Synthesis of Aryl Ketones by the Pd-Catalyzed C-H Activation of Arenes and Intermolecular Carbopalladation of Nitriles

Article abstract of DOI:10.1021/ja038687l

The palladium-catalyzed reaction of simple arenes and nitriles provides good to excellent yields of aryl ketones or the corresponding hindered imines. The addition of a small amount of DMSO increases the yields dramatically. Both intermolecular and intramolecular examples of this process are successful. This novel chemistry is believed to involve palladium-catalyzed C?H activation, followed by carbopalladation of the nitrile. Copyright

Full text of DOI:10.1021/ja038687l

Supporting Information
Synthesis of Aryl Ketones by the Pd-Catalyzed C-H Activation
of Arenes and Intermolecular Carbopalladation of Nitriles
Chengxiang Zhou and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
larock@iastate.edu
General
1
13
The H and C NMR spectra were recorded at 300 or 400 and 75 or 100 MHz,
respectively. Thin layer chromatography was performed using commercially prepared 60-
mesh silica gel plates (Whatman K6F), and visualization was effected with short
wavelength UV light (254 nm). Low-resolution mass spectra were recorded on a Finnigan
TSQ700 triple quadruple mass spectrometer (Finnigan MAT, San Jose, CA). High-
resolution mass spectra were recorded on a Kratos MS50TC double focusing magnetic
sector mass spectrometer using EI at 70 eV. The arenes and nitriles were purchased from
Sigma-Aldrich Co. and were used without further purification. All palladium salts were
donated by Johnson Matthey Inc. and Kawaken Fine Chemicals Co., Ltd. All boronic
acids were donated by Frontier Scientific Co., Ltd.
The intermolecular reaction of nitriles and arenes (Table 2, entries 1 - 8)
The arene (2.0 mmol), the nitrile (1.0 mmol), Pd(OAc) (0.10 mmol), DMSO (0.10
2
mL) and TFA (2.5 mL) were placed in a 6 dram vial. The vial was sealed and the
contents were stirred and heated at the indicated temperature for 24 h. The ketone
products were obtained using the following acid work-up procedure and the ketimine
products were obtained by using the following basic work-up procedure.
Acidic work-up. Water (15 mL) was added to the vial and the resulting mixture was
o
heated at 70 C for 2 h. The mixture was then cooled and extracted with diethyl ether
three times. The combined organic layers were dried over anhydrous MgSO and the
4
solvent was evaporated under reduced pressure. The crude product was purified by
chromatography on a silica gel column.
Basic Work-up. The reaction mixture was cooled to room temperature, and then
K CO was added to the vial until no CO bubbles were generated (Caution: a large
2
3
2
amount of CO is generated due to the reaction of TFA and K CO ). The resulting
2
2
3
mixture was extracted with diethyl ether three times. The combined organic layers were
dried over anhydrous MgSO and the solvent was evaporated under reduced pressure.
4
The crude product was purified by chromatography on a silica gel column.
The intramolecular reaction of arylalkanenitriles (Table 2, entries 9 - 10)
The nitrile (0.2 mmol), Pd(OAc) (0.03 mmol), DMSO (0.2 mL) and TFA (5.0 mL)
2
were placed in a 6 dram vial. The vial was sealed and the contents were stirred and
heated at the indicated temperature for 24 h. The resulted mixture was then worked up
according to the above acidic work-up procedure.
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The intermolecular reaction of nitriles and boronic acids (Scheme 2)
The nitrile (5.0 mmol), the boronic acid (1.0 mmol), Pd(OAc) (0.10 mmol), DMSO
2
(
0.10 mL) and TFA (2.5 mL) were placed in a 6 dram vial. The vial was sealed and the
o
contents were stirred and heated at 90 C for 24 h. The resulted mixture was then worked
up according to the above acidic or basic work-up procedure.
Characterization data:
Me NH
Me
Me
1
1
2
,4,6-Trimethylbenzophenone imine. Light yellow oil; H NMR (300 MHz,
CDCl ) δ 2.10 (s, 6H), 2.34 (s, 3H), 6.92 (s, 2H), 7.35-7.45 (m, 3H), 7.73 (dd, J = 8.1, 1.8
3
1
3
Hz, 2H), 8.80-9.70 (s, 1H); C NMR (75 MHz, CDCl ) δ 19.85, 21.35, 128.00, 128.60,
3
-
1
1
28.85, 131.42, 134.58, 137.64, 137.75, 138.15, 179.05; IR (CDCl , cm ) 3265, 3063,
3
+
2
925, 2866, 1606, 1573, 1469, and 1448; MS (EI) m/z (rel intensity) 223 (M , 22), 222
(
100), 207 (40); HRMS (EI) calcd for C H N 223.1361, found: 223.1367.
1
6
17
NH Me
MeO
Me
Me
1
2
,4,6-Trimethylphenyl-4’-methoxyphenylmethanimine. Yellow oil; H NMR
(
300 MHz, CDCl ) δ 2.09 (s, 6H), 2.33 (s, 3H), 3.83 (s, 3H), 6.86-6.91 (m, 4H), 7.66 (d, J
3
1
3
=
8.7 Hz, 2H), 8.0-9.2 (s, 1H); C NMR (75 MHz, CDCl ) δ 19.76, 21.31, 55.54, 114.05,
3
-1
1
3
2
28.51, 129.64, 130.66, 134.46, 137.84, 138.36, 162.16, 178.02; IR (CDCl , cm ) 3260,
3
+
005, 2926, 2854, 1596, 1569, 1510, and 1460; MS (EI) m/z (rel intensity) 253 (M , 28),
52 (100), 237 (22); HRMS (EI) calcd for C H NO 253.1467, found: 253.1471.
1
7
19
NH Me
Br
Me
Me
1
2
,4,6-Trimethylphenyl-4’-bromophenylmethanimine. Light red oil; H NMR (300
MHz, CDCl ) δ 2.07 (s, 6H), 2.32 (s, 3H), 6.91 (s, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.59 (d,
3
13
J = 8.7 Hz, 2H), 8.8-10.2 (s, 1H); C NMR (75 MHz, CDCl
3
) δ 19.80, 21.34, 126.00,
-1
1
28.68, 129.52, 132.02, 134.42, 136.91, 137.53, 138.26, 177.77; IR (CDCl , cm ) 3254,
3
3
027, 2920, 2858, 1611, 1586, 1561, and 1483; MS (EI) m/z (rel intensity) 302 (100),
3
00 (100), 287 (20), 285 (21), 222 (35); HRMS (EI) calcd for C H BrN 301.0466,
1
6
16
found: 301.0473.
S-2

O
2
1
6
,6-Dimethyl-6,7,8,9-tetrahydrobenzocyclohepten-5-one.
H NMR (400 MHz,
CDCl ) δ 1.17 (s, 6H), 1.66 (t, J = 6.8 Hz, 2H), 1.89 (m, 2H), 2.76 (t, J = 6.8 Hz, 2H),
3
1
3
7
.10 (d, J = 7.6 Hz, 1H), 7.24-7.26 (m, 2H), 7.32-7.35 (m, 1H); C NMR (75 MHz,
CDCl ) δ 23.38, 25.93, 31.16, 37.73, 46.17, 126.72, 127.19, 128.69, 130.89, 137.47,
3
-1
1
41.50, 215.33; IR (CDCl , cm ) 3023, 2935, 2865, 1679, 1599, 1472, and 1453; MS
3
+
(
EI) m/z (rel intensity) 188 (M , 14), 130 (85), 120 (100); HRMS (EI) calcd for C H O
1
3
16
1
88.1201, found: 188.1205.
O
(
H C) C
3 3
O
1
2
-(tert-Butyl)dibenz[b,e]oxepin-11(6H)-one. Colorless oil; H NMR (400 MHz,
CDCl ) δ 1.35 (s, 9H), 5.17 (s, 2H), 6.99 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 7.6 Hz, 1H),
3
1
3
7
.45-7.48 (m, 1H), 7.53-7.56 (m, 3H), 7.89 (d, J = 8.4 Hz, 1H), 8.23 (s, 1H); C NMR
(
75 MHz, CDCl
3
) δ 31.56, 34.63, 73.76, 120.52, 124.79, 127.93, 128.17, 129.39, 129.65,
-
1
1
32.81, 133.35, 135.86, 140.96, 145.05, 159.48, 191.71; IR (CDCl , cm ) 3032, 2963,
3
+
2
868, 1642, 1605, 1490, and 1463; MS (EI) m/z (rel intensity) 266 (M , 29), 251 (100);
HRMS (EI) calcd for C H O 266.1307, found: 266.1311.
1
8
18
2
References:
1
) Luo, F. H.; Chu, C. I.; Cheng, C. H. Organometallics 1998, 17, 1025.
2
) Dunkelblum, E.; Hart, H.; Suzuki, M. J. Am. Chem. Soc. 1977, 99, 5074.
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