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LETTER
H.; Papageorgiou, G.; Wilkins, R. F. J. Chem. Soc., Chem.
Commun. 1988, 1161. (e) Shono, T.; Tsubata, K.; Okinaga,
N. J. Org. Chem. 1984, 49, 1056. (f) Hosomi, A.; Iijima, S.;
Sakurai, H. Tetrahedron Lett. 1982, 23, 547.
natural amino acid derivatives such as b-alanine and as-
partic acid. We also found that a series of these N,O-acetal
would effectively function as a glycine cation equivalent.
In particular, an N,O-acetal with a bis(trimethylsilyl)ami-
no group was found to be effective in the single-step prep-
aration of N-unprotected amino acid derivatives.
(7) When the similar reaction was carried out with only TMSCl
(1.2 equiv), the desired Mannich-type reaction did not
proceed. In addition, when the reaction was carried out with
less than 10 mol% of the hafnium catalyst, e.g., 5 mol%, the
product yield of 7 decreased to 80%; TfOH and TMSOTf
were ineffective for the present Mannich-type reaction.
(8) General Procedure for the Synthesis of N,O-Acetals 2
To a freshly distilled THF solution (100 mL), the
corresponding secondary amine (24 mmol), i-Pr2NEt (4.1
mL, 24 mmol), and methyl 2-bromo-2-methoxyacetate (11
mL, 20 mmol) were successively added, and the solution
was stirred at r.t. After 2 h, the reaction was quenched by
adding a sat. aq soln (2 mL) of NaHCO3. The aqueous layer
was extracted with CHCl3, the organic phase was combined,
dried over anhyd Na2CO3, filtered, and evaporated under
reduced pressure. The crude product was distilled to give the
corresponding N,O-acetals 2.
Acknowledgment
This work was partially supported by a fund for the ‘High-Tech Re-
search Center’ project for private universities, a matching fund sub-
sidy from MEXT, 2000–2004, and 2005–2007, and by a grant from
the Japan Private School Promotion Foundation, 2008.
References and Notes
(1) (a) Nájera, C.; Sansano, J. M. Chem. Rev. 2007, 107, 4584.
(b) Taggi, A. E.; Hafez, A. M.; Lectka, T. Acc. Chem. Res.
2003, 36, 10. (c) Arend, M.; Westermann, B.; Risch, N.
Angew. Chem. Int. Ed. 1998, 37, 1044. (d) Williams, R. M.;
Hendrix, J. A. Chem. Rev. 1992, 92, 889. (e) a-Amino Acid
Synthesis, In Tetrahedron; O’Donnell, M. J., Ed.;
Tetrahedron Symposia in Print, Elsevier: Amsterdam, .
(f) Wagner, I.; Musso, H. Angew. Chem., Int. Ed. Engl. 1983,
22, 816.
(2) (a) Kano, T.; Hato, Y.; Yamamoto, A.; Maruoka, K.
Tetrahedron 2008, 64, 1197. (b) Dziedzic, P.; Cordova, A.
Tetrahedron: Asymmetry 2007, 18, 1033. (c) Jacobsen, M.
F.; Ionita, L.; Skrydstrup, T. J. Org. Chem. 2004, 69, 4792.
(d) Janczuk, A.; Zhang, W.; Xie, W.; Lou, S.; Cheng, J.;
Wang, P. G. Tetrahedron Lett. 2002, 43, 4271.
General Procedure for the Hf(OTf)4-Catalyzed
Mannich-Type Reaction of a Silyl Ether with an N,O-
Acetal
An N,O-acetal (0.50 mmol), a silyl ether (0.60 mmol), and
Hf(OTf)4 (38.8 mg, 0.0500 mmol) were successively mixed
together in CH2Cl2 (2 mL) at r.t. with stirring. The resulting
solution was stirred until the reaction reached completion, as
shown by TLC (SiO2, hexane–EtOAc = 4:1). The reaction
was quenched with a sat. aq soln (2 mL) of NaHCO3. The
combined organic layer was dried over Na2CO3 and
evaporated under reduced pressure. The crude product was
purified by SiO2 column chromatography (hexane and
hexane–EtOAc) to afford amino acid derivatives.
Spectral Data for Selected Compounds
(e) Johannsen, M. Chem. Commun. 1999, 2233.
(f) Manabe, K.; Oyamada, H.; Sugita, K.; Kobayashi, S.
J. Org. Chem. 1999, 64, 8054. (g) Hagiwara, E.; Fujii, A.;
Sodeoka, M. J. Am. Chem. Soc. 1998, 120, 2474.
(h) Colvin, E. W.; McGarry, D.; Nugent, M. J. Tetrahedron
1988, 44, 4157. (i) Fiaud, J.-C.; Kagan, H. B. Tetrahedron
Lett. 1970, 11, 1813.
2-(1-Piperidinyl)butanedioic Acid 1-Methyl 4-Ethyl
Ester (7)
Pale yellow oil. 1H NMR (500 MHz, CDCl3): d = 1.24 (t, 3
H, J = 7 Hz), 1.39–1.42 (m, 2 H), 1.52–1.55 (m, 4 H), 2.41
(m, 2 H), 2.58–2.63 (m, 3 H), 2.81–2.86 (m, 1 H), 3.69–3.72
(m, 4 H), 4.13 (q, 2 H, J = 7 Hz). 13C NMR (125 MHz,
CDCl3): d = 14.0, 24.2, 26.3, 34.2, 50.8, 51.1, 60.3, 64.1,
171.2, 171.3. MS (EI): m/z (%) = 243 (100) [M+]. HRMS:
m/z calcd for C12H21NO4: 243.1471; found: 243.1469.
2-Diallylamino-3,3-Dimethyl-butanedioic Acid 1-Ethyl
4-Methyl Ester (15)
(3) (a) Janey, J. M.; Hsiao, Y.; Armstrong, J. D. J. Org. Chem.
2006, 71, 390. (b) Ferraris, D.; Young, B.; Dudding, T.;
William, J.; Drury, I.; Lectka, T. Tetrahedron 1999, 55,
8869. (c) Ferraris, D.; Dudding, T.; Young, B.; Drury, W. J.;
Lectka, T. J. Org. Chem. 1999, 64, 2168. (d) Kobayashi, S.;
Ishitani, H.; Komiyama, S.; Oniciu, D. C.; Katritzky, A. R.
Tetrahedron Lett. 1996, 37, 3731. (e) Tsukamoto, T.;
Kitazume, T. Chem. Lett. 1992, 21, 1377. (f) Okano, K.;
Morimoto, T.; Sekiya, M. Chem. Pharm. Bull. 1985, 33,
2228. (g) Okano, K.; Morimoto, T.; Sekiya, M. J. Chem.
Soc., Chem. Commun. 1984, 883. (h) Ben-Ishai, D.; Sataty,
I.; Bernstein, Z. Tetrahedron 1976, 32, 1571. (i) Zoller, U.;
Ben-Ishai, D. Tetrahedron 1975, 31, 863.
Pale yellow oil. 1H NMR (500 MHz, CDCl3): d = 1.21 (t, 3
H, J = 7.0 Hz), 1.23 (s, 3 H), 1.26 (s, 3 H), 3.00–3.10 (m, 2
H), 3.30–3.40 (m, 2 H), 3.70 (s, 3 H), 3.83 (s, 1 H), 4.00–4.20
(m, 2 H), 5.10–5.20 (m, 4 H), 5.70–5.80 (m, 2 H). 13C NMR
(125 MHz, CDCl3): d = 14.0, 19.9, 25.3, 45.9, 50.9, 56.4,
60.4, 66.8, 117.1, 136.4, 172.3, 177.2. MS–FAB: m/z (%) =
284 (100) [M+ + H]. HRMS–FAB: m/z calcd for C15H25NO4:
284.1857; found: 284.1862.
(4) Sugiura, M.; Mori, C.; Hirano, K.; Kobayashi, S. Can. J.
Chem. 2005, 83, 937.
(9) The E/Z ratio of amino acid derivatives 3–5 is nearly in
agreement with that of the starting material, enol silyl ether 1.
(10) Selected papers for formation of a primary amino group by
hydrolytic cleavage of an N–Si bond, see: (a) Gong, Y.;
Kato, K.; Kimoto, H. Bull. Chem. Soc. Jpn. 2002, 75, 2637.
(b) Gong, Y.; Kato, K. J. Fluorine Chem. 2001, 108, 83.
(c) Tanino, K.; Takahashi, M.; Murayama, K.; Kuwajima, I.
J. Org. Chem. 1992, 57, 7009. (d) Bestmann, H. J.; Wölfel,
G. Angew. Chem., Int. Ed. Engl. 1984, 23, 53.
(5) (a) Sakai, N.; Asano, J.; Shimano, Y.; Konakahara, T.
Tetrahedron 2008, 64, 9208. (b) Sakai, N.; Asano, J.;
Shimano, Y.; Konakahara, T. Synlett 2007, 2675. (c) Sakai,
N.; Hirasawa, M.; Hamajima, T.; Konakahara, T. J. Org.
Chem. 2003, 68, 483. (d) Sakai, N.; Hamajima, T.;
Konakahara, T. Tetrahedron Lett. 2002, 43, 4821.
(6) Selected papers for metal-promoted Mannich-type reaction
using carbon nucleophiles and N,O-acetals, see:
(a) Huguenot, F.; Brigaud, T. J. Org. Chem. 2006, 71, 2159.
(b) DeNinno, M. P.; Eller, C.; Etienne, J. B. J. Org. Chem.
2001, 66, 6988. (c) Loh, T.-P.; Liung, S. B. K. W.; Tan,
K.-L.; Wei, L.-L. Tetrahedron 2000, 56, 3227. (d) Heaney,
(e) Morimoto, T.; Takahashi, T.; Sekiya, M. J. Chem. Soc.,
Chem. Commun. 1984, 794.
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