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T. Yamauchi et al. / Tetrahedron 61 (2005) 1731–1736
added dropwise to a stirred solution of oxazolidine (1e)
(0.5 mmol) in dry THF (5 mL) at rt under nitrogen over
10 min period. After the reaction mixture was stirred for
20 h, it was quenched with a small amount of water and
diluted with ether (10 mL). The resulting white precipitate
was filtered off, and the filtrate was washed with saturated
aqueous NH4Cl (10 mL). The aqueous phase was extracted
with ether (2!10 mL). The combined organic extract was
washed with brine, dried over anhydrous Na2SO4, and
concentrated under reduced pressure to leave a oily residue,
which was subjected to column chromatography on silica
gel with hexane–ether (2:1) to give a diastereomeric mixture
of amine (2e) (85% yield, 94:6 mixture). Diastereomers
were separated by column chromatography on silica gel
with hexane–ether (3:1) to give pure (S,R)-2e as
colorless oil. [a]2D4ZK68.0 (c 1.40, CHCl3). MS m/z: CI,
374 (MCC1, base peak); EI, 373 (MC), 342 (MC
KCH2OH), 133 (base peak). IR (CHCl3, cmK1): 3440 (O–H).
1H NMR (CDCl3) d: 1.51 (3H, d, JZ7.1 Hz), 1.55 (1H, br),
2.05 (6H, s), 2.22 (3H, s), 3.66 (1H, d, JZ12.7 Hz), 3.86
(1H, dd, JZ9.4, 4.9 Hz), 4.01 (1H, d, JZ12.7 Hz), 4.02
(1H, q, JZ7.1 Hz), 4.15 (1H, dd, JZ10.7, 4.9 Hz), 4.26
(1H, dd, JZ10.7, 9.4 Hz), 6.77 (2H, s), 6.87–7.01 (4H, m),
7.13–7.29 (6H, m). 13C NMR (CDCl3) d: 16.03q, 19.75q,
20.78q, 43.82t, 54.71d, 61.10t, 61.65d, 126.49d, 126.99d,
127.57d, 128.08d, 128.25d, 128.78d, 129.23d, 132.45s,
136.27s, 138.21s, 139.96s, 143.97s. Anal. Calcd for
C26H31NO: C, 83.60; H, 8.37; N, 3.75. Found: C, 83.79;
H, 8.51; N, 3.72.
Acknowledgements
This work was supported in part by a grant from the
Ministry of Education, Culture, Sports, Science and
Technology of Japan and the promotion and Mutual Aid
Corporation for Private Schools of Japan.
References and notes
1. For reviews on organometallic additions to imine and their
derivatives, see: (a) Enders, D.; Reinhold, U. Tetrahedron:
Asymmetry 1997, 8, 1895–1946. (b) Bloch, R. Chem. Rev. 1998,
98, 1407–1438. (c) Alvaro, G.; Savoia, D. Synlett 2002,
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2. (a) Takahashi, H.; Hsieh, B. C.; Higashiyama, K. Chem. Pharm.
Bull. 1990, 38, 2429–2434. (b) Higashiyama, K.; Inoue, H.;
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K. Chem. Pharm. Bull. 1998, 46, 384–389. (d) Yamauchi, T.;
Takahashi, H.; Higashiyama, K. Heterocycles 1998, 48,
1813–1823. (e) Ishii, A.; Miyamoto, F.; Higashiyama, K.;
Mikami, K. Tetrahedron Lett. 1998, 39, 1199–1202. (f)
Poerwono, H.; Higashiyama, K.; Takahashi, H. J. Org. Chem.
1998, 63, 2711–2714.
3. (a) Maruoka, K.; Imoto, H.; Saito, S.; Yamamoto, H. J. Am.
Chem. Soc. 1994, 116, 4131–4132. (b) Maruoka, K.; Ito, M.;
Yamamoto, H. J. Am. Chem. Soc. 1995, 117, 9091–9092. (c)
Ooi, T.; Miura, T.; Kondo, Y.; Maruoka, K. Tetrahedron Lett.
1997, 38, 3947–3950. (d) Ooi, T.; Kondo, Y.; Kon-I, K.;
Maruoka, K. Chem. Lett. 1998, 403–404. (e) Saito, S.; Sone, T.;
Shimada, K.; Yamamoto, H. Synlett 1999, 81–83. (f) Marx, A.;
Yamamoto, H. Synlett 1999, 584–586. (g) Saito, S.; Shiozawa,
M.; Yamamoto, H. Angew. Chem., Int. Ed. 1999, 38,
1769–1771. (h) Saito, S.; Yamazaki, S.; Yamamoto, H.
Angew. Chem., Int. Ed. 2001, 40, 3613–3617. (i) Saito, S.;
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T.; Ishihara, K.; Saito, S.; Yamamoto, H. Angew. Chem., Int.
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4.3. General procedure for removal of the N-2,4,6-
trimethylbenzyl group from (R,R)- and (S,R)-2e
A single diastereomer of (R,R)- and (S,R)-2e (0.134 mmol)
and trifluoroacetic acid (5 mL) was stirred at 50 8C for 3
days, and then diluted with water (20 mL). The resulting
aqueous phase was basified with 10% NaOH solution and
extracted with CH2Cl2 (3!20 mL). The combined extracts
were washed with brine, dried over anhydrous Na2SO4, and
concentrated under reduced pressure to leave a oily residue,
which was subjected to column chromatography on silica
gel with ethyl acetate–hexane (1:2) to give (R,R)- and (S,R)-
3, respectively.
4. (a) Denmark, S.; Seierstad, M. J. Org. Chem. 1999, 64,
1610–1619. (b) Kanemasa, S.; Ueno, N.; Shirahase, M.
Tetrahedron Lett. 2002, 43, 657–660.
5. (a) Takahashi, H.; Suzuki, Y.; Kametani, T. Heterocycles 1983,
20, 607–610. (b) Takahashi, H.; Niwa, H.; Higashiyama, K.
Heterocycles 1988, 27, 2099–2102. (c) Pridgen, L. N. J. Org.
Chem. 1991, 56, 1340–1344. (d) Higashiyama, K.; Inoue, H.;
Takahashi, H. Tetrahedron 1994, 50, 1083–1092. (e) Poerwono,
H.; Higashiyama, K.; Yamauchi, T.; Takahashi, H. Hetero-
cycles 1997, 46, 385–400. (f) Poerwono, H.; Higashiyama, K.;
Yamauchi, T.; Kubo, H.; Ohmiya, S.; Takahashi, H.
Tetrahedron 1998, 54, 13955–13970.
4.3.1. Synthesis of (Z,R)-N-isopropyliminium–aluminum
complex (4h) for NOE experiment. A mixture of 2,6-
diphenylphenol (0.148 g, 0.6 mmol) and Me3Al (0.1 mL,
0.2 mmol; 2 M in toluene) in dry CH2Cl2 was stirred at rt
under nitrogen for 30 min to afford the solution of ATPH.6
Then the solution was concentrated under reduced pressure
and residue was solved in CDCl3 (0.5 mL). To this solution
was added the solution of oxazolidine (1c) (0.1 mmol) in
CDCl3 (0.5 mL) and stirred at rt for 2 h to obtain the CDCl3
solution of iminium–aluminum complex (4h). The solution
was used for NOE experiment without purification and the
data was showed some peak for complicated chart: 1H NMR
(CDCl3) d: 0.55 (3H, brd), 0.75 (3H, brd), 1.41 (3H, br),
1.54 (1H, br), 2.67 (1H, br), 2.99 (1H, br), 3.50 (1H, brdd),
6.52 (2H, brd).
6. The assignment of 1H NMR spectrum on 10 and 20 position of 4h
determined as follows. 20-Dideuteriumed iminium–aluminum
complex (4h0) was obtained from (R)-phenylglycine with
LiAlD4 for 5 steps by the similar procedure.4 In 4h0, the signals
1
of H NMR spectrum on 20 position (d: 1.54, 2.67 ppm) were
not observed, and the signal on 10 position (d: 3.50 ppm) was
observed. Therefore, the assignment of 1H NMR spectrum on 10
and 20 position of 4h was determined.