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D. K. Mohapatra et al.
PAPER
1H NMR (300 MHz, CDCl3): δ = 7.23 (d, J = 8.6 Hz, 2 H), 6.86 (d,
J = 8.6 Hz, 2 H), 5.89–5.80 (m, 1 H), 5.62 (dd, J = 10.0, 1.3 Hz, 1
H), 4.65–4.55 (m, 1 H), 4.49–4.34 (m, 3 H), 4.25–4.04 (m, 1 H),
3.90–3.76 (m, 4 H), 3.71–3.59 (m, 1 H), 3.55–3.46 (m, 1 H), 3.26
(dd, J = 10.7, 4.7 Hz, 1 H), 3.15 (dd, J = 6.7, 10.5 Hz, 1 H), 2.12 (dt,
J = 5.8, 2.8 Hz, 1 H), 2.05–1.95 (m, 2 H), 1.93–1.20 (m, 5 H).
13C NMR (75 MHz, CDCl3): δ = 159.1, 148.2, 130.5, 128.9, 128.5,
124.9, 113.7, 75.2, 73.3, 72.3, 67.4, 66.1, 64.4, 55.3, 38.9, 34.8,
33.6, 30.5, 5.5.
ESI-MS: m/z = 485 [M + Na]+.
ESI-HRMS: m/z calcd for C26H42O5SiNa [M + Na]+: 485.2693;
found: 485.2684.
(4R,6R)-6-(tert-Butyldimethylsiloxy)-7-{(2R,6S)-6-[2-(4-meth-
oxybenzyloxy)ethyl]-5,6-dihydro-2H-pyran-2-yl}hept-1-en-4-ol
(14)
To a solution of the terminal epoxide 13 (1.8 g, 3.86 mmol) in an-
hydrous THF (40 mL) under N2 atmosphere, CuI (74 mg, 0.386
mmol) was added and the resulting mixture was stirred at r.t. for 30
min. It was cooled to −20 °C and vinylMgBr (1.0 M in THF, 11.2
mL) was slowly added to it. The reaction mixture was stirred at the
same temperature for 30 min and slowly warmed to r.t. After com-
pletion of the reaction (monitored by TLC), the mixture was
quenched with sat. aq NH4Cl solution (30 mL) and diluted with
EtOAc (30 mL). The organic layer was separated and the aqueous
layer was extracted with EtOAc (3 × 40 mL). The combined organic
layers were washed with brine (50 mL), dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The crude prod-
uct was purified by column chromatography (silica gel, hexane–
EtOAc, 5:1); this afforded the desired homoallyl alcohol 14 (1.71 g,
90%) as a colorless liquid.
ESI-MS: m/z = 503 [M + H]+.
ESI-HRMS: m/z calcd for C21H27IO6Na [M + Na]+: 525.0745;
found: 525.0777.
(S)-1-{(2R,6S)-6-[2-(4-Methoxybenzyloxy)ethyl]-5,6-dihydro-
2H-pyran-2-yl}-3-[(S)-oxiran-2-yl]propan-2-ol (4)
To a solution of iodocarbonate 5 (3.8 g, 7.56 mmol) in MeOH (60
mL), K2CO3 (3.1 g, 22.7 mmol) was added and the resulting mixture
was stirred at r.t. for 1 h. After completion of the reaction (moni-
tored by TLC), MeOH was evaporated under reduced pressure. The
residue was diluted with H2O (30 mL) and extracted with EtOAc (3
× 50 mL). The combined organic phase was washed with brine (75
mL), dried over anhydrous Na2SO4, and concentrated under re-
duced pressure; this gave the crude product, which on purification
by column chromatography (silica gel, hexane–EtOAc, 5:2) afford-
ed the desired epoxy alcohol 4 (2.49 g, 95%) as a colorless liquid.
[α]D25 −17.2 (c 1.3, CHCl3).
IR (neat): 3459, 2931, 2856, 1612, 1513, 1249, 1081 cm−1.
1H NMR (300 MHz, CDCl3): δ = 7.20 (d, J = 9.0 Hz, 2 H), 6.82 (d,
J = 9.0 Hz, 2 H), 5.81–5.56 (m, 3 H), 5.05–4.96 (m, 2 H), 4.42 (d,
J = 11.3 Hz, 1 H), 4.36 (d, J = 11.3 Hz, 1 H), 4.32–4.24 (m, 1 H),
4.14–4.02 (m, 1 H), 3.82–3.74 (m, 5 H), 3.53–3.42 (m, 2 H), 2.05 (t,
J = 6.7 Hz, 2 H), 198–1.88 (m, 2 H), 1.88–1.83 (m, 1 H), 1.62–1.48
(m, 2 H), 1.46–1.40 (m, 3 H), 0.89 (br s, 9 H), 0.10–0.09 (m, 6 H).
13C NMR (75 MHz, CDCl3): δ = 159.3, 135.2, 130.4, 129.5, 129.2,
124.0, 117.2, 113.8, 71.9, 69.4, 68.2, 67.6, 65.8, 63.2, 55.3, 45.0,
42.6, 40.6, 34.9, 31.1, 25.9, 18.0, −4.2, −4.4.
[α]D25 −6.2 (c 1.7, CHCl3).
IR (neat): 3483, 3033, 2996, 1739, 1612, 1463, 1302 cm−1.
1H NMR (300 MHz, CDCl3): δ = 7.20 (d, J = 8.2 Hz, 2 H), 6.81 (d,
J = 8.2 Hz, 2 H), 5.86–5.72 (m, 1 H), 5.61 (d, J = 9.9 Hz, 1 H), 4.48–
4.36 (m, 3 H), 4.13–3.97 (m, 1 H), 3.96–3.83 (m, 1 H), 3.78 (s, 3 H),
3.64–3.41 (m, 2 H), 3.07–2.93 (m, 1 H), 2.80–2.65 (m, 2 H), 2.49–
2.39 (m, 1 H), 2.08–1.47 (m, 8 H).
13C NMR (75 MHz, CDCl3): δ = 159.1, 130.4, 129.2, 129.1, 124.1,
113.7, 72.6, 71.3, 68.7, 66.7, 66.5, 65.5, 55.2, 50.2, 46.6, 39.8, 34.6,
30.2.
ESI-MS: m/z = 513 [M + Na]+.
ESI-HRMS: m/z calcd for C28H46O5SiNa [M + Na]+: 513.3006;
found: 513.2999.
ESI-MS: m/z = 371 [M + Na]+.
ESI-HRMS: m/z calcd for C20H28O5Na [M + Na]+: 371.1828; found:
371.1828.
tert-Butyl (2R,4R)-2-(tert-Butyldimethylsilyloxy)-1-{(2R,6S)-6-
[2-(4-methoxybenzyloxy)ethyl]5,6-dihydro-2H-pyran-2-
yl}hept-6-en-4-yl Carbonate (15)
To a solution of alcohol 14 (1.6 g, 3.26 mmol) in CH2Cl2 (40 mL),
(Boc)2O (1.49 mL, 6.53 mmol), followed by Et3N (0.91 mL, 6.53
mmol) and DMAP (39 mg, 0.326 mmol) were added at r.t. After
stirring for 5 h, the mixture was quenched with 5% aq KHSO4 (25
mL). The organic layer was separated and the aqueous layer was ex-
tracted with CH2Cl2 (3 × 40 mL). The combined organic layer was
washed with brine (2 × 70 mL), dried over anhydrous Na2SO4, and
concentrated under reduced pressure to give the crude product,
which on purification by column chromatography (silica gel,
hexane–EtOAc, 19:1) afforded the Boc-protected compound 15
(1.6 g, 88%) as a colorless liquid.
tert-Butyl((S)-1-{(2R,6S)-6-[2-(4-methoxybenzyloxy)ethyl]-5,6-
dihydro-2H-pyran-2-yl}-3-[(S)-oxiran-2-yl]propan-2-yloxy)di-
methylsilane (13)
To a stirred solution of alcohol 4 (2.1 g, 6.05 mmol) in CH2Cl2 (40
mL) at 0 °C was added 2,6-lutidine (1.05 mL, 9.05 mmol) and
TBSOTf (1.97 mL, 9.05 mmol). After 30 min, sat. aq NaHCO3 (40
mL) was added. The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 (3 × 40 mL). The combined organ-
ic layer was dried over NaSO4 and concentrated under reduced
pressure. The crude product was purified by flash column chroma-
tography (silica gel, hexane–EtOAc, 10:1) to furnish TBS ether 13
(1.93 g, 86%) as a colorless liquid.
[α]D25 −11.3 (c 1.0, CHCl3).
[α]D25 −5.6 (c 2.1, CHCl3).
IR (neat): 3033, 2928, 2856, 1731, 1612, 1513, 1464, 1249, 1091
cm−1.
IR (neat): 3033, 2928, 2856, 1731, 1612, 1513, 1464, 1249, 1091
cm−1.
1H NMR (300 MHz, CDCl3): δ = 7.19 (d, J = 8.4 Hz, 2 H), 6.81 (d,
J = 8.4 Hz, 2 H), 5.80–5.68 (m, 2 H), 5.60 (d, J = 10.4 Hz, 1 H),
5.12–5.02 (m, 2 H), 4.84–4.73 (m, 1 H), 4.42 (d, J = 11.5 Hz, 1 H),
4.36 (d, J = 11.5 Hz, 1 H), 4.29–4.20 (m, 1 H), 4.01–3.90 (m, 1 H),
3.78 (s, 3 H), 3.74–3.63 (m, 1 H), 3.53 (t, J = 6.7 Hz, 2 H), 2.35–
2.27 (m, 2 H), 1.98–1.90 (m, 2 H), 1.82–1.61 (m, 6 H), 1.45 (br s, 9
H), 0.89 (br s, 9 H), 0.06 (br s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 159.0, 153.0, 133.4, 130.2, 129.1,
123.7, 117.9, 113.7, 81.6, 73.2, 72.6, 68.9, 66.8, 65.8, 64.1, 55.2,
41.8, 40.2, 39.6, 35.7, 30.8, 27.7, 25.8, 18.0, −4.3, −4.7.
1H NMR (400 MHz, CDCl3): δ = 7.18 (d, J = 7.8 Hz, 2 H), 6.81 (d,
J = 7.8 Hz, 2 H), 5.79–5.72 (m, 1 H), 5.64 (d, J = 4.2 Hz, 1 H), 4.41
(d, J = 12.4 Hz, 1 H), 4.37 (d, J = 12.4 Hz, 1 H), 4.44–4.24 (m, 1 H),
4.11–4.02 (m, 1 H), 3.79 (s, 3 H), 3.77–3.69 (m, 1 H), 3.61–3.46 (m,
2 H), 2.96–2.89 (m, 1 H), 2.67–2.62 (m, 1 H), 2.36–2.30 (m, 1 H),
1.98–1.89 (m, 1 H), 1.82–1.70 (m, 3 H), 1.56–1.43 (m, 2 H), 1.42–
1.36 (m, 2 H), 0.89 (s, 9 H), 0.09 (s, 3 H), 0.06 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 159.1, 130.3, 129.1, 123.8, 113.7,
72.6, 69.1, 69.0, 66.6, 63.8, 55.2, 48.8, 46.6, 41.2, 40.9, 40.5, 35.7,
30.9, 29.6, 25.8, 17.9, −4.4, −4.7.
ESI-MS: m/z = 613 [M + Na]+.
Synthesis 2014, 46, 1639–1647
© Georg Thieme Verlag Stuttgart · New York