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stirred further at ꢀ78 ꢁC for 30 min, and allowed to warm
to room temperature over 2 h. The reaction was quenched
with saturated aqueous NH4Cl solution and the mixture
extracted with AcOEt. The organic layer was washed with
brine, dried over anhydrous Na2SO4 and concentrated in
vacuo. The residue was charged on a silica gel column
4.6.4. (2S,10R)-10-Isopropylpentyl 3,3,3-trifluoro-2-methoxy-
2-phenylpropanoate 7b. (R)-MTPA chloride (27 mg,
0.107 mmol) was added with stirring to a solution of (R)-
7a (6 mg, 0.046 mmol) in pyridine (0.46 mL). After stirring
overnight at room temp, the reaction was quenched with
water (5 mL) and the mixture was extracted with AcOEt.
The combined organic layer was washed with brine, dried
over anhydrous Na2SO4, and concentrated in vacuo. The
residue was dissolved in toluene (2 mL), concentrated in
vacuo twice for removing pyridine, and purified by pre-
parative TLC with hexane–AcOEt (9:1) to afford 7b
(14.4 mg, 99%). 1H NMR d: 0.83 (d, J = 6.4 Hz, 3H),
0.85 (d, J = 6.1 Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H), 1.20–
1.40 (m, 4H), 1.52–1.72 (m, 2H), 1.85–1.97 (m, 1H), 3.56
(s, 1H), 4.94 (dt, J = 4.6, 6.0 Hz, 1H), 7.37–7.42 (m, 3H),
7.55–7.58 (m, 2H). An authentic sample from racemic 7a
showed the additional signals ascribable to the (10S)-iso-
mer: 0.82 (t, J = 7.0 Hz, 3H), 0.91 (d, J = 6.9 Hz, 3H),
0.92 (d, J = 6.9 Hz, 3H), 1.10–1.37 (m, 4H), 1.49–1.69
(m, 2H), 1.85–2.00 (m, 1H), 3.56 (s, 1H), 4.97 (m, 1H),
7.38–7.42 (m, 3H), 7.55–7.56 (m, 2H). The ee of product
7a from the microbial origin was 96%, judging from their
NMR spectra.
(170 g). Elution with hexane–AcOEt (4:1) afforded
24
(3S,4RS)-5 (1.8 g, 76%). ½aꢁD ¼ þ175:3 (c 1.04, EtOH).
IR mmax 3527, 2962, 1446, 1302, 1146, 1084 cmꢀ1 1H
;
NMR d: 0.72 (d, J = 6.8 Hz, 3H), 1.00 (d, J = 6.4 Hz,
3H), 1.81 (dqq, J = 9.1, 6.4, 6.8 Hz, 1H), 2.66 (m, 2H),
2.95 (d, J = 1.8 Hz, 1H), 3.20 (t, J = 5.4 Hz, 1H), 3.77
(dd, J = 1.8, 9.1 Hz, 1H), 4.95 (dd, J = 1.3, 9.7 Hz, 1H),
5.00 (dd, J = 1.5, 16.0 Hz, 1H), 5.70 (m, 1H), 7.64 (m,
3H), 7.91 (m, 2H).
4.6.2. (3S,4RS)-2-Methyl-4-phenylsulfonyl-3-heptanol 6.
The alcohol (3S,4RS)-5 (1.7 g, 6.5 mmol) was dissolved
in EtOH (64 mL) and then 10% Pd–C (340 mg) was added.
The mixture was vigorously stirred under H2 (1 atm) at
room temperature for 15 h. The reaction mixture was fil-
tered through a pad of Celite, and the Celite pad was
washed with AcOEt. The combined organic solution was
concentrated in vacuo to afford 6 (1.7 g, 99%) as a diaste-
24
reomeric mixture (ca. 3:1). ½aꢁD ¼ þ14:7 (c 1.01, EtOH).
4.7. Reduction of 9: step-by-step procedure
IR mmax 3525, 2962, 1300, 1146, 1084, 729 cmꢀ1 1H
;
NMR d: major diastereomer; 0.70 (d, J = 6.8 Hz, 3H),
0.86 (t, J = 7.3 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H), 1.38
(m, 2H), 1.74 (dqq, J = 9.6, 6.6, 6.8 Hz, 1H), 1.88 (m,
2H), 2.98 (d, J = 2.0 Hz, 1H), 3.08 (t, J = 5.1 Hz, 1H),
3.66 (dd, J = 2.0, 9.6 Hz, 1H), 7.55–7.71 (3H, m), 7.89–
7.92 (m, 2H); minor diastereomer; 0.79 (t, J = 7.3 Hz,
3H), 0.94 (d, J = 6.8 Hz, 3H), 0.99 (d, J = 6.6 Hz, 3H),
1.38 (m, 2H), 1.58 (m, 2H), 2.02 (dqq, J = 5.2, 6.6,
6.8 Hz, 1H), 3.18 (dt, J = 5.1, 5.0 Hz, 1H), 3.44 (d,
J = 5.4 Hz, 1H), 3.72 (ddd, J = 5.1, 5.2, 5.4 Hz, 1H),
7.55–7.71 (m, 3H), 7.89–7.92 (m, 2H).
4.7.1. (3S,5S)-(ꢀ)-2,6-Dimethyl-3,5-heptanediol 12a by C.
floricola IAM 13315. The combined wet cells of C. flori-
cola (10 g) incubated as described above were re-suspended
in a reaction medium [containing glucose (5 g), phosphate
buffer (0.1 M, pH 6.0), total volume of 100 mL] in a 300-
mL round-bottomed flask, together with 6 (200 mg,
1.28 mmol). The reaction mixture was stirred for 28 h at
30 ꢁC. Antifoam AF emulsion (100 mg/mL, 0.5 mL) was
then added to the reaction mixture and the mixture was
azeotropically distilled in vacuo. The distillate was satu-
rated with NaCl and extracted with Et2O. The combined
organic extracts were washed with brine, dried over anhy-
drous Na2SO4 and concentrated in vacuo. The residue
was employed for the next step immediately without fur-
ther purification.
4.6.3. (R)-2-Methyl-3-heptanol 7a. A solution of the alco-
hol (3S,4RS)-6 (694 mg, 2.6 mmol) in Et2O (5.2 mL) and
ethylenediamine (1.2 mL, 18 mmol) was cooled to 0 ꢁC.
The mixture was degassed to remove any trace of O2 by
applying ultrasonic (70–80 W) under evacuation. Lithium
shot (Wako, 126-04913, 97 mg, 14 mmol) was added under
the flow of N2 and the mixture was vigorously stirred at
0 ꢁC. The color of the reaction mixture immediately turned
brown. After the proper period, the reaction was quenched
by the addition of saturated aqueous NH4Cl solution and
6 M HCl to adjust its pH to be 6. The mixture was then ex-
tracted several times with Et2O. The combined extract was
washed with water, 2 M aqueous NaOH solution, and
brine and dried over anhydrous Na2SO4 with activated
charcoal. The solvent was carefully removed by fractional
distillation at atmospheric pressure. The residue was puri-
fied by preparative TLC with hexane–AcOEt (4:1) and fur-
A solution of the crude product in anhydrous MeCN
(0.85 mL) was added slowly with stirring under Ar to a
solution of Me4NHB(OAc)3 (1.11 g, 4.2 mmol) in anhy-
drous MeCN (3.4 mL) and anhydrous AcOH (3.4 mL) at
ꢀ20 ꢁC. After stirring for 2 h at ꢀ20 ꢁC, the reaction was
quenched by the addition of saturated aqueous sodium
potassium tartrate solution (2 mL) and stirred vigorously
for 30 min. The mixture was extracted with AcOEt, and
the organic layer was washed with saturated aqueous NaH-
CO3 solution and brine, dried over anhydrous Na2SO4 and
concentrated in vacuo. The residue was charged on a silica
gel column (7 g). Elution with hexane–AcOEt (6:1) and the
further purification of some contaminated fractions with
preparative TLC with hexane–AcOEt (2:1), which was
developed twice, afforded (3S,5S)-12a (73.7 mg, 36%) as a
colourless solid; mp 88.5–90.0 ꢁC; IR mmax 3336, 2958,
ther by micro-distillation apparatus to afford (R)-7a
24
(87 mg, 26%). Bp 120 ꢁC/80 mmHg; ½aꢁD ¼ þ25:7 (c 0.46,
EtOH) {lit.22 [a]D = +27.7 (c 10, EtOH)} IR mmax 3359,
1
1
2958, 2933, 2873, 1468, 991 cmꢀ1; H NMR: d 0.91 (m,
1471, 1333, 1146, 1038, 795, 704 cmꢀ1; H NMR d: 0.91
9H), 1.29–1.48 (m, 6H), 1.57–1.73 (m, 1H), 3.36 (br s,
1H); 13C NMR d: 14.2, 17.2, 19.0, 22.9, 28.3, 33.5, 33.9,
76.7.
(d, J = 6.8 Hz, 6H), 0.96 (d, J = 6.6 Hz, 6H), 1.59 (dd,
J = 5.6, 5.7 Hz, 2H), 1.72 (dqq, J = 5.9, 6.6, 6.8 Hz, 2H),
2.34 (s, 2H), 3.63 (ddd, J = 5.6, 5.7, 5.9 Hz, 2H); 13C