H. J. Lee et al. / Tetrahedron Letters 55 (2014) 1183–1187
1464, 1251 cmꢀ1
1187
;
1H NMR (CDCl3, 300 MHz) d 2.83 (s, 3H), 6.66–6.80 (m, 2H),
6.83 (d, J = 7.8 Hz, 1H), 7.06–7.16 (m, 2H), 7.18 (dd, J = 3.6 and 0.9 Hz, 1H), 7.50
(dd, J = 5.1 and 0.9 Hz, 1H), 8.56 (br s, 1H); 13C NMR (CDCl3, 75 MHz) d 23.92,
109.42, 121.36, 122.92, 123.17, 125.37, 126.60, 127.34, 127.50, 128.57, 139.67,
143.72, 147.40, 169.72; ESIMS m/z 242 [M+H]+.
Compound 2i-Z: yellow solid, mp 191–192 °C; IR (KBr) 3474, 1697, 1606, 1444,
1259 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.62 (s, 3H), 6.64 (d, J = 8.1 Hz, 1H),
;
7.17 (dd, J = 8.1 and 1.8 Hz, 1H), 7.30-7.36 (m, 2H), 7.37–7.45 (m, 3H), 7.58 (d,
J = 1.8 Hz, 1H), 8.16 (br s, 1H); 13C NMR (CDCl3, 75 MHz) d 25.75, 110.32,
123.27, 124.31, 125.64, 126.89, 127.53, 128.04, 128.06, 128.46, 138.95, 141.79,
155.42, 167.40; ESIMS m/z 270 [M+H]+, 272 [M+H+2]+. Anal. Calcd for
C
16H12ClNO: C, 71.25; H, 4.48; N, 5.19. Found: C, 71.53; H, 4.71; N, 5.32.
Compound 2i-E: yellow solid, mp 209–210 °C; IR (KBr) 3445, 1693, 1614, 1468,
1303 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.81 (s, 3H), 6.05 (d, J = 1.8 Hz, 1H),
;
6.76 (d, J = 8.4 Hz, 1H), 7.04 (dd, J = 8.4 and 1.8 Hz, 1H), 7.22–7.32 (m, 2H),
7.44–7.58 (m, 3H), 8.93 (br s, 1H); 13C NMR (CDCl3, 75 MHz) d 22.95, 110.20,
123.18, 123.31, 124.72, 126.19, 126.56, 127.78, 128.82, 129.33, 138.02, 142.19,
157.61, 169.92; ESIMS m/z 270 [M+H]+, 272 [M+H+2]+.
Compound 2j-Z: yellow solid, mp 163–164 °C; IR (KBr) 3231, 1699, 1596, 1483,
1205 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.62 (s, 3H), 3.84 (s, 3H), 6.64 (d,
;
J = 8.4 Hz, 1H), 6.77 (d, J = 8.4 Hz, 1H), 7.24 (s, 1H), 7.28–7.50 (m, 5H), 8.34 (br s,
1H); 13C NMR (CDCl3, 75 MHz) d 25.59, 56.00, 109.71, 112.00, 112.68, 124.26,
125.21, 127.57, 127.98, 128.17, 134.45, 142.15, 154.16, 155.05, 167.98; ESIMS
m/z 266 [M+H]+. Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
77.12; H, 5.67; N, 5.36.
8. Typical procedure for the synthesis of 2e: To a stirred solution of oxindole (1a,
67 mg, 0.5 mmol), acetophenone (72 mg, 0.6 mmol), and pyridine (59 mg,
0.75 mmol) in dry THF (0.5 mL) was added dropwise a solution of Ti(OiPr)4
(284 mg, 1.0 mmol) in THF (0.3 mmL), and the reaction mixture was stirred at
room temperature for 4 h. After the usual aqueous extractive workup and
column chromatographic purification process (hexanes/ether, 2:1) 2e-Z
(92 mg, 78%) and 2e-E (18 mg, 15%) were obtained. Other compounds were
synthesized similarly, and the structures of known compounds 2a–e and 2k–p
were characterized by comparing their melting points and 1H NMR spectrum
with the reported.3,4 The selected spectroscopic data of unknown compounds
2f–j and 2q are as follows.
Compound 2j-E: yellow solid, mp 195–196 °C (dec.); IR (KBr) 3448, 1690, 1594,
1475, 1205 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.82 (s, 3H), 3.41 (s, 3H), 5.71 (d,
;
J = 2.4 Hz, 1H), 6.65 (dd, J = 8.4 and 2.4 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 7.24–
7.40 (m, 2H), 7.41–7.60 (m, 3H), 8.67 (br s, 1H); 13C NMR (CDCl3, 75 MHz) d
22.74, 55.18, 109.10, 109.71, 114.09, 124.12, 124.21, 126.40, 128.41, 129.20,
133.42, 142.70, 154.52, 155.90, 170.24; ESIMS m/z 266 [M+H]+.
Compound 2q-Z: yellow solid, mp 131–132 °C; IR (KBr) 1704, 1606, 1488,
1275 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.56 (s, 3H), 3.06 (s, 3H), 6.74 (d,
;
J = 7.8 Hz, 1H), 7.00 (t, J = 7.8 Hz, 1H), 7.15–7.42 (m, 6H), 7.58 (d, J = 7.8 Hz, 1H);
13C NMR (CDCl3, 75 MHz) d 25.45, 25.61, 107.68, 121.66, 123.47, 123.56,
123.85, 127.24, 127.98, 128.02, 128.39, 142.49, 143.25, 153.02, 166.22; ESIMS
m/z 250 [M+H]+. Anal. Calcd for C17H15NO: C, 81.90; H, 6.06; N, 5.62. Found: C,
81.72; H, 6.18; N, 5.39.
Compound 2q-E: yellow solid, mp 123–124 °C; IR (KBr) 1695, 1604, 1485,
1469 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.74 (s, 3H), 3.20 (s, 3H), 6.06 (d,
;
J = 7.8 Hz, 1H), 6.56 (t, J = 7.8 Hz, 1H), 6.68 (d, J = 7.8 Hz, 1H), 7.06 (t, J = 7.8 Hz,
1H), 7.16–7.26 (m, 2H), 7.32–7.48 (m, 3H); 13C NMR (CDCl3, 75 MHz) d 22.81,
25.70, 107.41, 121.31, 122.61, 122.77, 123.40, 126.45, 128.03, 128.28, 129.13,
142.21, 142.98, 154.84, 168.23; ESIMS m/z 250 [M+H]+.
Compound 2f-Z: yellow solid, mp 211–212 °C; IR (KBr) 3446, 1687, 1590, 1508,
1338 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 2.63 (s, 3H), 6.80 (d, J = 7.8 Hz, 1H),
7.10 (t, J = 7.8 Hz, 1H), 7.28 (t, J = 7.8 Hz, 1H), 7.46 (d, J = 8.7 Hz, 2H), 7.65 (d,
J = 7.8 Hz, 1H), 7.98 (br s, 1H), 8.27 (d, J = 8.7 Hz, 2H); ESIMS m/z 281 [M+H]+.
Anal. Calcd for C16H12N2O3: C, 68.56; H, 4.32; N, 9.99. Found: C, 68.78; H, 4.64;
N, 9.75.
Compound 2f-E: yellow solid, mp 239–240 °C; IR (KBr) 3446, 1695, 1616, 1592,
11. The major isomer 2e-Z obtained from acetophenone was not isomerized during
the separation, and it can be stored at room temperature. However, 2e-Z was
isomerized slowly to 2e-E in solution state even at room temperature, and the
isomerization was accelerated at 60 °C in the presence of pyridine. Actually, an
isolated pure 2e-Z was converted to a mixture (E/Z, 7:1) when we let the THF
solution at 60 °C in the presence of pyridine (1.0 equiv) for 24 h. The three Z-
isomers of 2f, 2j and 2q were isomerized to their E-isomers more rapidly than
other compounds in solution state. The contribution for the isomerization via
the canonical structure V (Scheme 2) might be increased for the p-nitrophenyl
and N-methyl derivatives.
1515, 1344 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.80 (s, 3H), 6.08 (d, J = 7.8 Hz,
;
1H), 6.66 (t, J = 7.8 Hz, 1H), 6.82 (d, J = 7.8 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.51
(dd, J = 6.9 and 1.8 Hz, 2H), 7.81 (br s, 1H), 8.38 (dd, J = 6.9 and 1.8 Hz, 2H); 13
NMR (CDCl3 + DMSO-d6, 75 MHz) 21.65, 109.49, 120.67, 122.05, 122.41,
C
d
124.27, 124.72, 127.65, 128.54, 147.22, 149.33, 149.83, 149.85, 169.05; ESIMS
m/z 281 [M+H]+.
Compound 2g-Z: yellow solid, mp 203–204 °C; IR (KBr) 3236, 1698, 1615, 1502,
1264 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.70 (s, 3H), 6.60 (d, J = 7.5 Hz, 1H),
;
7.02 (t, J = 7.5 Hz, 1H), 7.11 (t, J = 7.5 Hz, 1H), 7.40–7.52 (m, 3H), 7.63 (d,
J = 7.5 Hz, 1H), 7.74–7.89 (m, 4H), 8.24 (br s, 1H); 13C NMR (CDCl3, 75 MHz) d
25.75, 109.62, 121.52, 124.11, 124.22, 124.25, 125.94, 126.21, 126.37, 126.58,
127.27, 127.72, 128.33, 128.39, 133.11, 133.15, 139.86, 140.72, 153.12, 167.84;
ESIMS m/z 286 [M+H]+. Anal. Calcd for C20H15NO: C, 84.19; H, 5.30; N, 4.91.
Found: C, 84.26; H, 5.61; N, 4.77.
Compound 2g-E: yellow solid, mp 175–176 °C; IR (KBr) 3193, 1691, 1613,
1502, 1366 cmꢀ1
;
1H NMR (CDCl3, 300 MHz) d 2.89 (s, 3H), 6.18 (d, J = 7.8 Hz,
12. The generation of a titanium enolate of oxindole (1a) would be facile as
compared to N-methyloxindole (1d). The formation of a titanium enolate I in
the case of 1a could be facilitated by an initial formation of an amide enolate
(Scheme 1).
1H), 6.52 (t, J = 7.8 Hz, 1H), 6.84 (d, J = 7.8 Hz, 1H), 7.05 (t, J = 7.8 Hz, 1H), 7.42
(d, J = 8.7 Hz, 1H), 7.47–7.62 (m, 2H), 7.80 (s, 1H), 7.82–8.00 (m, 3H), 8.83 (br s,
1H); 13C NMR (CDCl3, 75 MHz) d 22.98, 109.36, 121.30, 123.16, 123.34, 123.98,
124.77, 125.56, 126.56, 126.60, 127.87, 128.15, 128.27, 128.99, 133.01, 133.46,
139.68, 140.22, 155.29, 170.24; ESIMS m/z 286 [M+H]+.
13. During the evaluation process, one of the referees asked to show an example of
unsymmetrical aliphatic ketone. Thus we examined the reaction of 1a and 2-
butanone under the typical conditions, Ti(OiPr)4/pyridine (1.5/1.0), at room
temperature for 1 h. The corresponding Knoevenagel condensation product
was obtained in high yield (95%) as an inseparable E/Z mixture (1:5 based on
1H NMR). 1H NMR (CDCl3, 300 MHz) d Z-isomer (major): 1.19 (t, J = 7.5 Hz, 3H),
2.37 (s, 3H), 3.11 (q, J = 7.5 Hz, 2H), 6.85 (d, J = 7.5 Hz, 1H), 7.01 (t, J = 7.5 Hz,
1H), 7.18 (t, J = 7.5 Hz, 1H), 7.51 (d, J = 7.5 Hz, 1H), 8.26 (br s, 1H), E-isomer
(minor): 1.26 (t, J = 7.5 Hz, 3H), 2.59 (s, 3H), 2.70 (q, J = 7.5 Hz, 2H), 6.87 (d,
J = 7.5 Hz, 1H), 7.01 (t, J = 7.5 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.49 (d, J = 7.5 Hz,
1H), 8.29 (br s, 1H).
Compound 2h-Z: yellow solid, mp 181–182 °C; IR (KBr) 3446, 1686, 1616,
1578, 1464, 1231 cmꢀ1 1H NMR (CDCl3, 300 MHz) d 2.73 (s, 3H), 6.79 (d,
;
J = 7.8 Hz, 1H), 7.01 (t, J = 7.8 Hz, 1H), 7.10 (dd, J = 5.1 and 3.6 Hz, 1H), 7.19 (t,
J = 7.8 Hz, 1H), 7.49 (dd, J = 5.1 and 1.2 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.61 (dd,
J = 3.6 and 1.2 Hz, 1H), 8.31 (br s, 1H); 13C NMR (CDCl3, 75 MHz) d 26.58,
109.49, 121.57, 124.08, 124.40, 124.71, 127.16, 128.33, 128.36, 130.52, 140.14,
142.13, 144.98, 167.60; ESIMS m/z 242 [M+H]+. Anal. Calcd for C14H11NOS: C,
69.68; H, 4.59; N, 5.80. Found: C, 69.82; H, 4.52; N, 5.64.
Compound 2h-E: yellow solid, mp 193–194 °C; IR (KBr) 3452, 1692, 1612,