A. Scettri et al. / Tetrahedron: Asymmetry 19 (2008) 2149–2152
2151
alkaloid. In all cases, the reactions can be performed without a sol-
4.2.2. 3-(3-Methoxyphenyl)-1-phenyl-3(phenylamino)propan-
1-one 3g
White solid m/z 332 [M+H+], 354 [M+Na+]; IR (KBr, neat) 3365,
1675, 1576, 1487 cmꢀ1; [
D = ꢀ12.5 (c 0.5, CHCl3) 40% ee; HPLC
vent, thanks to the very good solubility in aniline of the differently
substituted chalcones used. The simple experimental procedure,
the solvent-free conditions and, thus the absence of work-up, short
reaction times, good conversions and enantioselectivities are the
notable advantages of the protocol.
a]
analysis Chiralpak AD-H hexane/iPrOH 90:10 flow rate 0.6 ml tR
(major) = 31.95, tR (minor) = 36.87 min; 1H NMR (CDCl3,
400 MHz): d 7.92 (2H, d, J = 7.8 Hz); 7.57 (1H, t, J = 7.2 Hz); 7.45
(2H, t, J = 7.8 Hz); 7.25 (1H, t, J = 7.7 Hz); 7.12–7.01 (4H, m);
6.79–6.77 (1H, m); 6.67 (1H, t, J = 7.3 Hz); 6.58 (2H, d, J = 7.8 Hz);
4.98 (1H, dd, J = 8.3; 5.1 Hz); 4.55 (1H, br s); 3.77 (3H, s); 3.51
(1H, dd, J = 16.1; 5.1 Hz); 3.43 (1H, dd, J = 16.1; 8.3 Hz); 13C NMR
(CDCl3, 400 MHz): d 198.7; 160.5; 147.6; 145.4; 134.6; 133.4;
129.1; 128.1; 119.7; 118.22; 114.4; 133.3; 112.2; 55.7; 54.8;
46.8; Anal. Calcd for C22H21NO2: C, 79.73; H, 6.39; N, 4.23. Found:
C, 79.60; H, 6.50; N, 4.10.
4. Experimental
4.1. General
All chemicals were purchased from Sigma–Aldrich and were
used without any further purification. TLC was performed on Sil-
ica Gel 60 F254 0.25 mm on glass plates (Merck) and non-flash
chromatography was performed on silica gel (0.063–0.200 mm)
(Merck). All 1H NMR and 13C NMR spectra were recorded with a
DRX 400 MHz Bruker instrument, by using CDCl3 (d = 7.26 ppm
in 1H NMR spectra and d = 77.0 ppm in 13C NMR spectra) as sol-
vent (400.135 MHz for 1H and 100.03 MHz for 13C). Data for 1H
NMR are reported as follows: chemical shift (d in ppm, multiplic-
ity (s singlet, d doublet, t triplet, dd doublet of doublets, m mul-
tiplet) and coupling constant (J in hertz). Optical rotations were
measured on a JASCO DIP-1000 polarimeter operating at the so-
dium D line at room temperature. Concentration is given in g/
100 ml. IR spectra were recorded on a Bruker spectrometer. The
HPLC analyses were performed with Waters Associates equipment
(Waters 2487 Dual k absorbance Detector) using CHIRALPK AD-H
column with Hexane/Isopropyl alcohol mixtures and flow rate as
indicated. HPLC methods were calibrated with the corresponding
racemic mixtures.
4.2.3. 1-(4-Xhlorophenyl)-3-phenyl-3-(phenylamino)propan-1-
one 3m
Yellow solid m/z 336 [M+H+], 338 [M+Na+]; IR (KBr, neat) 3448,
1679, 1504, 1285; [
a
]D = ꢀ5.8 (c 0.55, CHCl3) 31% ee; HPLC analysis
Chiralpak AD-H hexane/iPrOH 80:20 flow rate 0.6 ml tR (ma-
jor) = 18.6, tR (minor) = 23.6 min; 1H NMR (CDCl3, 400 MHz): d
7.83 (2H, d, J = 8.5 Hz); 7.45–7.40 (4H, m) 7.33 (2H, t, J = 7.3 Hz);
7.27–7.23 (1H, m); 7.11 (2H, t, J = 8.2 Hz); 6.69 (1H, t, J = 8.2 Hz);
6.58 (2H, d, J = 8.2 Hz); 5.02 (1H, ft, J = 5.9 Hz); 4.54 (1H, br s);
3.47 (1H, dd, J = 16.1; 5.5 Hz); 3.41 (1H, dd, J = 16.1; 7.2 Hz); 13C
NMR (CDCl3, 400 MHz): d 197.6; 147.4; 145.9; 143.3; 140.4;
130.1; 129.7; 129.4; 127.9; 126.9; 121.9; 118.4; 114.3; 55.18;
46.7; Anal. Calcd for C21H18ClNO: C, 75.11; H, 5.40; N, 4.17; O,
4.76. Found: C, 75.05; H, 5.50; N, 4.12.
Mass spectrometry analysis was carried out using an electro-
spray spectrometer Waters 4 micro quadruple.
The elemental analyses were calculated with FLASH EA 1112
Thermo equipment.
The known compounds (Table 2, entries 1, 2, 4, 5, 7 and 11)
have been identified by comparison of spectral data with those re-
ported.7 The absolute configurations of the optically active com-
pounds 3g and 3n were determined on the basis of the measured
specific rotations compared with literature values.8 All the other
absolute configurations were assigned by analogy.
4.2.4. 1-(4-Methoxyphenyl)-3-phenyl-3-(phenylamino)propan-
1-one 3i
White solid m/z 332 [M+H+], 354 [M+Na+]; 370 [M+K+]; IR (KBr,
neat) 3430, 1680, 1547, 1261, 1171; [
a]D = ꢀ5.2 (c 0.5, CHCl3) 49%
ee; HPLC analysis Chiralpak AD-H hexane/iPrOH 90:10 flow rate
0.6 ml tR (major) = 43.9, tR (minor) = 51.5 min; 1H NMR (CDCl3,
400 MHz): d 7.89 (2H, d, J = 8.8 Hz); 7.44 (2H, d, J = 7.5 Hz); 7.32
(2H, t, J = 7.5 Hz); 7.24 (1H, t, J = 7.2 Hz); 7.08 (2H, d, J = 8.8 Hz);
6.65 (1H, t, J = 7.3 Hz); 6.55 (2H, d, J = 7.7 Hz); 4.97 (1H, dd,
J = 7.7; 5.0 Hz); 4.61 (1H, br s); 3.86 (3H, s); 6.45 (1H, dd,
J = 15.7; 5.0 Hz); 3.34 (1H, dd, J = 15.7; 7.7 Hz); 13C NMR (CDCl3,
400 MHz): d 197.2; 164.1; 147.5; 143.6; 131.1; 129.5; 129.2;
127.7; 126.8; 118.1; 114.3; 114.2; 55.9; 55.4; 46.4; Anal. Calcd
for C22H21NO2: C, 79.73; H, 6.39; N, 4.23. Found: C, 79.57; H,
6.45; N, 4.15.
4.2. Typical experimental procedure
To
a mixture of chalcone (0.25 mmol) and cinchonine
(0.05 mmol), 2 equiv (0.5 mmol) of aniline was added and the
resulting solution was stirred at room temperature for 24 h.
TLC indicated the completion of the reaction. The crude mix-
ture was directly purified by column chromatography (silica
gel, petroleum ether/ethyl acetate mixtures) to obtain pure
products.
4.2.5. 3-Phenyl-3-(phenylamino)-1-p-tolylpropan-1-one 3l
White solid m/z 316 [M+H+] 338 [M+Na+]; IR (KBr, neat) 3387,
1667, 1602, 1504; [
a]
D = ꢀ16.0 (c 0.5, CHCl3) 52% ee; HPLC analysis
Chiralpak AD-H hexane/iPrOH 98:2 flow rate 0.8 ml tR (ma-
jor) = 35.6, tR (minor) = 39.7 min; 1H NMR (CDCl3, 400 MHz): d
7.83 (2H, d, J = 8.2 Hz); 7.46 (2H, d, J = 7.2 Hz); 7.34 (2H, t,
J = 7.2 Hz); 7.26–7.24 (3H, m); 7.11 (2H, t, J = 7.4 Hz); 6.69 (1H, t;
J = 7.4 Hz); 6.57 (2H, d, J = 8.2 Hz); 5.01 (1H, dd, J = 7.6; 5.1 Hz);
4.60 (1H, br s); 3.50 (1H, dd, J = 16.0; 5.1 Hz); 3.39 (1H, dd,
J = 16.0; 7.6 Hz); 2.41 (3H, s); 13C NMR (CDCl3, 400 MHz): d
198.4, 147.5; 144.8; 143.6; 135.2; 129.8; 129.5; 129.3; 128.8;
127.7; 126.8; 118.2; 114.2; 55.3; 46.7; 22.1; Anal. Calcd for
C22H21NO: C, 83.78; H, 6.71; N,4.44. Found: C, 83.60; H, 6.60, N,
4.35.
4.2.1. 1-Phenyl-3-(phenylamino)-3-p-tolylpropan-1-one 3c
White solid m/z 316.5 [M+H+], 338 [M+Na+]; IR (KBr, neat) 3446,
1683, 1661, 1580; [a]D = +3.9 (c 0.5, CHCl3) 42% ee; HPLC analysis
Chiralpak AD-H hexane/iPrOH 98:2 flow rate 0.7 ml tR (ma-
jor) = 55.29, tR (minor 57.65 min; 1H NMR (CDCl3, 400 MHz): d
7.92 (2H, d, J = 7.4 Hz); 7.56 (1H, t, J = 7.4 Hz); 7.45 (2H, t,
J = 7.6 Hz); 7.3 (2H, d, J = 7.9 Hz); 7.15–708 (4H, m); 6.66 (1H, t,
J = 7.4 Hz); 6.57 (2H, d, J = 7.9 Hz); 4.99 (1H, ft, J = 7.1); 4.52 (1H,
br s), 3.52 (1H, dd, J = 16.1; 5.2 Hz); 3.41 (1H, dd; J = 16.1;
7.6 Hz); 2.32 (3H, s) 13C NMR (CDCl3, 400 MHz): d 198.3; 147.5;
140.4; 137.4; 133.8; 129.9; 129.5; 129.1; 128.6; 126.7; 117.1;
114.2; 54.9; 46.8; 21.5. Anal. Calcd for C22H21NO: C, 83.78; H,
6.71; N, 4.44. Found: C, 83.60; H, 4.32; N, 4.30.
Acknowledgment
We are grateful to MIUR for financial support.