E. Winterfeldt et al.
FULL PAPER
15.76 (q), 20.99 (t), 23.31 (t), 27.39 (t), 28.08 (t), 49.05 (d), 52.45 (d), 55.04
(d), 55.31 (q), 60.13 (d), 60.14 (s), 61.68 8s), 63.54 (s), 87.21 (s), 113.64 (d),
122.43 (d), 127.84 (d), 130.19 (s), 135.82 (d), 139.02 (d), 15832 (d), 159.24
(d), 171.06 (s), 203.23 (s); MS: m/z (%): 418 (5) [M ], 338 (4), 323 (11), 267
(7), 241 (100), 240 (4), 197 (9), 165 (5), 121 (5); HRMS: m/z: calcd for
After 20 min stirringat 0 8C a solution of spirobutenolide 5 (10 mg,
0.025 mmol, 1 equiv) in dry THF (1 mL) was added. The reaction was
quenched after 2.5 h with sat. aq. NH4Cl. The reaction mixture was
extracted with ethyl acetate and the combined organic layers were dried
(MgSO4). Purification of the raw material by flash chromatography (PE/
C26H26O5: 418.1780; found: 418.1780.
Et2O 2:1) yielded a yellow foam (14 mg, 0.025 mmol, 100%). [a]D20
À38.28 (c 1.06, CHCl3); IR (CHCl3): nÄ 2982 (m), 2932 (m), 2865 (w),
1767 (s), 1730 (s), 1614 (w), 1516 (m), 1250 (m), 1181 (m), 1089 (m), 1028
(m); 1H NMR (400 MHz, CDCl3): d 0.49 (brd, J 13 Hz, 1H), 0.73 (s,
3H), 0.85 1.61 (m, 2H), 1.23 (m, 2H), 1.28 (t, J 7 Hz, 6H), 1.90 (m, 1H),
2.22 (d, J 12 Hz, 1H), 2.41 (dd, J 9, 19 Hz, 1H), 2.56 (m, 2H), 3.30 (d,
J 8 Hz, 1H), 3.45 (t, J 9 Hz, 1H), 3.78 (d, 1H), 3.79 (s, 3H), 4.21 (q, J
7 Hz, 4H), 6.15 (d, J 6 Hz, 1H), 6.38 (d, J 6 Hz, 1H), 6.86 (d, J 9 Hz,
2H), 7.23 (d, J 9 Hz, 2H), 7.43 (d, J 6 Hz, 1H); MS: m/z (%): 562 (11)
Bisepoxide 24: tBuOOH (0.02 mL, 5.5 equiv, 80%)and 1,8-diazabicy-
clo[5.4.0]undec-7-en (DBU) (0.2 mL) were added to
a solution of
spirobutenolide 5 (10 mg, 0.025 mmol) in dry CH2Cl2 (1 mL). After 15 h
of stirringat RT the reaction was quenched with sat. aq. NaHSO 3 and the
reaction mixture extracted with CH2Cl2. The combined organic layers were
dried (MgSO4), concentrated, purified by chromatography (PE/Et2O 4:1)
and yielded a white foam (5 mg, 0.012 mmol, 46%). [a]2D0 4.08 (c 0.33,
CHCl3); IR (CHCl3): nÄ 2927 (vs), 2854 (m), 1790 (m), 1780 (m), 1723 (s),
1252 (s), 1181 (m), 1058 (m), 910 (w); 1H NMR (400 MHz, CDCl3): d 0.59
(brd, J 13 Hz, 1H), 0.80 (s, 3H), 0.80 1.64 (m, 6H), 1.97 (m, 1H), 2.98 (d,
J 10 Hz, 1H), 3.39 (d, J 4 Hz, 1H), 3.70 (d, J 4 Hz; 1H), 3.79 (s, 3H),
3.95 (d, J 2 Hz, 1H), 4.07 (d, J 10 Hz, 1H), 4.21 (d, J 2 Hz, 1H), 5.85
(d, J 6 Hz, 1H), 6.19 (d, J 6 Hz, 1H), 6.86 (d, J 9 Hz, 2H), 7.11 (d, J
9 Hz, 2H).
[M ], 517/17), 402 (28), 322 (48), 304 (100), 278 (62), 254 (34); HRMS: m/z:
calcd for C33H38O8: 562.2567; found: 562.2568.
Methanol adduct 26: NaOMe (10 mg, 0.019 mmol, 3 equiv) was added to a
solution of spirobutenolide 5 (25 mg, 0.06 mmol, 1 equiv) in dry MeOH
(3 mL). After stirringfor 1 day at RT the reaction mixture was extracted
with CH2Cl2. The combined organic layers were washed with sat. aq.
NH4Cl, dried (MgSO4) and concentrated. Chromatographic purification
NOE experiment
(PE/Et2O 2:1) yielded a white foam (25 mg, 0.06 mmol, 96%). [a]D20
2.98 ) 0.80 (0.12%),4.07 (0.13%), 4.21 (0.19%);
À97.88 (c 1.50, CHCl3); IR (CHCl3): nÄ 2984 (w), 2932 (w), 2856 (w),
1764 (m), 1708 (w), 1600 (w), 1516 (m), 1464 (w), 1264 (s), 1096 (w);
1H NMR (400 MHz, CDCl3): d 0.50 (brd, J 13 Hz, 1H), 0.78 (s, 3H),
0.79 1.63 (m, 5H), 1.92 (m, 1H), 2.48 (dd, J 4, 19 Hz, 1H), 2.63 (dd, J 2,
19 Hz, 1H), 3.20 (d, J 10 Hz, 1H), 3.25 (dd, J 2, 4 Hz, 1H), 3.35 (s, 3H),
3.76 (d, J 10 Hz, 1H), 3.80 (s, 3H), 6.04 (d, J 6 Hz, 1H), 6.10 (d, J
6 Hz, 1H), 6.13 (d, J 5.5 Hz, 1H), 6.86 (d, J 9 Hz, 2H), 7.20 (d, J 9 Hz,
2H), 7.81 (d, J 5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 16.23 (q),
21.08 (t), 23.50 (t), 27.29 (t), 28.35 (t), 40.74 (t), 47.28 (d), 53.87 (d), 55.29 (q),
47.21 (q), 59.74 (s), 61.89 (s), 66.22 (s), 82.85 (d), 88.31 (s), 113.32 (d), 121.19
(d), 128.25 (d), 130.76 (s), 135.57 (d), 139.87 (d), 158.11 (s), 161.68 (d),
13C NMR (100 MHz, CDCl3): d 14.21 (q), 27.79 (t), 29.79 (t), 30.76 (t),
30.49 (t), 32.03 (t), 50.67 (d), 51.78 (d), 52.61 (d), 54.63 (d), 55.30 (q), 56.27
(d), 59.31 (s), 60.01 (d), 61.86 (s), 63.66 (s), 83.04 8s), 113.68 (d), 129.89 (s),
136.52 (d), 138.06 (d), 158.39 (s), 168.14 (s), 203.23 (s); MS: m/z (%): 434
(3) [M ], 402 (2), 266 (3), 240 (100), 219 (82), 197 (7), 71 (9); HRMS: m/z:
calcd for C26H26O6: 434.1729; found: 434.1728.
Cyclopentadiene adduct 22: A solution of spirobutenolide 5 (10 mg,
0.03 mmol, 1 equiv) and cyclopentadiene (3 mg, 0.04 mmol, 1.3 equiv) in
dry CH2Cl2 (1 mL) was introduced into a Teflon hose and submitted to
14 kbar for one week. Purification of the raw material by flash chromatog-
raphy (PE/Et2O 1:2) yielded a white solid (14 mg, 0.03 mmol; 100%).
[a]2D0 38.78 (c 0.99, CHCl3); IR (CHCl3): nÄ 2932 (m),2864 (w), 1757 (s),
1694 (m), 1613 (w), 1516 (m), 1464 (w), 1287 (w), 1252 (m), 1182 (m), 1089
(m), 1038 (m), 928 (w), 829 cmÀ1(m); 1H NMR (400 MHz; CDCl3): d 0.58
(brd, J 13 Hz, 1H), 0.66 (s, 3H), 2.00 (dt, 1H, J 4, 12 Hz, 1H), 2.16
(brd, J 13 Hz, 1H), 2.40 (d, J 10 Hz, 1H), 2.79 (dd, J 3, 11 Hz, 1H),
2.89 (brs, 1H), 2.99 (dd, J 3, 11 Hz, 1H), 3.06 (brs, 1H), 3.79 (s, 3H), 5.92
(d, J 6 Hz, 1H), 6.03 (dd, J 3, 5 Hz, 1H), 6.22 (d, J 6 Hz, 1H), 6.26 (d,
J 6 Hz, 1H), 6.31 (dd, J 3, 5 Hz, 1H), 6.86 (d, J 9 Hz, 2H), 7.19 (d, J
9 Hz, 2H), 7.38 (d, J 6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 15.69
(q), 21.23 (t), 23.50 (t), 26.97 (t), 27.58 (t), 28.91 (t), 45.06 (d), 45.39 (d),
51.31 (d), 53.16 (d), 54.27 (d), 55.26 (q), 55.44 (d), 61.83 (s), 64.71 (s), 66.98
(s), 91.48 (s), 113.49 (d), 118.04 (d), 128.44 (d), 129.40 (s), 135.69 (d), 136.29
(d), 136.35 (d), 139.01(d), 158.43 (s), 161.92 (d), 171.92 (s), 211.51 (s); MS:
171.75 (s), 207.80 (s); MS: m/z (%): 434 (1) [M ], 402 (3), 310 (81), 280 (5),
240 (60), 220 (16), 205 (57), 167 (10), 149 (100), 97 (15), 84 (33); HRMS:
m/z: calcd for C27H30O5: 434.2093; found: 434.2102.
Methyl acetoacetate adduct (wistarin precursor) 28:
A solution of
spirobutenolide (100 mg, 0.25 mmol, 1 equiv). N-Methylmorpholine
5
(0.4 mL) and methyl acetoacetate (0.1 mL, 87 mg, 0.75 mmol, 3 equiv) in
dry CH2Cl2 (4 mL) was introduced into a Teflon hose and submitted to
14 kbar for one week. Purification of the raw material by flash chromatog-
raphy (PE/Et2O 1:1) yielded 28 (121 mg, 0.23 mmol, 93%) as a white foam.
[a]2D0 À101.08 (c 0.92, CHCl3); IR (CHCl3): nÄ 2928 (s), 2858 (w), 1785
(s), 1708 (s), 1639 (m), 1614 (w), 1516 (s), 1439 (m), 1381 (w), 1253 (s), 1183
(w), 1153 (w), 1104 (w), 1074 (m), 909 (m), 792 (s); 1H NMR (400 MHz,
CDCl3): d 0.46 (brd, J 12 Hz, 1H), 0.77 (s, 3H), 0.79 1.71 (m, 5H), 1.85
(m, 1H), 2.08 (dd, J 12, 18 Hz, 1H), 2.21 (s, 3H), 2.42 (brd, J 12 Hz,
1H), 2.52 (dd, J 7, 17 Hz, 1H), 2.57 (d, J 9 Hz, 1H), 2.70 (d, J 18 Hz,
1H), 3.17 (dd, J 5, 18 Hz, 1H), 3.64 (dd, J 7, 12 Hz, 1H), 3.70 (s, 3H),
3.79 (d, J 8 Hz, 1H), 3.80 (s, 3H), 4.70 (d, J 5 Hz, 1H), 6.30 (d, J 6 Hz,
1H), 6.42 (d, J 6 Hz, 1H), 6.87 (d, J 9 Hz, 2H), 7.23 (d, J 9 Hz, 2H).
m/z (%): 468 (2) [M ], 402 (2), 280 (1), 266 (1), 240 (100), 197 (14), 149 (8);
HRMS: m/z: calcd for C31H32O4: 468.2301; found: 468.2303.
Methoxybutadiene adduct 23: A solution of spirobutenolide 5 (30 mg,
0.08 mmol, 1 equiv) and catalytic amounts of TEMPO and methoxybuta-
diene (2 mg, 0.016 mmol, 2 equiv) in dry CH2Cl2 (2 mL) was introduced
into a Teflon hose and submitted to 14 kbar for 6 d. Purification of the raw
material by flash chromatography (PE/Et2O 1:1) yielded a white solid
(38 mg, 0.08 mmol, 100%). [a]D20 5.68 (c 0.56, CHCl3); IR (CHCl3): nÄ
2929 (s), 2856 (w), 1759 (s), 1612 (w), 1516 (m), 1464 (m), 1253 (m), 1230
NOE experiment:
3.64 ) 2.52 (7.8%), 6.30 (2.2%), 6.42 (13.5%);
4.70 ) 2.08 (3.0%), 2.57 (5.1%), 3.17 (2.3%);
13C NMR (100 MHz, CDCl3): d 16.05 (q), 20.29 (q), 20.90 (t), 23.85 (t),
27.42 (t), 28.23 (t), 30.43 (s), 31.84 (d), 37.37 (t), 43.79 (t), 50.35 (d), 51.69 (q),
54.70 (d), 55.30 (q), 62.71 (s), 63.21 (s), 69.83 (s), 77.98 (d), 87.91 (s), 104.97
(s), 113.35 (d), 128.70 (d), 129.08 (d), 137.20 (d), 139.49 (d), 158.41 (s),
1
(w), 1082 (s), 909 (m), 860 cmÀ1(s); H NMR (400 MHz, CDCl3): d 0.45
(brd, J 13 Hz, 1H), 0.74 (s, 3H), 0.79 1.75 (m, 6H), 1.84 (m, 1H), 2.05
(brm, 2H), 2.41 (brs, 1H), 2.78 (brs, 1H), 2.87 (d, J 9 Hz, 1H), 3.34 (s,
3H), 3.79 (s, 3H), 3.79 (m, 1H), 3.85 (m, 1H), 5.73 (m, 1H), 5.91 (m,
1H),5.98 (brd, J 5 Hz, 1H), 6.16 (brd, J 6 Hz, 1H), 6.30 (d, J 6 Hz,
1H), 6.85 (d, J 9 Hz, 2H), 7.23 (d, J 9 Hz, 2H), 7.95 (brs, 1H); 13C NMR
(100 MHz, CDCl3): d 16.13 (q), 19.30 (t), 23.89 (t), 27.02 (t), 27.34 (t),
28.44 (t), 30.43 (t), 30.69 (d), 48.67 (d), 55.30 (s), 57.24 (s), 62.15 (t), 91.18
(s), 113.18 (d), 125.62 (d), 128.95 (d), 128.97 (d), 130.26 (s), 131.01 (d),
136.23 (d), 158.14 (s), because of the width of the peaks, it was not possible
164.04 (s), 167.03 (s), 173.49 (s), 208.19 (s); MS: m/z (%): 519 (M 1, 6),
473 (5), 391 (12), 307 (37), 240 (43), 154 (100); HRMS: m/z: calcd for
C31H34O7: 518.2306; found: 518.2308.
Retro-Diels Alder product 30: Methyl acetoacetate adduct 28 (45 mg,
0.09 mmol) was sublimed at 2 Â 10À2 mbar into a pyrolysis tube heated to
3008C. Diene 1 was trapped on a coolingfinger. Purification of the raw
material by flash chromatography (PE/Et2O 1:1) yielded a white foam
(25 mg, 0.09 mmol, 100%). [a]D20 À198.68 (c 1.03, CHCl3); IR (CHCl3):
nÄ 2927 (m), 2855 (w), 1798 (s), 1695 (s), 1636 (m), 1437 (w), 1384 (m),
1285 (w), 1198 (m), 1107 (s), 1042 (m), 860 (w); 1H NMR (400 MHz,
CDCl3): d 2.25 (m, 1H), 2.31 (s dd, J 13.5/17 Hz, 3H), 2.63 (d, J
18 Hz, 1H), 2.90 (dd, J 4/17 Hz, 1H), 3.02 (dd, J 4.5/18 Hz, 1H), 3.68
to identify more signals; MS: m/z (%): 486 (20) [M ], 473 (47), 472 (100),
434 (22), 410 (21), 402 (35), 358 (55), 296 (48); HRMS: m/z: calcd for
C31H34O5: 486.2406; found: 486.2403.
Diester 25: Malonic diethylester (0.01 mL, 0.05 mmol, 2 equiv) was added
at 08C to a solution of NaH (3 mg, 0.05 mmol, 2 equiv) in dry THF (2 mL).
3856
¹ 2003 Wiley-VCH VerlagGmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2003, 9, 3849 3858