M.-L. Han et al. / Tetrahedron: Asymmetry 22 (2011) 222–225
225
of a 2.5 M solution of n-BuLi in hexane. The resulting solution was
stirred at ꢀ35 °C for 30 min, and then 7.0 mL (55.0 mmol,
1.1 equiv) of Me3SiCl was added slowly at the same temperature.
The reaction mixture was stirred for 1 h and then 60 mL
(150 mmol, 3 equiv) of a 2.5 M solution of n-BuLi was added drop-
wise. After the addition was completed, the reaction mixture was
stirred at ꢀ35 °C for 4 h. The reaction mixture was slowly warmed
to room temperature and stirred overnight. The reaction mixture
was cooled to ꢀ35 °C again, and an appropriate carbonyl com-
pound (55 mmol, 1.1 equiv) was added slowly over 0.5 h. The reac-
tion mixture was stirred for another 3 h at the same temperature,
and then warmed to room temperature. After stirring for another
10 h, a solution of 1 M aqueous HCl was added slowly until the
reaction mixture became clear in both phases. The aqueous phase
was extracted with ether (3 ꢁ 50 mL). Combined organic layers
were dried over Na2SO4 and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography
(petroleum ether/acetate/triethylamine, 4/1/0.4) to give the tar-
geted amino alcohols 4a–d and recover the unreacted (S)-1-phen-
ylethylamine 5.
80 °C for 30 min under argon atmosphere. After cooling to room
temperature, 2-propanol (15 mL), KOH (0.6 mL, 0.1 M in 2-propa-
nol), acetophenone (0.5 mmol, dissolved in 5 mL of 2-propanol)
were added. The resulting solution was stirred at ꢀ10 °C, and the
reaction was monitored by GC or HPLC. The mixture was neutral-
ized with dilute HCl and 2-propanol was removed under reduced
pressure. The residue was diluted with ethyl acetate (25 mL) and
the organic solution was washed with brine (3 ꢁ 20 mL) and dried
over anhydrous MgSO4. After evaporation of the solvent, the
residue was subjected to short column chromatography on silica
gel (hexane/ethyl acetate as eluent) for ee and conversion
determination.
Acknowledgments
We are grateful for the generous financial supports from the
National Natural Science Foundation of China (20873145,
20972156, and 20802076), and the Planned Science and Technol-
ogy Project of Dalian (2009E11SF132).
References
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Prepared as a white solid from paraformaldehyde in 16.1% yield.
½
a 2D0
ꢂ
¼ ꢀ18:3 (c 0.38, ethanol); 1H NMR (400 MHz, CDCl3): d 1.59–
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½
a 2D0
ꢂ
¼ ꢀ3:3 (c 0.38, ethanol); 1H NMR (400 MHz, CDCl3): d 1.55–
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1.68 (m, 9H), 3.51 (s, 3H), 4.85–4.87 (m, 1H), 7.21–7.44 (m, 4H);
13C NMR (100 MHz, CDCl3): d 24.6, 32.8, 33.0, 48.1, 73.3, 126.5,
126.9, 127.0, 127.3, 143.5, 146.5; HRMS (m/z) calcd for
C
11H17NO: 179.1310, found: 179.1310.
4.2.3. 1-{2-[(S)-1-Aminoethyl]phenyl}cyclohexanol 4c
Prepared as colorless oil from cyclohexanone in 11.9% yield.
½
a 2D0
ꢂ
¼ þ10:2 (c 0.35, ethanol); 1H NMR (400 MHz, CDCl3): d
1.24–1.99 (m, 13H), 3.24 (m, 1H), 7.22–7.48 (m, 4H); 13C NMR
(100 MHz, CDCl3): d 22.1, 22.3, 24.0, 25.8, 39.2, 40.0, 47.9, 73.9,
126.4, 126.9, 127.0, 127.5, 143.2, 147.2; HRMS (m/z) calcd for
C
14H21NO: 219.1623, found: 219.1626.
4.2.4. {2-[(S)-1-Aminoethyl]phenyl}diphenylmethanol 4d
Prepared as a white solid from benzophenone in 37.9% yield.
½
a 2D0
ꢂ
¼ ꢀ73:2 (c 0.38, ethanol); 1H NMR (400 MHz, CDCl3): d 1.33
(d, J = 6.4 Hz, 3H), 4.18 (m, 1H), 6.63–6.65 (m, 1H), 7.06–7.10 (m,
1H), 7.26–7.28 (m, 10H), 7.50–7.51 (m, 1H); 13C NMR (100 MHz,
CDCl3): d 23.8, 47.1, 82.4, 126.4, 126.7, 126.8, 126.9, 127.3, 127.7,
127.8, 128.6, 130.7, 142.3, 146.9, 147.9, 149.1; HRMS (m/z) calcd
for C21H21NO: 303.1623, found: 303.1626.
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4.3. General procedure for the transfer hydrogenation of
aromatic ketones
A mixture of [RuCl2(p-cymene)]2 (1.5 mg, 0.0025 mmol) and
(S)-4a (3.0 mg, 0.02 mmol) in 2 mL of 2-propanol was stirred at