Synthesis of Trifluormethylated Azines
yield.26 p-Methoxybenzyl bromide was prepared according to a
literature procedure.27
m/z (%) 327 (M+, 4), 296 (1), 258 (12), 121 (100); HRMS (EI)
calcd for C16H16NO3F3 (M+), 327.1082; found, 327.1079. Anal.
Calcd for C16H16NO3F3: C, 58.72; H, 4.93; N, 4.28; F, 17.41.
Found: C, 58.79; H, 4.94; N, 4.31; F, 17.37.
General Procedure for Trifluoromethylation of Azinium
Salts. A flame-dried 10 mL round-bottom flask was charged with
dry CH2Cl2 (4.0 mL), azinium salt (2.00 mmol), TMSCF3 (341
mg, 356 µL, 2.4 mmol), Ph3SnF (221 mg, 0.6 mmol), and spray-
dried KF (174 mg, 3.0 mmol). After 24 h of vigorous stirring in an
argon atmosphere at room temperature, the reaction mixture was
poured on water (10 mL), diluted with CH2Cl2 (ca. 5 mL), and the
phases were separated. The organic phase was dried over anhydrous
Na2SO4 and evaporated, and the products purified by column
chromatography on silica gel using 5:1 or 10:1 hexanes-AcOEt
or 5:1 hexanes-Et2O.
1-(p-Methoxybenzyl)-2-trifluoromethyl-3-methoxycarbonyl-
1,2-dihydropyridine (3d). Pale yellow oil: IR (film, νmax, cm-1
)
2953, 2840, 1694, 1612, 1515, 1438, 1290, 1257, 1175, 1125, 1091,
1
995, 844, 742, 709; H NMR (500 MHz, CDCl3) δ 3.70 (3H, s,
OCH3), 3.77 (3H, s, OCH3), 4.47 (2H, AB, 2JHH ) 15.5 Hz, NCH2),
3
3
5.08 (1H, t, JHH ) 6.7 Hz, CHdCHN), 5.16 (1H, qd, JHF ) 7.2
3
3
Hz, JHH ) 0.9 Hz, CHCF3), 6.58 (1H, d, JHH ) 6.9 Hz, CHd
CHN), 6.86 (2H, d, 3JHH ) 8.7 Hz, PMB), 7.11 (2H, d, 3JHH ) 8.6
Hz, PMB), 7.36 (1H, d, 3JHH ) 6.5 Hz, CHdC(CO2Me)); 13C NMR
2
(125 MHz, CDCl3) δ 51.4, 55.1, 56.8 (q, JCF ) 31.4 Hz), 58.7,
1-(p-Methoxybenzyl)-2-trifluoromethyl-1,2-dihydroquino-
line (2a). Colorless oil: IR (film, νmax, cm-1) 3037, 2957, 2838,
1646, 1612, 1600, 1513, 1493, 1456, 1400, 1304, 1248, 1159, 1119,
96.3, 101.4, 114.3, 125.6 (q, 1JCF ) 291.6 Hz), 127.7, 128.8, 138.0,
142.3, 159.5, 166.2; 19F NMR (376 MHz, CDCl3) δ -78.27 (d,
3JFH ) 7.5 Hz, CF3); MS (EI 70 eV) m/z (%) 327 (M+, 2), 258
(13), 121 (100); HRMS (EI) calcd for C16H16NO3F3 (M+), 327.1082;
found, 327.1092. Anal. Calcd for C16H16NO3F3: C, 58.72; H, 4.93;
N, 4.28; F, 17.41. Found: C, 58.94; H, 4.96; N, 4.27; F, 17.45.
5-Cyano-1-(p-methoxybenzyl)-2-trifluoromethyl-1,2-dihydro-
pyridine (2e). Pale yellow oil: IR (film, νmax, cm-1) 2938, 2206,
1
1035, 955, 837, 819, 772, 748; H NMR δ 3.78 (3H, s, OCH3),
2
3
4.38 (1H, d, JHH ) 15.3 Hz, NCH2), 4.44 (1H, m, J ) 6.9 Hz,
CHCF3), 4.82 (1H, d, 2JHH ) 15.4 Hz, NCH2), 5.60 (1H, dd, 3JHH
3
) 9.5 Hz, 5.9 Hz, CHCHCF3), 6.68 (1H, d, JHH ) 8.4 Hz, CHd
CHCH), 6.71 (2H, m, Harom), 6.85 (2H, dm, 3JHH ) 8.8 Hz, PMB),
3
4
7.02 (1H, dd, JHH ) 7.4 Hz, JHH ) 1.5 Hz, Harom), 7.09 (1H, m,
3
arom), 7.19 (2H, dm, JHH ) 8.8 Hz, PMB); 13C NMR δ 53.8,
1
H
1643, 1612, 1572, 1514, 1303, 1252, 1175, 1132, 1027, 851; H
2
NMR δ 3.82 (3H, s, OCH3), 4.45 (2H, AB, 2JHH ) 15.1 Hz, NCH2),
55.2, 58.1 (q, JCF ) 30.2 Hz), 112.7, 114.1, 114.5, 118.1, 121.6,
125.2 (q, 1JCF ) 290.5 Hz), 127.6, 128.6, 128.7, 129.5, 131.0, 143.2,
159.0; 19F NMR δ -77.48 (d, 3JFH ) 6.7 Hz, CF3); MS (EI 70 eV)
m/z (%) 319 (M+, 5), 250 (20), 121(100); HRMS (EI) calcd for
C18H16NOF3 (M+), 319.1184; found, 319.1174. Anal. Calcd for
C18H16NOF3: C, 67.70; H, 5.05; N, 4.39. Found: C, 67.37; H, 4.96;
N, 4.20.
3
3
4.52 (1H, m, J ) 6.4 Hz, CHCF3), 4.99 (1H, dd, JHH ) 9.6 Hz,
5.6 Hz, CHCHCF3), 6.24 (1H, d, 3JHH ) 9.5 Hz, CHdCHCHCF3),
3
4
6.93 (2H, d, JHH ) 8.7 Hz, PMB), 7.00 (1H, d, JHH ) 0.9 Hz,
CHdCCN), 7.16 (2H, d, 3JHH ) 8.8 Hz, PMB); 13C NMR δ 55.3,
2
4
56.9 (q, JCF ) 31.9 Hz), 59.0 (q, JCF ) 1.7 Hz), 80.5, 104.9,
114.6, 119.7, 124.3 (q, 1JCF ) 288.8 Hz), 125.8, 126.3, 129.3, 147.3,
160.0; 19F NMR δ -78.19 (d, 3JFH ) 6.4 Hz, CF3); MS (EI 70 eV)
m/z (%) 294 (M+, 4), 121 (100); HRMS (EI) calcd for C15H13N2-
OF3 (M+), 294.0980; found, 294.0984. Anal. Calcd for C15H13N2-
OF3: C, 61.22; H, 4.45; N, 9.52; F, 19.37. Found: C, 61.72; H,
4.41; N, 9.46; F, 17.55.
1-Benzyl-5-methyl-2-trifluoromethyl-1,2-dihydropyridine (2b).
Yellow oil, decomposes after a few hours at RT: 1H NMR (200
3
MHz, CDCl3) δ 1.81 (3H, s, Me), 4.25 (1H, q, JHF ) 7.3 Hz,
3
CHCF3), 4.43 (2H, s, NCH2), 4.96 (1H, t, JHH ) 6.2 Hz, CHd
CHN), 6.04 (1H, d, 3JHH ) 5.0 Hz, CHCHdCH), 6.16 (1H, d, 3JHH
) 7.1 Hz, CHCHdCH), 7.15-7.60 (5H, m, Ph); 13C NMR (50
MHz, CDCl3) δ 21.5 (d, 4JCF ) 2.2 Hz), 58.5, 62.1 (q, 2JCF ) 29.3
Hz), 96.9, 112.5, 124.1, 126.4 (q, 4JCF ) 293.3 Hz), 127.0, 127.6,
128.7, 133.6, 137.8.
3-Cyano-1-(p-methoxybenzyl)-2-trifluoromethyl-1,2-dihydro-
pyridine (3e). Pale yellow oil: IR (film, νmax, cm-1) 2937, 2201,
1
1613, 1515, 1465, 1252, 1175, 1124, 1033, 709; H NMR δ 3.83
2
(3H, s, OCH3), 4.46 (2H, AB, JHH ) 15.0 Hz, NCH2), 4.60 (1H,
2-Benzhydryl-1-trifluoromethyl-1,2-dihydroisoquinoline (2c).
White solid: mp 109-111 °C; IR (KBr, νmax, cm-1) 3030, 1622,
1597, 1563, 1491, 1454, 1249, 1217, 1162, 1116, 953, 768, 748,
qd, 3JHF ) 6.7 Hz, 4JHH ) 1.1 Hz, CHCF3), 5.08 (1H, t, 3JHH ) 6.9
Hz, NCHdCH), 6.64 (1H, d, 3JHH ) 7.0 Hz, NCHdCH), 6.92 (2H,
d, 3JHH ) 8.7 Hz, PMB), 6.95 (1H, d, 3JHH ) 6.6 Hz, CHdCCN),
7.16 (2H, d, 3JHH ) 8.8 Hz, PMB); 13C NMR δ 55.3, 57.5 (q, 2JCF
) 32.0 Hz), 58.9, 81.4, 96.3, 114.6, 118.9, 125.0 (q, 1JCF ) 291.4
Hz), 126.6, 129.0, 142.4, 142.6, 159.9; 19F NMR δ -78.46 (d, 3JFH
) 7.0 Hz, CF3); MS (EI 70 eV) m/z (%) 294 (M+, 9), 225 (4), 188
(9), 121 (100); HRMS (EI) calcd for C15H13N2OF3 (M+), 294.0980;
found, 294.0982; Anal. Calcd for C15H13N2OF3: C, 61.22; H, 4.45;
N, 9.52; F, 19.37. Found: C, 61.71; H, 4.71; N, 9.48; F, 17.35.
5-Benzoyl-1-(p-methoxybenzyl)-2-trifluoromethyl-1,2-dihy-
dropyridine (2f). Pale yellow oil: IR (CH2Cl2, νmax, cm-1) 3061,
2937, 1642, 1612, 1564, 1514, 1417, 1327, 1303, 1253, 1214, 1167,
1
3
729, 699, 686; H NMR δ 5.00 (1H, q, JHF ) 7.3 Hz, CHCF3),
3
5.39 (d, JHH ) 7.5 Hz, NCHdCH), 5.87 (1H, s, CHPh2), 6.01
(1H, dm, 3JHH ) 7.5, 5JHF ) 1.3 Hz, NCHdCH), 6.96 (1H, d, 3JHH
3
4
) 7.5 Hz, Harom), 7.01 (1H, dd, JHH ) 7.7 Hz, JHH ) 1.1 Hz,
H
arom), 7.07 (1H, td, 3JHH ) 7.5 Hz, 4JHH ) 1.3 Hz, Harom), 7.16-
7.37 (11H, m, Harom, Ph); 13C NMR δ 62.3 (q, JCF ) 29.3 Hz),
70.8, 98.9, 119.7, 123.5, 125.2, 125.7 (q, 1JCF ) 289.7 Hz), 127.4,
127.8, 128.1, 128.1, 128.6, 128.7, 129.1, 129.9, 131.7, 133.9, 139.0,
2
3
5
140.6; 19F NMR δ -77.55 (dd, JFH ) 7.7 Hz, JFH ) 1.1 Hz,
CF3); MS (EI 70 eV) m/z (%) 365 (M+, 8), 296 (13), 167 (100),
152 (15); HRMS (EI) calcd for C23H18NF3 (M+), 365.1391; found,
365.1395. Anal. Calcd for C23H18NF3: C, 75.60; H, 4.97; N, 3.83;
F, 15.60. Found: C, 75.75; H, 5.07; N, 3.82; F, 15.69.
1
1130, 1111, 1024, 723, 705; H NMR δ 3.78 (3H, s, OMe), 4.43
(1H, 2JHH ) 15.0 Hz, NCH2), 4.49-4.60 (2H, m, CHCF3, NCH2),
3
5.12 (1H, dd, JHH ) 9.7 Hz, 5.5 Hz, CHdCHCHCF3), 6.87 (2H,
3
3
1-(p-Methoxybenzyl)-2-trifluoromethyl-5-methoxycarbonyl-
d, JHH ) 8.6 Hz, PMB), 7.04 (1H, d, JHH ) 9.7 Hz, CHd
CHCHCF3), 7.10 (2H, d, 3JHH ) 8.6 Hz, PMB), 7.24 (1H, s, NCHd
CCOPh), 7.35-7.42 (2H, m, Ph), 7.42-7.49 (1H, m, Ph), 7.52-
7.58 (2H, m, Ph); 13C NMR δ 55.2, 57.4 (q, 2JCF ) 31.5 Hz), 59.3
(d, JCF ) 1.3 Hz), 104.7, 110.2, 114.5, 124.6 (q, 1JCF ) 288.8 Hz),
126.1, 127.1, 128.1, 128.6, 129.0, 130.6, 139.3, 150.1, 159.8, 190.9;
1,2-dihydropyridine (2d). Pale yellow oil: IR (film, νmax, cm-1
)
2952, 1693, 1640, 1573, 1514, 1436, 1296, 1252, 1171, 1123, 1025,
1
850, 736; H NMR δ 3.71 (3H, s, OCH3), 3.80 (3H, s, OCH3),
3
4.47 (1H, m, CHCF3), 4.49 (2H, s, NCH2), 4.94 (1H, dd, JHH
)
9.6 Hz, 5.5 Hz, CHdCHCHCF3), 6.74 (1H, d, 3JHH ) 9.6 Hz, CHd
CHCHCF3), 6.90 (2H, d, 3JHH ) 8.7 Hz, PMB), 7.16 (2H, d, 3JHH
) 8.7 Hz, PMB), 7.52 (1H, d, 4JHH ) 0.7 Hz, NCHdC(CO2Me));
13C NMR δ 50.9, 55.2, 57.1 (q, 2JCF ) 31.0 Hz), 59.0, 100.0, 103.2,
114.4, 124.6 (q, 1JCF ) 288.8 Hz), 126.7, 126.9, 129.0, 146.4, 159.7,
166.3; 19F NMR δ -78.20 (d, 3JFH ) 6.6 Hz, CF3); MS (EI 70 eV)
3
19F NMR δ -77.62 (d, JFH ) 6.5 Hz, CF3); MS (EI 70 eV) m/z
(%) 373 (M+, 4), 304 (14), 251 (8), 121 (100), 105 (24), 77 (22);
HRMS (EI) calcd for C21H18NO2F3 (M+), 373.1290; found,
373.1276. Anal. Calcd for C21H18NO2F3: C, 67.55; H, 4.86; N,
3.75; F, 15.26. Found: C, 67.18; H, 5.16; N, 3.63; F, 15.31.
3-Benzoyl-1-(p-methoxybenzyl)-2-trifluoromethyl-1,2-dihy-
dropyridine (3f). Yellow oil: IR (CH2Cl2, νmax, cm-1) 3060, 2936,
(26) Gingras, M. Tetrahedron Lett. 1991, 32, 7381.
(27) Ruder, S. M.; Ronald, R. C. Tetrahedron Lett. 1987, 28, 135.
1
1627, 1513, 1251, 1207, 1176, 1113, 1064, 1029, 719, 643; H
J. Org. Chem, Vol. 72, No. 15, 2007 5579