A. Abate et al. / Tetrahedron: Asymmetry 13 (2002) 899–904
903
4.11. 3-(3-Isopropylphenyl)but-2-enoic acid ethyl ester
12
32°C. The mixture was then treated with a solution of
derivative 9 (9.0 g, 0.048 mol) in ethanol (10 mL). After
48 h at rt Celite (1 kg) was added, and the reaction
mixture filtered, washing the Celite pad with ethyl
acetate. The filtrate was adjusted to pH 4 with aqueous
HCl (2N), and extracted with ethyl acetate. The organic
layer was dried (Na2SO4) and concentrated under
reduced pressure. The residue was chromatographed,
eluting with hexane/ethyl acetate 8:2. An alcoholic frac-
tion was recovered (5.52 g) with the following composi-
tion (GC/MS): 2 (49%), (Z)-13 (21%), (E)-13 (30%). To
purify alcohol 2 from allylic alcohols, this fraction was
dissolved in CH2Cl2 (30 mL) and treated with man-
ganese(IV) oxide. The reaction mixture was heated
under reflux for 8 h, filtered, and the filtrate was
concentrated under reduced pressure. The residue was
chromatographed to remove the unsaturated aldehyde
from the unreacted alcohol (+)-2. Derivative (+)-2 was
thus recovered in pure form (1.95 g, 21%): [h]2D0=+16.6
A solution of compound 10 (21.0 g, 0.130 mol) and
(triphenyl-l5-phosphanylidene)–acetic acid ethyl ester
(68.4 g, 0.195 mol) in toluene (100 mL) was heated
under reflux for 2 h. After the usual work-up, the
residue was chromatographed eluting with hexane/ethyl
acetate 8:2, to afford ester derivative 12 (17.8 g, 69%):
(E)/(Z)=10/1 (1H NMR, lCHꢀC (Z)-12 5.93, d, J=1.15
1
Hz); H NMR major diastereoisomer: l 7.45–7.00 (4H,
m, aromatic hydrogens), 6.14 (1H, q, J=1.15, CHꢀC),
4.22 (2H, q, J=6.9, COOCH2), 2.97 (1H, m,
(CH3)2CH), 2.59 (3H, d, J=1.15, CH3Cꢀ), 1.32 (3H, t,
J=6.9, COOCH2CH3), 1.27 (6H, d, J=6.6, (CH3)2CH);
GC/MS: (i) (E)-12 tR=21.88 min, m/z: 232 (M+, 81),
217 (16), 187 (30), 171 (50), 144 (100); (ii) (Z)-12
tR=19.96 min, m/z: 232 (M+, 75), 217 (15), 187 (31),
171 (50), 144 (100).
1
(c 1.25, CHCl3); e.e.=97% (chiral HPLC); H NMR: l
4.12. 3-(3-Isopropylphenyl)but-2-enol 13
7.30–7.00 (4H, m, aromatic hydrogens), 3.57 (2H, m,
CH2OH), 2.87 (2H, m, (CH3)2CH+CH3CH), 1.85 (2H,
q, J=6.5, CH2CH2OH), 1.27 (3H, d, J=6.9, CH3CH),
1.25 (6H, d, J=7.0, (CH3)2CH); GC/MS: tR=17.63
min; m/z: 192 (M+, 54), 174 (4), 147 (92), 131 (63), 105
(100).
To a solution of 12 (17.0 g, 0.073 mol) in toluene (100
mL) a solution of Red-Al (3.5 M, 27.1 mL, 0.095 mol)
was added dropwise at 0°C. The reaction mixture was
stirred at rt for 2 h, poured into ice, quenched with a
5% HCl solution, and extracted with ethyl acetate. The
organic phase was dried (Na2SO4), concentrated under
reduced pressure. The residue was chromatographed
eluting with hexane/ethyl acetate 8:2, to give derivative
13 (10.4 g, 75%): (E)/(Z)=10/1 (1H NMR, lCHꢀC (Z)-
13=5.69, tq, J=7.1, 1.15 Hz); 1H NMR major
diastereoisomer: l 7.45–7.00 (4H, m, aromatic hydro-
gens), 5.97 (1H, tq, J=6.7, 1.15, CHꢀC), 4.35 (2H, d,
J=6.7, CH2OH), 2.90 (1H, m, (CH3)2CH), 2.08 (3H, d,
J=1.15, CH3Cꢀ), 1.26 (6H, d, J=6.9, (CH3)2CH); GC/
MS: (i) (E)-13 tR=20.34 min, m/z: 190 (M+, 38), 175
(15), 157 (7), 147 (100); (ii) (Z)-13 tR=17.98 min, m/z:
190 (M+, 23), 175 (9), 157 (4), 147 (100).
4.15. (+)-3-(3-Isopropylphenyl)but-2-anal (+)-1
A solution of derivative (+)-2 (1.80 g, 9.4 mmol) in
CH2Cl2 (5 mL) was added to a solution of pyridinium
chlorochromate (4.31 g, 0.020 mol) in CH2Cl2 (10 mL).
The reaction was stirred at rt for 2 h. After the stan-
dard work up, the residue was chromatographed elut-
ing with hexane/ethyl acetate 9:1, to afford, after
bulb-to-bulb distillation, derivative (+)-1 (1.09 g, 61%)
in pure form: [h]D20=+27.9 (c 1.26, CHCl3).
Acknowledgements
4.13. 3-(3-Isopropylphenyl)but-2-enal 9
A mixture of allylic alcohol 13 (10.0 g, 0.053 mol) and
manganese(IV) oxide (1.5 equiv.) in methylene chloride
(50 mL) was heated under reflux for 8 h. The mixture
was filtered and the filtrate was concentrated under
reduced pressure. The residue was chromatographed
eluting with hexane/ethyl acetate 8:2, to recover alde-
hyde 9 (8.91 g, 90%): (E)/(Z) 5:1 (1H NMR, (Z)-9 l
CHO=9.48, d, J=8.1; lCHꢀC=6.14, dq, J=8.1, 1.15;
lMeCꢀC=2.32, d, J=1.15). 1H NMR major
diastereoisomer: l 10.19 (1H, d, J=7.7, CHO), 7.45–
7.00 (4H, m, aromatic hydrogens), 6.41 (1H, dq, J=7.7,
1.15, CHꢀC), 2.95 (1H, m, (CH3)2CH), 2.58 (3H, d,
J=1.15, CH3Cꢀ), 1.27 (6H, d, J=6.9, (CH3)2CH); GC/
MS: (i) (E)-9 tR=20.11 min, m/z: 188 (M+, 2), 187 (7),
173 (5), 145 (100); (ii) (Z)-9 tR=18.48 min, m/z: 188
(M+, 2), 187 (7), 173 (5), 145 (100).
COFIN-Murst is acknowledged for financial support.
The authors would like to thank Dr. Philip Kraft, Mrs.
Caroline Denis and Mr. J. J. Rouge (Givaudan Du¨ben-
dorf AG, Fragrance Research) for the olfactory
descriptions of Florhydral® samples.
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4.14. (+)-3-(3-Isopropylphenyl)but-2-anol (+)-2
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A suspension of baker’s yeast (1.5 kg) and
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D-glucose