D. K. Mohapatra, S. Maity, T. S. Rao, J. S. Yadav, B. Sridhar
anhydrous Na2SO4, and concentrated under reduced pressure,
FULL PAPER
H), 3.84 (m, 1 H), 3.09 (m, 1 H), 2.82 (t, J = 4.7 Hz, 1 H), 2.52
(m, 1 H), 2.04 (m, 1 H), 1.95–1.88 (m, 2 H), 1.60 (m, 1 H), 1.22 which upon purification by column chromatography on silica gel
(d, J = 6.6 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 128.9, (ethyl acetate/hexane = 1:9) afforded 5 (2.5 g, 84%) as a colorless
124.4, 70.3, 63.9, 49.9, 47.3, 37.4, 31.9, 20.9 ppm.
liquid. IR (neat): ν = 2946, 2831, 1698, 1667, 1603, 1493, 1460,
˜
1395, 1207, 1148, 1050 cm–1. 1H NMR (300 MHz, CDCl3): δ =
4.57 (t, J = 3.3 Hz, 2 H), 3.54 (s, 6 H), 2.85–2.77 (m, 2 H), 2.73–
2.67 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 151.6, 90.1,
53.4, 30.6, 24.6 ppm.
Ethyl (R)-5-Hydroxy-6-[(2S,6S)-6-methyl-5,6-dihydro-2H-pyran-2-
yl]hex-2-ynoate (11): n-BuLi (1.6 m in hexane, 6.5 mL, 16.3 mmol)
was added dropwise to a stirred solution of ethyl propiolate
(0.56 mL, 5.8 mmol) in anhydrous THF (20 mL) at –78 °C and the
mixture was stirred for 30 min at this temperature. Epoxide 10
(0.3 g, 1.9 mmol) was subsequently added, followed by the drop-
wise addition of BF3·OEt2 (0.82 mL, 5.8 mmol). The resulting col-
orless solution was warmed to 0 °C over 1 h and the reaction was
quenched by the addition of H2O (10 mL). The reaction mixture
was extracted with ethyl acetate (3ϫ 25 mL). The combined or-
ganic layers were dried with anhydrous Na2SO4 and concentrated
in vacuo to afford the crude product, which upon purification by
column chromatography on silica gel (ethyl acetate/hexane = 1:4)
gave homopropargyl alcohol 11 (0.398 g, 81%) as a colorless liquid.
Rf = 0.40 (SiO2, 30% ethyl acetate in hexane). [α]2D5 = +31.6 (c =
Ethyl 2-{(R)-2-(tert-Butyldimethylsilyloxy)-3-[(2S,6S)-6-methyl-5,6-
dihydro-2H-pyran-2-yl]propyl}-4,6-dimethoxybenzoate (3): A mix-
ture of acetylenic ester 4 (0.224 g, 0.58 mmol), diene 5 (0.246 g,
1.8 mmol), and a catalytic amount of N,N-dimethylaniline was
heated in a sealed tube at 200 °C for 48 h. After completion of the
reaction (as indicated by TLC), the residue was purified by column
chromatography on silica gel (ethyl acetate/hexane = 1:9) to afford
the desired Alder–Rickert product 3 (0.168 g, 60%) as a colorless
liquid. Rf = 0.65 (SiO2, 10% ethyl acetate in hexane). [α]2D5 = +34.0
(c = 0.65, CHCl ). IR (neat): ν = 2929, 2855, 1725, 1604, 1462,
˜
3
1219, 1158, 1090, 1055 cm–1. 1H NMR (500 MHz, CDCl3): δ =
1.38, CHCl ). IR (neat): ν = 3416, 2924, 2855, 2235, 1709, 1366, 6.39 (d, J = 2.0 Hz, 1 H), 6.33 (d, J = 2.0 Hz, 1 H), 5.71 (m, 1 H),
˜
3
1251, 1072 cm–1. H NMR (500 MHz, CDCl3): δ = 5.83 (ddd, J = 5.63 (m, 1 H), 4.35 (q, J = 6.8 Hz, 2 H), 4.27 (d, J = 9.8 Hz, 1 H),
1
10.2, 5.1, 3.0 Hz, 1 H), 5.62 (m, 1 H), 4.49 (m, 1 H), 4.20 (q, J =
4.16 (m, 1 H), 3.80 (s, 3 H), 3.79 (s, 3 H), 3.56 (m, 1 H), 2.77 (d, J
7.2 Hz, 2 H), 4.09 (m, 1 H), 3.89 (ddd, J = 10.8, 6.8, 4.2 Hz, 1 H), = 6.8 Hz, 2 H), 1.94–1.83 (m, 2 H), 1.71 (m, 1 H), 1.40 (m, 1 H),
3.19 (d, J = 5.1 Hz, 1 H), 2.60 (d, J = 2.6 Hz, 1 H), 2.57 (d, J = 1.36 (t, J = 6.8 Hz, 3 H), 1.13 (d, J = 5.9 Hz, 3 H), 0.87 (s, 9 H),
2.8 Hz, 1 H), 2.12 (m, 1 H), 1.98–1.82 (m, 2 H), 1.69 (m, 1 H), 1.29
–0.05 (s, 3 H), –0.08 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
(t, J = 7.2 Hz, 3 H) 1.22 (d, J = 6.2 Hz, 3 H) ppm. 13C NMR = 168.2, 160.8, 157.9, 138.8, 130.2, 123.6, 117.5, 107.0, 96.7, 69.6,
(75 MHz, CDCl3): δ = 153.6, 128.6,124.4, 85.8, 74.8, 68.9, 67.0,
64.5, 61.9, 38.6, 31.4, 27.3, 20.4, 13.9 ppm. ESI-HRMS: m/z calcd.
for C14H21O4 [M + H]+: 253.1434; found 253.1454.
68.9, 62.9, 60.9, 55.9, 55.2, 42.2, 40.7, 32.2, 29.6, 25.9, 21.1, 14.2,
–4.7, –4.9 ppm. ESI-HRMS: m/z calcd. for C26H43O6Si [M + H]+:
479.2823; found 479.2848.
Ethyl (R)-5-(tert-Butyldimethylsilyloxy)-6-[(2S,6S)-6-methyl-5,6-di-
hydro-2H-pyran-2-yl]hex-2-ynoate (4): 2,6-Lutidine (1.3 mL,
10.6 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate
(1.4 mL, 5.3 mmol) were added to a stirred solution of 11 (0.9 g,
3.5 mmol) in anhydrous CH2Cl2 (30 mL) at 0 °C. The reaction was
allowed to stir for 15 min at 0 °C and quenched with a saturated
aqueous solution of sodium hydrogen carbonate (25 mL). The or-
ganic layer was separated and the aqueous layer was extracted with
CH2Cl2 (3ϫ 40 mL). The combined organic layer was washed with
brine (75 mL), dried with anhydrous Na2SO4, and concentrated un-
der reduced pressure to obtain the crude product, which upon puri-
fication by column chromatography on silica gel (ethyl acetate/hex-
(R)-6,8-Dimethoxy-3-{[(2S,6S)-6-methyl-5,6-dihydro-2H-pyran-2-
yl]methyl}isochroman-1-one (12): TBAF (1 m solution in THF,
0.4 mL, 0.4 mmol) was added at 0 °C to a stirred solution of Alder–
Rickert product 3 (0.1 g, 0.20 mmol) in anhydrous THF (5 mL).
The reaction mixture was warmed to room temperature and stir-
ring was continued for 6 h at the same temperature. After comple-
tion of the reaction (monitored by TLC), it was quenched by the
addition of H2O (5 mL). THF was removed under reduced pressure
and the aqueous layer was extracted with ethyl acetate (3ϫ 10 mL).
The combined organic layer was washed with brine (25 mL), dried
with anhydrous Na2SO4, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel
ane = 1:49) afforded 4 (1.3 g, 96%) as a colorless liquid. Rf = 0.55 (ethyl acetate/hexane = 2:3) to give the desired product 12 (0.062 g,
(SiO2, 5% ethyl acetate in hexane). [α]2D5 = +43.0 (c = 0.8, CHCl3).
93%) as a white amorphous solid. Rf = 0.65 (SiO2, 10% ethyl acet-
IR (neat): ν = 2929, 2857, 2236, 1714, 1464, 1366, 1251, 1085 cm–1.
ate in hexane), m.p. 128–130 °C. [α]2D5 = +42.0 (c = 0.9, CHCl3). IR
˜
1H NMR (300 MHz, CDCl3): δ = 5.79 (m, 1 H), 5.67 (m, 1 H),
4.26 (d, J = 10.6 Hz, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 4.14 (m, 1
H), 3.77 (m, 1 H), 2.53 (d, J = 5.9 Hz, 2 H), 1.99–1.88 (m, 2 H),
1.65–1.49 (m, 2 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.18 (d, J = 6.2 Hz,
(neat): ν = 2922, 2852, 1722, 1603, 1462, 1219 cm–1 1H NMR
.
˜
(300 MHz, CDCl3): δ = 6.39 (s, 1 H), 6.31 (s, 1 H), 5.82 (ddt, J =
7.5, 5.3, 2.3 Hz, 1 H), 5.64 (d, J = 10.6 Hz, 1 H), 4.62 (dt, J = 10.6,
6.0 Hz, 1 H), 4.52 (s, 1 H), 3.92 (s, 3 H), 3.86 (s, 3 H), 3.80–3.72
3 H), 0.89 (s, 9 H), 0.11 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): (m, 1 H), 2.97–2.82 (m, 2 H), 2.07–1.87 (m, 4 H), 1.19 (d, J =
δ = 153.7, 129.8, 124.0, 86.3, 74.7, 68.7, 67.2, 63.2, 61.7, 40.7, 32.2,
28.3, 25.8, 21.1, 18.0, 14.0, –4.7 ppm. ESI-HRMS: m/z calcd. for
C20H38NO4Si [M + NH4]+: 384.2565; found 384.2577.
6.8 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 164.3, 163.0,
162.4, 143.8, 129.1, 124.3, 107.2, 103.9, 97.8, 74.5, 68.4, 63.7, 56.1,
55.5, 38.8, 35.5, 31.9, 20.9 ppm. ESI-HRMS: m/z calcd. for
C18H23O5 [M + H]+: 319.1540; found 319.1568.
1,5-Dimethoxycyclohexa-1,4-diene (5): A solution of 3-methoxy-
anisole (3.0 mL, 21.7 mmol) in anhydrous diethyl ether (8 mL) and
liquid NH3 (90 mL) was treated by slow addition of lithium (0.76 g,
(R)-6,8-Dimethoxy-3-{[(2R,6S)-6-methyltetrahydro-2H-pyran-2-
yl]methyl}isochroman-1-one (13): A catalytic amount of PtO2 was
108.6 mmol). After stirring for 15 min, absolute ethanol (6 mL) was added in one portion to a solution of 12 (36 mg, 0.1 mmol) in ethyl
added over 30 min. The color of the mixture changed from blue to
colorless. Excess ammonia was allowed to evaporate and the crude
mixture was quenched with a saturated aqueous solution of ammo-
nium chloride (20 mL). The organic layer was separated and the
aqueous layer was extracted with diethyl ether (2ϫ 30 mL). The
combined organic layer was washed with brine (50 mL), dried with
acetate (2 mL). The reaction vessel was evacuated under vacuum
and placed under H2 balloon pressure. The reaction mixture was
allowed to stir at room temperature for 1 h until complete con-
sumption of the starting material, as indicated by TLC. The reac-
tion was filtered through a small pad of Celite and washed with
ethyl acetate (2ϫ 5 mL). The combined organic layer was concen-
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Eur. J. Org. Chem. 2013, 2859–2863