The Journal of Organic Chemistry
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(electrospray) m/z calcd for C39H50NaO9Si (M + Na) 713.3116,
found 713.3111.
mmol) was added to a stirred solution of 10.1 (31 mg, 0.047 mmol) in
PhH (2.5 mL). The mixture turned green after the addition. t-BuOOH
(5.5 M in decane, 20 μL, 0.11 mmol) was added dropwise to the
stirred mixture; the color changed immediately to burgundy. TLC
(silica, EtOAc) showed that the starting material had been consumed
after 30 min. The mixture was then diluted with EtOAc (2.5 mL) and
quenched with saturated aqueous Na2SO3 (2.5 mL). The mixture was
stirred for 1 h until the organic phase was clear. The organic phase was
then washed with water (2.5 mL) and brine, dried (MgSO4), and
evaporated. Flash chromatography of the residue over silica gel
(Pasteur pipet, 7 cm), using 5:95 MeOH−EtOAc, gave 10.2 (28 mg,
91%) as a colorless oil which was mixture of two inseparable isomers
(1.6:1 based on NMR): FTIR (cast film) 3444, 3071, 3048, 2931,
2883, 2858, 2247, 1472, 1428, 1389, 1363, 1281, 1247, 1197, 1169,
A sample for X-ray analysis was crystallized from EtOAc−hexane.
2-(Methoxycarbonyl)cyclohexane-1-carboxylic Acid (8.3).21
AcOH (212 μL, 3.71 mmol) was added to a stirred solution of 8.220
(isomer mixture) (74.5 mg, 0.371 mmol) and NaNO2 (0.077 g, 1.11
mmol) in dry DMSO (1.5 mL). The reaction mixture was stirred at 40
°C for 8 h and then diluted with water (30 mL) and acidified with
hydrochloric acid (3 N) to below pH 2. The resulting mixture was
extracted with Et2O (5 × 30 mL), and the combined organic extracts
were dried (MgSO4) and evaporated. Flash chromatography of the
residue over silica gel (1 × 15 cm), using 1:1 hexane−EtOAc, gave 8.3
(56 mg, 81%) as a pale yellow oil, which was a single isomer of
1
unestablished stereochemistry: H NMR (CDCl3, 400 MHz) δ 1.36−
1
1112, 1089, 1041, 1008 cm−1; H NMR (CDCl3, 400 MHz) (major
1.64 (m, 4 H), 1.72−1.88 (m, 2 H), 1.96−2.10 (m, 2 H), 2.80−2.92
(m, 2 H), 3.79 (s, 3 H), 10.2−10.8 (br s, 1 H).
isomer signals) δ 1.06 (s, 9 H), 1.44−1.64 (m, 4 H), 1.78−2.03 (m, 3
H), 2.14−2.36 (m, 3 H), 2.59 (s, 1 H), 2.86 (d, J = 1.2 Hz, 1 H), 3.12
(d, J = 5.4 Hz, 1 H), 3.34 (d, J = 5.4 Hz, 1 H), 3.39 (s, 3 H), 3.52−3.59
(m, 2 H), 3.59−3.76 (m, 5 H), 3.76−3.90 (m, 3 H), 4.72 (s, 2 H), 5.11
(d, J = 4.8 Hz, 1 H), 5.53 (s, 1 H), 7.35−7.52 (m, 6 H), 7.62−7.72 (m,
4 H); 13C NMR (CDCl3, 100 MHz) (major isomer signals) δ 19.0 (s),
26.8 (q), 33.9 (t), 34.8 (t), 36.6 (t), 37.3 (d), 37.4 (d), 42.1 (s), 42.3
(d), 54.1 (t), 59.0 (q), 60.55.(t), 60.60 (t), 61.48 (d), 65.0 (t), 65.7
(t), 65.9 (t), 67.0 (t), 71.8 (t), 95.6 (t), 102.9 (d), 104.0 (s), 127.70
(d), 127.74 (d), 127.8 (d), 129.8 (d), 133.17 (s), 133.24 (s), 135.58
(d), 135.60 (d), 141.5 (s); exact mass (electrospray) m/z calcd for
C38H52NaO9Si (M + Na) 703.3273, found 703.3268.
Methyl (1R,5S,6S,7R,8R,9R,11S,13S)-rel-9-(2-Hydroxyethyl)-
6-[2-[(2-methoxyethoxy)methoxy]ethyl]-12-(nitromethyl)-15-
oxo-2,14-dioxapentacyclo[7.4.2.01,8.05,13.07,11]pentadecane-11-
carboxylate (9.1). MeNO2 (24 μL, 0.43 mmol) and Bu4NF (1 M in
THF, 33 μL, 0.033 mmol) were added to a stirred solution of 6.9 (10
mg, 0.0145 mmol) in THF (0.15 mL), and stirring was continued for 6
h, by which time all the starting material had been consumed (TLC
control, silica, 1:1 hexane−EtOAc). The reaction mixture was
evaporated and flash chromatography of the residue over silica gel
(Pasteur pipet, 4 cm), using 2:98 MeOH−EtOAc, gave 9.1 (6 mg,
85%) as a colorless oil: FTIR (cast film) 3467, 2925, 2886, 1779, 1727,
1556, 1458, 1435, 1384, 1307, 1239, 1189, 1158, 1114, 1100, 1060
cm−1; 1H NMR (CDCl3, 500 MHz) δ 1.02 (s, 1 H), 1.32−1.54 (m, 2
H), 1.60−1.72 (m, 1 H), 1.85−2.02 (m, 5 H), 2.08−2.18 (m, 2 H),
2.32 (d, J = 14.8, 1 H), 2.84−2.91 (m, 2 H), 3.17 (dd, J = 9.7, 4.8, 1
H), 3.40 (s, 3 H), 3.46−3.72 (m, 6 H), 3.74 (s, 3 H), 3.80−3.90 (m, 3
H), 3.98 (dd, J = 12.9, 5.4 Hz, 1 H), 4.37 (dd, J = 12.8, 9.9 Hz, 1 H),
4.49 (dd, J = 12.8, 4.8 Hz, 1 H), 4.69 (s, 2 H); 13C NMR (CDCl3, 125
MHz) δ 30.8 (t), 31.8 (d), 35.5 (t), 37.1 (t), 38.5 (d), 38.6 (d), 39.8
(d), 45.9 (t), 47.8 (d), 49.9 (s), 51.4 (s), 52.3 (d), 53.0 (q), 59.1 (q),
59.2.(t), 60.7 (t), 65.0 (t), 67.1 (t), 71.8 (t), 76.3 (t), 95.6 (t), 106.9
(s), 174.9 (s), 177.8 (s); exact mass (electrospray) m/z calcd for
C24H35NNaO11 (M + Na) 536.2102, found 536.2100.
[(1S,5R,6R,9R,14R)-rel-(9-[2-[(tert-Butyldiphenylsilyl)oxy]-
ethyl]-6-[2-[(2-methoxyethoxy)methoxy]ethyl]-16-
[ ( t r i e t h y l s i l y l ) o x y ] - 2 , 1 2 , 1 5 - t r i o x a p e n t a c y c l o -
[7.5.2.01,8.05,14.01,13]hexadec-7-en-11-yl)methoxy]triethylsilane
(10.3). 2,6-Lutidine (20 μL, 0.165 mmol) followed by Et3SiOSO2CF3
(35 μL, 0.165 mmol) were added to a stirred and cooled (0 °C)
solution of 10.2 (28 mg, 0.041 mmol) in CH2Cl2 (1.5 mL). After 40
min, the ice bath was removed, and stirring was continued for 2.5 h.
The mixture was quenched with saturated aqueous NaHCO3 (0.1
mL), diluted with water, and extracted with CH2Cl2 (3 × 4 mL). The
combined organic extracts were dried (MgSO4) and evaporated. Flash
chromatography of the residue over silica gel (Pasteur pipet, 7 cm),
using 3:7 EtOAc−hexane, gave 10.3 (30 mg, 81%) as a colorless oil
(1S,5R,6R,9S,13R)-rel-9-[2-[(tert-Butyldiphenylsilyl)oxy]-
ethyl]-11-(hydroxymethyl)-6-[2-[(2-methoxyethoxy)methoxy]-
ethyl]-2,14-dioxatetracyclo[7.4.2.01,8.05,13]pentadeca-7,11-
dien-15-ol (10.1). DIBAL-H (1 M in PhMe, 0.9 mL, 0.9 mmol) was
added dropwise to a stirred and cooled (−78 °C) solution of 6.9 (32
mg, 0.05 mmol) in THF (2 mL). Stirring at −78 °C was continued for
3.5 h, and the cold bath was replaced by an ice bath. After 5 min, the
mixture was quenched with Na2SO4·10H2O. The ice bath was
removed, Et2O (2 mL) was added, and stirring was continued for 40
min. The mixture was filtered through a fritted funnel. Evaporation of
the filtrate and flash chromatography of the residue over silica gel
(Pasteur pipet, 7 cm), using EtOAc, gave 10.1 (30 mg, 97%) as a
colorless oil which was a 3:1 mixture of two stereoisomers: FTIR (cast
film) 3421, 3071, 3048, 2930, 2877, 2858, 1472, 1428, 1389, 1363,
1
which was a mixture of two inseparable isomers (6:1 based on H
NMR): FTIR (cast film) 3071, 3049, 2934, 2954, 2876, 1461, 1428,
1
1414, 1241, 1199, 1111, 1092, 1019 cm−1; H NMR (CDCl3, 500
MHz) (major isomer signals) δ 0.46−0.68 (m, 12 H), 0.82−098 (m,
18 H), 1.06 (s, 9 H), 1.44−1.54 (m, 1 H), 1.54−1.81 (m, 3 H), 1.82−
2.04 (m, 3 H), 2.1 (d, J = 15.4 Hz, 1 H), 2.14−2.26 (m, 2 H), 2.51 (s,
1 H), 2.57 (d, J = 1.3 Hz, 1 H), 3.08 (d, J = 10.4 Hz, 1 H), 3.41 (s, 3
H), 3.49 (d, J = 10.4 Hz, 1 H), 3.52−3.59 (m, 2 H), 3.59−3.70 (m, 5
H), 3.70−3.88 (m, 3 H), 4.73 (s, 2 H), 4.96 (s, 1 H), 5.44 (s, 1 H),
7.35−7.52 (m, 6 H), 7.62−7.72 (m, 4 H); 13C NMR (CDCl3, 100
MHz) (major isomer signals) δ 4.3 (t), 4.8 (t), 6.7 (q), 6.8 (q), 19.1
(s), 26.9 (q), 34.2 (t), 36.1 (t), 36.3 (t), 37.37 (d), 37.40 (d), 42.2 (s),
43.0 (d), 54.5 (t), 59.1 (q), 60.0.(t), 60.9 (t), 64.0 (d), 65.1 (t), 65.9
(t), 66.9 (t), 69.7 (t), 71.8 (t), 95.6 (t), 102.9 (d), 104.0 (s), 127.0 (d),
127.61 (d), 127.62 (d), 129.5 (d), 133.8 (s), 133.9 (s), 135.5 (d),
135.6 (d), 142.1 (s); exact mass (electrospray) m/z calcd for
C50H80NaO9Si3 (M + Na) 931.5002, found 931.5006.
1
1281, 1246, 1199, 1039, 1008 cm−1; H NMR (CDCl3, 400 MHz)
(major isomer signals) δ 1.04 (s, 9 H), 1.49−1.64 (m, 4 H), 1.80−2.03
(m, 3 H), 2.10−2.42 (m, 4 H), 2.54 (s, 1 H), 3.33 (d, J = 4.0 Hz, 1 H),
3.39 (s, 3 H), 3.52−3.60 (m, 4 H), 3.64−3.71 (m, 2 H), 3.74−3.90
(m, 6 H), 4.70 (s, 2 H), 5.19 (s, 1 H), 5.27 (d, J = 4.0 Hz, 1 H), 5.54
(s, 1 H), 6.75−6.8 (m, 1 H), 7.35−7.45 (m, 6 H), 7.62−7.72 (m, 4
H); 13C NMR (CDCl3, 100 MHz) (major isomer signals) δ 19.0 (s),
26.8 (q), 33.8 (t), 34.2 (t), 36.3 (t), 37.1 (d), 37.6 (d), 45.8 (s), 46.1
(d), 53.8 (t), 59.0 (q), 60.7 (t), 61.1 (t), 66.1 (t), 66.9 (t), 70.8 (t),
71.8 (t), 95.5 (t), 103.4 (d), 104.3 (s), 124.0 (d), 127.7 (d), 127.9 (d),
129.72 (d), 129.75 (d), 133.26 (s), 133.35 (s), 135.59 (d), 135.61 (d),
137.9 (s), 140.4 (s); exact mass (electrospray) m/z calcd for
C38H52NaO8Si (M + Na) 687.3324, found 687.3321.
(1R,2R)-2-(Nitromethyl)cyclohexane-1-carbaldehyde
(11.3).24 MeNO2 (50 μL, 0.9 mmol) followed by (2S)-2-[diphenyl-
[(trimethylsilyl)oxy]methyl]pyrrolidine25 (11.2) (30 mg, 30% mmol)
and AcOLi (11 mg, 0.03 mmol) were added to a solution of 11.1 (33
mg, 0.3 mmol) in 9:1 CH2Cl2−MeOH (0.8 mL) at room temperature.
Stirring was continued for 24 h, and the mixture was diluted with water
and extracted with CH2Cl2 (4 × 3 mL). The combined organic
extracts were dried (MgSO4) and evaporated. Flash chromatography
of the residue over silica gel (Pasteur pipet, 7 cm), using hexane−
EtOAc, gave 11.3 (48 mg, 94%) as an oil, which was a 6:1 mixture of
diastereoisomers in favor of the trans compound: FTIR (cast film on
the mixture) 2935, 2859, 1722, 1647, 1551, 1526, 1449, 1382, 1352,
(1S,5R,6R,9R,14R)-rel-9-[2-[(tert-Butyldimethylsilyl)oxy]-
ethyl]-11-(hydroxymethyl)-6-[2-[(2-methoxyethoxy)methoxy]-
ethyl]-2,12,15-trioxapentacyclo[7.5.2.01,8.05,14.011,13]hexadec-
7-en-16-ol (10.2). A stock solution of VO(acac)2 (25 mg) in PhH (1
mL) was prepared, and an aliquot of this solution (0.1 mL, 0.009
1
1238 cm−1; H NMR (CDCl3, 500 MHz) (major isomer signals) δ
1008
dx.doi.org/10.1021/jo302467w | J. Org. Chem. 2013, 78, 996−1013