
a
]
D
þ9.6 (c 0.05, Et2O). HREIMS: calcd for
D
ꢃ
C16H20O3 (Mþ ) 260.1412; found 260.1412.
4.13. Tributylstannylmethyl iodide (23)
4.16. (10E,30S,40E)-5-(30-Hydroxymethylhexa-10,40-dienyl)-2,2-
dimethyl-4H-benzo[e][1,3]dioxin [(S)-26]
To an ice-cooled suspension of imidazole (FW: 68.08, 1.70 g,
24.9 mmol) in CH2Cl2 (20 mL) was added PPh3 (FW: 262.3, 3.28 g,
12.5 mmol), and then dropwise a solution of Bu3SnCH2OH (22, FW:
321.09, 2.04 g, 6.23 mmol) in THF (10 mL). The mixture was stirred
at room temperature for 12 h. Then the mixture was poured into
a satd aq Na2S2O3 soln and extracted with hexane. The organic layer
To a suspension of KH (FW: 40.11, 30% oil dispersion, 30 mg,
0.22 mmol) in THF (0.3 mL) was added (R)-11 (FW: 260.33, 23 mg,
0.088 mmol) in THF (0.7 mL) at 0 ꢁC and the mixture was stirred for
10 min. Then Bu3SnCH2I (FW: 430.98, 57 mg, 0.13 mmol) was added