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A. Srikrishna, K. Anebousel6y / Tetrahedron Letters 43 (2002) 2769–2771
Scheme 1.
Scheme 2. Reagents, conditions and yields: (a) Ref. 3; (b) LAH, Et2O, −70°C, 3 h, 90%; (c) MeC(OEt)3, EtCOOH, sealed tube,
180°C, 72 h, 35%; (d) 20% KOH in MeOH, reflux, 24 h, 88%; (e) i. (COCl)2, C6H6, rt, 3 h, ii. CH2N2, Et2O, 0°C–rt, 3 h; (f) Cu,
anhydrous CuSO4, cyclohexane, W-lamp, reflux, 5 h; 56% (from acid 13b); (g) KH, THF, 0°C, 2 h, MeI, rt, 22 h, 75%; (h) Li,
liq. NH3, THF, 10 min, 75% (for 17), 64% (for 21); (i) O3/O2, CH2Cl2–MeOH (3:1), −70°C; Ac2O, NEt3, DMAP, C6H6, reflux,
6 h, 50% (for 18), 64% (for 19+20); (j) Ac2O, py, DMAP, rt, 24 h, 84%; (k) Ph3P+CH3 I−, K+ tAmO−, C6H6, rt, 3 h, 72%; (l) LAH,
Et2O, 0°C–rt, 3 h, 90%.
NMR (75 MHz, CDCl3+CCl4): l 215.8 (C), 170.0 (C), 76.0 (CH), 53.1
the diazo ketone 14 into the tricyclic ketone 15. Regio-
(CH), 43.5 (C), 40.0 (CH), 39.1 (C), 33.8 (C), 28.1 (CH), 24.6 (CH3),
and stereoselective alkylation of the tricyclic ketone‡ 15
24.4 (CH2), 22.1 (CH3), 21.8 (CH3), 21.4 (CH3), 15.9 (CH3), 15.7
(CH3). For the keto−acetate 21: Mp 100–102°C. [h]2D4 +16.7 (c 1.56,
‡ All the compounds exhibited spectral data consistent with their
structures. Yields refer to isolated and chromatographically pure
compounds. Spectral data for the tricyclic ketone 15: Mp 94–95°C.
[h]D25 +145 (c 1, CHCl3). IR (thin film): wmax/cm−1 1708, 1635, 897.
1H NMR (300 MHz, CDCl3+CCl4): l 4.85 (1H, s), 4.70 (1H, s), 2.25
(1H, dd, J 13.8 and 4.8 Hz), 2.21 (1H, d, J 19.2 Hz), 2.02–1.90 (1H,
m), 1.90 (1H, d, J 19.2 Hz), 1.74 (3H, s), 1.80–1.65 (1H, m), 1.61 (1H,
d, J 9.3 Hz), 1.37 (1H, dt, J 14.2 and 6.3 Hz), 1.32 (3H, s), 1.22 (3H,
s), 1.10 (3H, s), 0.78 (3H, s). 13C NMR (75 MHz, CDCl3+CCl4): l
211.0 (C), 146.6 (C), 113.7 (CH2), 53.8 (CH), 52.8 (CH2), 43.4 (C),
42.6 (CH), 38.1 (C), 35.1 (C), 29.6 (CH), 29.1 (CH3), 24.2 (CH2), 23.5
(CH3), 22.9 (CH3), 22.7 (CH3), 20.4 (CH3). For the compound 16:
[h]D24 +90 (c 1, CHCl3). IR (neat): wmax/cm−1 1716, 1636, 892. 1H NMR
(300 MHz, CDCl3+CCl4): l 4.85 (1H, s), 4.71 (1H, s), 2.28 (1H, dd,
J 14.0 and 5.0 Hz), 2.03 (1H, q, J 7.3 Hz), 2.01–1.90 (1H, m), 1.82–1.64
(1H, m), 1.72 (3H, s), 1.58 (1H, d, J 9.0 Hz), 1.46 (1H, dt, J 14.4 and
6.0 Hz), 1.29 (3H, s), 1.08 (3H, s), 1.06 (3H, s), 0.99 (3H, d, J 7.3
Hz), 0.80 (3H, s). 13C NMR (75 MHz, CDCl3+CCl4): l 213.3 (C),
146.6 (C), 113.5 (CH2), 54.0 (CH), 51.1 (CH), 45.6 (C), 41.3 (CH),
39.2 (C), 33.9 (C), 29.5 (CH), 29.0 (CH3), 24.1 (CH2), 22.5 (2 C, CH3),
21.1 (CH3), 17.1 (CH3), 12.6 (CH3). For the keto-acetate 19: [h]D24
−24.6 (c 1.14, CHCl3). IR (neat): wmax/cm−1 1738, 1715. 1H NMR (300
MHz, CDCl3+CCl4): l 4.64 (1H, dd, J 7.2 and 3.0 Hz), 2.60 (1H, q,
J 7.3 Hz), 2.53 (1H, td, J 16.5 and 7.4 Hz), 1.97 (3H, s), 1.76 (1H,
d, J 16.5 Hz), 1.65 (1H, d, J 10.2 Hz), 1.60–1.40 (1H, m), 1.29 (3H,
CHCl3). IR (thin film): wmax/cm−1 1726. 1H NMR (300 MHz,
CDCl3+CCl4): l 4.78 (1H, br s), 3.17 (1H, q, J 6.7 Hz) 2.24 (1H, d,
J 18.6 Hz), 2.05 (3H, s), 1.98 (1H, d, J 18.6 Hz), 1.95 (1H, td, J 14.4
and 3.0 Hz), 1.78 (1H, dt, J 13.8 and 3.0 Hz), 1.64 (1H, qd, J 14.4
and 3.0 Hz), 1.26 (3H, s), 1.09 (3H, d, J 6.7 Hz), 1.09 (3H, s), 1.06–1.02
(1H, m), 0.96 (3H, s), 0.89 (3H, s). 13C NMR (75 MHz, CDCl3+CCl4):
l 219.8 (C), 169.6 (C), 79.2 (CH), 53.4 (CH2), 50.7 (CH), 47.7 (C),
39.9 (C), 39.5 (C), 31.4 (CH2), 26.2 (CH3), 24.6 (CH3), 23.3 (CH3),
23.0 (CH2), 21.4 (CH3), 14.5 (CH3), 13.0 (CH3). For the thapsenyl
acetate 23: [h]2D1 −8.1 (c 1.36, CHCl3). IR (neat): wmax/cm−1 1740, 1651,
874. 1H NMR (300 MHz, CDCl3+CCl4): l 4.81 (1H, s), 4.77 (1H,
s), 4.70 (1H, s), 3.40–3.25 (1H, m), 2.43 (1H, qd, J 16.0 and 3.0 Hz),
2.05 (3H, s), 1.96 (1H, d, J 16.0 Hz), 1.95–1.75 (3H, m), 1.65–1.54
(1H, m), 1.09 (3H, s), 1.07 (3H, d, J 6.9 Hz), 1.0 (3H, s), 0.94 (3H,
s), 0.79 (3H, s). 13C NMR (75 MHz, CDCl3+CCl4): l 170.0 (C), 156.4
(C), 105.7 (CH2), 79.8 (CH), 49.2 (C), 49.1 (CH2), 43.5 (CH), 42.3
(C), 39.9 (C), 30.4 (CH2), 26.0 (CH3), 24.7 (CH3), 23.3 (CH3), 23.2
(CH2), 21.5 (CH3), 17.9 (CH3), 14.0 (CH3). For thapsenol 24: Mp
105–107°C. [h]2D5 +16.3 (c 0.8, CHCl3). IR (thin film): wmax/cm−1 3478,
1646, 874. 1H NMR (300 MHz, CDCl3+CCl4): l 4.78 (1H, s), 4.73
(1H, s), 3.60–3.45 (2 H, m), 2.42 (1H, qd, J 16.1 and 2.9 Hz), 2.05–1.85
(3H, m), 1.60–1.35 (3H, m), 1.08 (3H, s), 1.06 (3H, s), 1.06 (3H, d,
J 6.9 Hz), 0.90 (3H, s), 0.78 (3H, s). 13C NMR (75 MHz, CDCl3+
CCl4): l 156.8 (C), 105.4 (CH2), 78.4 (CH), 49.4 (CH2), 49.2 (C), 43.6
(CH), 42.5 (C), 40.2 (C), 29.8 (CH2), 26.2 (2 C, CH3 and CH2), 25.0
(CH3), 23.4 (CH3), 18.1 (CH3), 14.2 (CH3).
s), 1.13 (3H, s), 1.09 (3H, d, J 7.0 Hz), 1.08 (3H, s), 0.87 (3H, s). 13
C