D
H. J. Gim, M. E. Jung
Paper
Synthesis
(2E,4E)-2-Acetyl-5-(diisopropylamino)penta-2,4-dienenitrile (9a)
13C NMR (100 MHz, CDCl3): = 187.1, 162.4, 159.6, 153.9, 131.6,
(Table 1, entry 2)
130.6, 120.8, 113.3, 98.7, 93.0, 55.3, 50.3, 48.4, 23.6, 19.8.
HRMS (ESI): m/z [M + H]+ calcd for C19H25N2O2: 313.1916; found:
313.1919.
Compound 9a (yellow solid, 93 mg, 0.423 mmol, 9%) was obtained
from Weinreb amide 2a (494 mg, 4.701 mmol) and 2-chloropyridine
(1; 652.7 mg, 5.749 mmol) in THF (8 mL) using the general procedure;
mp 163.8–164.7 °C.
1H NMR (400 MHz, CDCl3): = 7.86 (d, J = 12.4 Hz, 1 H), 7.24 (d, J =
12.4 Hz, 1 H), 5.80 (t, J = 12.4 Hz, 1 H), 4.13 (sept, J = 6.8 Hz, 1 H), 3.70
(sept, J = 6.8 Hz, 1 H), 2.34 (s, 3 H), 1.28 (d, J = 6.8 Hz, 12 H).
13C NMR (100 MHz, CDCl3): = 191.8, 156.8, 154.2, 120.4, 97.9, 94.3,
50.3, 48.4, 27.7, 23.5, 19.7.
HRMS (ESI): m/z [M + H]+ calcd for C13H21N2O: 221.1654; found:
221.1655.
(2E,4E)-2-Benzoyl-5-(piperidin-1-yl)penta-2,4-dienenitrile (12d);
Typical Procedure
To a solution of piperidine (265.6 mg, 308 L, 3.119 mmol) in THF (3
mL) was slowly added n-BuLi (1.6 M solution in n-hexane, 2.33 mL) at
–78 °C and the reaction mixture was stirred at 0 °C for 30 min. Then
2-chloropyridine (1; 303.5 mg, 2.633 mmol) was added dropwise to
the reaction mixture at –78 °C and it was stirred for 30 min. A solu-
tion of Weinreb amide 2 (368 mg, 2.228 mmol) in THF (1 mL) was
slowly added to the mixture at –78 °C and it was gradually warmed to
22 °C and stirred for 12 h. After sat. aq NH4Cl was added to the mix-
ture, it was diluted and extracted with EtOAc. The combined organic
layers were washed with brine, dried (MgSO4), filtered, and concen-
trated in vacuo. The resulting crude residue was purified by column
chromatography (n-hexane/EtOAc 1:1) to give 12d (65.3 mg, 0.245
mmol, 11%) as a brown solid; mp 163.4–164.3 °C.
1H NMR (400 MHz, CDCl3): = 7.98 (d, J = 12.8 Hz, 1 H), 7.79–7.82 (m,
2 H), 7.40–7.49 (m, 3 H), 7.18 (d, J = 12.0 Hz, 1 H), 5.87 (dd, J = 12.4 Hz,
1 H), 3.46 (m, 4 H), 1.17 (s, 6 H).
13C NMR (100 MHz, CDCl3): = 188.6, 159.4, 157.4, 139.0, 131.2,
128.3, 128.1, 120.2, 98.0, 93.9, 56.0, 47.0, 26.6, 25.1, 23.7.
(2E,4E)-2-(3-Chlorobenzoyl)-5-(diisopropylamino)penta-2,4-di-
enenitrile (9c) (Table 1, entry 4)
Compound 9c (yellow solid, 81.7 mg, 0.258 mmol, 9%) was obtained
from Weinreb amide 2c (572.4 mg, 2.867 mmol) and 2-chloropyri-
dine (1; 390.7 mg, 3.441 mmol) in THF (5.5 mL) using the general pro-
cedure; mp 242.9–244.0 °C.
1H NMR (400 MHz, CDCl3) = 8.02 (d, J = 12.8 Hz, 1 H), 7.76 (t, J = 1.6
Hz, 1 H), 7.73 (ddd, J = 7.6, 1.6, 1.2 Hz, 1 H), 7.44 (ddd, J = 8.0, 2.0, 1.2
Hz, 1 H), 7.36 (dd, J = 8.0, 7.6 Hz, 1 H), 7.33 (d, J = 12.4 Hz, 1 H), 5.99
(dd, J = 12.4 Hz, 1 ), 4.20 (sept, J = 6.8 Hz, 1 H), 3.74 (sept, J = 6.8 Hz, 1
H), 1.30 (d, J = 6.8 Hz, 12 H).
HRMS (ESI): m/z [M + H]+ calcd for C17H19N2O: 267.1497; found:
267.1490.
13C NMR (100 MHz, CDCl3) = 180.1, 159.8, 155.0, 140.9, 134.3, 131.2,
129.4, 128.4, 126,4 120.1, 99.4, 92.7, 50.7, 48.9, 23.6, 19.8.
HRMS (ESI): m/z [M + H]+ calcd for C18H22ClN2O: 317.1421; found:
317.1422.
(2E,4E)-2-Benzoyl-5-(diethylamino)penta-2,4-dienenitrile (12a)
Compound 12a (yellow solid, 30.3 mg, 0.119 mmol, 6%) was obtained
from Weinreb amide 2 (330 mg, 1.998 mmol) and 2-chloropyridine
(1; 272.2 mg, 2.397 mmol) using Et2NH in THF (3.5 mL); mp 114.8–
116.2 °C.
(2E,4E)-2-(4-Chlorobenzoyl)-5-(diisopropylamino)penta-2,4-di-
enenitrile (9d) (Table 1, entry 5)
Compound 9d (yellow solid, 16.1 mg, 0.051 mmol, 3%) was obtained
from Weinreb amide 2d (408.2 mg, 2.045 mmol) and 2-chloropyri-
dine (1; 278.6 mg, 2.454 mmol) in THF (4 mL) using the genearl pro-
cedure; mp 200.3–201.1 °C.
1H NMR (400 MHz, CDCl3): = 8.03 (d, J = 12.8 Hz, 1 H), 7.79 (d, J = 8.4
Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 12.0 Hz, 1 H), 5.99 (dd, J =
12.4 Hz, 1 H), 4.19 (sept, J = 6.8 Hz, 1 H), 3.73 (sept, J = 6.8 Hz, 1 H),
1.30 (d, J = 6.8 Hz, 12 H).
1H NMR (400 MHz, CDCl3): = 7.97 (d, J = 12.8 Hz, 1 H), 7.79–7.81 (m,
2 H), 7.41–7.49 (m, 3 H), 7.21 (d, J = 12.0 Hz, 1 H), 5.81 (dd, J = 12.8,
12.4 Hz, 1 H), 3.41 (q, J = 7.2 Hz, 2 H), 3.37 (q, J = 7.2 Hz, 2 H), 1.27 (t,
J = 7.2 Hz, 3 H), 1.25 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): = 188.8, 159.4, 157.3, 139.1, 131.3,
128.4, 128.1, 120.1, 98.5, 94.1, 51.2, 43.6, 14.5, 12.0.
HRMS (ESI): m/z [M + H]+ calcd for C16H19N2O: 255.1497; found:
255.1502.
13C NMR (100 MHz, CDCl3): = 187.2, 159.7, 154.8, 137.5, 137.4,
129.8, 128.3, 120.3, 99.2, 92.6, 50.6, 48.7, 23.5, 19.8.
HRMS (ESI): m/z [M + H]+ calcd for C18H22ClN2O: 317.1421; found:
317.1420.
(2E,4E)-2-Benzoyl-5-(diisobutylamino)penta-2,4-dienenitrile
(12c)
Compound 12c (yellow solid, 82 mg, 0.264 mmol, 10%) was obtained
from Weinreb amide 2 (436.5 mg, 2.642 mmol) and 2-chloropyridine
(1; 360 mg, 3.171 mmol) using i-Bu2NH in THF (4.5 mL); mp 121.0–
122.1 °C.
(2E,4E)-5-(Diisopropylamino)-2-(4-methoxybenzoyl)penta-2,4-di-
enenitrile (9f) (Table 1, entry 7)
Compound 9f (9.6 mg, 0.031 mmol, 1%) was prepared from Weinreb
amide 2f (530 mg, 2.715 mmol) and 2-chloropyridine (1; 369.9 mg,
3.258 mmol) in THF (3 mL) using the general procedure; mp 188.1–
189.4 °C.
1H NMR (400 MHz, CDCl3): = 8.06 (d, J = 12.8 Hz, 1 H), 7.91 (d, J = 8.8
Hz, 2 H), 7.29 (d, J = 12.0 Hz, 1 H), 6.93 (d, J = 8.8 Hz, 2 H), 5.97 (dd, J =
12.4 Hz, 1 H), 4.18 (sept, J = 6.8 Hz, 1 H), 3.85 (s, 3 H), 3.71 (sept, J = 6.8
Hz, 1 H), 1.29 (d, J = 6.4 Hz, 1 H).
1H NMR (400 MHz, CDCl3): = 7.98 (d, J = 12.8 Hz, 1 H), 7.81–7.84 (m,
2 H), 7.41–7.51 (m, 3 H), 7.21 (d, J = 12.0 Hz, 1 H), 5.83 (dd, J = 12.4 Hz,
1 H), 3.15 (d, J = 7.6 Hz, 2 H), 3.12 (d, J = 7.6 Hz, 2 H), 2.15 (m, 1 H),
1.97 (m, 1 H), 0.97 (d, J = 6.4 Hz, 6 H), 0.92 (d, J = 6.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): = 188.7, 159.4, 158.9, 139.0, 131.3,
128.3, 128.1, 119.9, 98.8, 94.3, 64.9, 56.6, 27.9, 26.7, 20.2, 19.7.
HRMS (ESI): m/z [M + H]+ calcd for C20H27N2O: 311.2123; found:
311.2125.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–E