The Journal of Organic Chemistry
Note
17.3. 19F NMR (376 MHz, CDCl3): δ −62.67. HRMS−ESI (m/z): [M
+ Na]+ calcd for C12H12F3NNaO, 266.0763; found: 266.0764.
1-(3-Phenylpropyl)-2-pyrrolidinone (3ah). Yellow liquid (101 mg,
In conclusion, a catalytic lactam synthesis was developed
from lactones and amines using the readily available Ir complex
[Cp*IrCl2]2 and sodium acetate. The mechanistic studies
revealed an interesting domino reaction involving the following
sequential reactions: aminolysis of lactone, N-alkylation of
amine with hydroxyamide, and intramolecular transamidation
of aminoamide.
1
>97%). H NMR (499 MHz, CDCl3): δ 7.31−7.27 (m, 2H), 7.22−
7.17 (m, 3H), 3.35 (t, J = 7.8 Hz, 4H), 2.64 (t, J = 7.8 Hz, 2H), 2.37 (t,
J = 8.3 Hz, 2H), 1.98 (quin, J = 7.3 Hz, 2H), 1.86 (quin, J = 7.7 Hz,
2H). The spectral data were consistent with those reported in the
literature.23
3-Methyl-1-(phenylmethyl)-2-pyrrolidinone (3ba). Brown liquid
1
(68 mg, 72%). H NMR (499 MHz, CDCl3) 7.36−7.23 (m, 5H),
EXPERIMENTAL SECTION
■
4.50−4.42 (m, 2H), 3.21−3.13 (m, 2H), 2.52 (sext, J = 7.8 Hz, 1 H),
2.26−2.16 (m, 1H), 1.65−1.55 (m, 1H), 1.25 (d, J = 7.3 Hz, 3H).
HRMS−EI (m/z): [M]+ calcd for C12H15NO, 189.1154; found,
189.1153. The spectral data were consistent with those reported in the
literature.24
1,4-Dihydro-2-(phenylmethyl)-3(2H)-isoquinolinone (3ca). Brown
liquid (109 mg, 92%). 1H NMR (300 MHz, CDCl3): δ 7.41−7.09 (m,
9H), 4.79 (s, 2H), 4.41 (s, 2H), 3.74 (s, 2H). The spectral data were
consistent with those reported in the literature.25
General Considerations. Unless otherwise noted, all reactions
were carried out using standard Schlenk techniques or in an Ar-filled
glovebox. NMR spectra were recorded in CDCl3 or toluene-d8, and
residual solvent signals were used as the reference. Chemical shifts are
reported in ppm, and coupling constants are reported in Hz.
Multiplicity is indicated by one or more of the following: singlet (s),
doublet (d), triplet (t), quartet (q), quintet (quin), sextet (sext), and
multiplet (m). High resolution mass spectrometry (HRMS) was
performed using the fast atom bombardment (FAB) ionization mode,
electrospray ionization (ESI) Q-TOF mode, and electron ionization
(EI) mode. GC analysis was carried out using a GC system equipped
with an HP-5 column and FID detector. NHC precursor (1,3-
diisopropylimidazolium bromide),19 N-benzyl-4-hydroxybutanamide
(A),7a and N-benzyl-4-(benzylamino)butanamide (B)7a were prepared
based on literature procedures. Other chemicals were purchased from
commercial suppliers and used as received without further purification.
General Procedure for Lactam Synthesis from Lactones and
Amines. Inside an Ar-filled glovebox, 1 mol % of [Cp*IrCl2]2 (3.98
mg, 0.005 mmol), 2 mol % NaOAc (0.82 mg, 0.010 mmol), 4 Å
molecular sieves (ca. 35 mg), and toluene (1.2 mL) were added to an
oven-dried 5 mL Schlenk tube equipped with a magnetic spin bar and
septum. After the tube with the catalytic system was removed from the
box, 0.50 mmol lactone and 1.00 mmol amine were added to the tube
under an Ar flow using the Schlenk technique. Then, the reaction
mixture was stirred at 110 °C for 36 h before cooling to room
temperature. All of the volatiles were removed in vacuo, and the
resulting residue was purified by flash column chromatography
(hexane/EtOAc = 4:1 v/v or DCM/MeOH = 30:1 v/v) to afford
the corresponding lactam.
1,4-Dihydro-2-(4-methoxyphenylmethyl)-3(2H)-isoquinolinone
(3cb). Yellow liquid (114 mg, 85%). IR (neat): 1711, 1667, 1611,
1512, 1460, 1334, 1285, 1246, 1176, 1032, 820, 741 cm−1. H NMR
1
(499 MHz, CDCl3): δ 7.32 (m, 5H), 7.12 (d, J = 7.8 Hz, 1H), 6.90 (d,
J = 8.3 Hz, 2H), 4.73 (s, 2H), 4.40 (s, 2H), 3.82 (s, 3H), 3.72 (s, 2H).
13C NMR (101 MHz, CDCl3): δ 169.0, 159.1, 132.0, 131.1, 129.4,
128.6, 127.5, 127.2, 126.6, 125.1, 114.1, 55.3, 50.0, 49.4, 37.3. HRMS−
FAB (m/z): [M + H]+ calcd for C17H18NO2, 268.1338; found,
268.1338.
1,4-Dihydro-2-(4-methylphenylmethyl)-3(2H)-isoquinolinone
(3cc). Yellow liquid (119 mg, 95%). IR (neat): 1711, 1669, 1430,
1380, 1349, 1309, 1284, 1248, 1047, 741, 697 cm−1. H NMR (499
1
MHz, CDCl3): δ 7.28−7.08 (m, 8H), 4.73 (s, 2H), 4.38 (s, 2H), 3.71
(s, 2H), 2.34 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 169.0, 137.2,
133.5, 132.1, 131.2, 129.3, 128.0, 127.5, 127.2, 126.5, 125.1, 50.1, 49.7,
37.3, 21.1. HRMS−FAB (m/z): [M + H]+ calcd for C17H18NO,
252.1388; found, 252.1386.
1,4-Dihydro-2-(4-chlorophenylmethyl)-3(2H)-isoquinolinone (3
cd). Yellow liquid (135 mg, >97%). IR (neat): 1639, 1491, 1408,
1348, 1284, 1090, 1048, 1015, 881, 740, 698 cm−1. H NMR (499
1
MHz, CDCl3): δ 7.32−7.20 (m, 7H), 7.10 (d, 1H), 4.74 (s, 2H), 4.40
(s, 2H), 3.72 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 169.0, 135.2,
133.4, 132.0, 131.0, 129.3, 128.9, 127.6, 127.3, 126.6, 125.1, 50.2, 49.3,
37.3. HRMS−FAB (m/z): [M + H]+ calcd for C16H15ClNO,
272.0842; found, 272.0848.
1-(Phenylmethyl)-2-pyrrolidinone (3aa). Yellow liquid (57 mg,
1
65%). H NMR (300 MHz, CDCl3): δ 7.29−7.15 (m, 5H), 4.38 (s,
2H), 3.20 (t, J = 7.5 Hz, 2H), 2.39 (t, J = 8.3 Hz, 2H), 1.92 (quin, J =
7.9 Hz, 2H). The spectral data were consistent with those reported in
the literature.20
1,4-Dihydro-2-(4-trifluoromethylphenylmethyl)-3(2H)-isoquinoli-
none (3ce). Dark yellow liquid (107 mg, 70%). IR (neat): 1670, 1326,
1286, 1162, 1112, 1067, 1048, 745 cm−1. 1H NMR (499 MHz, CDCl3)
δ 7.59 (d, J = 8.3 Hz, 2H), 7.53(t, J = 7.8 Hz, 1H), 7.39 (d, J = 8.3 Hz,
2H), 7.25−7.18 (m, 2H), 7.10 (d, J = 7.3 Hz, 1H), 4.82 (s, 2H) 4.41
(s, 2H), 3.73(s, 2H). 13C NMR (101 MHz, CDCl3): δ 169.3, 140.7,
131.9, 130.8, 128.1, 127.7, 127.3, 126.7, 125.7, 125.7, 125.6, 125.1,
50.5, 49.7, 37.3. 19F NMR (376 MHz, CDCl3): δ −62.58. HRMS−CI
(m/z): [M + H]+ calcd for C17H15F 3NO, 306.1106; found, 306.1109.
1,4-Dihydro-2-(2-phenylethyl)-3(2H)-isoquinolinone (3cf). Or-
ange liquid (53 mg, 53%). IR (neat): 1712, 1664, 1455, 1390, 1352,
1287, 1269, 1146, 1048, 751, 700 cm−1. 1H NMR (300 MHz, CDCl3):
δ 7.32−7.17 (m, 8H), 7.07 (d, J = 7.0 Hz, 1H), 4.32 (s, 2H) 3.78 (t, J
= 7.4 Hz, 2H), 3.62 (s, 2H), 2.95 (t, J = 7.3 Hz, 2H). 13C NMR (75
MHz, CDCl3): δ 168.8, 139.0, 132.4, 131.5, 128.8, 128.5, 127.5, 127.1,
126.4, 126.4, 125.0, 51.8, 49.1, 37.7, 33.9. HRMS−EI (m/z): [M]+
calcd for C17H17NO, 251.1310; found, 251.1310.
1-[(4-Methoxyphenyl)methyl]-2-pyrrolidinone (3ab). Brown
liquid (64 mg, 62%). H NMR (499 MHz, CDCl3): δ 7.18 (d, J =
8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 4.39 (s, 2H), 3.81 (s, 2H), 3.25
(t, J = 7.1 Hz, 2H), 2.43(t, J = 8.1 Hz, 2H), 1.98 (quin, J = 7.7 Hz,
2H). The spectral data were consistent with those reported in the
literature.21
1
1-[(4-Methylphenyl)methyl]-2-pyrrolidinone (3ac). Brown liquid
(62 mg, 65%). IR (neat): 1679, 1514, 1461, 1423, 1285, 1261, 806,
754, 662 cm−1. 1H NMR (499 MHz, CDCl3): δ 7.14 (s, 4H), 4.42 (s,
2H), 3.25 (t, J = 7.1 Hz, 2H), 2.46 (t, J = 8.1 Hz, 2H), 2.34 (s, 3H),
1.98 (quin, J = 7.6 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ174.8,
137.2, 133.5, 129.3, 128.1, 46.5, 46.2, 30.9, 21.0, 17.6. HRMS−EI (m/
z): [M]+ calcd for C12H15NO, 189.1154; found: 189.1153.
1-[(4-Chlorophenyl)methyl]-2-pyrrolidinone (3ad). Brown liquid
1
(84 mg, 80%). H NMR (499 MHz, CDCl3): δ 7.31 (d, J = 8.3 Hz,
2H), 7.19 (d, J = 8.8 Hz, 2H), 4.43 (s, 2H), 3.26 (t, J = 7.2 Hz, 2H),
2.45 (t, J = 8.3 Hz, 2H), 2.01 (quin, J = 7.6 Hz, 2H). The spectral data
were consistent with those reported in the literature.22
1-[(4-Trifluoromethylphenyl)methyl]-2-pyrrolidinone (3ae). Yel-
low liquid (105 mg, 86%). IR (neat): 1683, 1417, 1323, 1291, 1161,
1110, 1065, 1018, 819 cm−1. 1H NMR (499 MHz, CDCl3): δ 7.60 (d,
J = 8.3 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 4.51 (s, 2H), 3.29 (t, J = 7.3
Hz, 2H), 2.47 (t, J = 8.3 Hz, 2H), 2.04 (quin, J = 7.5 Hz, 2H). 13C
NMR (101 MHz, CDCl3): δ 174.7, 140.5, 129.2 (q, J = 32.0 Hz),
127.8, 125.1 (q, J = 3.8 Hz), 124.5 (q, J = 271.6 Hz), 46.3, 45.6, 30.3,
1,4-Dihydro-2-butyl-3(2H)-isoquinolinone (3cg). Brown liquid (72
mg, 71%). IR (neat): 1711, 1665, 1602, 1353, 1247, 1223, 740, 685
1
cm−1. H NMR (499 MHz, CDCl3): δ 7.29−7.15 (m, 4H), 4.46 (s,
2H), 3.61 (s, 2H), 3.52 (t, J = 7.3 Hz, 2H), 1.58 (quin, J = 7.3 Hz,
2H), 1.35 (sext, J = 7.3 Hz, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C NMR
(75 MHz, CDCl3): δ 168.7, 132.6, 131.6, 127.5, 127.2, 126.5, 125.0,
50.9, 46.7, 37.6, 29.5, 20.1, 13.9. HRMS−EI (m/z): [M]+ calcd for
C13H17NO, 203.1310; found, 203.1311.
D
J. Org. Chem. XXXX, XXX, XXX−XXX