N. Kise et al. / Tetrahedron Letters 42 (2001) 7637–7639
7639
reactions in THF gave completely racemic [1,2]
migrated product 6 in high yields (runs 1 and 2). Using
less polar Et2O, toluene, or hexane as a solvent, (R)-6
(retention) was produced in 33–38% ee, although the
yields were decreased (runs 3–6). The ee values of the
obtained 6 were determined by their acid hydrolysis to
a-methylphenylglycine (7) which specific rotations were
compared with reported data; (R)-7: lit.9 [a]D23−85.5 (c
1.0, 1 M HCl).
York, 1991; (b) Stanton, M. G.; Gagne`, M. R. J. Org.
Chem. 1997, 62, 8240; (c) Wright, S. W.; Hageman, D. L.;
Wright, A. S.; McClure, L. D. Tetrahedron Lett. 1997, 38,
7345; (d) Strazzolini, P.; Scuccato, M.; Giumanini, A. G.
Tetrahedron 2000, 56, 3625.
5. Preparation of 1a: To an ice-cooled solution of benzyl-
amine (1.07 g, 10 mmol) in CH2Cl2 (10 mL) was added
dropwise a solution of (Boc)2O (2.18 g, 10 mmol) in
CH2Cl2 (10 mL). After the mixture was stirred at room
temperature for 30 min, the solvent was removed in
vacuo. To the crude N-Boc–protected benzylamine,
(Boc)2O (3.27 g, 15 mmol) and DMAP (0.2 g) were added
and the mixture was stirred at 80°C for 2 h. The product
1a was purified by column chromatography on silica gel
Several methods have been reported for the selective
deprotection of the N-Boc group in N-Boc-protected
t-butyl esters of a-aminoacids.10 Actually, the treatment
of 2a with 1 equiv. of p-TsOH in ether afforded p-
TsOH salt of phenylglycine t-butyl ester (8) selectively
(Eq. (3)).
1
(98% yield): H NMR (CDCl3): l 1.45 (s, 18 H), 4.76 (s,
2 H), 7.28 (brs, 5 H); 13C NMR (CDCl3): l 27.9 (q), 49.4
(t), 82.3 (s), 126.8 (d), 127.0 (d), 128.1 (d), 138.3 (s), 152.3
(s).
p-TsOH•H2O
Ph
CO2Bu-t
Ph
CO2Bu-t
ether
25 ºC, 12 h
6. Hara, O.; Ito, M.; Hamada, Y. Tetrahedron Lett. 1998,
39, 5537.
NH2•p-TsOH
8 90%
NHBoc
2a
7. Raucher, S.; Koolpe, G. A. J. Org. Chem. 1978, 43, 3794.
8. Typical procedure is as follows. To a suspension of
t-BuOK (0.14 g, 1.25 mmol) and diisopropylamine (0.175
mL, 1.25 mmol) in THF (5 mL) was added 1.6 M n-BuLi
in hexane (0.78 mL, 1.25 mmol) at −78°C and the mix-
ture was stirred for 15 min. To the mixture, a solution of
1a (0.307 g, 1 mmol) in THF (5 mL) was added dropwise
and additional stirring was continued for 30 min at this
temperature. The reaction mixture was diluted with 1 M
HCl (20 mL) and the mixture was extracted with ether
(10 mL×3). The product 2a was isolated by column
chromatography on silica gel (97% yield): 1H NMR
(CDCl3): l 1.38 (s, 9H), 1.43 (s, 9H), 5.20 (d, 1H, J=7.6
Hz), 5.57 (d, 1H, J=7.6 Hz), 7.27–7.40 (m, 5H); 13C
NMR (CDCl3): l 27.6 (q), 28.2 (q), 57.9 (d), 79.5 (s), 81.9
(s), 126.6 (d), 127.7 (d), 128.3 (d), 137.4 (s), 154.5 (s),
169.8 (s).
9. Vachal, P.; Jacobsen, E. N. Org. Lett. 2000, 2, 867.
10. (a) Gray, C. J.; Khoujah, A. M. Tetrahedron Lett. 1969,
2647; (b) Hiskey, R. G.; Beacham, III, L. M.; Matl, V. G.
J. Org. Chem. 1972, 37, 2472; (c) Goodacre, J.; Ponsford,
R. J.; Stirling, I. Tetrahedron Lett. 1975, 3609; (d) Gib-
son, F. S.; Bergmeier, S. C.; Rapoport, H. J. Org. Chem.
1994, 59, 3216; (e) Lin, L. S.; Lanza, Jr., T.; de Laszlo, S.
E.; Truong, Q.; Kamenecka, T.; Hagmann, W. K. Tetra-
hedron Lett. 2000, 41, 7013.
(3)
In summary, we have demonstrated that [1,2] Boc
migration was effected by the treatment of N,N-di-Boc-
protected benzylamines with KDA/t-BuOLi. This reac-
tion provides a useful method for the synthesis of
t-butyl esters of phenylglycines from benzylamines.
References
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