November 1998
SYNLETT
1253
reduction of the two carboxylic groups of 8 was performed by treatment
with LiAlH4 and the resulting diol 9 was deoxygenated at the benzylic
position by hydrogenation affording the alcohol C-11 10.12
Transformation of the latter alcohol to the corresponding iodide and the
subsequent coupling13 with the Grignard reagent 11 catalysed by CuI
gave 12,14 allowing the whole bisabolane framework to be constructed.
Hydrolysis of the phenolic methyl ether by treatment with Me3SiCl/
NaI15 gave (S)-(+)-curcuphenol 116 showing the same analytical data
reported in the literature3b. To confirm that the absolute stereochemistry
was unchanged we reduced the corresponding mesylate derivative using
lithium in ammonia4 to give (S)-(+)-curcumene 2.17
and showing the following analytical data: Anal. Calcd for
20
C16
H18O4: C, 70.05; H, 6.56. Found: C, 69.95; H, 6.58. [α]D
=
+14.4° (c 5, CHCl3); 1H NMR (250 MHz, CDCl3) δ 1.26 (d, 3H,
J=6Hz, CHCH3), 1.37 (t, 3H, J=7.5Hz, COOCH2CH3), 2.80-3.10
(m, 2H, furylCH2CH), 3.47-3.53 (m, 1H, CHCH3), 4.35 (q, 2H,
J=7.5Hz, COOCH2CH3), 5.92 (m, 1H, furyl ring), 6.23 (m, 1H,
furyl ring), 7.15-7.35 (2m, 2H, 1H furyl ring + 1H aromatic ring),
7.55 (m, 2H, aromatic ring); EI-MS m/z 275 (M+ +1), 274 (M+),
239, 193, 165, 81; FT-IR (nujol): (cm-1) 733, 768, 1230, 1295,
1425, 1587, 1714, 2980, 3416.
12) The alcohol 10 shows the following analytical data: Anal. Calcd
20
Thus, the synthetic method that we proposed did not produce
racemization. Moreover, the starting materials and reagents are
inexpensive and the overall yield is good.
for C12H18O2: C, 74.18; H, 9.26. Found: C, 74.33; H, 9.20. [α]D
1
= +17.8° (c 4.5, CHCl3); H NMR (250 MHz, CDCl3) δ 1.25 (d,
3H, J=6.5Hz, CHCH3), 1.55-1.72 (m, 1H, CH2CH2CH), 1.80-
1.98 (m, 1H, CH2CH2CH), 2.20 (s, 1H, CH2OH), 2.33 (s, 3H,
ArMe), 3.27-3.45 (m, 2H, CH2CH2OH), 3.45-3.58 (m, 1H,
CHCH3), 3.82 (s, 3H, OMe), 6.69 (s, 1H, aromatic ring), 6.77 (d,
1H, J=8Hz, aromatic ring), 7.08 (d, 1H, J=8Hz, aromatic ring); EI-
MS m/z 194 (M+), 161, 149, 119, 91; FT-IR (nujol): (cm-1) 812,
1042, 1259, 1462, 1612, 2959, 3376.
The present route may be applicable not only to curcuphenol, but also to
other members of the bisabolane family. In effect, alcohol 10 can be a
useful chiral precursor for the synthesis of natural sesquiterpene
phenols18 which show the same absolute configuration at the benzylic
centre.
References and Notes
13) Deguini-Boumechal, F.; Linstrumelle, G. Tetrahedron Lett., 1976,
36, 3225.
1)
a) ApSimon, J.; ‘The Total Synthesis of Natural Products’, vol. 5,
Wiley and Sons, 1983, p. 35.
14) The alcohol 10 in CH2Cl2 (15 mmoles, 0.3M solution) was treated
with tosyl chloride (20 mmoles) and pyridine (30 mmoles) and
stirred at room temperature until no more starting alcohol was
detected by TLC analysis (4h). The mixture was then washed with
an excess of HCl 5% aq., and extracted with CH2Cl2. The organic
phase was concentrated under reduced pressure and the residue
was treated with NaI (150 mmoles, 0.2M in dry acetone) at reflux
for 3h. The reaction mixture was diluted with water, extracted
with diethyl ether and the organic phase was washed with a
solution of Na2S2O3 (1%). The crude iodide was purified by
chromatography and then dissolved in dry THF. The obtained
solution (0.5M) was cooled to –40°C and treated under nitrogen
with CuI (3 mmoles) and Grignard 11 (23 mmoles). The reaction
was allowed to warm to 0°C and stirred at this temperature for 6h.
Work-up with NH4Cl aq., extraction with diethyl ether and
purification of the crude product by chromatography on a silica
gel column eluting with hexane-ethyl acetate (95:5) gave pure 12
in 61% overall yield and showing the following analytical data:
Anal. Calcd for C16H24O: C, 82.70; H, 10.33. Found: C, 82.55; H,
2)
a) Takano, S.; Goto, E.; Ogasawara, K. Tetrahedron Lett., 1982,
23, 5567. b) Asaoka, M.; Shima, K.; Takei, H. Tetrahedron Lett.,
1987, 28, 5669. c) Takano, S.; Yanase, M.; Sugihara, T.;
Ogasawara, K. J. Chem. Soc., Chem. Commun., 1988, 1538.
3)
a) Fusetani, N.; Sugano, M.; Matsunaga, S.; Hashimoto, K.
Experientia, 1987, 43, 1234. b) Wright, A.E.; Pomponi, S.A.;
McConnell, O.J.; Kohmoto, S.; McCarthy, P.J. J. Nat. Prod.,
1987, 50, 976.
4)
5)
McEnroe, F.J.; Fenical, W. Tetrahedron, 1978, 34, 1661.
Ono, M.; Ogura, Y.; Hatogai, K.; Akita, H. Tetrahedron:
Asymmetry, 1995, 6, 1829.
6)
7)
Ghisalberti, E.L.; Jefferies, P.R.; Stuart, A.D. Austr. J. Chem.,
1979, 32, 1627.
a) Brenna, E.; Fuganti, C.; Perozzo, V.; Serra, S. Tetrahedron,
1997, 53, 15029. b) Brenna, E.; Fuganti, C.; Serra, S. J. Chem.
Soc., Perkin Trans. 1, 1998, 901. c) Brenna, E.; Fuganti, C.; Serra,
S. Synlett, 1998, 365.
10.26. [α]D = +1.5° (c 4.5, CHCl3); 1H NMR (250 MHz,
20
8)
9)
Fuganti, C.; Grasselli, P. J. Chem. Soc., Chem. Commun., 1982,
205; Fuganti, C.; Grasselli, P.; Servi, S.; Högberg, H. E., J. Chem.
Soc., Perkin Trans.1, 1988, 3061
CDCl3) δ 1.17 (d, 3H, J=7Hz, CHCH3), 1.40-1.70 (m, 2H,
C=CHCH2), 1.53 (s, 3H, MeCMe), 1.68 (s, 3H, MeCMe), 1.80-
2.05 (m, 2H, CH2CH2CH), 2.33 (s, 3H, ArMe), 2.98-3.20 (m, 1H,
CHCH3), 3.80 (s, 3H, OMe), 5.11 (bt, 1H, C=CHCH2), 6.67 (s,
1H, aromatic ring), 6.73 (d, 1H, J=7.5Hz, aromatic ring), 7.04 (d,
1H, J=7.5H, aromatic ring); EI-MS m/z 232 (M+), 217 (M+-Me),
175, 162, 149, 135, 119, 105, 91, 41; FT-IR (nujol): (cm-1) 811,
1045, 1260, 1462, 1505, 1580, 1612, 2858.
a) Parikh, J.R.; Doering, W.E. J. Am. Chem. Soc., 1967, 89, 5505.
b) Evans, D.A.; Bartroli, J. Tetrahedron Lett., 1982, 23, 807.
10) Hudson, R.F.; Chopard, P.A. Helv. Chim. Acta, 1963, 46, 2178.
11) Ethyl chloroformate (50 mmoles) was added in one portion to a
THF solution of acid 6 (20 mmoles, 0.2 M) and then Et3N (60
mmoles) was added keeping the temperature under 20°C. The
reaction mixture was stirred for 20 min. at room temperature, then
treated with a excess of HCl 5% aq., and extracted with diethyl
ether. The organic phase was concentrated under reduced pressure
to give a residue which was a carboxyethyl derivative of phenol 7.
The latter was treated with ethanolic NaOH (50 mmoles) at room
temperature for 10 min., diluted with an excess of HCl 5% and
then extracted with ethyl acetate. The organic phase was dried
over sodium sulfate and concentrated under reduced pressure. The
residue was chromatographed on a silica gel column eluting with
hexane-ethyl acetate (5:1 – 2:1) to give the phenol 7 in 90% yield
15) Olah, G. A.; Narang, S. C.; Balaram Gupta, B. G.; Malhotra, R. J.
Org. Chem., 1979, 44, 1247.
16) To a stirred solution of the ether 12 (10 mmoles) and NaI (12
mmoles) in dry CH3CN (40 ml) under nitrogen was added
ClSiMe3 (12 mmoles). The mixture was heated at reflux for 2 h,
then quenched with water and extracted with diethyl ether. The
organic layer was washed with a solution of Na2S2O3 (1%), dried
over Na2SO4 and concentrated under reduced pressure. The
residue was chromatographed on a silica gel column eluting with
hexane-ethyl acetate (95:5 – 9:1) to give curcuphenol 1 in 81%