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D. Uraguchi et al.
CLUSTER
was extracted with EtOAc (3×) and the organic extracts were
washed with sat. aq NaCl. The combined organic phase was dried
over Na2SO4, filtered, and concentrated. The residue was purified
by column chromatography on silica gel using hexane–EtOAc
(10:1) as eluent to give 3aa (91%) as colorless paste. The ee was de-
termined by chiral stationary phase HPLC analysis [DAICEL
CHIRALCEL OD-H, hexane–2-PrOH (1000:1), flow rate = 0.5
mL/min, tR = 39.0 (R) and 48.3 (S) min]. The absolute configuration
References
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1
was determined after complete deprotection. H NMR (300 MHz,
CDCl3): d = 7.85 (d, J = 7.5 Hz, 2 H), 7.52 (t, J = 7.5 Hz, 1 H), 7.41
(t, J = 7.5 Hz, 2 H), 7.19–7.12 (m, 5 H), 5.68 (ddt, J = 16.8, 9.9, 7.2
Hz, 1 H), 5.21 (dd, J = 16.8, 1.8 Hz, 1 H), 5.12 (dd, J = 9.9, 1.8 Hz,
1 H), 3.23 (d, J = 13.5 Hz, 1 H), 3.16 (d, J = 13.5 Hz, 1 H), 2.77 (dd,
J = 13.5, 7.2 Hz, 1 H), 2.70 (d, J = 13.5, 7.2 Hz, 1 H).
Deprotection of Alkylated Azlactone 3aa to a,a-Disubstituted
a-Amino Acid 4
A solution of 3aa (0.09 mmol) in 90% aq TFA (1.8 mL) was stirred
for 12 h at 100 °C. After cooling to r.t., the reaction mixture was
concentrated, and the resulting residue was purified by ion-ex-
change resin (Amberlite IR120; H+ form) according to the literature
procedure.12 Analytically pure a,a-disubstituted a-amino acid 4 was
obtained in 81% yield, and its absolute configuration was deter-
mined to be R by comparison of optical rotation with the literature
value. [a]D25 –22.9 (c 1.0, H2O) for 91% ee; lit.13 [a]D20 +27.3 (c 1.0,
H2O). 1H NMR (300 MHz, CD3OD):d = 7.36–7.24 (m, 5 H), 5.86
(dddd, J = 15.9, 10.8, 8.4, 6.3 Hz, 1 H), 5.25 (d, J = 15.9 Hz, 1 H),
5.24 (d, J = 10.8 Hz, 1 H), 3.29 (d, J = 14.4 Hz, 1 H), 2.96 (d,
J = 14.4 Hz, 1 H), 2.78 (dd, J = 14.4, 6.3 Hz, 1 H), 2.43 (dd,
J = 14.4, 8.4 Hz, 1 H).
Acknowledgment
This work has been partially supported by the Global COE Program
in Chemistry of Nagoya University, Grant-in-Aid from the Ministry
of Education, Culture, Sports, Science and Technology, Japan, and
the Naito Science & Engineering Foundation.
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Synlett 2009, No. 4, 658–660 © Thieme Stuttgart · New York