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J. Nam et al. / Tetrahedron 59 (2003) 2397–2401
128.7, 128.0, 126.7, 79.1, 63.1, 46.2, 41.2, 37.0, 33.5, 9.7.
Anal. calcd for C21H26BrNO2: C, 62.38; H, 6.48; N, 3.46.
Found: C, 62.25; H, 6.54; N, 3.74.
and the S-enantiomer (minor) had a retention time of
11.1 min.)
4.2.4. (R)-Methyl-2-p-anisyloxy-4-phenylbutanoate (8).
A colorless oil was obtained in 61% yield. 1H NMR (CDCl3,
400 MHz) 7.29–7.18 (m, 5H), 6.83–6.80 (m, 4H), 4.52 (dd,
J¼4.5, 8.4 Hz, 1H), 3.76 (s, 3H), 3.72 (s, 3H), 2.83 (m, 2H),
2.24 (m, 2H); 13C NMR (CDCl3, 100 MHz) 172.9, 154.9,
152.3, 141.1, 129.0, 128.9, 126.6, 116.8, 115.1, 76.7, 56.1,
52.7, 34.9, 31.7. The spectral data of 8 were identical to
those of the authentic material reported previously.3h The
enantiomeric ratio of 8 was determined to be 86:14 (96:4 at
2308C substitution) in favor of the R enantiomer by CSP-
HPLC using racemic material as a standard. (Chiralcel OD
column; 10% 2-propanol in hexane; 0.9 mL/min; the
R-enantiomer (major) had a retention time of 9.2 min, and
the S-enantiomer (minor) had a retention time of 8.2 min.)
The absolute configuration of (R)-8 was assigned by the
conversion to methyl-2-hydroxy-4-phenylbutanoate using
ceric ammonium nitrate (CAN) and comparison of the well
established CSP-HPLC analysis data.3e (Chiralcel OD
column; 10% 2-propanol in hexane; 1.0 mL/min; the
R-enantiomer (major) had a retention time of 10.7 min,
and the S-enantiomer (minor) had a retention time of
8.1 min.)
4.2. General procedure for asymmetric preparation of
a-hydroxy carboxylic acid derivatives 5–8
To a solution of (aRS)-a-bromo esters in CH3CN (ca.
0.1 M) at room temperature was added Et3N (1.1 equiv.).
The resulting reaction mixture was stirred at room
temperature for an appropriate time, and then PMPO2Naþ
(0.9 equiv.) in CH3CN was slowlyadded at08C. (PMPO2Naþ
was prepared by adding sodium hydride (1.2 equiv., 60%
dispersion in mineral oil, An excess amount of NaH was
used for the better yields in substitutions12) to a stirred
solution of p-methoxyphenol (0.9 equiv.) in CH3CN and
stirring for 0.5 h under a nitrogen atmosphere). After 14 h
stirring under a nitrogen atmosphere, the mixture was
treated with extractive work up and the solvent was
evaporated. The crude mixture and Et3N (0.2 equiv.) in
methanol were refluxed for 7 h. The solvent was evaporated
and the crude material was purified by column
chromatography.
4.2.1. (R)-Methyl-2-p-anisyloxybutanoate (5). A colorless
oil was obtained in 61% yield. 1H NMR (CDCl3, 400 MHz)
6.85–6.79 (m, 4H), 4.48 (t, J¼6.3 Hz, 1H), 3.76 (s, 3H),
3.74 (s, 3H), 1.96 (m, 2H), 1.07 (t, J¼7.4 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) 172.9, 154.9, 152.5, 116.9, 115.1, 79.2,
56.1, 52.5, 26.7, 10.1. Anal. calcd for C12H16O4: C, 64.27;
H, 7.19. Found: C, 64.28; H, 7.17. The enantiomeric ratio of
5 was determined to be 96:4 in favor of the R enantiomer by
CSP-HPLC using racemic material as a standard. (Chiralcel
OD column; 10% 2-propanol in hexane; 0.5 mL/min; the
R-enantiomer (major) had a retention time of 13.0 min, and
the S-enantiomer (minor) had a retention time of 11.1 min.)
Acknowledgements
This work was supported by Korea Research Foundation
Grant. (KRF 2000-015-DP0263).
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