T. Kawabata et al. / Tetrahedron Letters 43 (2002) 1465–1467
1467
Acknowledgements
J. Med. Chem. 1999, 42, 1367; (c) Schafmeister, C. E.; Po,
J.; Verdine, G. L. J. Am. Chem. Soc. 2000, 122, 5891.
6. Recently, excellent catalytic methods for asymmetric syn-
thesis of a-allylated a-amino acid derivatives have been
developed, see: (a) Kuwano, R. Ito, Y. J. Am. Chem. Soc.
1999, 121, 3236; (b) Ooi, T.; Takeuchi, M.; Kameda, M.;
Maruoka, K. J. Am. Chem. Soc. 2000, 122, 5228.
7. For examples, see: (a) Evans, D. A.; Ennis, M. D.;
Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737; (b)
Kimura, K.; Murata, K.; Otsuka, K.; Ishizuka, T.;
Haratake, M.; Kunieda, T.; Tetrahedron Lett. 1992, 33,
4461; (c) Tanaka, F.; Node, M.; Takana, K.; Mizuchi,
M.; Hosoi, S.; Nakayama, M.; Taga, T.; Fuji, K. J. Am.
Chem. Soc. 1995, 117, 12159; (d) Refs. 3b,d.
This work was supported by a Grant-in-Aid for Scien-
tific Research on Priority Areas (No. 706: Dynamic
Control of Stereochemistry) from the Ministry of Edu-
cation (Monbusho), Japan.
References
1. Chirality whose properties are time- and temperature-
dependent is referred to as dynamic chirality: Kawabata,
T.; Suzuki, H.; Nagae, Y.; Fuji, K. Angew. Chem., Int.
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Kawabata, T.; Chen, J.; Suzuki, H.; Nagae, Y.;
Kinoshita, T.; Chancharunee, S.; Fuji, K. Org. Lett.
2000, 2, 3883.
3. For examples of asymmetric synthesis of a,a-disubsti-
tuted a-amino acid derivatives utilizing intrinsic chirality
of parent a-amino acids, see: (a) Seebach, D.; Boes, M.;
Naef, R.; Schweizer, W. B. J. Am. Chem. Soc. 1983, 105,
5390; (b) Vedejs, E.; Fields, S. C.; Schrimpf, M. R. J.
Am. Chem. Soc. 1993, 115, 11612; (c) Ferey, V.; Toupet,
L.; Gall, T. L.; Mioskowski, C. Angew. Chem., Int. Ed.
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R.; Hitchcock, S. R.; Powell, D. R.; Schrimpf, M. R. J.
Am. Chem. Soc. 1999, 121, 2460.
4. For related asymmetric a-substitution of a-amino acid
derivatives without using external chiral sources, see: (a)
Seebach, D.; Wasmuth, D. Angew.Chem., Int. Ed. Engl.
1981, 20, 971; (b) Beagley, B.; Betts, M. J.; Pritchard, R.
G.; Schofield, A.; Stoodley, R. J.; Vohra, S. J. Chem.
Soc., Chem. Commun. 1991, 924; (c) Betts, M. J.;
Pritchard, R. G.; Schofield, A.; Stoodley, R. J.; Vohra, S.
J. Chem., Soc. Perkin Trans 1 1999, 1067.
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9. Treatment of 4 (R=Me) with 6 M HCl (reflux, 4 h) gave
(S)-a-methyl phenylalanine, [h]2D1=−18 (c 0.5, H2O). Lit.
[h]2D0=−22 (c 1, H2O): Kruizinga, W. H.; Bolster, J.;
Kellog, R. M.; Kamphuis, J.; Boesten, W. H.; Meijer, E.
M.; Schoemaker, H. E. J. Org. Chem. 1988, 53, 1826.
10. A typical experimental procedure for a-alkylation: A
KHMDS solution (Brown, C. A. J. Org. Chem. 1974, 39,
3913) in THF (0.46 M, 1.43 mL, 0.66 mmol) was diluted
with 3 mL of toluene. A solution of 3 (129 mg, 0.30
mmol; dried azeotropically with toluene prior to use) in
toluene (2.0 mL) was added to the KHMDS solution at
−78°C. After stirring for 30 min, a solution of cinnamyl
iodide (110 mg, 0.45 mmol) in toluene (1.0 mL) was
added. Stirring was continued for 17 h at −78°C. The
mixture was poured into saturated aq NH4Cl and
extracted with ethyl acetate. The organic phase was
washed with saturated aq. NaHCO3 and brine, dried over
anhydrous sodium sulfate, filtered, and concentrated in
vacuo. The residue was purified by preparative TLC
(SiO2, EtOAc:hexane=1:3) to give 4 (R=CH2CH=
CHPh) (146 mg, 89% yield). Enantiomeric excess of 4 was
determined by HPLC analysis with Daicel Chiralpak AD,
hexane:2-propanol=97:3, flow 0.8 mL/min, tR=82, 89
min.
11. The enhancement of ee in a-allylation of 3 is not due to
a longer half-life of the enolate intermediate to racemiza-
tion. The half-life to racemization of an enolate generated
from 1 and KHMDS is 22 h at −78°C, which is long
enough for the chiral enolate to undergo a-allylation
without significant loss of its enantiomeric purity.
5. a-Allylated a-amino acids are versatile components of
functional peptides, see: (a) Abell, A. D.; Gardiner, J.;
Phillips, A. J.; Robinson, W. T. Tetrahedron Lett. 1998,
39, 9563; (b) Boatman, P. D.; Ogbu, C. O.; Eguchi, M.;
Kim, H.; Nakanishi, H.; Cao, B.; Shea, J. P.; Kahn, M.