B. Xu et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
5
instrument using Chiralpak AS-H and AD-H (4.6 mm ꢁ 25 cm)
column. High-resolution mass spectra (HRMS) were recorded
on an Agilent Technologies 1260 Infinity instrument. Optical
rotations were obtained by a 1 mL cell with a 1 dm path length
on a Perkin–Elmer-343 digital polarimeter.
4.2.5. (1R,2R)-N1-Benzyl-N1-pentylcyclohexane-1,2-diamine,
catalyst 3e
Colorless and transparent oil: ½a D25
ꢂ
¼ ꢀ25:5 (c 1.0, CHCl3); 1H
NMR d 0.85 (s, 3H), 1.14–1.30 (m, 7H), 1.52–1.94 (m, 5H), 2.19–
2.35 (dd, J = 12.3 2H), 3.31–3.41 (m, 3H), 3.72–3.76 (d, J = 10.5,
1H), 4.28–4.32 (d, J = 13.2, 1H), 4.63–4.69 (d, J = 15.6, 1H), 4.75
(br s, 2H), 7.54 (m, 5H) ppm; 13C NMR d 13.91, 22.39, 22.57,
24.99, 25.77, 28.52, 29.41, 34.85, 49.48, 51.13, 54.18, 65.77,
126.46, 127.98, 128.52, 140.83 ppm; HRMS (ESI) m/z calcd for
4.2. General procedure for the synthesis of catalyst 3
At first,
4 (4.28 g, 20.0 mmol, 1 equiv) and benzaldehyde
(10.60 g, 100.0 mmol; 5 equiv) were added to a 250-mL round bot-
tomed flask with methanol (100 mL) and stirred for 30 min at
room temperature. Then the reaction mixture was cooled to 0 °C,
and NaBH4 (3.78 g; 100 mmol; 5 equiv) was added. After 2.5 h,
cooling was stopped, and NaCNBH3 (2.48 g, 40 mmol; 2 equiv)
and the corresponding alkyl aldehyde (100 mmol; 5 equiv) were
added. Five hours later, 10 mL of H2O was added to stop the reac-
tion. The residue was purified through column chromatography on
silica gel (eluent, petroleum ether). The petroleum ether was re-
moved in vacuo, the resulting residue was taken up in 4 M HCl
(100 mL) and stirred for 12 h. The resulting solution was washed
three times with CH2Cl2 and adjusted to pH 13 with 4 M NaOH.
The aqueous layer was extracted three times with ethyl acetate
(120 mL), washed with brine (60 mL), and dried (Na2SO4). Solvent
removal in vacuo afforded crude 3 as a colorless and transparent oil
which was distilled in vacuo to afford pure 3.
C
18H30N2 [M+H]+ 274.2465, found: 275.2467.
4.2.6. (1R,2R)-N1-Benzyl-N1-heptylcyclohexane-1,2-diamine,
catalyst 3f
Colorless and transparent oil: ½a D25
ꢂ
¼ ꢀ23:6 (c 1.0, CHCl3); 1H
NMR d 0.82 (d, J = 6.9, 2H), 1.14–1.28 (m, 9H), 1.36–1.47 (m, 2H),
1.58–1.64 (t, J = 9.5 2H), 1.82–1.91 (m, 4H), 2.07–2.22 (m, 1H),
2.32–2.48 (m, 1H), 3.24 (s, 1H), 3.51–3.52 (d, J = 5.4, 2H), 3.78 (s,
1H), 4.22–4.26 (d, J = 13.2, 1H), 4.32–4.37 (d, J = 12.9, 1H), 4.74
(br s, 4.74), 7.55 (m, 5H) ppm; 13C NMR d 15.96, 24.45, 24.96,
25.21, 25.50, 27.06, 28.77, 30.36, 33.11, 33.34, 51.59, 53.91,
61.04, 66.23, 131.21, 131.96, 132.44, 133.16 ppm; HRMS (ESI)
m/z calcd for C20H34N2 [M+H]+ 302.2789, found: 303.2785.
4.3. General procedure for direct asymmetric aldol reactions
At first, 0.5 mmol of aryl aldehyde or isatin was added to a
mixture of ketone (cyclohexanone or acetone, 5 equiv), 15 or
20 mol % catalyst, 30 or 40 mol % acid, and 2.0 mL of solvent at
reaction temperature. The reaction mixture was stirred for the
indicated time and then purified through flash column chromatog-
raphy on a silica gel (petroleum ether/ethyl acetate) to afford the
pure products.
4.2.1. (1R,2R)-N1-Benzylcyclohexane-1,2-diamine, catalyst 3a
Colorless and transparent oil: ½a D25
ꢂ
¼ ꢀ31:5 (c 1.0, CHCl3); 1H
NMR d 1.32–1.46 (m, 2H), 1.58–1.62 (d, J = 11.1, 2H), 1.81–1.97
(m, 2H), 2.16–2.20 (d, J = 12.6, 1H), 2.43–2.47 (d, J = 13.2, 1H),
3.39–3.52 (m, 2H), 4.19–4.23 (d, J = 12.9, 1H), 4.46–4.50 (d,
J = 12.9, 1H), 4.75 (br s, 2H), 7.50 (m, 5H) ppm; 13C NMR d 25.01,
25.12, 28.81, 32.05, 51.53, 53.94, 61.06, 131.97, 132.46, 132.49,
133.90 ppm; HRMS (ESI) m/z: calcd for
C
13H20N2 [M+H]+
Acknowledgments
204.1698, found: 205.1699.
4.2.2. (1R,2R)-N1-Benzyl-N1-methylcyclohexane-1,2-diamine,
The authors are grateful to the National Natural Science
Foundation of China (Project No. 21271041) for financial aid to this
work. Li would like to thank the Scientific Research Innovation
Project for College Graduates of Jiangsu Province (Project
CXZZ12-0118).
catalyst 3b
Colorless and transparent oil: ½a D25
ꢂ
¼ ꢀ29:3 (c 1.0, CHCl3); 1H
NMR d 1.37 (s, 2H), 1.51 (s, 1H), 1.68 (s, 1H), 1.80 (s, 1H), 1.95 (s,
1H), 2.21 (s, 1H), 2.34 (s, 1H), 2.78–2.85 (t, J = 13.2, 3H), 3.47 (s,
1H), 3.68 (s, 1H), 4.43 (s, 2H), 4.69 (br s, 2H), 7.53 (m, 5H) ppm;
13C NMR d 24.76, 25.08, 25.47, 32.98, 37.55, 51.81, 61.59, 67.30,
131.05, 132.13, 133.15, 133.79 ppm; HRMS (ESI) m/z: calcd for
References
C
14H22N2 [M+H]+ 218.1845, found: 219.1909.
4.2.3. (1R,2R)-N1-Benzyl-N1-ethylcyclohexane-1,2-diamine,
catalyst 3c
Colorless and transparent oil: ½a D25
ꢂ
¼ ꢀ27:3 (c 1.0, CHCl3); 1H
NMR d 1.20–1.41 (m, 8H), 1.54–1.78 (m, 2H), 1.91–1.95 (d,
J = 11.4, 1H), 2.21–2.37 (m, 2H), 3.27–3.48 (m, 2H), 3.78–3.81 (d,
J = 9.6, 1H), 4.32–4.36 (d, J = 13.5, 1H), 4.75 (br s, 2H), 7.55 (m,
5H) ppm; 13C NMR d 12.41, 25.30, 28.81, 32.06, 33.10, 48.83,
51.54, 57.54, 65.48, 131.06, 132.30, 132.97, 133.87 ppm; HRMS
(ESI) m/z calcd for C15H24N2 [M+H]+ 233.1936, found: 233.2042.
4.2.4. (1R,2R)-N1-Benzyl-N1-propylcyclohexane-1,2-diamine,
catalyst 3d
Colorless and transparent oil: ½a D25
ꢂ
¼ ꢀ25:3 (c 1.0, CHCl3); 1H
NMR d 0.94–0.96 (d, J = 7.5, 3H), 1.30–1.41 (m, 3H), 1.69–1.94
(m, 5H), 2.19–2.35 (m, 2H), 3.13–3.21 (m, 2H), 3.38 (s, 1H), 3.73–
3.76 (d, J = 10.2, 1H), 4.28–4.32 (d, J = 13.6, 1H), 4.64–4.69 (d,
J = 17.5, 1H), 4.75 (br s, 2H), 7.54 (m, 5H) ppm; 13C NMR d 12.82,
20.75, 25.22, 25.29, 25.48, 33.08, 51.51, 55.10, 58.07, 65.86,
131.20, 132.25, 133.12, 133.75 ppm; HRMS (ESI) m/z calcd for
C
16H26N2 [M+H]+ 246.2169, found: 247.2165.