NJC
Paper
and the required filtrate was washed with water and extracted adduct 5. An enantiomeric excess of 5 was determined using
with DCM; the combined organic layer was washed with brine, chiral stationary-phase HPLC analysis.
dried over sodium sulphate and concentrated. The crude product
Characterization of the Michael adduct (5)
was purified using column chromatography using 5% ethylacetate
and n-hexane as an eluent. Pale yellow solid, yield is 96%, m.p.
Diethyl 2-(3-oxo-3-phenyl-1-p-tolylpropyl)malonate (5a).
86–87 1C; 1H NMR (400 MHz, CDCl3) dH 7.35 (s, 3H), 4.45 1H NMR (300 MHz, CDCl3) dH 7.82 (d, J = 7.5 Hz, 2H), 7.44
(s, 6H). 13C NMR (100 MHz, CDCl3) dC 139.00, 129.55, 32.19.
(t, J = 7.3 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.06 (d, J = 7.9 Hz, 2H),
6.96 (d, J = 7.9 Hz, 2H), 4.19–4.08 (m, 4H), 3.89 (q, J = 7.1 Hz,
2H), 3.72 (d, J = 9.7 Hz, 1H), 3.36 (dt, J = 16.6, 8.2 Hz, 1H), 2.18
(s, 3H), 1.18 (t, J = 7.1 Hz, 3H), 0.95 (t, J = 7.1 Hz, 3H). 13C NMR
(75 MHz, CDCl3) dC 197.69, 168.44, 167.81, 137.37, 136.85,
136.63, 133.00, 129.09, 128.13, 128.06, 61.62, 61.33, 57.70,
42.72, 40.46, 21.03, 14.04, 13.79. The enantiomeric excess was
determined using HPLC. [Phenomenex Chiralpack, 254 nm,
hexane: IPA = 50 : 2, 1 mL minÀ1]: 7.58 min (minor), 35.46 min
(major).
Synthesis of mesitylene based CMPTCs (9)
A mixture of 1,3,5-tribromomesitylene 6 (0.1 g, 10 mmol), and
cinchona derivatives 818 (8a/8b, 30 mmol) was dissolved in 5 ml
of THF and heated to reflux overnight; the white solid was
filtered, washed with diethylether and dried to get pure tri-site
chiral PTC (86% yield of 9a and 88% yield of 9b).
Mesitylene based benzylcinchonine (9a)
Diethyl 2-(1-(4-chlorophenyl)-3-oxo-3-phenylpropyl)malonate
(5b). 1H NMR (300 MHz, CDCl3) dH 8.03 (d, J = 7.0 Hz, 2H),
7.62–7.56 (m, 3H), 7.55–7.51 (m, 2H), 7.40 (d, J = 8.5 Hz, 2H),
4.19–4.08 (m, 4H), 3.89 (q, J = 7.1 Hz, 2H), 3.72 (d, J = 9.7 Hz, 1H),
3.36 (dt, J = 16.6, 8.2 Hz, 1H), 1.18 (t, J = 7.1 Hz, 3H), 0.95 (t, J =
7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) dC 197.69, 168.44, 167.81,
137.93, 133.30, 132.85, 129.51, 129.15, 128.59, 128.42, 61.62,
61.33, 57.70, 42.72, 40.46, 14.04, 13.79. The enantiomeric excess
was determined using HPLC. [Phenomenex Chiralpack, 254 nm,
hexane: IPA = 50: 2, 1 mL minÀ1]: 4.52 min (minor), 23.68 min
(major).
1H NMR (400 MHz, DMSO) dH 9.04 (d, J = 4.4 Hz, 3H), 8.45
(d, J = 8.5 Hz, 3H), 8.20 (d, J = 8.4 Hz, 3H), 8.01 (d, J = 8.8 Hz,
3H), 7.92 (t, J = 7.6 Hz, 3H), 7.87–7.78 (m, 6H), 7.62 (d, J =
7.5 Hz, 6H), 7.51 (t, J = 7.5 Hz, 6H), 7.41 (d, J = 7.4 Hz, 3H), 6.61
(s, 3H), 5.96 (ddd, J = 17.3, 10.3, 6.9 Hz, 6H), 5.20 (d, J = 12.8 Hz,
3H), 5.09 (d, J = 10.6 Hz, 3H), 4.94 (t, J = 14.4 Hz, 6H), 4.79 (d, J =
12.5 Hz, 3H), 4.65 (d, J = 11.8 Hz, 3H), 4.02 (s, 6H), 3.91 (d, J =
9.0 Hz, 3H), 3.81 (s, 3H), 3.69 (s, 3H), 3.10 (d, J = 7.7 Hz, 3H),
1.97 (s, 3H), 1.74 (dd, J = 20.6, 9.1 Hz, 6H), 1.35 (s, 3H). 13C NMR
(100 MHz, DMSO) dC 150.31, 148.05, 147.99, 141.43, 140.52,
137.80, 137.26, 137.02, 129.85, 129.75, 128.62, 128.44, 128.38,
128.11, 127.87, 125.16, 123.74, 119.79, 116.28, 79.28, 78.98, 70.91,
70.23, 58.94, 36.55, 30.80, 26.51, 25.78. ESI-MS (M)3+; 1510.67.
Diethyl 2-(1-(4-methoxyphenyl)-3-oxo-3-phenylpropyl)malonate
1
(5c). H NMR (300 MHz, CDCl3) d 8.11 (d, J = 7.0 Hz, 2H), 7.75–
7.66 (m, 3H), 7.61 (d, J = 7.5 Hz, 2H), 7.04 (d, J = 8.7 Hz, 2H), 4.19–
4.08 (m, 4H), 3.89 (q, J = 7.1 Hz, 2H), 3.72 (d, J = 9.7 Hz, 1H), 3.36
(dt, J = 16.6, 8.2 Hz, 1H), 2.39 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H), 0.95
(t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) dC 197.69, 168.44,
167.81, 161.52, 144.51, 132.38, 130.06, 128.39, 128.24, 119.59,
114.26, 61.62, 61.33, 57.70, 55.22, 42.72, 40.46, 14.04, 13.79. The
enantiomeric excess was determined using HPLC. [Phenomenex
Chiralpack, 254 nm, hexane: IPA = 50 : 2, 1 mL minÀ1]: 13.17 min
(minor), 49.49 min (major).
Diethyl 2-(1-(4-nitrophenyl)-3-oxo-3-phenylpropyl)malonate
(5d). 1H NMR (300 MHz, CDCl3) d 8.31 (d, J = 8.8 Hz, 2H),
7.82 (dd, J = 17.9, 11.1 Hz, 3H), 7.66 (dd, J = 11.4, 7.6 Hz, 2H),
7.60–7.51 (m, 2H), 4.19–4.08 (m, 4H), 3.89 (q, J = 7.1 Hz, 2H),
3.72 (d, J = 9.7 Hz, 1H), 3.36 (dt, J = 16.6, 8.2 Hz, 1H), 1.18 (t, J =
7.1 Hz, 3H), 0.95 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) dC
197.69, 168.44, 167.81, 148.56, 141.05, 137.53, 133.38, 128.94,
128.83, 128.60, 124.22, 61.62, 61.33, 57.70, 42.72, 40.46, 14.04,
13.79. The enantiomeric excess was determined using HPLC.
Mesitylene based allylcinchonine (9b)
1H NMR (400 MHz, DMSO) d 9.05 (d, J = 4.2 Hz, 3H), 8.49 (d, J =
8.5 Hz, 3H), 8.17 (d, J = 7.9 Hz, 3H), 7.94–7.89 (m, 3H), 7.86
(d, J = 7.9 Hz, 3H), 7.73 (d, J = 4.3 Hz, 3H), 6.53 (s, 3H), 6.35–6.26
(m, 3H), 6.02–5.95 (m, 3H), 5.55–5.45 (m, 6H), 5.34 (d, J =
9.8 Hz, 6H), 5.16 (d, J = 10.6 Hz, 6H), 4.86 (d, J = 12.2 Hz, 3H),
4.43 (dd, J = 12.8, 5.3 Hz, 3H), 4.02 (s, 12H), 3.76 (s, 3H), 3.21
(s, 3H), 1.96 (s, 3H), 1.76 (s, 12H), 1.24 (s, 3H). 13C NMR
(100 MHz, DMSO) dC 150.41, 150.16, 147.93, 136.99, 134.25,
129.68, 129.12, 128.10, 127.61, 125.13, 124.08, 119.68, 118.15,
116.56, 79.00, 78.64, 72.91, 69.06, 55.83, 53.77, 35.87, 26.15,
22.22, 21.01. ESI-MS (M3+); 1359.75.
General method for the synthesis of enantioselective catalytic
Michael addition of a,b-unsaturated compounds with
diethylmalonate under CMPTC conditions
A mixture of chalcone 318,19 (a–h, 0.1 mmol), diethylmalonate 4 [Phenomenex Chiralpack, 254 nm, hexane: IPA = 50 : 2, 1 mL
(0.12 mmol) and CMPTCs (5 mol%) 9 (9a/9b) was dissolved in minÀ1]: 17.70 min (minor), 101.52 min (major).
1 ml toluene and 0.5 ml of 10% K2CO3 was added. Then the
Diethyl 2-(3-(4-bromophenyl)-3-oxo-1-p-tolylpropylpropyl)malonate
reaction mixture was ultrasonicated for 1 h. The reaction (5e). 1H NMR (300 MHz, CDCl3) d 7.88 (d, J = 8.2 Hz, 2H), 7.67–
mixture was extracted with ethylacetate, washed with water 7.57 (m, 4H), 6.94 (d, J = 8.6 Hz, 2H), 4.19–4.08 (m, 4H), 3.89
(3 Â 2 ml), then washed with brine (5 ml), dried over sodium (q, J = 7.1 Hz, 2H), 3.72 (d, J = 9.7 Hz, 1H), 3.36 (dt, J = 16.6,
sulphate and concentrated. The crude material was purified 8.2 Hz, 1H), 2.18 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H), 0.95 (t, J =
using column chromatography on silica gel (ethylacetate and 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) dC 197.69, 168.44,
n-hexane as eluents), to afford the corresponding Michael 167.81, 161.87, 137.23, 131.85, 130.36, 129.96, 127.42, 118.98,
3100 | New J. Chem., 2015, 39, 3098--3104
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