M. Kawasaki et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 27–33
31
chromatographed {silica gel, hexane/ethyl acetate = 2:1 (v/v)} to
The organic phase was washed with a saturated sodium chloride
solution, and then dried over Na SO . After removal of the sol-
give (RS)-5 (0.051 g, 42%) and 6 (0.050 g, 35%) as colorless oils.
2
4
1
(
RS)-5: H NMR: 7.16 (2H, d, J = 8.0), 7.10 (2H, d, J = 8.0), 4.19
vents, the residue was chromatographed {silica gel, hexane/ethyl
acetate = 2:1 (v/v)} to give (S)-8 as a colorless oil (0.669 g, 92%).
The ee of (S)-8 was determined with HPLC {CHIRALPACK AS-H,
(
1H, dd, J = 4.8, J = 11.2), 4.08 (1H, dd, J = 6.4, J = 11.2), 3.61 (1H, dd,
J = 4.4, J = 11.2), 3.51 (1H, dd, J = 6.4, J = 11.2), 2.88 (1H, septet, J = 6.9),
.65 (1H, dd, J = 7.6, J = 14.0), 2.59 (1H, dd, J = 7.6, J = 14.0), 2.07–2.16
1H, m), 2.09 (3H, s), 1.24 (6H, d, J = 6.8); 13C NMR: 171.72, 146.84,
1
2
(
hexane/2-propanol = 50:1 (v/v)} and found to be >99%; H NMR:
7.14 (2H, d, J = 8.0), 7.09 (2H, d, J = 8.4), 3.53 (1H, dd, J = 5.8, J = 10.6),
3.46 (1H, dd, J = 6.2, J = 10.6), 2.88 (1H, septet, J = 6.9), 2.70 (1H, dd,
J = 6.4, J = 13.6), 2.40 (1H, dd, J = 8.0, J = 13.6), 1.87–1.99 (1H, m),
1
2
36.56, 128.95, 126.54, 64.07, 62.18, 42.48, 33.89, 33.70, 24.03,
−1
+
0.91; IR (neat): 3448, 1739, 1039 cm ; MS (m/z) 250 (M ); HRMS
+
13
calcd for C15H22O3 (M ), 250.1569. Found: 250.1568.
1.24 (6H, d, J = 6.8), 0.92 (3H, d, J = 6.8); C NMR: 146.40, 137.87,
1
6:
H NMR: 7.15 (2H, d, J = 8.0), 7.07 (2H, d, J = 8.0), 4.08 (2H,
129.03, 126.29, 67.75, 39.32, 37.80, 33.68, 24.06, 16.57; IR (neat):
−
1
+
+
dd, J = 5.2, J = 10.8), 4.02 (2H, dd, J = 6.4, J = 11.2), 2.87 (1H, septet,
J = 6.9), 2.66 (2H, d, J = 7.6), 2.27–2.36 (1H, m), 2.06 (6H, s), 1.23
3339, 1035 cm ; MS (m/z) 192 (M ); HRMS calcd for C13H20O (M ),
192.1514. Found: 192.1515.
1
3
(
6
(
6H, d, J = 6.8); C NMR: 171.01, 146.98, 135.89, 128.90, 126.59,
−
1
3.83, 39.07, 34.18, 33.69, 24.00, 20.86; IR (neat): 1741 cm ; MS
m/z) 292 (M ); HRMS calcd for C17H24O4 (M ), 292.1675. Found:
4.2.7. (S)-Cyclamen aldehyde
+
+
{(S)-2-methyl-3-(4-isopropylphenyl)propanal} (S)-1a
2
92.1673.
A solution of (S)-8 (0.507 g, 2.64 mmol) in dry CH Cl (14 mL)
2
2
was slowly added to a suspension of Dess–Martin periodinane
4.2.4. (R)-2-Hydroxymethyl-3-(4-isopropylphenyl)propyl acetate
(1.237 g, 2.917 mmol) in dry CH Cl2 (14 mL) at room temper-
2
(
R)-5
Lipase PS (0.960 g) was added to a solution of 4 (1.014 g,
.868 mmol) in vinyl acetate (45 ml). The resulting suspension was
ature. The reaction mixture was stirred for 1 h and quenched
with ether (30 mL) and a saturated sodium hydrogen carbonate
solution (50 mL) containing Na S O of 2.5 g. The resulting mix-
4
2
2
3
magnetically stirred at room temperature. Samples were with-
drawn from the vial and analyzed by gas chromatography. The
reaction was stopped by filtration of the lipase when the ratio of
the peak area of the monoester 5 to the total that of the diol 4
and the diacetate 6 reached about 99 to 1. It took 21 min. The fil-
trate was concentrated under reduced pressure. The residue was
chromatographed {silica gel, hexane/ethyl acetate = 2:1 (v/v)} to
give (R)-5 as colorless oil (1.173 g, 97%). The 1H NMR spectra data
were identical to those of (RS)-5. The ee of (R)-5 was determined
with HPLC {CHIRALPACK AY-H, hexane/2-propanol = 9:1 (v/v)} and
ture was extracted three times with ether. The organic phase
was washed with a saturated sodium chloride solution, and then
dried over Na SO . After removal of the solvents, the residue was
2
4
chromatographed {silica gel, hexane/acetone = 5:1 (v/v)} to give a
◦
colorless oil, which was distilled (155–163 C/1.5 mmHg) to give
(S)-1a as a colorless oil (0.318 g, 64%). The ee of (S)-1a was deter-
mined with HPLC {CHIRALCEL OZ-H, hexane/2-propanol = 300:1
1
(v/v)} and found to be 99%. The H NMR spectra data were identi-
2
1
◦
cal to those of commercial cyclamen aldehyde; [˛]D +6.5 (c 2.3,
CHCl ).
3
found to be >99%; [˛]D23 +22.5 (c 1.1, EtOH).
◦
4.3. Determination of the absolute configuration of (S)-1a
4
(
.2.5.
S)-2-Methanesulfonyloxymethyl-3-(4-isopropylphenyl)propyl
acetate (S)-7
Methanesulfonyl chloride (1.079 g, 9.419 mmol) was slowly
4.3.1. (S)-2-methyl-3-(4-isopropylphenyl)propyl
methanesulfonate (S)-9
Methanesulfonyl chloride (2.257 g, 19.70 mmol) was slowly
added to a solution of (R)-5 (1.134 g, 4.530 mmol) and dry pyri-
added to a solution of (S)-8 (1.857 g, 9.657 mmol, >99% ee) and dry
◦
◦
dine (1.089 g, 13.77 mmol) in dry CH Cl (8 mL) at 0 C. The reaction
pyridine (2.766 g, 34.97 mmol) in dry CH Cl2 (10 mL) at 0 C. The
2
2
2
mixture was stirred overnight at room temperature and quenched
at 0 C with deionized water. The resulting mixture was then
reaction mixture was stirred overnight at room temperature and
quenched at 0 C with deionized water. The resulting mixture was
◦
◦
extracted with ether. The organic phase was washed with deionized
water, and a saturated sodium chloride solution in this order, and
then dried over Na SO . After removal of the solvents, the residue
then extracted with ether. The organic phase was washed with a
saturated sodium chloride solution in this order, and then dried
over Na SO . Removal of the solvent gave (S)-9 as a colorless oil
2
4
2
4
was chromatographed {silica gel, hexane/acetone = 2:1 (v/v)} to
give (S)-7 as a colorless oil (1.372 g, 93%). The 1H NMR spectral
data showed that (S)-7 was contaminated with the methanesul-
fonyl chloride (0.088 g), and the purity of (S)-7 was termed 94%. The
yield was estimated from the 1H NMR spectral analysis; 1H NMR:
(2.346 g, 90%), which was used in the next reaction without purifi-
cation; 1H NMR: 7.15 (2H, d, J = 8.0), 7.08 (2H, d, J = 8.4), 4.09 (1H,
dd, J = 5.6, J = 9.6), 4.03 (1H, dd, J = 6.0, J = 9.6), 2.98 (3H, s), 2.88 (1H,
septet, J = 6.9), 2.70 (1H, dd, J = 6.8, J = 13.6), 2.50 (1H, dd, J = 7.4,
J = 13.8), 2.12–2.24 (1H, m), 1.24 (6H, d, J = 6.8), 1.00 (3H, d, J = 6.8);
13
7
4
.17 (2H, d, J = 8.0), 7.09 (2H, d, J = 8.4), 4.22 (1H, dd, J = 4.8, J = 10.0),
.16 (1H, dd, J = 5.6, J = 10.0), 4.15 (1H, dd, J = 4.8, J = 11.2), 4.04 (1H,
C NMR: 147.04, 136.54, 129.18, 126.64, 73.96, 38.88, 37.34, 35.13,
−
1
+
33.85, 24.19, 16.63; IR (neat): 1355, 1175 cm ; MS (m/z) 270 (M );
+
dd, J = 6.8, J = 11.2), 2.99 (3H, s), 2.88 (1H, septet, J = 6.9), 2.70 (2H,
HRMS calcd for C14H22O S (M ), 270.1290. Found: 270.1292.
3
d, J = 7.2), 2.34–2.43 (1H, m), 2.08 (3H, s), 1.24 (6H, d, J = 6.8); 13
C
NMR: 170.83, 147.33, 135.10, 128.93, 126.75, 68.55, 63.03, 39.60,
4.3.2. (S)-1-bromo-2-methyl-3-(4-isopropylphenyl)propane
(S)-10
−
1
3
7.24, 33.70, 33.58, 23.99, 20.82; IR (neat): 1739, 1362, 1175 cm
;
–
+
+
MS (m/z) 233 (M – OSO CH ); HRMS calcd for C15H21O2 (M
The crude methanesulfonate (S)-9 (2.304 g, ca. 8.521 mmol) and
anhydrous lithium bromide (1.543 g, 17.77 mmol) were dissolved
in dry acetone (40 mL). The mixture was refluxed overnight under
an argon atmosphere. After cooling to room temperature, deion-
ized water was added. The mixture was extracted three times with
ether. The extract was washed with a saturated sodium chloride
2
3
OSO CH ), 233.1542. Found: 233.1541.
2
3
4.2.6. (S)-2-methyl-3-(4-isopropylphenyl)-1-propanol (S)-8
A solution of (S)-7 with a purity of 94% (1.335 g, 3.8 mmol;
See Section 4.2.5) in dry Et O (15 mL) was slowly added to a
2
suspension of LiAlH4 (0.294 g, 7.75 mmol) in dry Et O (10 mL) at
solution, then dried over Na SO4 and concentrated under reduced
2
2
◦
room temperature. The reaction mixture was refluxed overnight
pressure. The residue was distilled (152–191 C/1.0 mmHg) to give
◦
(S)-10 as a colorless oil (2.004 g, 93%); 1H NMR: 7.15 (2H, d, J = 8.0),
under an argon atmosphere and quenched at 0 C with deionized
water. The resulting mixture was extracted three times with ether.
7.10 (2H, d, J = 8.4), 3.39 (1H, dd, J = 4.8, J = 10.0), 3.30 (1H, dd, J = 5.6,