Y. Kawanami et al. / Tetrahedron 56 (2000) 175–178
177
(S)-4-Methyl-1,1-diphenyl-2-piperidino-1-pentanol 1a.
(S)-Leucine ethyl ester hydrochloride (391 mg, 2.0 mmol)
was suspended in Et2O (10 ml) and neutralized with 10%
aqueous NaOH solution. The aqueous solution was sepa-
rated and extracted with Et2O (2×5 ml) and the ethereal
solution was dried over MgSO4. The solution of the result-
ing amino-acid ester in THF (1 ml) was slowly added to
PhMgBr (2M solution in THF, 4 ml, 8.0 mmol) and the
mixture was stirred for 12 h at room temperature. An
aqueous saturated NH4Cl solution was added to the reaction
mixture and the THF solution was decanted. The aqueous
solution was twice washed with ethyl acetate. After
evaporation of the combined organic solution, the residue
was flash chromatographed (hexane/ethyl acetate, 1:1) to
748, 700 cmϪ1
;
1H NMR (CDCl3) d 0.95 (d, 3H,
J6.2 Hz), 1.01 (d, 3H, J4.8 Hz), 1.10–2.24 (m, 13H),
2.32–3.08 (m, 9H), 4.74 (s, 1H), 6.87–7.46 (m, 10H); 13C
NMR (CDCl3) d 143.5, 143.0, 128.3, 125.5, 125.4, 77.2,
73.5, 67.2, 39.3, 38.1, 35.9, 30.0, 29.8, 27.2, 26.5, 24.6,
24.2. Anal. Calcd for C27H39NO: C, 82.39; H, 9.99; N,
3.56%. Found: C, 82.23; H, 9.85; N, 3.44%.
Typical procedure for enantioselective addition of
diethylzinc to aldehyde: (R)-1-phenyl-1-propanol. To a
solution of 1d (197 mg, 0.5 mmol, 10 mol%) in hexane
(10 ml) was added benzaldehyde (0.51 ml, 5 mmol) under
an argon atmosphere and the resulting solution was stirred at
room temperature. After 20 min, diethylzinc (1.0M solution
in hexane, 10 ml, 10 mmol) was added to the mixture at 0ЊC
and stirred for 12 h. After being quenched with aqueous
saturated NH4Cl solution, the mixture was extracted with
CH2Cl2, dried (MgSO4), and concentrated. The residue was
purified by flash column chromatography (hexane/ethyl
acetate 4:1) to give (R)-1-phenyl-1-propanol (618 mg,
91%) and the recovered 1d (189 mg, 96%). The ee was
determined to be 97% by HPLC analysis using a DAICEL
Chiralcel OB column (hexane/i-PrOH 98:2, flow rate:
0.5 ml minϪ1). For 1-(4-chlorophenyl)-1-propanol, 1-(4-
methylphenyl)-1-propanol and 1-(2-naphthyl)-1-propanol,
1
give the amino alcohol (242 mg, 45%); H NMR d 0.86
(d, 3H, J6.4 Hz), 0.88 (d, 3H, J6.2 Hz), 0.95–1.45 (m,
3H), 1.96 (br s, 1H), 3.96 (dd, 1H, J3.0, 9.1 Hz), 6.95–
7.70 (m, 10H). To the amino alcohol in acetonitrile (9 ml),
1,5-diiodopentane (132 ml, 0.9 mmol) and K2CO3 (248 mg,
1.8 mmol) were added, and the mixture was refluxed for
24 h. After filtration of the reaction mixture and evapora-
tion, the residue was dissolved in CH2Cl2 and dried over
MgSO4. The residue was flash chromatographed (hexane/
ethyl acetate, 20:1) to give a colorless oil 1a (221 mg, 73%):
[a]2D5 Ϫ28.0 (c 2.93, CHCl3); IR (neat) 3380, 3070, 3030,
1
2920, 2860, 1720, 1660, 1495, 1450, 750, 705 cmϪ1; H
OB
column
(hexane/i-PrOH
98:2,
flow
rate:
NMR d 0.87 (d, 3H, J6.2 Hz), 1.07 (d, 3H, J6.4 Hz),
1.17–1.90 (m, 9H), 2.20–2.66 (m, 4H), 3.51 (dd, 1H,
J4.6, 9.2 Hz), 4.90 (s, 1H), 6.95–7.60 (m, 10H); 13C
NMR (CDCl3) d 145.8, 144.7, 128.0, 127.9, 127.7, 127.0,
126.9, 126.5, 77.4, 69.1, 52.8, 37.9, 27.1, 26.3, 24.6, 24.3,
21.1. Anal. Calcd for C23H31NO: C, 81.85; H, 9.26; N, 4.15%.
Found: C, 81.72; H, 9.29; N, 4.11%.
0.5 ml minϪ1). For 3-undecanol, 5-methyl-3-hexanol, and
1-cyclohexyl-1-propanol, after benzoylation, OD column
(hexane/i-PrOH 200:1, flow rate: 0.3 ml minϪ1). For
3-nonanol, after 4-nitrobenzoylation, AD column (hexane/
i-PrOH 200:1, flow rate: 1.0 ml minϪ1).
Acknowledgements
(S)-4-Methyl-1,1-bis(4-t-butylphenyl)-2-piperidino-1-
pentanol 1b. Prepared according to a previously described
procedure, 34 and 51%: [a]2D5 Ϫ27.1 (c 1.29, CHCl3); IR
(neat) 3250, 3080, 2950, 2850, 2800, 1655, 1605, 1508,
We are grateful to Professor T. Katsuki for helpful
discussions.
1460, 1360, 1265, 1165, 1100, 1015, 820, 750 cmϪ1
;
1H-NMR (CDCl3) d 0.86 (d, 3H, J6.2 Hz), 1.06 (d, 3H,
J5.9 Hz), 1.14–1.74 (m, 27H), 2.15–2.65 (m, 4H), 3.50
(dd, 1H, J4.6, 9.2 Hz), 6.20 (br s, 1H), 7.02–7.50 (m, 8H);
13C NMR (CDCl3) d 149.6, 149.1, 142.9, 141.6, 127.6,
127.4, 124.7, 123.6, 77.0, 69.1, 52.8, 37.8, 34.3, 31.4,
31.3, 31.1, 27.1, 26.4, 24.6, 24.4, 21.1. Anal. Calcd for
C31H47NO: C, 82.79; H, 10.53; N, 3.11%. Found: C,
82.65; H, 10.64; N, 3.02%.
References
1. (a) Gwley, R. E.; Aube, J. Principles of Asymmetric Synthesis;
Pergamon: London, 1996. (b) Noyori, R. Asymmetric Catalysis in
Organic Synthesis; Wiley: New York, 1994. (c) Seyden-Penne, J.
Chiral Auxiliaries and Ligands in Asymmetric Synthesis; Wiley:
New York, 1995.
2. Oguni, N.; Omi, T. Tetrahedron Lett. 1984, 25, 2823. For
review, see: (a) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833. (b)
Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30,
49.
(S)-5-Butyl-2-methyl-4-piperidino-5-nonanol 1c. Prepared
according to a previously described procedure, 35 and 61%:
[a]2D5 ϩ4.80 (c 2.93, CHCl3); IR (neat) 3400, 2920, 2860,
3. Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem.
Soc. 1986, 108, 6071.
1
1482, 1380, 1162, 1095 cmϪ1; H NMR (CDCl3) d 0.92
(t, 6H, J6.7 Hz), 0.96 (d, 6H, J6.7 Hz), 1.05–2.07 (m,
21H), 2.35–3.04 (m, 5H), 4.40 (s, 1H); 13C NMR (CDCl3) d
74.2, 67.7, 36.6, 35.6, 36.1, 27.4, 26.7, 25.8, 25.5, 24.9,
24.4, 23.9, 23.6, 21.3. Anal. Calcd for C19H39NO: C,
76.70; H, 13.21; N, 4.71%. Found: C, 76.62; H, 13.32; N,
4.62%.
4. Soai, K.; Ookawa, A.; Kaba, T.; Ogawa, K. J. Am. Chem. Soc.
1987, 109, 7111.
5. Soai, K.; Yokoyama, S.; Hayasaka, T. J. Org. Chem. 1991, 56,
4264.
6. Delair, P.; Einhorn, C.; Einhorn, J.; Luche, J. L. Tetrahedron
1995, 51, 165.
7. Beliczey, J.; Giffels, G.; Kragl, U.; Wandrey, C. Tetrahedron:
Asymmetry 1997, 8, 1529.
8. Partly presented at the 74th Meeting of Japan Chemical Society,
Kyoto, March 1998, Abstr. No. 2, 1D6 02 (p 982) and the 76th
Meeting, Kanagawa, March 1999, Abstr. No. 2, 4C1 18 (p 976).
(S)-6-Methyl-3-(2-phenylethyl)-1-phenyl-4-piperidino-3-
heptanol 1d. Prepared according to a previously described
procedure, 47 and 71%: [a]2D5 ϩ11.1 (c 1.9, CHCl3); IR
(neat) 3360, 3060, 3020, 2920, 1710, 1600, 1495, 1452,