Synthesis of 7,11-Guaien-8,12-olides
J . Org. Chem., Vol. 65, No. 20, 2000 6707
1
C15H20O3 (M+) required 248.1412; H NMR (400 MHz) δ 5.34
(hexanes-EtOAc); [R]26 +60.8 (c 1.25); IR (KBr) 3500-3400,
D
(1H, br s), 4.42 (1H, dd, J ) 2.4, 7.2), 2.91-2.85 (1H, m), 2.50-
2.40 (1H, m), 2.44 (1H, q, J ) 7.6), 2.42 (1H, dd, J ) 7.2, 14.0),
2.31 (1H, dd, J ) 7.6, 8.4), 2.13 (1H, dd, J ) 8.8, 14.4), 1.82
(1H, br d, J ) 17.2), 1.77 (1H, d, J ) 14.4), 1.71 (3H, br s),
1.52 (1H, ddd, J ) 1.2, 2.4, 14.0), 1.29 (3H, s), 1.25 (3H, d, J
) 7.6); 13C NMR (200 MHz) δ 177.9, 140.7 (C), 125.2, 85.5 (CH),
85.1, 84.4 (C), 44.2, 44.0, 43.0 (CH), 40.7, 34.1, 28.4 (CH2), 26.0,
14.9, 8.1 (CH3).
1730, 1683 cm-1; MS m/e 337 (M+ + C2H5, 1), 249 (40), 231
(100), 230 (18); HRMS 337.2011, C17H24O5 (M+ + C2H5 required
337.2015; 1H NMR (400 MHz) δ 4.94 (1H, dt, J ) 1.6, 7.2),
3.50 (1H, ddd, J ) 3.0, 8.7, 12.3), 2.71 (1H, br d, J ) 8.8), 2.62
(1H, br d, J ) 16.0), 2.27 (1H, dd, J ) 7.2, 16.0), 1.90-1.70
(5H, m), 1.84 (3H, d, J ) 2.4), 1.79 (3H, s), 1.53 (3H, s), 1.60-
1.45 (1H, m), 1.38 (3H, s); 13C NMR (200 MHz) δ 174.9, 169.9,
160.2, 122.8, 84.1, 81.5 (C), 80.2, 51.1, 48.0 (CH), 37.1, 33.1
(CH2), 27.2, 25.3 (CH3), 24.8, 24.0 (CH2), 22.2, 8.1 (CH3).
4r-H yd r oxy-7r,10r-ep oxy-1,5,11rH ,8âH -gu a ia n -8,12-
olid e (19). From compound 18 (36 mg, 0.115 mmol) and
according to the procedure for the synthesis of 12 (reaction
time 3 h) was obtained compound 19 (26 mg, 85%): solid; mp
10r-Acetoxy-3r,4r-ep oxy-1,5rH,8âH-gu a i-7(11)-en -8,12-
olid e (15) a n d 10r -Acetoxy-3â,4â-ep oxy-1,5rH,8âH-gu a i-
7(11)-en -8,12-olid e (16). To a solution of compound 11 (119
mg, 0.41 mmol) in MeOH (3.5 mL) was added MMPP (243 mg,
0.49 mmol), and the mixture was stirred overnight at room
temperature. The reaction was quenched with saturated
aqueous NaHCO3 and extracted with CH2Cl2, and the organic
layers were washed with aqueous 10% Na2S2O3 and brine and
dried over Na2SO4. The usual workup and chromatography
(5:5 to 3:7 hexane/EtOAc) afforded 92 mg (75%) of compound
15 and 22 mg (18%) of compound 16. Data for compound 15:
135-136 °C (hexanes-EtOAc); [R]18 -21.9 (c 1.28); IR (KBr)
D
3345, 1772, 1376 cm-1; MS m/e 267 (M+ + 1, 15), 249 (100),
248 (20), 231 (19), 175 (12); HRMS 267.1591, C15H23O4 (M+
+
1) required 267.1596; 1H NMR (400 MHz) δ 4.52 (1H, dd, J )
1.6, 6.8), 2.58-2.49 (1H, m), 2.50 (1H, q, J ) 7.2), 2.46 (1H,
dd, J ) 6.8, 15.4), 2.23 (1H, td, J ) 3.6, 14.1), 2.20 (1H, q, J )
10.8), 2.00-1.90 (1H, m), 1.80-1.70 (1H, m), 1.66 (1H, br d, J
) 15.4), 1.56 (1H, br s), 1.47 (1H, d, J ) 10.8), 1.33 (3H, s),
1.26 (3H, d, J ) 7.2), 1.25 (3H, s), 1.20-1.15 (2H, m); 13C NMR
(200 MHz) δ 177.6, 85.2 (C), 86.9 (CH), 84.0, 80.7 (C), 45.1,
44.4, 44.1 (CH), 41.0, 38.7 (CH2), 27.7 (CH3), 27.0, 25.7 (CH2),
23.5, 7.9 (CH3).
foam; [R]26 +55.7 (c 1.94); IR (KBr) 1737, 1734, 1687 cm-1
;
D
MS m/e 307 (M+ + 1, 3), 275 (53), 248 (85), 247 (58), 246 (100),
229 (87); HRMS 307.1545, C17H23O5 (M+ + 1) required
307.1545; 1H NMR (400 MHz) δ 4.93 (1H, br d, J ) 7.2), 3.30
(1H, s), 2.87 (1H, ddd, J ) 5.6, 6.8, 12.0), 2.82 (1H, dd, J )
3.2, 13.2), 2.67 (1H, br d, J ) 16.4), 2.17 (1H, ddd, J ) 3.2,
5.6, 13.2), 2.10 (1H, dd, J ) 7.2, 16.4), 2.04 (1H, dd, J ) 6.8,
13.6), 1.93 (1H, t, J ) 13.2), 1.85 (3H, d, J ) 2.0), 1.79 (3H, s),
1.52 (3H, s), 1.50 (3H, s), 1.55-1.49 (1H, m); 13C NMR (200
MHz) δ 174.6, 169.4, 159.1, 122.8, 83.2 (C), 79.9 (CH), 64.5
(C), 60.0, 43.3, 41.9 (CH), 33.4, 28.1 (CH2), 27.2 (CH3), 24.7
4r-H yd r oxy-7r,10r-ep oxy-1,5,11rH ,8âH -gu a ia n -8,12-
olid e [(+)-Zed ola cton e A] (en t-6). To a solution of LDA
prepared from i-Pr2NH (0.2 mL, 1.5 mmol), THF (2.5 mL), and
1.6 M n-BuLi in hexane (0.94 mL, 1,5 mmol) at -78 °C under
argon was added via syringe a solution of compound 19 (11
mg, 0.041 mmol) in THF (0.3 mL). The mixture was stirred at
-78 °C for 1 h, and then the reaction was quenched with an
aqueous solution of NH4Cl, the system was opened, and the
temperature allowed to rise to room temperature. The usual
workup and chromatrography (1:9 hexane/EtOAc) afforded 5
mg (45%) of starting material 19 and 5.5 mg (50%) of
(CH2), 22.0, 15.5, 7.9 (CH3). Data for compound 16: oil; [R]24
D
+14.5 (c 1.10); IR (NaCl) 1744, 1736 cm-1; MS m/e 307 (M+
+
1, 6), 248 (39), 247 (100), 246 (39), 229 (39); HRMS 307.1549,
1
C
17H23O5 (M+ + 1) required 307.1545; H NMR (200 MHz) δ
4.84 (1H, br dd, J ) 6.6, 9.7), 3.35-3.22 (1H, m), 3.28 (1H, s),
2.88-2.76 (2H, m), 2.47-2.36 (2H, m), 2.10-1.95 (3H, m), 1.90
(3H, s), 1.80 (3H, br s), 1.47 (3H, s), 1.43 (3H, s); 13C NMR
(200 MHz) δ 174.0, 169.9, 160.8, 122.9, 84.4 (C), 79.3 (CH),
68.9 (C), 64.4, 47.6, 44.3 (CH), 42.9, 29.6, 23.8 (CH2), 22.9, 22.5,
16.2, 8.1 (CH3).
compound ent-6: oil; [R]23 +18.0 (c 0.30, MeOH); IR (NaCl)
D
3417, 1736, 1677 cm-1; MS m/e 267 (M+ + 1, 100), 249 (56),
231 (89), 177 (35), 107 (22); HRMS 267.1589, C15H23O4 (M+
+
1
1) required 267.1596; H NMR (400 MHz, CDCl3) δ 4.91 (1H,
br d, J ) 5.0), 2.72 (1H, dd, J ) 3.6, 12.4), 2.73-2.69 (1H, m),
2.32 (1H, dd, J ) 6.8, 16.0), 2.08 (1H, dd, J ) 2.8, 16.0), 1.98
(1H, ddd, J ) 3.6, 5.6, 13.6), 1.91-1.75 (3H, m), 1.82 (3H, d,
J ) 2.0), 1.75-1.69 (1H, m), 1.60 (2H, br s), 1.54-1.45 (1H,
m), 1.39 (3H, s), 1.23 (3H, s); 1H NMR (400 MHz, pyridine-d5)
δ 6.01 (1H, br d, J ) 8.0), 5.12 (1H, ddd, J ) 2.0, 3.1, 7.2),
5.10 (1H, br s), 3.27 (1H, dt, J ) 8.0, 11.2), 2.78 (1H, dd, J )
3.7, 12.4), 2.52-2.40 (1H, m), 2.44 (1H, dd, J ) 7.2, 15.6), 2.18
(1H, dd, J ) 3.1, 15.6), 2.08-1.98 (2H, m), 1.97 (1H, dd, J )
12.4, 13.2), 1.92-1.88 (1H, m), 1.83 (3H, d, J ) 2.0), 1.68-
1.56 (1H, m), 1.52 (3H, s), 1.33 (3H, s); 13C NMR (250 MHz,
CDCl3) δ 175.0, 160.7, 122.9 (C), 81.7 (CH), 80.5, 73.5 (C), 51.6,
51.1 (CH), 37.5, 36.3 (CH2), 32.0, 25.1 (CH3), 24.9, 24.6 (CH2),
8.1 (CH3); 13C NMR (400 MHz, pyridine-d5) δ 175.6, 162.5,
122.0 (C), 81.3 (CH), 80.7, 72.5 (C), 52.9, 51.5 (CH), 38.5, 37.9
(CH2), 31.6 (CH3), 25.6 (CH3), 25.3 (CH2), 25.2, 8.2 (CH3).
10r-Acetoxy-3â-p h en ylselen yl-4r-h yd r oxy-1,5rH,8âH-
gu a i-7(11)-en -8,12-olid e (17). NaBH4 (39 mg, 1.03 mmol) was
added in portions to a solution of PheSeSePh (290 mg, 0.86
mmol) in DMF (2.3 mL) under Ar at room temperature for 2
h. To this solution were added via syringe AcOH (24 µL, 0.42
mmol), compound 15 (77 mg, 0.25 mmol) in DMF (4 mL), and
Ti(i-PrO)4 (150 µL, 0.48 mmol), and the mixture was stirred
for 22 h. After this time, the reaction was quenched with water
and extracted with EtOAc. Usual workup and chromatography
(5:5 hexane/EtOAc) afforded 6 mg (8%) of 15 and hydroxy
selenide 17 (99 mg, 87%): solid; mp 154-155 °C (hexanes-
EtOAc); IR (KBr) 3550-3350, 1735, 1684 cm-1; 1H NMR (200
MHz) δ 7.58-7.55 (2H, m), 7.30-7.23 (3H, m), 4.85 (1H, br t,
J ) 5.2), 3.54 (1H, dd, J ) 7.7, 10.7), 3.22 (1H, dt, J ) 8.1,
12.2), 2.80 (1H, dd, J ) 3.9, 11.7), 2.60 (1H, dd, J ) 6.6, 14.5),
2.40-2.20 (4H, m), 1.84 (3H, s), 1.85-1.95 (1H m), 1.80 (3H,
d, J ) 1.5), 1.50 (3H, s), 1.38 (3H, s); 13C NMR (200 MHz) δ
174.6, 169.9, 160.6 (C), 133.3 (CH), 129.8 (C), 129.1, 127.3
(CH), 123.0, 83.5, 81.9 (C), 79.4, 52.7, 49.0, 45.7 (CH), 39.0,
35.0 (CH2), 24.4 (CH3), 24.2 (CH2), 22.5, 22.2, 7.9 (CH3).
10r-Acetoxy-4r-h yd r oxy-1,5rH,8âH-gu a i-7(11)-en -8,12-
olid e (18). Hydroxy selenide 17 (42 mg, 0.09 mmol) in EtOH
(0.7 mL) was treated with deactivated ethanolic W-2 Raney
Ni35 (0.9 mL, ca. 0.5 g) at room temperature. After 30 min the
mixture was filtered through a short plug of silica gel (EtOAc)
to yield compound 18 (28 mg, 99%): solid, mp 165-167 °C
Ack n ow led gm en t. Financial support from Euro-
pean Commission (FAIR CT96-1781) and from Direcio´n
General de Investigacio´n Cient´ıfica y Te´cnica (DGICYT,
Grant PB 94-0985) is gratefully acknowledged. One of
us (V.B.) is specially thankful to Conselleria de Cultura,
Educacio´ i Ciencia (Generalitat Valenciana) for a grant.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 4-10, 12, and 15-19 .This material is
(35) (a) Mozingo, R. Organic Syntheses; Wiley & Sons: New York,
1955; Collect. Vol III, p 181. (b) W-2 Raney Ni was deactivated by
heating the ethanolic suspension at 60 °C for 3-4 days.
J O000927H