that the methyl doublet at 1.24 ppm became a double doublet
Experimental
(J 6.8, 1.5). The optical purity of the first sample was deter-
mined by comparison of the area of two peaks of a doublet
and was ee >95%. A further confirmation of this analytical
data was obtained by GC analysis of the two above mentioned
samples which showed 95.5% ee. Program temperature for the
GC chiral analysis: 70 ЊC 3 min, 3.5 ЊC minϪ1, 140 ЊC 1 min, 8 ЊC
minϪ1, 180 ЊC 20 min; injector 60 ЊC, detector 180 ЊC. Retention
times: (R,R)-MTPA ester 43.4 min, (S,R)-MTPA ester 43.75
min; carrier N2 (0.8 bar).
Optical rotations were measured on a Propol automatic digital
polarimeter, and are given in 10Ϫ1 deg cm2 gϪ1. IR spectra were
recorded on a Perkin-Elmer 2000 FTIR spectrometer. 1H NMR
spectra were recorded in CDCl3 solutions at room temperature
unless otherwise stated, on a Bruker AC-250 spectrometer (250
1
MHz H). The chemical-shift scale is based on internal tetra-
methylsilane. J-Values are given in Hz. Mass spectra were
measured on a FINNIGAN-MAT TSQ 70 spectrometer. TLC
analyses were performed on Merck Kieselgel 60 F254 plates. All
the chromatographic separations were carried out on silica gel
columns. GC analysis was performed on a DANI 86.10 HT
with a FID detector, fitted with a CHROMPACK CHIRASIL
DEX CB column, 25 m × 0.25 mm i.d.
(S)-(؉)-3-(p-Tolyl)butanal 8
(S)-(ϩ)-3-(p-Tolyl)butan-1-ol 7, 800 mg (4.9 mmol) in CH2Cl2
(5 mL) was added in one portion to a solution of pyridinium
chlorochromate (1.57 g, 7.3 mmol) in CH2Cl2 (30 ml) and
stirred at room temperature until no more starting alcohol was
detected by TLC analysis (2 h). The mixture was then diluted
with diethyl ether (80 ml) and filtred on a layer of Celite. The
organic phase was washed with water, dried on Na2SO4 and
concentrated under reduced pressure. Bulb to bulb distillation
of the residue (oven temperature 80 ЊC/0.2 Torr) give 8 as a
colourless oil, in 93% yield (0.75 g, 4.6 mmol); [α]D20 = ϩ39.6
(c 1, CHCl3) (Found: C, 81.51; H, 8.66; C11H14O requires C,
81.43; H, 8.63%); νmax (film)/cmϪ1 2964, 1723 (CO), 1516,
1454, 817; δH 1.30 (3H, d, J 7, ArCHMe), 2.32 (3H, s,
ArMe), 2.55–2.75 (2H, m, CHCH2CHO), 3.17–3.42 (1H, m,
ArCHMe), 7.11 (4H, s, ArH), 9.70 (1H, t, J 2, CHCH2-
CHO); m/z (EI) 162 (Mϩ, 23%), 147 (27), 119 (Mϩ Ϫ CH2CH2-
CHO, 100), 91 (16).
Baker’s yeast reduction of alcohol 6
A 10 l open cylindrical glass vessel equipped with a mechanical
stirrer was charged with tap water (4 l) and glucose (250 g).
Fresh baker’s yeast (1 kg) was added in small pieces to the
stirred mixture and the fermentation allowed to proceed for 2 h.
Resin XAD 1180 (100 g) was added in one portion and the
substrate (20 g, 123 mmol) dissolved in the minimum amount
of ethanol (50 ml) was added dropwise. The vigorous stirring
was continued for 5 days at room temperature, while a slow
stream of air was passed through the mixture. During this time
additional baker’s yeast (250 g) and glucose (100 g) were added
each time after 48, 72 and 96 h since the fermentation started.
The resin was then separated by filtration on a sintered glass
funnel (porosity 0, >160 µm) and the water phase extracted
again with further resin (50 g). The combined resin crops were
extracted with ethyl acetate (4 × 150 ml) and the acetate solu-
tion was washed with brine. The dried organic phase (Na2SO4)
was concentrated under reduced pressure to give an oil (22 g).
The latter was dissolved in CHCl3 and treated with MnO2 (60 g)
stirring the mixture at reflux for 5 h. The residue obtained upon
filtration and evaporation of the CHCl3 phase was purified by
column chromatography using hexane–ethyl acetate (9:1—3:1)
as eluent to give 3-(p-tolyl)but-2-en-1-al (12 g, 75 mmol) and
pure (S)-(ϩ)-3-(p-tolyl)butan-1-ol 7 (4.3 g, 26 mmol) as a pale
yellow oil, 21% yield, ee 95% (the optical purity was determined
as described below). A further purification by bulb to bulb
distillation (oven temperature 110 ЊC/0.5 Torr) afforded 7 as a
colourless oil without significant loss of weight. [α]D20 = ϩ31.6
(c 1, CHCl3), lit.,4 [α]D = ϩ33 (c 1.89, CHCl3) (Found: C, 80.35;
H, 9.77; C11H16O requires C, 80.44; H, 9.74%); νmax (film)/cmϪ1
3336 (OH), 2959, 1515, 1455, 1045, 816; δH 1.25 (3H, d, J 7,
ArCHMe), 1.75–1.88 (2H, m, CHCH2CH2OH), 2.10 (1H, s,
CH2OH), 2.31 (3H, s, ArMe), 2.73–2.92 (1H, m, ArCHMe),
3.42–3.63 (2H, m, CH2CH2OH), 7.09 (4H, s, ArH); m/z (EI)
164 (Mϩ, 47%), 146 (Mϩ Ϫ H2O, 6), 131 (38), 119 (Mϩ Ϫ CH2-
CH2OH, 100), 105 (12), 91 (7).
(S)-(؉)-3-(p-Tolyl)butyl iodide 9
(S)-(ϩ)-3-(p-Tolyl)butan-1-ol 7 (1 g, 6.1 mmol) in CH2Cl2 (5
mL) was treated with tosyl chloride (1.5 g, 7.9 mmol) and pyrid-
ine (0.65 ml, 8 mmol) and stirred at room temperature for 5 h.
The mixture was then diluted with diethyl ether (100 ml),
washed with HCl 5% aq. (50 ml) and dried over Na2SO4. The
solvent was eliminated under reduced pressure and the residue
was treated with NaI (3 g, 20 mmol) in dry acetone (30 ml) at
reflux for 2 h. The reaction mixture was diluted with water (100
ml), extracted with diethyl ether and the organic phase was
washed with a solution (1%, 80 ml) of Na2S2O3. The crude
iodide was purified by chromatography and bulb to bulb distil-
lation (oven temperature 95 ЊC/0.2 Torr) to give 9 as a colour-
less oil (1.1 g, 4 mmol, 65% yield); [α]D20 = ϩ54 (c 2, CHCl3)
(Found: C, 48.30; H, 5.37; I, 46.33; C11H15I requires C, 48.19;
H, 5.47; I, 46.29%); νmax (film)/cmϪ1 2960, 2925, 1514, 1454,
1236, 1171, 816, 699; δH 1.24 (3H, d, J 7, ArCHMe), 2.0–2.15
(2H, m, CHCH2CH2I), 2.32 (3H, s, ArMe), 2.70–3.25 (3H, m,
ArCHMe ϩ CH2CH2I), 7.10 (4H, s, ArH); m/z (EI) 274 (Mϩ,
24%), 127 (9), 119 (100), 91 (17), 77 (5).
(S)-(؉)-Curcumene 1
Determination of the optical purity of 7
The iodide 9 (600 mg, 2.2 mmol) in dry THF (10 ml) was cooled
to Ϫ40 ЊC and treated under nitrogen with CuI (80 mg, 0.4
mmol) and Grignard 10 (3.5 mmol, 1 M solution in THF). The
reaction was allowed to warm to 0 ЊC and stirred at this tem-
perature for 5 h. Work-up with NH4Cl aq., extraction with
diethyl ether and concentration of the dried (Na2SO4) organic
phase gave crude 1. Purification of the latter by chrom-
atography and bulb to bulb distillation (oven temperature
90 ЊC/0.3 Torr) afforded pure (S)-(ϩ)-curcumene as a colour-
less oil (340 mg, 1.7 mmol, 77% yield); [α]D20 = ϩ43 (c 2, CHCl3)
(Found: C, 88.97; H, 10.85; C15H22 requires C, 89.04; H,
10.87%); νmax (film)/cmϪ1 2962, 2923, 2857, 1515, 1516, 1453,
1376, 816; δH 1.21 (3H, d, J 7, ArCHMe), 1.53 (3H, s, CHCMe-
Me), 1.50–1.68 (2H, m, CH2CHC), 1.67 (3H, s, CHCMeMe),
1.80–1.95 (2H, m, CHCH2CH2), 2.32 (3H, s, ArMe), 2.55–2.65
(1H, m, ArCHMe), 5.07 (1H, br t, J 6, CH2CHC), 7.07 (4H, s,
(S)-(ϩ)-3-(p-Tolyl)butan-1-ol 7 (100 mg, 0.6 mmol), in CCl4
(0.5 ml) was treated with (R)-(ϩ)-MTPACl20 [(R)-(ϩ)-α-
methoxy-α-(trifluoromethyl)phenylacetyl chloride] (280 mg, 1.2
mmol) and pyridine (0.5 ml) at room temperature for 24 h. The
mixture was diluted with diethyl ether (80 ml) and washed in
turn with 5% HCl aq. (100 ml) and NaHCO3 sat. (50 ml). The
organic phase was dried, concentrated under reduced pressure
and purified by column chromatography to give the pure (S,R)
ester (205 mg, 95%); δH 1.24 (3H, d, J 6.8, ArCHMe), 1.85–2.04
(2H, m, CHCH2CH2OH), 2.32 (3H, s, ArMe), 2.65–2.83 (1H,
m, ArCHMe), 3.55 (3H, s, OMe), 4.05–4.30 (2H, m,
CH2CH2OMTPA), 6.95–7.14 (4H, m, ArH), 7.35–7.55 (5H, m,
ArH). A sample of racemic 7 was prepared from 5 by hydro-
genation (H2, Pd/C) and LiAlH4 reduction. The (R)-(ϩ)-MTPA
ester of the latter compound had an identical spectrum except
J. Chem. Soc., Perkin Trans. 1, 1999, 279–282
281