Decarboxylative acylation of arenes with mandelic acid derivatives via palladium-catalyzed oxidative sp2 C-H activation

Article abstract of DOI:10.1039/c4ra14107e

An efficient palladium catalyzed decarboxylative acylation of arenes with mandelic acid derivatives via oxidative sp² C-H activation in the presence of tert-butyl hydroperoxide has been developed. The acylation reaction is assisted by a pyridine directing group. The starting materials are inexpensive and readily available. This method provides an economical and convenient way to synthesize aryl ketones.

Full text of DOI:10.1039/c4ra14107e

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DOI: 10.1039/C4RA14107E
An efficient approach for the palladium catalyzed decarboxylative cross-coupling of
electron-deficient arenes with mandelic acid.

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Journal Name
RSCPublishing
ARTICLE
Decarboxylative Acylation of Arenes with Mandelic
Acid Derivatives via Palladium-Catalyzed Oxidative
sp2 C-H Activation
Cite this: DOI: 10.1039/x0xx00000x
Xia Liu,a Ze Yi,a Jianhui Wang,a* and Guiyan Liu * ,
b
Received 00th January 2012,
Accepted 00th January 2012
An efficient palladium catalyzed decarboxylative acylation of arenes with mandelic acid
derivatives via oxidative sp2 CꢀH activation in the presence of tertꢀbutyl hydroperoxide has
been developed. The acylation reaction is assisted by a pyridine directing group. The starting
materials are inexpensive and readily available. This method provides an economical and
convenient way to synthesize aryl ketones.
DOI: 10.1039/x0xx00000x
www.rsc.org/
oxocarboxylic acids in the presence of palladium catalysis.10
The palladiumꢀcatalyzed decarboxylative acylation of
Introduction
Aryl ketones are an important intermediate in the synthesis of
drugs, dyes, pesticides and other fine chemicals.1 The Friedelꢀ
Crafts acylation of aromatic compounds is the classical route to
synthesize aryl ketones.2 This method usually requires harsh
reaction conditions, and the reaction produces hazardous
reagents. In addition, the reaction typically requires electronꢀ
rich aromatic substrates since electronꢀdeficient aromatic
substrates do not easily react. Thus much research has been
devoted to developing efficient alternative routes to synthesize
aryl ketones.
In recent years, transitionꢀmetalꢀcatalyzed CꢀH bond
activation with subsequent functionalization has been widely
used in organic chemistry and this has produced many
appealing results.3 The activation of CꢀH bonds has obvious
advantages, but it also produces challenges. For example,
organic molecules usually contain multiple bonds with
dissociation energies that are similar to the CꢀH bonds. So
selectively activating a specific CꢀH bond is a major problem.
Some substrates like indole have specific electronic effects
whereby they can selectively activate a CꢀH bond. However,
for most substrates, a directing group needs to be introduced.
The directing group forms coordination compounds with
azobenzenes with αꢀoxocarboxylic acids was developed by
Wang in 2013.11 In the same year, Tan,12 Kim,13 Wang14 and
Zhang15 reported respectively the palladiumꢀcatalyzed
decarboxylative acylation of oximes, phenylacetamides,
azoxybenzenes, and 2ꢀaryloxypyridines with αꢀoxocarboxylic
acids. All these methods provided a novel way to synthesize
aryl ketones.
Mandelic acid and its derivatives are important building
blocks in bioactive compounds.16 They have been widely used
as starting material and reagents for synthetic purposes.17 Many
derivatives are commercially available. Herein, a palladiumꢀ
catalyzed decarboxylative acylation of arenes with mandelic
acid derivatives via CꢀH activation in the presence of tertꢀbutyl
hydroperoxide (TBHP) as an oxidant is described. This method
has fewer reaction steps than previously reported methods.
Experimental
General Information
1H NMR spectra were obtained on a 400 or 600 MHz
spectrometer and 13C NMR spectra were obtained on a 600
MHz spectrometer with CDCl3 as the solvent. All 1H NMR and
transitionꢀmetal
catalysts
to
control
the
selective
1
13C NMR chemical shifts are referenced to the residual H and
functionalization of the molecule. Recently, the direct selective
functionalization of arenes by CꢀH bond activation has attracted
considerable attention since this is an environmentally friendly
alternative for aryl ketone synthesis.4 A representative example
is transitionꢀmetalꢀcatalyzed oxidative sp2 CꢀH bond acylations
with aldehydes.5,6
13C solvent (relative to TMS) and are reported in units of ppm.
GCꢀMass spectra were recorded on a Luniere Tech. Ltd
TRACEDSQ instrument. Unless otherwise noted, all reactions
were performed in air. Reactions were monitored by analytical
thin layer chromatography on 0.20 mm Anhui Liangchen silica
gel plates. Silica gel (200ꢀ300 mesh) (from Anhui Liangchen
Chem. Company, Ltd.) was used for flash chromatography.
Arylpyridines18 and the mandelic acids derivatives19 were
prepared according to the relevant literature procedures. The
other chemicals or reagents were obtained from commercial
sources and used directly.
Transitionꢀmetalꢀcatalyzed
decarboxylative
coupling
reactions are very attractive since these reactions do not require
the use of stoichiometric organometallic reagents and they do
not generate toxic metal salt wastes.7,8 In addition, the raw
materials are inexpensive and readily available. In 2010, Ge et
al9 reported the palladiumꢀcatalyzed orthoꢀdecarboxylative
acylation of 2ꢀarylpyridines and acetanilides with αꢀ
oxocarboxylic acids. Two years later, Wang demonstrated the
decarboxylative acylationcyclic of enamides with αꢀ
General Procedure for the Preparation of 3 and 4.
This journal is © The Royal Society of Chemistry 2013
J. Name., 2013, 00, 1-3 | 1

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DOI: 10.1039/C4RA14107E
Pd(OAc)2 (2.2 mg, 0.01 mmol), 1a-o (or 1a) (0.2 mmol), 2a (or 154.1, 148.6, 141.6, 137.6, 135.1, 132.1, 129.3, 129.2, 128.6,
2b-k) (0.4 mmol) and TBHP (70% aqueous solution, 1.0 mmol) 127.7, 125.9, 121.5, 121.0, 112.8, 55.8. Analytical Data. Calcd
were placed in a 10ꢀmL glass vial. The vial was immersed in an (found) for C19H15NO2: C, 78.87 (78.41); H, 5.23 (5.67).
oil bath at 120°C and the reaction mixture was stirred for 20 h.
(4-Methoxy-2-pyridin-2-yl-phenyl)-phenyl-methanone (3g) 20
The reaction temperature was then lowered to room
1
temperature and the mixture was extracted with methylene
A light yellow solid. Yield: 95%. H NMR (600 MHz, CDCl3)
chloride (3×5 mL). The combined organic layers were dried
δ (ppm): 3.90 (s, 3H), 6.97 (m, 2H), 7.20 (m, 3H), 7.31 (m,
over magnesium sulfate and the solvent was then evaporated
and the residue was purified by column chromatography on
silica gel.
2H), 7.47 (m, 2H), 7.64 (d, J = 7.6 Hz, 2H), 8.37 (d, J = 4.0 Hz,
1H). 13C NMR (150 MHz, CDCl3) δ (ppm): 197.4, 161.0,
156.92, 149.0, 142.1, 138.2, 136.0, 131.9, 131.6, 131.3, 129.3,
127.8, 123.1, 121.9, 114.4, 113.6, 55.4. Analytical Data. Calcd
(found) for C19H15NO2: C, 78.87 (78.52); H, 5.23 (5.13).
Phenyl(2-(pyridin-2-yl)phenyl)methanone (3a)5b
1
A light yellow solid. Yield: 82%. H NMR (600 MHz, CDCl3)
(5-Fluoro-2-pyridin-2-yl-phenyl)-phenyl-methanone (3h) 20
δ (ppm): 6.99 (t, 1H), 7.25 (t, 2H), 7.36ꢀ7.39 (t, 1H), 7.48 (m,
5H), 7.68 (d, 2H), 7.76 (d,
J
= 7.8 Hz, 1H), 8.35 (d, 1H). 13C
1
A light yellow solid. Yield: 90%. H NMR (400 MHz, CDCl3)
NMR (150 MHz, CDCl3) δ (ppm): 198.2, 156.8, 149.1, 139.7,
139.5, 137.9, 136.3, 132.3, 130.2, 129.5, 129.1, 128.8, 128.5,
128.0, 122.6, 121.9. Analytical Data. Calcd (found) for
C18H13NO: C, 83.37 (83.86); H, 5.05 (4.97).
δ (ppm): 6.98 (m, 1H), 7.24 (m, 4H), 7.38 (m, 1H), 7.46 (d,
8.0 Hz, 1H), 7.54 (m, 1H), 7.67 (d, = 7.6 Hz, 2H), 7.74 (m,
1H), 8.31 (d,
= 4.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
(ppm): 196.4, 162.5, 155.6, 148.9, 141.4, 137.2, 136.3, 135.6,
132.5, 130.5, 129.3, 128.1, 122.3, 121.9, 116.8, 116.5.
Analytical Data. Calcd (found) for C18H12FNO: C, 77.97
J =
J
J
(5-Methyl-2-(pyridin-2-yl) phenyl) (phenyl) methanone (3b) 20
A pale yellow solid. Yield: 90%. 1H NMR (400 MHz, CDCl3) δ (77.64); H, 4.36 (4.32).
(ppm): 2.45(s, 3H), 6.96 (t,
2H), 7.34 (m, 5H), 7.66 (t,
J
J
= 8.0 Hz, 1H), 7.24 (t,
=8.0 Hz, 3H), 8.33 (d,
J
J
= 8.4 Hz,
= 4.0 Hz,
(5-Chloro-2-pyridin-2-yl-phenyl)-phenyl-methanone (3i) 20
1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 198.5, 156.7,
148.9, 139.4, 138.7, 138.0, 136.8, 136.2, 132.2, 130.9, 129.6,
129.4, 128.6, 128.0, 122.5, 121.7, 21.2. Analytical Data. Calcd
(found) for C19H15NO: C, 83.49 (83.26); H, 5.53 (5.32).
1
A light yellow solid. Yield: 81%. H NMR (400 MHz, CDCl3)
δ (ppm): 6.97 (m, 1H), 7.25 (m, 2H), 7.37 (m, 1H), 7.47 (m,
4H), 7.67 (m, 3H), 8.30 (d,
J
= 4.0 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ (ppm): 196.4, 155.3, 148.9, 140.8, 137.7,
137.2, 136.3, 134.6, 132.5, 130.0, 129.8, 129.2, 128.8, 128.0,
122.2, 122.1. Analytical Data. Calcd (found) for C18H12ClNO:
(3-Methyl-2-(pyridin-2-yl)phenyl)(phenyl)methanone (3c) 20
1
A light yellow solid. Yield: 85%. H NMR (400 MHz, CDCl3): C, 73.6 (73.55); H, 4.12 (4.01).
δ (ppm): 2.26 (s, 3H), 7.01 (m, 1H), 7.24 (m, 3H), 7.34 (m,
(5-Bromo-2-pyridin-2-yl- phenyl)-phenyl-methanone (3j) 5b
A pale yellow solid. Yield: 73%. 1H NMR (600 MHz, CDCl3) δ
4H), 7.42 (m, 1H), 7.61 (m, 2H), 8.42 (m, 1H). 13C NMR (100
MHz, CDCl3): δ (ppm):198.5, 157.5, 149.1, 139.8, 139.3,
137.6, 136.7, 135.0, 132.5, 132.5, 129.9, 127.9, 127.7, 126.3,
125.3, 121.7, 20.1. Analytical Data. Calcd (found) for
C19H15NO: C, 83.49 (83.66); H, 5.53 (5.48).
(ppm): 7.03 (t, 1H), 7.27 (t,
J
= 7.8 Hz, 2H), 7.39 (t, 1H), 7.47
(d,
(d,
J
J
= 7.8 Hz, 1H), 7.56 (t, J = 3.8 Hz, 1H), 7.64 (m, 5H), 8.34
= 4.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ (ppm):
196.5, 155.6, 149.1, 141.2, 138.4, 137.3, 136.5, 133.1, 132.6,
131.8, 130.2, 129.4, 128.2, 122.9, 122.4, 122.2. Analytical
A light yellow solid. Yield: 78%. H NMR (600 MHz, CDCl3) Data. Calcd (found) for C18H12BrNO: C, 63.92 (64.01); H, 3.58
δ (ppm): 2.50 (s, 3H), 7.01 (t, 1H), 7.24 (t, 1H), 7.33 (m, 7H), (3.48).
(4-Methyl-2-(pyridin-2-yl)phenyl)(phenyl)methanone (3d) 20
1
7.66 (d,
J
= 7.2 Hz, 2H), 8.40 (d, 1H). 13C NMR (150 MHz,
(4-Nitro-2-pyridin-2-yl-phenyl)-phenyl-methanone (3k)
CDCl3) δ (ppm): 198.3, 157.2, 149.1, 140.6, 139.9, 138.0,
136.6, 136.2, 132.3, 130.1, 129.8, 129.6, 129.4, 129.1, 128.4,
128.0, 21.5. Analytical Data. Calcd (found) for C19H15NO: C,
83.49 (84.26); H, 5.53 (5.25).
1
A pale pink solid. Yield: 48%. H NMR (400 MHz, CDCl3): δ
(ppm): 7.13 (t, 1H), 7.32 (t, 2H), 7.38 (t, 1H), 7.61 (t, 2H), 7.85
(t, 1H), 8.18 (d, 1H), 8.30 (d, 1H), 8.38 (m, 2H), 8.69 (d, 1H).
13C NMR (100 MHz, CDCl3): δ (ppm): 197.2, 157.5, 154.2,
149.2, 145.2, 144.1, 137.0, 136.8, 133.1, 131.7, 130.2, 128.4,
(5-Methoxy-2-(pyridin-2-yl)phenyl)(phenyl)methanone (3e) 20
1
A pale yellow solid. Yield: 85%. H NMR (400 MHz, CDCl3): 124.7, 123.6, 122.5. Analytical Data. Calcd (found) for
δ (ppm): 3.85 (s, 3H), 6.91 (m, 1H), 7.05 (d,
7.10 (m, 1H), 7.23 (m, 2H), 7.34 (m, 1H), 7.43 (d,
1H), 7.48 (m, 1H), 7.68 (m, 3H), 8.28 (d,
= 4.4 Hz, 1H). 13C
NMR (CDCl3, 100 MHz): δ197.7, 159.7, 156.1, 148.7, 140.7,
137.6, 136.1, 132.2, 131.8, 129.8, 129.2, 127.9, 121.9, 121.2,
115.9, 113.9, 55.4. Analytical Data. Calcd (found) for
C19H15NO2: C, 78.87 (77.96); H, 5.23 (5.28).
J
= 2.0 Hz, 1H), C18H12N2O3: C, 71.05 (71.33); H, 3.97 (3.95). HRMS (ESI)
J
= 7.6 Hz, m/z: 305.0926 [M + H]+ (calcd. 305.0925)
J
Ethyl 3-benzoyl-4-(pyridin-2-yl)benzoate (3l) 6c
1
A light yellow solid. Yield: 84%. H NMR (400 MHz, CDCl3):
δ (ppm): 1.40 (t, 3H), 4.40 (q, 2H), 7.10 (t, 1H), 7.28 (t, 2H),
7.41 (t, 1H), 7.55 (d, 1H), 7.62 (m, 2H), 8.11 (d, 1H), 8.23 (m,
3H), 8.44 (d, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm):
200.5, 165.7, 155.6, 148.9, 143.0, 139.7, 137.4, 136.9, 132.6,
(3-Methoxy-2-pyridin-2-yl-phenyl)-phenyl-methanone (3f) 20
1
A light yellow solid. Yield: 92%. H NMR (400 MHz, CDCl3) 131.2, 131.1, 130.0, 128.9, 128.2, 123.1, 122.7, 61.4, 14.3.
δ (ppm): 3.83 (s, 3H), 6.93 (m, 1H), 7.12 (d,
J = 8.0 Hz, 2H), Analytical Data. Calcd (found) for C21H17NO3: C, 76.12
7.23 (m, 2H), 7.35 (m, 1H), 7.42 (m, 1H), 7.49 (m, 1H), 7.56 (76.77); H, 5.17 (4.97).
(d,
J = 7.6 Hz, 1H), 7.66 (d, J = 7.6 Hz, 2H), 8.33 (d, J = 4.8
Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 197.4, 156.5,
Ethyl 3-benzoyl-2-(pyridin-2-yl)benzoate (3m)
2 | J. Name., 2012, 00, 1-3
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1
A light yellow solid. Yield: 93%. H NMR (400 MHz, CDCl3): 13C NMR (100 MHz, CDCl3) δ (ppm): 196.6, 165.1, 156.6,
δ (ppm): 2.04 (t, 3H), 4.93 (q, 2H), 6.91 (t, 1H), 7.03 (d, 1H), 148.9, 139.4, 139.2, 136.3, 134.4, 131.8, 130.2, 128.9, 128.7,
7.25 (m, 3H), 7.53 (m, 1H), 7.72 (m, 4H), 7.94 (d, 1H), 8.53 (d, 128.5, 122.5, 122.0, 115.0. Analytical Data. Calcd (found) for
1H). 13C NMR (100 MHz, CDCl3): δ (ppm): 200.4, 167.5, C18H12FNO: C, 77.97 (77.87); H, 4.36 (4.28).
160.0, 154.7, 145.8, 137.8, 137.4, 137.2, 135.0, 134.4, 132.1,
(4-Chlorophenyl)-(2-(pyridin-2-yl)-phenyl)-methanone (4f) 20
131.5, 128.8, 128.5, 126.1, 123.0, 121.5, 65.6, 14.1. Analytical
A pale yellow solid. Yield: 82%. 1H NMR (400 MHz, CDCl3) δ
Data. Calcd (found) for C21H17NO3: C, 76.12 (75.96); H, 5.17
(5.09). HRMS (ESI) m/z: 354.1105 [M + Na]+ (calcd.
(ppm): 7.06 (m, 1H), 7.23 (d, 2H), 7.51 (m, 7H), 7.77 (d, 1H),
8.38 (d, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 196.9,
354.1101).
156.4, 148.9, 139.3, 139.1, 138.6, 136.7, 136.3, 130.8, 130.3,
129.0, 128.8, 128.7, 128.4, 122.7, 122.2. Analytical Data. Calcd
A light yellow solid. Yield: 81%. H NMR (400 MHz, CDCl3) (found) for C18H12ClNO: C, 73.60 (73.91); H, 4.12 (4.08).
1-(3-Benzoyl-4-pyridin-2-yl-phenyl)-ethanone (3n) 20
1
δ: 2.87 (s, 3H), 7.07 (m, 1H), 7.27 (m, 2H), 7.40 (m, 1H), 7.56
(4-Bromophenyl)-(2-(pyridin-2-yl)-phenyl)-methanone (4g) 20
(d,
J = 7.2 Hz, 1H), 7.61 (m, 1H), 7.68 (m, 2H), 7.89 (d, 1H),
1
8.10 (d, 1H), 8.19 (dd,
J
= 1.8, 8.1 Hz, 1H), 8.40 (d, J = 4.6 Hz,
A pale yellow solid. Yield: 83%. H NMR (400 MHz, CDCl3):
1H). 13C NMR (100 MHz, CDCl3) δ: 197.8, 197.5, 156.1,
149.9, 143.6, 139.9, 137.2, 137.0, 136.6, 132.5, 130.9, 129.0,
128.8, 127.5, 127.1, 122.9, 121.1, 26.7. Analytical Data. Calcd
(found) for C20H15NO2: C, 79.72 (79.52); H, 5.02 (5.18).
δ (ppm): 7.04 (t, 1H), 7.40 (d, 2H), 7.53 (m, 7H), 7.77 (d,
J =
7.7 Hz, 1H), 8.35 (d, 1H). 13C NMR (100 MHz, CDCl3): δ
(ppm): 196.5, 156.4, 148.9, 139.3, 139.1, 136.9, 136.6, 131.3,
130.8, 130.3, 129.0, 128.7, 128.6, 127.3, 122.4, 122.2.
Analytical Data. Calcd (found) for C18H12BrNO: C, 63.92
(63.55); H, 3.58 (3.61).
Benzo[h]quinolin-10-yl(phenyl)-methanone (3o) 20
1
A light yellow solid. Yield: 94%. H NMR (400 MHz, CDCl3)
δ: 7.31 (m, 3H), 7.42 (m, 1H), 7.62 (d,
(2-Chlorophenyl)-(2-(pyridin-2-yl)-phenyl)-methanone (4h) 21
J
= 7.6 Hz, 1H), 7.75
A pale yellow solid. Yield: 73%. 1H NMR (400 MHz, CDCl3) δ
(m, 4H), 7.91 (d,
J
= 8.8 Hz, 1H), 8.06 (m, 2H), 8.52 (d, = 4.0
J
Hz, 1H), 8.40 (d, 1H). 13C NMR (100 MHz, CDCl3) δ: 198.7,
147.1, 144.6, 139.2, 138.9, 135.3, 133.8, 131.7, 129.0, 128.7,
128.5, 12.8.1, 127.8, 127.7, 127.0, 126.4, 126.1, 121.7.
Analytical Data. Calcd (found) for C20H13NO: C, 84.78 (85.45);
H, 4.62 (4.51).
(ppm): 7.05 (t,
(m, 7H), 7.79 (d,
J
= 6.0 Hz, 1H), 7.24 (d,
J
= 8.5 Hz, 2H), 7.54
J
J
= 7.7 Hz, 1H), 8.36 (d,
= 4.4 Hz, 1H). 13C
NMR (100 MHz, CDCl3) δ (ppm): 196.5, 155.4, 149.2, 142.8,
142.8, 140.2, 137.3, 136.5, 132.7, 129.4, 129.2, 128.2, 126.8,
126.7, 126.0, 125.9, 122.8, 122.6. Analytical Data. Calcd
(found) for C18H12ClNO: C, 73.60 (73.16); H, 4.12 (3.97).
(2-Pyridin-2-yl-phenyl)-o-tolyl-methanone (4b) 5b
(2-Brophenyl)-(2-(pyridin-2-yl)-phenyl)-methanone (4i) 20
A pale yellow solid. Yield: 70%. 1H NMR (400 MHz, CDCl3) δ
A pale yellow solid. Yield: 88%. 1H NMR (400 MHz, CDCl3) δ
(ppm): 2.60 (s, 3H), 6.90 (m, 2H), 7.07 (d,
7.13 (m, 2H), 7.40 (d, = 8.0 Hz, 1H), 7.48 (m, 3H), 7.61 (m,
2H), 8.41 (d,
= 4.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
(ppm) 199.7, 157.3, 148.6, 140.6, 140.1, 139.0, 138.0, 136.0,
131.1, 130.8, 130.3, 130.2, 129.6, 128.9, 128.3, 124.6, 122.3,
121.6, 20.8. Analytical Data. Calcd (found) for C19H15NO: C,
83.49 (83.67); H, 5.53 (5.42).
J = 7.6 Hz, 1H),
J
(ppm): 6.96 (m, 3H), 7.21 (m, 1H), 7.41 (m, 7H), 8.50 (d,
J =
4.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 196.7,
157.2, 149.1, 140.7, 139.6, 138.9, 136.3, 134.0, 131.7, 131.3,
131.1, 130.6, 129.4, 128.7, 126.5, 122.8, 121.9, 121.5.
Analytical Data. Calcd (found) for C18H12BrNO: C, 63.92
(64.26); H, 3.58 (3.28).
J
(2-Pyridin-2-yl-phenyl)-p-tolyl-methanone (4c) 20
(4-Nitro-phenyl)-(2-pyridin-2-yl-phenyl)-phenyl-methanone (4j)
21
1
A pale yellow solid. Yield: 82%. H NMR (400 MHz, CDCl3):
δ (ppm): 2.33 (s, 3H), 7.28 (d, 3H), 7.48 (m, 7H), 7.78 (d,
J =
A pale yellow solid. Yield: 48%. 1H NMR (400 MHz, CDCl3) δ
7.6 Hz, 1H), 8.47 (d, 1H). 13C NMR (100 MHz, CDCl3): δ
(ppm): 197.8, 156.9, 148.8, 143.2, 136.6, 135.2, 130.2, 130.1,
129.8, 129.2, 129.1, 129.0, 128.8, 128.5, 123.2, 122.1, 21.7.
Analytical Data. Calcd (found) for C19H15NO: C, 83.49 (84.01);
H, 5.53 (5.36).
(ppm): 7.01 (q,
8.06 (m, 2H), 8.24 (d,
J
= 4.5 Hz, 1H), 7.56 (m, 5H), 7.78 (m, 3H),
J
= 4.8 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ (ppm): 196.1, 155.7, 149.5, 148.7, 143.3, 139.2,
138.5, 136.9, 130.9, 129.7, 129.3, 129.1, 128.3, 123.3, 122.4,
122.0. Analytical Data. Calcd (found) for C18H12N2O3: C, 71.05
(71.42); H, 3.97 (4.08).
(4-Methoxyphenyl)-(2-(pyridin-2-yl)-phenyl)-methanone (4d) 20
A pale yellow solid. Yield: 68%. 1H NMR (400 MHz, CDCl3) δ
(3-Nitro-phenyl)-(2-pyridin-2-yl-phenyl)-phenyl-methanone
(4k) 21
(ppm): 3.74 (s, 3H), 6.73 (d,
7.44 (m, 5H), 7.65 (d, = 8.8 Hz, 2H), 7.73 (d,
8.37 (d,
= 4.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm):
J
= 8.4 Hz, 2H), 6.98 (m, 1H),
J
J
= 7.6 Hz, 1H),
1
A light yellow solid. Yield: 42%. H NMR (400 MHz, CDCl3)
J
δ (ppm): 6.99 (m, 1H), 7.45 (t,
J
= 7.9 Hz, 1H), 7.56 (m, 5H),
J = 7.9 Hz, 1H), 8.18 (m, 2H),
196.8, 162.8, 156.8, 148.9, 139.6, 139.3, 136.1, 131.7, 130.6,
129.8, 128.8, 128.6, 128.2, 122.7, 121.7, 113.2, 55.2. Analytical
Data. Calcd (found) for C19H15NO2: C, 78.87 (78.33); H, 5.23
(5.12).
7.81 (d, = 7.6 Hz, 1H), 8.01 (d,
J
8.43 (s, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm): 195.6,
155.9, 148.7, 148.0, 139.9, 139.4, 138.3, 136.8, 134.5, 130.9,
129.3, 129.2, 129.1, 128.5, 126.3, 123.7, 122.3, 122.1.
Analytical Data. Calcd (found) for C18H12N2O3: C, 71.05
(71.26); H, 3.97 (3.28).
(4-Fluorophenyl)-(2-(pyridin-2-yl)-phenyl)-methanone (4e) 20
A pale yellow solid. Yield: 85%. 1H NMR (400 MHz, CDCl3) δ
(ppm): 6.90 (m, 2H), 7.01 (m, 1H), 7.49 (m, 3H), 7.56 (m, 2H),
Results and Discussion
7.68 (m, 2H), 7.76 (d, J = 7.6 Hz, 1H), 8.34 (d, J = 4.8 Hz, 1H).
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First 2ꢀphenylpyridine (1a) was coupled with mandelic acid Table 2. A number of functional groups on the phenyl rings
2a) in the presence of 5 mol % of catalyst in a mixed solvent including methyl, methoxyl, fluoro, chloro, bromo, nitro,
(
of 1,4ꢀdioxane/AcOH/DMSO (7.5/1.5/1, v/v/v) (Table 1). ethoxycarbonyl and acetyl groups gave good to high yields of
Pd(II) complexes are effective catalysts for the carboꢀ the corresponding carboacylation products under the optimal
functionalization of aryl CꢀH bonds. Therefore, Pd(OAc)2 was reaction conditions (73ꢀ95%, 3aꢀ3j, 81ꢀ93%, 3lꢀ3n). These
our initial choice for the catalyst and Ag2CO3 (3 equiv) was results show that the reaction is not sensitive to the electronic
used as the oxidant. The reaction was conducted for 20 h at 120 properties of the phenylpyridines substituents since both
oC with stirring and the desired product 3a was isolated in a low electronꢀdonating and electronꢀwithdrawing groups reacted. It
yield of only 36% (entry 1).
is notable that 1k which contains mꢀNO2 reacted to give a
moderate yield (48% of 3k) and benzo[ ]quinoline (1o)
produced a yield of 94% of 3o
h
Table 1. Optimization of the catalyst, the oxidant and the solvent a
.
Table 2. Scope of 2ꢀphenylpyridinesa,b
a Conditions: 1a-o (0.2 mmol), mandelic acid 2a (0.4 mmol), Pd(OAc)2
(5 mol %), TBHP (1.0 mmol), 120 oC, 20 h in air; b Isolated yields; c 1o
is benzo[h]quinoline.
Table 3. Scope of Mandelic Acidsa,b
a Reaction conditions: 2ꢀphenylpyridine 1a (0.2 mmol), mandelic acid
2a (0.4 mmol), catalyst (5 mol %), 120 oC, 20 h in air (entries 8 and 9 in
oxygen); b1,4ꢀdioxane/AcOH/DMSO (7.5/1.5/1, v/v/v, c = 0.1 M); c
Isolated yield; d Yield determined by GCꢀMS.
Next the Ag2CO3 was replaced with Ag2O as the oxidant
and the yield only increased to 42% (entry 2). Different ratios
of oxidant to coꢀoxidant were tested (entries 3ꢀ5) and the best
results (76% yield) were obtained for 1 equiv of K2S2O8 as coꢀ
oxidant with 2 equiv of Ag2O (entry 5). When the catalyst was
changed to PdCl2 and the other conditions remain unchanged,
the yield did not improve (entry 6). When O2 was used as the
oxidant, only trace yields were obtained no matter which
catalyst or solvent was used (entries 8 and 9). When no catalyst
a Conditions: 1a (0.2 mmol),
2b-k (0.4 mmol), Pd(OAc)2 (5 mol %),
was used, the reaction did not proceed (entries 7 and 15). Next
3 equiv of TBHP was used as the oxidant with no solvent and
with Pd(OAc)2 as the catalyst. This produced a coupling yield
of 74%, (entry 16). Using TBHP with a solvent like PhCl,
xylene, diglyme, or DMSO, did not further improve the yield
(entries 10ꢀ14). When the loading of TBHP was increased to 5
equiv, a high yield (82%) was obtained (entry 17). Based on
these results, 5.0 eq TBHP and 5.0% (mol) Pd(OAc)2 were
chosen as the optimal conditions.
TBHP (1.0 mmol), 120 oC, 20 h in air; b Isolated yields.
The effects of substituents on the mandelic acid were then
studied (Table 3). The reaction proceeded smoothly for 2ꢀ
phenylpyridine (1a
) and mandelic acids (2b-2i) bearing
different substituted groups on the benzene rings including
methyl, methoxyl, fluoro, chloro, and bromo groups. The
products (4b-4i) were obtained in good yields (68ꢀ88%). The
position of the substituent on the mandelic acid phenyl ring
A variety of substituted 2ꢀphenylpyridines (1a-o) were
tested in the coupling reaction and the results are shown in
4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C4RA14107E
only had a slight effect on the reaction yield. It is important to
note that moderate yields (4j, 48% and 4k, 42%) were still
obtained when the strong electronꢀwithdrawing group, NO2,
Normal University, Tianjin, 300387, P. R. China, Eꢀmail:
guiyanliu2013@163.com.
was on the mandelic acid phenyl ring.
1 a) H. G. Frank and J. W. Stadelhofer, Industrial Aromatic Chemistry,
SpringerꢀVerlag, Berlin, 1988; b) H. Surburg and J. Panten, Common
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Germany, 2006.
On the basis of the experimental results and previous
literature, a plausible mechanism is illustrated in Scheme 1.
First the palladium catalyst reacts with 2ꢀphenylpyridine by a
chelationꢀdirected CꢀH activation to form intermediate (A)
2 G. Sartori and R. Maggi, Advances in FriedelꢀCrafts Acylation
Reactions; CRC Press: Fl, 2010.
(step i). The reaction of
along with the release of CO2. With the aid of TBHP, the
benzaldehyde forms acyl radical ( ). This process is radicalꢀ
2 with TBHP generates intermediate B,
3
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reaction mechanism has been reported by Li and Sun.5,6c In step
(ii), intermediate (A) reacts with acyl radical (C) to form either
the reactive Pd(IV) or the dimeric Pd(III).22,6c The final step
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release the product
catalytic cycles.
4 and to regenerate Pd(II) for subsequent
4
Rout, A. Banerjee, S. Nandi and B. K. Patel. Org. Lett. 2012, 14
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An efficient approach for the palladium catalyzed
decarboxylative crossꢀcoupling of electronꢀdeficient arenes
with mandelic acid in the presence of TBHP as an oxidant has
been developed. This method is capable of the direct acylation
of sp2 CꢀH bonds.
7
8
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