S. Amslinger et al.
leum ether to afford yellow crystals of compound 4 (216 mg, 0.530 mmol,
58%) as the pure Z isomer. M.p. 1258C; 1H NMR (400 MHz, CDCl3):
d=7.67 (d, J=2.0 Hz, 1H), 7.65 (s, 1H; b-H), 7.39–7.33 (m, 2H), 6.88 (d,
J=8.5 Hz, 1H), 6.55 (dd, J=8.4, 2.3 Hz, 1H), 6.50 (d, J=2.2 Hz, 1H),
3.92 (s, 6H; 2ꢅ(OCH3)), 3.87 (s, 3H; OCH3), 3.79 ppm (s, 3H; OCH3);
13C NMR (101 MHz, CDCl3): d=190.4 (C=O), 163.2, 159.0, 151.0, 148.5,
142.3 (b-CH), 131.4 (CH), 126.7, 125.4 (CH), 122.6, 120.5, 112.7 (CH),
110.6 (CH), 104.7 (CH), 98.9 (CH), 56.0 (OCH3), 55.9 (OCH3), 55.8
(OCH3), 55.5 ppm (OCH3); IR (neat): n˜ =1637, 1602, 1589, 1511, 1259,
EtOAc/petroleum ether 3:7) to afford E-a-aryl-chalcones. The pure iso-
mers from preparative TLC isomerized upon handling and analysis in
solution to E/Z mixtures. The configuration of the double bond was as-
signed based on literature data to be the same as for starting material
4.[15b]
(E)-1-(2,4-Dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-(4-nitrophenyl)-
prop-2-en-1-one (8): Yellow solid (65%, E isomer); m.p. 598C; the E/Z
ratio observed later for the isomerized product in CDCl3 is 4:1; E-8:
1H NMR (300 MHz, CDCl3): d=8.24–8.18 (m, 2H), 7.48–7.43 (m, 3H),
7.32 (s, 1H; b-H), 6.73–6.64 (m, 2H), 6.56 (dd, J=8.5, 2.2 Hz, 1H), 6.44
(dd, J=5.5, 1.9 Hz, 2H), 3.86 (s, 3H; OCH3), 3.84 (s, 3H; OCH3), 3.74 (s,
3H; OCH3), 3.49 ppm (s, 3H; OCH3); 13C NMR (75 MHz, CDCl3): d=
195.7 (C=O), 163.3, 158.9, 150.4, 148.5, 147.1, 144.6, 142.1 (b-CH), 138.5,
131.5 (CH), 131.4 (2 CH), 126.9, 124.8 (CH), 123.5 (2 CH), 121.8, 112.7
(CH), 110.7 (CH), 104.8 (CH), 98.6 (CH), 55.8 (OCH3), 55.6 (OCH3),
1247, 1212, 1145, 1018, 819 cmꢀ1; MS (EI): m/z (%): 406 [M +] (14), 327
C
(49), 165 (100); HRMS (EI): calcd for C19H19BrO5: 406.0416 [M +];
C
found 406.0423.
ACHTUNGTRENNUNG(Z/E)-1-(2,4-Dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-iodoprop-2-
en-1-one (5): a-Iodo chalcone 5 was prepared according to the general
procedure starting from Et4NI (784 mg, 3.05 mmol, 2.0 equiv) and DMP
55.5 (OCH3), 55.3 ppm (OCH3); IR (neat): n˜ =2936, 2837, 1640, 1593,
(1.29 g, 3.05 mmol, 2.0 equiv) in dry CH2Cl2 (3.5 mL). Chalcone
1
+
1511, 1459, 1341, 1259, 1208, 1022 cmꢀ1; MS (EI): m/z (%): 449 [M
]
C
(500 mg, 1.53 mmol, 1.0 equiv) was added and the reaction mixture was
stirred until no more change was observed by TLC (5 days). The product
was purified on preparative TLC plates to afford the yellow solid 5
(200 mg, 0.440 mmol, 29%) as a Z/E mixture of 93:7. M.p. 978C; Z-5:
1H NMR (400 MHz, CDCl3): d=7.67 (d, J=1.9 Hz, 1H), 7.64 (s, 1H; b-
H), 7.33 (d, J=8.4 Hz, 1H), 7.29 (dd, J=8.5, 1.9 Hz, 1H), 6.87 (d, J=
8.4 Hz, 1H), 6.52 (dd, J=8.4, 2.2 Hz, 1H), 6.48 (d, J=2.2 Hz, 1H), 3.91
(s, 3H; OCH3), 3.90 (s, 3H; OCH3), 3.84 (s, 3H; OCH3), 3.77 ppm (s,
3H; OCH3); 13C NMR (101 MHz, CDCl3): d=191.8 (C=O), 163.3, 159.0,
150.9, 148.6 (b-CH), 148.3, 131.6 (CH), 127.7, 124.9 (CH), 119.6, 112.0
(CH), 110.5 (CH), 104.7 (CH), 104.2, 98.9 (CH), 56.0 (OCH3), 55.9
(OCH3), 55.8 (OCH3), 55.5 ppm (OCH3); IR (neat): n˜ =1631, 1598, 1510,
1259, 1231, 1212, 1144, 1017, 817 cmꢀ1; MS (ESI+) m/z (%): 455 [M+
H]+ (100); HRMS (ES-MS): calcd for C19H20IO5: 455.0350 [M+H]+;
found 455.0347.
(47), 311 (24), 165 (91); HRMS (EI): calcd for C25H23NO7: 449.1475
AHCTUNGTRENNUNG
[M +]; found 449.1482.
C
(E)-1-(2,4-Dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-phenylprop-2-
en-1-one (9): Yellow solid (65%, E); m.p. 508C; the E/Z ratio observed
later for the isomerized product in CDCl3 is 3:2; E-9: 1H NMR
(400 MHz, CDCl3): d=7.42 (d, J=8.4 Hz, 1H), 7.39–7.35 (m, 2H), 7.31–
7.27 (m, 3H), 7.23 (s, 1H; b-H), 6.76–6.68 (m, 2H), 6.53 (dd, J=8.4,
2.2 Hz, 1H), 6.44 (dd, J=9.6, 2.1 Hz, 2H), 3.83 (s, 3H; OCH3), 3.82 (s,
3H; OCH3), 3.74 (s, 3H; OCH3), 3.39 ppm (s, 3H; OCH3); 13C NMR
(101 MHz, CDCl3): d=196.8 (C=O), 162.7, 158.8, 149.8, 148.1, 140.8 (b-
CH), 140.5, 137.0, 131.2 (CH), 130.1 (2 CH), 128.5 (2 CH), 127.8, 127.4
(CH), 125.2 (CH), 122.6, 112.3 (CH), 110.3 (CH), 104.4 (CH), 98.6 (CH),
55.7 (OCH3), 55.6 (OCH3), 55.4 (OCH3), 55.0 ppm (OCH3) ; IR (neat):
n˜ =2934, 2837, 1642, 1593, 1512, 1261, 1245, 1207, 1141, 1020 cmꢀ1; MS
(ESI+): m/z (%): 405 [M+H]+ (100); HRMS (ES-MS): calcd for
C25H25O5: 405.1697 [M+H]+; found 405.1701.
(E)-1-(2,4-Dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-(trifluorome-
thyl)prop-2-en-1-one (12):[28] A mixture of a-bromo chalcone 4 (200 mg,
0.491 mmol, 1.0 equiv), CuI (112 mg, 0.589 mmol, 1.2 equiv), and
MFSDA (456 mL, 3.58 mmol, 7.3 equiv) in dry DMF (20 mL) was stirred
at 758C under a N2 atmosphere for 3 days. Upon completion of the reac-
tion, the mixture was diluted with Et2O (40 mL) and filtered. The solu-
tion was poured into H2O (40 mL) and the mixture extracted with Et2O
(4ꢅ40 mL). The combined extracts were washed with H2O (3ꢅ5 mL),
dried over MgSO4, filtered, and concentrated in vacuo. The product was
purified on preparative TLC plates (SiO2, CHCl3/MeOH, 99:1) to afford
compound 12 (120 mg, 0.303 mmol, 62%) as a pale yellow oil. The ste-
(E)-1-(2,4-Dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-(4-methoxyphe-
nyl)prop-2-en-1-one (10): Yellow solid (75%, E); m.p. 458C; the E/Z
ratio observed later for the isomerized product in CDCl3 is 8:1; E-10:
1H NMR (300 MHz, CDCl3): d=7.41 (d, J=8.4 Hz, 1H), 7.21–7.16 (m,
3H), 6.93–6.88 (m, 2H), 6.77–6.68 (m, 2H), 6.54–6.50 (m, 2H), 6.42 (d,
J=2.2 Hz, 1H), 3.84 (s, 3H; OCH3), 3.83 (s, 3H; OCH3), 3.80 (s, 3H;
OCH3), 3.74 (s, 3H; OCH3), 3.47 ppm (s, 3H; OCH3); 13C NMR
(75 MHz, CDCl3): d=197.3 (C=O), 162.7, 159.0, 158.9, 149.7, 148.1, 140.5
(b-CH), 140.3, 131.3 (2 (CH)), 131.2 (CH), 129.1, 128.1, 125.0 (CH),
122.8, 114.0 (2ꢅ(CH)), 112.5 (CH), 110.4 (CH), 104.4 (CH), 98.6 (CH),
55.7 (OCH3), 55.6 (OCH3), 55.4 (OCH3), 55.2 (OCH3), 55.2 ppm
(OCH3); IR (neat): n˜ =2939, 2835, 1638, 1595, 1575, 1508, 1460, 1241,
1207, 1127, 1020 cmꢀ1; MS (ESI+): m/z (%): 435 [M+H]+ (100); HRMS
(ES-MS): calcd for C26H27O6: 435.1802 [M+H]+; found 435.1800.
ACHTUNGTRENNUNGreochemistry of compound 12 was assigned as the E isomer based on its
19F NMR shift.[46] 1H NMR (400 MHz, CDCl3): d=7.82 (d, J=8.8 Hz,
1H), 7.11 (d, J=1.4 Hz, 1H; b-H), 6.86 (dd, J=8.3, 2.0 Hz, 1H), 6.78 (d,
J=2.0 Hz, 1H), 6.70 (d, J=8.4 Hz, 1H), 6.44 (dd, J=8.8, 2.3 Hz, 1H),
6.34 (d, J=2.3 Hz, 1H), 3.80 (s, 6H; 2OCH3), 3.77 (s, 3H; OCH3),
3.64 ppm (s, 3H; OCH3); 13C NMR (101 MHz, CDCl3): d=189.7 (C=O),
165.7, 162.0, 150.1, 148.5, 134.2 (CH), 133.8 (q, J=5.9 Hz, b-CH), 130.2
(q, J=29.3 Hz, a-C), 125.4, 123.4 (CH), 122.8 (q, J=274.0 Hz, CF3),
119.6, 111.7 (CH), 110.7 (CH), 105.5 (CH), 98.5 (CH), 55.7 (OCH3), 55.5
(OCH3), 55.49 (OCH3), 55.48 ppm (OCH3); 19F NMR (376 MHz, CDCl3):
d=ꢀ62 ppm (d, J=1.1 Hz); IR (neat): n˜ =3005, 2939, 2842, 1642, 1593,
1515, 1252, 1111, 1021 cmꢀ1; MS (ESI+): m/z (%): 397 [M+H]+ (100);
HRMS (ES-MS): calcd for C20H20F3O5: 397.1257 [M+H]+; found
397.1265.
(E)-1-(2,4-Dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)-2-nitroprop-2-en-
1-one (11):[21] A mixture of nitroacetophenone 19 (589 mg, 2.62 mmol,
1.0 equiv), 3,4-dimethoxybenzaldehyde (21; 696 mg, 4.19 mmol,
1.6 equiv), b-alanine (19.6 mg, 0.220 mmol, 0.084 equiv), and glacial
AcOH (420 mL, 7.34 mmol, 2.8 equiv) in benzene (15 mL) was heated to
reflux overnight by using a Dean–Stark apparatus. The reaction mixture
was washed with H2O (3ꢅ10 mL) then the aqueous layer was extracted
with CH2Cl2 (3ꢅ10 mL), the organic extracts were combined and dried
over MgSO4. The solvent was evaporated in vacuo and the resulting resi-
due was subjected to column chromatography (SiO2, petroleum ether/
EtOAc, 7:3) to afford 11 (820 mg, 2.20 mmol, 84%) as a yellow solid,
m.p. 448C. The stereochemistry of compound 11 was assigned as the E
isomer based on literature.[47] 1H NMR (400 MHz, CDCl3): d=8.15 (d,
J=8.9 Hz, 1H), 7.94 (s, 1H; b-H), 7.08 (dd, J=8.5, 2.0 Hz, 1H), 6.91 (d,
J=2.1 Hz, 1H), 6.81 (d, J=8.4 Hz, 1H), 6.63 (dd, J=8.9, 2.3 Hz, 1H),
6.41 (d, J=2.3 Hz, 1H), 3.88 (s, 6H; 2ꢅOCH3), 3.76 (s, 3H; OCH3),
3.68 ppm (s, 3H; OCH3); 13C NMR (101 MHz, CDCl3): d=184.3 (C=O),
166.6, 162.2, 152.1, 149.0, 147.5, 133.5 (CH), 133.2 (b-CH), 126.3 (CH),
122.6, 118.6, 112.3 (CH), 111.1 (CH), 106.8 (CH), 98.3 (CH), 56.0
(OCH3), 55.9 (OCH3), 55.7 (OCH3), 55.6 ppm (OCH3); IR (neat): n˜ =
2939, 2839, 166, 1590, 1508, 1313, 1249, 1018 cmꢀ1; MS (ESI+): m/z (%):
General procedure for synthesis of a-aryl chalcones 8, 9 and 10:[15b]
mixture of a-bromo chalcone 4 (150 mg, 0.368 mmol, 1.0 equiv), the cor-
responding boronic acid (0.442 mmol, 1.2 equiv), [Pd2A(dba)3]·CHCl3
A
CTHUNGTRENNUNG
(8.0 mg, 0.0080 mmol, 0.022 equiv), and PPh3 (4.0 mg, 0.015 mmol,
0.042 equiv) was dissolved in toluene (2.2 mL) and n-PrOH (0.75 mL)
and degassed. After stirring for 10 min, HNEt2 (50 mL, 0.478 mmol,
1.3 equiv) and H2O (0.60 mL) were added, the mixture was degassed
again and then stirred under reflux for 24 h. After cooling to room tem-
perature, it was poured into EtOAc (50 mL). The organic layer was
washed with 0.2m NaOH (25 mL), 0.05m HCl (25 mL), and H2O (2ꢅ
25 mL), dried over MgSO4, and filtered. The solvent was removed in
vacuo and the product was purified on preparative TLC plates (SiO2,
15392
ꢃ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 15384 – 15395