Jung and Im
JOCArticle
color changes were observed in the aqueous layer. The organic
layer was washed with brine and dried over MgSO4. The mixture
was filtered and concentrated via rotary evaporation. Flash
column chromatography of the residue on silica gel (170 mL,
hexane:ether, 6:4) afforded 728 mg (89%) of the alcohol ester 57
as a clear oil. 1H NMR (CDCl3, 500 MHz) δ 5.61 (1H, br d, J =
4.5 Hz), 4.23 (1H, dd, J = 10.9, 4.0 Hz), 4.11 (1H, m), 3.99 (1H,
dd, J = 10.9, 6.4 Hz), 1.88-2.04 (3H, m), 1.70 (3H, s), 1.68 (1H,
m), 1.43 (1H, dddd, J = 13.0, 13.0, 11.5, 5.9 Hz), 1.28 (1H, m),
1.20 (9H, s), 1.23 (1H, br s), 1.03 (3H, d, J = 6.8 Hz); 13C NMR
(CDCl3, 125 MHz) δ 178.7, 139.6, 123.2, 67.8, 64.8, 41.7, 38.8,
33.4, 31.2, 27.1, 23.3, 20.3, 15.5; IR (thin film) 3441 (br, s), 2969
(m), 2932 (m), 2910 (m), 2875.9 (m), 1728 (s), 1713 (m), 1480 (m),
1458 (w), 1398 (m), 1286 (m), 1163 (s), 955 (w); HRMS-ESI (m/
z) [M þ Na]þ calcd for C15H26O3Na 277.1780, found 277.1786.
(()-(R)-2-[(1R,2S)-2-[(1,1-Dimethylethyl)dimethylsilyloxy]-
4-methylcyclohex-3-enyl]propan-1-ol (58). To an oven-dried and
argon-purged 50 mL round-bottomed flask were added the
alcohol 57 (290 mg, 1.14 mmol, 1 equiv), dimethylformamide
(10 mL), and imidazole (388 mg, 5.70 mmol, 5 equiv). tert-
Butyldimethylsilyl chloride (753 mg, 2.85 mmol, 2.5 equiv) was
added, and the reaction was stirred at 23 °C for 16 h, during
which time the contents changed color from clear to deep yellow.
The reaction was poured into a 1:1 mixture of distilled water and
ether (6ꢀ the volume of the dimethylformamide). The layers
were separated, and the aqueous layer was diluted with addi-
tional distilled water. The aqueous layer was extracted with
ether, and the combined organic layers were washed with brine
and dried over MgSO4. The mixture was filtered and concen-
trated via rotary evaporation. Flash column chromatography of
the residue on silica gel (90 mL, hexane:ether, 95:5) afforded a
mixture of the protected diol along with minor amounts of
TBSOH. The compound was taken onto the next step without
(w), 884 (w), 831 (s), 773 (s); HRMS-ESI (m/z) [M þ Na]þ calcd
for C16H32O2SiNa 307.2069, found 307.2072.
(()-(R)-2-[(1R,2S)-2-[(1,1-Dimethylethyl)dimethylsilyloxy]-
4-methylcyclohex-3-enyl]propanal (54). To an oven-dried and
argon-purged 10 mL round-bottomed flask were added the
alcohol 58 (280 mg, 0.98 mmol, 1 equiv), dichloromethane
˚
(2 mL, 2 mL/1 mmol substrate), and powdered 4 A molecular
sieves (500 mg, 500 mg/1 mmol substrate). 4-Methylmorpholine
N-oxide (173 mg, 1.48 mmol, 1.5 equiv) was added, and the
reaction was stirred at 23 °C for 10 min. Tetrapropylammonium
perruthenate (TPAP, 35 mg, 0.10 mmol, 0.1 equiv) was added in
one portion, and the reaction was stirred for 30 min. The mixture
was filtered through a short plug of silica gel and rinsed with
dichloromethane. The filtrate was concentrated via rotary eva-
poration, and flash column chromatography of the residue on
silica gel (55 mL, hexane:ether, 97:3) afforded 213 mg of the
aldehyde 54 (78%) as a clear oil. 1H NMR (CDCl3, 500 MHz) δ
9.75 (1H, d, J = 2.2 Hz), 5.41 (1H, m), 4.24 (1H, m), 2.49 (1H,
dqd, J = 7.2, 7.2, 2.2 Hz), 1.89-2.00 (2H, m), 1.76-1.87 (2H,
m), 1.67 (3H, s), 1.60 (1H, m), 1.09 (3H, d, J = 7.1 Hz), 0.86 (9H,
s), 0.04 (3H, s), 0.02 (3H, s); 13C NMR (CDCl3, 125 MHz) δ
204.9, 137.4, 124.0, 66.8, 46.3, 41.9, 29.7, 25.9, 23.1, 21.4, 18.1,
12.1, -3.9, -4.5; IR (thin film) 2955 (s), 2929 (s), 2883 (m), 2857
(s), 1724 (s), 1472 (w), 1462 (w), 1252 (m), 1051 (m), 1030 (m),
988 (m), 918 (w), 884 (w), 834 (m), 812 (w), 775 (m).
(()-3RS-[1RS,2SR-{2-([(1,1-Dimethylethyl)dimethylsilyloxy]-4-
methylcyclohex-3-enyl)-3RS-methyl-1EZ-propenyl}]-1RS,3RS,
4SR-1,3,4-trimethyl-7-oxabicylo[2.2.1]hex-ane (53a/53b and 53c/
53d). To an oven-dried and argon-purged 100 mL round-
bottomed flask were added the racemic aldehyde 54 (226 mg,
0.8 mmol, 1 equiv), the racemic sulfone 55 (337 mg, 0.96 mmol,
1.2 equiv), and tetrahydrofuran (10 mL). The mixture was
cooled to -78 °C, and LiHMDS (1 M solution in hexane, 1.04
mL, 1.04 mmol, 1.3 equiv) was added dropwise via syringe. The
reaction was allowed to stir for 2 h at -78 °C, and then it was
warmed to 23 °C and stirred for 1 h. The mixture was diluted
with ether and the layers were separated. The aqueous layer was
extracted with ether and the combined organic layers were
washed with brine and dried over MgSO4. The mixture was
filtered and concentrated via rotary evaporation. Flash column
chromatography of the residue on silica gel (70 mL, hexane:
ether, 97:3) afforded 290 mg of the Julia-Kocienski products
53a/53b and 53c/53d (87%) as a clear oil. The E and Z isomers
were separated via careful gradient flash column chromatogra-
phy on silica gel (55 mL, hexane 100% f hexane:ether 97:3 via
0.5% increase of ether at each step) to afford 140 mg of 53c/53d
and 135 mg of 53a/53b as clear oils. 1H NMR (CDCl3, 500 MHz)
δ 53a/53b, isomer 1 5.68 (1H, dd, J = 10.5, 10.5 Hz), 5.43 (1H, br
s), 5.12 (1H, dd, J = 10.8, 10.8 Hz), 4.16 (1H, m), 2.70 (1H, m),
2.27 (1H, m), 1.84-2.00 (3H, m), 1.65 (3H, s), 1.53-1.72 (3H,
m), 1.35-1.46 (4H, m), 1.32 (3H, s), 1.31 (3H, s), 1.008 (3H, d,
J = 6.9 Hz), 0.912 (3H, d, J = 6.9 Hz), 0.89 (9H, s), 0.09 (3H, s),
0.052 (3H, s), isomer 2 5.64 (1H, dd, J = 10.8, 10.8 Hz), 5.46
(1H, br s), 5.12 (1H, dd, J = 10.8, 10.8 Hz), 4.17 (1H, m), 2.70
(1H, m), 2.27 (1H, m), 1.84-2.00 (3H, m), 1.65 (3H, s),
1.53-1.72 (3H, m), 1.35-1.46 (4H, m), 1.32 (3H, s), 1.31 (3H,
s), 1.013 (3H, d, J = 6.9 Hz), 0.907 (3H, d, J = 6.9 Hz), 0.89 (9H,
1
calculation of yield. H NMR (CDCl3, 500 MHz) δ 5.48 (1H,
m), 4.11 (1H, dd, J = 10.7, 3.7 Hz), 4.10 (1H, m), 3.98 (1H, dd,
J = 10.7, 6.7 Hz), 1.84-2.00 (3H, m), 1.67 (3H, s), 1.61 (1H, m),
1.55 (1H, m), 1.24 (1H, m), 1.19 (9H, s), 1.00 (3H, d, J = 6.9 Hz),
0.86 (9H, s), 0.06 (3H, s), 0.03 (3H, s); 13C NMR (CDCl3, 125
MHz) δ 178.6, 137.9, 123.9, 67.6, 65.8, 41.7, 38.8, 33.2, 31.2,
27.1, 25.6, 23.3, 20.2, 18.1, 15.3, -3.3, -4.7; IR (thin film) 2957
(s), 2930 (s), 2884 (m), 2857 (m), 1731 (s), 1472 (m), 1462 (m),
1398 (w), 1361 (w), 1285 (m), 1253 (m), 1161 (s), 1059 (s), 1033
(m), 993 (m), 884 (w), 835 (m), 808 (w), 775 (m); HRMS-ESI (m/
z) [M þ Na]þ calcd for C21H40O3SiNa 391.2644, found
391.2639.
To an oven-dried and argon-purged 50 mL round-bottomed
flask were added the protected diol (420 mg, 1.14 mmol, 1 equiv)
and dichloromethane (11 mL). The reaction was cooled to
-78 °C, and a 1 M solution of diisobutylaluminum hydride in
dichloromethane (2.85 mL, 2.85 mmol, 2.5 equiv) was added
dropwise via syringe. The reaction was stirred at -78 °C for 1 h,
then quenched with saturated potassium tartrate solution. The
reaction was warmed to 23 °C and the layers were separated. The
aqueous layer was extracted with ether and the combined
organic layers were washed with brine. The reaction was then
dried over MgSO4, filtered, and concentrated via rotary eva-
poration. Flash column chromatography of the residue on silica
gel (60 mL, hexane:ether, 7:3) afforded 280 mg of the alcohol 58
(86% over 2 steps) as a clear oil. 1H NMR (CDCl3, 500 MHz) δ
5.49 (1H, m), 4.28 (1H, m), 3.62 (1H, ddd, J = 10.7, 5.3, 5.3 Hz),
3.57 (1H, ddd, J = 10.7, 6.3, 5.2 Hz), 2.37 (1H, dd, J = 6.2, 5.2
Hz), 1.86-2.01 (2H, m), 1.70-1.79 (1H, m), 1.66 (3H, s),
1.56-1.63 (2H, m), 1.31 (1H, dddd, J = 12.0, 8.2, 3.7, 3.7
Hz), 0.99 (3H, d, J = 7.0 Hz), 0.88 (9H, s), 0.08 (3H, s), 0.06 (3H,
s); 13C NMR (CDCl3, 125 MHz) δ 138.2, 123.9, 67.3, 66.6, 42.8,
36.2, 30.8, 25.8, 23.2, 21.0, 18.2, 15.4, -3.4, -4.3; IR (thin film)
3345 (br, s), 2956 (s), 2928 (s), 2884 (s), 2857 (s), 1472 (m), 1462
(m), 1378 (w), 1360 (w), 1252 (m), 1127 (w), 1057 (s), 994 (s), 919
1
s), 0.09 (3H, s), 0.046 (3H, s); H NMR (CDCl3, 500 MHz) δ
53c/53d 5.51 (1H, br s), 5.43 (1H, dd, J = 15.3, 8.2 Hz), 5.32 (1H,
dd, J = 15.3, 8.6 Hz), 4.08 (1H, m), 2.28 (1H, m), 1.82-2.07 (3H,
m), 1.75-1.78 (1H, m), 1.65 (3H, s), 1.48-1.63 (6H, m),
1.36-1.43 (1H, m), 1.30 (3H, d, J = 6.3 Hz), 0.99 (3H, d, J =
6.9 Hz), 0.87 (9H, s), 0.03 (3H, s), 0.009 (3H, s); 13C NMR
(CDCl3, 125 MHz) δ 53a/53b, major isomer 138.82, 137.2,
126.2, 124.8, 86.0, 84.8, 68.6, 56.4, 49.0, 44.1, 39.3, 33.0, 31.9,
31.0, 25.98, 23.27, 20.4, 19.8, 18.16, 17.8, 17.4, -3.8, -4.2, minor
isomer 138.77, 137.5, 126.7, 124.7, 86.1, 84.9, 68.0, 56.4, 49.2,
44.7, 39.2, 33.1, 32.0, 31.2, 26.01, 23.30, 20.3, 19.9, 18.6, 18.20,
J. Org. Chem. Vol. 74, No. 22, 2009 8751