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S. Falgner et al. / Journal of Organometallic Chemistry 695 (2010) 2614e2617
1.60
(
dN), 2.13
(
dA), and 2.28
(
dB
)
(7 H, ABMNX3 system,
(224.2 g, 817 mmol). Bp.: 120 ꢀC/12 mbar. Anal. Calc. (C13H26O4Si):
2JAB ¼ 14.5 Hz,
2JMN ¼ 15.2 Hz,
3JAX ¼ 7.5 Hz,
3JBX ¼ 7.6 Hz,
C, 56.90; H, 9.55; M, 274.43. Found: C, 56.6; H, 9.6%. 1H NMR
4JBN ¼ 0.8 Hz, SiCHMHNCCHAHBC(HX)3), 1.01 (dX), 3.98 (dA), and 4.08
(500.1 MHz, C6D6):
d
0.19 (9 H, s, SiCH3), 1.02 (3 H, t, JHH ¼ 7.5 Hz,
3
(
dB) (5 H, ABX3 system, 2JAB ¼ 10.8 Hz, 3JAX ¼ 3JBX ¼ 7.1 Hz, OCHAHBC
CCH2CH3), 1.06 (dX), 4.07 (dA), and 4.13 (dB) (10 H, ABX3 system,
(HX)3). 13C NMR (125.8 MHz, C6D6):
d
0.0 (SiCH3), 9.0 (CCH2CH3),
2JAB ¼ 10.8 Hz, JAX ¼ 7.0 Hz, JBX ¼ 7.2 Hz, OCHACHBC(HX)3), 1.60 (2
3
3
3
14.1 (OCH2CH3), 21.9 (SiCH2C), 29.1 (CCH2CH3), 62.4 (OCH2CH3),
H, s, SiCH2C), 2.25 (2 H, q, JHH ¼ 7.5 Hz, CCH2CH3). 13C NMR
67.6 (CCH2CH3), 170.3 (C(O)OCH2CH3), 174.9 (C(O)Cl). 29Si NMR
(125.8 MHz, C6D6):
d
ꢁ0.1 (SiCH3), 9.2 (CCH2CH3), 14.0 (OCH2CH3),
(99.4 MHz, C6D6):
d
ꢁ0.4]. The intermediate rac-7 (crude product,
21.6 (SiCH2C), 29.5 (CCH2CH3), 56.5 (CCH2CH3), 60.8 (OCH2CH3),
not further purified) was dissolved in acetone (40 mL), and the
resulting solution was added dropwise within 15 min to a stirred
suspension of sodium azide (2.91 g, 44.8 mmol) in acetone (50 mL)
at 0 ꢀC. The mixture was allowed to warm to 20 ꢀC and was then
stirred at this temperature for 4 h. The resulting precipitate was
separated by suction filtration, washed with acetone (3 ꢂ 10 mL),
and discarded. The filtrate (including the wash solutions) was then
heated under reflux for 16 h, the mixture was allowed to cool to
20 ꢀC, and the solvent was removed under reduced pressure [4].
Subsequently, hydrochloric acid (6 M, 300 mL) was added to the
residue in a single portion at 20 ꢀC, and the resulting mixture was
heated under reflux for 3 h. The solvent was removed under
reduced pressure, and the solid residue was dissolved in water
(150 mL). The resulting aqueous solution was extracted with
diethyl ether (3 ꢂ 50 mL), and the aqueous phase was freeze-dried
to afford a colorless powder [rac-3$HCl; the NMR data of the
product (solvent, D2O) were identical with those obtained for rac-
3], which was dissolved in a mixture of methanol (112 mL) and an
aqueous sodium hydroxide solution (1 M, 33.0 mL; 33.0 mmol of
NaOH) [8]. The solution was kept undisturbed at 20 ꢀC for one day,
and the resultant precipitate was separated by filtration and
washed with diethyl ether (2 ꢂ 30 mL) to afford rac-3 in 44% yield
as a colorless crystalline solid (3.36 g, 17.7 mmol). Mp.: 264 ꢀC
(dec.). Anal. Calc. (C8H19NO2Si): C, 50.75; H, 10.12; N, 7.40; M,
189.33. Found: C, 50.6; H, 10.0; N, 7.5%. 1H NMR (500.1 MHz, D2O):
172.4 (C(O)OCH2CH3). 29Si NMR (99.4 MHz, C6D6):
d
ꢁ0.3.
4.5. Preparation of rac-2-(ethoxycarbonyl)-2-[(trimethylsilyl)-
methyl]butanoic acid (rac-6)
Potassium hydroxide (6.44 g, 115 mmol) was added in a single
portion at 20 ꢀC to a stirred solution of 5 (27.4 g, 99.8 mmol) in
ethanol (100 mL). The mixture was heated under reflux for 16 h and
was then allowed to cool to 20 ꢀC. The solvent was removed under
reduced pressure and water (400 mL) was added. The aqueous
phase was extracted continuously with diethyl ether (700 mL) over
a period of 6 h using a perforator, and the extract was discarded.
The remaining aqueous solution was acidified with concentrated
hydrochloric acid (10 mL) and was then extracted continuously
with diethyl ether (700 mL) over a period of 9 h using a perforator.
The organic phase was dried over anhydrous sodium sulfate, the
solvent was removed under reduced pressure, and the residue was
purified by bulb-to-bulb distillation (160 ꢀC, 0.02 mbar) to afford
rac-6 in 77% yield as a colorless liquid (18.9 g, 76.7 mmol). Anal.
Calc. (C11H22O4Si): C, 53.63; H, 9.00; M, 246.38. Found: C, 53.6; H,
9.1%. 1H NMR (500.1 MHz, DMSO-d6):
d e0.03 (9 H, s, SiCH3), 0.76 (3
H, t, 3JHH ¼ 7.5 Hz, CCH2CH3), 1.13 (dA) and 1.15 (dB) (2 H, AB system,
2JAB ¼ 15.0 Hz, SiCHAHBC), 1.15 (dX), 4.04 (dA), and 4.09 (dB) (5 H,
2
3
ABX3 system, JAB ¼ 10.9 Hz, JAX ¼ 3JBX ¼ 7.1 Hz, OCHAHBC(HX)3),
1.79 (2 H, q, JHH ¼ 7.5 Hz, CCH2CH3), 12.7 (1 H, br. s, C(O)OH). 13
C
3
d
0.00 (9 H, s, SiCH3), 0.88 (dX), 1.80 (dA), and 2.00 (dB) (5 H, ABX3
NMR (125.8 MHz, DMSO-d6):
d e0.3 (SiCH3), 8.7 (CCH2CH3), 13.9
2
3
3
system, JAB ¼ 14.9 Hz, JAX ¼ 7.5 Hz, JBX ¼ 7.6 Hz, CCHAHBC(HX)3),
(OCH2CH3), 20.5 (SiCH2C), 28.2 (CCH2CH3), 55.5 (CCH2CH3), 60.5
2
(OCH2CH3), 172.3 (C(O)OCH2CH3), 173.4 (C(O)OH). 29Si NMR
1.23 (dA) and 1.28 (dB) (2 H, AB system, JAB ¼ 14.8 Hz, SiCHAHBC),
NH3 not detected (H/D exchange). 13C NMR (125.8 MHz, D2O):
d 0.0
(99.4 MHz, DMSO-d6):
d
ꢁ0.4.
(SiCH3), 8.7 (CCH2CH3), 26.9 (SiCH2C), 32.0 (CCH2CH3), 65.1
(CCH2CH3), 175.9 (C(O)OH). 15N NMR (30.4 MHz, D2O):
ꢁ330.3.
29Si NMR (99.4 MHz, D2O):
ꢁ1.3.
d
4.6. Resolution of rac-3 by analytical HPLC
d
The enantiomers of 3 were partially separated by analytical
liquid chromatography (HPLC), starting from rac-3 and using
a chiral stationary phase. The experimental conditions were as
follows: LC pump, SunChrom SunFlow 100; detector, SunChrom
4.3. Preparation of diethyl [(trimethylsilyl)methyl]malonate (4)
This compound was prepared according to refs. [1d] and [1e].
Spectra Flow 600
(
l
¼ 204.2 nm); column thermostat, Spark
Mistral; column temperature, 10 ꢀC; column (25 cm, i.d. 4.60 mm),
Chirobiotic R (macrocyclic glycopeptide phase (Ristotecin A) on
4.4. Preparation of diethyl ethyl[(trimethylsilyl)methyl]
malonate (5)
spherical silica; particle size, 5 mm); mobile phase (purchased from
Compound 4 (211.1 g, 857 mmol) was added dropwise within
30 min to a stirred freshly prepared solution of sodium ethoxide in
ethanol [prepared from sodium (21.7 g, 944 mmol) and ethanol
(400 mL)] under reflux conditions. The resulting mixture was
heated under reflux for 2 h, iodoethane (146.9 g, 942 mmol) was
then added dropwise under reflux conditions within 1 h, and the
resultant mixture was then heated under reflux for 24 h. Subse-
quently, the mixture was allowed to cool to 20 ꢀC and was then
neutralized with a few drops of concentrated hydrochloric acid. The
solvent and the excess iodoethane were removed under reduced
pressure, water (400 mL) was added to the residue, the aqueous
phase was extracted with diethyl ether (3 ꢂ100 mL), and the
combined organic solutions were washed with an aqueous sodium
thiosulfate solution (1 M, 3 ꢂ 75 mL) and then dried over anhy-
drous sodium sulfate. The solvent was removed under reduced
pressure, and the residue was purified by distillation in vacuo
(Vigreux column) to afford 5 in 95% yield as a colorless liquid
LGC Promochem), water/acetonitrile [65:35 (v/v)], isocratic; flow,
0.5 mL minꢁ1; sample concentration, 10 mg mLꢁ1 aqueous phos-
phoric acid solution (4 mL Lꢁ1); injection volume, 5
mL.
References and notes
[1] (a) G. Reginato, A. Mordini, P. Meffre, A. Tenti, M. Valacchi, K. Cariou, Tetrahedr.
Asymmetry 17 (2006) 922e926;
(b) F. Cavelier, D. Marchand, J. Martinez, Chem. Biodivers.
5 (2008)
1279e1287;
(c) D. Marchand, J. Martinez, F. Cavelier, Eur. J. Org. Chem. (2008) 3107e3112;
(d) S. Falgner, D. Schmidt, R. Bertermann, C. Burschka, R. Tacke, Organome-
tallics 28 (2009) 2927e2930 and references therein;
(e) S. Falgner, C. Burschka, S. Wagner, A. Böhm, J.O. Daiss, R. Tacke, Organ-
ometallics 28 (2009) 6059e6066;
(f) M. Mortensen, R. Husmann, E. Veri, C. Bolm, Chem. Soc. Rev. 38 (2009)
1002e1010.
[2] (a) N. Imawaka, M. Tanaka, H. Suemune, Helv. Chim. Acta 83 (2000) 2823e2835;
(b) M. Oba, M. Tanaka, M. Kurihara, H. Suemune, Helv. Chim. Acta 85 (2002)
3197e3218;