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M. Brichacek et al. / Tetrahedron 66 (2010) 4832–4840
was filtered through neutral alumina (activity grade 1) washing
with ethyl acetate and then purified by flash chromatography on
silica gel (10% ether/90% pentane, KMnO4) to yield of 2,5-dihy-
drofuran 7 (22.0 mg, 88%, 0.11 mmol), (Crude diastereomeric ratio
0.138 mmol) was added, and the reaction was left to stir for 40 min
at ꢀ78 ꢁC. After 40 min, triethyl amine was added (0.0699 g,
0.691 mmol), and after an additional 20 min, the reaction was
warmed to 0 ꢁC in an ice bath. After 30 min, the reaction was fil-
tered through a plug of Celite with 50% diethyl ether/pentane. The
solvent was removed in vacuo, 0.5 mL of diethyl ether was added,
and the solution was cooled to 0 ꢁC. In the meantime, methyl tri-
phenylphosphonium bromide (0.247 g, 0.691 mmol) was added to
a 10 mL flask containing diethyl ether (3.5 mL), cooled to 0 ꢁC, and
13:1, purified >20:1 cis/trans). 1H NMR (500 MHz, CDCl3)
d 7.52–
7.00 (m, 5H), 5.85 (d, J¼6.0, 1H), 5.78 (d, J¼6.0, 1H), 4.99–4.90 (m,
2H), 4.66–4.54 (m, 2H), 3.54–3.47 (m, 2H), 1.29 (d, J¼6.3, 3H); 13C
NMR (125 MHz, CDCl3) d 138.5, 133.1, 128.5, 127.8, 127.7, 127.1, 85.5,
82.5, 74.1, 73.6, 23.0; IR (neat) 3312, 3089, 3064, 3031, 2971, 2924,
2859, 1453, 1366, 1094 cmꢀ1; HRMS (EIþ) m/z 202.0996 [calculated
mass for C13H14O2 (MꢀHþ2 ) 202.0994].
equipped with
a stir bar. Potassium tert-butoxide (0.0814 g,
0.725 mmol) was added to the solution. After 1 h, 1.5 mL of this
solution (2 equiv) was added to the crude aldehyde solution. Upon
completion, the reaction was quenched with ammonium chloride
and diluted with diethyl ether. The layers were separated, and the
organic layer was washed with saturated NaCl and dried over
MgSO4. The solvent was removed in vacuo. The product was puri-
fied by chromatography (5% ethyl acetate/95% hexanes) to give
vinyl tetrahydrofuran 11 (0.0047 g, 18%). The NMR data matched
that previously published in the literature.5a 1H NMR (600 MHz,
2.1.5. Diol 8. To a stirred flask containing acetone (5.6 mL), water
(5.6 mL), dihydrofuran
7 (1.00 g, 4.93 mmol), and 4-methyl-
morpholine N-oxide (1.01 g, 8.63 mmol) was added OsO4 (2.5% in
tBuOH, 0.25 mL). After 24 h, the reaction was quenched with a so-
lution of sodium bisulfite and diluted with ethyl acetate. The layers
were separated, and the aqueous layer was extracted with ethyl
acetate (3ꢂ). The combined organic portions were dried over
Na2SO4. The solvent was removed in vacuo and was purified by
chromatography (30–70% ethyl acetate/70–30% hexanes) to give
CDCl3)
d
5.90 (ddd, J¼17.08, 10.50, 6.43, 1H), 5.39 (td, J¼17.23, 1.35,
1H), 5.23 (td, J¼10.50, 1.28, 1H), 4.45 (dd, J¼6.99, 4.95, 1H), 4.28
(ddd, J¼17.44, 6.60, 4.89, 2H), 4.07–3.89 (m, 1H), 1.55 (s, 3H), 1.34 (s,
3H), 1.33 (d, J¼6.41, 3H).
diol 8 (1.03 g, 88%). 1H NMR (400 MHz, CDCl3)
d 7.38–7.26 (m, 5H),
4.56 (d, J¼1.1, 2H), 3.96 (t, J¼5.5, 1H), 3.91 (q, J¼4.8, 1H), 3.81 (ap,
J¼6.2, 1H), 3.66 (ddd, J¼14.4, 8.5, 4.6, 1H), 3.59 (dd, J¼4.7, 0.9, 2H),
3.15 (br s, 1H), 3.04 (br s, 1H), 1.28 (d, J¼6.3, 3H). 13C NMR (126 MHz,
2.1.9. Silyl ether 12. To a 250 mL flask was added 2,4-hexadien-1-ol
(3.4 g, 34.6 mmol, 1 equiv) and CH2Cl2 (100 mL). A stir bar was
added followed by imidazole (4.2 g, 61.7 mmol, 1.8 equiv). Lastly,
tert-butylchlorodiphenylsilane (12.6 g, 45.8 mmol, 1.3 equiv) was
added and the reaction was stirred for 10 h at room temperature.
The reaction was diluted with diethyl ether and washed with 1 M
HCl. The solvent was removed in vacuo and then purified by column
chromatography (2.5% ether/97.5% pentane, anisaldehyde) to yield
11.5 g of product (34.2 mmol, 99%). 1H NMR (400 MHz, CDCl3)
CDCl3)
d 138.1, 128.6, 127.9(7), 127.9(6), 82.8, 79.6, 76.4, 73.8, 72.8,
71.0, 19.0. IR (neat) 3388, 2906, 1496, 1452, 1094, 1019, 738,
696 cmꢀ1. HRMS (ESI) m/z 239.1275 [calculated mass for C13H19O4
(Mþ) 239.1283].
2.1.6. Acetonide 9. To a 100 mL flask equipped with a stir bar was
added methylene chloride (40 mL), diol 8 (1.03 g, 4.32 mmol),
pyridinium p-toluenesulfonate (0.22 g, 0.86 mmol), and 2,2-
dimethoxypropane (4.5 g, 43.2 mmol). The reaction was left to stir
for 3 h. It was diluted with methylene chloride and washed with
NaHCO3 and brine. The solution was dried over Na2SO4 and pu-
rified by chromatography (10–30% ether/90–70% pentane) to give
d
7.87–7.74 (m, 4H), 7.55–7.38 (m, 6H), 6.33 (dd, J¼15.0, 10.7, 1H),
6.23–6.06 (m, 1H), 5.83–5.66 (m, 2H), 4.32 (d, J¼3.8, 2H), 1.83 (d,
J¼6.6, 3H), 1.16 (s, 9H). 13C NMR (101 MHz, CDCl3)
d 135.7, 133.9,
131.3, 130.4, 129.8, 129.6, 129.1, 127.8, 64.5, 27.0, 19.5, 18.3. IR (neat)
3023, 2932, 1959, 1824, 1472, 1427, 1380, 1112, 1050, 988, 823, 702,
606, 491 cmꢀ1. HRMS (EIþ) m/z 336.19001 [calculated mass for
C22H28OSi (Mþ) 336.19095].
acetonide 9 (0.88 g, 67%). 1H NMR (500 MHz, CDCl3)
d 7.40–7.26
(m, 5H), 4.59 (s, 2H), 4.55 (dd, J¼6.96, 4.47, 1H), 4.25 (dd, J¼6.94,
5.05, 1H), 4.06 (dd, J¼9.55, 4.40, 1H), 4.03–3.91 (m, 1H), 3.64–3.52
(m, 2H), 1.53 (s, 3H), 1.33 (s, 3H), 1.31 (d, J¼6.3, 3H); 13C NMR
(125 MHz, CDCl3)
d
138.2, 128.6, 128.0, 127.9, 114.9, 86.2, 83.2,
2.1.10. Vinyl oxiranes 13 and 14. To a 500 mL flask equipped with
a stir bar was added methylene chloride (320 mL), silyl ether 12
(12.2 g, 36.3 mmol), Na2HPO4 (9.81 g, equal mass with m-CPBA),
and m-CPBA (70%, 9.81 g, 39.8 mmol, 1.1 equiv). After 1 h, the re-
action was cooled to 0 ꢁC and filtered through Celite washing with
diethyl ether. It was then diluted with additional diethyl ether and
washed with 1 M NaOH, a saturated NaHCO3 solution, water, and
dried over MgSO4. The solvent was removed in vacuo to give a clear
oil that was purified by column chromatography (2.5% ether/97.5%
pentane, anisaldehyde). The regioisomeric vinyl oxirane products
are readily separable and yielded 7.2 g of 13 and 5.5 g of 14 (1.3:1
ratio, 36.0 mmol, 99%). Vinyl oxirane 13. 1H NMR (400 MHz, CDCl3)
82.6, 80.9, 73.8, 70.7, 27.6, 25.7, 19.2; IR (neat) 3088, 3062, 3031,
2982, 2932, 2870, 1497, 1454, 1372, 1253, 1240, 1211, 1158, 1118,
1076 cmꢀ1
;
HRMS (EIþ) m/z 278.1515 [calculated mass for
C16H22O4 (Mþ) 278.1518].
2.1.7. Primary alcohol 10. To a 50 mL flask equipped with a stir bar
was added methanol (25 mL), acetonide 9 (0.80 g, 2.87 mmol), and
10% Pd/C (0.029 g). A balloon of hydrogen gas was then added. After
18 h, the reaction was filtered through Celite with ethyl acetate. The
solvent was removed in vacuo to afford primary alcohol 10 (0.50 g,
93%). 1H NMR (500 MHz, CDCl3)
d
4.61 (dd, J¼6.99, 4.51, 1H), 4.23
(dd, J¼6.96, 5.23, 1H), 4.12–3.88 (m, 2H), 3.82 (ddd, J¼11.93, 4.90,
3.37, 1H), 3.67 (ddd, J¼12.00, 7.63, 4.45, 1H), 2.00 (dd, J¼7.62, 5.03,
1H), 1.53 (s, 3H), 1.33 (s, 3H), 1.31 (d, J¼6.35, 3H); 13C NMR
d
7.69–7.64 (m, 4H), 7.43–7.33 (m, 6H), 5.97 (ddd, J¼15.5, 4.6, 4.1,
1H), 5.54 (ddt, J¼15.4, 7.9, 1.9, 1H), 4.21 (dd, J¼4.3, 1.8, 2H), 3.08 (dd,
J¼7.9, 2.1, 1H), 2.89 (qd, J¼5.2, 2.2, 1H), 1.33 (d, J¼5.2, 3H), 1.06 (s,
(125 MHz, CDCl3)
d
115.0, 86.3, 84.3, 81.8, 80.7, 63.0, 27.6, 25.6, 19.1;
9H). 13C NMR (101 MHz, CDCl3)
d 135.6, 135.6, 134.1, 133.6, 133.5,
IR (neat) 3466, 2982, 2934, 2878, 1456, 1382, 1263, 1241, 1212, 1158,
1122, 1076 cmꢀ1; HRMS (EIþ) m/z 189.1123 [calculated mass for
C9H17O4 (MþHþ) 189.1127].
129.9, 127.9, 127.3, 63.7, 59.3, 56.6, 27.0, 19.4, 17.8. IR (neat) 2960,
2857, 1428, 1112, 963, 823, 703, 491 cmꢀ1. HRMS (EIþ) m/z
295.11565 [calculated mass for C18H19O2Si (MꢀtBuþ) 295.11544].
Vinyl oxirane 14. 1H NMR (400 MHz, CDCl3)
d 7.77–7.63 (m, 4H),
2.1.8. Vinyl tetrahydrofuran 11. Stock solutions of all reagents were
prepared. To a 5 mL flask equipped with a stir bar was added CH2Cl2
(1 mL) and a solution of oxalyl chloride (0.0210 g, 0.166 mmol). The
solution was cooled to ꢀ78 ꢁC and DMSO was added (0.0259 g,
0.332 mmol). After 15 min, primary alcohol 10 (0.0260 g,
7.49–7.29 (m, 6H), 5.98–5.82 (m, 1H), 5.20 (ddq, J¼15.3, 8.2, 1.6, 1H),
3.83 (dd, J¼11.8, 3.5, 1H), 3.75 (dd, J¼11.8, 4.5, 1H), 3.21 (dd, J¼8.2,
2.1, 1H), 3.04 (ddd, J¼4.5, 3.5, 2.2, 1H), 1.72 (dd, J¼6.6, 1.6, 3H), 1.06
(s, 9H). 13C NMR (101 MHz, CDCl3)
d 135.8, 135.7, 133.4(4), 133.3(8),
132.0, 129.9, 128.3, 127.9(0), 127.8(9), 64.0, 60.1, 56.4, 26.9, 19.4, 18.1.