Botella and Na´jera
3
Method C. A 15 mL pressure tube was charged with the
aryl bromide (1 mmol), alkene (1.5 mmol), (dicyclohexyl)-
methylamine (0.321 mL, 1.5 mmol), catalyst (0.1-1 mol % Pd,
see the tables), and DMA (2 mL) for monoarylation reactions.
For diarylation 0.5 mmol of alkene was used. The mixture was
heated at 120 °C, and the reaction was monitored by GLC.
The same workup as before was performed.
22 Hz), 117.7, 128.6, 129.4, 130.1, 130.4 (d, JCF ) 8.8 Hz),
135.0 (d, 4JCF ) 2.2 Hz), 136.8, 161.9, 164.0 (d, 1JCF ) 251 Hz);
MS m/z (rel int) 223 (M+, 100), 222 (54), 208 (19), 202 (14),
196 (23), 183 (44), 175 (10), 111, (12), 98 (27), 88 (27), 85 (20),
75 (12); HRMS calcd for C15H10FN 223.0797, found 223.0794.
Ethyl (E)-3-(4-chlorophenyl)but-2-enoate (5l): oil; Rf
0.45 (hexane/EtOAc 9/1); IR (film) ν (cm-1) ) 1716 (CdO), 1629
1
Compounds 4e,f,h,i are commercially available, and com-
pounds 4a,30 4b,31 4c,d,32 4g,33 5a,11a 5c,11a 5d,34 5e,35 5f,36 5h,37
5k,38 5m,39 5o,10b 6f,40 6g,8b and 6h41 have been previously
reported and were characterized by comparison with their
reported data. The configuration of new compounds 5 was
determined by NMR NOESY experiments. Physical, analytical,
and spectroscopic data of new synthesized compounds follow.
Ethyl (E)-3-(4-fluorophenyl)-3-phenylpropenoate (5b):
oil; Rf 0.40 (hexane/EtOAc 9/1); IR (film) ν (cm-1) ) 1723 (Cd
(CdC), 1274, 1173 (C-O); H NMR δ ) 1.31 (t, 3H, J ) 7.1
Hz), 2.55 (d, 3H, J ) 0.9 Hz), 4.21 (q, 2H, J ) 7.1 Hz), 6.11 (q,
1H, J ) 0.9 Hz), 7.33 (d, 2H, J ) 8.6 Hz), 7.40 (d, 2H, J ) 8.6
Hz); 13C NMR δ ) 14.3, 17.8, 59.9, 117.6, 127.6, 128.7, 135.0,
140.6, 154.0, 166.6; MS m/z (rel int) 226 (M+ + 2, 12), 224 (M+,
34), 195 (35), 179 (77), 152 (22), 115 (100); HRMS calcd for
C12H13ClO2 224.0604, found 224.0614.
(E)-3-(4-Chlorophenyl)-3-phenylpropenamide (5n): mp
116-118 °C; Rf 0.19 (hexane/EtOAc 1/1); IR (KBr) ν (cm-1) )
1
1
O), 1600 (CdC), 1227, 1161 (CO), 1265 (ArCF); H NMR δ )
3471, 3322, 3176 (NH2), 1658 (CdO); H NMR δ ) 5.32 (brs,
1H), 6.03 (brs, 1H), 6.33 (s, 1H), 7.16-7.42 (m, 9H); 13C NMR
δ ) 122.0, 128.7, 128.9, 129.0, 129.2, 130.8, 135.2, 137.7, 139.1,
149.9, 168.5; MS m/z (rel int) 259 (M+ + 2, 18), 258 (M+ + 1,
41), 257 (M+, 50), 256 (M+-1, 100), 241 (24), 213 (17), 212 (11),
205 (17), 179 (15), 178 (70), 177 (24), 176 (33), 152 (14), 151
(14), 139 (13), 110 (23), 105 (12), 89 (19), 88 (27), 77 (15), 76
(19), 75 (20), 51 (28). Anal. Calcd for C15H12ClNO: C, 69.91;
H, 4.69; N, 5.43. Found: C, 69.74; H, 4.69; N, 5.99.
Ethyl (E)-3-(4-acetylphenyl)but-2-enoate (5p): oil; Rf
0.34 (hexane/EtOAc 9/1); IR (KBr) ν (cm-1) ) 1713 (CO2), 1684
(CdO), 1628 (CdC), 1264, 1174 (CO); 1H NMR δ ) 1.25 (t,
3H, J ) 7.1 Hz), 2.51 (d, 3H, J ) 1.1 Hz), 2.55 (s, 3H), 6.11 (q,
2H, J ) 1.1 Hz), 7.48 (d, 2H, J ) 8.3 Hz), 7.89 (d, 2H, J ) 8.3
Hz); 13C NMR δ )14.3, 17.9, 26.7, 60.1, 118.9, 126.6, 128.6,
137.1, 146.7, 154.0, 166.5, 197.5; MS m/z (rel int) 232 (M+, 100),
218 (13), 217 (97), 203 (43), 189 (75), 187 (35), 161 (22), 152
(31), 146 (13), 145 (36), 144 (12), 138 (10), 131 (25), 115 (44);
HRMS calcd for C14H16O3 232.1099, found 232.1091.
1.11 (t, 3H, J ) 7.1 Hz), 4.05 (q, 2H, J ) 7.1 Hz), 6.31 (s, 1H),
7.00-7.04 (m, 2H), 7.17-7.37 (m, 7H); 13C NMR δ ) 14.0, 60.2,
115.5 (d, 2JCF ) 22.0 Hz), 117.3, 128.0, 128.3, 129.1, 130.2 (d,
3JCF ) 8.9 Hz), 137.0 (d, 4JCF ) 3.3 Hz), 138.8, 155.4, 163.5 (d,
1JCF ) 250.3 Hz), 166.0; MS m/z (rel int) 270 (M+, 52), 242
(16), 241 (17), 179 (100), 198 (84), 197 (64), 196 (96), 183 (39),
177 (24), 176 (35), 170 (14), 123 (26), 105 (27), 98 (25), 77 (20),
51 (23); HRMS calcd for C17H15FO2 270.1056, found 270.1066.
(E)-3-(4-Fluorophenyl)-3-phenylpropenoic acid (5g):
mp 164-166 °C; Rf 0.48 (hexane/EtOAc 1/1); IR (KBr) ν (cm-1
)
) 2916 (OH), 1696 (CdO), 1213 (ArCF); 1H NMR δ ) 6.27 (s,
1H), 6.98-7.04 (m, 2H), 7.17-28 (s, 4H), 7.36-7.38 (m, 3H);
2
13C NMR δ ) 115.5 (d, JCF ) 22.0 Hz), 116.2, 128.0, 128.6,
129.2, 130.4 (d, 3JCF ) 8.8 Hz), 136.9 (d, 4JCF ) 3.3 Hz), 138.2,
1
157.9, 163.7 (d, JCF ) 250.3 Hz), 170.7; MS m/z (rel int) 242
(M+, 100), 241 (69), 225 (20), 224 (12), 223 (44), 222 (22), 198
(11), 197 (47), 196 (66), 195 (12), 194 (18), 183 (30), 177 (12),
176 (15), 170 (13), 165 (11), 98 (11); HRMS calcd for C15H11-
FO2 242.0743, found 242.0744.
tert-Butyl 3,3-diphenylpropenoate (6a): mp 75-78 °C;
(E)-3-(4-Fluorophenyl)-3-phenylpropenamide (5i): mp
Rf 0.46 (hexane/EtOAc 9/1); IR (KBr) ν (cm-1) ) 1717 (CdO),
114-116 °C; Rf 0.13 (hexane/EtOAc 1/1); IR (KBr) ν (cm-1) )
1
1624 (CdC), 1264, 1144 (CO); H NMR δ ) 1.28 (s, 9H), 6.28
1
3322, 3176 (NH2), 1651 (CdO); H NMR δ ) 5.08 (brs, 1H,),
(s, 1H), 7.18-7.38 (m, 10H); 13C NMR δ ) 27.8, 80.3, 119.9,
127.86, 127.89, 128.2, 128.3, 129.1, 129.2, 139.4, 141.0, 154.3,
165.8; MS m/z (rel int) 280 (M+, 4), 224 (100), 223 (91), 207
(27), 179 (69), 178 (60), 165 (10), 152 (9), 105 (9), 102 (8), 77
(11), 57 (44). Anal. Calcd for C19H20O2: C, 81.40; H, 7.19.
Found: C, 81.41; H, 7.24.
5.55 (brs, 1H), 6.33 (s, 1H), 6.98-7.03 (m, 2H), 7.21-7.29 (m,
2
4H), 7.42-7.46 (m, 3H); 13C NMR δ ) 115.5 (d, JCF ) 22.0
Hz), 121.6, 129.0, 129.1, 129.3, 129.9 (d, 3JCF ) 8.8 Hz), 136.7
4
1
(d, JCF ) 3.3 Hz), 138.0, 150.0, 163.4 (d, JCF ) 250.3 Hz),
168.4; MS m/z (rel int) 241 (M+, 51), 240 (100), 225 (17), 197
(27), 196 (63), 176 (22), 146 (13), 123 (11), 120 (10), 105 (13),
98 (20), 97 (12), 85 (13), 77 (14), 75 (16), 51 (27); HRMS cald
for C15H12FNO 241.0903, found 241.0878.
tert-Butyl 3,3-di(4-fluorophenyl)propenoate (6b): mp
98-99 °C; Rf 0.63 (hexane/EtOAc 5/1); IR (KBr) ν (cm-1) )
1
1682 (CdO), 1598 (CdC), 1299, 1148 (CO), 1220 (ArCF); H
(E)-3-(4-Fluorophenyl)-3-phenylpropenonitrile (5j): oil;
NMR δ ) 1.32 (s, 9H), 6.22 (s, 1H), 6.97-7.26 (m, 8H, ArH);
Rf 0.32 (hexane/EtOAc 9/1); IR (film) ν (cm-1) ) 2216 (CN);
13C NMR δ ) 27.8, 80.6, 115.0 (d, 2JCF ) 22 Hz), 115.4 (d, 2JCF
1H NMR δ ) 5.69 (s, 1H), 7.03-7.09 (m, 2H), 7.25-7.31 (m,
3
3
) 22 Hz), 130.0 (d, JCF ) 8.8 Hz), 131.0 (d, JCF ) 7.7 Hz),
2
2H), 7.40-7.48 (m, 5H); 13C NMR: δ ) 94.7, 115.6 (d, JCF
)
135.0 (d, 4JCF ) 3.3 Hz), 137.0 (d, 4JCF ) 3.3 Hz), 152.4, 162.6
1
1
(d, JCF ) 248 Hz), 163.4 (d, JCF ) 249 Hz), 165.4; MS m/z
(rel int) 316 (M+, 3), 260 (100), 259 (42), 243 (30), 215 (33),
214 (37), 201 (17), 165 (10), 123 (14), 57 (62). Anal. Calcd for
C19H18F2O2: C, 72.14; H, 5.74. Found: C, 71.93; H, 5.55.
tert-Butyl 3,3-di(4-chlorophenyl)propenoate (6c): mp
121 °C; Rf 0.68 (hexane/EtOAc 5/1); IR (KBr) ν (cm-1) ) 1689
(30) Sato, Y.; Takeuchi, S. Synthesis 1983, 734-735.
(31) Gillespie, K. M.; Sanders, C. J.; O’Shaughessy, P.; Westmore-
land, I.; Thickitt, C. P.; Scott, P. J. Org. Chem. 2002, 67, 3450-3458.
(32) Huang, Z.-Z.; Ye, S.; Xia, W.; Yu, Y.-H.; Tang, Y. J. Org. Chem.
2002, 67, 3096-3103.
(33) Tsuge, O.; Sone, K.; Urano, S.; Matsuda, K. J. Org. Chem. 1982,
47, 5171-5177.
1
(CdO), 1588 (CdC), 1314, 1164 (C-O); H NMR δ ) 1.31 (s,
(34) Lampe, W. J.; Chou, Y.-L.; Hanna, R. G.; Di Meo, S. V.; Erhardt,
P. W.; Hagedorn, A. A., III; Ingebretsen, W. R.; Cantor, E. J. Med.
Chem. 1993, 36, 1041-1047.
9H), 6.25 (s, 1H), 7.11-7.19 (m, 4H), 7.29 (d, 2H, J ) 8.6 Hz),
7.36 (d, 2H, J ) 8.6 Hz); 13C NMR δ ) 27.9, 80.8, 120.5, 128.3,
128.7, 129.4, 130.6, 134.2, 135.5, 137.3, 139.1, 152.0, 165.2;
MS m/z (rel int) 348 (M+, 4), 292 (100), 275 (28), 212 (56), 176
(56), 139 (17), 75 (14), 57 (61).Anal. Calcd for C19H18Cl2O2: C,
65.34; H, 5.19. Found: C, 65.22; H, 5.15.
tert-Butyl 3,3-di(4-methoxyphenyl)propenoate (6d): oil;
Rf 0.46 (hexane/EtOAc 5/1); IR (film) ν (cm-1) ) 2837 (OMe),
1711 (CO), 1604 (CdC); 1H NMR δ ) 1.33 (s, 9H), 3.80 (s, 3H),
3.84 (s, 3H), 6.14 (s, 1H), 6.82 (dd, 2H, J ) 6.9, 2.1 Hz), 6.89
(dd, 2H, J ) 6.9, 2.1 Hz), 7.13 (dd, 2H, J ) 6.9, 2.1 Hz), 7.21
(dd, 2H, J ) 6.9, 2.1 Hz); 13C NMR δ ) 27.9, 55.2, 55.3, 79.9,
113.2, 113.6, 117.4, 129.9, 130.9, 131.8, 134.0, 154.3, 159.5,
160.5, 166.1; MS m/z (rel int) 340 (M+, 27), 284 (100), 267 (30),
(35) Farina, V.; Krishnan, B.; Marshall, D. R.; Roth, G. P. J. Org.
Chem. 1993, 58, 5434-5444.
(36) Miguel del Corral, J. M.; Gordaliza, M.; Castro, M. A.; Salinero,
M. A.; Dorado, J. M.; San Feliciano, A. Synthesis 2000, 154-164.
(37) Wiley: R. H.; van der Plas, H. C. J. Chem. Eng. Data 1965, 10,
72-73.
(38) Nanni, D.; Pareschi, P.; Rizzoli, C.; Sgarabotto, P.; Tundo, A.
Tetrahedron, 1995, 51, 9045-9062.
(39) Budhram, R. S.; Palaniswamy, V. A.; Eisenbraun, E. J. J. Org.
Chem. 1986, 51, 1402-1406.
(40) Gokel, G. W.; DiBiase, S. A. Lipisko, B. A. Tetrahedron Lett.
1976, 17, 3495-3496.
(41) Colwell, W. T.; Lange, J. H.; Henry, D. W. J. Med. Chem. 1968,
11, 749-752.
4368 J. Org. Chem., Vol. 70, No. 11, 2005