The Journal of Organic Chemistry
Article
20
1
1612, 1588, 1517, 1464, 1380, 1302, 1250, 1102, 1035, 1006, 830, 728
cm−1.
olefin 30 as a viscous clear oil. [α]D = +43.6 (c 0.75, CHCl3); H
NMR (500 MHz, CDCl3) δ (ppm): 7.69−7.66 (m, 4H), 7.46−7.37
(m, 8H), 6.90 (d, J = 8.8 Hz, 2H), 5.60 (s, 1H), 5.13 (d, J = 1.8 Hz,
1H), 4.85 (d, J = 1.9 Hz, 1H), 4.32 (m, 1H), 4.07 (dd, J = 10.3, 4.7 Hz,
1H), 3.97 (d, J = 9.4 Hz, 1H), 3.81 (s, 3H), 3.77−3.64 (m, 3H), 3.43
(td, J = 9.6, 4.7 Hz, 1H), 2.72 (dd, J = 13.8, 6.4 Hz, 1H), 2.25 (d, J =
13.8 Hz, 1H), 2.06 (m, 1H), 1.72 (m, 1H), 1.06 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ (ppm): 160.2, 139.9, 135.8, 135.7, 133.9, 133.8,
130.4, 129.8, 129.8, 127.8, 127.8, 127.7, 113.7, 107.5, 101.6, 80.7, 71.6,
To the above primary alcohol (2.78 g, 8.96 mmol, 1 equiv) in
CH2Cl2 (45 mL) was added imidazole (1.20 g, 17.92 mmol, 2 equiv)
at room temperature. The solution was cooled to 0 °C upon which
TBDPS-Cl (2.1 mL, 8.06 mmol, 0.9 equiv) was added. After 30 min,
the reaction was diluted with water and the crude product was
extracted with CH2Cl2 (×3), washed with brine, and dried over
Na2SO4. Purification by flash chromatography (20% to 60% EtOAc/
hexanes) gave 2.78 g (76% yield) of silyl ether 29 as a white foam.
70.0, 67.5, 60.5, 55.4, 38.2, 33.1, 29.9, 27.0, 19.3; FT-IR (neat) νmax
=
20
[α]D = +19.2 (c 2.3, CHCl3); 1H NMR (500 MHz, CDCl3) δ
3073, 2956, 2928, 2856, 1615, 1519, 1461, 1428, 1250, 1099, 1036,
824, 704, 504 cm−1; HRMS-ESI (+) m/z calcd for C33H40O5SiNa [M
+ Na]+: 567.2543, found 567.2549.
(ppm): 7.69−7.66 (m, 4H), 7.44−7.37 (m, 8H), 6.90 (d, J = 8.8 Hz,
2H), 5.51 (s, 1H), 4.31 (m, 1H), 4.09 (dd, J = 10.3, 4.3 Hz, 1H),
4.01−3.96 (m, 1H), 3.81 (s, 3H), 3.78−3.62 (m, 3H), 3.43−3.41 (m,
2H), 2.46 (d, J = 2.2 Hz, 1H), 2.08 (m, 1H), 2.01−1.90 (m, 2H), 1.75
(m, 1H), 1.06 (s, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm): 160.3,
135.7, 135.7, 133.8, 133.7, 130.0, 129.9, 129.8, 127.8, 127.8, 127.7,
113.9, 102.1, 84.8, 70.8, 69.5, 66.5, 64.1, 60.6, 55.5, 36.0, 34.0, 27.0,
19.3; FT-IR (neat) νmax = 3468, 3070, 2954, 2929, 2855, 1616, 1588,
1521, 1464, 1426, 1380, 1302, 1250, 1172, 1088, 1038, 999, 827, 739,
704, 616, 503 cm−1; HRMS-ESI (+) m/z calcd for C32H41O6Si [M +
H]+: 549.2667, found 549.2670.
((2R,3S,6S)-6-(2-((tert-Butyldiphenylsilyl)oxy)ethyl)-3-((4-
methoxybenzyl)oxy)-4-methylenetetrahydro-2H-pyran-2-yl)-
methanol (31). To benzylidene acetal 30 (1.95 g, 3.58 mmol, 1
equiv) in toluene (36 mL) at −78 °C was added DIBAL-H (10.7 mL,
10.74 mmol, 3 equiv, 1 M in hexanes) dropwise. The reaction was
warmed to 0 °C, and after 1 h, a few drops of MeOH were added.
Then, it was diluted with EA and quenched with sodium potassium
tartrate. After warming to room temperature and stirring vigorously for
1 h, the crude product was extracted with EtOAc (×3), washed with
brine, and dried over Na2SO4. Purification by flash chromatography
(10% to 50% EtOAc/hexanes) afforded 1.36 g (69% yield) of alcohol
31 as a clear oil. [α]D20 = +44.3 (c 0.41, CHCl3); 1H NMR (500 MHz,
CDCl3) δ (ppm): 7.67−7.64 (m, 4H), 7.44−7.36 (m, 6H), 7.26 (d, J =
8.7 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 5.06 (s, 1H), 4.99 (s, 1H), 4.60
(d, J = 11.4 Hz, 1H), 4.34 (d, J = 11.5 Hz, 1H), 4.10 (m, 1H), 3.86−
3.80 (m, 4H), 3.71−3.64 (m, 4H), 3.53 (m, 1H), 2.32 (qd, J = 13.2,
4.6 Hz, 2H), 1.93 (dd, J = 7.7, 4.2 Hz, 1H), 1.84 (m, 1H), 1.64 (m,
1H), 1.04 (s, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm): 159.4,
141.7, 135.7, 133.9, 133.8, 130.2, 129.8, 129.7, 127.8, 114.0, 111.6,
76.7, 76.2, 70.9, 69.1, 61.1, 60.3, 55.4, 37.7, 35.4, 27.0, 19.3; FT-IR
(neat) νmax = 3449, 3069, 2951, 2930, 2855, 1613, 1514, 1426, 1249,
1110, 1086, 1038, 824, 739, 700, 504 cm−1; HRMS-ESI (+) m/z calcd
for C33H42O5SiNa [M + Na]+: 569.2699, found 569.2701.
tert-Butyl(2-((2S,5S,6R)-5-((4-methoxybenzyl)oxy)-4-methyl-
ene-6-vinyltetrahydro-2H-pyran-2-yl)ethoxy)diphenylsilane
(32). To a two-neck flask charged with flame-dried 4 Å MS was added
alcohol 31 (756 mg, 1.38 mmol, 1 equiv) in CH2Cl2 (12 mL) and
NMO (243 mg, 2.07 mmol, 1.5 equiv) in CH2Cl2 (2 mL) via cannula
at room temperature. After stirring for 20 min, TPAP (49 mg, 0.14
mmol, 0.1 equiv) was added to the reaction flask. After 15 min, the
reaction was quenched with DMS, filtered over a silica plug, rinsed
with EtOAc, and concentrated. The crude aldehyde was used directly
for the next reaction.
tert-Butyl(2-((4aR,6S,8aS)-2-(4-methoxyphenyl)-8-
methylenehexahydropyrano[3,2-d][1,3]dioxin-6-yl)ethoxy)-
diphenylsilane (30). To a two-neck flask charged with flame-dried 4
Å MS was added alcohol 29 (1.06 g, 1.93 mmol, 1 equiv) in CH2Cl2 (8
mL) and NMO (452 mg, 3.86 mmol, 2 equiv) in CH2Cl2 (2 mL) via
cannula at room temperature. After stirring for 20 min, TPAP (68 mg,
0.193 mmol, 0.1 equiv) was added to the reaction flask. After 30 min,
the black mixture was filtered over Celite, rinsing with CH2Cl2, and the
filtrate was concentrated. Purification by flash chromatography (30%
to 40% EtOAc/hexanes) gave 863 mg (80% yield) of the
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corresponding ketone as a white foam. [α]D = +30.3 (c 0.57,
CHCl3); 1H NMR (500 MHz, CDCl3) δ (ppm): 7.68−7.64 (m, 4H),
7.45−7.37 (m, 8H), 6.88 (d, J = 8.8 Hz, 2H), 5.52 (s, 1H), 4.70 (m,
1H), 4.31 (dd, J = 9.3, 1.1 Hz, 1H), 4.18 (dd, J = 9.8, 4.2 Hz, 1H),
3.82−3.73 (m, 6H), 3.67 (m, 1H), 2.96 (ddd, J = 14.3, 7.5, 1.4 Hz,
1H), 2.43 (dd, J = 14.3, 1.5 Hz, 1H), 1.98 (m, 1H), 1.76 (m, 1H), 1.05
(s, 9H); 13C NMR (125 MHz, CDCl3) δ (ppm): 200.2, 160.4, 135.7,
135.7, 133.5, 133.5, 130.0, 129.9, 129.3, 127.9, 127.9, 127.8, 113.8,
102.2, 83.8, 73.0, 69.9, 67.6, 59.8, 55.4, 45.4, 34.6, 29.9, 27.0, 19.3; FT-
IR (neat) νmax = 3070, 2959, 2928, 2856, 1736, 1615, 1516, 1464,
1428, 1250, 1129, 1111, 824, 704, 504 cm−1; HRMS-ESI (+) m/z
calcd for C32H38O6SiNa [M + Na]+: 569.2336, found 569.2334.
To the above ketone (2.30 g, 4.28 mmol, 1 equiv) in Et2O (16 mL)
at 0 °C was added TMSCH2MgCl (6.0 mL, 6.0 mmol, 1.4 equiv, 1 M
in Et2O) dropwise. After 10 min, the reaction was quenched with satd
NH4Cl. The crude product was extracted with EtOAc (×3), washed
with brine, and dried over Na2SO4. Purification by flash chromatog-
raphy (10% to 20% EtOAc/hexanes) gave 2.40 g (88% yield) of the
To Ph3PCH3Br (2.46 g, 6.90 mmol, 5 equiv) in freshly distilled
THF (7 mL) was added BuOK (5.5 mL, 5.52 mmol, 4 equiv, 1 M in
t
THF) dropwise at 0 °C. After stirring for 1 h at 0 °C, a portion of the
yellow stock solution (3.5 mL, 1.52 mmol, 1.1 equiv, 0.44 M) was
added via syringe dropwise to the crude aldehyde (1.38 mmol, 1
equiv) in THF (7 mL) at 0 °C. After 10 min, the reaction was
quenched with satd NH4Cl. The crude product was extracted with
EtOAc (×3), washed with brine, and dried over Na2SO4. Purification
by flash chromatography (5% to 20% EtOAc/hexanes) provided 231
20
corresponding quaternary alcohol as a white foam. [α]D = +24.1 (c
0.72, CHCl3); 1H NMR (500 MHz, CDCl3) δ (ppm): 7.70−7.67 (m,
4H), 7.42−7.37 (m, 8H), 6.91 (d, J = 8.8 Hz, 2H), 5.55 (s, 1H), 4.21
(m, 1H), 4.13 (dd, J = 10.2, 5.0 Hz, 1H), 3.86 (m, 1H), 3.82 (s, 3H),
3.80−3.76 (m, 1H), 3.72−3.68 (m, 1H), 3.63 (t, J = 10.3 Hz, 1H),
3.37 (d, J = 9.2 Hz, 1H), 2.49 (m, 1H), 1.99−1.86 (m, 4H), 1.25 (d, J
= 14.7, 1H), 1.05 (s, 9H), 0.89 (d, J = 14.9 Hz, 1H), 0.06 (s, 9H); 13C
NMR (125 MHz, CDCl3) δ (ppm): 160.3, 135.8, 135.7, 134.1, 134.0,
130.3, 129.7, 129.7, 127.8, 127.7, 127.6, 113.8, 101.9, 84.5, 71.8, 69.8,
61.1, 60.9, 55.4, 40.2, 34.9, 30.0, 29.9, 27.0, 19.4, 0.6; FT-IR (neat)
νmax = 3482, 2957, 2927, 2855, 1616, 1520, 1466, 1429, 1249, 1104,
836, 703, 501 cm−1; HRMS-ESI (+) m/z calcd for C36H50O6Si2Na [M
+ Na]+: 657.3044, found 657.3048.
20
mg (31% yield) olefin 32 as a clear oil. [α]D = +36.0 (c 0.37,
CHCl3); 1H NMR (500 MHz, CDCl3) δ (ppm): 7.67−7.65 (m, 4H),
7.43−7.35 (m, 6H), 7.26 (d, J = 8.5 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H),
5.84 (ddd, J = 17.2, 10.8, 5.7 Hz, 1H), 5.28 (d, J = 17.5 Hz, 1H), 5.21
(d, J = 10.8 Hz, 1H), 5.05 (s, 1H), 4.97 (s, 1H), 4.56 (d, J = 11.8 Hz,
1H), 4.38 (m, 1H), 4.30 (d, J = 11.8 Hz, 1H), 4.04 (m, 1H), 3.87−
3.80 (m, 4H), 3.70 (m, 1H), 3.64 (d, J = 3.1 Hz, 1H), 2.32 (m, 1H),
2.19 (dd, J = 13.1, 3.2 Hz, 1H), 1.86 (m, 1H), 1.71 (m, 1H), 1.03 (s,
9H); 13C NMR (125 MHz, CDCl3) δ (ppm): 159.3, 141.3, 135.7,
135.7, 135.0, 134.1, 134.0, 130.5, 129.7, 127.7, 118.3, 113.9, 113.3,
79.3, 78.2, 69.6, 68.7, 60.3, 55.4, 38.0, 37.3, 29.9, 27.0, 19.3; FT-IR
(neat) νmax = 3072, 2956, 2925, 2856, 1612, 1513, 1464, 1428, 1247,
1111, 1087, 821, 737, 704, 613, 501 cm−1; HRMS-ESI (+) m/z calcd
for C34H42O4SiNa [M + Na]+: 565.2750, found 565.2764.
To the above alcohol (2.39 g, 3.76 mmol, 1 equiv) in freshly
distilled THF (19 mL) at 0 °C was added KHMDS (9 mL, 4.52 mmol,
1.2 equiv, 0.5 M in PhMe) dropwise. The yellow solution was warmed
to room temperature. After 1.5 h, the reaction was quenched with satd
NH4Cl. The crude product was extracted with EtOAc (×3), washed
with brine, and dried over Na2SO4. Purification by flash chromatog-
raphy (10% to 20% EtOAc/hexanes) afforded 1.96 g (96% yield) of
I
J. Org. Chem. XXXX, XXX, XXX−XXX