3.2. Typical Procedure for the Michael Addition
Catalyst V (7.1 mg, 0.012 mmol) was dissolved into dicloromethane to prepare the solution of catalyst V (20.0 mL, 0.6 mmol/L). To the above solution (0.5 mL, containing catalyst 0.0003 mmol, 0.3 mol%) was added malononitrile (8 mg, 0.12 mmol), chalcones 3 (0.1 mmol) subsequently. The resulting mixture was then stirred at room temperature for 36 h. The corresponding adducts 4 were isolated through flash silica gel chromatography (eluent, ethyl acetate/petroleum ether).
(R)-2-(3-oxo-1,3-diphenylpropyl)malononitrile (4a) [
19,
25]: 99% yield; white solid; 90%
ee, determined by HPLC (Daicel Chiralcel OD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 23.8 min (
major), 38.6 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.97 (d,
J = 7.3 Hz, 2H), 7.65–7.60 (m, 1H), 7.52–7.42 (m, 7H), 4.65 (d,
J = 5.1 Hz, 1H), 3.96 (dt,
J = 8.1, 5.2 Hz, 1H), 3.71–3.66 (m, 2H).
(R)-2-(3-oxo-3-phenyl-1-p-tolylpropyl)malononitrile (4b) [
19,
23,
25]: 97% yield; colorless oil; 86%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 10.8 min (
major), 15.6 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.98–7.93 (m, 2H), 7.64–7.58 (m, 1H), 7.48 (dd,
J = 10.6, 4.8 Hz, 2H), 7.33 (d,
J = 8.1 Hz, 2H), 7.24–7.21 (m, 2H), 4.62–4.56 (m, 1H), 3.92 (dt,
J = 8.2, 5.4 Hz, 1H), 3.67–3.52 (m, 2H), 2.35 (s, 3H).
(R)-2-(1-(4-methoxyphenyl)-3-oxo-3-phenylpropyl)malononitrile (4c) [
19,
25]: 92% yield; colorless oil; 86%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 14.2 min (
major), 23.2 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 8.02–7.93 (m, 2H), 7.66–7.59 (m, 1H), 7.50 (dd,
J = 10.6, 4.8 Hz, 2H), 7.40–7.34 (m, 2H), 6.99–6.91 (m, 2H), 4.61 (d,
J = 5.0 Hz, 1H), 3.92 (dt,
J = 8.5, 5.2 Hz, 1H), 3.82 (s, 3H), 3.67–3.63 (m, 2H).
(R)-2-(1-(4-fluorophenyl)-3-oxo-3-phenylpropyl)malononitrile (4d) [
19,
25]: 94% yield; white solid; 90%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 10.4 min (
major), 16.4 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.97 (dd,
J = 8.3, 1.1 Hz, 2H), 7.66–7.60 (m, 1H), 7.50 (t,
J = 7.7 Hz, 2H), 7.47–7.42 (m, 2H), 7.15–7.09 (m, 2H), 4.62 (d,
J = 5.1 Hz, 1H), 4.01–3.93 (m, 1H), 3.72–3.60 (m, 2H).
(R)-2-(1-(4-chlorophenyl)-3-oxo-3-phenylpropyl)malononitrile (4e) [
19,
23,
25]: 72% yield; white solid; 85%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 11.4 min (
major), 18.7 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.96 (dd,
J = 8.3, 1.2 Hz, 2H), 7.64 (s, 1H), 7.51 (t,
J = 7.7 Hz, 2H), 7.41 (d,
J = 1.5 Hz, 4H), 4.63 (d,
J = 5.1 Hz, 1H), 3.95 (d,
J = 8.4 Hz, 1H), 3.68–3.63 (m, 2H).
(R)-2-(1-(4-bromophenyl)-3-oxo-3-phenylpropyl)malononitrile (4f) [
25]: 45% yield; white solid; 85%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 11.6 min (
major), 18.8 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.96 (d,
J = 7.9 Hz, 2H), 7.64 (t,
J = 7.2 Hz, 1H), 7.57 (d,
J = 8.2 Hz, 2H), 7.50 (t,
J = 7.6 Hz, 2H), 7.34 (d,
J = 8.2 Hz, 2H), 4.62 (d,
J = 5.0 Hz, 1H), 3.93 (dd,
J = 8.3, 5.2 Hz, 1H), 3.67–3.59 (m, 2H).
(R)-2-(1-(3-chlorophenyl)-3-oxo-3-phenylpropyl)malononitrile (4g) [
19]: 72% yield; white solid; 90%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 9.8 min (
major), 12.2 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.95 (dd,
J = 8.3, 1.1 Hz, 2H), 7.60 (d,
J = 7.4 Hz, 1H), 7.50–7.43 (m, 3H), 7.38–7.33 (m, 3H), 4.61 (d,
J = 5.2 Hz, 1H), 3.98–3.90 (m, 1H), 3.66–3.62 (m, 2H).
(R)-2-(1-(3-methoxyphenyl)-3-oxo-3-phenylpropyl)malononitrile (4h) [
19]: 65% yield; white solid; 85%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 90/10, 25 °C, 1.0 mL min
−1, 254 nm): t
R = 16.9 min (
major), 19.5 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.98–7.93 (m, 2H), 7.63–7.58 (m, 1H), 7.48 (dd,
J = 10.7, 4.8 Hz, 2H), 7.33 (t,
J = 8.0 Hz, 1H), 7.03–6.89 (m, 3H), 4.62 (d,
J = 5.2 Hz, 1H), 3.95–3.89 (m, 1H), 3.82 (s, 3H), 3.66–3.64 (m, 2H).
(R)-2-(1-(2-methoxyphenyl)-3-oxo-3-phenylpropyl)malononitrile (4i) [
19,
25]: 52% yield; white solid; 35%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 90/10, 25 °C, 1.0 mL min
−1, 254 nm): t
R = 11.7 min (
major), 13.2 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.97–7.92 (m, 2H), 7.58 (d,
J = 7.4 Hz, 1H), 7.47 (t,
J = 7.7 Hz, 2H), 7.35–7.29 (m, 2H), 6.99–6.91 (m, 2H), 4.66 (d,
J = 6.6 Hz, 1H), 4.44 (d,
J = 6.8 Hz, 1H), 3.88 (s, 3H), 3.73–3.64 (m, 2H).
(R)-2-(3-oxo-1-phenyl-3-p-tolylpropyl)malononitrile (4j) [
47]: 64% yield; colorless oil; 88%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 12.3 min (
major), 18.5 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.86 (d,
J = 8.2 Hz, 2H), 7.46–7.38 (m, 5H), 7.28 (d,
J = 8.0 Hz, 2H), 4.65 (d,
J = 5.1 Hz, 1H), 3.97–3.88 (m, 1H), 3.66–3.61 (m, 2H), 2.42 (s, 3H).
(R)-2-(3-(4-methoxyphenyl)-3-oxo-1-phenylpropyl)malononitrile (4k) [
25]: 76% yield; colorless oil; 80%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 19.9 min (
major), 31.5 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.95 (d,
J = 9.0 Hz, 2H), 7.44 (d,
J = 5.8 Hz, 5H), 6.95 (d,
J = 8.9 Hz, 2H), 4.69 (d,
J = 5.0 Hz, 1H), 3.97–3.91 (m, 1H), 3.88 (s, 3H), 3.65–3.59 (m, 2H).
(R)-2-(3-(4-fluorophenyl)-3-oxo-1-phenylpropyl)malononitrile (4l) [
25]: 99% yield; colorless oil; 80%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 11.5 min (
major), 13.6 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 8.04–7.96 (m, 2H), 7.47–7.38 (m, 5H), 7.20–7.13 (m, 2H), 4.62 (d,
J = 5.2 Hz, 1H), 3.99–3.92 (m, 1H), 3.67–3.63 (m, 2H).
(R)-2-(3-(4-chlorophenyl)-3-oxo-1-phenylpropyl)malononitrile (4m) [
25]: 57% yield; white solid; 80%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 12.9 min (
major), 15.5 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.92–7.87 (m, 2H), 7.48–7.44 (m, 2H), 7.44–7.39 (m, 5H), 4.60 (d,
J = 5.2 Hz, 1H), 3.98–3.91 (m, 1H), 3.65–3.62 (m, 2H).
(R)-2-(3-(4-bromophenyl)-3-oxo-1-phenylpropyl)malononitrile (4n) [
19,
25]: 41% yield; white solid; 79%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 80/20, 25 °C, 0.8 mL min
−1, 254 nm): t
R = 14.3 min (
major), 17.2 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.80 (d,
J = 8.4 Hz, 2H), 7.61 (d,
J = 8.4 Hz, 2H), 7.41 (s, 5H), 4.58 (d,
J = 5.2 Hz, 1H), 3.97–3.89 (m, 1H), 3.63–3.60 (m, 2H).
(R)-2-(3-oxo-1,3-di-p-tolylpropyl)malononitrile (4o) [
25]: 70% yield; white solid; 86%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 90/10, 25 °C, 1.0 mL min
−1, 254 nm): t
R = 14.6 min (
major), 22.3 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 7.84 (d,
J = 8.2 Hz, 2H), 7.32 (d,
J = 8.1 Hz, 2H), 7.26 (d,
J = 8.0 Hz, 2H), 7.20 (d,
J = 7.9 Hz, 2H), 4.59 (d,
J = 5.1 Hz, 1H), 3.89 (d,
J = 8.3 Hz, 1H), 3.62–3.58 (m, 2H), 2.40 (s, 3H), 2.34 (s, 3H).
(R)-2-(3-oxo-1-phenyl-3-(pyridin-2-yl)propyl)malononitrile (4p) [
26]: 55% yield; white solid; 22%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 90/10, 25 °C, 1.0 mL min
−1, 254 nm): t
R = 17.9 min (
major), 20.8 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 8.69 (ddd,
J = 4.7, 1.6, 0.9 Hz, 1H), 8.03–7.99 (m, 1H), 7.85 (td,
J = 7.7, 1.7 Hz, 1H), 7.52 (ddd,
J = 7.6, 4.8, 1.2 Hz, 1H), 7.48–7.45 (m, 2H), 7.44–7.37 (m, 3H), 4.52 (d,
J = 5.1 Hz, 1H), 4.08 (dd,
J = 17.5, 4.7 Hz, 1H), 3.97–3.87 (m, 2H).
(R)-2-(1-(naphthalen-1-yl)-3-oxo-3-phenylpropyl)malononitrile (4q) [
25]: 50% yield; white solid; 39%
ee, determined by HPLC (Daicel Chiralcel AD-H,
n-hexane/
i-PrOH = 90/10, 25 °C, 1.0 mL min
−1, 254 nm): t
R = 15.4 min (
major), 17.4 min (
minor).
1H NMR (400 MHz, CDCl
3): δ 8.13 (d,
J = 8.5 Hz, 1H), 8.00–7.96 (m, 2H), 7.91 (dd,
J = 18.2, 8.0 Hz, 2H), 7.70 (d,
J = 7.1 Hz, 1H), 7.66–7.56 (m, 3H), 7.50 (dt,
J = 10.1, 7.8 Hz, 3H), 5.03 (d,
J = 6.7 Hz, 1H), 4.70 (d,
J = 5.3 Hz, 1H), 3.86–3.83 (m, 2H).