2054 J . Org. Chem., Vol. 67, No. 7, 2002
Hong et al.
product isolated by extractive workup. The product was
purified by flash chromatography on silica gel using 50/50
ether/hexanes to give ester 29a as a yellow oil (2.42 g, 65%).
MgSO4 and concentrated in vacuo to give silyl ether 33 (7:1
trans:cis) as yellow oil (4.69 g, 74%) (trans ether 33): IR (film)
3481, 3070, 2944, 1729, 1673, 1243 cm-1; 1H NMR (270 MHz,
CDCl3) δ trans isomer: 0.12 (s, 9H), 1,75 (s, 3H), 1.78 (s, 3H),
2.3-2.8 (m, 2H), 2.5 (m, 1H), 4.1 (d, J ) 12.0 Hz, 1H), 4.83
(m, 2H), 6.65 (m, 1H); 13C NMR (68 MHz, CDCl3) δ 0.45, 15.8,
19.9, 30.8, 51.1, 77.3, 113,1, 134.3, 143,7, 144.8, 199.6; MS (m/
z) 238, 223, 182.
TBS Eth er 34. HF (48%, 0.365 mL, 10.1 mmol) was added
over 10 min to a mixture of cis- and trans-trimethylsiloxyke-
tones 33 (2.00 g, 8.40 mmol) in CH3CN (20 mL) at 0 °C. The
reaction mixture was allowed to warm to room temperature,
stirred for 30 min, and then concentrated in vacuo and the
residue extracted three times with CH2Cl2. The combined
organics were washed with saturated NaHCO3 solution,
saturated NaCl solution, and then dried over MgSO4. Flash
chromatography with 20/80 ethyl acetate/hexanes gave the
corresponding alcohol (0.56 g, 40%) as a pale yellow oil. IR
(film) 3453,3070, 2925, 1668 cm-1; 1H NMR (270 MHz, CDCl3)
δ trans 1.8 (s, 6H), 2.4 (m, 2H), 2.7 (m, 2H), 3.8 (bs, 1H), 4.15
(d, J ) 11.9 Hz, 1H), 4.9 (m, 1 H), 6.75 (m, 1H); 13C NMR (68
MHz, CDCl3) δ 15.5, 18.8, 30.7, 51.1, 74.5, 113.6,133.1, 144.2,
145.7, 200.6; MS (m/z) 166, 161, 148, 137, 120, 109, 82, 77,
54, 41, 39.
1
IR (film) 1734 cm-1; H NMR (270 MHz, CDCl3) δ 1.1 (d, J )
6.9 Hz, 6H), 2.0 (m, 4H), 2.5 (hept, J ) 6.9 Hz, 1H), 3.4 (s,
3H), 3.5 (t, J ) 4.5 Hz, 2H); 3.7 (m, 2H), 3.9 (dd, J ) 2.7 Hz,
8.6 Hz, 1H,), 4.7 (d, J ) 7.1 Hz, 1H), 4.8 (d, J ) 7.1 Hz, 1H),
5.1 (d, J ) 17.4 Hz, 1H), 5.2 (d, J ) 10.5 Hz, 1H), 6.0 (m, 2H),
6.2 (dd, J ) 17.6 Hz, 10.9 Hz, 1H); 13C NMR (67 MHz, CDCl3)
δ 18.9, 19.1, 23.4, 23.5, 34.4, 59.1, 67.2, 71.7, 78.2, 80.8, 95.2,
115.9, 126.6, 131.6, 140.1, 176.0. Anal. Calcd for C16H26O5: C,
64.41; H, 8.78. Found: C, 64.36; H, 8.67.
Acid 31a . (Method vii). To a solution of LDA (0.64 mmol)
in THF (10 mL) at -78 °C was added ester 29a (0.076 g, 0.25
mmol) in THF (5 mL) via cannula. The reaction mixture was
stirred at -78 °C for 30 min and then warmed to -10 °C and
stirred an additional 30 min, after which it was quenched by
addition of HOAc (0.38 g, 6.4 mmol). The reaction mixture was
poured into 1 N HCl and the crude product isolated by
extractive workup. The residue was purified by flash chroma-
tography on silica gel using ether followed by 1/99 HOAc/ether
acid 31a as a colorless oil (0.053 g, 70%). IR (film) 1720, 1701
1
cm-1; H NMR (270 MHz, CDCl3) δ 1.2 (s, 6H), 1.7 (m, 1H),
1.9 (m, 1H), 2.1 (m, 1H), 2.3 (m, 3H), 3.4 (s, 3H), 3.5 (t, J )
4.9 Hz, 2H); 3.7 (m, 2H), 4.2 (m, 1H), 4.8 (d, J ) 6.9 Hz, 1H),
5.4 (t, J ) 7.2 Hz, 1H), 5.8 (m, 1H), 6.3 (d, J ) 10.2 Hz, 1H);
13C NMR (67 MHz, CDCl3) δ 22.3, 24.7, 24.8, 28.2, 37.1, 42.6,
59.0, 66.8, 71.9, 74.4, 92.4, 122.2, 124.0, 130.3, 135.1, 183.4.
Anal. Calcd for C16H26O5: C, 64.41; H, 8.78. Found: C, 64.57;
H, 8.81.
Imidazole (0.104 g, 1.5 mmol) and TBDMSCl (0.108 g, 0.71
mmol) were added to a solution of the alcohol (0.100 g, 0.6
mmol) in dry DMF (1 mL). The reaction mixture was stirred
at 50 °C for 10 h and then diluted with CH2Cl2 and filtered.
The filtrate was washed once with water, dried over anhydrous
MgSO4, and concentrated in vacuo. Flash chromatography
with 5/95 ethyl acetate/hexane yielded TBS ether 34 (0.15 g,
p-Nitr oben zyl Am id e of Acid 31b. To a solution of acid
31b (0.077 g, 0.27 mmol) in DMF (5 mL) at 0 °C were added
NEt3 (0.14 g, 1.35 mmol), diphenylphosphoryl azide (0.15 g,
0.56 mmol), and p-nitrobenzylamine hydrochloride (0.077 g,
0.41 mmol). The reaction mixture was allowed to warm to room
temperature and stirred for 16 h. The mixture was then
washed with water and extracted with ethyl acetate. The
organic phase was washed with water and saturated NaCl
solution, dried over MgSO4, and concentrated in vacuo. The
residue was purified by flash chromatography on silica gel
using 20/80 ethyl acetate/hexanes to give the amide as a yellow
oil (0.84 g, 74%, 8:1 mixture of diastereomers). IR (film) 1651,
1520, 1346 cm-1; 1H NMR (major isomer) (270 MHz, CDCl3) δ
1.2 (d, J ) 6.5 Hz, 3H), 1.7 (m, 1H), 1.9 (m, 1H), 2.1 (m, 1H),
2.3 (m, 3H), 2.5 (m, 1H), 3.4 (s, 3H), 3.5 (m, 2H); 3.7 (m, 2H),
4.2 (m, 1H), 4.5 (d, J ) 6.1 Hz, 1H), 4.7 (dd, J ) 17.2 Hz, 7.1
Hz, 2H), 5.4 (t, J ) 7.5 Hz, 1H), 5.9 (m, 1H), 6.1 (t, J ) 4.6
Hz, 1H), 6.3 (d, J ) 10.5 Hz, 1H), 7.4 (d, J ) 8.5 Hz, 2H), 8.2
(d, J ) 8.7 Hz, 2H); 13C NMR (major isomer) (67 MHz, CDCl3)
δ 17.8, 23.4, 28.3, 31.6, 41.6, 42.8, 59.0, 66.8, 71.9, 74.4, 92.5,
122.1, 123.9, 125.6, 128.3, 130.6, 134.4, 146.3, 147.2, 176.0.
Anal. Calcd for C22H30N2O6: C, 63.14; H, 7.23; N, 6.69.
Found: C, 63.07; H, 6.97; N, 6.71.
92%) as a colorless liquid. IR (film) 3453,3070, 2925, 1677 cm-1
;
1H NMR (270 MHz, CDCl3) δ 0.01 (s, 3H), 0.19 (s, 3H), 0.86
(s, 9H), 1.74 (s, 3H), 1.76 (s, 3H), 2.4 (m, 2 H), 2.77 (ddd, J )
5.3, 11.7, 15.6 Hz, 1H), 4.12(d, J ) 11.7 Hz, 1H), 4.85 (s, 2H),
6.64(m, 1H); 13C NMR (68 MHz, CDCl3) δ -5.5, -3.5, 15.8,
18.7, 20.2, 25.7, 25.9, 30.5, 51.4, 113.6, 134.2, 143.4, 144.4, 200;
MS (m/z) 265(M + 1), 223, 205, 193, 181, 165, 143, 129, 105,
75. Anal. Calcd for C16H28O2Si: C, 68.52; H, 10.06. Found: C,
68.32; H, 9.91.
Alcoh ol 35. n-BuLi (0.14 g, 0.35 mmol) was added to a
solution of tetravinyltin (0.019 g, 0.083 mmol) in THF (5 mL)
at -78 °C. The cooling bath was removed, and the reaction
mixture was stirred at room temperature for 1 h. The mixture
was then cooled to -78 °C and TBS ether 34 (0.100 g, 0.35
mmol) added. The cooling bath was removed and the reaction
stirred at room temperature for 6 h. The reaction mixture was
poured into saturated NaHCO3 and isolated by extractive
workup. The residue was purified by flash chromatography
with 2/98 ethyl acetate/hexanes to give alcohol 35 (0.076 g,
70%) as a white solid, mp: 88-91 °C. IR (film) 3426 cm-1; 1H
NMR (270 MHz, CDCl3) δ 0.02 (s, 3H), 0.05 (s, 3H), 0.84 (s,
9H), 1.6 (s, 3H), 1.7 (s, 3H), 2.07 (m, 2H), 2.50 (ddd, J ) 8.3,
10.2, 15.3 Hz, 1H), 3.04 (s, 1 H), 3.67 (d, J ) 10.3 Hz, 1H),
4.83 (s, 2H), 5.24 (d, J ) 10.1, 1H), 5.44 (d, J ) 17.0 Hz, 1H),
5.56 (s, 1H), 5.62 (dd, J ) 10.3, 17.1 Hz, 1H); 13C NMR (68
MHz, CDCl3) δ -3.6, -3.4, 18.5, 18.7, 22.1, 26.3, 30.0, 44.7,
76.0, 77.8, 113.3, 116.1, 124.5, 134.5, 143.1, 145.8; MS (m/z)
251,198, 159, 141, 131, 105, 95, 75. Anal. Calcd for C18H32O2-
Si: C, 70.07; H, 10.45. Found: C, 70.28; H, 10.35.
Isobu tyr a te Ester 36. TBAF (0.58 g, 0.64 mmol) was added
to a solution of TBS ether 35 (0.100 g, 0.32 mmol) in THF (5
mL) at 0 °C. The reaction mixture was allowed to warm to
room temperature, stirred at room temperature for 30 min,
and then concentrated in vacuo. The residue was dissolved in
ether and washed with water. The organic layer was washed
with saturated NaCl solution, dried over anhydrous MgSO4,
and concentrated in vacuo. The residue was purified by flash
chromatography with 20/80 ethyl acetate/hexanes to furnish
the corresponding diol 36 (0.056 g, 90%). IR (film) 3412, 1612,
1250 cm-1; 1H NMR (270 MHz, CDCl3) δ 1.61 (s, 3H), 1.72 (s,
3 H), 2.0 (m, 3H), 2.59 (m, 2H), 3.56 (d, J ) 8.7 Hz, 1H), 4.91
(s, 1 H), 4.93 (s, 1H), 5.33 (d, J ) 10.5 Hz,1H), 5.46 (d, J )
17.1 Hz, 1H), 5.59 (m, 1H), 5.74 (dd, J ) 10.5, 17.0 Hz, 1H);
13C NMR (68 MHz, CDCl3) d; 18.7, 18.9, 30.1, 44.2, 73.3, 75.2,
Tr im eth ylsilyl Eth er 33.34,36 nBuLi (15.7 g, 37 mmol) was
slowly added to a solution of diisopropylamine (3.75 g, 37.1
mmol) in THF (50 mL) at -78 °C. The solution was stirred
for 10 min, and then (S)-carvone (32) (5.0 g, 33.2 mmol) was
added. The solution was stirred for 10 min, and then TMSCl
(7.6 g, 70 mmol) added dropwise at -78 °C. The solution was
allowed to warm to room temperature and stirred for 2 h. The
reaction mixture was poured into cold NaHCO3 solution and
extracted three times with hexane. The combined organic
layers were dried over MgSO4 and concentrated in vacuo to
afford a the enol silane as a yellow oil (6.93 g, 94%): IR (film)
3065, 2952, 1675, 1251 cm-1 1H NMR (270 MHz, CDCl3) δ
;
0.2 (s, 9H), 1.70 (s, 3 H), 1.72 (s, 3H), 2.2 (m, 2H), 3.0 (m, 1
H), 4.7 (s, 1 H), 4.8 (m, 1 H), 5.5 (m, 1 H); 13C NMR (68 MHz,
CDCl3) δ 0.2, 17.4, 20.6, 28.7, 41.9, 105.8, 110.1, 123.1, 131.9,
148.4, 149.9; MS (m/z) 222, 207, 149, 133.
m-CPBA (9.17 g, 31.9 mmol) was added to a solution of the
enol silane (5.88 g, 26.6 mmol) in CH2Cl2 (200 mL) at 0 °C
over 10 min. The solution was stirred for 1 h at 0 °C and then
poured into saturated Na2S2O3 solution. The organic phase was
washed with saturated NaHCO3 solution and saturated NaCl
solution. The combined organic extracts were dried over