1876 J. Am. Chem. Soc., Vol. 123, No. 9, 2001
Lee and Corey
MHz, CDCl3) δ 9.29 (s, 1H), 7.37 (m, 2H), 6.97 (app. t, 1H, J ) 7.2
Hz), 6.84 (d, 1H, J ) 8.4 Hz), 5.54 (s, 2H), 5.16 (m, 1H), 5.10 (m,
3H), 3.81 (s, 3H), 2.76 (d, 1H, J ) 12.8 Hz), 2.46 (m, 1H), 2.06 (m,
15H), 1.69 (dd, 1H, J ) 10.4, 15.2 Hz), 1.68 (s, 3H), 1.61 (s, 3H),
1.60 (s, 9H), 0.98 (dd, 1H, J ) 2.8, 13.6 Hz), 0.75 (dd, 1H, J ) 12.4,
13.6 Hz), 0.34 (s, 3H), 0.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
191.4, 163.9, 137.1, 135.13, 135.06, 134.8, 131.3, 131.2, 130.0, 127.5,
125.3, 124.3, 124.2, 124.0, 121.4, 120.7, 109.5, 75.1, 54.9, 39.9, 39.79,
39.76, 39.6, 35.2, 33.4, 30.0, 26.9, 26.8, 26.7, 25.8, 23.4, 17.8, 16.4,
16.14, 16.11, -1.5, -1.8; HMRS (ESI) calcd for [C37H55BrO2Si] ([M
+ H]+) 639.3233, found 639.3204. Diastereoselectivity, the exo/endo
ratio, was determined by 1H NMR analysis of the crude mixture.
Enantioselectivity was determined by reduction with NaBH4 to the
corresponding alcohol (vide infra), conversion to the (R)-MTPA ester
dried over Na2SO4, filtered, and concentrated in vacuo to afford a clear
crude oil. Purification by column chromatography (gradient elution with
25-67% EtOAc-hexanes) afforded 53.1 mg (71%) of the correspond-
ing glycol intermediate as a colorless oil: [R]23D +1.6 (c 0.90, CHCl3,
97% ee); Rf 0.58 (EtOAc); FTIR (thin film) 3382, 2961, 2923, 2854
1
cm-1; H NMR (400 MHz, CDCl3) δ 5.59 (d, 1H, J ) 9.9 Hz), 5.42
(ddd, 1H, J ) 2.4, 4.9, 9.9 Hz), 5.11 (m, 4H), 3.75 (dd, 1H, J ) 9.2,
11.4 Hz), 3.64 (br d, 1H, J ) 11.4 Hz), 3.54 (d, 1H, J ) 11.0 Hz),
3.47 (d, 1H, J ) 11.0 Hz), 3.19 (br s, 1H), 3.02 (br s, 1H), 2.42 (m,
1H), 2.12 (m, 1H), 2.03 (m, 15H), 1.82 (dd, 1H, J ) 5.7, 12.8 Hz),
1.68 (s, 3H), 1.60 (s, 12H), 1.50 (dd, 1H, J ) 11.0, 12.8 Hz); 13C
NMR (100 MHz, CDCl3) δ 137.1, 135.1, 135.0, 132.8, 131.3, 124.6,
124.4, 124.2, 124.1, 121.5, 75.5, 67.8, 64.4, 43.1, 39.8, 39.71, 39.70,
35.8, 34.5, 33.9, 26.7, 26.64, 26.63, 25.7, 17.7, 16.3, 16.03, 16.00;
HMRS (ESI) calcd for [C28H46O3] ([M + H]+) 431.3525, found
431.3540.
1
derivative, and H NMR integration (500 MHz, CD3CN): δ 4.74 (d,
1H, major), 4.68 (d, 1H, minor).
Conversion of 15 to Epoxide 16. To a solution of Diels-Alder
adduct 15 (305 mg, 0.477 mmol) in 6 mL of THF at room temperature
was added 100 µL of water and NaBH4 (18.0 mg, 0.477 mmol). After
5 min, the reaction mixture was poured into 100 mL of water and
extracted with three 125-mL portions of Et2O. The organic phases were
combined and dried over MgSO4, filtered, and concentrated to afford
the intermediate crude alcohol, which was used without further
purification: 1H NMR (500 MHz, CDCl3) δ 7.36 (m, 2H), 6.95 (app.
t, 1H, J ) 7.0 Hz), 6.82 (d, 1H, J ) 8.0 Hz), 5.55 (ddd, 1H, J ) 2.4,
4.9, 10.1 Hz), 5.47 (d, 1H, J ) 10.1 Hz), 5.15 (m, 1H), 5.11 (m, 3H),
3.82 (d, 1H, J ) 12.5 Hz), 3.80 (s, 3H), 3.70 (d, 1H, J ) 12.5 Hz),
2.78 (br d, 1H, J ) 12.0 Hz), 2.49 (m, 1H), 1.97 (m, 16H), 1.68 (s,
3H), 1.60 (s, 12H), 1.39 (dd, 1H, J ) 10.0, 13.5 Hz), 1.31 (dd, 1H, J
) 3.5, 13.5 Hz), 0.59 (app. t, 1H, J ) 12.8 Hz), 0.33 (s, 3H), 0.29 (s,
3H).
The crude alcohol was dissolved in 8 mL of 2-propanol and cooled
to -30 °C. Sodium methoxide (129 mg, 2.39 mmol) was added, and
the resulting mixture was stirred at -30 °C for 24 h and then warmed
to 0 °C over 6 h. H2O (10 mL) was added and the resulting mixture
was concentrated to remove most of the 2-propanol. The crude material
was poured into 100 mL of water and extracted with three 125-mL
portions of Et2O. The organic phases were combined, dried over
MgSO4, filtered, and concentrated to afford a colorless oil. Purification
by flash chromatography on silica gel (elution with 25-33% benzene-
hexanes with 0.1% Et3N) afforded 207 mg (77%) of epoxide 16 as a
colorless oil: [R]23D -67.4 (c 0.69, CHCl3, 97% ee); Rf 0.49 (benzene-
hexanes 1:1); FTIR (thin film) 2916, 2853, 1588 cm-1; 1H NMR (400
MHz, CDCl3) δ 7.39 (dd, 1H, J ) 1.8, 7.3 Hz), 7.34 (ddd, 1H, J )
1.8, 7.3, 8.2 Hz), 6.94 (app. td, 1H, J ) 1.0, 7.3 Hz), 6.81 (d, 1H, J )
8.2 Hz), 5.57 (ddd, 1H, J ) 2.6, 4.8, 9.9 Hz), 5.43 (br d, 1H, J ) 10.3
Hz), 5.12 (m, 4H), 3.79 (s, 3H), 2.62 (d, 1H, J ) 5.1 Hz), 2.60 (dd,
1H, J ) 1.3, 5.1 Hz), 2.32 (m, 1H), 2.03 (m, 14H), 1.91 (app. t, 1H,
J ) 11.7 Hz), 1.79 (m, 1H), 1.69 (s, 3H), 1.61 (s, 6H), 1.60 (s, 6H),
1.32 (dd, 1H, J ) 3.7, 14.3 Hz), 1.18 (dd, 1H, J ) 5.7, 12.6 Hz), 0.94
(dd, 1H, J ) 11.4, 14.3 Hz), 0.32 (s, 3H), 0.30 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 164.1, 136.7, 135.1, 134.9, 134.8, 131.5, 131.1, 130.6,
130.0, 126.8, 124.3, 124.1, 124.0, 121.8, 120.3, 109.3, 61.5, 56.0, 54.9,
39.9, 39.8, 39.7, 38.4, 37.9, 34.3, 32.5, 26.84, 26.75, 26.71, 25.8, 19.3,
17.8, 16.3, 16.11, 16.08, -1.56, -1.64; HMRS (FAB) calcd for
[C37H56O2Si] ([M + Na]+) 583.3947; found 583.3941.
Ketal 17. To triol intermediate above (53.1 mg, 0.123 mmol) in
2.05 mL of THF was added CSA (14.3 mg, 0.0616 mmol) and 1,1-
dimethoxycyclopentane (51.4 µL, 48.2 mg, 0.370 mmol). After being
stirred at room temperature for 14 h, the reaction mixture was poured
into 50 mL of a half-saturated solution of NaHCO3 and extracted with
three 50-mL portions of Et2O. The combined organic phases were
washed with 50 mL of saturated NaCl solution, dried over MgSO4,
filtered, and concentrated to afford a colorless oil. Purification by flash
chromatography on silica gel (elution with 5% EtOAc-hexanes)
afforded 53.3 mg (87%) of ketal 17 as a colorless oil: [R]23 -4.5 (c
D
1.1, CHCl3, 97% ee); Rf 0.56 (EtOAc-hexanes 1:3); FTIR (thin film)
3533, 2963, 2925, 2854 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.57 (d,
1H, J ) 9.9 Hz), 5.45 (ddd, 1H, J ) 2.2, 5.1, 9.9 Hz), 5.10 (m, 4H),
3.81 (d, 1H, J ) 8.8 Hz), 3.73 (dd, 1H, J ) 9.2, 11.7 Hz), 3.69 (d, 1H,
J ) 8.8 Hz), 3.57 (ddd, 1H, J ) 2.9, 10.3, 11.7 Hz), 3.44 (d, 1H, J )
10.3 Hz), 2.42 (m, 1H), 2.19 (m, 1H), 2.02 (m, 14H), 1.83 (m, 5H),
1.69 (m, 5H), 1.68 (s, 3H), 1.60 (s, 12H); 13C NMR (100 MHz, CDCl3)
δ 137.2, 135.1, 134.9, 133.3, 131.3, 124.9, 124.4, 124.2, 124.0, 121.3,
119.1, 83.4, 74.3, 65.0, 46.0, 39.8, 39.71, 39.70, 37.03, 36.99, 36.6,
34.4, 33.9, 26.7, 26.6 (2C), 25.7, 23.3, 23.2, 17.7, 16.3, 16.00, 15.99;
HMRS (ESI) calcd for [C33H52O3] ([M + H]+) 497.3994, found
497.4013.
Epoxy Alcohol 18. To homoallylic alcohol 17 (38.1 mg, 0.0767
mmol) was added a solution of aluminum tert-butoxide (18.9 mg,
0.0767 mmol) in 380 µL of toluene followed by anhydrous tert-
butylhydroperoxide (11.6 µL, 10.4 mg, 0.115 mmol). After being stirred
at room temperature for 2 h, the reaction crude was purified directly
by flash chromatography on silica gel (gradient elution with 10-15%
EtOAc-hexanes) to afford 34.4 mg (88%) of epoxy alcohol 18 as a
colorless oil: [R]23D -1.4 (c 0.56, CHCl3, 97% ee); Rf 0.18 (EtOAc-
hexanes 1:3); FTIR (thin film) 3455, 2964, 2925, 2870, 2856 cm-1
;
1H NMR (400 MHz, CDCl3) δ 5.17 (m, 1H), 5.10 (m, 3H), 3.98 (dd,
1H, J ) 7.3, 11.4 Hz), 3.86 (m, 1H), 3.75 (d, 1H, J ) 8.4 Hz), 3.63 (d,
1H, J ) 8.4 Hz), 3.25 (dd, 1H, J ) 3.7, 5.1 Hz), 3.07 (d, 1H, J ) 3.7
Hz), 2.75 (br d, 1H, J ) 7.0 Hz), 2.25 (m, 2H), 2.06 (m, 10H), 1.97
(m, 4H), 1.85 (m, 2H), 1.83-1.65 (m, 7H), 1.68 (s, 3H), 1.64 (s, 3H),
1.59 (s, 9H), 1.33 (dd, 1H, J ) 4.4, 12.5 Hz); 13C NMR (100 MHz,
CDCl3) δ 137.8, 135.1, 135.0, 131.3, 124.4, 124.2, 124.0, 121.0, 119.3,
81.4, 74.4, 61.7, 54.5, 54.1, 42.0, 39.8, 39.7 (2C), 37.0, 36.8, 35.1,
32.4, 31.8, 26.7, 26.63, 26.60, 25.7, 23.4, 23.0, 17.7, 16.1, 16.01, 15.99;
HMRS (ESI) calcd for [C33H52O4] ([M + Na]+) 535.3763, found
535.3745.
Transformation of Epoxide 16 to the Corresponding Glycol. To
a solution of epoxide 16 (97.6 mg, 0.174 mmol) in 10.6 mL of EtOH-
i-PrOH (4:1) was added LiOH solution (3.00 N in water, 5.80 mL,
17.4 mmol). The resulting solution was heated to 70 °C under a N2
atmosphere for 72 h, poured into 100 mL of water, and extracted with
five 100-mL portions of EtOAc. The organic phases were combined,
dried over Na2SO4, filtered, and concentrated to afford a colorless oil,
which was redissolved in 4 mL of CH2Cl2 and treated with trifluoro-
acetic acid (33.5 µL, 49.6 mg, 0.435 mmol). After 3.5 h, the reaction
mixture was concentrated and sparged with two 4-mL portions of CH2-
Cl2 to remove excess TFA. The crude mixture was then redissolved in
4 mL of THF-MeOH (1:1). KF (50.5 mg, 0.870 mmol), KHCO3 (87.1
mg, 0.870 mmol), and H2O2 (aqueous solution, 30% w/v, 197 µL, 1.74
mmol) were added and the resulting mixture was stirred vigorously
for 24 h. The reaction mixture was then diluted with 100 mL of water,
Transformation of Alcohol 18 to Exocyclic Olefin 19. To a solution
of epoxy alcohol 18 (34.4 mg, 0.0671 mmol) and o-nitrophenylsele-
nocyanate (22.9 mg, 0.101 mmol) in 1.34 mL of benzene was added
tributylphosphine (30.1 µL, 24.4 mg, 0.121 mmol). The resulting dark
red solution was heated at 75 °C and became orange in color within 5
min. After 2 h, the reaction mixture was cooled to room temperature,
diluted with 2.7 mL of THF, and cooled to 0 °C. H2O2 (aqueous
solution, 30% w/v, 38.0 µL, 11.4 mg, 0.335 mmol) was added. After
being stirred at 0 °C for 7 h, the reaction mixture was poured into 60
mL of H2O and extracted with two 60-mL portions of CH2Cl2. The
organic phases were combined, dried over Na2SO4, filtered, and
concentrated to afford a yellow oil. Purification by flash chromatography
on silica gel (elution with 5% EtOAc-hexanes) afforded 27.1 mg (82%)