Stereoselective Synthesis of α-Alkylidene β-Oxo Amides
br, conjugated carbonyl groups), 1599, 1441, 1261, 1175 cm .
–
1
(
= 22.0, 26.8, 41.6, 128.6, 129.9, 130.4, 132.9, 137.1, 139.7, 166.6,
195.5 ppm. FTIR (CHCl ): ν˜ = 3422 (NH free), 3025, 2967, 2930,
2870, 1667 (br, conjugated carbonyl groups), 1599, 1506, 1454,
+
GC–MS (70 eV): m/z (%) = 295 (18) [M] , 294 (45), 252 (10), 203
89), 161 (100). HRMS (ESI): calcd. for C18
[M + H]+
96.1287; found 296.1285.
3
(
H18NO
3
–
1
+
2
1262 cm . GC–MS (70 eV): m/z (%) = 231 (33) [M] , 230 (31),
84 (77), 173 (81), 131 (100), 103 (33). HRMS (ESI): calcd. for
[M + H]+ 232.1338; found 232.1337.
1
(
Z)-2-(4-Methylbenzylidene)-3-oxo-N-phenylbutanamide (2c): White
1
14 2
C H18NO
solid (223 mg, 80%); m.p. 118–121 °C. H NMR (400.13 MHz,
CDCl ): δ = 2.33 (s, 3 H, PhCH ), 2.45 (s, 3 H, CH C=O), 7.14–
.16 (m, 3 H, Ph), 7.33 (t, J = 7.7 Hz, 2 H, Ph), 7.46 (d, J = 8.1 Hz,
H, Ph), 7.53 (d, J = 8.1 Hz, 2 H, Ph), 7.58 (s, 1 H, HC=C), 7.92
O) ppm. 13C NMR (100.62 MHz,
): δ = 21.5, 27.0, 120.3, 124.9, 129.1, 129.8, 129.9, 130.3,
): ν˜ =
418 (NH free), 3315 (NH), 3058, 2952, 2856, 1682 (br, conjugated
3
3
3
(
Z)-2-Benzylidene-N-butyl-3-oxobutanamide (2k): Pale yellow oil
7
2
1
(
7
1
125 mg, 51%). H NMR (400.13 MHz, CDCl
3
): δ = 0.88 (t, J =
), 1.26 (sextet, J = 7.3 Hz, 2 H, CH CH ),
.47 (quintet, J = 7.3 Hz, 2 H, CH CH CH ), 2.41 (s, 3 H,
C=O), 3.34 (q, J = 7.3 Hz, 2 H, NHCH CH ), 5.97 (br. s, 1
H, NH, exchange with D O), 7.36–7.39 (m, 3 H, Ph), 7.52–7.55
.3 Hz, 3 H, CH
2
CH
3
2
3
(br. s, 1 H, NH, exchange with D
2
2
2
3
CDCl
3
CH
3
2
2
135.7, 137.5, 141.4, 141.7, 165.8, 196.0 ppm. FTIR (CHCl
3
2
3
13
(m, 3 H, Ph and HC=C) ppm. C NMR (100.62 MHz, CDCl
3
): δ
13.6, 19.9, 26.8, 30.9, 39.5, 128.7, 129.8, 130.5, 132.9, 137.1,
): ν˜ = 3424 (NH free), 3026,
967, 2930, 2871, 1667 (br, conjugated carbonyl groups), 1599,
–
1
carbonyl groups), 1599, 1499, 1441 cm . GC–MS (70 eV): m/z (%)
=
=
+
279 (12) [M] , 278 (25), 264 (61), 236 (13), 187 (65), 145 (100).
1
2
1
40.1, 167.4, 195.7 ppm. FTIR (CHCl
3
+
HRMS (ESI): calcd. for C18
80.1336.
2
H18NO [M + H] 280.1338; found
2
–1
+
506, 1452, 1260 cm . GC–MS (70 eV): m/z (%) = 245 (25) [M] ,
(
(
=
=
Z)-3-Oxo-N-phenyl-2-[4-(trifluoromethyl)benzylidene]butanamide 244 (16), 202 (68), 188 (21) 173(62), 131 (100), 103 (35). HRMS
1
+
2d): Yellow oil (246 mg, 74%). H NMR (400.13 MHz, CDCl
2.49 (s, 3 H, CH
3
3
): δ
C=O), 7.17 (t, J = 7.4 Hz, 1 H, Ph), 7.33 (t, J
8.1 Hz, 2 H, Ph), 7.49 (d, J = 8.1 Hz, 2 H, Ph), 7.59–7.67 (m, 5
O) ppm.
): δ = 27.2, 120.3, 124.8 (q, J =
), 125.2, 125.8, 129.0, 129.2, 130.0, 132.1 (q, J =
2.8 Hz, Cipso-CF ), 136.3, 137.1, 138.3, 139.4, 164.7, 195.9 ppm.
): ν˜ = 3415 (NH free), 3325 (NH), 3064, 2965, 2874,
683 (br, conjugated carbonyl groups), 1600, 1522, 1498, 1360,
15 20 2
(ESI): calcd. for C H NO [M + H] 246.1495; found 246.1494.
(
Z)-N-Benzyl-2-(4-methoxybenzylidene)-3-oxobutanamide (2l):
1
Dark yellow oil (195 mg, 63%). H NMR (400.13 MHz, CDCl
3
): δ
H, Ph and HC=C), 8.06 (br. s, 1 H, NH, exchange with D
2
1
3
= 2.39 (s, 3 H, CH C=O), 3.82 (s, 3 H, OCH ), 4.55 (d, J = 5.8 Hz,
C NMR (100.62 MHz, CDCl
60 Hz, CF
3
3
3
2
2
H, CH NH), 6.25 (br t, J = 5.8 Hz, 1 H, NH, exchange with
2
3
3
D
2
O), 6.79 (d, J = 8.8 Hz, 2 H, Ph), 7.24–7.34 (m, 5 H, Ph), 7.44
3
1
3
(d, J = 8.8 Hz, 2 H, Ph), 7.47 (s, 1 H, HC=C) ppm. C NMR
100.62 MHz, CDCl ): δ = 26.6, 43.9, 55.3, 114.3, 125.2, 127.6,
FTIR (CHCl
1
1
3
(
3
–1
+
128.2, 128.7, 132.1, 134.6, 137.3, 140.7, 161.7, 167.7, 195.8 ppm.
FTIR (CHCl ): ν˜ = 3434 (NH free), 3325 (NH), 3032, 2962, 2933,
1662 (br, conjugated carbonyl groups), 1601, 1524, 1455,
324, 1240 cm . GC–MS (70 eV): m/z (%) = 333 (24) [M] , 332
(35), 290 (15), 264 (20), 241 (21), 199 (100). HRMS (ESI): calcd.
3
+
for C18
15 3 2
H F NO [M + H] 334.1056; found 334.1057.
–
1
+
1
258 cm . GC–MS (70 eV): m/z (%) = 309 (33) [M] , 266 (27), 161
(Z)-2-(Furan-2-ylmethylene)-3-oxo-N-phenylbutanamide (2h): Dark
(
+
77), 106 (100), 91 (57). HRMS (ESI): calcd. for: C19 [M
H] 310.1444; found 310.1446.
H20NO
3
[
25 ] 1
yellow solid (199 mg, 78 %); m.p. 89–90 °C.
400.13 MHz, CDCl ): δ = 2.43 (s, 3 H, CH C=O), 6.50 (dd, J =
.7, 3.5 Hz, 1 H, furyl), 7.07 (d, J = 3.5 Hz, 1 H, furyl), 7.15 (t, J
H NMR
+
(
1
=
3
3
(
Z)-N-Phenyl-2-(4-methoxybenzylidene)-3-oxo-3-phenylpropan-
7.5 Hz, 1 H, Ph), 7.35 (t, J = 7.9 Hz, 2 H, Ph), 7.42 (s, 1 H,
1
amide (2m): Yellow oil (232 mg, 65%). H NMR (400.13 MHz,
CDCl ): δ = 3.79 (s, 3 H, OCH ), 6.85 (d, J = 7.1 Hz, 2 H, Ph),
.87 (d, J = 7.0 Hz, 2 H, Ph), 7.10–7.68 (m, 9 H, Ph and HC=C),
.88 (d, J = 7.0 Hz, 2 H, Ph), 8.84 (br. s, 1 H, NH, exchange with
HC=C), 7.52 (d, J = 1.7 Hz, 1 H, furyl), 7.64 (d, J = 7.5 Hz, 2 H,
Ph), 8.44 (br. s, 1 H, NH, exchange with D
O) ppm. 13C NMR
100.62 MHz, CDCl ): δ = 27.0, 113.2, 119.6, 120.2, 124.7, 128.5,
29.0, 131.3, 137.7, 146.7, 149.2, 164.8, 196.0 ppm. FTIR (CHCl ):
3
3
2
6
7
D
1
1
(
(
1
3
13
3
O) ppm. C NMR (100.62 MHz, CDCl
20.2, 124.5, 125.0, 126.3, 128.5, 128.6, 128.9, 129.8, 132.6, 132.8,
37.8, 145.6, 161.8, 164.0, 195.6 ppm. FTIR (CHCl ): ν˜ = 3410
3
): δ = 55.3, 114.2,
2
ν˜ = 3419 (NH free), 3309 (NH), 3062, 2962, 1725, 1680 (br, conju-
gated carbonyl groups), 1600, 1542, 1521, 1469, 1440, 1244,
1
3
–1
+
202 cm . GC–MS (70 eV): m/z (%) = 255 (24) [M] , 226 (10), 212
NH), 3032, 2965, 1670 (br, conjugated carbonyl groups), 1600,
(16), 163 (39), 121 (100). HRMS (ESI): calcd. for: C15 [M
H14NO
3
–1
+
1
531, 1212 cm . GC–MS (70 eV): m/z (%) = 357 (17) [M] , 356
+
+
H] 256.0974; found 256.0972.
(
25), 265 (45), 105 (100), 77 (45). HRMS (ESI): calcd. for:
[M + H]+ 358.1444; found 358.1446.
23 3
C H20NO
(
Z)-2-Benzylidene-N-tert-butyl-3-oxobutanamide (2i): Pale yellow
[14b] 1
solid (135 mg, 55%); m.p. 113–114 °C.
H NMR (400.13 MHz,
C=O), 5.56
2
O), 7.35–7.41 (m, 3 H, Ph), 7.48
(
Z)-N-Butyl-2-benzylidene-3-oxo-3-phenylpropanamide (2n): Dark
CDCl
3
): δ = 1.38 [s, 9 H, C(CH
br. s, 1 H, NH, exchange with D
s, 1 H, HC=C), 7.58–7.60 (m, 2 H, Ph) ppm. C NMR
100.62 MHz, CDCl ): δ = 27.0, 28.3, 51.9, 128.7, 130.0, 130.5,
33.1, 137.7, 139.1, 166.8, 195.8 ppm. FTIR (CHCl ): ν˜ = 3423
NH free), 3022, 2967, 2931, 2871, 1667 (br, conjugated carbonyl
3 3 3
) ], 2.42 (s, 3 H, CH
1
yellow oil (239 mg, 78%); H NMR (400.13 MHz, CDCl
(t, J = 7.3 Hz, 3 H, CH CH ), 1.34 (sextet, J = 7.3 Hz, 2 H,
CH CH ), 1.52 (quintet, J = 7.3 Hz, 2 H, CH CH CH ), 3.35 (q,
J = 7.3 Hz, 2 H, NHCH CH ), 6.83 (s br, 1 H, NH, exchange with
O), 7.11–7.29 (m, 6 H, Ph), 7.41–7.45 (m, 2 H, Ph), 7.85 (dd, J
3
): δ = 0.91
(
(
(
1
(
1
3
2
3
2
3
2
2
3
3
2
2
3
D
2
1
3
–1
= 8.4, 1.3 Hz, 2 H, Ph), 8.15 (s, 1 H, HC=C) ppm. C NMR
(100.62 MHz, CDCl ): δ = 13.7, 20.0, 31.4, 39.9, 125.9, 128.3,
128.5, 129.5, 129.5, 129.6, 129.8, 133.6, 134.0, 142.0, 163.2,
1
1
groups), 1598, 1509, 1454, 1264 cm . GC–MS (70 eV): m/z (%) =
2
+
3
45 (28) [M] , 244 (8), 230 (15), 188 (35), 173 (100), 131 (88).
+
HRMS (ESI): calcd. for C15
46.1497.
2
H20NO [M + H] 246.1495; found
99.4 ppm. FTIR (CHCl
665 (br, conjugated carbonyl groups), 1595, 1448, 1219 cm . GC–
3
): ν˜ = 3402 (NH), 3032, 2965, 2935, 2874,
2
–
1
(
Z)-2-Benzylidene-N-isopropyl-3-oxobutanamide (2j): Pale yellow
+
MS (70 eV): m/z (%) = 307 (27) [M] , 306 (19), 235 (24), 208 (41),
78 (18), 105 (100), 77 (52). HRMS (ESI): calcd. for: C20
M + H]+ 308.1651; found 308.1649.
[
26] 1
solid (139 mg, 60 %); m.p. 78–80 °C.
H NMR (400.13 MHz,
], 2.41 (s, 3 H,
], 5.84 (br. d, 1 H, NH,
O), 7.35–7.44 (m, 3 H, Ph), 7.54 (s, 1 H, HC=C), Supporting Information (see footnote on the first page of this arti-
1
[
H22NO
2
CDCl
CH C=O), 4.19–4.30 [m, 1 H, CH(CH
exchange with D
.56–7.59 (m, 2 H, Ph) ppm. 13C NMR (100.62 MHz, CDCl
3 3 2
): δ = 1.13 [d, J = 6.6 Hz, 6 H, CH(CH )
3
3 2
)
2
1
13
7
3
): δ
cle): H and C NMR spectra of 2a–2d and 2h–2n.
Eur. J. Org. Chem. 2014, 5932–5938
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5937