A. Srikrishna, S. S. V. Ramasastry / Tetrahedron Letters 46 (2005) 7373–7376
7375
in benzene at reflux, using a Dean–Stark water trap.
Reaction of the resulting bisketal 12 with lithium alumi-
num hydride (LAH) in ether at 0 °C furnished alcohol
13 in 90% yield. Treatment of the alcohol 13 with so-
dium hydride in the presence of 20 mol % of imidazole,
followed by addition of dry carbon disulfide and methyl
iodide, furnished the dithiocarbonate 14 in 88% yield.
Thermal reaction of 14 with tributyltin hydride in the
presence of 10 mol % of azobisisobutyronitrile (AIBN)
in refluxing benzene furnished the bisketal 15 in 85%
yield. Treatment of the bisketal 15 with aqueous hydro-
15th carbon of solavetivone 1 was introduced via conju-
gate addition to the dienone 16. Generation of the
kinetic TMS enol ether of the enone 5 with lithium
hexamethyldisilazide (LHMDS), trimethylsilyl chloride
and triethylamine, followed by oxidative desilylation15
with palladium acetate in acetonitrile generated the
cross-conjugated dienone, nor-anhydro-b-rotunol 16,
in 90% yield. Treatment of the dienone 16 with lithium
dimethylcuprate in dry ether at ꢁ30 °C furnished, as ex-
pected, a 1:1 epimeric mixture of solavetivone 1 and 10-
epi-solavetivone 17 in 93% yield. On the other hand,
reaction of the dienone 16 with lithium dimethylcuprate,
trimethylsilyl chloride and triethylamine, followed by
oxidative desilylation15 of the resultant TMS dienolate
chloric acid in THF at room temperature for 1 h, then
25
furnished the diketone 6, ½aꢀD ꢁ24.2 (c 1.24, CHCl3),
in 97% yield. After exploring various conditions, piper-
idine and acetic acid was found to be the best reagent
combination for the regioselective intramolecular aldol
condensation of dione 6. Thus, refluxing a benzene solu-
tion of the diketone 6 with piperidine and acetic acid for
1 h using a Dean–Stark water trap furnished the key
intermediate, nor-solavetivone 5 in 87% yield. The
with palladium acetate in acetonitrile generated anhy-
24
dro-b-rotunol 2, ½aꢀD +53.3 (c 1.52, EtOH) [Lit.1
+52.0 (c 0.7, EtOH)], in 90% yield, which exhibited
spectral data identical to those of an authentic
sample.1,10
Next, syntheses of solanascone 3 and dehydrosolanas-
cone 4 were investigated. Since the introduction of the
C-10 methyl group in solavetivone 1 resulted in an epi-
meric mixture (16 ! 1+17), it was decided to introduce
the secondary methyl group after construction of the
tetracyclic carbon framework using the shape of the
tetracyclic framework to direct addition of the methyl
group from the exo face. Accordingly, photochemical
irradiation of a degassed methanolic solution of the en-
one 5 with a 450 W Hanovia medium pressure mercury
vapor lamp for 2 h furnished the tetracyclic ketone 18
in 80% yield. Generation of the TMS enol ether of ke-
tone 18 with LHMDS, trimethylsilyl chloride and trieth-
ylamine in THF at ꢁ70 °C, followed by treatment with
palladium acetate in acetonitrile at room temperature
furnished the enone 19 in quantitative yield. Addition
of lithium dimethylcuprate to dehydro-nor-solanascone
19 at ꢁ70 °C, followed by stirring at ꢁ30 °C for 1.5 h
Yields refer to isolated and chromatographically pure compounds.
All the compounds exhibited spectral data (IR, 1H and 13C NMR,
and mass) consistent with their structures. Selected spectral data for
(ꢁ)-(2R,5R)-2-isopropenyl-6-methylspiro[4.5]dec-6-en-8-one 5:
25
½aꢀD ꢁ162.5 (c 0.24, CHCl3). IR (neat): mmax/cmꢁ1 1673, 1614, 886.
1H NMR (300 MHz, CDCl3+CCl4): d 5.75 (1H, s), 4.73 (1H, s), 4.71
(1H, s), 2.70–2.55 (1H, m), 2.45–2.37 (2H, m), 2.05–1.92 (4H, m), 1.95
(3H, s), 1.87 (1H, dd, J 12.9 and 6.6 Hz), 1.75 (3H, s), 1.67–1.54 (3H,
m). 13C NMR (75 MHz, CDCl3+CCl4): d 198.1 (C), 166.6 (C), 146.9
(C), 127.0 (CH), 109.3 (CH2), 46.4 (C), 46.0 (CH2), 40.0 (CH2), 36.4
(CH2), 36.0 (CH2), 34.7 (CH2), 31.4 (CH2), 21.3 (CH3), 20.1 (CH3).
Mass: 204 (M+, 9), 189 (8), 176 (11), 161 (31), 148 (30), 147 (41), 133
(44), 123 (46), 121 (40), 108 (52), 105 (47), 91 (73). HRMS: m/z Calcd
for C14H21O (M+1): 205.1592. Found: 205.1592. For (+)-(2R,5S)-2-
25
isopropenyl-6-methylspiro-[4.5]dec-6,9-dien-8-one 16: ½aꢀD +31.8 (c
0.22, CHCl3). IR (neat): mmax/cmꢁ1 1665, 1625, 881. 1H NMR
(300 MHz, CDCl3+CCl4): d 6.94 (1H, d, J 9.9 Hz), 6.10 (1H, dd, J 9.9
and 1.8 Hz), 6.07 (1H, s), 4.76 (2H, br s), 2.90–2.74 (1H, m), 2.20–1.70
(6H, m), 2.03 (3H, s), 1.78 (3H, s). 13C NMR (75 MHz,
CDCl3+CCl4): d 185.7 (C), 162.0 (C), 155.2 (CH), 146.0 (C), 127.8
(CH), 125.0 (CH), 110.0 (CH2), 50.0 (C), 46.8 (CH), 41.8 (CH2), 36.0
(CH2), 32.2 (CH2), 21.4 (CH3), 19.7 (CH3). Mass: 202 (M+, 8), 187
(10), 174 (11), 159 (35), 146 (38), 131 (32), 121 (71), 105 (20), 91 (100).
HRMS: m/z Calcd for C14H19O (M+H): 203.1436. Found: 203.1442.
For (+)-(1R,4R,5S,7S,11S)-5,11-dimethyltetracyclo[5.3.1.11,4.05,11]-
furnished solanascone 3 in 67% yield. The synthetic
24
sample exhibited optical rotation {½aꢀD +20.5 (c 0.78,
1
CHCl3) [lit.3 +20.3 (c 1.97, CDCl3)]} and H and 13C
NMR spectral data identical to those of the natural
compound. On the other hand, reaction of enone 19
with lithium dimethylcuprate, trimethylsilyl chloride,
and triethylamine, followed by treatment of the resul-
25
dodecan-8-one 18: ½aꢀD +24.1 (c 0.58, CHCl3). IR (neat): mmax/cmꢁ1
1707. 1H NMR (300 MHz, CDCl3+CCl4): d 2.43 (1H, dd, J 12.0 and
6.3 Hz), 2.40–2.30 (1H, m), 2.32 (1H, d, J 7.5 Hz), 2.20–1.85 (5H, m),
1.74 (1H, br s), 1.55–1.35 (3H, m), 1.20–1.06 (2H, m), 1.13 (3H, s),
1.05 (3H, s). 13C NMR (75 MHz, CDCl3+CCl4): d 217.5 (C), 48.1
(CH), 47.72 (C), 47.69 (C), 44.7 (CH, C-4), 44.5 (C), 39.5 (CH2), 36.8
(CH2), 35.7 (CH2), 29.1 (CH2), 26.2 (CH2), 23.7 (CH2), 17.4
(CH3), 16.0 (CH3). Mass: 189 (M+ꢁCH3, 1), 161 (4), 142 (5), 129
tant TMS enol ether with palladium acetate in acetoni-
25
trile furnished dehydrosolanascone 4, ½aꢀD +117.8 (c
0.28, CHCl3), in 93% yield, which exhibited the 1H
and 13C NMR spectral data identical to those of a nat-
ural sample.4
In conclusion, we have accomplished enantiospecific
total syntheses of the phytoalexins solavetivone 1 and
epi-solavetivones 17, anhydro-b-rotunol 2, solanascone
3, and dehydrosolanascone 4 in a highly regio- and
stereoselective manner from (R)-carvone 8. In the pres-
ent synthesis, anhydro-b-rotunol 2 was obtained in thir-
teen steps in 15% overall yield, and solanascone 3 and
dehydrosolanascone 4 were obtained in 14 steps in
10% and 14% overall yield, respectively. Investigations
on the synthesis of higher oxygenated solanascones
and solavetivones for evaluating their biological profile
are in progress.
(11), 125 (5), 111 (5), 87 (100). HRMS: m/z Calcd for C14H21
O
(M+1): 205.1592. Found: 205.1596. For (+)-(1S,4R,5S,7S,11S)-5,11-
25
dimethyltetracyclo[5.3.1.11,4.05,11]dodec-9-en-8-one 19: ½aꢀD +102.2
(c 0.46, CHCl3). IR (neat): mmax/cmꢁ1 1671. 1H NMR (300 MHz,
CDCl3+CCl4): d 7.02 (1H, d, J 9.9 Hz), 5.98 (1H, d, J 9.9 Hz),
2.57 (1H, dd, J 12.3 and 6.3 Hz), 2.12 (1H, t, J 12.6 Hz), 2.05 (1H,
dd, J 12.6 and 6.3 Hz), 1.80–1.32 (7H, m), 1.12 (3H, s), 1.01 (3H, s).
13C NMR (75 MHz, CDCl3+CCl4): d 200.9 (C), 152.6 (CH),
131.0 (CH), 50.2 (C), 49.0 (CH2), 47.6 (C), 46.9 (CH), 44.1 (C),
43.5 (CH), 36.4 (CH2), 27.8 (CH2), 24.1 (CH2), 17.2 (2C, CH3). Mass:
174 (M+ꢁCO, 2), 173 (15), 157 (14), 149 (40), 105 (21), 97 (32), 91
(34). HRMS: m/z Calcd for C14H19O (M+1): 203.1436. Found:
203.1442.