M. Ostermeier, B. Brunner, C. Korff, G. Helmchen
FULL PAPER
2.8 mL were consumed [corresponding to 90% conversion of (S)-
3
1H NMR (CDCl3): δ ϭ 1.14 (d, J ϭ 6.6 Hz, 3 H, CH3), 2.11 (dd,
4]. The mixture was then filtered through celite and the filtrate 2J ϭ 20.1, 3J ϭ 10.5 Hz, 1 H, CHCϭO), 2.57Ϫ2.74 (m, 2 H,
extracted with ethyl acetate (3 ϫ 10 mL). The organic phases were
combined, dried (Na2SO4) and concentrated in vacuo to give un-
changed ester (S)-4. The aqueous layer was acidified with 2
H2SO4 until pH 2 was reached and then extracted with ethyl acetate
(3 ϫ 10 mL). The combined organic layers were dried (Na2SO4),
and the solvent was removed in vacuo to yield a mixture of half
esters (S)-6 and (S)-8. Their ratio was determined by 1H NMR
spectroscopy.
CHCϭO and CH), 3.84 (dd, 2J ϭ 8.8, 3J ϭ 6.3 Hz, 1 H, CHO),
4.39 (dd, 2J ϭ 8.8, 3J ϭ 7.4 Hz, 1 H, CHO) ppm. 13C NMR
(CDCl3): δ ϭ 17.90 (q, CH3), 33.36 (d, CH), 36.10 (t, CH2CϭO),
74.65 (t, CH2O), 177.21 (s, CϭO) ppm. HRMS (EI) [Mϩ]
(C5H8O2): calcd. 100.0524; found 100.0520. C5H8O2 (100.12) calcd.
C 59.98, H 8.05, found C 59.73, H 8.04.
Methyl
(3S)-4-{[tert-Butyl(diphenyl)silyl]oxy}-3-methylbutanoate
[(S)-14]]: tert-Butyldiphenylsilyl chloride (38.80 g, 141.5 mmol) was
added dropwise to a solution of crude (S)-12 (17.00 g, 128.6 mmol),
prepared as described above, and imidazole (13.13 g, 192.9 mmol)
in anhydrous DMF (100 mL). After 3 h the reaction mixture was
treated with water (50 mL) and extracted with diethyl ether (3 ϫ
120 mL). The combined organic layers were washed once with 1
HCl (100 mL) and sat. NaHCO3 solution (100 mL) and dried with
Na2SO4. The solvent was removed in vacuo and the residue puri-
fied by column chromatography (silica, petroleum ether/Et2O 9:1;
TLC: Rf ϭ 0.58) to yield ester (S)-14 as a colorless oil (16.2 g, 83%).
[α]2D0 ϭ Ϫ4.9 (c ϭ 3.7 CHCl3). 1H NMR (CDCl3): δ ϭ 0.93 (d,
3J ϭ 6.5 Hz, 3 H, CHCH3), 1.03 [s, 9 H, SiC(CH3)3], 2.12 (dd, 2J ϭ
14.3, 3J ϭ 8.12 Hz, 1 H, CH2COO), 2.21 (m, 1 H, CHCH3),
2.58 (dd, 2J ϭ 14.3, 3J ϭ 4.7 Hz, 1 H, CH2COO), 3.43 (dd, 2J ϭ
For determination of the enantiospecificity of the hydrolysis cata-
lyzed by Mucor javanicus lipase (MJL), racemic 4 was hydrolyzed
as described above, except that the reaction was stopped at 40%
conversion. Determination of the enantiomeric excess was carried
out as described above.
(3S)-3-Methyldihydrofuran-2(3H)-one [(S)-11]: A cold solution (0
°C) of mono ester (S)-6 (1.00 g, 6.85 mmol) in methanol (3.5 mL)
was treated with 2 aqueous KOH solution (3.4 mL, 6.85 mmol).
After 15 min the solution was concentrated and the residue dried
in vacuo. The residual oil was dissolved in ethanol (30 mL) and
the solution was cooled in an ice bath. Powdered anhydrous CaCl2
(1.92 g, 17.3 mmol) was added and the suspension was stirred for
15 min. Then a suspension of NaBH4 (1.03 g, 24.7 mmol) in etha-
nol (10 mL) was added and the mixture was stirred at room tem-
perature for 12 h. The mixture was cooled to 0 °C and acidified
(pH, 1) with 3 HCl. After 30 min the mixture was extracted with
diethyl ether (3 ϫ 25 mL). The combined organic layers were dried
with Na2SO4 and concentrated in vacuo. The residue was purified
by Kugelrohr distillation (90 °C, 0.6 mbar) to yield lactone (S)-11
as colorless, volatile oil (405 mg, 58%). [α]2D0 ϭ Ϫ20.1 (c ϭ 2.0,
EtOH), ref.[1a] [α]2D0 ϭ Ϫ22.9 (c ϭ 2, EtOH). 1H NMR (CDCl3):
δ ϭ 1.22 (d, 3J ϭ 7.4 Hz, 3 H, CH3), 1.81Ϫ1.93 (m, 1 H, CHCHH),
2.35Ϫ2.43 (m, 1 H, CHCHH), 2.50Ϫ2.60 (m, 1 H, CH), 4.13 (dt,
3J ϭ 7.4, 2J ϭ 9.2 Hz, 1 H, C(HH)O], 4.28 (dt, 3J ϭ 2.7, 2J ϭ
9.0 Hz, 1 H, C(HH)O] ppm. 13C NMR (CDCl3): δ ϭ 14.98 (q,
CH3), 30.53 (t, CHCH2), 33.97 (d, CH), 66.12 (t, CH2O), 180.05
(s, CO) ppm. HRMS (EI) [Mϩ] (C5H8O2): calcd. 100.0524; found
100.0523. C5H8O2 (100.12) calcd. C 59.98, H 8.05, found C 59.69,
H 8.04.
3
2
3
9.8, J ϭ 6.3 Hz, 1 H, CH2OSi), 3.53 (dd, J ϭ 9.8, J ϭ 5.2 Hz,
1 H, CH2OSi), 3.63 (s, 3 H, CO2CH3), 7.61Ϫ7.64 (m, 10 H, Ph)
ppm. 13C NMR (CDCl3): δ ϭ 16.63 (q, CHCH3), 19.29 [s,
SiC(CH3)3], 26.83 [q, SiC(CH3)3], 33.02 (d, CH), 38.05 (t,
CH2CO2), 51.38 (q, CO2CH3); 68.08 (t, CH2OSi), 127.63 (d, Ph-
C), 129.59 (d, Ph), 133.71 (s, Ph-Cipso), 135.60 (d, Ph), 173.64 (s,
CO2) ppm. HRMS (FABϩ) [Mϩ ϩ H] (C22H31O3Si): calcd.
371.2042; found 371.2031. C22H30O3Si (370.56) calcd. C 71.31,
H 8.16, found C 71.16, H 8.16.
(3S)-4-{[tert-Butyl(diphenyl)silyl]oxy}-3-methylbutan-1-ol [(S)-15]:
A 1 solution of diisobutylaluminum hydride in toluene (108 mL,
107.9 mmol) was slowly added to a cold (Ϫ78 °C) solution of ester
(S)-14 (16.00 g, 43.2 mmol) in anhydrous THF (80 mL). After 2 h
the reaction mixture was warmed to Ϫ20 °C and was then stirred
for 1 h. Then 1 aqueous NH4Cl solution (60 mL) was added, and
the reaction mixture was allowed to reach room temperature. The
reaction mixture was extracted with ethyl acetate (3 ϫ 75 mL), and
the combined organic layers were dried with Na2SO4 and concen-
trated in vacuo. The residue was purified by column chromatogra-
phy (silica, petroleum ether/EtOAc, 4:1; TLC: Rf ϭ 0.22) to yield
(S)-15 as a colorless oil (13.32 g, 90%). [α]2D0 ϭ Ϫ2.0 (c ϭ 2.3
CHCl3), ref.[31] [α]2D0 ϭ 4.7 (c ϭ 3.3 CHCl3). 1H NMR (CDCl3):
δ ϭ 0.88 (d, 3J ϭ 6.8, 3 H, CHCH3), 1.04 [s, 9 H, SiC(CH3)3],
Methyl (3S)-4-Hydroxy-3-methylbutanoate [(S)-12]: BH3·SMe2
(25.7 mL, 257 mmol) was added dropwise to a cold (Ϫ30 °C) solu-
tion of (S)-6 (30.00 g, 205.5 mmol) in dry THF (150 mL). The mix-
ture was warmed to 0 °C over a period of 1.5 h. After 0.5 h meth-
anol (50 mL) was added and volatiles were removed in vacuo. This
procedure was repeated twice. The resultant (S)-12 (27.11 g, 98%),
a colorless liquid, was pure according to 1H NMR and was used
1.44Ϫ1.56 (m,
1 H, CH2CH2CH) 1.60Ϫ1.74 (m, 1 H,
1
CH2CH2CH), 1.75Ϫ1.87 (m, 1 H, CHCH3), 3.44Ϫ3.55 (m, 2 H,
CHSi), 3.59Ϫ3.76 (m, 2 H, HOCH2), 7.33Ϫ7.70 (m, 10 H, Ph)
ppm. 13C NMR (CDCl3): δ ϭ 17.19 (q, CHCH3), 19.22 [s,
SiC(CH3)3], 26.83 [q, SiC(CH3)3], 33.27 (d, CH), 37.35 (t,
CH2CH2CH), 61.19 (t, HOCH2), 69.25 (t, CH2OSi), 127.65 (d, Ph),
129.65 (d, Ph), 133.53 (s, PhCipso), 135.66 (d, Ph) ppm. HRMS
(FABϩ) [Mϩ ϩ H] (C21H31O2Si): calcd. 343.2093; found 343.2106.
C21H30O2Si (342.55) calcd. C 73.63, H 8.83, found C 73.55,
H 8.83.
without further purification for the next steps. H NMR (CDCl3):
δ ϭ 0.95 (d, 3J ϭ 6.6 Hz, 3 H, CCH3), 1.79 (br. s, 1 H, OH),
2.10Ϫ2.23 (m, 1 H, CH), 2.24 (dd, 2J ϭ 14.7, 3J ϭ 6.6 Hz, 1 H,
2
3
CHCϭO), 2.43 (dd, J ϭ 14.7, J ϭ 6.2 Hz, 1 H, CHCϭO), 3.43
(dd, 2J ϭ 10.7, 3J ϭ 6.6 Hz, 1 H, CHOH), 3.55 (dd, 2J ϭ 10.7,
3J ϭ 5.2 Hz, 1 H, CHOH), 3.66 (s, 3 H, OCH3) ppm. 13C NMR
(CDCl3): δ ϭ 16.69 (q, CCH3), 33.02 (d, CH), 38.28 (t, CH2CϭO),
51.55 (q, OCH3), 67.55 (t, CH2OH), 173.84 (s, CϭO) ppm. HRMS
(FABϩ) [Mϩ Ϫ H2O] (C6H10O2): calcd. 114.0681; found 114.0687;
[Mϩ Ϫ MeOH] (C5H8O2): calcd. 100.0524; found 100.0520.
Acknowledgments
(4S)-4-Methyldihydrofuran-2(3H)-one [(S)-13]: A mixture of (S)-12
(9.00 g, 68.1 mmol) and pTsOH·H2O (20 mg, 0.11 mmol) was This work was supported by the Deutsche Forschungsgemeinschaft
´
and the Fonds der chemischen Industrie (Kekule scholarship for
stirred for 15 min and then fractionally distilled in vacuo (88Ϫ90
°C/55 mbar) to yield (S)-13 (5.2 g, 84%), colorless oil. [α]2D0 ϭ Ϫ24.8 M. O.). We thank Dr. R. Stürmer, BASF AG, for enzymes and
(c ϭ 4.35, MeOH), ref.[1a] [α]2D0 ϭ Ϫ24.7 (c ϭ 4, MeOH; 97.2% ee).
Degussa AG for rhodium salts.
3458
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 3453Ϫ3459