V. N. Kovalenko, O. G. Kulinkovich / Tetrahedron: Asymmetry 22 (2011) 26–30
29
crystals (10.45 g, quantitative yield, mp 66–67 °C); [
2.0, CHCl3). The IR and NMR spectroscopic data corresponded to
those of racemic acid trans-1.
a
]
D = +120.5 (c
(dq, J = 7.9, 6.3 Hz, 1H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3): d
13.7, 31.2, 38.8, 52.7, 63.5, 168.2. The 1H and 13C NMR spectroscopic
data corresponded to those reported in the literature11 for racemic
ester 9. Anal. Calcd for C6H8Cl2O2 (183.03): C, 39.37; H, 4.41. Found:
C, 39.46; H, 4.44.
4.3.5. Isolation of racemic acid trans-1 from the mother liquors
The combined mother liquors after crystallizations of acid trans-
1 with (S)-(+)-
a
-phenylethylamine were evaporated under re-
4.7. Methyl (1R,3S)-2,2-dichloro-3-methylcyclopropanecarb-
oxylate (1R,3S)-9
duced pressure. To the residue 10% aqueous H2SO4 (100 mL) and
Et2O (100 mL) were added, and the mixture was vigorously stirred
until the residue was dissolved. The organic layer was separated
and the aqueous layer was extracted with Et2O (4 ꢂ 100 mL). The
combined organic phases were washed with 10% aqueous H2SO4
(50 mL), brine (50 mL), dried over MgSO4, and concentrated under
reduced pressure to give the acid trans-1 as a viscous oil (15.0 g);
Compound (1R,3S)-9 was obtained from acid (1R,3S)-1 in accor-
dance with the procedure for ester (1S,3R)-9 (yield 94%);
[a]D = +118.5 (c 1.2, CHCl3). The IR and NMR spectroscopic data
corresponded to those of compound (1S,3R)-9.
[
a
]
D = ꢀ19.0 (c 2.0, CHCl3). The residue was dissolved upon heating
4.8. Methyl (3R)-4,4,4-trimethoxy-3-methylbutanoate (3R)-10
in petroleum ether (30 mL). The resulting solution was cooled to
ꢀ10 °C and kept at this temperature for 12 h. The crystals formed
were separated by filtration and washed with cold petroleum ether
(20 mL). The acid trans-1 was obtained as white crystals (9.85 g,
A solution of MeONa (90 mmol) in MeOH (45 mL) was added
dropwise to a stirred and ice cooled solution of ester (1S,3R)-9
(7.50 g, 41.0 mmol) in MeOH (30 mL). After the addition was com-
plete, the cooling bath was removed, and the mixture was heated
to 40 °C and stirred for 2 h. The reaction was then cooled to 0 °C,
quenched with cold water (200 mL) and extracted with CH2Cl2
(5 ꢂ 40 mL). The combined organic phases were washed with brine
(20 mL), dried over Na2SO4, and concentrated under reduced pres-
sure (100–150 mmHg). Distillation of the residue afforded com-
pound (3R)-10 as a colorless liquid (6.93 g, 82%, bp 48–50 °C,
29%, mp 66–67 °C); [a]D = 0 (c 2.0, CHCl3).
4.4. (1S,3R)-2,2-Dichloro-3-methyl-N-[(1S)-1-phenylethyl]
cyclopropanecarboxamide 7
A mixture of acid (1S,3R)-1 (0.17 g, 1.0 mmol) and thionyl chlo-
ride (0.3 mL, 4.1 mmol) was refluxed for 3 h, the excess thionyl
chloride was removed under reduced pressure (20 mmHg), the res-
1 mmHg); [a]D = +9.2 (c 7.5, Et2O). IR (CCl4): m ;
max = 1741 cmꢀ1
idue was dissolved in CH2Cl2, and (S)-(ꢀ)-
a
-phenylethylamine
1H NMR (400 MHz, CDCl3): d 0.96 (d, J = 6.8 Hz, 3H), 2.13 (dd,
J = 15.4, 9.5 Hz, 1H), 2.45–2.54 (m, 1H), 2.63 (dd, J = 15.4, 4.1 Hz,
1H), 3.29 (s, 9H), 3.65 (s, 3H); 13C NMR (100 MHz, CDCl3): d 14.2,
35.5, 36.4, 50.4 (3C), 51.4 114.6, 173.8. Anal. Calcd for C9H18O5
(206.24): C, 52.41; H, 8.80. Found: C, 52.49; H, 8.82.
(0.25 g, 2.1 mmol) was added. After keeping at room temperature
for 1 h, the mixture was diluted with Et2O (5 mL), washed with
10% H2SO4 (1 mL), water (1 mL), saturated aqueous NaHCO3
(1 mL), and then dried with Na2SO4. Evaporation of the solvent un-
der reduced pressure gave crude amide 7 as a white solid (0.21 g,
77%, mp 160–163 °C). IR (CCl4):
m
max = 3437, 1686 cmꢀ1
;
1H NMR
4.9. Methyl (3S)-4,4,4-trimethoxy-3-methylbutanoate (3S)-10
(400 MHz, CDCl3): d 1.29 (d, J = 6.3 Hz, 3H), 1.51 (d, J = 6.9 Hz,
3H), 1.84 (d, J = 7.8 Hz, 1H), 2.19 (dq, J = 7.8, 6.3 Hz, 1H), 5.10–
5.17 (m, 1H), 6.38 (br s, 1H), 7.23–7.35 (m, 5H); 13C NMR
(100 MHz, CDCl3): d 13.6, 21.8, 29.1, 40.3, 49.7, 63.2, 126.3 (2C),
127.4, 128.6 (2C), 142.8, 164.3.
Compound (3S)-10 was obtained from ester (1R,3S)-9 in accor-
dance with the procedure for mono-orthoester (3R)-10 (yield 82%);
[a
]D = ꢀ9.2 (c 7.5, Et2O). Spectroscopic data corresponded to those
of compound (3R)-10.
4.5. (1R,3S)-2,2-Dichloro-3-methyl-N-[(1S)-1-phenylethyl]cyclo-
4.10. Dimethyl (2R)-2-methylsuccinate (2R)-12
propanecarboxamide 8
A solution of compound (3R)-10 (3.00 g, 14.5 mmol) in Et2O
(30 mL) was vigorously stirred with 5% aqueous HCl (30 mL) for
10 min. The organic layer was separated and the aqueous layer
was extracted with diethyl ether (3 ꢂ 20 mL). The combined or-
ganic phases were washed with water (10 mL), saturated aqueous
NaHCO3, brine (10 mL), and dried over Na2SO4. Evaporation of the
solvent under reduced pressure gave diester (2R)-12 as a colorless
Compound 8 was obtained from acid (1R,3S)-1 in accordance
with the procedure for amide 7 (yield 73%, white solid, mp 130–
133 °C). IR (CCl4):
CDCl3): d 1.29 (d, J = 6.3 Hz, 3H), 1.48 (d, J = 6.9 Hz, 3H), 1.91 (d,
J = 7.9 Hz, 1H), 2.19 (dq, J = 7.9, 6.3 Hz, 1H), 5.10–5.17 (m, 1H),
6.43 (br s, 1H), 7.23–7.33 (m, 5H); 13C NMR (100 MHz, CDCl3): d
13.6, 21.4, 29.1, 40.5, 49.4, 63.2, 126.2 (2C), 127.4, 128.6 (2C),
142.5, 164.4.
m .
max = 3437, 1688 cmꢀ1 1H NMR (400 MHz,
liquid which was pure by NMR (2.30 g, 99%); [
a]D = +5.0 (c 3.2,
CHCl3) {lit.8
[a]
D = +4.75 (c 2.9, CHCl3), >95% ee}.
4.6. Methyl (1S,3R)-2,2-dichloro-3-methylcyclopropanecarb-
oxylate (1S,3R)-9
4.11. Dimethyl (2S)-2-methylsuccinate (2S)-12
Compound (2S)-12 was obtained from mono-orthoester (3S)-10
in accordance with the procedure for diester (2R)-12 (yield 99%);
To a solution of acid (1S,3R)-1 (7.60 g, 45.0 mmol) in MeOH
(20 mL), 96% H2SO4 (3 mL, 54 mmol) was added. The mixture was
refluxed for 3 h, then cooled to room temperature, diluted with
water (50 mL), and extracted with CH2Cl2 (3 ꢂ 30 mL). The com-
bined organic phases were washed with water (10 mL), saturated
aqueous NaHCO3 (10 mL), and brine (10 mL), dried over Na2SO4,
and concentrated under reduced pressure (100–150 mmHg). Distil-
lation of the residue afforded methyl ester (1S,3R)-9 as a colorless
[
a
]
D = ꢀ5.0 (c 3.2, CHCl3) {lit.8
[
a
]
D = ꢀ4.9 (c 2.9, CHCl3), >96% ee}.
The NMR spectroscopic data corresponded to those of compound
(2R)-12.
4.12. (2R)-2-Methylbutane-1,4-diol (2R)-13
A solution of diester (2R)-12 (10 mg, 62 lmol) in THF (0.5 mL)
liquid (7.75 g, 94%, bp 72–73 °C, 12–13 mmHg); [
1.2, CHCl3). IR (CCl4):
max = 3026, 1745 cmꢀ1 1H NMR (400 MHz,
CDCl3): d 1.36 (d, J = 6.3 Hz, 3H), 2.09 (d, J = 7.9 Hz, 1H), 2.20
a
]
D = ꢀ118.0 (c
was added under argon to a stirred and ice cooled solution of
LiAlH4 (5.0 mg, 0.13 mmol) in THF (0.5 mL). The cooling bath was
removed, and the mixture was stirred at room temperature for
m
;