E. J. Tisdale et al. / Tetrahedron 59 (2003) 6873–6887
6885
water and brine. The ether layer was dried over MgSO4,
filtered and concentrated and the crude material was purified
by column chromatography (5% Et2O/hexane) to yield 10
(36.1 mg, 73.3 mmol, 70%).
17.9, 21.2; HRMS calcd for C23H36O7Si (M2Hþ)
451.2157, found 451.2161.
6.1.30. Carboxylic acid 7. Compound 43 (5.6 mg,
12.4 mmol) was dissolved in methanol (0.25 mL) and
stirred at 258C. To this solution was added 2N HCl (aq)
(0.13 mL) dropwise. After 1 h, the reaction mixture was
partitioned between ethyl acetate and water. The ethyl
acetate layer was dried over MgSO4, filtered and concen-
trated. The crude material was purified by preparative TLC
(0.5% AcOH/Et2O) to afford 7 (4.2 mg, 11.5 mmol, 93%).
Compound 10. Rf¼0.65 (50% Et2O/hexane); IR (film) nmax
3087, 2982, 2952, 1741, 1456, 1346, 1287, 1123, 1066, 836;
1H NMR (400 MHz, CDCl3) d 7.46 (s, 1H), 6.19 (dd,
J¼17.6, 10.8 Hz, 1H), 6.18 (dd, J¼17.4, 10.8 Hz, 1H), 5.14
(s, 2H), 5.07 (d, J¼17.6 Hz, 1H), 5.06 (d, J¼17.6 Hz, 1H),
4.98 (dd, J¼10.8, 0.8 Hz, 1H), 4.97 (dd, J¼10.8, 0.8 Hz,
1H), 3.73–3.77 (m, 2H), 1.71 (s, 6H), 1.47 (s, 6H), 1.45 (s,
6H), 0.94–0.98 (m, 2H), 20.01 (s, 9H); 13C NMR
(100 MHz, CDCl3) d160.9, 149.0, 148.3, 147.1, 143.3,
143.0, 140.2, 112.9, 112.8, 110.7, 108.5, 106.2, 94.1, 85.3,
84.4, 77.2, 66.6, 27.0, 26.9, 25.8, 18.1, 21.2; HRMS calcd
for C26H40O7Si1 (MþNaþ) 515.2435, found 515.2413.
Compound 7. Rf¼0.25 (0.01% AcOH/Et2O); IR (film) nmax
1
3359, 1745, 1692; H NMR (400 MHz, CDCl3) d 7.21 (s,
1H), 6.18 (br s, 1H), 4.59–4.56 (m, 1H), 2.76 (dd, J¼14.0,
10.5 Hz, 1H), 2.66–2.62 (m, 1H), 2.28 (d, J¼9.5 Hz, 1H),
2.06 (d, J¼13.0 Hz, 1H), 1.84 (dd, J¼13.0, 9.5 Hz, 1H),
1.60 (s, 6H), 1.56 (s, 3H), 1.25 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 201.6, 167.8, 145.5, 136.3, 130.6, 118.7, 85.0,
84.7, 83.6, 83.0, 50.8, 35.5, 30.4, 29.8, 29.3, 26.5, 18.4;
HRMS calcd for C17H22O6 (M2Hþ) 321.1337, found
321.1351.
6.1.28. Ketone 42. Alkene 10 (35.7 mg, 72.5 mmol) was
dissolved in toluene (0.75 mL) and stirred under argon at
1108C. After 45 min, the reaction mixture was concentrated
under reduced pressure. The crude material was purified by
preparative TLC (50% Et2O/hexane) to yield 42 (30.3 mg,
61.6 mmol, 85%).
6.1.31. Acetate 45. Claisen/Diels–Alder adduct 42
(15.7 mg, 31.9 mmol) was dissolved in methanol
(0.35 mL) and stirred at 258C. To this solution was added
2N HCl (aq) (0.25 mL) dropwise. After 1 h, the reaction
mixture was partitioned between ethyl acetate and water.
The ethyl acetate layer was dried over MgSO4, filtered and
concentrated. The crude material was purified by prepara-
tive TLC (80% Et2O/hexane) to afford 44 (11.0 mg,
30.3 mmol, 95%). This material was then transferred to a
sealed tube, dissolved in CHCl3 (0.50 mL) and stirred at
08C. To this solution was added pyridine (24.5 mL,
0.30 mmol), acetyl chloride (21.5 mL, 0.30 mmol), acetic
anhydride (28.6 mL, 0.30 mmol) and DMAP (0.4 mg,
3.0 mmol). The reaction mixture was then allowed to heat
at 808C. After 20 h, the reaction appeared to be complete
and was then partitioned between CHCl3 and water. The
chloroform layer was then dried over MgSO4, filtered and
concentrated. The crude material was purified by prepara-
tive TLC (75% Et2O/hexane) to yield 45 (11.3 mg,
27.9 mmol, 92%). X-Ray quality crystals were grown by
first dissolving the pure product in a minimal amount of
ether and then allowing the solvent to slowly evaporate over
the course of 2 days.
Compound 42. Rf¼0.65 (50% Et2O/hexane); IR (film) nmax
2953, 1741, 1283, 1071, 836; 1H NMR (400 MHz, CDCl3) d
7.58 (s, 1H), 5.02 (d, J¼8.0 Hz, 1H), 4.94 (d, J¼7.6 Hz,
1H), 4.41–4.36 (m, 1H), 3.81–3.68 (m, 2H), 2.71 (dd,
J¼13.9, 10.3 Hz, 1H), 2.67–2.62 (m, 1H), 2.55 (d,
J¼9.9 Hz, 1H), 2.43 (d, J¼13.2 Hz, 1H), 1.79 (dd,
J¼13.2, 9.9 Hz, 1H), 1.68 (s, 3H), 1.67 (s, 3H), 1.60 (s,
3H), 1.53 (s, 3H), 1.50 (s, 3H), 1.24 (s, 3H), 0.95 (d,
J¼8.1 Hz, 1H), 0.93 (d, J¼8.1 Hz, 1H), 0.02 (s, 9H); 13C
NMR (100 MHz, CDCl3) d200.7, 158.7, 140.3, 135.6,
125.5, 117.5, 104.9, 92.5, 84.2, 83.9, 83.4, 83.1, 66.1, 49.0,
32.6, 30.2, 29.0, 28.7, 28.4, 27.9, 25.7, 18.3, 21.2; HRMS
calcd for C26H40O7Si (MþNaþ) 515.2435, found 515.2439.
6.1.29. Carboxylic acid 43. Acetonide 42 (24.6 mg,
49.9 mmol) was dissolved in methanol (0.50 mL) and
stirred at 08C. 10% NMe4OH (aq) (0.60 mL, 55.7 mmol)
was then added dropwise turning the reaction mixture
slightly yellow. The reaction mixture was allowed to warm
to 258C and stir for an additional 30 minutes. After the
reaction was shown to be complete by TLC, acetic acid was
added to neutralize the reaction mixture. The reaction
mixture was then partitioned between ethyl acetate and
water. The ethyl acetate layer was dried over MgSO4,
filtered and concentrated. The crude material was purified
by preparative TLC (75% Et2O/hexane) to yield 43
(12.7 mg, 27.9 mmol, 56%).
Compound 45. Rf¼0.4 (75% Et2O/hexane); IR (film) nmax
2987, 1744, 1228, 1048, 880; 1H NMR (400 MHz, CDCl3) d
7.46 (s, 1H), 4.49–4.45 (m, 1H), 2.75 (dd, J¼13.6, 10.4 Hz,
1H), 2.67–2.62 (m, 1H), 2.59 (d, J¼13.2 Hz, 1H), 2.56 (d,
J¼10.0 Hz, 1H), 2.23 (s, 3H), 1.83 (dd, J¼12.8, 10.0 Hz,
1H), 1.70 (s, 3H), 1.68 (s, 3H), 1.62 (s, 3H), 1.56 (s, 3H),
1.52 (s, 3H), 1.29 (s, 3H); 13C NMR (100 MHz, CDCl3) d
196.4, 168.7, 158.6, 139.4, 135.7, 124.0, 117.2, 104.9, 84.3,
83.4, 83.2, 82.8, 48.3, 31.4, 30.2, 29.0, 28.7, 28.03, 27.95,
25.7, 21.1, 18.2; HRMS calcd for C22H28O7 (MþNaþ)
427.1727, found 427.1727.
Compound 43. Rf¼0.2 (75% Et2O/hexane); IR (film) nmax
3359, 1745, 1692, 1250, 837; 1H NMR (400 MHz, CDCl3) d
7.53 (s, 1H), 6.13 (br s, 1H), 5.03 (d, J¼8.0 Hz, 1H), 4.92 (d,
J¼8.0 Hz, 1H), 4.60–4.56 (m, 1H), 3.84–3.70 (m, 2H),
2.71 (dd, J¼14.0, 10.0, 1H), 2.64–2.59 (m, 1H), 2.39 (d,
J¼13.2 Hz, 1H), 2.28 (d, J¼10.0 Hz, 1H), 1.73 (dd, J¼13.2,
10.0 Hz, 1H), 1.59 (s, 6H), 1.55 (s, 3H), 1.24 (s, 3H), 0.96 (t,
J¼8.4 Hz, 2H), 0.03 (s, 9H); 13C NMR (100 MHz, CDCl3) d
201.9, 167.5, 142.9, 135.2, 128.3, 118.3, 92.5, 84.3, 84.1,
83.7, 82.4, 66.1, 50.0, 32.7, 30.1, 29.1, 28.7, 25.9, 18.3,
6.1.32. Ester 48. To a solution containing 43 (10.0 mg,
22.1 mmol) and quinone 6 (7.3 mg, 26.5 mmol) in aceto-
nitrile (0.50 mL) was added DIPEA (15.2 mL, 44.2 mmol)
turning the reaction mixture into a deep purple solution.