PAPER
Spiroketal Segment of (+)-Spiroxaline Methyl Ether
1139
(S)-1-(Benzyloxy)-6-(trimethylsilyl)hex-5-yn-3-ol (3)
4.22–4.33 (m, 1 H), 4.40–4.51 (m, 3 H), 4.59–4.66 (m, 1 H), 7.20–
7.45 (m, 16 H), 7.65–7.72 (m, 4 H).
To a stirred solution of trimethylsilylacetylene (7.14 mL, 50.56
mmol) in THF (60 mL) at –78 °C was added n-BuLi (1.60 M in hex-
ane, 30.54 mL, 48.87 mmol) and the reaction mixture was stirred for
30 min. To the above mixture was added dropwise BF3⋅OEt2 (6.44
mL, 52.24 mmol) at –78 °C, the stirring continued for 10 min, and
then the epoxide 2 (3.00 g, 16.85 mmol) in THF (10 mL) was added
dropwise to the above mixture. The mixture was stirred further for
1 h at –78 °C and quenched with sat. aq NH4Cl (5 mL). The mixture
was concentrated in vacuo and the obtained residue was dissolved
in EtOAc (60 mL). The organic layer was washed with H2O (15
mL), brine (15 mL), and dried (Na2SO4). Removal of the solvent in
vacuo followed by silica gel column chromatography of the result-
ing residue using EtOAc–PE (8:92) as eluent afforded pure product
3 as a colorless oil;12 yield: 4.13 g (89%); [a]D25 +3.4 (c 1.0 CHCl3).
13C NMR (100 MHz, CDCl3): d = 19.2, 22.8, 22.9, 24.3, 27.0, 33.3,
33.5, 34.4, 34.5, 34.8, 62.5, 62.7, 66.5, 69.09, 69.13, 71.6, 72.9,
74.47, 74.50, 81.6, 81.7, 83.10, 83.13, 127.4, 127.52, 127.54, 127.6,
127.7, 127.8, 128.3, 129.45, 129.54, 134.1, 134.2, 134.6, 135.9,
138.4.
ESIMS: m/z = 657 [M + Na]+.
Anal. Calcd for C41H50O4Si: C, 77.56; H, 7.94. Found: C, 77.27; H,
8.36.
(2R,9S)-2,9,11-Tris(benzyloxy)undec-6-yn-5-ol (8)
Similarly, starting from compound 4 (918 mg, 3.12 mmol) and us-
ing the benzyl-protected 6 (500 mg, 2.60 mmol), product 8 was ob-
tained as a colorless oil, following the above procedure; yield: 949
mg (75%); [a]D25 +23.1 (c 0.5 CHCl3).
IR (neat): 3444, 2176 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.15 (s, 9 H), 1.70–2.00 (m, 2 H),
2.44 (dd, J = 8, 2 Hz, 2 H), 3.07 (br s, 1 H), 3.57–3.80 (m, 2 H),
3.87–4.04 (m, 1 H), 4.52 (s, 2 H), 7.20–7.40 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 0.02, 28.5, 35.3, 68.5, 69.3, 73.2,
87.0, 103.3, 127.6, 127.7, 128.4, 137.8.
IR (CHCl3): 3433, 2252 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.21 (d, J = 6 Hz, 3 H), 1.55–2.10
(m, 6 H), 2.51 (d, J = 6 Hz, 2 H), 2.62 (br s, 1 H), 3.40–3.65 (m, 3
H), 3.65–3.85 (m, 1 H), 4.30–4.55 (m, 6 H), 4.64 (d, J = 12 Hz, 1
H), 7.20–7.40 (m, 15 H).
13C NMR (50 MHz, CDCl3): d = 19.3, 19.5, 24.3, 31.9, 32.1, 33.7,
33.9, 34.4, 62.4, 66.5, 70.2, 71.6, 72.9, 74.4, 74.5, 81.6, 83.1,
127.45, 127.53, 127.6, 127.7, 127.8, 128.3, 138.3, 138.6.
ESIMS: m/z = 277 [M + H]+, 299 [M + Na]+, 315 [M + K]+.
1-{[(S)-1-(Benzyloxy)hex-5-yn-3-yloxy]methyl}benzene (4)
To a stirred suspension of NaH (60% dispersion in mineral oil, 1.33
g, 27.89 mmol) in DMF (40 mL) was added alcohol 3 (3.50 g, 12.68
mmol) in DMF (15 mL) at 0 °C. At the end of 45 min, benzyl bro-
mide (1.50 mL, 27.89 mmol) was added to the reaction mixture and
further stirred at 25 °C for 4 h. The mixture was quenched with sat.
aq NH4Cl (5 mL) and extracted with EtOAc (100 mL). The organic
layer was washed with brine (25 mL) and dried (Na2SO4). Removal
of the solvent in vacuo followed by silica gel column chromatogra-
phy of the resulting residue using EtOAc–PE (5:95) as eluent af-
forded the pure product 4 as a colorless oil;13 yield: 2.87 g (77%);
[a]D25 +43.2 (c 1.7 CHCl3).
ESIMS: m/z = 504 [M + NH4]+, 509 [M + Na]+, 525 [M + K]+.
HRMS (ESI): m/z calcd for C32H38O4 + Na [M + Na]+: 509.2667;
found: 509.2648.
(2R,9S)-9,11-Bis(benzyloxy)-2-[(tert-butyldiphenylsilyl)oxy]un-
dec-6-yn-5-one (9)
To a stirred solution of alcohol 7 (1.00 g, 1.57 mmol) in CH2Cl2
(1.50 mL) at r.t. was added TEMPO (24 mg, 0.15 mmol) and reac-
tion the mixture was further stirred for 10 min, followed by the ad-
dition of iodobis(acetoxy)benzene (558 mg, 1.73 mmol). The
mixture was stirred for 45 min and then diluted with CH2Cl2 (5 mL).
The mixture was washed with sat. aq Na2S2O3 (5 mL) and extracted
with CH2Cl2 (3 × 5 mL). The combined organic extracts were
washed with sat. aq NaHCO3 (2 mL), brine (2 mL), and dried
(Na2SO4). Removal of the solvent in vacuo followed by silica gel
column chromatography of the resulting residue using EtOAc–PE
(7:93) as eluent afforded the pure product 9 as a colorless oil; yield:
847 mg (85%); [a]D25 +24.5 (c 0.6 CHCl3).
IR (neat): 3306, 2120 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.81–2.10 (m, 2 H), 2.01 (t, J = 4
Hz, 1 H), 2.47 (dd, J = 6, 2 Hz, 2 H), 3.48–3.67 (m, 2 H), 3.67–3.85
(m, 1 H), 4.38–4.51 (m, 2 H), 4.46 (d, J = 12 Hz, 1 H), 4.66 (d,
J = 12 Hz, 1 H), 7.15–7.45 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 24.0, 34.3, 66.5, 70.2, 71.6, 72.9,
74.1, 80.9, 127.5, 127.6, 127.7, 127.8, 128.3 (2 C), 138.3, 138.4.
ESIMS: m/z = 295 [M + H]+, 317 [M + Na]+.
IR (CHCl3): 2214, 1715, 1671, 1610 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.01 (d, J = 8 Hz, 3 H), 1.04 (s, 9
H), 1.70–1.87 (m, 2 H), 1.87–2.00 (m, 2 H), 2.50–2.70 (m, 4 H),
3.50–3.65 (m, 2 H), 3.79–3.95 (m, 2 H), 4.40–4.50 (m, 3 H), 4.63
(d, J = 12 Hz, 1 H), 7.20–7.45 (m, 16 H), 7.60–7.70 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 19.2, 23.0, 24.7, 27.0, 33.0, 34.6,
41.2, 66.2, 68.4, 71.9, 73.0, 73.8, 82.2, 90.4, 127.4, 127.57, 127.60,
127.68, 127.73, 127.8, 128.36, 128.38, 129.5, 129.6, 134.0, 134.5,
135.77, 135.81, 138.0, 138.3, 187.8.
(2R,9S)-9,11-Bis(benzyloxy)-2-[(tert-butyldiphenylsilyl)oxy]un-
dec-6-yn-5-ol (7)
To a stirred solution of 4 (1.03 g, 3.52 mmol) in THF (30 mL) at
–78 °C was added n-BuLi (1.60 M in hexane, 2.20 mL, 3.52 mmol)
and the reaction mixture was stirred for 45 min. A solution of alde-
hyde 5 (1.00 g, 2.94 mmol) in THF (10 mL) was added dropwise to
the above mixture and it was further stirred at –78 °C for 1 h. The
reaction was quenched with sat. aq NH4Cl (5 mL) and the THF was
removed in vacuo. The obtained residue was dissolved in EtOAc
(50 mL) and the organic layer was washed with H2O (15 mL), brine
(15 mL), and dried (Na2SO4). Removal of the solvent in vacuo fol-
lowed by silica gel column chromatography of the resulting residue
using EtOAc–PE (1:9) as eluent afforded the pure product 7 as a
colorless oil; yield: 1.34 g (72%); [a]D25 +23.0 (c 0.6 CHCl3).
ESIMS: m/z = 655 [M + Na]+.
HRMS (ESI): m/z calcd for C41H48O4Si + Na [M + Na]+: 655.3219;
found: 655.3194.
(2R,9S)-2,9,11-Tris(benzyloxy)undec-6-yn-5-one (10)
Similarly, starting from compound 8 (510 mg, 1.04 mmol), product
10 was obtained as a colorless oil, following the above procedure;
yield: 426 mg (84%); [a]D25 +29.7 (c 0.5 CHCl3).
IR (CHCl3): 2253, 2215, 1670 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.18 (d, J = 6 Hz, 3 H), 1.93 (sext,
J = 6 Hz, 4 H), 2.50–2.78 (m, 4 H), 3.42–3.65 (m, 3 H), 3.83
IR (CHCl3): 3367, 2251, 1611 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.03 (d, J = 8 Hz, 3 H), 1.05 (s, 9
H), 1.55–1.77 (m, 4 H), 1.82–2.03 (m, 2 H), 2.41–2.55 (m, 2 H),
3.51–3.66 (m, 2 H), 3.69–3.79 (m, 1 H), 3.90 (sept, J = 8 Hz, 1 H),
Synthesis 2011, No. 7, 1137–1141 © Thieme Stuttgart · New York