C. Chen et al. / Tetrahedron: Asymmetry 17 (2006) 2761–2767
2765
NMR d 9.84 (s, 2H), 8.31–8.29 (d, J = 6.9 Hz, 2H), 8.20 (s,
4H), 7.86–7.71 (m, 6H), 7.61–7.56 (m, 2H), 7.29–7.22 (m,
4H), 3.21–3.04 (m, 4H), 2.41–2.23 (m, 4H); 13C NMR d
162.5, 149.5, 146.2, 145.1, 137.3, 135.4, 134.8, 130.4,
129.5, 129.2, 129.0, 127.9, 127.5, 121.7, 120.0, 118.6, 59.9,
37.4, 31.1; HRMS (MALDI) Calcd for C37H28N4O2:
561.2289. Found 561.2285.
(M+, 20). Anal. Calcd for C22H23ClO5: C 65.59, H 5.75.
Found: C 65.48, H 6.05; 53% ee [HPLC conditions: Chira-
pak OJ column (25 cm · 0.46 cm ID), n-hexane/
i-PrOH = 90:10, flow rate = 1 mL/min, wavelength =
254 nm, tR = 12.3 min (major), tR = 15.65 min (minor)];
26
½aꢀD ¼ þ17:0 (c 0.5, CH2Cl2).
4.3.4. Diethyl 2-(1-(3-methoxyphenyl)-3-oxo-3-phenylprop-
yl)malonate 3d. Colorless oil, yield 72%; 1H NMR d
7.83–7.80 (d, J = 8.4 Hz, 2H), 7.47–7.31 (m, 3H), 7.10–
7.05 (t, J = 8.4 Hz, 1H), 6.78–6.61 (m, 3H), 4.15–4.05 (m,
3H), 3.94–3.87 (q, J = 6.9 Hz, 2H), 3.75–3.66 (m, 4H),
3.45–3.32 (m, 2H), 1.18–1.13 (t, J = 6.9 Hz, 3H), 0.98–
0.93 (t, J = 6.9 Hz, 3H); 13C NMR d 197.5, 168.3, 167.7,
159.5, 142.2, 136.9, 133.0, 129.3, 128.5, 128.1, 120.4,
114.1, 112.5, 61.6, 61.3, 57.5, 55.1, 42.5, 40.8, 13.9, 13.7;
MS (EI) m/z 398 (M+, 10). Anal. Calcd for C23H26O6: C
69.33, H 6.58. Found: C 69.41, H 6.40; 49% ee [HPLC con-
ditions: Chirapak AS column (25 cm · 0.46 cm ID), n-hex-
ane/i-PrOH = 95:5, flow rate = 1 mL/min, wavelength =
4.3. Typical procedure for Co(II)-catalyzed asymmetric
Michael addition of malonate to chalcone
A mixture of Co(OAc)2 (1.0 mg, 0.005 mmol) and ligand 1a
(3.5 mg, 0.0075 mmol) in EtOH (2 mL) was stirred at room
temperature for 2 h. Chalcone (26 mg, 0.125 mmol) and
malonate (56 mg, 0.34 mol) were added sequentially and
stirred. Et2Zn (0.15 mL, 1 M in n-hexane) was injected into
the reaction mixture every 15 h. The reaction was moni-
tored by TLC for a full conversion. The reaction mixture
was filtered and concentrated in vacuum and the crude
product was purified on a silica gel column with petroleum
ether/ethyl acetate (9:1) to afford the addition product. The
analyses were illustrated as follows.
254 nm, tR = 16.7 min (minor), tR = 19.1 min (major)];
26
½aꢀD ¼ þ12:0 (c 0.5, CH2Cl2).
4.3.1. Diethyl 2-(3-oxo-1,3-diphenylpropyl)malonate 3a.10
4.3.5. Diethyl 2-(1-(4-chlorophenyl)-3-oxo-3-phenylprop-
yl)malonate 3e.16 White solid, yield 76%; mp 113–
1
White solid, yield 78%; mp 69–71 ꢁC; H NMR d 7.91–
7.88 (d, J = 7.2 Hz, 2H), 7.55–7.51 (t, J = 7.2 Hz, 1H),
7.44–7.40 (t, J = 8.1 Hz, 2H), 7.26–7.16 (m, 5H), 4.21–
4.16 (m, 3H), 4.00–3.92 (q, J = 7.2 Hz, 2H), 3.83–3.80 (d,
J = 8.7 Hz, 1H), 3.58–3.41 (m, 2H), 1.27–1.22 (t,
J = 7.2 Hz, 3H), 1.03–0.98 (t, J = 7.2, 3H); 50% ee [HPLC
conditions: Chirapak OJ column (25 cm · 0.46 cm ID),
n-hexane/i-PrOH = 70:30, flow rate = 1 mL/min, wave-
1
115 ꢁC; H NMR d 7.90–7.88 (d, J = 7.2 Hz, 2H), 7.57–
7.52 (t, J = 7.2 Hz, 1H), 7.46–7.40 (t, J = 8.1 Hz, 2H),
7.22 (s, 4H), 4.22–4.13 (m, 3H), 4.02–3.94 (q, J = 8.1 Hz,
2H), 3.80–3.76 (d, J = 9.6 Hz, 1H), 3.57–3.38 (m, 2H),
1.27–1.22 (t, J = 7.2 Hz, 3H), 1.07–1.03 (t, J = 7.2 Hz,
3H); 57% ee [HPLC conditions: Chirapak OJ column
(25 cm · 0.46 cm ID), n-hexane/i-PrOH = 90:10, flow
length = 254 nm, tR = 26.1 min (major) for (R)-enantio-
rate = 1 mL/min, wavelength = 254 nm, tR = 14.7 min
26
mer, tR = 38.5 min (minor) for (S)-enantiomer]; ½aꢀD
¼
26
(major), tR = 17.1 min (minor)]; ½aꢀD ¼ þ13:6 (c 0.5,
þ12:4 (c 0.25, CH2Cl2).
CH2Cl2).
4.3.2. Diethyl 2-(1-(2-chlorophenyl)-3-oxo-3-phenylprop-
yl)malonate 3b. Colorless oil, yield 76%; 1H NMR d
7.92–7.91 (d, J = 7.2 Hz, 2H), 7.53–7.49 (t, J = 7.2 Hz,
1H), 7.42–7.38 (t, J = 8.0 Hz, 2H), 7.30–7.39 (m, 2H),
7.15–7.08 (m, 2H), 4.68–4.62 (m, 1H), 4.21–3.99 (m, 5H),
3.71–3.58 (m, 2H), 1.12–1.16 (t, J = 7.2 Hz, 3H), 1.08–
1.04 (t, J = 7.2 Hz, 3H); 13C NMR d 197.4, 168.3, 167.8,
137.9, 136.8, 134.2, 133.1, 130.1, 129.5, 128.6, 128.3,
128.1, 126.8, 61.6, 61.5, 55.3, 40.5, 37.5, 14.0, 13.8; MS
(EI) m/z 402 (M+, 2). Anal. Calcd for C22H23ClO5: C
65.59, H 5.75. Found: C 65.79, H 6.24; 49% ee [HPLC con-
ditions: Chirapak OJ column (25 cm · 0.46 cm ID), n-hex-
ane/i-PrOH = 90:10, flow rate = 1 mL/min, wavelength =
4.3.6. Diethyl 2-(1-(4-nitrophenyl)-3-oxo-3-phenylprop-
yl)malonate 3f.16 White solid, yield 76%; mp 111–
113 ꢁC; H NMR d 8.12–8.10 (d, J = 8.8 Hz, 2H), 7.90–
7.87 (d, J = 8.8 Hz, 2H), 7.56–7.46 (m, 5H), 4.30–4.18
(m, 3H), 4.02–3.96 (q, J = 7.2 Hz, 2H), 3.85–3.83 (d,
J = 9.2 Hz, 1H), 3.62–3.49 (m, 2H), 1.26–1.22 (t,
J = 7.2 Hz, 3H), 1.07–1.03 (t, J = 7.2, 3H); 53% ee [HPLC
conditions: Chirapak OJ column (25 cm · 0.46 cm ID), n-
hexane/i-PrOH = 70:30, flow rate = 1 mL/min, wave-
1
length = 254 nm, tR = 20.1 min (major), tR = 31.5 min
26
(minor)]; ½aꢀD ¼ þ19:4 (c 0.5, CH2Cl2).
254 nm, tR = 14.8 min (major), tR = 22.0 min (minor)];
½aꢀD ¼ þ35:3 (c 0.15, CH2Cl2).
4.3.7. Diethyl 2-(3-(3-chlorophenyl)-3-oxo-1-phenylpropyl)-
malonate 3g. White solid, yield 78%; mp 69–70 ꢁC; H
26
1
NMR d 7.83 (s, 1H), 7.78–7.76 (d, J = 7.6 Hz, 1H), 7.49–
7.47 (d, J = 9.2 Hz, 1H), 7.37–7.33 (t, J = 7.6 Hz, 1H),
7.25–7.16 (m, 5H), 4.25–4.12 (m, 3H), 3.97–3.92 (q,
J = 7.2 Hz, 2H), 3.81–3.79 (m, 1H), 3.54–3.39 (m, 2H),
1.25–1.22 (t, J = 7.2 Hz, 3H), 1.02–0.98 (t, J = 7.6 Hz,
3H); 13C NMR d 196.5, 168.5, 167.9, 140.5, 138.5, 135.0,
133.2, 130.1, 128.7, 128.4, 127.4, 126.6, 61.9, 61.6, 57.6,
42.9, 40.9, 14.2, 14.1; MS (EI) m/z 402 (M+, 3). Anal.
Calcd for C22H23ClO5: C 65.59, H 5.75. Found: C 65.46,
H 6.12; 53% ee [HPLC conditions: Chirapak OJ column
(25 cm · 0.46 cm ID), n-hexane/i-PrOH = 90:10, flow rate =
4.3.3. Diethyl 2-(1-(3-chlorophenyl)-3-oxo-3-phenylpropyl)-
1
malonate 3c. White solid, yield 76%; mp 79–81 ꢁC; H
NMR d 7.90–7.88 (d, J = 7.2 Hz, 2H), 7.55–7.52 (t,
J = 7.2 Hz, 1H), 7.44–7.41 (t, J = 7.2 Hz, 2H), 7.26 (s,
1H), 7.19–7.13 (m, 3H), 4.20–4.13 (m, 3H), 4.01–3.96 (q,
J = 7.2 Hz, 2H), 3.79–3.77 (d, J = 9.2 Hz, 1H), 3.57–3.41
(m, 2H), 1.25–1.22 (t, J = 7.2 Hz, 3H), 1.06–1.03
(t, J = 7.2 Hz, 3H); 13C NMR d 197.3, 168.3, 167.7, 142.9,
136.8, 134.3, 133.4, 129.9, 123.8, 128.6, 128.3, 127.6, 62.0,
61.7, 57.5, 42.4, 40.5, 14.2, 14.0; MS (EI) m/z 402