Luparia et al.
JOCArticle
with CH2Cl2. Combined organic layers were dried over MgSO4
and concentrated under vacuum. The crude material was purified
by flash column chromatography (hexane/EtOAc 93:7) to yield
sulfone 16 (226 mg, 81%) as a white solid. [R]20D = -62.0 (c =
1.0, CH2Cl2). IR (cm-1) film: 3065, 2923, 2833, 1447, 1302, 1151,
1087, 783, 755, 740. 1H NMR (300 MHz, CDCl3): δ 7.96-7.89
(m, 2H), 7.68-7.51 (m, 3H), 3.22 (dd, J = 4.5, 15.1 Hz, 1H), 2.88
(dd, J = 3.3, 15.1 Hz, 1H), 2.17 (br s, 1H), 2.05 (br d, 17 Hz, 1H),
2.00-1.42 (m, 10H), 1.32-1.15 (m, 1H), 0.90 (2 overlapped s,
totally 6H). 13C NMR (75 MHz, CDCl3): δ 140.7 (s), 133.6 (d),
129.5 (s), 129.4 (d), 128.2 (d), 59.3 (t), 43.6 (d), 32.4 (s), 31.9 (t),
30.3 (t), 28.9 (t), 28.3 (t), 27.6 (q), 26.3 (q), 23.5 (t), 23.1 (t). Anal.
Calcd for C19H26O2S: C, 71.66; H, 8.23. Found: C, 71.83; H, 8.34.
(S,3E)-4-[(S)-1,2,3,4,5,6,7,8-Octahydro-2,2-dimethylnaphthalen-
1-yl]but-3-en-2-ol O-TBS Ether (18): Representative Procedure of
Julia-Lythgoe Olefination. n-BuLi (1.6 M in hexane, 488 μL,
0.78 mmol, 1.1 equiv) was added dropwise to a cold (-78 °C)
solution of sulfone 16 (226 mg, 1 equiv) in dry THF (7.1 mL) under
Ar. The resulting yellow mixture was stirred at -78 °C for 30 min,
and then aldehyde (S)-MeCH(O-TBS)CHO30 (154 mg, 0.82 mmol,
1.15 equiv) in THF (2 mL) was added via cannula. The reaction
was stirred for 90 min at -78 °C and then was diluted with Et2O
and quenched with satd aq NH4Cl. The layers were separated, and
the aqueous phase was extracted with Et2O. The combined organic
layers were washed with brine, dried over MgSO4, and concen-
trated under vacuum affording crude 17. Thisresiduewasdissolved
in HPLC-grade MeOH (24.6 mL), cooled to -30 °C, and treated
with Na2HPO4 (2.45 g) and 20% Na/Hg alloy (1.04 g). After 1 h at
-30 °C, the reaction mixture was filtered, and the solvent was
removed under vacuum at g60 mmHg. The resulting crude oil was
dissolved in CH2Cl2 and washed with satd aq NH4Cl. The aqueous
layer was extracted with CH2Cl2, and the combined organic
extracts were dried over MgSO4 and concentrated under vacuum.
The crude product was purified by FCC on silica gel (hexane) to
(s), 55.2 (d), 32.8 (s), 32.3 (t), 30.6 (t), 29.6 (t), 28.6 (t), 27.9 (q),
27.0 (q), 26.9 (q), 23.7 (t), 23.5 (t). Anal. Calcd for C16H24O: C,
82.70; H, 10.41. Found: C, 82.83; H, 10.35.
[(S)-6,6-Dimethyl-2-[(phenylsulfinyl)methyl]cyclohex-2-enyl]-
methanol O-tert-Butyldiphenylsilyl Ether (21). Phenylthiol (2.15
mL, 21.0 mmol, 2 equiv) was added dropwise to a stirred
solution of N-chlorosuccinimide (2.8 g, 21.0 mmol, 2 equiv) in
dry toluene (77.5 mL) at 0 °C under Ar. The mixture was then
stirred at rt for 1 h, during which time it became orange-yellow
with a white precipitate.44 A 58 mL portion of the supernatant
toluene solution of PhSCl (1.5 equiv) was slowly added with a
gas-tight syringe to a stirred solution of allylic alcohol 2015a
(4.28 g, 10.5 mmol) in dry NEt3 (15 mL) at rt under Ar. The
yellow-orange solution of PhSCl discolored immediately, and
the reaction mixture became a white slurry. After 1 h, the
mixture was diluted with Et2O and H2O. The layers were
separated, and the aqueous phase was extracted with Et2O.
The combined organic layers were dried over MgSO4, filtered,
and concentrated under vacuum to give a crude oil which was
purified by FCC on silica gel (from hexane/EtOAc 85:15 to 4:1).
Sulfoxide 21 (4.91 g, 91%, mixture of diastereomers) was
obtained as a pale yellow oil. IR (cm-1) film: 3070, 2957,
2929, 2856, 1472, 1443, 1427, 1112, 1086, 1049, 998, 823, 745,
702, 613. 1H NMR (300 MHz, CDCl3): δ 7.75-7.28 (m, 15H),
5.80 and 5.48 (2 br s, 1H overall), 3.82-3.63 (m, 2H), 3.59-3.17
(m, 2H), 2.25-1.50 (m, 4H), 1.25-1.12 (m, 1H), 1.01 (2s, 9H),
0.96, 0.93, 0.85 (3s, 6H overall). Anal. Calcd for C32H40O2SSi:
C, 74.37; H, 7.80. Found: C, 74.48; H, 7.91.
[(S)-6,6-Dimethyl-2-[2-(trimethylsilyl)-1-(phenylsulfonyl)ethyl]-
cyclohex-2-enyl]methanol O-tert-Butyldiphenylsilyl Ether (25). To
a cold (-78 °C) stirred solution of sulfone 24 (4.02 g, 7.5 mmol, 1
equiv) in dry THF (75.4 mL) under Ar was added DMPU (1.8 mL,
15.0 mmol, 2 equiv) followed by dropwise addition of BuLi (1.6 M
in hexane, 5.4 mL, 8.7 mmol, 1.15 equiv). The resultant yellow
solution was left at -78 °C for 20 min, and then ICH2SiMe3 (1.3
mL, 8.7 mmol, 1.15 equiv) was added. After having been stirred for
1 h at -78 °C, the mixture was diluted with Et2O and quenched by
addition of satd aq NH4Cl. The layers were separated and the aq.
phase was extracted with Et2O. The combined organic extracts
were dried over Na2SO4 and concentrated in vacuo. The crude oil
was chromatographed on silica gel (hexane/EtOAc 95:5) to provide
TMS-sulfone 25 (86%) as a pale yellow oil. IR (cm-1) film: 3071,
2956, 1472, 1447, 1428, 1305, 1265, 1249, 1143, 1112, 1084, 856, 824,
803, 737, 703, 615. 1H NMR (300 MHz, CDCl3): δ 7.78-7.27 (m,
15H), 6.19 (br s, 1H), 4.15-4.12 (dd, J = 6.6, 8.5 Hz, 1H), 3.81 (dd,
J = 5.3, 11.4 Hz, 1H), 3.54 (dd, J = 5.0, 11.4 Hz, 1H), 2.18-1.97
(m, 3H), 1.35-1.20 (m, 4H), 1.10 (s, 9H), 0.87 (s, 3H), 0.85 (s, 3H),
0.02 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 138.5 (s), 135.8 (d),
133.9 (s), 133.7 (s), 133.0 (d), 132.1 (s), 131.1 (d), 129.9 (d), 129.8
(d), 129.4 (d), 128.6 (d), 127.9 (d), 127.7 (d), 64.3 (d), 63.4 (t), 51.9
(d), 34.5 (t), 32.4 (s), 28.8 (q), 27.1 (q), 24.3 (q), 23.2 (t), 20.2 (t), 19.2
(s), -0.4 (q). Anal. Calcd for C36H50O3SSi2: C, 69.85; H, 8.14.
Found: C, 70.02; H, 8.27.
afford product 18 (175 mg, 70% from 16) as a white oil. [R]20
=
D
-167.0 (c = 1.8, CH2Cl2). IR (cm-1) film: 2927, 1472, 1362, 1254,
1147, 1080, 1004, 834, 775, 665. 1H NMR (300 MHz, CDCl3): δ
5.48-5.26 (m, 2H), 4.27 (distorted quint, J about 6.2 Hz, 1H), 1.99
(d, J = 7.3 Hz, 1H), 1.90-1.77 (m, 5H), 1.70-1.39 (m, 6H), 1.22
(d, J = 6.3 Hz, 3H), 1.27-1.12 (m, 1H), 0.89 (s, 9H), 0.87 (s, 3H),
0.80 (s, 3H), 0.05 (s, 3H), 0.04 (s, 3H). 13C NMR (75 MHz, CDCl3):
δ 136.3 (d), 130.1 (d), 128.5 (s), 127.4 (s), 69.9 (d), 54.3 (d), 32.5 (t),
32.3(s), 30.4(t), 29.3(t),28.5(t), 27.6(q), 27.2(q), 26.0(q), 25.3(q),
23.6 (t), 23.4 (t), 18.5 (s), -4.4 (q), -4.6 (q). Anal. Calcd for
C22H40OSi: C, 75.79; H, 11.56. Found: C, 75.92; H, 11.72.
(3E)-4-[(S)-1,2,3,4,5,6,7,8-Octahydro-2,2-dimethylnaphthalen-
1-yl]but-3-en-2-one (7): Representative Procedure of Allylic Alco-
hol Oxidation. Crude alcohol obtained by standard deprotection
of 18 (see the Supplementing Information) (0.5 mmol, slightly
contaminated by TBSF) was dissolved in dry CH2Cl2 (5 mL) and
treated with DMP (255 mg, 0.5 mmol, 1 equiv) at rt. After being
stirred for 1 h, the mixture was diluted with CH2Cl2 and poured
into satd aq NaHCO3 and Na2S2O3. The layers were separated,
and the aqueous phase was extracted with CH2Cl2. The com-
bined organic layers were dried over MgSO4, filtered, and
concentrated at P > 200 mmHg. The crude product was purified
by FCC on silica gel (pentane/Et2O 98/2) to afford the desired
R,β-unsaturated ketone 7 (91 mg, 78% yield over two steps) as a
colorless pleasant-smelling oil. ee = 95% determined by chiral
GC with the following temperature program: 80 °C (3 min) f 1°/
min f 130 °C (40 min) f 2°/min f 170 °C (0 min) f 4°/min f
200 °C (4 min). (-)-7: tR 106.3. (þ)-7: tR 106.8. [R]20D = -295.3
(c = 1.3, CH2Cl2). IR (cm-1) film: 2924, 2884, 1697, 1675, 1618,
1446, 1363, 1252, 992, 738. 1H NMR (300 MHz, CD2Cl2): δ 6.62
(dd, J = 9.7, 15.8 Hz, 1H), 6.01 (br d, J = 15.8 Hz, 1H), 2.24 (s,
3H), 2.23 (d, J = 9.7 Hz, 1H), 2.01-1.85 (m, 5H), 1.74-1.51 (m,
6H), 1.35-1.23 (m, 1H), 0.95 (s, 3H), 0.87 (s, 3H). 13C NMR (75
MHz, CD2Cl2): δ 198.5 (s), 149.8 (d), 132.4 (d), 129.7 (s), 126.6
[(S)-6,6-Dimethyl-2-vinylcyclohex-2-enyl]methanol
O-tert-
Butyldiphenylsilyl Ether (23). TBAF (1 M in THF, 18.2 mL,
18.2 mmol, 2.5 equiv) was added to a stirred solution of 25 (4.51
g, 7.3 mmol, 1 equiv) in dry THF (15 mL) at rt. The reaction
mixture was stirred for 40 min, followed by dilution with Et2O
and H2O. The layers were separated, and the aqueous phase was
extracted with Et2O. The combined organic extracts were dried
over Na2SO4 and concentrated under vacuum. The crude
material was purified by FCC on silica gel (hexane) to provide
diene 23 (2.48 g, 84%) as a colorless oil. [R]20D = -45.3 (c = 1.2,
CH2Cl2). IR (cm-1) film: 3072, 2957, 1472, 1428, 1390, 1362,
1
1136, 1111, 1056, 992, 894, 824, 795, 739, 701. H NMR (300
(44) Hua, D. H.; Venkataraman, S.; Ostrander, R. A.; Sinai, G. Z.;
NcCann, P. J.; Coulter, M. J.; Xu, M. R. J. Org. Chem. 1988, 53, 507–515.
J. Org. Chem. Vol. 74, No. 18, 2009 7109