Palladium(0) nanoparticle-catalyzed sp2 C-H activation: A convenient route to alkyl-aryl ketones by direct acylation of aryl bromides and iodides with aldehydes

Article abstract of DOI:10.1016/j.tetlet.2010.05.067

Palladium(0) nanoparticles efficiently catalyze aliphatic aldehyde C-H functionalization by aryl halides to produce alkyl-aryl ketones in good yields. A wide range of substituted aryl and hetero-aryl bromides/iodides and open-chain aldehydes of varied chain length participated in this reaction.

Full text of DOI:10.1016/j.tetlet.2010.05.067

Tetrahedron Letters 51 (2010) 3811–3814
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Tetrahedron Letters
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Palladium(0) nanoparticle-catalyzed sp2 C–H activation: a convenient route
to alkyl–aryl ketones by direct acylation of aryl bromides and iodides
with aldehydes
*
Laksmikanta Adak, Sukalyan Bhadra, Brindaban C. Ranu
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Palladium(0) nanoparticles efficiently catalyze aliphatic aldehyde C–H functionalization by aryl halides to
produce alkyl–aryl ketones in good yields. A wide range of substituted aryl and hetero-aryl bromides/
iodides and open-chain aldehydes of varied chain length participated in this reaction.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 8 April 2010
Revised 10 May 2010
Accepted 17 May 2010
Available online 21 May 2010
Keywords:
C–H activation
Palladium nanoparticles
Aryl halides
Aldehydes
Alkyl–aryl ketone
The C–H activation by a transition metal catalyst is a very useful
tool in organic synthesis and has wide applications in functionali-
zation of C–H to C–C, C–X, C–O, and C–N bonds.1 There are also
several reports of C–C double and triple bond activations;2 how-
ever, the C@O activation is limited.3 The direct introduction of car-
bonyl group into a phenyl ring by aldehyde C–H activation is a very
useful proposition. The rhodium-catalyzed activation of aldehydes
by organometallic reagents4a and addition of aldehyde to alkenes
to produce diaryl ketones4b are noteworthy among others.5 The
nickel-catalyzed coupling of aryl iodides with aromatic alde-
hydes6a and palladium(II)-catalyzed addition of salicylaldehydes
to aryl iodides6b for the synthesis of diaryl ketones are of much
importance. Recently, Xiao and co-workers reported an elegant
synthesis of alkyl–aryl ketone by direct acylation of aryl bromides
with aldehydes catalyzed by Pd(II) species7a and Cheng7b demon-
strated an efficient route to diaryl ketones by reaction of 2-aryl
pyridine and aryl aldehydes.
Alkyl–aryl ketones are of much importance as useful intermedi-
ates in pharmaceutical, fragrance, dye, and agrochemical
industries.10
To standardize the reaction conditions a series of experiments
were carried out with various palladium salts and additives using
different solvents and varied reaction parameters for a representa-
tive reaction of bromobenzene and octanal. The results are sum-
marized in Table 1. A variety of palladium salts such as Pd(OAc)2,
PdCl2, and Pd(NO3)2 in combination with different additives
including K2CO3, KOBut, Et3N, n-BuNH2, n-Bu2NH, and pyrrolidine
were investigated in solvents such as DMF, DMSO, H2O, toluene,
and THF to best fit the reaction. It was found that the best results
were obtained using Pd(OAc)2 and tetrabutylammonium bromide
(TBAB) in combination with pyrrolidine and 4 Å molecular sieves
in DMF at 100 °C for 10 h (Table 1, entry 12). The absence of TBAB
reduces the yield of product considerably (Table 1, entry 14). It is
believed that TBAB acts as a stabilizer for Pd nanoparticles prevent-
ing them from fast agglomerization and thus helps in the progress
of the reaction.8d The preformed Pd nanoparticles are not equally
active in this reaction possibly due to their inherent tendency for
agglomerization (Table 1, entry 18). No efficient reaction was
The use of metal nanoparticles as efficient catalysts in organic
reactions has attracted considerable interest in recent times in
the context of green chemistry because of their benign character
and ease of preparation.8 As a part of our continuing activities to
explore the novel applications of metal nanoparticles9 we report
here
a Pd(0) nanoparticle-catalyzed C–H functionalization of
O
aliphatic aldehyde by aryl halides leading to an easy route to
alkyl–aryl ketone (Scheme 1).
R1
O
X
+
Pd(OAc)2, TBAB
R1
n
H
Pyrrolidine, 4Aº MS
DMF, 100 ºC
n
R
R
* Corresponding author. Tel.: +91 33 24734971; fax: +91 33 24732805.
E-mail address: ocbcr@iacs.res.in (B.C. Ranu).
Scheme 1. Direct acylation of aryl halides with aldehydes.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.067

3812
L. Adak et al. / Tetrahedron Letters 51 (2010) 3811–3814
Table 1
Standardization of reaction conditionsa
O
O
Br
Pd salt, TBAB
additive, solvent
N2
+
n
H
n
Entry Pd salt
Additive
—
Solvent
Temp
(°C)
Time
(h)
Yield
(%)
1
Pd(OAc)2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
H2O
100
120
120
120
120
120
100
130
100
24
18
18
18
18
18
10
18
22
24
24
10
0
0
0
2
3
4
Pd(OAc)2 K2CO3
Pd(OAc)2 KOBut
Pd(OAc)2 Et3N
0
5
6
7
8
Pd(OAc)2 n-BuNH2
Pd(OAc)2 n-Bu2NH
Pd(OAc)2 Pyrrolidine
Pd(OAc)2 Pyrrolidine
Pd(OAc)2 Pyrrolidine
Pd(OAc)2 Pyrrolidine
Pd(OAc)2 Pyrrolidine
Pd(OAc)2 Pyrrolidine,
4 Å MS
Pd(OAc)2 Pyrrolidine, 4 Å
MS
Pd(OAc)2 Pyrrolidine, 4 Å
MS
<5
12
30
70
0
0
0
83
9
10
11
12
Toluene 110
THF
DMF
70
100
13b
14c
DMF
DMF
130
100
24
10
43
50
Figure 1. TEM image of Pd-nanoparticles formed in the reaction mixture.
15
16
Pd(OAc)2 4 Å MS
DMF
DMF
100
100
24
10
0
54
PdCl2
Pyrrolidine, 4 Å
MS
17
18
Pd(NO3)2 Pyrrolidine, 4 Å
MS
DMF
DMF
100
100
10
10
60
48
PdNPsd
Pyrrolidine, 4 Å
MS
a
Reaction conditions: a mixture of bromobenzene (1 mmol), octanal (1.2 mmol),
Pd salt (4 mol %), TBAB (1 mmol), additive (2 mmol), and solvent (4 mL) was heated.
b
Undesired tarry material was obtained.
Reaction was carried out in the absence of TBAB.
Pd nanoparticles were prepared separately.
c
d
observed in the absence of 4 Å molecular sieves (Table 1, entry 7).
The amount of Pd(OAc)2 was also optimized to 4 mol %.
Thus, in a typical experimental procedure,11 a mixture of aryl
bromide, aldehyde, Pd(OAc)2, TBAB, pyrrolidine, and 4 Å molecular
sieves in DMF was heated at 100 °C for a certain period of time as
required to complete the reaction (TLC). The standard work-up and
purification by column chromatography provided the pure
product.
Figure 2. SAED pattern of crystalline Pd-nanoparticles.
To determine the active catalytic species in this reaction, an ex-
tract from the reaction mixture of bromobenzene and octanal after
4 h from the start of the reaction showed the formation of nano-
particles of 5–8 nm size by TEM (Transmission Electron Micro-
scope) image (Fig. 1). The identity of these particles as palladium
was confirmed by the selected area electron diffraction (SAED) pat-
tern ( Fig. 2) which exhibited four diffused rings due to (1 1 1),
(2 0 0), (2 2 0), and (3 1 1) reflections of fcc Pd and indicated the
crystalline nature of nanoparticles. The study of this reaction by
UV (DMF) spectroscopy showed a peak at 415 nm corresponding
to Pd(II) before the start of the reaction and disappearance of this
peak with the progress of the reaction by 4 h indicated the forma-
tion of Pd(0) (Fig. 3).
A series of diversely substituted aryl halides underwent acyla-
tion with a variety of aliphatic aldehydes by this procedure to pro-
duce the corresponding alkyl–aryl ketones. The results are
summarized in Table 2. Although the aryl iodides and bromides
are highly reactive, the corresponding chlorides are considerably
less reactive (Table 2, entry3). Thus chloro and fluoro groups pres-
ent in aryl iodides and bromides remained unaffected during acy-
lations. Both electron-donating and electron-withdrawing
substituted aryl bromides participated in this reaction although
electron-donating substituents led to marginally higher yield.
Figure 3. UV spectra of Pd at the initial and in the reaction mixture after the
reaction.

L. Adak et al. / Tetrahedron Letters 51 (2010) 3811–3814
3813
Table 2
Table 2 (continued)
Palladium nanoparticle-catalyzed acylation of aryl and heteroaryl halides with
aldehydes
Entry
R
X
Aldehyde
Time (h)
12
Yielda (%)
80
Ref.
O
O
O
R1
X
Pd(OAc)2, TBAB
1
N
H
17
Br
R
n
+
H
Pyrrolidine, 4Aº MS
DMF, 100 ºC
H
O
n
4
4
R
R
Entry
R
X
Aldehyde
Time (h)
Yielda (%)
90
Ref.
18
Br
15
62
N
H
O
a
1
2
3
4
5
6
7
8
H
I
7.0
8.5
13
13
13
7a
7a
14
15
Isolated yields of pure products.
H
O
6
6
6
5
5
8
3
2
2
The substituents at m- or p- position did not make much difference
in reactivity although o-substituted aryl halides did not undergo
acylation possibly due to steric factors. The aldehydes are uni-
formly reactive irrespective of their chain length. The most signif-
icant feature of this Pd(0) nanoparticle-catalyzed procedure is
efficient participation of heteroaryl bromides and iodides. Thus,
several heteroaryl units bearing thiophenyl, pyridyl, indolyl, and
quinolinyl moieties produced the corresponding alkyl ketones in
moderate to good yields. The direct acylation of heteroaryl halides
by aliphatic aldehydes has not been addressed earlier except one
report demonstrating only one reaction of thiophenyl bromide in
lower yield (58%).7a
The reactions are generally clean, although in a few reactions
small amounts (2–5%) of dimeric products from self-coupling of
aryl halides are formed. These were easily separated during purifi-
cation of product by column chromatography. Several functional-
ities such as OMe, F, Cl, COMe, NH2, and OH were compatible
with the reaction conditions. Interestingly when this reaction
was performed under identical conditions in the presence of tetra-
kis(triphenylphosphine)palladium(0), no acylation was observed.
Cheng and co-workers7b also reported that Pd(0) was totally inef-
fective for their C–H functionalization by aryl pyridines and to
the best of our knowledge we are not aware of any aldehyde C–
H functionalization by aryl halides using Pd(0). This demonstrates
the importance of Pd(0) nanoparticles for this aldehyde C–H acti-
vation. Furthermore, it was reported that palladium nanoparticle-
catalyzed reaction of aryl bromides and aliphatic aldehydes in
the presence of tetrabutyl ammonium salt, ionic liquid, and potas-
sium carbonate led to biaryl formation by Ullmann reaction with-
out any acylation of aldehyde.12 Thus, this combination of
palladium nanoparticles, pyrrolidine, and molecular sieves in
DMF is a best fit for aldehyde C–H activation by aryl halides.
It is suggested that the reaction follows a similar reaction
pathway as proposed by Xiao and co-workers7a As outlined in
H
H
Br
Cl
I
83
32
84
76
80
70
68
H
O
15
H
O
p-OMe
p-OMe
p-Me
p-Cl
8
10
9
H
O
Br
Br
Br
I
H
O
H
O
12
10
H
O
p-COCH3
H
O
9
10
11
p-COCH3
m-OMe
m-F
Br
Br
Br
13
15
62
59
72
H
O
16
Ph
H
O
9.0
H
O
10
10
6
12
13
14
15
16
m-NH2
p-OH
Br
Br
Br
Br
I
12
12
10
10
18
88
64
80
78
54
O
H
O
Ar-X
Base.HX
Base
R
Oxidative
addition
H
H
Pd(0)
Enamine
formation
with
H
O
Ar
Reductive
eimination
(II)Pd
pyrrolidine
X
H
N
R
Pd(II)
Ar
H
O
5
X
N
Ar
S
N
R
Ar
N
H
β-Hydride
H
O
Pd(II)
N
6
elimination
X
R
(II)Pd
H2O
O
Insertion
R
X
A
17
Ph
π-Complex
H
R
2
Ar
Scheme 2. Probable mechanism of acylation reaction.

3814
L. Adak et al. / Tetrahedron Letters 51 (2010) 3811–3814
at 100 °C under argon for 8.5 h (TLC). The reaction mixture was extracted with
Et2O (4 Â 15 mL). The extract was washed with water, brine, and then dried
(Na2SO4). Evaporation of solvent left the crude product, which was purified by
column chromatography over silica gel (60–120 mesh) (hexane/ether 97:3) to
Scheme 2, in situ-generated Pd nanoparticles undergo oxidative
addition with the aryl halide followed by Heck coupling with the
enamine, formed in situ by the reaction of aldehyde and pyrroli-
dine, to provide an intermediate A with the insertion of aryl group
provide 1-phenyl-octan-1-one as
a colorless liquid (169 mg, 83%). The
spectroscopic data (IR, 1H NMR, and 13C NMR) of this compound are in good
agreement with those reported earlier.13 This procedure was followed for all
the reactions listed in Table 2. Many of these products are known compounds
and were easily identified by comparison of their spectroscopic data with those
reported (see Table 2). The unknown compounds were properly characterized
by their IR, 1H NMR, 13C NMR, and HRMS data.
at the
a-position of the heteroatom. The intermediate A on b-hy-
dride elimination followed by hydrolysis furnished the product, al-
kyl–aryl ketone. Reductive elimination of HX from the catalyst
surface releases Pd(0).
In conclusion, we have developed an efficient procedure for
aldehyde C–H functionalization by aryl halides catalyzed by palla-
dium nanoparticles. A wide range of substituted aryl and hetero-
aryl iodides and bromides underwent acylations by a variety of
aliphatic aldehydes providing an easy access to alkyl–aryl ketones.
The significant advantage of this protocol is successful application
to several diverse heteroaryl halides. Furthermore, this work dem-
onstrates the potential and clear distinction of palladium(0) nano-
particles over palladium(0).
1-(4-Acetyl-phenyl)-butan-1-one (Table 2, entries 8 and 9): brown gummy
liquid; IR (neat): 2961, 2931, 2875, 1684, 1605, 1456, 1265, 1215 cmÀ1 1H
;
NMR (CDCl3, 300 MHz) d 0.99 (t, J = 7.4 Hz, 3H), 1.73–1.80 (m, 2H), 2.63 (s, 3H),
2.96 (t, J = 7.3 Hz, 2H), 8.01 (s, 4H); 13C NMR (CDCl3, 75 MHz) d 13.9, 17.7, 26.9,
41.0, 128.3 (2C), 128.6 (2C), 140.1, 140.4, 197.7, 199.9; HRMS Calcd for
C12H14O2 ([M+Na]+): 213.0892. Found: 213.0872.
1-(3-Fluoro-phenyl)-dodecan-1-one (Table 2, entry 11): yellow liquid; IR (neat):
2924, 2855, 1693, 1589, 1466, 1442, 1248, 1151, 896, 758 cmÀ1 1H NMR
;
(CDCl3, 300 MHz) d 0.87 (t, J = 6.3 Hz, 3H), 1.18–1.25 (m, 16H), 1.67–1.74 (m,
2H), 2.93 (t, J = 7.3 Hz, 2H), 7.20–7.26 (m, 1H), 7.39–7.43 (m, 1H), 7.62 (d,
J = 9.4 Hz, 1H), 7.72 (d, J = 7.6 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 14.2, 22.8,
24.3, 28.8, 28.9, 29.0, 29.4, 29.6, 29.7, 32.0, 38.9, 114.9 (d, J = 28.8 Hz, 1C), 119.9
(d, J = 21.3 Hz, 1C), 123.9, 130.3, 139.2, 163.0 (d, J = 246.2 Hz, 1C), 199.3; HRMS
Calcd for C18H27FO [M+Na]+: 301.1944. Found: 301.1941.
Acknowledgments
1-(3-Amino-phenyl)-dodecan-1-one (Table 2, entry 12): yellow liquid; IR (neat):
3462, 3370, 2953, 2924, 2853, 1678, 1624, 1602, 1456, 1323, 1288, 1190,
We are pleased to acknowledge the financial support from DST,
Govt. of India under J. C. Bose fellowship to B.C.R. (SR/S2/JCB-11/
2008). L.A. and S.B. are thankful to CSIR for their fellowships.
993 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.86 (t, J = 6.3 Hz, 3H), 1.22–1.30 (m,
;
16H), 1.67–1.71 (m, 2H), 2.86–2.93 (m, 2H), 3.86 (br s, 2H), 6.83–6.87 (m, 1H),
7.18–7.32 (m, 3H); 13C NMR (CDCl3, 75 MHz) d 14.1, 22.7, 24.5, 29.3, 29.4, 29.5,
29.6, 29.7, 31.4, 38.7, 114.1, 118.5, 119.6, 129.4, 138.2, 146.6, 200.9; HRMS
Calcd for C18H29NO ([M+Na]+): 298.1709. Found: 298.1705.
References and notes
1-(4-Hydroxy-phenyl)-octan-1-one (Table 2, entry 13): brown low melting
solid; IR (neat): 3312, 3300, 2957, 2928, 2856, 1659, 1602, 1583, 1491, 1456,
1269, 1224, 1166 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.91–0.97 (m, 3H), 1.34–
;
1. (a) Ackermann, L.; Vicente, R.; Althammer, A. Org. Lett. 2008, 10, 2299–2302;
(b) Wang, D.; Wasa, M.; Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 7190–
7191; (c) Ueda, S.; Nagasawa, H. Angew. Chem., Int. Ed. 2008, 47, 6411–6413; (d)
Wan, X.; Ma, Z.; Li, B.; Zhang, K.; Cao, S.; Zhang, S.; Shi, Z. J. Am. Chem. Soc. 2006,
128, 7416–7417; (e) Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc.
2006, 128, 7134–7135; (f) Desai, L. V.; Stowers, K. J.; Sanford, M. S. J. Am. Chem.
Soc. 2008, 130, 13285–13293; (g) Imamoto, K.; Saito, T.; Katsuno, M.;
Sakamoto, T.; Hiroya, K. Org. Lett. 2007, 9, 2931–2934.
2. (a) Jun, C.-H.; Hwang, D.-C.; Na, S.-J. Chem. Commun. 1998, 1405–1406; (b)
Tsukada, N.; Mitsuboshi, T.; Setoguchi, H.; Inou, Y. J. Am. Chem. Soc. 2003, 125,
12102–12103; (c) Lail, M.; Arrowood, B. N.; Gunnoe, T. B. J. Am. Chem. Soc. 2003,
125, 7506–7507; (d) Thalji, R. K.; Ellman, J. A.; Bergman, R. G. J. Am. Chem. Soc.
2004, 126, 7192–7193.
1.42 (m, 8H), 1.73–1.83 (m, 2H), 2.98 (t, J = 7.3 Hz, 2H), 6.34 (broad, 1H), 6.98
(d, J = 8.7 Hz, 2H), 7.96 (d, J = 8.7 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 14.2, 22.7,
25.1, 29.3, 29.5, 31.8, 38.5, 115.8 (2C), 129.3, 130.9 (2C), 161.9, 200.9.
1-Naphthalen-1-yl-heptan-1-one (Table 2, entry 14): yellow liquid; IR (neat):
3049, 2955, 2928, 2857, 1682, 1593, 1509, 1464, 1234, 1172, 1087, 800 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 0.90–0.94 (m, 3H), 1.33–1.42 (m, 6H), 1.75–1.83
(m, 2H), 3.06 (t, J = 7.3 Hz, 2H), 7.47–7.62 (m, 3H), 7.84–7.89 (m, 2H), 7.98 (d,
J = 8.2 Hz, 1H), 8.56 (d, J = 8.3 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 14.0, 22.5,
24.7, 29.0, 31.7, 42.3, 124.4, 125.8, 126.4, 127.1, 127.8, 128.4, 130.1, 132.3,
133.9, 136.5, 205.2.
1-Thiophen-2-yl-octan-1-one (Table 2, entry 15): yellow liquid; IR (neat): 2955,
2928, 2854, 1663, 1518, 1415, 1234 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.84–
;
3. Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41, 222–234.
4. (a) Pucheault, M.; Darses, S.; Genet, J.-P. J. Am. Chem. Soc. 2004, 126, 15356–
15357; (b) Ishiyama, T.; Hartwig, J. J. Am. Chem. Soc. 2000, 122, 12043–12044.
5. (a) Zanardi, A.; Mata, J. A.; Paris, E. Organometallics 2009, 28, 1480–1483; (b) Ko,
S.; Kang, B.; Chang, S. Angew. Chem., Int. Ed. 2005, 44, 455–457; (c) Takemiya,
A.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 14800–14801; (d) Lerebours, R.;
Camacho-soto, A.; Wolf, C. J. Org. Chem. 2005, 70, 8601–8604.
0.92 (m, 3H), 1.17–1.35 (m, 8H), 1.70–1.78 (m, 2H), 2.88 (t, J = 7.4 Hz, 2H),
7.09–7.12 (m, 1H), 7.59 (d, J = 4.92 Hz, 1H), 7.68 (d, J = 3.7 Hz, 1H); 13C NMR
(CDCl3, 75 MHz) d 13.9, 22.5, 24.7, 29.0, 29.2, 31.6, 39.4, 127.9, 131.6, 133.2,
144.4, 193.5.
1-(1H-Indol-4-yl)-hexan-1-one (Table 2, entry 17): brown gummy liquid; IR
(neat): 3316, 2957, 2930, 2870, 2860, 1685, 1651, 1612, 1454, 1350, 1248,
1094, 758 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.95–0.99 (m, 3H), 1.26–1.47 (m,
;
6. (a) Huang, Y.-C.; Majumdar, K. K.; Cheng, C.-H. J. Org. Chem. 2002, 67, 1682–
1684; (b) Satoh, T.; Itaya, T.; Miura, M.; Nomura, M. Chem. Lett. 1996, 823–824.
7. (a) Ruan, J.; Saidi, O.; Iggo, J. A.; Xiao, J. J. Am. Chem. Soc. 2008, 130, 10510–
10511; (b) Jia, X.; Zhang, S.; Wang, W.; Luo, F.; Cheng, J. Org. Lett. 2009, 10,
3120–3123.
4H), 1.80–1.88 (m, 2H), 3.11 (t, J = 7.3 Hz, 2H), 6.71 (s, 1H), 7.33 (s, 1H), 7.47 (d,
J = 8.6 Hz, 1H), 7.92 (d, J = 8.6 Hz, 1H), 8.40 (s, 1H), 9.22 (br s, 1H); 13C NMR
(CDCl3, 75 MHz) d 14.1, 22.6, 24.8, 31.8, 38.6, 104.1, 111.3, 122.0, 122.7, 126.0,
127.5, 129.6, 138.7, 201.6; HRMS Calcd for C14H17NO ([M+Na]+) 238.1208.
Found: 238.1206.
8. (a) Astruc, D. Inorg. Chem. 2007, 46, 1884–1894; (b) Astruc, D.; Lu, F.; Aranzaes,
J. R. Angew. Chem., Int. Ed. 2005, 44, 7852–7872; (c) Polshettiwar, V.; Baruwati,
B.; Varma, R. S. Green Chem. 2009, 11, 127–131; (d) Reetz, M. T.; Westermann,
E. Angew. Chem., Int. Ed. 2000, 39, 165–168; (e) Durand, J.; Teuma, E.; Gomez, M.
Eur. J. Inorg. Chem. 2008, 3577–3586.
9. (a) Ranu, B. C.; Chattopadhyay, K. Org. Lett. 2007, 9, 2409–2412; (b) Ranu, B. C.;
Chattopadhyay, K.; Adak, L. Org. Lett. 2007, 9, 4595–4598; (c) Ranu, B. C.; Dey,
R.; Chattopadhyay, K. Tetrahedron Lett. 2008, 49, 3430–3432; (d) Dey, R.;
Chattopadhyay, K.; Ranu, B. C. J. Org. Chem. 2008, 73, 9461–9464; (e) Saha, D.;
Chattopadhyay, K.; Ranu, B. C. Tetrahedron Lett. 2009, 50, 1003–1006; (f) Adak,
L.; Chattopadhyay, K.; Ranu, B. C. J. Org. Chem. 2009, 74, 3982–3985.
10. Surburg, H.; Panten, J. Common Fragrance and Flavor Materials, 5th ed.; Wiley-
VCH: Weinheim, Germany, 2006.
1-Quinolin-3-yl-hexan-1-one (Table 2, entry 18): brown solid; mp: 62–64 °C; IR
(KBr): 3057, 2947, 2931, 2850, 1688, 1682, 1620, 1572, 1454, 1176, 1126,
954 cmÀ1 1H NMR (CDCl3, 300 MHz) d 0.89–0.99 (m, 3H), 1.24–1.47 (m, 4H),
;
1.78–1.82 (m, 2H), 3.08 (t, J = 7.3 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.82 (t,
J = 7.3 Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H), 8.69 (s, 1H), 9.42
(s, 1H); 13C NMR (CDCl3, 75 MHz) d 14.0, 22.6, 23.9, 31.5, 38.9, 126.9, 127.6,
129.3, 129.4, 129.5, 131.9, 136.9, 149.2, 149.8, 199.3; HRMS Calcd for C15H17NO
([M+H]+): 228.1383. Found: 228.1384.
12. Calo, V.; Nacci, A.; Monopoli, A.; Cotugno, P. Chem. Eur. J. 2009, 15, 1272–1279.
13. Vechorkin, O.; Hu, X. Angew. Chem., Int. Ed. 2009, 48, 2937–2940.
14. Shimizu, K.-i.; Niimi, K.; Satsuma, A. Catal. Commun. 2008, 9, 980–983.
15. Bellale, E. V.; Bhalerao, D. S.; Akamanchi, K. G. J. Org. Chem. 2008, 73, 9473–
9475.
16. Rao, M. L. N.; Giri, S.; Jadhav, D. N. Tetrahedron Lett. 2009, 50, 6133–6138.
17. Iwai, T.; Nakai, T.; Mihara, M.; Ito, T.; Mizuno, T.; Ohno, T. Synlett 2009, 1091–
1094.
11. General experimental procedure for acylation reaction: representative one for
acylation of bromobenzene with octanal (Table 2, entry 2):
a mixture of
bromobenzene (157 mg, 1 mmol), octanal (154 mg, 1.2 mmol), Pd(OAc)2 (9 mg,
4 mol %), tetrabutyl ammonium bromide (323 mg, 1 mmol), pyrrolidine
(142 mg, 2 mmol), and 4 Å MS (1 g) in DMF (4 mL) was heated with stirring